Volume 71, Number 3, May-June 2019

Siriraj Medical Journal

SMJ

ISSN 2629-995X

ORIGINAL ARTICLE

175 Managing Difficult Cannulations in Endoscopic Retrograde

Cholangiopancreatography: A Prospective Randomized

Control Trial Study of Precut Needle Knife Sphicterotomy

versus Transpancreatic Sphicterotomy Technique

Surachai Siripornadulsilp, Nisit Tongsiri

181 Mosapride Reduces Prolonged Postoperative Ileus after

Open Colorectal Surgery in the Setting of Enhanced Recovery

after Surgery (ERAS): A Matched Case-Control Study

Varut Lohsiriwat

189 Cardiaovascular Disease Risk Factors in Thai Natural

Menopause with First-Time Diagnosis of Low Bone Mass

Density

Kitirat Techatraisak, Pattra Wisarnsirirak

196 Comparative Study of Health-Related Quality of Life

between Colorectal Cancer Patients with Temporary and

Permanent Stoma

Natharom Chutikamo, et al.

201 An Agreement of Two Tonometers: Goldmann Applanation

and Non-Contact Scheimflug Technology in Healthy,

Ocular Hypertension and Open-angle Glaucoma Patients

Sakaorat Petchyim, et al.

207 The Use of Dual Energy Computerized Tomography to

Detect Residual Viable Hepatocellular Carcinoma after

Transarterial Chemoembolization

Pharida Pengwan, et al.

214 The Effects of the Thai Traditional Medicine of Abdominal

Massage on Defecation in Post Lumbar Laminectomy Patients

Prapapin Siripohn, et al.

220 Prevalence and Factors Associated with Abnormal Cervical

Cell among the Hmong and Mien Hill Tribe Women in

Pha Yao Province, Thailand

Supansa Kuntasorn, et al.

228 Resilience in Medical Doctors within the Areas of the

Southern Thailand Insurgency

Chonnakarn Jatchavala, Jarurin Pitanupong

234 Detection of Specific Autoantibodies in Sera with Negative

Antinuclear Antibody by Indirect Immunofluorescence

Assay but Positive by Enzyme Immunoassay

Ronnachai Viriyataveekul, Jaruda Kobkitjaroen

240 Identification of Apigenin and Luteolin in

Artemisia annua L. for the Quality Control

Rattana Phadungrakwittaya, et al.

REVIEW ARTICLE

246 Telemedicine – Meaning, Challenges and Opportunities

Ittipong Khemapech, et al

www.smj.si.mahidol.ac.th

E-mail: sijournal@mahidol.ac.th

International Association of Surgeons

Gastroenterologists & Oncologists

Thailand Chapter

Thai Association for Gastrointestinal

Endoscopy

Indexed by

By Rattana Phadungrakwittaya, et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

234

Viriyataveekul et al.

Ronnachai Viriyataveekul, M.D., Jaruda Kobkitjaroen, M.D.

Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ailand.

Detection of Specic Autoantibodies in Sera with

Negative Antinuclear Antibody by Indirect

Immunouorescence Assay but Positive by

Enzyme Immunoassay

Corresponding author: Jaruda Kobkitjaroen

E-mail: jaruda.kob@mahidol.ac.th

Received 16 March 2018 Revised 27 November 2018 Accepted 21 February 2019

ORCID ID: http://orcid.org/0000-0002-6553-2185

http://dx.doi.org/10.33192/Smj.2019.36

ABSTRACT

Objective: e aim of this study was to investigate the predictive value of positive enzyme immunoassay (EIA) for

detection of specic autoantibodies in sera negative for antinuclear antibody (ANA) by indirect immunouorescence

(IIF) assay, but positive for ANA by EIA.

Methods: Eighty sera that tested negative for ANA by IIF, but positive for ANA by EIA were included. All sera

were tested for specic autoantibodies by line immunoassay (LIA). e positive predictive value (PPV) of EIA was

calculated using LIA result as a reference standard. Medical records of patients were reviewed. Clinical ndings at

the time of blood sampling for ANA testing and at 5 years aer sampling were obtained.

Results: Twenty-eight sera (35%) were found to be positive by LIA. e PPV of EIA for detection of specic

autoantibodies at the manufacturer’s recommended cut-o was 35.0% (95% CI: 24.5-45.5%). e most prevalent

antibodies were anti-SSA/Ro60 (64.3%, 95% CI: 46.5-82.0%), anti-Ro52 (25.0%, 95% CI: 9.0-41.0%), and anti-SSB/

La (10.7%, 95% CI: 0-22.2%). A diagnosis of systemic autoimmune rheumatic disease was established in 7 patients

(25%) at the time of blood sampling, and 4 patients (14.3%) were diagnosed with non-rheumatic autoimmune disease.

Conclusion: EIA testing in IIF-ANA negative sera yielded a chance to detect antinuclear antibodies. However, the

poor PPV of EIA may have low benet in real-life clinical practice. Anti-SSA/Ro60 was the most prevalent antibody

detected. A high proportion of LIA-ANA positive patients were not diagnosed as autoimmune disease at the time

of antibody detection.

Keywords: Antinuclear antibody; extractable nuclear antigen; enzyme immunoassay; indirect immunouorescence

assay (Siriraj Med J 2019;71: 234-239)

INTRODUCTION

Antinuclear antibodies (ANA) are essential

autoantibodies for screening and diagnosis of systemic

autoimmune rheumatic diseases (SARD), such as systemic

lupus erythematosus (SLE), as well as non-rheumatic

autoimmune diseases.

1-5

Certain specic antibodies are

included in the diagnostic criteria for certain specic

diseases.

6-9

Indirect immunouorescence (IIF) assay

is the gold standard method that is most commonly

used for detection of ANA.

IIF uses Hep-2 cells as

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

235

Original Article

SMJ

a substrate, which provides almost all of the antigens

that are required for ANA testing. However, enzyme

immunoassay (EIA) is more rapid and simple than IIF

for detecting ANA. EIA contains disease-relevant native

or recombinant antigens that are coated on a microtiter

plate. IIF using Hep-2 cells could yield a false-negative

result for anti-Ro and anti-Jo-1 antibodies, while EIA

could detect them.

11,12

However, EIA has been associated

with both false-positive and false-negative results.

During 2010, the Clinical Pathology Laboratory at Siriraj

Hospital implemented a protocol that calls for IIF to be

used for initial screening of ANA. In cases of negative

result by IIF, secondary screening is performed using

EIA. We observed that among sera positive for ANA by

EIA, some sera samples were positive and some were

negative for specic antibodies subsequently requested

by the physician.

Accordingly, the aim of this study was to investigate

the predictive value of positive EIA for detection of

specic autoantibodies in sera negative for ANA by IIF,

but positive for ANA by EIA. e secondary objective

was to determine and report the prevalence and clinical

ndings of certain antibodies.

MATERIALS AND METHODS

Patient sera

Sera negative for ANA by IIF, but positive for ANA

by EIA were randomly selected from stored sera sent

to the Clinical Pathology Laboratory at Siriraj Hospital

for ANA testing during 2010. Sera were stored at -20°C

before analysis. Siriraj Hospital is ailand’s largest

national tertiary referral center.

Medical records of patients whose sera were included

in this study were reviewed. Clinical ndings at the time

of blood sampling for ANA testing and at 5 years aer

sampling were obtained and recorded.

e protocol for this study was approved by the

Siriraj Institutional Review Board (SIRB), Faculty of

Medicine Siriraj Hospital, Mahidol University, Bangkok,

ailand (Si 211/2557).

IIF assay

IIF assay was performed using a Mosaic HEp-

20-10/Liver (Monkey) Kit (Euroimmun AG, Lübeck,

Germany). Briey, sera were diluted to 1:100 and then

incubated with Hep-20-10 cells. e Hep-20-10 cells

contained an increased spectrum of Hep-2 cells in the

mitotic phase. Aer staining with uorescent conjugate,

slides were visualized under a uorescent microscope at

400x. Fluorescence intensity was compared with that of

the end-point positive control. Fluorescence intensity

equal to or greater than the uorescence intensity of the

end-point positive control was considered a positive

result.

EIA testing

EIA testing was performed using an IMTEC-ANA

Screen Kit (Human Diagnostics, Wiesbaden, Germany).

e microtiter strips came coated with HeLa cell nuclei.

Sera were diluted to 1:101 before being added to the

plates. e manufacturer dened any value above 55

U/ml as being a positive result.

Antigen-specic assays

Line immunoassay (LIA) was performed using an

IMTEC-ANA-LIA Kit (Human Diagnostics). e strips

contain the following antigens: nucleosomes, histones,

SmD1, nRNP, SSA/Ro60, Ro52, SSB/La, Scl-70, CENP-B,

Jo-1, and ribosomal P proteins (Rib-P). Sera showing

positive reactivity on the Human Diagnostics LIA were

tested again using a EUROLINE ANA Profile 3 Kit

(Euroimmun AG) to conrm the result. e strips in that

kit contain the following antigens: nRNP, Sm, SSA/Ro60,

Ro-52, SSB/La, Scl-70, PM/Scl, Jo-1, CENP-B, PCNA,

dsDNA, nucleosomes, histones, Rib-P, and AMA M2.

Sera were diluted to 1:101 before incubation with the

strips. Positive reactivity on both LIA kits for at least 1

identical antibody (Ab) type was considered a positive

result.

Statistical analysis

All data were collected and analyzed using Microso

Excel 2016 spreadsheet soware (Microso Corporation,

Redmond, WA, USA). Rate of positive or negative LIA,

predictive value of positive EIA, prevalence of each

specic antibody, and 95% condence interval (CI) were

calculated.

RESULTS

Eighty sera that tested negative for ANA by IIF,

but that tested positive for ANA by EIA were included.

An overview of LIA results from both LIA test kits is

shown in Fig 1. Seven sera with positive LIA by only

the Human Diagnostics LIA (samples 31-37), and 2

sera positive for dierent antibody types using either

the Human Diagnostics LIA or the Euroimmun LIA

(samples 29-30) were considered negative LIA (Table 1).

erefore, 28 sera (35%) were considered positive LIA

(samples 1-28).

e manufacturer’s recommended cut-o value of 55

U/mL could not discriminate positive from negative LIA

(Fig. 2). Using the LIA result as a reference standard, the

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

236

Viriyataveekul et al.

Fig 1. Overview of LIA results of 80 sera negative for ANA by IIF, but positive for ANA by EIA.

Abbreviations: Ab = antibody; EIA = enzyme immunoassay; IIF = indirect immunouorescence assay; LIA = line immunoassay, - = negative;

+ = positive

Fig 2. Comparison of EIA values between positive and negative LIA.

Abbreviations: EIA= enzyme immunoassay; LIA= line immunoassay; Neg= negative; Pos= positive

positive predictive value (PPV) of EIA for the detection

of specic autoantibodies at this value was 35.0% (95%

CI: 24.5-45.5%). e PPV of dierent EIA values are

shown in Table 2.

e most prevalent antibodies were anti-SSA/Ro60

(64.3%, 95% CI: 46.5-82.0%), anti-Ro52 (25%, 95% CI:

9.0-41.0%), and anti-SSB/La (10.7%, 95% CI: 0-22.2%)

(Table 1). A diagnosis of SARD was established in 7 of

28 patients (25%) at the time of blood sampling. Four

patients (14.3%) were diagnosed with non-rheumatic

autoimmune disease. Seventeen patients had insucient

evidence for diagnosing autoimmune disease (60.7%).

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

237

Original Article

SMJ

TABLE 1. EIA values, specic antibodies, and clinical ndings of 37 sera showing reactivity on LIA.

Sample

EIA Human Diagnostics Euroimmun

no. (U/ml) LIA LIA

Clinical ndings

1 95 Ro60 Ro60 Urticarial vasculitis

2 98 Ro60 Ro60 Chronic urticaria, allergic rhinitis

3 94 Ro60 Ro60 Tubulointerstitial disease of unknown cause

4 305 Ro60, Ro52 Ro60, Ro52 Dead fetus in utero at 13 weeks

5 252.57 Ro60, Ro52, La Ro60, Ro52, La SLE

6 113.63 Ro60, SmD1, Rib-P Ro60, Sm, Rib-P Discoid LE, lupus profundus

7 >500 Ro60 Ro60, Ro52 SLE

8 139 Ro60 Ro60, Ro52 Amaurosis fugax

9 114 Ro60 Ro60, Ro52 RA, secondary Sjogren syndrome

10 193.41 Ro60 Ro60, AMA-M2 Primary biliary cirrhosis

11 >500 Ro60 Ro60, histone Nonalcoholic steatohepatitis

12 486 Ro60 Ro60, Rib-P AIH

13 206 Ro60 Ro60, Ro52, AMA-M2 Nephrotic syndrome (FSGS)

14 198.6 Ro60 Ro60, Ro52, La, CENP-B RA, leukopenia

15 120.3 Ro60, nRNP Ro60 DM, AKI on top of CKD

16 211 Ro60, Ro52 Ro60, Ro52, PM/Scl Chronic ITP

17 90 Ro60, SmD1, nucleosome Ro60, Ro52 Alopecia areata

18 288.3 Ro60, histone, nucleosome Ro60, dsDNA Lupus nephritis type IV

19 58.41 Ro52 Ro52 Myofascial pain syndrome

20 106 Ro52 Ro52,Ro60 Commonvariableimmunedeciency

21 63 Ro52 Ro52, AMA-M2 Chronic hepatitis C

22 117 Ro52, Jo-1 Ro52, Jo-1 RA

23 148.54 CENP-B CENP-B Suspected AIH

24 72 Jo-1 Jo-1 Progressive obstructive jaundice of

unknown cause

25 88.9 La La Beta-thalassemia/Hb E disease, AIHA

26 83 La La, Jo-1 Erythema nodosum

27 124.29 Scl-70 Scl-70 Chronic urticaria

28 96.87 SmD1 Sm Unilateral posterior uveitis

29 78.9 SmD1 Ro60 N/A

30 146 nRNP Sm N/A

31 68 Ro60 - N/A

32 72 SmD1 - N/A

33 77.8 SmD1 - N/A

34 135 Histone - N/A

35 158 nRNP - N/A

36 107.4 SmD1, Ro60 - N/A

37 81 Nucleosome, histone, nRNP - N/A

Abbreviations: Ab= antibody; AIH= autoimmune hepatitis; AKI= acute kidney injury; AIHA= autoimmune hemolytic anemia; CKD=

chronic kidney disease; DM= diabetes mellitus; FSGS= focal segmental glomerulosclerosis; ITP= immune thrombocytopenia; LE= lupus

erythematosus; N/A= not applicable; RA= rheumatoid arthritis; SLE= systemic lupus erythematosus

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

238

Viriyataveekul et al.

Five years later, 13 of those (76.5%) had not developed

autoimmune disease, and 4 patients (samples 19, 21, 23,

and 28) had missing data.

DISCUSSION

e present study set forth to investigate for specic

antibodies in sera negative for ANA by IIF, but positive

for ANA by EIA. We found a higher rate of positive

specic antibodies than previous study (35% vs. 16.9%).

Compared to previous studies that performed antigen-

specic assay in all IIF-ANA negative sera and who found

a rate of positivity of 0.7-14%

15-17

, we demonstrated that

screening with EIA-ANA before performing antigen-

specic assay in IIF-ANA negative sera may increase

the probability of identifying specic antibodies.

e manufacturer’s recommended cut-o value

yielded a low PPV. Even though the EIA value was as

high as 250 U/mL, the PPV of 75% was not suciently

high. erefore, a positive result from this EIA kit may

not be applicable to real-life clinical practice. However,

reporting the EIA result along with its specic PPV may

provide benet relative to a decision to request or not

request antigen-specic assay.

Similar to previous studies

14,16

, the most prevalent

antibodies identied in this study were anti-SSA/Ro60,

anti-Ro52, and anti-SSB/La, and these antibodies have been

recognized as being associated with Sjogren syndrome

and SLE.

Anti-SSA/Ro60 was shown to have association

with both subacute cutaneous lupus erythematosus

and neonatal lupus erythematosus.

20,21

In the present

study, a large proportion of patients with positive LIA

were not diagnosed as autoimmune disease by the 5-year

follow-up. However, the presence of autoantibodies oen

portends the development of disease that does not fully

clinically manifest until years into the future. Anti-SSA/

Ro60 could be detected before the onset of symptoms

and diagnosis of SLE at intervals as long as 9.1 and 10.4

years, respectively.

22,23

is study has some mentionable limitations. First

and consistent with the retrospective nature of this

study, some data was missing or incomplete. Second,

the number of included samples was relatively small.

ird, random samples were selected from routine ANA

testing; therefore, our ndings may not be generalizable

to patients tested in specialized clinic. Fourth and last,

we investigated only one EIA kit that uses HeLa cell

nuclear extract, which may be dierent from other EIA

kits that use dierent combinations of dened native or

recombinant antigens.

CONCLUSION

EIA testing in IIF-ANA negative sera yielded a

chance to detect antinuclear antibodies. However, the

poor PPV of EIA may have low benet in real-life clinical

practice. Anti-SSA/Ro60 was the most prevalent antibody

detected. A high proportion of LIA-ANA positive patients

were not diagnosed as autoimmune disease at the time

of antibody detection.

ACKNOWLEDGMENTS

e authors gratefully acknowledge Ms. Jintana

Jaiyen for assistance with specimen collection, and the

laboratory technicians in the Clinical Pathology Serology

Laboratory of Siriraj Hospital for performing the LIA

test.

Conict of interest: e LIA kits used in this study

were provided free of charge by their distributors. e

authors declare no other conicts of interest.

TABLE 2. Positive predictive values of dierent EIA values.

EIA value Positive LIA Negative LIA PPV

(U/mL) n n (95% CI)

>260 5 0 100% (100-100)

>250 6 2 75.0% (45.0-100)

>200 8 3 72.7% (46.4-99.0)

>150 10 9 52.6% (30.2-75.1)

>100 18 19 48.6% (32.5-64.8)

>55 28 52 35.0% (24.5-45.5)

Abbreviations: EIA= enzyme immunoassay; LIA= line immunoassay; PPV= positive predictive value; CI= condence interval

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

239

Original Article

SMJ

REFERENCES

1. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rotheld

NF, et al. e 1982 revised criteria for the classication of

systemic lupus erythematosus. Arthritis Rheum 1982;25:

1271-7.

2. Hochberg MC. Updating the American College of Rheumatology

revised criteria for the classification of systemic lupus

erythematosus. Arthritis Rheum 1997;40:1725.

3. Solomon DH, Kavanaugh AJ, Schur PH, American College

of Rheumatology Ad Hoc Committee on Immunologic Testing

G. Evidence-based guidelines for the use of immunologic tests:

antinuclear antibody testing. Arthritis Rheum 2002;47:434-44.

4. Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK,

Cancado EL, et al. International Autoimmune Hepatitis Group

Report: review of criteria for diagnosis of autoimmune hepatitis.

J Hepatol 1999;31:929-38.

5. Hennes EM, Zeniya M, Czaja AJ, Pares A, Dalekos GN, Krawitt

EL, et al. Simplied criteria for the diagnosis of autoimmune

hepatitis. Hepatology 2008;48:169-76.

6. Alarcon-Segovia D, Cardiel MH. Comparison between 3

diagnostic criteria for mixed connective tissue disease. Study

of 593 patients. J Rheumatol 1989;16:328-34.

7. Tanimoto K, Nakano K, Kano S, Mori S, Ueki H, Nishitani H,

et al. Classication criteria for polymyositis and dermatomyositis.

J Rheumatol 1995;22:668-74.

8. Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S,

Lanfranchi H, et al. American College of Rheumatology

classication criteria for Sjogren’s syndrome: a data-driven,

expert consensus approach in the Sjogren’s International

Collaborative Clinical Alliance cohort. Arthritis Care Res

(Hoboken) 2012;64:475-87.

9. van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron

M, Tyndall A, et al. 2013 classication criteria for systemic

sclerosis: an American college of rheumatology/European

league against rheumatism collaborative initiative. Ann Rheum

Dis 2013;72:1747-55.

10. Agmon-Levin N, Damoiseaux J, Kallenberg C, Sack U, Witte T,

Herold M, et al. International recommendations for the assessment

of autoantibodies to cellular antigens referred to as anti-nuclear

antibodies. Ann Rheum Dis 2014;73:17-23.

11. Blomberg S, Ronnblom L, Wallgren AC, Nilsson B, Karlsson-

Parra A. Anti-SSA/Ro antibody determination by enzyme-linked

immunosorbent assay as a supplement to standard

immunouorescence in antinuclear antibody screening. Scand

J Immunol 2000;51:612-7.

12. Bahrt KM, McCarty GA. A negative uorescent antinuclear

antibody test in a patient with Jo-1 antibody. J Rheumatol

1985;12:624-5.

13. Bayer PM, Fabian B, Hubl W. Immunouorescence assays (IFA)

and enzyme-linked immunosorbent assays (ELISA) in autoimmune

disease diagnostics--technique, benefits, limitations and

applications. Scand J Clin Lab Invest Suppl 2001;235:68-76.

14. Dahle C, Skogh T, Aberg AK, Jalal A, Olcen P. Methods of

choice for diagnostic antinuclear antibody (ANA) screening:

benet of adding antigen-specic assays to immunouorescence

microscopy. J Autoimmun 2004;22:241-8.

15. Homan IE, Peene I, Veys EM, De Keyser F. Detection of specic

antinuclear reactivities in patients with negative anti-nuclear

antibody immunouorescence screening tests. Clin Chem

2002;48:2171-6.

16. Lee SA, Kahng J, Kim Y, Park YJ, Han K, Kwok SK, et al.

Comparative study of immunouorescent antinuclear antibody

test and line immunoassay detecting 15 specic autoantibodies

in patients with systemic rheumatic disease. J Clin Lab Anal

2012;26:307-14.

17. Sener AG, Afsar I, Demirci M. Evaluation of antinuclear

antibodies by indirect immunouorescence and line immunoassay

methods’: four years’ data from Turkey. APMIS 2014;122:1167-

70.

18. Provost TT. Anti-Ro(SSA) and anti-La(SSB) antibodies in lupus

erythematosus and Sjogren’s syndrome. Keio J Med 1991;40:

72-7.

19. McCaulie DP. Cutaneous diseases in adults associated with

anti-Ro/SS-A autoantibody production. Lupus 1997;6:158-66.

20. Cimaz R, Spence DL, Hornberger L, Silverman ED. Incidence

and spectrum of neonatal lupus erythematosus: a prospective

study of infants born to mothers with anti-Ro autoantibodies.

J Pediatr 2003;142:678-83.

21. Jaeggi E, Laskin C, Hamilton R, Kingdom J, Silverman E.

e importance of the level of maternal anti-Ro/SSA antibodies

as a prognostic marker of the development of cardiac neonatal

lupus erythematosus a prospective study of 186 antibody-

exposed fetuses and infants. J Am Coll Cardiol 2010;55:2778-

84.

22. Arbuckle MR, McClain MT, Rubertone MV, Scoeld RH,

Dennis GJ, James JA, et al. Development of autoantibodies

before the clinical onset of systemic lupus erythematosus. N

Engl J Med 2003;349:1526-33.

23. Eriksson C, Kokkonen H, Johansson M, Hallmans G, Wadell

G, Rantapaa-Dahlqvist S. Autoantibodies predate the onset

of systemic lupus erythematosus in northern Sweden. Arthritis

Res er 2011;13:R30.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

240

Phadungrakwittaya et al.

Rattana Phadungrakwittaya, M.Sc.*, Sirikul Chotewuttakorn, M.Sc.*, Manoon Piwtong, B. ATM.**,

Onusa amsermsang, Ph.D.**, Tawee Laohapand, M.D., Ph.D.**, Pravit Akarasereenont, M.D., Ph.D.*,**

*Department of Pharmacology, **Center of Applied ai Traditional Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok

10700, ailand.

Identication of Apigenin and Luteolin in Artemisia

annua L. for the Quality Control

Corresponding author: Rattana Phadungrakwittaya

E-mail: rattana_phadung@hotmail.com

Received 24 August 2017 Revised 9 November 2017 Accepted 8 December 2017

ORCID ID: http://orcid.org/0000-0002-8107-4946

http://dx.doi.org/10.33192/Smj.2019.37

ABSTRACT

Objective: To identify active compounds and establish the chemical ngerprint of Artemisia annua L. for the

quality control.

Methods: in-layer chromatography (TLC) conditions were developed to screen for 2 common avonoids (apigenin

and luteolin). ree mobile phases were used to isolate these avonoids in 80% ethanolic extract of A. annua.

Hexane : ethyl acetate : acetic acid (31:14:5, v/v) and toluene : 1,4-dioxane : acetic acid (90:25:4, v/v) were used in

normal phase TLC (NP-TLC), and 5.5% formic acid in water : methanol (50:50, v/v) were used in reverse phase TLC

(RP-TLC). Chromatograms were visualized under visible light aer spraying with Fast Blue B Salt. Apigenin and

luteolin bands were checked by comparing their Rf values and UV-Vis absorption spectra with reference markers.

Results: Apigenin and luteolin were simultaneously detected with good specicity in RP-TLC condition, while

only apigenin was detected in NP-TLC condition. Apigenin band intensity was higher than luteolin band intensity

in both conditions.

Conclusion: is knowledge can be applied to the development of quality control assessments to ensure product

ecacy and consistency.

Keywords: Artemisia annua L.; TLC ngerprint; apigenin; luteolin (Siriraj Med J 2019;71: 240-245)

INTRODUCTION

Artemisia annua L., commonly known as sweet

wormwood, is an annual plant in the Asteraceae (Compositae)

family. is herb is native to Asia and throughout much

of China. It ourishes in the temperate zone, and also

grows wild in central Europe. Aqueous preparations

of dried A. annua have traditionally been used to treat

fever, malaria, skin diseases, jaundice, and hemorrhoids

in China. In ailand, A. annua has been used to treat

fever, asthma, skin disease, circulatory disorders (e.g.,

dizziness), and as an expectorant and an anthelmintic.

A. annua is also used as an herbal ingredient in some

ai herbal recipes that are published in e National

List of Essential Medicines.

Several previous studies

reported that A. annua possesses various pharmacological

activities, including antimalarial, antinociceptive, anti-

inammatory, antioxidant, anticancer, and antimicrobial

actions.

3-10

Moreover, the essential oil from this plant is

postulated to inhibit the growth of Gram-positive bacteria,

Gram-negative bacteria, and yeast, and to depress the

central nervous system.

11-13

These reported findings

support the historical claims and traditional belief that

A. annua is an eective herbal medicine for treatment of

dierent diseases. e chemical component of A. anuua

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

241

Original Article

SMJ

that makes it eective for treating the parasitic diseases

of malaria is artemisinin, a sesquiterpene lactone.

4-5

A large number of flavonoides, including apigenin,

luteolin, kaempferol, quercetin, casticin, and artemetin,

have also been reported to be present in A. annua.

14-15

Reported vital pharmacological activities eectuated by

avonoids in A. annua include antioxidant, inhibition

of immune mediators of angiogenesis, prophylactic

eects in malaria and related fevers, and antimalaria

parasite.

8,16-20

Luteolin and apigenin are flavonoids that are

commonly found in different plant species that are

associated with a broad spectrum of pharmacological

activities, including antimalarial, anti-inammatory,

antioxidant, and anticancer.

20-23

However, the ecacy

of drugs that contain avonoids can vary according to

environmental conditions and season of harvest or growth

stage.

24-26

in-layer chromatography (TLC) is currently

the method of choice for identifying a wide variety of

substance classes, because it is a simple, rapid, inexpensive,

and substances are identied visually. A new method for

simultaneously quantifying apigenin and luteolin using

reverse-phase TLC in some medicinal plants was recently

reported.

e development of a screening method that

could reliably identify the presence of apigenin and luteolin

in A. annua, and then a chromatogram ngerprint of

A. annua would facilitate quality control assessments

of harvested A. annua to ensure the reproducibility of

ingredients and the consistent ecacy of the product.

Accordingly, the aim of this study was to develop a

screening method to identify apigenin and luteolin in

A. annua, and then establish a chromatogram ngerprint

of A. annua.

MATERIALS AND METHODS

Chemicals and plant materials

All reagents used were of analytical grade. Methanol,

ethanol, and hexane were purchased from Scharlau

(Barcelona, Spain), and toluene, formic acid, and acetic

acid were purchased from Merck (Darmstadt, Germany).

Ethyl acetate was purchased from Riedel-de Haen (Seelze,

Germany), and 1, 4 dioxane was purchased from Carlo

Erba Reagents, (Val de Reuil, France). Apigenin, luteolin,

and Fast Blue B Salt were purchased from Calbiochem

(San Diego, California, USA), Extrasynthese, (Genay,

France), and Sigma-Aldrich (St. Louis, Missouri, USA),

respectively. HPTLC Silica gel 60 F

254

(NP-TLC) and TLC

Silica gel 60 RP-18 F

254S

(RP-TLC) were purchased from

Merck (Darmstadt, Germany). Pulverized aerial plant

material of A. annua, was obtained from the Manufacturing

Unit of Herbal Medicines and Products, Center of Applied

ai Traditional Medicine (CATTM), Faculty of Medicine

Siriraj Hospital, Mahidol University, Bangkok, ailand.

Instruments

The CAMAG TLC system (CAMAG Chemie-

Erzeugnisse & Adsorptionstechnik AG, Muttenz,

Switzerland) consisted of a CAMAG Linomat 5 sample

applicator, a CAMAG Automatic Developing Chamber

(ADC2), and a CAMAG TLC Scanner 3. Densitometry

documentation was performed under UV light (254 and

366 nm) and visible light using Reprostar 3 densitometer

with CCD camera. CAMAG winCATS soware was

used to control the system and analyze the data.

Preparation of standard solutions

One milligram of apigenin was dissolved in 2 milliliters

of methanol, and 1 mg of luteolin was dissolved in 1

milliliter of methanol. Stock solutions were maintained

in a refrigerator at -20°C until use.

Preparation of sample solutions

To obtain the optimal solvent for the extraction of

A. annua, three common solvents were used, including

100% methanol, 100% ethanol, and 80% ethanol. Ten

milliliters of each solvent was added to 1 gram of pulverized

aerial plant material of A. annua and sonicated for

60 minutes. e 3 mixtures were then centrifuged at

4,000 rpm for 10 minutes at 25°C. e supernatant was

separated and evaluated using the TLC systems.

TLC analysis

We employed 3 dierent mobile phase systems

– two normal-phase (NP) and one reverse-phase (RP)

TLC. e 2 NP-TLC mobile phase systems consisted

of hexane : ethyl acetate : acetic acid (31:14:5, v/v) and

toluene : 1,4-dioxane : acetic acid (90:25:4, v/v). e

RP-TLC mobile phase system consisted of 5.5% formic

acid in water : methanol (50:50, v/v). Sample volumes of

A. annua extracts applied on HPTLC and RP-TLC plates

were varied to obtain the best separation and the most

obvious chromatogram ngerprints. One microliter

(µL) of luteolin and 2 µL of apigenin were mixed and

loaded alongside the sample as markers. Development

duration was approximately 20 minutes or the solvent

migration distance was at least 7.5 cm. Developed plates

were dried in cold air for approximately 5 minutes.

Extracted chromatogram ngerprints were visualized

under both ultraviolet light (UV) (254 and 366 nm)

and visible light aer spraying with Fast Blue B Salt

(FBS). Chromatograms were further sprayed with 10%

NaOH to intensify the result. Presence of apigenin and/

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

242

Phadungrakwittaya et al.

or luteolin was determined by comparing rate of ow

(Rf) values and absorption spectra with those of their

respective markers.

RESULTS

Chromatogram ngerprints of ethanol, methanol,

and 80% ethanol extracts of the aerial part of A. annua

aer FBS staining are shown in Fig 1. Eighty percent

ethanol was determined to be the optimal extraction

solvent. Chromatogram ngerprints of A. annua extract

under UV light (254 and 366 nm) and visible light aer

FBS staining of NP-TLC and RP-TLC are shown in

Fig 2. e Rf values in NP-TLC (2 solvent systems) and

RP-TLC (1 solvent system) were 0.21, 0.24, and 0.09 for

apigenin marker, and 0.10, 0.13, and 0.15 for luteolin

marker, respectively (Fig 3, Table 1). Bands identied in

the chromatogram of A. annua using RP-TLC expressed

migration distance, color, and absorption spectrum

similar to that of apigenin and luteolin markers. Using

NP-TLC, only bands of apigenin was identied (Fig 4).

Accordingly, RP-TLC was found to be the most suitable

method for simultaneously identifying both apigenin and

luteolin in 80% ethanolic extract of A. annua. e band

intensity of apigenin was higher than that of luteolin in

both NP-TLC and RP-TLC.

Fig 1. RP-TLC chromatogram of ethanol, methanol, and

80% ethanol extracts of the aerial part of A. annua detected

under visible light aer spraying with FBS and intensication

by spraying with 10% NaOH.

Fig 2. Chromatogram ngerprint of A. annua developed in a NP-TLC plate with A) hexane : ethyl acetate : acetic acid (31:14:5 v/v);

B) toluene : 1,4-dioxane : acetic acid (90:25:4, v/v); and, C) in an RP-TLC plate with 5.5% formic acid in water : methanol (50:50, v/v).

Visualization was performed under UV light (254 and 366 nm) and visible light aer spraying with FBS.

Fig 3. Chromatograms of apigenin and luteolin in a mixed marker solution developed in a NP-TLC plate with A) hexane : ethyl acetate :

acetic acid (31:14:5, v/v); B) toluene : 1,4-dioxane : acetic acid (90:25:4, v/v); and, C) in an RP-TLC plate with 5.5% formic acid in water :

methanol (50:50, v/v). Bands were detected under visible light aer FBS staining.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

243

Original Article

SMJ

TABLE 1. Rf values of reference markers by mobile phase

Fig 4. Detection of apigenin and luteolin in A. annua under visible light aer spraying with FBS and intensication with 10% NaOH in 3

condition systems: A) 80% ethanolic extract of A. annua; B) mixed marker solution; C) absorbent overlay of apigenin marker along with

the sample; and, D) absorbent overlay of luteolin marker along with the sample.

Mobile phase Marker Plate type Rf

Hexane : ethyl acetate : acetic acid Apigenin NP-TLC 0.21

(31:14:5, v/v) Luteolin NP-TLC 0.10

Toluene : 1,4-dioxane : acetic acid Apigenin NP-TLC 0.24

(90:25:4, v/v) Luteolin NP-TLC 0.13

5.5% formic acid in water: methanol Apigenin RP-TLC 0.09

(50:50, v/v) Luteolin RP-TLC 0.15

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

244

Phadungrakwittaya et al.

DISCUSSION

Artemisinin is a potent antimalarial drug against

Plasmodium falciparum that can be found at a range of

concentration of 0.01-0.5% of dry weight of A. annua.

at study also reported for avonoid compounds in this

plant. Apigenin and luteolin were 2 of several avonoids

identied in the leaves and stems of A. annua. ese

compounds were isolated and characterized by comparing

their UV, MS, and 1H NMR spectra with the literature

and reference compounds.

Luteolin and apigenin are

reported to be associated with a broad spectrum of

pharmacological activities, including antimalarial, anti-

inammation, antioxidant, and anticancer.

20-23

in-layer

chromatography (TLC) is suitable for initial identication

of substances prior to more advanced analysis using

more sophisticated analytical instruments. e optimal

yield of apigenin and luteolin found in 80% ethanolic

extract allowed for further identication of apigenin and

luteolin in A. annua using the three mobile systems. In

this study, RP-TLC enabled simultaneous detection of

apigenin and luteolin with specicity while NP-TLC

could detect with specicity only for apigenin compound.

A previous study reported the use of RP-TLC to identify

various avonoids, including apigenin and luteolin.

However and based on our review of the literature, no

comparison has been made between the eciency of

NP-TLC and RP-TLC. Our nding showed that RP-

TLC can identify the two substances of interest and

established that RP-TLC is more suitable for detecting

the presence of apigenin and luteolin in A. annua. e

superiority demonstrated by RP-TLC over NP-TLC can

be explained by the low selectivity of NP-TLC. e UV-

Vis absorption prole of the similar in position band to

luteolin reference compound under NP-TLC condition

was not similar to that of standard. is indicates that

the band might not be free of any interference that was

present in the extract. In this study, the fact that the band

of apigenin appeared more intensely than the band of

luteolin suggests that the aerial parts of the A. annua used

in this experiment contained more apigenin than luteolin.

is result contrasts with the result of a previous study

that reported the same amount of luteolin and apigenin

isolated from ethyl acetate extract of the leaves and

stems of A. annua (0.015% on dry weight).

In addition

to dierent types of sample preparations and dierent

methods of analysis being the cause of variations in

avonoid content, variation may also be due to geographical

area, season of harvest, or phenological growth stages.

e previous study on the eects of geographical area

and polluted environment on avonoid contents in

Artemisia vulgaris and Veronica chamaedrys by using

TLC technique reported that apigenin in V. chamaedrys

was increased at the alpine regions, while the content of

quercetin 3,7,3’-trimethyl ether in A. vulgaris appeared

to be independent of altitude, but it was inuenced

positively by environmental pollution.

e study on

the seasonal variation in 15 phenolic compounds of 80%

ethanolic extract of Rhododendron tomentosum leaf

found that the quantity of all een phenolic compounds

showed signicant seasonal variation, but there was no

seasonal variation of their total sum.

e qualitative and

quantitative avonoid aglycones variations in relation to

the dierent phenological stages were also observed in

Artemisia absinthium and Artemisia vulgaris by using

HPLC. e detected avonoids in A. absinthium were

stable in their qualitativem but dierent in their contents

while the avonoid proles of A. vulgaris exhibited

qualitative and quantitative variability during the life

cycle.

CONCLUSION

is study found RP-TLC to be most suitable for

simultaneously identifying both apigenin and luteolin in

80% ethanolic extract of A. annua. is knowledge can be

applied to the development of quality control assessments

of harvested A. annua to ensure the reproducibility of

ingredients and the consistent ecacy of the product.

ACKNOWLEDGMENTS

e authors gratefully acknowledge Assoc. Prof.

Dr. Chulathida Chomchai of the Siriraj Poison Control

Center, Faculty of Medicine Siriraj Hospital, Mahidol

University for assistance with manuscript development.

e chemicals, experimentation equipment, and herbal

ingredients used in this study were provided by the

Department of Pharmacology and the Center of Applied

ai Traditional Medicine, Faculty of Medicine Siriraj

Hospital, Mahidol University.

Conict of interest: e authors hereby declare no

personal or professional conicts of interest regarding

any aspect of this study.

Funding disclosure: This study was funded by a

Chalermphrakiat Grant, Faculty of Medicine Siriraj

Hospital, Mahidol University, ailand.

REFERENCES

1. Bunyapraphatsara N, Chokchaicharoenporn O, editors.

Indigenous medicinal herbs (1). 1

ed. Bangkok: Prachachon

Press; 1996.

2. National Essential Drug List 2009, National Drug Committee,

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

245

Original Article

SMJ

Ministry of Public Health, ailand, List of Herbal Medicinal

Products A.D. 1999, 2006, 2012.

3. Mesa LE, Lutgen P, Velez ID, Segura AM, Robledo SM. Artemisia

annua L., Potential Source of Molecules with Pharmacological

Activity in Human Diseases. AJPCT 2015;3:436-50.

4. Woerdenbag HJ, Lugt CB, Pras N. Artemisia annua L.: a source

of novel antimalarial drugs. Pharm Weekbl Sci 1990;12:169-81.

5. Elfawal MA, Towler MJ, Reich NG, Golenbock D, Weathers

PJ, Rich SM. Dried whole plant Artemisia annua as an antimalarial

therapy. PLoS One 2012;7:e52746.

6. Favero Fde F, Grando R, Nonato FR, Sousa IM, Queiroz NC,

Longato GB, Zafred RR, Carvalho JE, Spindola HM, Foglio

MA. Artemisia annua L.: evidence of sesquiterpene lactones’

fraction antinociceptive activity. BMC Complement Altern

Med 2014;14:266.

7. Kim WS, Choi WJ, Lee S, Kim WJ, Dong Lee C, Sohn UD,

et al. Anti-inammatory, antioxidant and antimicrobial eects

of artemisinin extracts from Artemisia annua L. Korean J

Physiol Pharmacol 2015;19:21-27.

8. Iqbal S, Younas U, Chan KW, Zia-Ul-Haq M, Ismail M.

Chemical composition of Artemisia annua L. leaves and

antioxidant potential of extracts as a function of extraction

solvents. Molecules 2012;17:6020-32.

9. Kim MH, Seo JY, Liu KH, Kim JS. Protective eect of Artemisia

annua L. extract against galactose-induced oxidative stress in

mice. PLoS One 2014;9:e101486.

10. Appalasamy S, Lo KY, Ch’ng SJ, Nornadia K, Othman AS,

Chan LK. Antimicrobial activity of artemisinin and precursor

derived from in vitro plantlets of Artemisia annua L. Biomed

Res Int 2014;2014:215872.

11. Marinas IC, Oprea E, Chiriuc MC, Badea IA, Buleandra M,

Lazar V. Chemical composi tion and antipathogenic activity

of Artemisia annua essential Oil from Romania. Chem

Biodivers 2015;12:1554-64.

12. Bilia AR,Santomauro F,Sacco C,Bergonzi MC,Donato R.

Essential oil of Artemisia annua L.: An extraordinary component

with numerous antimicrobial properties. Based Complement

Alternat Med 2014;2014:159819.

13. Perazzo FF, Carvalho JC, Carvalho JE, Rehder VL. Central

properties of the essential oil and the crude ethanol extract from

aerial parts of Artemisia annua L. Pharmacol Res 2003;48:

497-502.

14. Yang SL, Roberts MF, O’Neill MJ, Bucar F, Phillipson JD.

Flavonoids and chromenes from Artemisia annua. Phytochemistry

1995;38:255-7.

15. Bhakuni RS, Jain DC, Sharma RP, Kumar S. Secondary metabolites

of Artemisia annua and their biological activity. Curr Sci 2001;

80:35-48.

16. Song Y, Desta KT, Kim GS, Lee SJ, Lee WS, Kim YH, et al.

Polyphenolic prole and antioxidant eects of various parts

of Artemisia annua L. Biomed Chromatogr 2016; 30:588-95.

17. Zhu XX, Yang L, Li YJ, Zhang D, Chen Y, Kostecká P, et al.

Eects of sesquiterpene, avonoid and coumarin types of

compounds from Artemisia annua L. on production of mediators

of angiogenesis. Pharmacol Rep 2013;65:410-20.

18. Ogwang PE, Ogwal JO, Kasasa S, Ejobi F, Kabasa D, Obua C.

Use of Artemisia annua L. infusion for malaria prevention:

mode of action and benets in a Ugandan community. Br J

Pharm Res 2011;1:124-132.

19. Ferreira JF, Luthria DL, Sasaki T, Heyerick A. Flavonoids from

Artemisia annua L. as antioxidants and their potential synergism

with artemisinin against malaria and cancer. Molecules 2010;

15:3135-70.

20. Lehane AM, Saliba KJ. Common dietary avonoids inhibit the

growth of the intraery throcytic malaria parasite. BMC Res

Notes 2008;1:26.

21. Funakoshi-Tago M, Nakamura K, Tago K, Mashino T, Kasahara

T. Anti-inamma tory activity of structurally related avonoids,

apigenin, luteolin and setin. Int Immunopharmacol 2011;11:

1150-9.

22. López-Lázaro M. Distribution and biological activities of the

avonoid luteolin. Mini Rev Med Chem 2009;9:31-59.

23. Patel D, Shukla S, Gupta S. Apigenin and cancer chemoprevention:

progress, potential and promise (review). Int J Oncol 2007;30:

233-45.

24. Nikolova MT, Ivancheva SV. Quantitative avonoid variations

of Artemisia vulgaris L. and Veronica chamaedrys L. in relation

to altitude and polluted environment. Act Biol Szeg 2005;49:

29-32.

25. Black P, Saleem A, Dunford A, Guerrero-Analco J, Walshe-

Roussel B,Haddad P, et al. Seasonal variation of phenolic

constituents and medicinal activities of Northern Labrador

tea, Rhododendron tomentosum ssp. subarcticum, an Inuit and

cree First Nations traditional medicine. Planta Med 2011;77:

1655-62.

26. Nikolova M, Velickovic D. Phenological variations in the

surface avonoids of Artemisia vulgaris L. and Artemisia

absinthium L. Turk J Bot 2007;31:459-62.

27. Bhandari P, Kumar N, Gupta AP, Singh B, Kaul VK. A rapid

RP-HPTLC densitometry method for simultaneous determination

of major avonoids in important medicinal plants. J Sep Sci

2007;30:2092-6.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

246

Ittipong Khemapech, Ph.D., Watsawee Sansrimahachai, Ph.D., Manachai Toahchoodee, Ph.D.

Department of Digital Technology, School of Science and Technology, University of the ai Chamber of Commerce, Bangkok 10400, ailand.

Telemedicine – Meaning, Challenges and

Opportunities

Corresponding author: Ittipong Khemapech

E-mail: ittipong_khe@utcc.ac.th

Received 20 December 2018 Revised 18 April 2019 Accepted 19 April 2019

ORCID ID: http://orcid.org/0000-0002-1155-5082

http://dx.doi.org/10.33192/Smj.2019.38

ABSTRACT

Medical service is one of the crucial policies and decent medical service is required by the population in every

country. ere are three main obstacles which prevent people from obtaining proper medical cares and treatments.

First, the deciency of medical stas especially physicians which occur even in the developed countries. Second,

regarding an important demographic issue, an increase in the number of the elderly makes the medical services

more demanding. Finally, geographical aspect also plays a major role in healthcare inequality. e population

dwelling in rural or remote areas struggle from accessing proper medical services. Information and communication

technologies have become an important infrastructure upon which several domains can build in order to achieve

more eective solutions. Integrating such technologies into the medical discipline results in telemedicine which is

currently available across the globe. is article describes telemedicine in three key aspects including current state,

challenges and opportunities based upon existing studies and implementations.

Keywords: Health monitoring; telehealth; telemedicine (Siriraj Med J 2019;71: 246-252)

Khemapech et al.

INTRODUCTION

Population has been regarded as the most valuable

asset in every country. Apart from several aspects such as

education, health-related issues are crucially responsible

for the governmental agencies in order to provide proper

medical services. ere are many obstacles to achieving such

goals including economic, demographic and geographical

points of view. Deciency of qualied medical sta

signicantly causes uncovered medical services, especially

in the developing areas. In the global point of view,

according to the currently reported density of physicians

dened as a total number per ten thousand population,

all of the countries have such ratios which are lower than

60.

Most of the African countries have the ratios which

are lower than 5. On the other hand, countries in Europe

and in North America have higher ratios. However,

higher ratio does not demonstrate an equivalent access

to the medical services in all areas. People dwelling in

rural areas experience several diculties in obtaining the

same services compared to those living in urban areas.

Such problem has been worsened by an ongoing

aging society transformation. e elderly require medical

monitoring and warning system in order to avoid feasible

injuries and losses. According to the report conducted

by the United Nations

, some key ndings have been

concluded as follows:

• e number of people aged 60 years or over is

projected to grow by 56 percent between 2015

and 2030 and will be double or approximately

2.1 billion by the year 2050.

• According to the prediction, the number of people

aged 60 years or over is expected to increase

fastest in Latin America and the Caribbean

(71 percent), followed by Asia (66 percent),

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

247

Review Article

SMJ

Africa (64 percent), Oceania (47 percent), Northern

America (41 percent) and Europe (23 percent).

• e ratio of the elderly aged 80 years or over is

predicted to increase from 14 percent in 2015

to over 20 percent in 2050.

• Aging society transformation is occurring faster

in urban areas than in rural areas.

• e growth of aging society in many developing

countries is currently faster than that occurred

in developed countries.

Both requirements on deciency of medical personnel

and aging society transformation can be realized as a key

driver on leveraging health and well-being strategies in

order to provide decent and proper medical services to

the whole population.

Computer hardware and soware technologies have

been playing a major role in introducing automated systems

from which several domains such as medical aspect can

benet from. Several benets include increasing operation

reliability, accuracy and eciency, which results from

the computer system. Furthermore, communication

technologies tackle the services which mainly rely on

the physical distances and other environmental impacts.

People in the rural or dicult areas are thus able to access

medical services.

Leveraging computer-related technologies onto

medical disciplines has been conducted and the outcome

was initially one part of the “Health Telematics”. An

international Group Consultation on World Health

Organization (WHO)’s Telemedicine Policy in relation

to the Development of the Health-for-All Strategy in

the 21

Century was established and assembled in 1997.

e denition of telemedicine is accordingly proposed

as follows.

“Telemedicine is the delivery of health care services, where

distance is a critical factor, by all health care professionals

using information and communications technologies for

the exchange of valid information for diagnosis, treatment

and prevention of disease and injuries, research and

evaluation, and for the continuing education of health

care providers, all in the interests of advancing the health

of individuals and their communities.”

Telemedicine can be determined as an integration

of several components including information and

communication technologies, hardware and soware

technologies and medical services operating together in

order to provide required features or services to users

as shown in Fig 1. e underlying technologies are seen

as a black box to the users and they are responsible for

facilitating processes of each proposed service.

Information and communication technologies have

been regarded as a key infrastructure for facilitating data

exchange among relevant parties located at dierent

locations. Several domains deploy both technologies in

order to make their services more accessible. With recent

advancement in hardware and soware technologies,

Fig 1. Concept of telemedicine which consists

of several components. Medical services deploy

digital technology to provide more ecient

services regardless of distance and time.

Information and communication technologies

play a major role as an underlying infrastructure.

Hardware and soware technologies can be

considered as a medical service provider via

several features. e technologies are black

box to users.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

248

multimedia can be delivered via the Internet in real-time.

Such breakthrough enables the communications between

physicians or medical sta and patients or their family

members. Preliminary diagnosis and corresponding

medical consultancy can be performed and delivered.

Hence, the patients do not always need to personally

meet their physicians.

Apart from tackling distance limitation by

communication technology, a computerized system is

implemented and deployed in order to facilitate operational

procedures. Several components are developed and

work together. For example, mobile or web applications

consisting of several features are developed for both

physician and patient sides. Captured photos by the

patients via their mobiles are stored in the database

server and retrieved later by the physicians. In case of

emergency, the medical sta interrogate the patients or

the caregivers through the applications, then diagnose

and provide rst-aid suggestions online. Furthermore,

telemedicine can be used as a learning tool where the

physicians around the globe discuss and exchange their

opinions. Both distance and time limitations are therefore

overcome by telemedicine.

is article focuses on the telemedicine regarding

as an application of information and communication

technologies to the medical disciplines. Key issues

including its challenges and opportunities based upon

existing case studies are addressed. e remaining parts

of this article are organized as follows: current state of

telemedicine focusing on aging society is given in Section 2.

Section 3 outlines key challenging issues on telemedicine

based upon existing applications. Several opportunities

of telemedicine system deployment are addressed in

Section 4. Finally, conclusions are provided in Section 5.

Current state of telemedicine

Telemedicine is regarded as an integration of medical

services and information and communication technologies.

Underlying computer-based technologies can be pictured

as medical service delivery channels. Hence, several

existing medical services benet from such technologies

in order to tackle various limitations. is section focuses

on addressing current state of telemedicine application,

especially to aging society domain.

Telemedicine has been deployed or of interest in many

regions including developed countries

and developing

countries.

5,6

A wide range of medical services is currently

provided via telemedicine such as telelaboratory service,

telehealth education and ambulance.

e elderly normally

experience several common health issues such as chronic

health conditions, cognitive health and mental health

which make ability to move or travel to hospital become

more dicult, impractical or sometimes impossible.

e elderly have become one of the major target groups

for telemedicine. Remote medical diagnosis, care and

treatment can be performed at the elderly’s houses or

nearby hospitals via telemedicine. Not only providing

remote medical services, telemedicine also gives the

elderly a feeling of reassurance and safety.

A study based upon in-depth review and interview

outlines current state and future trends in telemedicine

application to aging society in Europe.

According to

the ndings, both devices and their associate services

are categorized into several generations. Basic services

using ordinary sensors such as alarm system including

safety and security monitoring

are in the rst generation

whereas detectors and tracking devices are in the second

generation. More advanced devices which use more than

one technology and provide additional functions are

in the third generation. More complex services such as

monitoring, consultation, diagnostic and tele-education

are found in the third generation. Furthermore, key trends

include medical services based upon mobile devices,

personal digital assistants, interactions between devices

and prediction.

Like other countries, ailand is transforming into an

aging society. According to the latest information, current

ratio of the population aged 60 or over is approximately

17%.

Moreover, in 2017, a physician and a nurse are

responsible for taking care of 1,843 and 405 ai people,

respectively.

In order to increase an opportunity for

ai people for obtaining medical and health services with

equality, eHealth strategy for 2017 – 2026 is outlined by

the Ministry of Public Health.

Regarding the strategy,

eHealth development in ailand has four phases as

follows:

• Investing and building a foundation for eHealth

development phase which is planned to take

1 year and 6 months.

• eHealth inclusion phase aims at involving all

sector of ailand to eHealth operations. is

phase is planned to spend 5 years.

• eHealth transformation phase aims to leverage

digital innovation to propose innovative medical

services. It is estimated to take 10 years to achieve

such goal.

• eHealth leadership phase to creating real economic

value in public health system and to provide

good quality of life to ai people. is big step

will take 20 years.

Even telehealth or telemedicine is also one of the

focused components as described in the strategy, it requires

Khemapech et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

249

Review Article

SMJ

underlying information and communication technologies

for delivering reliable medical services. eHealth foundations

are essential and thus rstly operated. Furthermore, several

plans for developing eHealth applications are based upon

the survey conducted in 2009. In case of telemedicine,

major barriers to implementing solutions include lack

of legal policies/regulation, organizational culture not

supportive, competing priorities, lack of knowledge of

applications and lack of technical expertise. In summary,

four information is required to support telemedicine

development including cost, infrastructure, legal and

ethical issues and patients’ perception.

ere are two approaches to implementing telemedicine.

e rst one is to join the existing communities. ailand

has been associated with the Telemedicine Development

Center of Asia (TEMDEC) since 2005. e rst hospital

that joined telemedicine program is Siriraj Hospital.

As of 2017, in total 144 programs have been recently

conducted in ailand. Moreover, most of the program

associations are conducted in Bangkok. Endoscopy and

surgery are the two main activities which performed via

telemedicine.

e other scheme is building our own

system. Even eHealth foundations development is in

progress, over 30 applications have been built by the

Ministry of Public Health and launched for public use.

Most of them provide useful health-related information

such as rst aid, medical institutions and diseases.

Challenges

Telemedicine has been recently deployed in many

countries both developed and developing ones. Like

other system applications, several challenges have been

arisen and they are outlined in this section. In total 5 key

issues based upon economic, technological and social

sides together with some existing studies are described.

• System Development Cost – Apart from the

required medical issues, enabling the population

especially those dwell in remote or developing

areas to benefit from the information and

communication technologies generates additional

costs. Such requirement can be considered as

a key policy in the 21

century

and it needs

to be driven by the government.

Both technologies

are core infrastructure and a large amount of budget

is required to invest in necessary computer

equipment and developing tools.

Hardware

and software installation and maintenance

together with qualied manpower and knowledge

transfer demonstrate one-time and periodic

investment.

• System Implementation – Several parties within

and across institutes are involved in an

implementation of telemedicine services.

other domains, telemedicine implementation

is not only technological but also managerial

prospects. Prior to implementing a telemedicine

project, several issues including technological

and societal aspects have to be carefully considered.

As telemedicine services are built upon existing

digital technologies, developing teams are normally

required to understand the underlying infrastructure

and the users’ requirements. Advancement in

digital technologies including hardware and

soware has been occurring and they are utilized

for transformation in several domains in order

to yield better solutions and competitive

advantages. Developing tools and devices have

been created and continuously improved to

conform to the latest advancement. e system

developers are always expected to properly select

and use the tools and the devices in order to

develop the next generation of telemedicine

solutions which conform to the requirements.

Moreover, obtaining precise requirements are

challenging as they need proper communication

and collaboration skills between groups of people

with different expertise and background.

Telemedicine aects traditional medical care

processes and several social concerns may arise. Key

concerns including legal, regulatory, security

and human resources issues together with

successful implementation of the telemedicine

services are addressed.

11,14

Building a telemedicine

service is therefore not only about completing

the system implementation but also about the

impacts of system utilization.

• Digital Literacy – is issue mostly aects the

elderly as they were born before the “digital

disruption” age where most systems or services

are integrated with the digital technology. Unlike

the following generations that digital technology

has become one of the major parts of their lives,

the elderly has to learn how to use some devices

such as smartphone and interact with applications

such as health technology-based applications.

Results show that the users aged over 65 years

old produce lower success rate and higher error

on assigned computer-based tasks compared to the

younger ones.

Several studies on technology

acceptance by the elderly including stakeholders’

perspectives, factors inuencing technology

and dynamics in technology have been conducted.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

250

According to survey on digital technology usage,

71 percent of the elderly aged over 65 years access

the Internet every day or almost every day.

Moreover, 27 and 18 percent of them own tablet

or e-book reader and smartphone, respectively.

Telemedicine service may build upon some existing

applications or has its own applications. erefore,

the user uses its services via several devices.

• Digital Technology Acceptance – Even digital

technology has been integrated to many activities

in our daily lives, some people including the

elderly still do not accept it regarding several

issues such as privacy and security.

8,11

A large

number of rms such as banks are developing

their own nancial services on web or mobile

applications in order to decrease operation

costs. Several campaigns or privileges are oered

to persuade their customers to go online. However,

dierent realization may be observed in the

healthcare domain. First, health-related personal

data is required to be securely transmitted over

digital networks and accurately destined to

predened receivers. Second, additional devices

such as wearable devices capable of measuring

heart rate or blood pressure are deployed to

sense and transmitted the measurements to the

receiving nodes. Such devices’ performance

especially their accuracy compared to standard

medical equipment is one of the major concerns.

Scope of the offering telemedicine services

should thus be concisely dened for the users’

accurate understandings.

4,8

Under some

circumstances, telemedicine can be used as a

monitoring tool for early detection and warning.

Hence, devices available in the market can be used.

Results indicate acceptance of telemedicine

to improve quality of care in rural areas and

during emergency situations.

• Diagnostic Accuracy – Accuracy of the diagnosis

is one of the key concerns especially when the

physicians and the patients are at dierent locations.

Face-to-face medical care usually brings condence

to patients, especially the elderly.

However,

a short period of medical interrogation and vital

sign measurement performed at a hospital may

not reect current symptoms due to the white

coat syndrome.

Physicians may obtain more

accurate results by applying continuous health

monitoring based upon electronic healthcare

approach. Several studies have been undertaken

in order to investigate the diagnostic accuracy of

the telemedicine applied to the emergency

department and ophthalmology.

19,20

e results

demonstrate telemedicine as a viable alternative

to the in-person and a valuable tool where medical

service is in high demand.

Opportunities

Most countries have been experiencing deciency of

physicians and aging society transformation. Population

dwelling in remote or developing areas tends to have lower

opportunities of decent medical care than those residing in

an urban or developed areas. Such limitations worsen the

situations especially in an emergency where urgent help

is needed. Telemedicine can be used to deliver medical

services regardless of distance and time via information

and communication technologies. Several studies and

reviews of applying telemedicine in developing countries

have been undertaken.

21-24

is section outlines feasible

opportunities of telemedicine.

• Cost Reduction – One of the main objectives of

digital technology integration is to provide

better services at lower cost. In case of telemedicine,

several operation costs such as traveling can be

reduced as the patients are able to get medical

services online. Several results indicate cost

eectiveness of telemedicine compared to other

methods.

25-27

Telemedicine can thus be considered

as an alternative diagnosis and treatment methods

in several cases. For example, it can be used

for the rst diagnosis or an emergency to provide

an urgent help. Moreover, hospitals benet from

applying telemedicine. Hospital bed or space

occupancy and resource utilization can be

improved as patients receive medical cares at

any places and anytime.

• Preventive Medicine Promotion – People sometimes

have symptoms which can be prevented. One

of the key benets of practicing preventive medicine

is to decrease feasible illnesses. It can be conducted

by several levels ranging from the governmental

agencies to individuals.

Health monitoring

concept together with telemedicine are the

main driver of applying preventive medicine.

In order to obtain the real-time vital sign readings,

wearable devices available in the market can be

used to sense and transmit the readings to the

medical sta.

Preliminary diagnosis and following

procedures are performed by using telemedicine.

Possible illnesses can thus be prevented or found

at an early stage.

• Medical Education – Most countries are still

Khemapech et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

251

Review Article

SMJ

experiencing the lack of medical staff and

specialists. Remote areas do not have professionals

to provide specic medical cares or treatments.

Such problems are worsened in case of emergency.

Apart from being a medical treatment platform,

telemedicine can be used as a continuing medical

education where medical sta and professionals

meet, learn and exchange their knowledge

and experiences. Successful cases of telemedicine

as an education platform are reported.

30,31

Sessions

can be conducted at any convenient sites where

attendees gather and participate an assigned

workshop.

• Healthcare Equality – Limitations of distance and

time are tackled by the information and

communication technologies. Telemedicine is

built on top of such technologies in order to

provide medical services. People around the

world can therefore access the services as soon as

they are connected to the Internet. Medical services

are not only delivered by local physicians.

Professionals residing at other areas can provide

diagnoses and treatments. Local or novice physicians

are capable of learning from medical specialists.

In order to achieve healthcare equality, collaboration,

regulation and standardization are required.

Governmental agencies and private institutes

have to cooperate and agree upon a set of

requirements. Regarding the digital technologies

related issues, several predened standards such

as communication protocols can be adopted.

• Service Diversity – With an advancement of

recent digital technology, data delivery and

processing are considerably improved. Instead of

basic data type, multimedia streaming over

the Internet is now more ecient. Processing

power is also remarkably increased while the

hardware price is continually decreased. Such

improvements support a variety of medical services

and enable real-time applications. A variety

of telemedicine services such as tele-pathology,

tele-dermatology, tele-nursing and tele-surgery

and their performance acceptance are addressed.

e key consideration on oering new service

is to select a set of suitable tools and technologies.

CONCLUSION

Two major indices reecting good quality of life are

healthiness and access to decent medical services. Lack

of medical personnel, demographical and geographical

problems are significant barriers of medical service

improvement. Telemedicine can be applied to aging society

transformation which causes higher demand of remote

medical care and treatment.Telemedicine is ocially dened

by the World Health Organization (WHO) as the delivery

of health care services where distance is a critical factor.

Major challenges of telemedicine utilization include system

development cost, system implementation, digital literacy,

digital technology acceptance and diagnostic accuracy.

Building a telemedicine service requires information

and communication technologies as the underlying

infrastructure. System integration needs some specialists

who can address users’ requirements and develop the

required system. Users’ acceptance of technology is

crucial to acquiring the advantages of telemedicine. A

revision of generated results is essential in order to avoid

diagnostic errors. Several opportunities of telemedicine

include cost reduction, preventive medicine promotion,

medical education, healthcare equality and service

diversity. Studies show that telemedicine signicantly

reduces cost of treatment as hospital visit is no longer

necessary. Regarding cost issues, not only the patients

but also the medical institutes benet from telemedicine.

Moreover, telemedicine facilitates health monitoring

and thus promotes preventive medicine. Knowledge

and experience transfer and exchange are feasible via

telemedicine. Medical personnel and corresponding services

are thus improved, and it is possible for the population

to have an equality in medical services. Finally, a variety

of medical services is observed, and additional services

can be oered due to technological advancement.

Telemedicine has been realized by many countries

as major tool to delivering decent and improved medical

services with equality. It is therefore included in national

healthcare strategies outlined by several nations. In

order to achieve the same operating standards, all of the

relevant parties have to involve and make agreements.

Telemedicine consists of several systems connected by

universally pre-dened data formats and protocols.

Making all medical institutes follow such formats will

denitely be time-consuming as some of them have

their own formats. Standard protocols have to be also

applied. Hence, telemedicine is not only building the new

system but also adjusting the legacy systems. Apart from

technological issue, several aspects must be taken into

consideration including economical and societal ones.

Inaccurate diagnosis and personal data leakage lead to

legal and ethical issues. Proper preparation and operating

procedures are signicantly required to successfully

apply telemedicine.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

252

REFERENCES

1. Who.int [Internet].Global health observatory data repository –

medical doctors [updated 2017; cited 2019Apr14] Available

from http://apps.who.int/gho/data/node.main HWFGRP_

0020?lang=en.

2. Un.org [Internet]. World population ageing [updated 2015; cited

2019 Apr 13]. Available from http://www.un.org/en/development/

desa/population/publications/pdf/ageing/ WPA2015_Report.

pdf.

3. Who.int [Internet]. A health telematics policy [updated 1997;

cited 2019 Apr 13]. Available from http://apps.who.int/iris/

bitstream/handle/10665/63857/WHO_DGO_98.1.pdf?

sequence=1&isAllowed=y.

4. Pacitaproject.eu [Internet]. Telecare technology for an ageing

society in Europe – current state and future developments

[updated 2013; cited 2019 Apr 13]. Available from http://www.

pacitaproject.eu/wp-content/uploads/2012/11/Telecare-

description-web.pdf.

5. Ganapathy K, Chawdhry V, Premanand S, Sarma A, Chandralekha

J, Kumar KY, et al. Telemedicine in the Himalayas: operational

challenges – a preliminary report. Telemed J E Health 2016;22:

821-35.

6. Chandwani RK, Dwivedi YK. Telemedicine in India: current

state, challenges and opportunities, Transforming Government:

People. Process and Policy 2015;9:393-400.

7. Rogers H, Madathil KC, Agnisarman S, Narasimha S, Ashok A,

Nair A, et al. A systematic review of the implementation

challenges of telemedicine systems in ambulances. Telemed J

E Health 2017;23:707-17.

8. Bujnowska-Fedal MM, Grata-Borkowska U. Use of telemedicine-

based care for the aging and elderly: promises and pitfalls.

Smart Homecare Technology and TeleHealth. 2015;8:91-105.

9. ailandometers.mahidol.ac.th [Internet]. ailandometers

[updated 2019 Apr 12; cited 2019 Apr 12]. Available from

http://www.thailandometers.mahidol.ac.th.

10. Social.nesdb.go.th [Internet]. e number of ai populations

per medical sta 1994 – 2017 [updated 2018 Nov 5; cited

2019 Apr 13] Available from http://social.nesdb.go.th/ SocialStat/

StatReport_Final.aspx?reportid=662&template=1R2C&year

type=M&subcatid=18

11. Moph.go.th [Internet]. eHealth strategy 2017 – 2026 [updated

2017 Aug; cited 2019 Apr 13] Available from https://ehealth.

moph.go.th/index.php/resources/dra-ehealth-strategy-ministry-

of-public-health-2016-2021?download=7:eng.

12. Shimizu S, Kudo K, Tomimatsu S, Moriyama T, Moriyama T,

Sadakari Y, et al. International telemedicine activities in ailand.

Siriraj Med J 2018;70:471-5.

13. Moph.go.th [Internet]. MoPH Application [cited 2019 Apr 10].

Available form https://www.moph.go.th/index.php/home/

app_moph.

14. Paho.org [Internet]. Framework for the implementation of

a telemedicine service [updated 2016; cited 2019 Apr 13].

Available fromhttp://iris.paho.org/xmlui/bitstream/handle/

123456789/28414/9789275119037_eng.pdf;sequence=1.

15. Sebastian Peek. Understanding technology acceptance by older

adults who are aging in place: a dynamic perspective, Ph.D.

esis, Tilburg University, 2017.

16. Pewresearch.org [Internet]. Older adults and technology use

[updated 2014; cited 2019 Apr 13]. Available from http://www.

pewresearch.org/wp-content/uploads/sites/9/ 2014/04/PIP_

Seniors-and-Tech-Use_040314.pdf.

17. Thomas GP, Christian AB, Suzanne KP, Renald L. Social

acceptance and population condence in telehealth in Quebec. B

MC Health Services Research 2015;15:72.

18. Briana C, Kelly H-Zolnierek, Krista H. White coat hypertension:

improving the patient-health care practitioner relationship,

Phychol Res Behav Manag 2015;8:133-41.

19. Izzo JA, Bhat R, Blumenthal J, Homan D, Watson J, et al.

Diagnostic accuracy of a rapid telemedicine encounter in the

emergency department. Ann Emerg Med 2017; 70(4):S127-S128.

20. Ausayakhun S, Skalet AH, Jirawison C, Keenan JD, Khouri C,

Nguyen K, et al. Accuracy and reliability of telemedicine for

diagnosis of cytomegalovirus retinitis. Am J Ophthalmol 2011;

152:1053-8.

21. Carlo C, Gabriele P, Giuseppe P. Telemedicine for developing

countries – a survey and some design issues. Appl Clin Inform

2016;7:1025-50.

22. Who.int [Internet]. Telemedicine – Opportunities and developments

in member states [updated 2010; cited 2019 Apr 13]. Available

from http://www.who.int/goe/publications /goe_telemedicine_

2010.pdf.

23. Aparajita D, Soumya D. Telemedicine: a new horizon in public

health in India. Indian J Community Med 2008;33:3-8.

24. Richard W, Nivritti GP, Richard ES. Telehealth in the developing

world. Royal Society of Medicine Press Ltd. London; 2009.

25. Connectwithcare.org [Internet]. Assessment of the feasibility

and cost of replacing in-person care with acute care telehealth

services [updated 2014; cited 2019 Apr 13]. Available from

http://www.connectwithcare.org/wp-content/uploads/2014/12/

Medicare-Acute-Care-Telehealth-Feasibility.pdf.

26. Agha Z, Schapira RM, Maker AH. Cost eectiveness of telemedicine

for the delivery of outpatient pulmonary care to a rural population.

Telemed J E Health 2002;8:281-91.

27. Stensland J, Speedie SM, Ideker M, House J, ompson T.

e relative cost of outpatient telemedicine services. Telemed

J 1999;5:245-56.

28. Clarke EA. What is preventive medicine? Can Fam Physician

1974;20:65-68.

29. Leelaloetphanit W, Leelaloetphanit W, Srikhuanjai K, Chomanan

P, Khemapech I. UbiNurSS on Mobile: a ubiquitous nursing

support system on mobile devices, Proceedings of the 5

IIAI

International Congress on Advanced Applied Informatics,

2016.p.71-76.

30. Randriambelonoro M, Bagayoko CO, Geissbuhler A. Telemedicine

as a tool for medical education: a 15-year journey inside the

RAFT network. Ann N Y Acad Sci 2018;1434:333-341.

31. Michael AER, Michael PC, Peter WC, Mary G. e use of

telemedicine for delivering continuing medical education in

rural communities. Telemedicine and e-Health 2005; 11:124-9.

32. Hassibian MR, Hassibian S. Telemedicine Acceptance and

Implementation in Developing Countries: Benets, Categories,

and Barriers. Razavi International Journal of Medicine [Internet].

Kowsar Medical Institute; 2016 Aug 21 [cited 2019 Apr 13];4(3).

Available from: http://dx.doi.org/10.17795/rijm38332.

Khemapech et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

175

Original Article

SMJ

Surachai Siripornadulsilp, M.D.*, Nisit Tongsiri, M.D.**

*Division of Surgery, Khon Kaen Hospital, Khon Kaen 40000, **Division of Surgery, Sakon Nakhon Hospital, Sakon Nakhon 47000, ailand.

Managing Difcult Cannulations in Endoscopic

Retrograde Cholangiopancreatography:

A Prospective Randomized Control Trial Study of

Precut Needle Knife Sphincterotomy versus

Transpancreatic Sphincterotomy Technique

Corresponding author: Surachai Siripornadulsilp

E-mail: siripornadulsilp@gmail.com

Received 5 October 2018 Revised 15 February 2019 Accepted 18 February 2019

ORCID ID: http://orcid.org/0000-0002-7917-4024

http://dx.doi.org/10.33192/Smj.2019.27

ABSTRACT

Objective: To evaluate the success rate of cannulations and rate of procedure-related complications between needle

knife sphincterotomy (NKS) and transpancreatic sphincterotomy (TPS) techniques, and to evaluate the most eective

cannulation time to proceed with NKS or TPS.

Methods: is study recruited 52 patients with inaccessible bile ducts by the standard cannulation at Khon Kaen

Hospital from May 2012 to May 2015. Patients were randomly allocated to the NKS group (N=21) or the TPS group

(N=21). Successful cannulations, and complications between NKS and TPS were collected and assessed.

Results: Successful cannulations by TPS and NKS were achieved in 14 cases (53.8%) and 13 cases (50%) respectively

(p value = 0.781). Post ERCP pancreatitis was found in 2 cases using TPS, and in 3 cases using NKS. ere were

3 cholangitis cases in TPS group, and 2 cholangitis cases in NKS group. Perforations were found in 3 cases and 1

case in TPS and NKS group, respectively. ere were 4 deaths in this study, one case in TPS group and 3 cases in

NKS group. Complications and mortality between TPS and NKS were not statistically signicant (P>0.05). Aer

40 minutes of the ERCPs, there was less chance for a successful cannulation. Unsuccessful cannulations between

TPS and NKS was not statistically dierent according to the Kaplan-Meier analysis.

Conclusion: TPS and NKS are able to increase successful cannulations. ere are no signicant dierences in the

cannulation success rate and rate of complications between the TPS and NKS. e appropriate time to terminate

a cannulation in dicult cases is found to be 40 minutes.

Keywords: ERCP; Transpancreatic precut sphicterotomy; needle knife sphicterotomy; dicult cannulation; time

for successful cannulation (Siriraj Med J 2019;71: 175-180)

INTRODUCTION

Endoscopic retrograde cholangiopancreatography

(ERCP) is challenging endoscopic procedure which has a

long learning curve. ERCP operators need to perform 180

ERCPs under supervision to achieve a 70-80% successful

cannulation.

A successful cannulation is dened as the

passing guide wire from the duodenal papilla to the

common bile duct which is the key to success in the

ERCP procedure.

2,3

According to a study of the outcomes

of ERCP at Khon Kaen Hospital, the success rate for

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

176

cannulations using the standard cannulation technique at

Khon Kaen Hospital was 78%.

is success rate was low

in comparison with expert ERCP centers which have a

successful cannulation rate of 90-95%.

erefore, Khon

Kaen Hospital has to increase its successful cannulation rate

in ERCP by using a special technique to overcome dicult

cannulations. ere are many cannulation techniques

to deal with dicult cannulations such as precut needle

knife sphicterotomy, transpancreatic sphicterotomy

technique, needle knife stulotomy, and endoscopic

ultrasound-guide cholangiography.

3,6

At Khon Kaen Hospital, we are familiar with the

needle knife sphicterotomy (NKS) technique and the

transpancreatic sphicterotomy (TPS) technique. NKS has

been used to overcome dicult cannulations by many

institutions for a long time with evidence of an increasing

successful cannulation rate to 92-96.9%

7-9

, and TPS, a

newer technique, described by Go in 1995

, has also

been used by ERCP operators with 72.5-97.3% cannulation

success rate.

11-15

According to previous studies, the

procedural related complications in NKS and TPS were

10-24.2%

7-9

and 11.1-5.8%

11,15

respectively. ere were

several studies that evaluated successful cannulation rates

and complication rates between NKS and TPS techniques.

e randomized controlled trial from Catalano et al.

demonstrated higher a successful cannulation rate in

TPS than with NKS while the complication rate was the

same; a study from Lee et al.

showed a similar successful

cannulation rate and complication rate between TPS

and NKS. erefore, the use of NKS or TPS to achieve

a successful cannulation rate is still being debated.

ere are several studies stating that prolonged a

cannulation time was associated with an increased rate

of post-ERCP pancreatitis (PEP).

17-20

Therefore, the

appropriate cannulation time should be balanced between

successful cannulation rates and complications, so the

most eective cannulation time to increase the chances

of a successful cannulation should be investigated.

e objectives of this study are to evaluate successful

cannulation rates and procedures related to complications

between the NKS and TPS techniques; to evaluate the

most eective required time for proceeding with either

NKS or TPS in an attempt to increase the chances of a

successful cannulation.

MATERIALS AND METHODS

is study was approved by Khon Kaen Hospital Ethics

Committee (issue number 56/01/2555) and registered in the

ai Clinical Trials Registry (TCTR number 20150224003).

Patients who had been treated with ERCP procedure at

the Endoscopic Unit, Department of Surgery, Khon Kaen

Hospital during May 2012 to May 2015 were recruited

into the study. All of the patients were treated with

ERCP by the rst author (S. Siripornadulsilp). Patients

with unstable vital sign, post-sphincterotomy patients,

patients with gastric outlet obstructions, and patients

with surgically altered anatomy were excluded. ere

were 286 patients who did not meet the exclusion criteria

and participated in the study. All the participants gave

informed consent before undergoing ERCP. Of the 286

participants, 52 had dicult cannulations which were

dened as lasting more than 10 minutes in attempting

to cannulate aer visualization of ampulla of Vater, or

there were more than three unintended pancreatic duct

cannulations.

e patients with dicult cannulation

conditions were randomly allocated to either the NKS

or the TPS group by sealed envelopes. ere were 26

patients in each group. NKS was dened as using a

needle-knife, specically a MicroKnife XL 5.5F, Boston

Scientic, El Coyol, Alajuela, Costa Rica, to perform an

incision at the upper margin of the papilla orice toward

the direction of bile duct until the underlying biliary

sphincter was visualized. TPS was dened as cutting

the septum between the pancreatic duct and bile duct

by sphicterotome toward the direction of the bile duct

aer selective cannulation of the pancreatic duct.

In our institution, ERCP patients were given intravenous

prophylactic antibiotic 15 minutes before the ERCP

procedure. e videoduodenoscopes were Olympus TJF

140, Olympus TJF 140R, Fujinon EO-250XT5, Olympus

TJF130, and Olympus TJF150. e patients were given

2% lidocaine viscus as a local anesthetic agent. During

ERCP, the patient’s vital signs and oxygen saturation

were monitored with a pulse oximetry by endoscopic

nurses. Aer ERCP, the patients were sent to the surgical

ward for observation for at least 24 hours. In this study,

a successful cannulation was dened as the insertion of a

sphincterotome to the common bile duct.

e ERCP-

related complications were dened as the “consensus

criteria” described by Cotton et al

; PEP was abdominal

pain with an increase in serum amylase of more than

three times the normal upper limit 24 hours aer ERCP.

Post-ERCP cholangitis was dened as abdominal pain

with fever of more than 38 degree Celsius that lasted

more than 24 hours aer ERCP and a demonstration of

obstructive jaundice in a liver function test. Hemorrhage

was clinical evidence of bleeding with a hemoglobin drop

of more than 2 g/dL. Perforation was the presence of

uid leakage or contrast media in the abdominal cavity

or retroperitoneal cavity during ERCP procedures or

from imaging studies.

Siripornadulsilp et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

177

Original Article

SMJ

e characteristics of the participants was demonstrated

with descriptive statistic. e Chi-square test and the

Fisher exact test were used in comparing categorial data

between NKS and TPS. e eective required time for

a successful cannulation was estimated by the Kaplan-

Meier method.

RESULTS

Baseline characteristics of the patients are shown

in Table 1.

ere was no dierence in the baseline characteristics

between the TPS patients and NKS patients. (Table 2)

ere was no dierence in successful cannulations

and procedural related complications between the TPS

and NKS patients. In this study, there were 4 procedural

related mortality cases. e indications for ERCP in these

patients were 2 CBD stone cases and 2 malignancy cases.

ere were 3 death cases in the NKS group and 1 death

case in TPS group. e causes of death are described in

Table 3.

ere were 51 patients of 52 patients that had complete

cannulation time data. e cannulation time was not

recorded in one patient. e patients were allocated and

treated with TPS or NKS according to the study protocol.

e median survival time (the median cannulation time)

was 30 minutes, and the 95% condence interval was 6.8-

53.2 minutes. e majority of successful cannulations were

in the rst 30 minutes. ere were only a few successful

cannulations aer 40 minutes as only one successful

cannulation occurred in the 40

to 60

minute of the

cannulation.

Fig 2 shows a comparison of non-successful

cannulations between TPS and NKS by using the Kaplan-

Meier method. Aer the 20

minute, there were 15 cases

in TPS group and there were 13 cases in the NKS group

who did not have successful cannulations. Aer the 40

minute, there were 6 cases in the TPS group and 8 cases

in NKS group that did not have successful cannulations.

e unsuccessful cannulations between TPS and NKS

showed no statistical signicance.

TABLE 1. Baseline characteristics of the patients between the TPS and NKS group.

Characteristics

TPS NKS

P-value

(N=26) (N=26)

Gender

Female N (%) 11 (42.3) 18 (69.2) 0.05*

Male N (%) 15 (57.7) 8 (30.8)

Age

Mean (SD) 61 (11.3) 59.6 (15.5)

Median (Min-Max) 61.5 (36-82) 61 (21-85)

Diabetes mellitus N (%) 5 (19.2) 6 (23.1) 1.00**

Hypertension N (%) 4 (15.4) 3 (11.5) 1.00**

IH N (%) 1 (3.8) 0 (0) 1.00**

CBD stone N (%) 6 (23.1) 9 (34.6) 0.36*

Biliary stricture N (%) 4 (15.4) 2 (7.7) 0.67**

Malignancy N (%) 16 (61.5) 14 (53.8) 0.58*

Bile Leakage N (%) 0 (0) 1 (3.8) 1.00**

*P-value from Chi-square test, **P-value from sher exact test

Abbreviations: IH = Ischemic heart disease, CBD = Common bile duct, TPS = transpancreatic sphicterotomy, NKS = needle knife

sphicterotomy

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

178

TABLE 2. Successful cannulation and complications between TPS and NKS group.

Techniques

TPS NKS

P-value

(N =26) (N =26)

Successful cannulation N (%) 14 (53.8) 13 (50) 0.78*

Complications

Pancreatitis N (%) 2 (7.7) 3 (11.5) 1.00**

Cholangitis N (%) 3 (11.5) 2 (7.7) 1.00**

Perforation N (%) 3 (11.5) 1 (3.8) 0.61*

Bleeding N (%) 0 (0) 0 (0) NA

Hypoxia N (%) 0 (0) 1 (3.8) 1.00**

Subcutaneous emphysema N (%) 1 (3.8) 0 (0) 1.00**

Death N (%) 1 (3.8) 3 (11.5) 0.61*

*P-value from Chi-square test, **P-value from sher exact test

Abbreviations: NA = Not applicable, TPS = transpancreatic sphicterotomy, NKS = needle knife sphicterotomy

TABLE 3. Causes of death.

Case Age Indication Technique Complication

1 41 CBD stone TPS Pancreatitis

2 57 CBD stone NKS Cholangitis

3 47 Malignancy NKS Pancreatitis and perforation

4 74 Malignancy NKS Pancreatitis and cholangitis

Abbreviations: CBD = Common bile duct, TPS = transpancreatic sphicterotomy, NKS = needle knife sphicterotomy

Fig 1. Kaplan-Meier Curve of All Patients.

Fig 2. Kaplan-Meier Curve of TPS and NKS.

Siripornadulsilp et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

179

Original Article

SMJ

DISCUSSION

In this study, successful cannulations in dicult

cannulation cases between TPS and NKS were the same

as the result of the previous study from Lee et al.

e

procedural related complications between TPS and NKS

were similar as the previous studies from Lee et al.

Catalano et al.

, and Zang et al.

Although TPS was

not shown to be better than NKS in increasing the rate

of successful cannulations, both cannulation techniques

could increase the rate of successful cannulations in

dicult cannulation cases. In this study, there were

286 participants who met the inclusion criteria and

52 (18.2%) of them were dicult cannulation cases.

According to the results of this study, for TPS and NKS,

each technique could increase the cannulation rate by

at least 50%; therefore, these techniques could raise

successful cannulation rates in ERCP patients in our

institution to over 90%. e crossover of TPS and NKS

techniques was reported to improve the nal successful

cannulation rates to 95.3%

; however, this study did not

decide to evaluate TPS and NKS in a crossover regime.

Although the successful cannulations and complications

between TPS and NKS were not statistically dierent,

there were more procedural related deaths in the NKS

group; moreover, technically, it is relatively easy to

perform pancreatic duct cannulations

16,25

and there is

no special instrument and additional time for placing

special instruments for TPS while NKS needs special

instruments such as a needle-knife (MicroKnife XL) and

additional time to place the needle-knife to the ampulla.

As a result, TPS is a more attractive method to overcome

dicult cannulation in comparison with NKS. However,

according to the European Society of Gastrointestinal

Endoscopy (ESGE), clinical guideline for papillary

cannulation and sphincterotomy techniques at ERCP,

in dicult cannulation cases that had no unintentional

pancreatic guide wire insertion, the initial technique

that should be used to overcome dicult cannulation

is NKS.

e most common complications in this study

were PEP and cholangitis. In this study, PEP occurred in

7.7% and 11.5% in the TPS and NKS groups respectively,

the rate of PEP was comparable with the rate of PEP in

the previous study from Lee et al.

which reported a

10.7% PEP occurrence in the TPS group and 5.3% in

the NKS group, while Zang et al.

reported 9.6% and

10.5% of PEP in the TPS and NKS group respectively.

In this study, the rate of cholangitis was 11.5% and 7.7%

in TPS and NKS respectively. e cholangitis rate was

high in comparison with the study from Lee et al.

which reported a cholangitis rates of 3% in TPS and no

cholangitis in NKS. In the study from Catalano et al.,

there was no reported cholangitis as a procedural

related complication.

e high rate of cholangitis in

this study might be due to the high incidence of hilar

cholangiocarcinoma in northeastern ailand.

erefore,

the rate of palliative biliary drainage for malignant cases

was also high. According to previous studies, palliative

endoscopic biliary drainage for hilar cholangiocarcinoma

was responsible for a high rate of cholangitis, ranging

from 8.8-40.7%.

28-31

e second objective of this study is to dene the most

eective required time for proceeding with either NKS

or TPS to increase the rate of successful cannulations. In

this study, the majority of successful cannulations were

in the rst 30 minutes. ere was only one successful

cannulation occurred in the 40

to 60

minute of the

cannulation. However, we did not evaluate the correlation

between increasing cannulation time and ERCP-related

complications.

CONCLUSION

In this study, both TPS and NKS increased successful

ERCP cannulations, but there was no dierence in successful

cannulations and procedural-related complications

between TPS and NKS. ere was little chance to make

a successful cannulation aer the 40

minute before a

cannulation.

ACKNOWLEDGMENTS

We would like to thank Greg Lamphear for his help

with editing and formatting this article.

REFERENCES

1. Jowell PS, Baillie J, Branch MS, Aronti J, Browning CL Bute

BP. Quantitative assessment of procedural competence. A

prospective study of training in endoscopic retrograde

cholangiopancreatography. Ann Intern Med 1996;125:983-9.

2. Baron TH, Peterson BT, Mergener K, Chak A, Cohen J, Deal

SE, et al. Quality indicators for endoscopic retrograde

Cholangiopancreatography. Gastrointest Endosc 2006;63:

S29-S34.

3. Qayed E, Reid AL, Willingham FF, Keilin S, Cai Q. Advances

in endoscopic retrograde cholangiopancreatography cannulation.

World Journal of Gastrointest Endosc 2010;2:130-7.

4. Siripornadulsilp S, Tongsiri N, Wongrach L, Piriyakarnon A,

Reangwannasak S, Tipsunthonsak N. Outcomes of Endoscopic

Retrograde Cholangiopancreatography in 942 cases. KKMJ

2011;35:35-39.

5. Huibregtse K. Complications of endoscopic sphincterotomy

and their prevention. N Engl J Med 1996;335:961-3.

6. Udd M, Kylanpaa L, Halttunen J. Management of dicult bile

duct cannulation in ERCP. World J Gastrointest Endosc

2010;2:97-103.

7. Gullichen R, Lavonius M, Laine S, Gronroos J. Needle knife

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

180

assisted ERCP. Surg Endosc 2005;19:1243-5.

8. Kasmin FE, Cohen D, Batra S, Cohen SA, Siegel JH. Needle knife

sphincterotomy in a tertiary referral center: efficacy and

complications. Gastrointest Endosc 1996;44:48-53.

9. Miao L, Li QP, Zhu MH, Ge XX, Yu H, Wang F, et al . Endoscopic

transpancreatic septotomy as a precutting techinque for dicult

bile duct cannulation. World J Gastroenterol 2015;21:3978-82.

10. Go JS. Common bile duct pre-cut sphincterotomy: transpancreatic

sphincter approach. Gastrointest Endosc 1995;41:502-6.

11. Kahaleh M, Tokar J, Mullick T, Bickston SJ, Yeaton P. Prospective

evaluation of pancreatic sphicterotomy as a precut technique

for biliary cannulation. Clin Gastroenterol Hepatol 2004;

2:971-7.

12. Kapetanos D, Kokozidis G, Christodoulou D, Mistakidis K,

Dimakopoulos K, Katodritou E, et al. Case series of transpancreatic

septotomy as precutting technique for difficult bile duct

cannulation. Endoscopy 2007;39:802-6.

13. Weber A, Roesch T, Pointner S, Born P, Neu B, Meining A,

et al. Transpancreatic precut sphincterotomy for cannulation

of inaccessible common bile duct: a safe and successful technique.

Pancreas 2008;36:187-91.

14. Halttunen J, Keranen I, Kylanpaa L. Pancreatic sphincterotomy

versus needle knife precut in dicult biliary cannulation. Surg

Endosc 2009;23:745-9.

15. Lee YJ, Park YK, Lee MJ, Lee KT, Lee KH, Lee JK, et al.

Dierent Strategies for Transpancreatic Septotomy and Needle

Knife Infundibulotomy Due to the Presence of Unintended

Pancreatic Cannulation in Dicult Billiary Cannulation. Gut

Liver 2015;9:534-9.

16. Catalano MF, Linder JD, Geene JE. Endoscopic transpancreatic

papillary septotomy for inaccessible obstructed bile ducts:

Comparison with standard pre-cut papillotomy. Gastrointest

Endosc 2004;60:557-61.

17. Borges AC, Almeida PC, Furlani SMT, Cury MS, Pleskow.

ERCP performance in a tertiary Brazilian center: focus on new

risk factors, complications and quality indicators. Arq Bras

Cir Dig 2018;31:e1348.

18. Funatsu E, Masuda A, Takenaka M, Nakagawa T, Shiomi

H, Yoshinaka H, et al. History of Post-Endoscopic Retrograde

Cholangiopancreatography Pancreatitis and Acute Pancreatitis

as Risk Factors for Post-ERCP Pancreatits. Kobe J Med Sci

2017;63:E1-E8.

19. Wang P, Li ZS, Liu F, Ren Xu, Lu NH, Fan ZN, et al. Risk

factors for ERCP-related complications: a prospective multicenter

study. Am J Gastroenterol 2009;104:31-40.

20. Sofuni A, Maguchi H, Mukai T, Kawakami H, Irisawa A, Kubota

K, et al. Endoscopic pancreatic duct stents reduce the incidence

of post-endoscopic retrograde cholangiopancreatography

pancreatitis in high-risk patients, Clin Gastroenterol Hepatol

2011; 9:851-8.

21. Laohavichitra K, Akaraviputh T, Methasate A, Leelakusolvong S,

Kachinton U. Comparison of early pre-cutting vs standard

technique for biliary cannulation in endoscopic retrograde

cholangiopancreatography: A personal experience. World J

Gastroenterol 2007;13:3734-7.

22. Baron TH, Peterson BT, Mergener K, Chak A, Cohen J, Deal SE,

et al. Quality indicators for endoscopic retrograde

Cholangiopancreatography. Gastrointest Endosc 2006;101:

892-7.

23. Cotton PB, Lehman G, Vennes J, Geenen JE, Russel RCG,

Meyers WC, et al. Endoscopic sphincterotomy complications

and their management: An attempt at consensus. Gastrointest

Endosc 1991;37:383-93.

24. Zang J, Zhang C, Gao J. Guidewire-assisted transpancreatic

sphincterotomy for dicult biliary cannulation: a prospective

randomized controlled trial. Surg Laparosc Ensosc Percu Tech

2014;24:429-33.

25. Yoo YW, Cha SW, Lee WC, Kim SH, Kim A, Cho YD. Double

guidewire technique vs transpancreatic precut sphincterotomy

in dicult biliary cannulation. World J Gastroenterol 2013;19:

108-14.

26. Green A, Uttaravichien T, Bhudhisawadi V, Chartbanchahai

W, Elkins DB,Marieng EO, et al. Cholangiocarcinoma in

North East ailand. Trop Geogr Med 1991;43:193-8.

27. Riesco-Lopez JM, Vazquez-Romero M, Rizo-Pascual JM,

Rivero-Fernandez M, Manzano-Fernandez R, Gonzalez-Alonso

R, et al. Ecacy and safety of ERCP in a low-volume hospital.

Rev Esp Enferm Dig (Madrid) 2013;105:68-73.

28. de Palma G. D, Galloro G, Siciliano S, Iovino p, Catanzano

C. Unilateral versus bilateral endoscopic hepatic duct drainage

in patients with malignant hilar biliary obstruction: results

of a prospective, randomized, and controlled study. Gastrointest

Endosc 2001;53:547-53.

29. Pisello F, Geraci G, Modica G, Sciume C. Cholangitis prevention

in endoscopic Klatskin tumor palliation: air cholangiography

technique. Langenbeck Arch Surg 2009;394:1109-14.

30. Walter T, Ho CS, Horgan AM, Warkentin A, Gallinger S, Greg

PD, et al. Endoscopic or percutaneous biliary drainage for

klatskin tumors. J Vasc Interv Radiol 2013;24:113-21.

Siripornadulsilp et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

181

Original Article

SMJ

Varut Lohsiriwat, M.D., Ph.D.

Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ailand.

Mosapride Reduces Prolonged Postoperative Ileus

after Open Colorectal Surgery in the Setting of

Enhanced Recovery after Surgery (ERAS):

A Matched Case-Control Study

Corresponding author: Varut Lohsiriwat

E-mail: bolloon@hotmail.com

Received 15 November 2018 Revised 1 April 2019 Accepted 5 April 2019

ORCID ID: http://orcid.org/0000-0002-2252-9509

http://dx.doi.org/10.33192/Smj.2019.28

ABSTRACT

Objective: To evaluate the eects of mosapride, a selective 5-hydroxytryptamine-4 agonist, on gastrointestinal

recovery in patients undergoing open colorectal surgery.

Methods: A prospectively collected database of the patients undergoing elective ‘open’ colorectal resection under

enhanced recovery aer surgery (ERAS) from May 2013 to April 2017 was reviewed. From April 2016, mosparide

was routinely given from postoperative day 1 to discharge date. Eighty-four patients receiving mosapride were

matched to 168 control patients (historical comparison with a ratio of 1:2). Surgical outcomes and postoperative

gastrointestinal recovery was compared.

Results: e patient characteristics were comparable except more patients in control group had perioperative

administration of NSAIDs. e mosapride group had a 1.5% higher compliance rate of ERAS protocol. e control

group had higher incidences of prolonged postoperative ileus (17.3% vs 7.1%; p=0.029) and prolonged postoperative

ileus requiring nasogastric tube decompression (8.9% vs 3.6%; p=0.19). Overall complication, clinical intestinal transit

and length of hospitalization were not signicantly dierent between groups. However, the patients with prolonged

postoperative ileus had signicantly prolonged hospitalization (p<0.001). Median length of hospital stay was 4 days

(IQR 4-5) in those without prolonged ileus (n=217), 5 days (IQR 5-6) in those with prolonged ileus without a need

of gastric decompression (n=17) and 10.5 days (IQR 7-14.5) in those with prolonged ileus requiring nasogastric

tube decompression (n=18) (p<0.001). A multivariate analysis showed that administration of mosapride was only

a protective factor for prolonged postoperative ileus (OR=0.37, 95% CI=0.15-0.93, p=0.029).

Conclusion: Postoperative administration of mosapride reduced the incidence of prolonged postoperative ileus

aer open colorectal surgery.

Keywords: Mosapride; postoperative ileus; colon; rectum; enhanced recovery aer surgery; ERAS; prokinetic drug;

prevention (Siriraj Med J 2019;71: 181-188)

INTRODUCTION

Postoperative ileus (POI) is a physiologic hypomotility

of the gastrointestinal tract occurring immediately

aer major abdominal or non-abdominal surgery. e

pathophysiology of POI is multifactorial and complex. It

is known to be associated with inammatory, neurological

and hormonal responses to surgery.

Prolonged POI

refers to this gastrointestinal dysfunction continuing

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

182

Lohsiriwat

past the expected timeframe – usually beyond 3 days

aer laparoscopic abdominal surgery and 5 days aer

open abdominal surgery.

Prolonged POI is one of the

most frequent and challenging complications following

colorectal surgery especially open procedure

because it

was associated with increased hospital cost and length

of hospital stay.

Patients with POI were also more likely

to develop other postoperative complications and to be

readmitted.

e incidences of prolonged POI following

colorectal surgery vary widely depending on the denition

and cut-o limit.

For example, a recent French cohort

of colorectal patients undergoing surgery with enhanced

recovery aer surgery (ERAS) program showed the rate

of prolonged POI ranged from 10% for a cut-o of 5

days to 40% for a cut-o of 3 days.

Since treatment options for prolonged POI are limited,

several methods of preventing or minimizing POI have

been advocated such as laparoscopic surgery

, epidural

analgesia

, administration of selective cyclooxygenase-2

inhibitors

, and ERAS pathway.

Regarding pharmacological

intervention, various prokinetic drugs such as

metoclopramide, erythromycin and cisapride have

been used to improve postoperative gastrointestinal

motility. In a systematic review of the aforementioned

agents, only cisapride showed a signicant reduction in

POI.

However, cisapride – a 5-hydroxytryptamine-4

(5-HT4) receptor agonist – was withdrawn from the

market worldwide because it caused potentially lethal

cardiac arrhythmia via its high anity blockade of cardiac

potassium channel.

Mosapride citrate (mosapride) is another prokinetic

drug that selectively activates 5-HT4 receptors on the

eerent cholinergic neurons of the gastrointestinal tract,

leading to increased acetylcholine release and hence

increased bowel contraction – without cardiac side eects.

Mosapride has been shown to reduce the duration of

POI aer hand-assisted laparoscopic colectomy

and

laparoscopic colectomy.

However, its eect on POI aer

open colorectal surgery has not been assessed especially

in the setting of ERAS pathway. e aim of the present

study was therefore to evaluate whether mosapride reduced

the incidence of prolonged POI and shorten the duration

of gastrointestinal recovery aer open colectomy and/

or proctectomy.

MATERIAS AND METHODS

Patients

is was a review of prospectively collected database

of patients undergoing elective ‘open’ segmental resection

(colectomy and/or proctectomy) within an ERAS pathway

from May 2013 to April 2017 in the Faculty of Medicine

Siriraj Hospital, Mahidol University, ailand. Patients

with clinical peritonitis or acute colonic obstruction were

excluded. e study was approved by the institutional

ethics committee (Si 014/2013) and written informed

consent was obtained from each patient.

ERAS protocol and pharmacologic intervention

All of the studied patients were operated on and

treated by a board-certified colorectal surgeon (the

author) who has applied an ERAS pathway into colorectal

surgery since 2010. ERAS strategies in our institute

were adopted from the ERAS society recommendations

for perioperative care in elective colorectal surgery.

14,15

Some details of our ERAS program have been described

previously.

9,16-18

Briey, a practice of perioperative pain

control with a preferential use of non-opioid analgesia,

mechanical bowel preparation for le-sided colon and

rectal surgery, prophylactic antibiotic regimen, prophylaxis

of postoperative nausea and vomiting, selective use of

diverting stoma aer colorectal anastomosis, no insertion

of nasogastric tube (NGT), early enteral feeding and

immediate mobilization was standardized. ere was

no postoperative administration of laxative and other

prokinetic drugs except ondansetron and/or metoclopramide

for treating postoperative nausea and vomiting. Of note,

from 1 April 2016 mosparide (mosapride citrate 15 mg;

about 0.75 USD/tablet) was routinely given to every

patient three times a day on postoperative day 1 until the

patients were discharged. ere is no signicant change

in our ERAS protocol during the study period except

the routine postoperative administration of mosapride

from April 2016.

If patients met the criteria of prolonged POI (dened

systematically by the combination of at least two of the

following ve criteria on or aer the fourth operative

day: nausea or vomiting, abdominal distension, inability

to tolerate oral diet over 24 hours, absence of gas or stool

passing over 24 hours, and radiological evidence of ileus)

rescue agents such as intravenous metoclopramide and/

or suppository bisacodyl would be given for reducing

the duration of ileus. For patients with vomiting and

distention, the placement of NGT was performed to

provide symptomatic relief. e NGT was placed until

patients had decreased drainage volume - together with

clinical or radiological improvement. Patients would be

discharged from the hospital if they had no fever, good

appetite, satisfactory gastrointestinal recovery and a good

level of ambulation. All of the patients were scheduled

for follow-up at 7-10 days and 30 days aer an operation.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

183

Original Article

SMJ

Data collection

Data including patient characteristics, operative details,

and postoperative outcomes were prospectively collected.

Patient characteristics included age, gender, body mass

index (BMI), American Society of Anesthesiologists (ASA)

grade, ColoRectal Physiological and Operative Severity

Score for the enUmeration of Mortality and Morbidity

(CR-POSSUM) score

, and preoperative nutritional

status based on the subjective global assessment (SGA).

Operative details included type of operation and operative

time. Overall ERAS protocol compliance of each case was

determined based on the ERAS society recommendations

for perioperative care in elective colorectal surgery.

14,15

Postoperative outcomes included postoperative

complications (graded I-V according to the Clavien-

Dindo classication system)

, time to global resumption

of intestinal transit (dened as interval from surgery to

the tolerance of solid food intake in association with

passage of stool)

, the incidence of prolonged POI (as

aforementioned criteria)

, the length of postoperative

stay, death and readmission within 30 days aer the

operation. Impact of prolonged POI on postoperative

hospitalization was also determined.

Sample size calculation

For 1-to-2 comparison, a minimum sample size

of 81 patients in mosapride group and 162 patients in

control group was estimated to show a 50% reduction in

the incidence of prolonged POI with a power of 90% and

a signicance level of 0.05.

Sample size calculations were

based on a recent prospective study in France

indicating

that 39.6% of patients undergoing colorectal surgery

within an ERAS protocol experienced prolonged POI

using the clinical denition of prolonged POI purposed

by Vather et al.

We calculated the sample size based

on this French study because a well-established ERAS

pathway was fully applied in this French university

hospital - like ours. Patients receiving mosapride were

matched with historical control patients on potentially

confounding factors for prolonged POI such as age,

co-morbidity, site of operation (colon vs rectum), stoma

formation and extension of surgical treatment.

Statistical analysis

All statistical analyses were performed using the

PASW Statistics soware (SPSS version 18.0 for Windows,

Illinois, USA). Continuous variables were expressed as

mean ± standard deviation or median (interquartile;

IQR), and were compared using the Student t-test or

Mann-Whitney U test. Categorical data were expressed as

number (percentage) and were compared using the Pearson

Chi-square test or Fisher exact probability test. Factors

potentially associated with or protective of prolonged

POI were analyzed using a univariate analysis. Only

signicant variables from the univariate analysis were

included in a multivariate model of logistic regression

(forward stepwise logistic regression analysis), and the

odds ratio with 95% condence intervals (95% CI) for

each variable was determined. A p-value of <0.05 was

considered statistically signicant.

RESULTS

Aer case-matching from a database of 305 cases,

252 patients were included - 84 in the mosapride group

and 168 in the historical control group (Fig 1). Patient

characteristics were comparable except more patients in

control group had perioperative administration of NSAIDs,

and mosapride group had a 1.5% higher compliance

rate of ERAS protocol (Table 1). Overall complication,

global resumption of intestinal transit and length of

hospitalization were not signicantly dierent between

the two groups (Table 2). However, the control group

had more incidence of prolonged POI and prolonged

POI requiring NGT insertion (17.3% vs 7.1%; p=0.029

and 8.9% vs 3.6%; p=0.19), respectively. Clinical factors

associated with prolonged POI were shown in Table 3.

A multivariate model of logistic regression showed that

postoperative administration of mosapride was only

a protective factor for prolonged POI (OR=0.37, 95%

CI=0.15-0.93, p=0.029).

Fig 1. Flow diagram of participant enrollment and analysis.

ere was no patient refusing consent to receive the drug or excluding

from analysis

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

184

Lohsiriwat

TABLE 1. Patient’s characteristics and intraoperative parameters.

Mosapride Control P-value

(n=84) (n=168)

Age, year 62.4 ± 12.9 64.1 ± 11.8 0.306

Male 44 (52.4) 95 (56.5) 0.531

BMI, kg/m

22.6 ± 4.1 22.9 ± 4.1 0.630

ASA class ≥ 3 13 (15.5) 42 (25.0) 0.084

CR-POSSUM predictive mortality, % 1.90 (1.30-2.60) 1.83 (0.98-2.58) 0.426

Hematocrit, % 37.4 ± 5.7 36.8 ± 5.4 0.335

Preoperative malnutrition

16 (19.0) 46 (27.4) 0.148

Previous laparotomy 7 (8.3) 13 (7.7) 0.869

Previous abdominal/pelvic irradiation 6 (7.1) 8 (4.8) 0.437

Cancer surgery 79 (94.0) 152 (90.5) 0.334

Tumor staging ≥ 3 41 (51.9) 89 (57.4) 0.422

Rectal surgery 47 (56.0) 93 (55.4) 0.929

Stoma creation 16 (19.0) 33 (19.6) 0.910

Major multi-organ resection

4 (4.8) 15 (8.9) 0.315

Detailed procedure 0.930

(Extended) right hemicolectomy 13 (15.5) 26 (15.5)

(Extended) left hemicolectomy 9 (10.7) 8 (4.8)

Sigmoidectomy 13 (15.5) 36 (21.4)

Hartmann procedure 7 (8.3) 16 (9.5)

(Sub) total colectomy 2 (2.4) 6 (3.6)

(Low) anterior resection 34 (40.5) 65 (38.7)

Abdominoperineal resection 6 (7.1) 11 (6.5)

Epidural analgesia 22 (26.2) 41 (24.4) 0.758

Duration of surgery, minute 184 ± 57 189 ± 77 0.577

Blood loss, mL 120 (50-200) 150 (100-250) 0.090

Perioperative administration of NSAIDs 34 (40.5) 91 (54.2) 0.040*

Total IV morphine consumption, mg/kg 0.43 (0-0.71) 0.26 (0.01-0.79) 0.964

Overall ERAS protocol compliance

###

, % 83.6 ± 4.4 82.1 ± 4.7 0.010*

*P-value < 0.05

Values are expressed as mean ± standard deviation, median (interquartile range) or number (percentage).

Malnutrition was dened as subjective global assessment (SGA) class B and class C.

Major multi-organ resection excluded the resection of appendix, gallbladder, ovaries and fallopian tubes, small bowel, and part of urinary

bladder (partial cystectomy).

###

Overall compliance of each patient was determined based on the ERAS® society recommendations for perioperative care in elective

colorectal surgery.

Abbreviations: ASA = American society of Anesthesiologists, BMI = body mass index, CR-POSSUM = ColoRectal Physiological and

Operative Severity Score for the enUmeration of Mortality and Morbidity, ERAS = enhanced recovery aer surgery, NSAIDs = non-steroidal

anti-inammatory drugs

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

185

Original Article

SMJ

TABLE 2. Postoperative outcomes.

Mosapride Control P-value

(n=84) (n=168)

Prolonged POI 6 (7.1) 29 (17.3) 0.029*

Prolonged POI requiring NGT insertion 3 (3.6) 15 (8.9) 0.193

Overall complication 12 (14.3) 34 (20.2) 0.249

Serious complication

4 (4.8) 8 (4.8) 1.000

Time to off intravenous uid, days 2 (2-3) 2 (2-3) 0.412

Global resumption of intestinal transit, days 3 (2-3.5) 3 (2-4) 0.868

Length of hospitalization, days 4 (4-5) 4 (4-5) 0.474

30-day readmission 1 (1.2) 7 (4.2) 0.275

*P-value < 0.05

Values are expressed as number (percentage) or median (interquartile range).

Serious complication was dened as the Clavien-Dindo classication of surgical complication grade III-V. Mosapride group had 4 patients

with serious complications as following: intraabdominal collection requiring reoperation, adhesive small obstruction requiring relaparotomy,

upper gastrointestinal bleeding requiring endoscopic intervention, and distal duodenal obstruction requiring endoscopic management.

Control group had 8 patients with serious complications as following: anastomotic leakage (3) requiring reoperation, pelvic collection

requiring percutaneous drainage, anastomotic bleeding requiring endoscopic clipping, upper gastrointestinal bleeding requiring endoscopic

intervention, and life-threatening congestive heart failure (1) and liver failure (1) requiring intensive care unit management.

Abbreviations: NGT = nasogastric tube, POI = postoperative ileus

TABLE 3. Clinical factors associated with prolonged postoperative ileus (PPOI).

No PPOI PPOI P-value Odds ratio

(n=217) (n=35) (95% CI)

Serious complication

8 (3.7) 4 (11.4) 0.068 3.37 (0.96-11.86)

ASA ≥ 3 44 (20.3) 11 (31.4) 0.138 1.80 (0.82-3.96)

ERAS compliance > 80% 117 (53.9) 15 (42.9) 0.224 0.64 (0.31-1.32)

Administration of NSAIDs 111 (51.2) 14 (40.0) 0.221 0.64 (0.31-1.32)

Administration of mosapride 78 (35.9) 6 (17.1) 0.029* 0.37 (0.15-0.93)

*P-value < 0.05

Values are expressed as number (percentage).

Serious complication was dened as the Clavien-Dindo classication of surgical complication grade III-V.

Abbreviations: ASA = American society of Anesthesiologists, ERAS = enhanced recovery aer surgery, NSAIDs = non-steroidal anti-

inammatory drugs

e length of hospitalization in patients with prolonged

POI was signicantly longer than those without such a

condition (p<0.001). Median length of postoperative stay

was 4 days (IQR 4-5) in those without prolonged POI

(n=217), 5 days (IQR 5-6) in those with prolonged POI

without a requirement of NGT decompression (n=17),

and 10.5 days (IQR 7-14.5) in those with prolonged

POI requiring NGT decompression (n=18) – which was

signicantly dierent between groups (Fig 2).

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

186

Lohsiriwat

Fig 2. Association between postoperative ileus and length of

hospitalization.

Abbreviations: NGT = nasogastric tube, POI = postoperative ileus

DISCUSSION

Prolonged POI is one of the most common problems

aer intra-abdominal surgery especially open laparotomy.

Since treatment options for prolonged POI are limited,

preventive measures of POI such as multimodal analgesia

application of ERAS pathway

and administration of

prokinetic drugs are essential.

12,13

is study demonstrated

that within an ERAS pathway postoperative administration

of mosapride reduced the incidence of prolonged POI aer

open colorectal surgery. To the best of our knowledge, this

is the rst clinical study examining the benecial eects

of mosapride on bowel function following open colorectal

operation – aer its favorable eects on shortening

time to gastrointestinal recovery have been shown in

hand-assisted laparoscopic colectomy and laparoscopic

colectomy for colon cancer.

12,13

Mosapride is a relatively new prokinetic drug available

in Asian countries such as Japan and ailand. It is a highly

selective 5-HT4 receptor agonist facilitating acetylcholine

release from the enteric cholinergic neurons within

myenteric and submucosal plexus. It has been shown to

accelerate gastric emptying rate

, shorten small bowel

transit

, stimulate colonic motility

and augment rectal

contraction.

Interestingly, in a recent animal study

mosapride has been shown to exert anti-inammatory

eects on the muscular wall of gastrointestinal tract

aer intestinal manipulation and therefore dramatically

inhibit POI.

Unlike other 5-HT4 receptor agonists

such as cisapride and tegaserod, mosparide has no eect

on cardiac potassium channels, dopamine receptors or

other 5-HT receptors thus resulting in a high prole of

safety.

Several prokinetic agents have been used to prevent

or reduce POI. Among the most common drugs used

are cisapride and metoclopramide. An animal study

comparing the prokinetic activities of mosapride with

these two drugs showed that all agents promoted gastric

emptying but only mosapride enhanced small bowel and

large bowel motility in a dose-response relationship.

another animal model, electrointestinography was used

to measure intestinal motility aer jejunocecostomy. e

authors found that bowel motility signicantly reduced

following surgery. However, in the treated group with

mosapride (daily for 5 days aer surgery), the contractile

amplitude of the small intestine was signicantly higher

than in the controls indicating that mosapride could

overcome the decline of intestinal motility aer bowel

anastomosis.

So far, there have been several animal

and human studies supporting the administration of

mosapride for facilitating bowel movement or reducing

POI aer gastrointestinal surgery.

12,13,27,28

e present study showed that patients receiving

mosapride had a lower incidence of prolonged POI and

a less requirement of NGT decompression for treating

prolonged POI. However, we failed to demonstrate a

faster time to global resumption of intestinal transit

(time to tolerance of solid food intake and passage of

stool aer an operation) in the mosapride group. e

reason for the absence of a signicant dierence in

gastrointestinal recovery between groups could be partly

explained by that an ERAS pathway markedly shortens

time to postoperative gastrointestinal recovery especially

in patients with high compliance

– like our patients. Also,

the sample size calculation of this study was based on the

hypothesis that mosapride could reduce an incidence of

prolonged POI by half - not based on time to tolerate

solid food or rst bowel movement. An ability to tolerate

solid food or passing stool may indicate only gastric and

rectal emptying and not necessarily the function of the

entire gastrointestinal tract. Given the limitations of

these individual endpoints, we used a combination of

clinical and radiologic grounds for dening prolonged

POI as our primary endpoints.

It could be argued that a lower incidence of prolonged

POI in mosapride group was associated with a slightly higher

compliance of ERAS protocol since ERAS compliance ≥

85% was shown to be a protective factor for prolonged

POI.

In our univariate analysis, high ERAS compliance,

perioperative use of NSAIDs and administration of

mosapride were associated with a lower incidence of

prolonged POI. However, in a multivariate analysis the

postoperative administration of mosapride was only

factor associated with a decrease in the incidence of

prolonged POI.

e benecial eects of mosapride on postoperative

gastrointestinal recovery in this study (open colorectal

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

187

Original Article

SMJ

surgery) were in line with the ndings of 2 randomized

control trials (minimally invasive surgery for colon cancer)

by Narita et al

and Toyomasu et al.

In addition to

a decreased incidence of prolonged POI by mosapride

in the present study, the two prospective clinical trials

revealed that mosapride reduced the duration of POI

(i.e. a faster time to rst bowel movement). It is worth

noting that the present study was conducted within

a full ERAS setting whereas the two trials were not -

since the scheme of early oral feeding was not applied.

Moreover, colorectal operations for malignancy and benign

diseases were included in the present study whereas only

patients with colon cancer were included in the others.

Notably, in all studies mosapride citrate (15 mg tablet

three times a day) was given from postoperative day 1

until patients were discharge or a maximum period

of 7-10 days.

12,13

It is interesting to determine whether

preoperative administration of mosapride will further

facilitate postoperative gastrointestinal recovery.

This study revealed that patients experiencing

prolonged POI had a signicantly longer postoperative

stay (e.g. 4 days in no prolonged POI vs 10.5 days in

prolonged POI requiring NGT) - which could aect

patient’s quality of life and increase in-hospital expense.

Since the overall incidence of prolonged POI in this

study was lower than we expected, the eect of POI on

length of hospitalization may be not clearly seen between

the study groups. However, prolonged POI remains a

challenging clinical reality for achieving early discharge in

the ERAS setting. Even in a European university hospital

with well-established ERAS protocol, the incidence

of prolonged POI requiring NGT decompression was

as high as 24.7% and the median length of hospital

stay increased from 5 days to 13 days if prolonged POI

occurred.

We acknowledge that other pharmacological

interventions such as perioperative administration of

the opioid receptor antagonist alvimopan (12 mg before

surgery and 12 mg twice daily until discharge) could

reduce POI but this drug is more expensive (63 USD

per 12 mg capsule) than mosapride tablet (0.75 USD per

tablet).

Chewing gum, a cheaper intervention, may be

a safe and well tolerated method to reduce POI but the

degree of improvement is small and of limited clinical

signicance.

is study has two major strengths. First, all patients

were operated on by single colorectal surgeon under a

well-established ERAS program. Moreover, there is no

signicant change in the ERAS protocol during the study

period except the routine postoperative administration

of mosapride from April 2016. It could suggest that a

decreased incidence of prolonged POI in the intervention

group is a direct eect of prokinetic drug administration

- as shown in our analysis. Second, the criteria for a

diagnosis of prolonged POI were dened and sample size

was appropriately calculated. A matched case-control

analysis was also used in this study.

However, some limitations of this study needed to be

addressed. First, it is non-randomized trial which could

lead to risk of bias. However, using the validated criteria

of prolonged POI and matched case-control analyzing

a prospectively collected database with well-established

ERAS protocol could in part cover the drawback of

non-randomized study and may reect more realistic

estimates of treatment outcomes. We acknowledge that

a prospectively randomized controlled trial is a better

way to study the eect of this prokinetic drug and the

present study could allow for a power analysis to dene an

appropriately-sized trial in the future. Second, only clinical

grounds and radiologic evaluation on or aer the fourth

operative day were used for diagnosing prolonged POI.

Ones could argue that other denitions of prolonged POI

and sophisticated methods of assessment e.g. intraluminal

pressure and migration of radiopaque markers may be used.

Since it is clear that a ‘standard’ denition and diagnosis

of prolonged POI remains elusive

, we used a widely-

accepted and validated clinical denition of prolonged

POI based on a recent systematic review and global survey

in 2013 due to its simplicity and reproducibility.

ird,

we recruited only patient undergoing open colorectal

surgery. Whether the benecial eect of mosapride on

postoperative gastrointestinal recovery will be evident in

other intraabdominal operations needs to be examined.

In conclusion, although laparoscopic surgery has become

a standard operation for colorectal diseases in many

countries, open laparotomy remains a common approach

in some regions of the world especially in the developing or

underdeveloped areas. Consistent with the ndings from

laparoscopic colon surgery

12,13

, this study demonstrated

that postoperative administration of mosapride reduced

the incidence of prolonged POI aer open colorectal

surgery. is prokinetic drug could potentially become

a part of ERAS protocol to reduce postoperative ileus.

ACKNOWLEDGMENTS

The author would like to thank Mr. Suthipol

Udompunthurak from Clinical Epidemiology Unit,

the Oce for Research and Development, Faculty of

Medicine Siriraj Hospital, for his kind assistance with

statistical analysis.

Conict of Interest: e author declares that he has no

completing interest.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

188

REFERENCES

1. Venara A, Neunlist M, Slim K, Barbieux J, Colas PA, Hamy A,

et al. Postoperative ileus: Pathophysiology, incidence, and

prevention. J Visc Surg 2016;153:439-46.

2. Delaney CP, Kehlet H, Senagore AJ, Bauer AJ, Beart R, Billingham

R, et al. Clinical Consensus Update in General Surgery: Postoperative

Ileus: Proles, Risk Factors, and Denitions-A Framework

for Optimizing Surgical Outcomes in Patients Undergoing Major

Abdominal and Colorectal Surgery. Clinical Consensus Update

in General Surgery, http://www.clinicalwebcasts.com/pdfs/

GenSurg_WEB.pdf2006.

3. Delaney CP, Marcello PW, Sonoda T, Wise P, Bauer J, Techner

L. Gastrointestinal recovery aer laparoscopic colectomy: results

of a prospective, observational, multicenter study. Surg Endosc

2010; 24:653-61.

4. Iyer S, Saunders WB, Stemkowski S. Economic burden of

postoperative ileus associated with colectomy in the United

States. J Manag Care Pharm 2009;15:485-94.

5. Murphy MM, Tevis SE, Kennedy GD. Independent risk factors

for prolonged postoperative ileus development. J Surg Res

2016;201:279-85.

6. Vather R, Trivedi S, Bissett I. Dening postoperative ileus:

results of a systematic review and global survey. J Gastrointest

Surg 2013;17:962-72.

7. Barbieux J, Hamy A, Talbot MF, Casa C, Mucci S, Lermite E,

et al. Does enhanced recovery reduce postoperative ileus aer

colorectal surgery? J Visc Surg 2017;154:79-85.

8. Fotiadis RJ, Badvie S, Weston MD, Allen-Mersh TG. Epidural

analgesia in gastrointestinal surgery. Br J Surg 2004;91:828-41.

9. Lohsiriwat V. Opioid-sparing eect of selective cyclooxygenase-2

inhibitors on surgical outcomes aer open colorectal surgery

within an enhanced recovery aer surgery protocol. World J

Gastrointest Oncol 2016;8:543-9.

10. Luckey A, Livingston E, Tache Y. Mechanisms and treatment

of postoperative ileus. Arch Surg 2003;138:206-14.

11. De Maeyer JH, Lefebvre RA, Schuurkes JA. 5-HT4 receptor

agonists: similar but not the same. Neurogastroenterol Motil

2008;20:99-112.

12. Narita K, Tsunoda A, Takenaka K, Watanabe M, Nakao K,

Kusano M. Effect of mosapride on recovery of intestinal

motility aer hand-assisted laparoscopic colectomy for carcinoma.

Dis Colon Rectum 2008;51:1692-5.

13. Toyomasu Y, Mochiki E, Morita H, Ogawa A, Yanai M, Ohno

T, et al. Mosapride citrate improves postoperative ileus of

patients with colectomy. J Gastrointest Surg 2011;15:1361-7.

14. Gustafsson UO, Scott MJ, Schwenk W, Demartines N, Roulin

D, Francis N, et al. Guidelines for perioperative care in elective

colonic surgery: Enhanced Recovery Aer Surgery (ERAS)

Society recommendations. World J Surg 2013;37:259-84.

15. Nygren J, acker J, Carli F, Fearon KC, Norderval S, Lobo DN,

et al. Guidelines for perioperative care in elective rectal/pelvic

surgery: Enhanced Recovery Aer Surgery (ERAS) Society

recommendations. World J Surg 2013;37:285-305.

16. Lohsiriwat V. Enhanced recovery aer surgery vs conventional care

in emergency colorectal surgery. World J Gastroenterol

2014;20:13950-5.

17. Lohsiriwat V. e inuence of preoperative nutritional status on

the outcomes of an enhanced recovery aer surgery (ERAS)

programme for colorectal cancer surgery. Tech Coloproctol

2014;18:1075-80.

18. Lohsiriwat V. Impact of an enhanced recovery program on

colorectal cancer surgery. Asian Pac J Cancer Prev 2014;15:

3825-8.

19. Tekkis PP, Prytherch DR, Kocher HM, Senapati A, Poloniecki

JD, Stamatakis JD, et al. Development of a dedicated risk-

adjustment scoring system for colorectal surgery (colorectal

POSSUM). Br J Surg 2004;91:1174-82.

20. Detsky AS, McLaughlin JR, Baker JP, Johnston N, Whittaker

S, Mendelson RA, et al. What is subjective global assessment

of nutritional status? JPEN J Parenter Enteral Nutr 1987;11:

8-13.

21. Dindo D, Demartines N, Clavien PA. Classication of surgical

complications: a new proposal with evaluation in a cohort of

6336 patients and results of a survey. Ann Surg 2004;240:

205-13.

22. Barbieux J, Hamy A, Talbot MF, Casa C, Mucci S, Lermite

E, et al. Does enhanced recovery reduce postoperative ileus

aer colorectal surgery? J Visc Surg 2017;154:79-85.

23. Nakamura M, Ohmiya N, Miyahara R, Ando T, Watanabe O,

Kawashima H, et al. Are symptomatic changes in irritable

bowel syndrome correlated with the capsule endoscopy transit

time? A pilot study using the 5-HT4 receptor agonist mosapride.

Hepatogastroenterology 2011;58:453-8.

24. Kanazawa M, Watanabe S, Tana C, Komuro H, Aoki M,

Fukudo S. Eect of 5-HT4 receptor agonist mosapride citrate

on rectosigmoid sensorimotor function in patients with irritable

bowel syndrome. Neurogastroenterol Motil 2011;23:754-e332.

25. Liu Z, Sakakibara R, Odaka T, Uchiyama T, Uchiyama T,

Yamamoto T, et al. Mosapride citrate, a novel 5-HT4 agonist and

partial 5-HT3 antagonist, ameliorates constipation in parkinsonian

patients. Mov Disord 2005;20:680-6.

26. Tsuchida Y, Hatao F, Fujisawa M, Murata T, Kaminishi M, Seto

Y, et al. Neuronal stimulation with 5-hydroxytryptamine 4

receptor induces anti-inammatory actions via alpha7nACh

receptors on muscularis macrophages associated with postoperative

ileus. Gut 2011; 60:638-47.

27. Okamura K, Sasaki N, Yamada M, Yamada H, Inokuma H.

Eects of mosapride citrate, metoclopramide hydrochloride,

lidocaine hydrochloride, and cisapride citrate on equine gastric

emptying, small intestinal and caecal motility. Res Vet Sci

2009;86:302-8.

28. Okamura K, Sasaki N, Kikuchi T, Murata A, Lee I, Yamada H,

et al. Eects of mosapride on motility of the small intestine

and caecum in normal horses aer jejunocaecostomy. J Vet

Sci 2009;10:157-60.

29. Grass F, Slieker J, Jurt J, Kummer A, Sola J, Hahnloser D, et al.

Postoperative ileus in an enhanced recovery pathway-a

retrospective cohort study. Int J Colorectal Dis 2017;32:675-81.

30. Kra M, Maclaren R, Du W, Owens G. Alvimopan (entereg)

for the management of postoperative ileus in patients undergoing

bowel resection. P T 2010;35:44-9.

31. Su’a BU, Pollock TT, Lemanu DP, MacCormick AD, Connolly

AB, Hill AG. Chewing gum and postoperative ileus in adults: a

systematic literature review and meta-analysis. Int J Surg

2015;14:49-55.

32. Wolthuis AM, Bislenghi G, Fieuws S, de Buck van Overstraeten

A, Boeckxstaens G, D’Hoore A. Incidence of prolonged

postoperative ileus aer colorectal surgery: a systematic review

and meta-analysis. Colorectal Dis 2016;18:O1-9.

Lohsiriwat

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

189

Original Article

SMJ

Kitirat Techatraisak, M.D., Ph.D., Pattra Wisarnsirirak, M.D.

Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ailand.

Cardiaovascular Disease Risk Factors in Thai

Natural Menopause with First-Time Diagnosis of

Low Bone Mass Density

Corresponding author: Kitirat Techatraisak

E-mail: kitirat.tec@mahidol.ac.th

Received 21 June 2018 Revised 26 September 2018 Accepted 5 March 2019

ORCID ID: http://orcid.org/0000-0001-8449-9379

http://dx.doi.org/10.33192/Smj.2019.29

ABSTRACT

Objective: To evaluate the prevalence of initial cardiovascular disease (CVD) risk factors in naturally postmenopausal

ai women with rst-time diagnosis of low bone mass density (BMD), and compare with those reported among

general ai women of the same age range during the same studied time.

Methods: A retrospective cross-sectional study of initial CVD risk factors of 473 naturally postmenopausal ai

women (45-60 years) with the rst-time diagnosis of osteopenia or osteoporosis without previous treatment for

CVD risk factors, except for hypertension(HT) and diabetes mellitus(DM), was performed. Only subjects with all

available initial CVD risk factors were recruited. Data included age, weight, height, waist circumference(WC), and

underlying diseases. Extracted initial CVD risk factors were: HT, DM, body mass index(BMI), cholesterol level,

triglyceride, high density lipoprotein , and family history of CVD. e main outcome was prevalence of initial

CVD risk factors with 95%CI. Results were compared with data of previous ai reports in women of the same age

during the same time period.

Results: All subjects (86.3% osteopenic, 13.7% osteoporotic) had on average 3.6 years since menopause. Prevalence

of women with initial CVD risk factors was 73.8%. e three most common risk factors were high BMI (48.6%),

high WC (37.8%) and high cholesterol (22.2%). Only high BMI was more prevalent than previously reported. In

contrast, the other factors were lower than previously published data.

Conclusion: With the exception of high BMI, initial CVD risk factors in this study were comparable to or lower

than those reported in general ai women of the same age during the same time period.

Keywords: CVD risk factors; low BMD; natural menopause; ai (Siriraj Med J 2019;71: 189-195)

INTRODUCTION

Osteopenia or osteoporosis is a condition that is

characterized by low bone mineral density (BMD) and

reduced bone strength increases risk of bone fractures.

However, the overall prevalence of osteoporosis, the more

severe condition, in postmenopausal ai women was

approximately 39%.

Many studies found cardiovascular

disease (CVD) to be associated with osteoporosis.

Tanko,

et al. reported that this increase in risk is proportional to

the severity of osteoporosis at the time of diagnosis.

ai

women diagnosed with low BMD (osteopenia/osteoporosis)

are usually prescribed calcium supplementation because

typical ai diet is low in calcium. Calcium is also a

key player in coagulation, and muscle and myocardial

contraction. us, a change in calcium metabolism may

participate in the development of CVD.

Traditional CVD risk factors are categorized as either

un-modiable risk factors (e.g. age, gender) or modiable

risk factors [e.g. hypertension (HT), diabetes mellitus

(DM), dyslipidemia (DLP), and obesity or overweight

status]. With an increase in older population and the

adoption of more and more Western lifestyle behaviors,

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

190

ailand is replacing its traditional high-carbohydrate

diets, consisting largely of rice and vegetables, with a diet

high in fat and sugar.

As a result, we can expect to see

commensurate increases in the prevalence of CVD. e

prevalence of several initial CVD risk factors has not been

simultaneously studied in naturally postmenopausal ai

women with rst time diagnosis of osteopenia/osteoporosis

and crucially needed calcium supplementation.

Accordingly, the primary aim of this study was

to investigate the prevalence of initial traditional CVD

risk factors in naturally postmenopausal ai women

at the rst-time diagnosis of osteopenia/osteoporosis.

e secondary objective was to compare our ndings

with results from previous studies in ai women in the

same age range during the same time period.

MATERIALS AND METHODS

is retrospective cross-sectional study was performed

at the Gynecologic Endocrinology Unit, Department of

Obstetrics and Gynecology, Faculty of Medicine Siriraj

Hospital. Aer the institutional ethical board approval

(Si 276/2014) was obtained, data were collected from

medical records between 1997 and 2014. Sample size

calculation was 500, which number included 10% for

data loss by using the formula . P was

the prevalence of HT, which was one of the CVD risk

factors (p=0.276) from the latest studied ai population

in 2012.

Allowable error (d) was 0.0414 and relative

error was 15%. e collected data were from the rst

participation in this unit. About 1,000 out-patient charts

were reviewed and only 473 charts, as in Fig 1, were

nally included when the following inclusion criteria

were met: natural menopause, 45-60 years, the rst-time

diagnosis of osteopenia or osteoporosis without previous

treatment. Patient charts with a history of metabolic bone

disorders, drug aecting calcium and bone metabolism,

congenital or valvular heart disease, or cancer with bone

metastasis were excluded. Reviewed data included age,

weight, height, waist circumference (WC), and underlying

diseases. CVD risk factors consisted of DM, HT, body

mass index (BMI), cholesterol (Chol), triglyceride (TG),

high density lipoprotein (HDL) and family history of

CVD (female <65 years, male <55 years).

Statistical analysis

PASW (SPSS) version 18 (SPSS Inc., Chicago, IL,

USA.) was used. e results were reported as mean±SD,

minimum, maximum and percentage with 95%CI. T- test

was used to compare continuous variables eg. BMI, Wt,

Ht, etc. Categorical data, eg. BMI≥ 23 kg/m

etc. was

analyzed by Pearson Chi-square test, and p-value <0.05

was statistically signicant. e data were also compared

with previously reported data of ai population.

RESULTS

473 patients with complete data were included in

the nal analysis. e mean age of patients was 53.5±4.1

years. All subjects were non-smoking with an average 3.6

years since menopause. Demographic data and clinical

characteristics are shown in Table 1. Mean WC, Chol,

TG, and HDL levels were all within normal ranges. Only

mean high BMI for Asian women (≥ 23.0 kg/m

) in

this study was higher than previously reported in ai

women. e overall prevalence of patients with traditional

initial CVD risk factors was 73.8%. While approximately

one-fourth of the subjects had no risk factor, 61 patients

(12.9%) had 4-6 risk factors, and only one patient had

all seven risk factors. e 3 most common risk factors

were high BMI (48.6%), high WC (37.8%), and Chol ≥

240 mg/dl (22.2%). e vast majority of women were

osteopenic (408 patients, 86.3%), with only 65 (13.7%)

women having osteoporosis (Fig 1).

Fig 1. Flow diagram of subject selection process.

Techatraisak et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

191

Original Article

SMJ

TABLE 1. Clinical characteristics, and prevalence and number of CVD risk factors, overall and by BMD group.

All subjects Osteopenia Osteoporosis P-value*

(n = 473) (n = 408) (n=65)

Mean±SD Mean±SD Mean±SD

Age (yrs) 53.5±4.1 53.4±4.0 53.7±4.1 0.595

Wt (kg) 55.7±8.7 56.0±8.6 53.8±8.5 0.066

Ht (cm) 154.7±5.2 154.8±5.1 154.3±5.7 0.501

BMI (kg/m

) 23.3±3.4 23.4±3.4 22.6±3.4 0.104

WC (cm) 78.1±8.3 78.3±8.3 76.6±8.1 0.113

Chol (mg/dl) 212.4±38.6 211.5±38.0 218.1±42.3 0.200

TG (mg/dl) 103.3±50.5 103.9±51.5 100.1±44.3 0.573

HDL (mg/dl) 65.5±15.9 64.6±16.0 67.5±15.4 0.177

Number of risk factor, cases (%)

HT 67 (14.2%) 48 (11.8%) 19 (29.2%) <0.001

DM 22 (4.7%) 17 (4.2%) 5 (7.7%) 0.210

BMI ≥ 23.0 (kg/m

) 230 (48.6%) 201 (49.3%) 29 (44.6%) 0.486

Chol ≥ 240 mg/dl 106 (22.2%) 85 (20.8%) 20 (30.8%) 0.073

TG ≥ 150 mg/dl 59 (12.5%) 53 (13%) 6 (9.2%) 0.394

HDL < 50 mg/dl 49 (10.4%) 46 (11.3%) 3 (4.6%) 0.102

WC > 80 cm 179 (37.8%) 159 (39%) 20 (30.8%) 0.205

Family history of CVD 94 (19.9%) 76 (18.6%) 18 (27.7%) 0.089

Number of risk factors, cases (%)

0-1 237 (50.1%) 207 (50.8%) 30 (46.2%)

2-3 174 (36.8%) 149 (36.5%) 25 (38.4%)

0.462

4-6 61 (12.9%) 51 (12.5%) 10 (15.4%)

7 1 (0.2%) 1 (0.2%) 0 (0%)

*P-value <0.05 indicates statistical signicance

Abbreviations: BMD=bone mineral density, Wt=weight, Ht=height, BMI=body mass index, WC=waist circumference, Chol=cholesterol,

TG=triglyceride, HDL=high density lipoprotein cholesterol, HT=hypertension, DM=diabetes mellitus, CVD=cardiovascular disease

}

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

192

Results of analysis between the osteopenia and

osteoporosis subgroups are shown in Table 1. Average

age, anthropometric parameters, and baseline laboratory

results were not signicantly dierent between groups.

HT, DM, high Chol and family history of CVD were

higher in the osteoporosis group than in the osteopenia

group. Of those, HT was the only risk factor that was

statistically signicantly higher in the osteoporosis group

than in the osteopenia group (p <0.001). Also, prevalence

of high BMI, high TG, low HDL and high WC were

lower in the osteoporosis group, but without statistical

signicance. e number of cases with 0-1, 2-3, 46 and

7 CVD risk factors were comparable between groups.

e prevalence of each initial CVD risk factor with

95% CI, and the prevalence reported from other studies

in ai women conducted during the same period are

shown in Table 2. BMI ≥23.0 kg/m

was more prevalent

in this study than in the 2010 report. HT, DM, high

WC, high TG, and low HDL were also lower than in

the previously published data. High Chol was also much

lower than one previously published study, but the cut-

o levels diered between the two studies (240 mg/dl

vs 200 mg/dl, respectively). Family history of CVD was

comparable with the 2006 report. Prevalence of DLP was

also relatively high in this study, but without available

previous data for comparison. Data from the National

Health Examination Survey (NHES) V for the year 2015

was not available for comparison at the time that this

manuscript was being prepared.

DISCUSSION

is study set forth to investigate the prevalence

of initial CVD risk factors in naturally postmenopausal

ai women with low BMD who crucially need calcium

supplementation aer the rst-time diagnosis of osteopenia/

osteoporosis at a large tertiary care hospital in ailand.

Only naturally postmenopausal women were studied,

because surgically postmenopausal women would likely

be younger and would likely not yet have developed low

BMD. Moreover, low BMD is not always identiable

soon aer oophorectomy in younger women. Given

that the average age of subjects was in the early naturally

postmenopausal period, osteopenia was found to be

more prevalent than osteoporosis. Interestingly, 26% of

the subjects at the average age of 53.5 years still did not

have any identiable traditional CVD risk factors, and

one-fourth of the cases had only one factor. However,

half of the patients in this study had ≥ 2 risk factors and

12.5% had ≥ 4 risk factors.

e cross-sectional data from the NHES III in 2004,

revealed a prevalence of overweight and obesity of 4.0%

in a sample of ai adults aged 35-59 years.

In another

report, ai women aged 46-55 years had the highest

risk of being overweight or obese, and this may be due

to the weight gain during important life transition events

like retirement and menopause.

In a study conducted

in Bangkok at another tertiary-care hospital, risk factors

of hypercholesterolemia increased among ai women:

advanced age (OR:3.19), and family history of DLP

(OR:1.59). It also reported that total Chol and TG were

strongly associated with age, BMI and family history of

DLP, while HDL was inversely associated with BMI.

that study, women aged 40-59 years had an OR of 1.77

(95%CI: 1.27-1.48) of developing hypercholesterolemia

compared to women aged <40 years. However, a positive

association between increasing age and BMI and total

Chol, TG and total Chol/HDL ratio were also noted.

Undoubtedly, overweight and obese women had higher

TG (p <0.001). A study in Taiwan by Tsai WL., also

found that the risk of hypercholesterolemia increased

with increasing BMI in both genders.

In addition,

women with a family history of DLP had a mean total

Chol higher than those without a family history of DLP

(p <0.001). In a study from Japan, Kawada T. observed

that odd ratios for hypercholesterolemia (≥ 240 mg/dl)

also increased across higher BMI quartiles (OR:1.0-4.6).

e average baseline characteristics of the patients

in this study were mostly within normal ranges and

approximately one fourth of the women had no initial

CVD risk factors. Regarding HT and DM in ailand,

the age-specic prevalence of individuals having one or

both conditions increased as age increased and peaked

at later age, ≥80 years. Prevalence of coexisting HI and

DM was reported to be highest in the 60-69 years’ age

group.

Total prevalence of DM was higher in urban

residents than in rural residents for both men and women

(p <0.001).

However, the proportions of DM cases with

HT did not signicantly decrease for either gender.

is study revealed some other interesting outcomes.

Firstly, the prevalence of high BMI, high Chol, and

family history of CVD, were comparable with the results

of other ai studies in patients of comparable ages.

In ailand, a signicant increase in the prevalence of

overweight and obesity was observed, from 1991 (25%)

to 2004 (48%) among ai adults aged 35-59 years.

Also, from 2004 to 2009, the proportion of women

with DM and abdominal obesity increased 18% and

the proportion of women who had DM and high Chol

increased 23.5%.

e increase in BMI and prevalence of

obesity in ailand were reported to be consistent with

rates of increase in other Asian countries.

It is known

that the risk of developing CVD increases twofold aer

Techatraisak et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

193

Original Article

SMJ

TABLE 2. Prevalence of each CVD risk factor compared with previous ai reports.

CVD risk factors Prevalence (%) 95%CI The other National Thai studies

Population Prevalence (%)

HT 14.2 11.3-17.6 Thai women aged 45-59 years 34.6

Central, Northern, North, South

Survey (urban/rural area) NHES III

DM 4.7 3.1-6.9 Thai women aged 45-59 years 12.8

Central, Northern, North, South

Survey (urban/rural area) NHES III

BMI ≥23 kg/m

48.6 44.2-53.1 3,275 women, average age 40.8 44.9

±16.6 years (women aged 36-45, 46-55,

56-65 with OR for overweight

2.5 (1.6-3.9), 4.8 (3.0-7.6), 2.9 (1.8-4.8)

respectively, p <0.001)

Nationally representative sample

covering all geographic regions of

Thailand

DLP 44.4 40-48.9 NA

Cholesterol ≥ 240 mg/dl 22.2 18.7-26.2 510 women aged 40-59 who 71.9

participated in annual health

examination at a tertiary-care hospital,

Bangkok (cholesterol ≥200 mg/dl)

TG ≥ 150 mg/dl 12.5 9.8-15.8 Thai women aged 40-59 years 40-49 years: 29.6%

Sampling by province, region, district, 50-59 years: 42.9%

village, the sex and agespecic group.

NHES IV

HDL > 50 mg/dl 10.4 7.9-13.4 Thai women aged 40-59 years Sampling 40-49 years: 56.4%

by province, region, district, village, the 50-59 years: 58.4%

sex and agespecic group. NHES IV

WC > 80 cm 37.8 33.6-42.3 Thai women aged 40-59 years Sampling 40-49 years: 51.0%

by province, region, district, village, the 50-59 years: 57.6%

sex and age- specic group. NHES IV

Family history of 19.9 16.5-23.7 851 women with known family history 19.8

CVD of CVD who participated in annual

health examination at a tertiary-care

hospital, Bangkok

Abbreviations: CVD=cardiovascular disease; CI=condence interval; HT=hypertension; NHES=National Health Examination Survey;

DM=diabetes mellitus; BMI=body mass index; OR=odds ratio; DLP=dyslipidemia; NA=not available; Chol=cholesterol; TG=triglycerides;

HDL=high density lipoprotein cholesterol; WC=waist circumference

ai NHES III= 2004 (Multistage, probability sampling of ai population aged ≥ 15 years) ai NHES IV = 2009 (Multistage, stratied

sampling of ai population aged ≥ 20 years) ai NHES V = 2015 (Published data not available at the time this manuscript was draed)

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

194

menopause. Decreased estrogen level may be associated

with CVD risk.

16,17

Prevalence of family history of CVD in

this study was similar to the other ai study conducted

during the same time period to which we compare our

results. is may explain why subjects in both studies

were homogenous ai Indochina population.

Secondly, the prevalence of HT, high WC, high TG

and low HDL were much lower in this study than in the

other studies to which each was compared. is may be

explained by the reason that the women in this study were

early naturally postmenopausal women who had received

the rst-time diagnosis of osteopenia/osteoporosis. is

interesting nding should be studied more extensively.

Many studies reported that postmenopausal women

have increased total Chol, increased LDL, increased

TG, increased lipoprotein (a), and decreased HDL. e

change in lipid prole may also be partly attributed to

increased abdominal adiposity in menopausal women.

Unfortunately, prevalence of DLP from previous study

was not available for comparison in this report.

Menopause causes a signicant increase in total

peripheral resistance and loss of arterial vasodilatation.

is may contribute to increases in BP.

Dierences in

the prevalence in this study and the comparative studies

shown in Table 2 could also be dierences in study design.

e population in this study was derived from a single-

center, tertiary care hospital. e proportions of subjects

with numbers of CVD risk factors (i.e. 0-1, 2-3, 4-6 and 7)

were not signicantly dierent between the two groups.

However, the prevalence of HT in the osteoporosis

group was signicantly higher than the osteopenia group

(p <0.001). is dierence may be explained by the older

mean age of patients in the osteoporosis group (p >0.05).

Family history of CVD is an un-modiable risk

factor, and other modiable risk factors, such as HT and

DM might increase in prevalence as women age. e

prevalence of HT reported from the NHES III study in

2004 and reported in 2008 among ai women increased

from 34.6% (45-59 yr), to 48.1% (60-69 yr) and 54.1%

(70-79 yr). Also, the prevalence of DM in that study

increased from 12.8% (45-59 yr), to 19.1% (60-69 yr)

and 16.1% (70-79yr).

e cross-sectional data from

the NHES IV reported in 2009 showed that high WC

also increased as ai women aged, from 51.0% (40-49

yr) to 57.6% (50-59yr). Result from the same report in

2009 showed, TG ≥150 mg/dl also increased with age,

from 29.6% (40-49 yr) to 42.9% (50-59 yr), while HDL

<50 mg/dl showed only a slight increase in prevalence

from 56.4% (40-49 yr) to 58.4% (50-59 yr). Results from

the National ai Food Consumption Survey in 2010 of

other samples covering all geographic regions of ailand,

showed that women aged 46-55 year had the highest OR

for BMI ≥23.0 kg/m

compared to women aged <45 years

and 56-65 years (OR:2.5 vs 2.9, respectively). e results

from previous ai reports imply that as ai women

age, they may have more traditional CVD risk factors.

is study showed that naturally postmenopausal

ai women with osteopenia/osteoporosis had initially

comparable or lower CVD risks than ai women in the

general population of the same ages during the same

study time frame. However, the CVD risk factors were

dierent among the osteopenia and osteoporosis groups

and need future study.

is study has some mentionable limitations. First

and consistent with the retrospective nature of this study,

some patient data may have been missing or incomplete

which they were excluded from the nal analysis. Second,

the patients we studied were hospital-based, from a

single center referred with mainly menopausal symptom

complaints. Behavioral and lifestyle characteristics such

as alcohol consumption, and exercise habits should also

be collected for analysis.

CONCLUSION

Prevalence of initial CVD risk factors in this study

was 73.8%. With the exception of high BMI, initial CVD

risk factors in this study subjects were comparable to or

lower than those found in ai women in the general

population of the same age during the same time period.

ACKNOWLEDGMENTS

e authors gratefully acknowledge Mr. Suttipol

Udompunturak, a statistician, for assistance with statistical

analyses.

Conict of Interest: e authors report no funding

sources in this work and declare no conict of interest.

REFERENCES

1. Limpaphayom KK, Taechakraichana N, Jaisamrarn U,

Bunyavejchevin S, Chaikittisilpa S, Poshyachinda M, et al.

Prevalence of osteopenia and osteoporosis in ai women.

Menopause 2001;8:65-9.

2. Warburton DE, Nicol CW, Gatto SN, Bredin SS. Cardiovascular

disease and osteoporosis: Balancing risk management. Vasc

HealthRiskManag2007;3:673-89.

3. Tanko LB, Christiansen C, Cox DA, Geiger MJ, McNabb MA,

Cummings SR. Relationship between osteoporosis and

cardiovascular disease in postmenopausal women. J Bone

Miner Res 2005;20:1912-20.

4. McGreevy C, Williams D. New insights about vitamin D and

cardiovascular disease. Ann Intern Med 2011;155:820-6.

5. Kosulwat V. e nutrition and health transition in ailand.

Public Health Nutr 2002;5:183-9

Techatraisak et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

195

Original Article

SMJ

6. Tiptaradol S, Aekplakorn W. Prevalence, awareness, treatment

and control of coexistence of diabetes and hypertension in

ai population. Int J Hypertens2012;2012:386453.

7. Aekplakorn W, Abbott-Klaer J, Premgamone A, Dhanamun

B, Chaikittiporn C, Chongsuvivatwong V, et al. Prevalence

and management of diabetes and associated risk factors by

regions of ailand: third National health examination survey

2004. Diabetes Care 2007;30:8-12.

8. Jitnarin N, Kosulwat V, Rojroongwasinkul N, Boonpragerm A,

Christopher KH, Walker SCP. Risk factor for overweight

and obesity among ai adults: Results of the National ai

Food Consumption Survey. Nutrient 2010;2:60-74.

9. Le D, Garcis A, Lohsoonthorn V, Williams WA.Michelle.

Prevalence and risk factors of hypercholesterolemia among

ai men and women receiving health examinations. Southeast

Asian J Trop Med Public Health 2006;37:1005-14.

10. Tsai WL, Yang CY, Lin SF, Fang FM. Impact of obesity on

medical problems and quality of life in Taiwan. Am J Epidemiol

2004;160:557-65.

11. Kawada T. Body mass index is a good predictor of hypertension

and hyperlipidemia in a rural Japan population. Intl J Obes

Relat Metab Disord 2002;26:725-9.

12. Aekplakorn W, Kessomboon P, Sangthong R, Chariyalertsak

S, Putwatana P, Inthawong R, et al. Urban and rural variation in

clustering of metabolic syndrome components in the ai

population: results from the fourth National Health Examination

Survey 2009. BMC Public Health 2011;11:854.

13. Ministry of Public Health, Bureau of Policy and Strategy.

ailand Health Prole, 2005-2007; Printing Press, the War

Veterans Organization of ailand: Bangkok, ailand, 2008.

14. Aekplakorn W, Chariyalertsak S, Kessomboon P, Sangthong

R, Inthawong R, Puttawatana P, et al. Prevalence and management

of diabetes and metabolic risk factors in ai adults. Diabetes

Care 2011;34:1980-5.

15. Aekplakorn W, Inthawong R, Kessomboon P, Sangthong R,

Charityalertsak S, Puttawattana P, et al. Prevalence and trends

of obesity and association with socioeconomic status in

ai adults: National health examination surveys, 1991-2009.

J Obes2014;2014:410259.

16. Molly CC. e emergence of the metabolic syndrome with

menopause. J Clin Endocrinol Metab 2003;88:2404-11.

17. Hanah NP, Alex JP. Metabolic implications of menopause.

Semin Reprod Med 2010;28:426-34.

18. Porapakkham Y, Pattaraarchachai J, Aekplakorn W. Prevalence,

awareness, treatment and control of hypertension and diabetes

mellitus among the elderly: the 2004 National Health Examination

Survey III, ailand. Singapore Med J 2008;49:868-73.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

196

Natharom Chutikamo, R.N.*, Rungrawee Navicharern, R.N., Ph.D.*, Varut Lohsiriwat, M.D., Ph.D.**

*Faculty of Nursing, Chulalongkorn University, Bangkok 10330, **Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University,

Bangkok 10700, ailand.

Comparative Study of Health-Related Quality of

Life between Colorectal Cancer Patients with

Temporary and Permanent Stoma

Corresponding author: Rungrawee Navicharern

E-mail: nrungrawee@yahoo.com

Received 31 January 2017 Revised 15 August 2018 Accepted 11 September 2018

ORCID ID: http://orcid.org/0000-0001-9647-9068

http://dx.doi.org/10.33192/Smj.2019.30

ABSTRACT

Objective: To compare the health-related quality of life (HRQOL) between colorectal cancer (CRC) patients with

temporary and permanent stoma.

Methods: is survey was a cross-sectional study that was conducted on 110 CRC patients living with stoma. A

validated ai version of Padilla and Grant’s HRQOL (as a cancer nursing outcome variable) was used. Enrolled

patients must have age between 40-60 years and live with stoma over a period of 3 months.

Results: ere were 83 patients with temporary stoma and 27 patients with permanent stoma. e majority was

male and got married. e common indication for temporary and permanent stoma was low anterior resection

and abdominoperineal resection, respectively. Overall mean HRQOL index was not signicantly dierent between

groups. ere was also no dierence in the mean QOL of each domain - namely physical well-being, psychological

well-being, body image concerns about stoma, social support concern, and diagnosis/treatment response between

those with temporary and permanent stoma. Notably, the domain of body image concern had the lowest QOL

index in both groups.

Conclusion: Postoperative health-related quality of life was not dierent between ai colorectal cancer patients

with temporary or permanent stoma. However, the patients with permanent stoma appeared to have non-signicant

higher score in every domain of health-related quality of life than those with temporary stoma.

Keywords: Health-related quality of life; colon cancer; rectal cancer; colostomy; ileostomy; stoma; temporary;

permanent; surgery (Siriraj Med J 2019;71: 196-200)

INTRODUCTION

Colorectal cancer (CRC) is one of major health

problems across the globe. A signicant increase in its

incidence has been observed worldwide in the recent

years.

In ailand CRC is now the third most commonly

diagnosed cancer in males and the fourth in females.

Currently, CRC-related death has reduced due to an

improvement in early detection and advances in cancer

treatment. However, some curative operations would

have stoma formation either temporary or permanent

purpose. Not surprisingly, the number of CRC survivors

with stoma is growing signicantly.

Presence of stoma

(colostomy/ileostomy) has been shown to adversely aect

patient’s wellbeing in several phases such as physical

and psychological aspects, social function, work and

productive life, relationships with partners and friends,

social activities and personal interests.

Chutikamo et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

197

Original Article

SMJ

Since temporary and permanent stoma is one of viable

treatment options for CRC

, it creates many challenges for

CRC patients especially in terms of health-related quality

of life (HRQOL). e patients with stoma formation face

the loss of sphincter control and inability to control gas

and may have several other prolems including anxiety

or fear of future living with relationships and family

diculty in social and sexual activities, sleep disturbance

the restriction of food intake and physical activities

and

changes in lifestyle.

All of these sequelae impacted their

HRQOL.

In CRC patients, non-sphincter preserving

operation (i.e. colostomy formation) was also shown to

negatively impact patients’ HRQOL.

HRQOL for patients with stoma is one of important

patient-reported outcome measures and could be regards

as one of the long-term comprehensive outcomes in CRC

patients. e World Health Organization denes HRQOL

as individuals’ perception of their life’s position in the

context of the culture and value systems in which they

live and in relation to their goals, expectations, standards

and concerns.

HRQOL in CRC patients with stoma

is a multidimensional construct measuring patients’

perception in several domains including physical well-

being, psychological well-being, body image concerns

about colostomy, social support concern, and diagnosis/

treatment (surgical) response.

Most published literatures about HRQOL of CRC

patients with stoma were conducted in Western or developing

countries - with some conicting results. For example,

Grumann et al

compared HRQOL in German patients

undergoing anterior resection (AR), low anterior resection

(LAR) and abdominoperineal resection (APR) for rectal

cancer. ey found that patients undergoing APR did

not have a poorer HRQOL than those undergoing AR

but patients undergoing LAR had a lower HRQOL than

those undergoing APR. In the Netherlands, Gooszen et

studied HRQOL in those with a temporary stoma

(37 loop ileostomy and 39 loop colostomy) and found

that stoma leakage, peristomal dermatitis, and stoma

retraction or prolapse had signicant impact on patients’

HRQOL. In Brazil, Fortes et al

and de Gouveia Santos

et al

evaluated HRQOL in CRC patients with temporary

and permanent colostomy and found that patients with

temporary stoma suered the same aection and poor

HRQOL as those with permanent colostomy.

In ailand, there have been some studies examining

HRQOL or factors related to HRQOL in patients with

stoma

16-18

, but there is no comparative study of HRQOL

in CRC patients with temporary or permanent stoma.

We believe that the information of HRQOL in those with

temporary or permanent stoma will help surgeons and

other related healthcare personals more understanding

and could improve patient’s care in such individuals in

the future. erefore, this study aimed to examine and

compare HRQOL in CRC patients with temporary or

permanent stoma in ai population.

MATERIALS AND METHODS

is study was a cross-sectional study examining

HRQOL in 110 CRC adult patients with either temporary

or permanent stoma.

Data were collected from July

2016 to October 2016 at 3 tertiary referral centers in

Bangkok, ailand - namely 1) Faculty of Medicine Siriraj

Hospital, Mahidol University, 2) King Chulalongkorn

Memorial Hospital and 3) National Cancer Institute.

e patients were systematically and randomly enrolled

with inclusion criteria of patient age between 40-60

years and having stoma over a period of 3 months. e

correspondents must have no symptoms and signs of

critical illness during interviewing, and understand and

response properly to the questionnaires. e eligible

cases were randomly enrolled. All subjects granted a

signed inform consent before an enrollment.

e interview questionnaires had 2 parts: general

details and HRQOL. The general details included

patients’ demographics, level of education, income,

tumor characteristics and operative details, their general

knowledge of CRC, self-care behaviors and social support.

For HRQOL, a validated ai version of Padilla and

Grant’s HRQOL (as a cancer nursing outcome variable)

was used

, including the domains related to physical,

mental, emotional and social functioning. e HRQOL

index ranges from 0 to 100 as the higher score the better

HRQOL. is index of HRQOL was divided into 3 levels:

low (HRQOL 0-33.33), moderate (33.34-66.67) and high

(66.68-100) level of HRQOL. Data were analyzed using

computer-based statistical program (SPSS/Window

version 17). Demographic data and HRQOL index were

analyzed using descriptive statistics and independence

student t-test to compare between HRQOL index of adult

CRC patients with temporary and permanent stomas. A

P-value < 0.05 was considered a statistical signicance.

RESULTS

Demographic data of patients with temporary and

permanent stoma

ere were 27 patients with permanent stoma with

mean age of 54.4 years. Seventeen (63%) were males and

25 patients (92.6%) were married. Stage III and IV rectal

cancer were the most common indication for stoma

formation as two-third had abdominoperineal resection.

At the time of HRQOL evaluation, the two-third of

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

198

Chutikamo et al.

patients had permanent stoma was more than 1 year. In

the other group, there were 83 patients with temporary

stoma with mean age of 54.9 years. Fiy-ve (66.3%)

were males and 78 patients (94%) were married. Stage

III colorectal cancer was the most common indication

for temporary stoma formation (mostly in case of low

anterior resection). At the time of HRQOL evaluation,

the two-third of patients had temporary stoma less than

1 year. Demographic data of patients with temporary

and permanent stoma are summarized in Table 1.

Health-related quality of life between colorectal cancer

patients with temporary and permanent stoma

Overall mean HRQOL index was not signicantly

dierent between groups. ere was also no dierence

in the mean QOL of each domain between those with

temporary and permanent stoma. Notably, the domain

of body image concern had the lowest QOL index in both

groups. Table 2 shows and compare the HRQOL index

between CRC patients with temporary and permanent

stoma.

DISCUSSION

is cross-sectional study of CRC patients with

stoma in ailand found that the overall HRQOL index

and its detailed domains were not signicantly dierent

between those with temporary and permanent stoma.

However, it is worth noting that ai CRC adult patients

with permanent stoma had non-signicantly higher

overall HRQOL index and HRQOL indexes of each

domain - namely physical well-being, psychological well-

being, body image concerns about stoma, social support

concern, and diagnosis/treatment response than those

with temporary stoma. ese results are similar to those

reported from Western countries. For example, Smith

et al

conducted a small cross-sectional study of patients

TABLE 1. Patients’ demographic data (n=110). e data are shown as mean ± standard deviation, or number

(percentage).

Variables Permanent Temporary

(n=27) (n=83)

Age (years) 54.4 ± 6.1 54.9 ± 5.5

Male 17 (63.0%) 55 (66.3%)

Marital status: Married 25 (92.6%) 78 (94.0%)

Education

No education 1 (3.7%) 1 (1.2%)

Primary school 11 (40.7%) 41 (49.3%)

High school 3 (11.1%) 13 (16.8%)

Bachelor degree or higher 12 (44.4%) 27 (32.5%)

Income (Bahts)

Less than 10,000 7 (25.9%) 21 (25.3%)

10,001-30,000 18 (66.7%) 54 (65.1%)

30,001-50,000 2 (7.4%) 8 (9.6%)

Cancer staging

Stage II 5 (18.5%) 10 (8.2%)

Stage III 11 (37.0%) 47 (42.7%)

Stage IV 11 (37.0%) 26 (23.6%)

Presence of stoma more than 1 year 18 (66.7%) 28 (33.7%)

Operative details

Low anterior resection 4 (14.8%) 53 (63.9%)

Abdominoperinal resection 18 (66.7%) 2 (2.4%)

Hartmann’s procedure 3 (11.1%) 11 (13.3%)

Colectomy 2 (7.4%) 17 (20.5%)

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

199

Original Article

SMJ

TABLE 2. Index score and level of health-related quality of life among patients with temporary and permanent stoma.

Type of stoma N Mean SD Level* P-value

Overall HRQOL Temporary stoma 83 66.41 14.32 Moderate 0.372

Permanent stoma 27 69.31 15.37 High

Physical well-being Temporary stoma 83 69.08 16.68 High 0.474

Permanent stoma 27 71.74 16.65 High

Psychological well-being Temporary stoma 83 64.68 16.43 Moderate 0.525

Permanent stoma 27 67.06 18.22 High

Body image concern Temporary stoma 83 54.56 21.98 Moderate 0.596

Permanent stoma 27 57.22 24.32 Moderate

Social concern Temporary stoma 83 76.83 13.52 High 0.427

Permanent stoma 27 79.26 14.50 High

Surgical response Temporary stoma 83 69.28 17.80 High 0.369

Permanent stoma 27 72.72 15.30 High

Nutrition response Temporary stoma 83 68.73 18.14 High 0.176

Permanent stoma 27 74.07 16.30 High

*Note: Level of HRQOL: low (0-33.33), moderate (33.34-66.67) and high (66.68-100)

with stoma in the United States and found that patients

with permanent stoma had high HQOL scores than

patients with temporary stoma. ese nding suggested

that patients with irreversible colostomies would adapt

more fully than would those with colostomies that were

potentially reversible. Our previous study indicated that

patient’s self-esteem, self-care and knowledge were also

signicant factors for determining HRQOL.

Regarding the physical well-being dimension of HRQOL

in ai CRC adult patients with stoma, both groups had

a comparable and high level of HRQOL. is result was

partly explained by the fact that almost of patients with

stoma already had good recovery from surgery and/or

adjuvant therapy although some patients with a temporary

stoma were in the middle of chemotherapy or radiation

session. Fortes et al14 reported that chemotherapy or

radiotherapy might have numerous inuences on HRQOL

in patients with stomas and the adverse symptoms may

last up to 1 year aer treatment.

Although there was no signicant dierence in the

score of psychological well-being dimension between

groups, patients with permanent stoma was regarded to

have a high level of QOL while those with temporary stoma

had a moderate level. ese results were consistent with

other studies in ailand.

17,20

e most frequent coping

strategy employed by individuals with temporary stoma

was escape and avoidance which was not so eective

because it did not permit the subject to approach the

problem directly. In contrast, the most frequent coping

strategy employed by patients with permanent stoma

was problem-solving which provided a more proactive

and mature behavior - allowing greater autonomy and

responsibility when coping with their stoma.

e body image concern dimension had the lowest

score in ai CRC adult patients with temporary and

permanent stoma. It is well known that stoma surgery

is a mutilating procedure and could aect their body

image directly and negatively. We found that patients

with stoma had some anxiety about stoma and fear of

stoma leakage (especially during performing physical

activities or sleep) which were consistent with other

reports.

15,21

In ailand, Teerathongdee

reported that

CRC patients with colostomy had a moderate level of

QOL in component of body image concern. Meanwhile,

Ransriwong

reported a low level of QOL in component

of self-image in those with stoma. However, the results

were extracted from early postoperative period (within

3 months aer surgery) - where the patients may not

cope with the body change.

Regarding the social concern dimension, both

groups had a high level of QOL. It could be explained

by the fact that, in ai culture, patients with stomas

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

200

were taken care of their stoma by their caregivers such

as their family members or spouses. Patients oen come

to clinic with their relatives and did not feel lonely or

abandoned.

For the dimension of surgical response and

nutrition, patients with either temporary or permanent

stoma dimension had a high level of QOL which was not

signicant dierent between groups. It is possible that

HRQOL in each dimension could gradually improve as

the time goes by because the patients can learn, adapt

and cope with stoma and their activities of daily living

such as eating and moving.

5,17

e strength of this study included a relative larger

sample size of enrolled patients than those previously

reported from ailand. e data were also collected from

3 tertiary care centers where colorectal surgeons, ostomy

nurse specialists and psychologists are available. ere are

also a dedicated ostomy clinics and specialized medical

supplies in these centers. However, it is unknown about

the HRQOL in ai CRC adult patients with stoma who

were operated on by non-colorectal surgeons or taken

care of by non-specialist nurses.

CONCLUSION

Postoperative health-related quality of life was

dierent between ai colorectal cancer patients with

temporary or permanent stoma. However, the patients

with permanent stoma appeared to have non-signicant

higher score in every domain of health-related quality

of life than those with temporary stoma. We believed

that, apart from focusing on oncological outcomes,

healthcare personals should aim to improve patient’s

health-related quality of life overall and in each domain

- partly by integrating knowledge, self-care as well as

patient-centered program in patients with stoma.

ACKNOWLEDGMENTS

is research was nancially supported by the 90

Anniversary of Chulalongkorn University, Rachadapisek

Sompote Fund.

REFERENCES

1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo

M, et al. Cancer incidence and mortality worldwide: Sources,

methods and major patterns in GLOBOCAN 2012. Int J Cancer

2015;136:359-86.

2. Imsamran W, Chaiwattana A, Wiangnon S, Pongnikorn D,

Suwanrungrung K, Sangrajrang S, et al. Cancer in ailand

Vol.VIII, 2010-2012 [Cited 2015 December 8]. Available from:

http://www.nci.go.th/en/index1.html.

3. American Cancer Society Colorecral cancer 2016 [Cited 2016

November 24]. Available from: http://www.cancer.org/cancer/

colonandrectumcancer/detailedguide/colorectal-cancer-what-

is-colorectal-cancer.

4. Burch J. Stoma Care. Singapore: Markono Print Media Ptd

Ltd; 2008.

5. Arndt V, Merx H, Stegmaier C, Ziegler H, Brenner H. Quality of

life in patients with colorectal cancer 1 year aer diagnosis

compared with the general population: a population-based

study. J Clin Oncol 2004;22:4829-36.

6. Zajac O, Spychala A, Murawa D, Wasiewicz J, Foltyn P, Polom

K. Quality of life assessment in patients with a stoma due to

rectal cancer. Rep Prac Oncol Radiother 2008;13:130-4.

7. Ang SG, Chen HC, Siah RJ, He HG, Klainin-Yobas P. Stressors

relating to patient psychological health following stoma surgery:

An integrated literature review. Oncol Nurs Forum 2013;40:

587-94.

8. King CR. Health related quality of life issues for individual

with colorectal cancer. In: Berg DT, editor. Contemporary

issues in colorectal cancer: A nursing perspective. London:

Jones and Bartlett Publishers; 2011.

9. Vonk-Klaassen SM, de Vocht HM, den Ouden ME, Eddes

EH, Schuurmans MJ. Ostomy-related problems and their

impact on quality of life of colorectal cancer ostomates: a

systematic review. Qual Life Res 2016;25:125-33.

10. World Health Organization. Quality of life 2016 [Cited 2016

December 1]. Available from: http://www.who.int/mental_health/

media/68.pdf.

11. Padilla GV, Grant MM. Health related quality of life as a cancer

nursing outcome variable. ANS Adv Nurs Sci 1985;8:45-60.

12. Grumann MM, Noack EM, Homann IA, Schlag PM. Comparison

of quality of life in patients undergoing abdominoperineal

extirpation or anterior resection for rectal cancer. Ann Surg

2001;233:149-56.

13. Gooszen AW, Geelkerken RH, Hermans J, Lagaay MB, Gooszen

HG. Quality of life with a temporary stoma: ileostomy vs.

colostomy. Dis Colon Rectum 2000;43:650-5.

14. Fortes RC, Monteiro TMRC, Kimura CA. Quality of life from

oncological patients with denitive and temporary colostomy.

J Coloproctol 2012;32:253-9.

15. de Gouveia Santos VL, Chaves EC, Kimura M. Quality of life

and coping of persons with temporary and permanent stomas.

J Wound Ostomy Continence Nurs 2006;33:503-9.

16. Chitmon N. Health-related quality of life patients with permanent

colostomy. Bangkok: Chulalongkorn University; 2006.

17. Decha W, Navicharern R. Predicting factors of quality of

life among colorectal cancer patients with colostomy recieving

chemotherapy. Kuakarun J Nurs 2016;23:113-47.

18. Chutikamo N, Navicharern R, Lohsiriwat V. Predicting factors

of quality of life in colorectal cancer adult patients with colostomy.

Royal ai Navy Med J 2017;44:103-16.

19. Smith DM, Loewenstein G, Jankovic A, Ubel PA. Happily

hopeless: Adaptation to a permanent, but not to a temporary,

disability. Health Psychol 2009;28:787-91.

20. Teerathongdee K. Factors predicting quality of life in aged

patients with colorectal cancer aer stomal surgery. ai

Cancer J 2014;34:68-78.

21. Gracia Pereira M, Figueiredo AP, Fincham FD. Anxiety,

depression, traumatic stress and quality of life in colorectal

cancer aer dierent treatments: A study with Portuguese

patients and their partners. Eur J Oncol Nurs 2012;16:227-32.

22. Ransriwong P. Quality of life in colorectal cancer patient aer

stoma surgery. Suan Dok J 2549;15:22-6.

Chutikamo et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

201

Original Article

SMJ

Sakaorat Petchyim, M.D., Panida Kosrirukvongs, M.D., Ankana Metheetrairut, M.D., Sucheera Sarunket, M.D.,

Henry Warouw, M.D., Jatupol Chokboonpiem, M.D.

Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University,

Bangkok 10700, ailand.

An Agreement of Two Tonometers: Goldmann

Applanation and Non-Contact Scheimug

Technology in Healthy, Ocular Hypertension and

Open-angle Glaucoma Patients

Corresponding author: Sakaorat Petchyim

E-mail: sakaoratpoy012@gmail.com

Received 10 January 2018 Revised 19 April 2018 Accepted 8 June 2018

ORCID ID: http://orcid.org/0000-0002-7550-8605

http://dx.doi.org/10.33192/Smj.2019.31

ABSTRACT

Objective: e primary objective was to nd an agreement of intraocular pressure (IOP) assessed by Goldmann

applanation tonometry (GAT) and Corvis in healthy, ocular hypertension (OHT) and primary open-angle glaucoma

(POAG). e secondary objective was to nd a reliability of intra-examiner and inter-examiner IOP measurement

by GAT and Corvis.

Methods: Fiy three eyes from 53 participants were included and were divided into healthy (N=20), OHT (N=13)

and POAG group (N=20). Only right eyes were selected for further statistical analysis except one patient with only

le eye eligible. e eyes with corneal pathologies, greater than 2.5 diopters astigmatism, or recent ocular surgery were

excluded. Randomized examining sequence between GAT and Corvis was applied. To minimize an aer measurement

IOP uctuation, ve minutes and two minutes gap between measurements were strictly applied for Corvis and GAT

respectively. e rst ten patients had 3 measurements per measurer and two measurers were assigned per machine

to evaluate intra-examiner and inter-examiner reliability. Intraclass correlation coecient was used to analyze the

reliability of the IOP measuring machine. Bland & Altman plot was used to analyze an agreement between the machines.

Results: High ICCs were found in both measurers using GAT (ICC of measurer 1 = 0.954, measurer 2 = 0.977) and

Corvis (ICC of measurer 1 = 0.920, measurer 2 = 0.927) which indicated excellent intra-examiner reliability. High ICCs

were found when comparing IOP between 2 measurers who used the same machine (GAT ICC = 0.928, Corvis ICC =

0.915) which indicated excellent inter-examiner reliability. GAT tends to yield higher IOP reading. e mean IOP were

13.93±3.849 by GAT and 12.15±4.030 by Corvis. e mean IOP dierences were 1.8, 1.7, 1.4 and 2.2 mmHg in total,

healthy, OHT and POAG group respectively. POAG had highest mean dierence and widest standard deviation which

might result from poor agreement between 2 machines. According to Bland & Altman plot the values were scattered and

no trend was found indicating higher or lower average IOP would result in higher or lower dierence between the two

machines. From the clinical point of view, 71.7% and 47.2% fall into IOP dierence range of ±3 and ±2 mmHg respectively.

Conclusion: Corvis-IOP is a good parameter with excellent intra-examiner and inter-examiner reliability. In clinical

practice, the usefulness of Corvis-IOP is limited especially in POAG patients according to the poor agreement with

gold standard GAT-IOP.

Keywords: Corvis; comparison; tonometry; tonometer; intraocular pressure measurement; repeatability (Siriraj

Med J 2019;71: 201-206)

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

202

INTRODUCTION

Introcular pressure (IOP) measurement is crucial

for glaucoma diagnosis and management. Gold standard

instrument is Goldmann applanation tonometer.

Unfortunately, there were some drawbacks using this

machine such as well-trained user is required to take

measurement, required anesthetic and uorescein eye

drops, need to calculate central corneal thickness (CCT)-

corrected IOP, CCT and corneal biomechanical properties

should be taken separately by dierent machine. Corvis

ST (Corneal visualization scheimug technology, Oculus,

Wetzlar, Germany) is an IOP measurement machine

approved by FDA in the year 2013. IOP and CCT from

Corvis demonstrated excellent repeatability from previous

studies.

1-3

ey do not need eye drops or well-trained

user. Corvis is an interesting new machine that should

be considered. Moreover, plenty of data such as CCT,

corneal biomechanical properties and IOP are retrieved

at same time. ere are insucient clinical studies to

conclude that these two machines showed acceptable

agreement. ere is controversy since some studies

showed good agreement,

1,2,4

but some did not.

The

primary aim of the study was to assess the usefulness of

Corvis by evaluating an agreement with gold standard

GAT in healthy, ocular hypertension (OHT) and primary

open-angle glaucoma (POAG).

MATERIALS AND METHODS

e study was a cross-sectional study approved by

the Ethics Committee (Si 622/2014) of our institution

which followed the tenets of the Declaration of Helsinki

and signed inform consent were obtained.

We included subjects who were 18 years old or older

in the study. Participant with corneal pathologies, for

example corneal edema or keratoconus was excluded.

Participant who had more than 2.5 diopters astigmatism,

recently underwent corneal or glaucoma surgery within

3 months, nystagmus and uncooperative were excluded.

In this study, we classied all participants into 3

groups which were healthy, ocular hypertension (OHT)

and primary open-angle glaucoma (POAG). Healthy

participant was dened as participant who had no evidence

of glaucoma or ocular hypertension from medical record

and complete eye examination by ophthalmologist.

Ocular hypertension was dened as participant who had

intraocular pressure (IOP) of 21 mmHg or more with

no evidence of glaucoma. Primary open angle glaucoma

was dened as participants who were diagnosed with

POAG.

Subject allocation was done in each participant group

by randomizing into 2 dierent examining sequences

as displayed in the diagram 1, in order to minimize the

eect of machine sequence on IOP measurement. e

sequence was created using http://www.randomization.

com.

Diagram 1. Examining sequence

Petchyim et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

203

Original Article

SMJ

Two experience opticians (Measurer 1 and 2) who

worked in special equipment room and trained for using

Corvis machine were responsible for Corvis measurement.

Meanwhile, GAT was done by two ophthalmologists

(S.P. as measurer 1 and S.K. as measurer 2) during an

eye examination. Visual acuity, eye refraction and central

corneal thickness (CCT) by using Visante OCT were

done by one experienced optician.

CCT is the main parameter that could aect IOP

measurement. ere is no best CCT-corrected equation for

GAT when comparing with Dynamic contour tonometer

(DCT).

To minimize the eect of central corneal thickness

(CCT), corrected GAT IOP was calculated from GAT

IOP and CCT (Visante OCT) by using Doughty & Zaman

equation. is equation came from meta-analysis and

big database. Meanwhile, corrected Corvis IOPs were

automatically generated and collected. e study selected

only corrected IOPs from both devices for statistical

analysis.

For the rst 10 eyes, we took three dierent IOP

measurements by using each machine to assess intra-

examiner reliability and all measurements were repeated

by another examiner to assess inter-examiner reliability.

e intra-examiner and inter-examiner ICCs were excellent

in both GAT and Corvis group, as showed in Table 1. For

the rest of participants, GAT and Corvis measurements

were done by only measurer 1.

Two minute and 5 minute gaps between each

measurement were applied for GAT and Corvis

respectively, to minimize the effect on IOP from

previous measurement. Only the data from right eye

was analyzed, except one patients who had only le eye

eligible for the study so the data from le eye was used.

Sample size and statistic

Intraclass correlation coecients (ICC) is used to

assess interrater and intrarater reliability. In order to

compare an agreement of two measurement devices,

Bland and Altman plot was applied. All the statistical

analyses were performed using SPSS version 18.0 soware.

Aiming for excellent correlation between Goldmann

applanation tonometer (GAT) and Corvis, we used the

following statistical formula to calculate sample size for

intraclass correlations coecients of 0.75. At a condent

level 95%, SD 0.15 resulted in sample size of 131.

n = 8z

α/2 {(1-ρI)

(1+(k-1)ρI)

}/{k(k-1)w

}+1

RESULTS

e study ended up with 53 eyes from 53 participants

(female = 36) which included 3 groups healthy (N=20),

OHT (N=13) and POAG (N=20). Mean age of participants

was 62.40±10.132 years old. Mean IOP from three dierent

measurements by 2 measurers were shown in Table 1.

Intraclass correlation coecients were calculated from

rst ten participants for both intra-examiner and inter-

examiner as shown in Table 2. e excellent reliability

was found according to ICC level ≥ 0.75 in all parameters.

As shown in Table 3, mean IOP was lowest in POAG

group. is result was from a treatment that aimed for

low target IOP in this group. OHT group had highest

mean IOP which was consistent with a key feature of

the disease and treatment was not aimed for as low as

the IOP in POAG. GAT tended to yield higher IOP

reading than Corvis in total participants and in each

group. ICC in total participants reected fair to excellent

correlation between GAT and Corvis. However, in each

group, POAG group had poor correlation as ICC level

< 0.4 and ICC in OHT and healthy group were <0.4 as

well if consider a lower bound of 95%CI.

Mean IOP dierence result from GAT IOP was

minus Corvis IOP which positive value means that

GAT tends to give higher IOP than Corvis. Mean IOP

dierences were 1.8, 1.7, 1.4 and 2.2 mmHg in total,

healthy, OHT and POAG respectively. POAG had highest

mean dierence and widest standard deviation which

TABLE 1. Mean IOP of GAT and Corvis by two measurers of rst ten participants.

GAT IOP (mmHg) Corvis IOP (mmHg)

Measurer 1 Measurer 2 Measurer 1 Measurer 2

mean ± SD mean ± SD mean ± SD mean ± SD

First time 14.81± 3.823 15.10± 4.795 12.41± 4.307 12.05± 4.995

Second time 14.63± 3.856 15.30± 4.218 11.99± 4.033 12.30± 5.321

Third time 14.40± 3.831 15.10± 4.067 11.93± 4.071 11.53± 4.309

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

204

TABLE 2. Intra-examiner and inter-examiner Intraclass correlation coecients.

TABLE 3. e correlation between GAT and Corvis in IOP measurements.

Intra-examiner Inter-examiner

GAT Corvis GAT Corvis

Measurer 1 Measurer 2 Measurer 1 Measurer 2

ICC 0.954 0.977 0.920 0.927 0.928 0.915

95%CI 0.929-0.972 0.937-0.994 0.877-0.950 0.835-0.982 0.728-0.982 0.665-0.979

Group GAT (mmHg) Corvis (mmHg) GAT-Corvis (mmHg) ICC (95%CI)

Mean±SD Mean±SD Mean±SD

Total 13.93±3.849 12.15±4.030 1.78±2.944 0.793(0.520-0.899)

Healthy 12.91±3.393 11.22±3.191 1.69±2.371 0.797(0.353-0.927)

OHT 17.90±2.611 16.45±3.559 1.45±2.860 0.701(0.107-0.906)

POAG 12.11±2.984 9.96±2.620 2.15±3.675 0.207(-0.648-0.674)

Abbreviations: OHT=Ocular hypertension, POAG=Primary open angle glaucoma

may result from poor agreement between 2 machines.

e value was scattered with no trend for which higher or

lower average IOP will result in higher or lower dierence

between the two machines. From clinical point of view,

71.7% and 47.2% fall into IOP dierence range of ±3

and ±2 mmHg respectively.

DISCUSSION

From the study, both Corvis and GAT demonstrated

excellent repeatability and reproducibility by dierent

examiners for IOP measurement. is is consistent with

previous studies that IOP from Corvis is a parameter that

showed excellent intra-examiner and inter-examiner

reliability both in healthy and glaucoma eyes.

1-3

Interestingly, there was no dierence or tendency

of IOP from the rst to the third measurement (Table 1).

at means repeated measurement with 5 minutes and 2

minutes gap for Corvis and GAT respectively was sucient

to lessen the IOP eect from previous measurements.

ere was no study about how long should the gap be,

but air-pu technology as Corvis should take longer than

an applanation for the eect of prior measurement to be

vanished. e gap could be smaller, so a well-designed

study will answer this question.

According to the results, IOP acquired from GAT

tends to be higher than Corvis in all groups of participants.

Hong et al.,

who enrolled healthy volunteers and glaucoma

patients in their study to investigate an agreement between

GAT and Corvis found the same bias, approximately 1.3

mmHg higher when acquiring IOP from GAT. From

the study of Tejwani et al., GAT showed overestimated

IOP from GAT when compared to other machines

including Corvis.

However, there were some studies

which reported higher IOP readings from Corvis when

compared to GAT.

5,8

It is to be noted that this study,

Hong et al. and Tejwani et al. studies had randomized

an examination sequence. In contrast, Smedowski et al.,

use xed examination sequence which could result in

a bias from aer-IOP measurement uctuation.

Although, ±3 mmHg IOP dierence seems to be

acceptable, but for precise decision making in the clinic

±2 mmHg range is more reasonable. From Bland and

Altman, only 47.2% of all participants fall in to ±2 mmHg

range of IOP dierence which indicated that Corvis and

GAT could not be used interchangeably in the clinic. It is

to be highlighted that POAG group demonstrated highest

mean IOP dierence and widest standard deviation. Keep

in mind that this study used CCT-corrected IOP, assuming

Petchyim et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

205

Original Article

SMJ

CCT eect should be minimal. Biomechanical corneal

properties might be the reason, as POAG patients still

using topical anti-glaucoma medications. Several studies

showed that topical prostaglandin cause an eect on

corneal biomechanical properties by increasing corneal

hysteresis.

9-12

It could aect accuracy of IOP measurement

including IOP uctuation which nally resulted in more

variation of IOP. Unfortunately, there is no study about

the direct eect of long term usage of topical prostaglandin

analogues on IOP measurement at this time.

e limitation of this study was a small sample size

and corneal biomechanical properties were not taken

into account. By the way this study’s primary aim was

to assess the clinical usefulness of the new machine,

Corvis by comparing with GAT rather than to analyze

factors that could aect IOP measurement.

In conclusion, Corvis-IOP is a good parameter with

excellent level of reliability. In the clinic, the usefulness

of Corvis-IOP is limited especially in POAG patients

according to the poor agreement with gold standard

GAT-IOP.

ACKNOWLEDGMENTS

ank you very much to Mr.Suthipong Udompunturak

who always gave support for statistics and Miss Supattra

Sawangkul who lled in SPSS and managed everything

behind the scenes.

Conict of Interests: All authors declare no conict

of interests.

REFERENCES

1. Hong J, Xu J, Wei A, Deng SX, Cui X, Yu X, et al. A new

tonometer-the Corvis ST tonometer: clinical comparison

with noncontact and Goldmann applanation tonometers.

Invest Ophthalmol Vis Sci 2013;54:659-65.

2. Reznicek L, Muth D, Kampik A, Neubauer AS, Hirneiss C.

Evaluation of a novel Scheimpug-based non-contact tonometer

in healthy subjects and patients with ocular hypertension and

glaucoma. Br J Ophthalmol 2013;97:1410-4.

3. Salvetat ML, Zeppieri M, Tosoni C, Felletti M, Grasso L, Brusini

P. Corneal Deformation Parameters Provided by the Corvis-

ST Pachy-Tonometer in Healthy Subjects and Glaucoma

Patients. J Glaucoma 2015;24:568-74.

Fig 1. Bland-Altman plot, an agreement of IOP measurement between GAT and Corvis.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

206

4. Bañeros-Rojas P,Martinez de la Casa JM,Arribas-Pardo

P,Berrozpe-Villabona C,Toro-Utrera P,García-Feijoó J.

Comparison between Goldmann, Icare Pro and Corvis ST

tonometry. Arch Soc Esp Oalmol2014;89:260-4. [Article in

Spanish]

5. Smedowski A, Weglarz B, Tarnawska D, Kaarniranta K, Wylegala

E. Comparison of three intraocular pressure measurement

methods including biomechanical properties of the cornea.

Invest Ophthalmol Vis Sci 2014;55:666-73.

6. Ang GS, Nicholas S, Wells AP. Poor utility of intraocular

pressure correction formulae in individual glaucoma and

glaucoma suspect patients. Clin Exp Ophthalmol2011;39:

111-8.

7. Tejwani S, Dinakaran S, Joshi A, Shetty R, Roy AS. A cross-

sectional study to compare intraocular pressure measurement

by sequential use of Goldman applanation tonometry, dynamic

contour tonometry, ocular response analyzer, and Corvis ST.

Indian J Ophthalmol2015;63:815-20.

8. Lanza M, Iaccarino S, Cennamo M, Irregolare C, Romano V,

Carnevale UA. Comparison between Corvis and other tonometers

in healthy eyes. Cont Lens Anterior Eye2015;38:94-8.

9. Tsikripis P, Papaconstantinou D, Koutsandrea C, Apostolopoulos

M, Georgalas I. e eect of prostaglandin analogs on the

biomechanical properties and central thickness of the cornea

of patients with open-angle glaucoma: a 3-year study on 108

eyes. Drug Des Devel er2013;7:1149-56. .

10. Liehneová I,Karlovská S. e glaucoma pharmacological

treatment and biomechanical properties of the cornea. Cesk

Slov Oalmol2014;70:167-76. [Article in Czech]

11. Bolivar G, Sanchez-Barahona C, Teus M, Castejon MA,

Paz-Moreno-Arrones J, Gutierrez-Ortiz C, et al. Eect of topical

prostaglandin analogues on corneal hysteresis. Acta

Ophthalmologica 2015;93:e495-8.

12. Wu N, Chen Y, Yu X, Li M, Wen W, Sun X. Changes in Corneal

Biomechanical Properties aer Long-Term Topical Prostaglandin

erapy. PloS One 2016;11:e0155527.

Petchyim et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

207

Original Article

SMJ

Pharida Pengwan, M.D., Voraparee Suvannarerg, M.D., Aphinya Charoensak, M.D.

Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ailand.

The Use of Dual Energy Computerized Tomography

to Detect Residual Viable Hepatocellular Carcinoma

after Transarterial Chemoembolization

Corresponding author: Aphinya Charoensak

E-mail: caphinya@gmail.com

Received 24 June 2017 Revised 23 July 2017 Accepted 8 December 2017

ORCID ID: http://orcid.org/0000-0001-5179-9279

http://dx.doi.org/10.33192/Smj.2019.32

ABSTRACT

Objective: To determine the value of the dual energy computerized tomography (DECT) for detection of residual

viable hepatocellular carcinoma (HCC) aer transarterial chemoembolization (TACE).

Methods: Single-source (ss) DECT of liver was performed in adult patients who were diagnosed as HCC and

treated with TACE at Siriraj Hospital during October 1

, 2013- December 31

, 2014. e diagnostic 5-point

performance score of conventional liver CT imaging set (CCTI) and iodinated material density imaging set (IMDI)

obtained simultaneously by using DECT, were evaluated by two radiologists. e follow up imaging at 6 months

was regarded as gold standard. e sensitivity and specicity were calculated by assigned score 4 or 5 lesions as

positive for the presence of HCC, assigned score 1 or 2 lesions as negative for viable tumor and assigned score 3

lesions as uncertain diagnosis. McNemar’s test was used to compare the sensitivity and specicity between CCTI

and IMDI. e reading time of both technique and radiation dose were recorded and the mean reading time were

compared using a paired t-test.

Results: Out of total 21 patients with 66 lesions, 81% were male and 19% were female with mean age 61.8 ± 10.2

years old. Aer monitoring for 6 months, 35 of the total 66 lesions were still viable HCCs and 31 lesions became

non-viable HCCs. CCTI had excellent inter-observer agreement while IMDI had moderate agreement (K = 0.931

and 0.534, respectively). e sensitivity of CCTI and IMDI for detection of viable tumor were 88.6% and 100%,

respectively (p-value cannot be computed). e specicity of CCTI and IMDI were 96.8% and 93.5%, respectively

(p-value = 1.000). e mean reading time of two radiologists for CCTI was 151.2 ± 134.7 seconds and 123.2 ±

126.8 seconds for IMDI (p-value = 0.048). Total radiation dose of dynamic liver CT was 1194.22 ± 179.44 mGy cm.

Conclusion: IMDI has higher sensitivity for detection of viable HCCs aer TACE and consumes less reading time

than CCTI.

Keywords: Dual energy CT; viable HCC; transarterial chemoembolization (Siriraj Med J 2019;71: 207-213)

INTRODUCTION

Hepatocellular carcinoma (HCC) is the most common

primary malignant tumor of liver and is the second

leading cause of cancer mortality worldwide.

1,2

ere

are more than 700,000 newly diagnosed cases each year

and more than 600,000 deaths each year throughout

the world in which the major risk factors are hepatitis

C virus and hepatitis B virus infection.

e treatment

of HCC depends on patient status, Child pugh score,

number of tumors and tumor staging.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

208

Pengwan et al.

Transarterial chemoembolization (TACE) is an

eective palliative treatment for unresectable tumor

which interrupts arterial blood supply by chemoembolic

agent and results in ischemic tumor necrosis. Dynamic

computed tomography (CT) or Magnetic Resonance

Imaging (MRI) of the liver are commonly used for assessing

tumor response aer TACE. However, due to limitation

of MRI availability in ailand, most patients are followed

up with CT modality.

Dual-energy imaging is a new development in CT

which improves lesion detection and characterization.

Using two dierent simultaneous energy settings in

dual-energy CT (DECT), allows the dierentiation of

materials on the basis of their energy-related attenuation

characteristics (material density). A single x-ray tube

is used in single-source DECT (ssDECT) with the fast

kVp switching between 80 kVp and 140 kVp to generate

computed monochromatic images, which have less beam

hardening, pseudo enhancement and provide a higher

contrast-to-noise ratio than polychromatic images obtained

by conventional CT.

e obtained data from DECT can

be reconstructed to virtual unenhanced images as well

as iodinated contrast material density images. Radiation

dose savings are possible if virtual unenhanced images

replace true unenhanced images.

Detection of viable tumor around the ethiodized

oil-laden lesions aer TACE is usually dicult. Prior

study found that the color-coded iodine CT imaging

(CICT) generated by dual-detector DECT, is comparable

to conventional liver CT protocol for detecting viable

HCCs and can reduce mean radiation dose by 18.3%

when omitting the unenhanced phase CT.

e purpose of the present study is to determine

the value of DECT to detect viable HCC aer TACE by

comparing two imaging sets of conventional liver CT

(CCTI) and iodinated material density imaging (IMDI),

obtained simultaneously by using DECT.

MATERIALS AND METHODS

Patient population

is study was a preliminary and prospective study

that was approved by Siriraj Institutional Review Board

(Si 546/2013). A total of 68 adult patients (age >18 years

old) who had been diagnosed as HCC and treated with

TACE in Siriraj Hospital during 1 October 2013 to 31

December 2014 were recruited and written informed

consent was obtained. The patients with infiltrative

or hypovascular HCC, those who were treated with

combination therapy, no availability of follow up imaging,

or loss to follow up were excluded from the study. Finally,

21 patients were included. Demographic and clinical

data of patients were recorded including age, sex, AFP

level, date and number of TACE treatments.

DECT scanning and post-processing

All included patients were followed up with liver CT

imaging by using ssDECT scanner (Discovery CT750HD;

GE Healthcare Technologies, Milwaukee, WI, USA)

aer TACE treatment about 4-6 weeks. DECT scan was

performed only in arterial phase by using Gemstone

Spectral Imaging (GSI) abdomen protocol number 3

with following scan protocol: detector coverage 40 mm.,

helical thickness 5.0 mm., pitch and speed 1.375:1 mm/

rotation, rotation time 0.5 second, display FOV 35 cm.,

CTDI Vol 18.33 mGy. Reconstruction option (GSI ASiR

20%) and standard reconstruction type with slice thickness

1.25 mm. and interval 1.25 mm. were used.

Pre-contrast phase and portovenous phase were

performed by using single energy CT of 120 kVp with

following scan protocol: detector coverage 40 mm., pitch

and speed 1.375:1 mm/rotation, rotation time 0.5 second,

auto mA (min 200 mA, max 500 mA), noise index 20,

and reconstruction 1.25 mm.

For iodine contrast medium adminstration, we

used Iopamiro (370 mg Iodine/ml) with Medrad-XDS

Stellant CT injection system (Bayer Healthcare LLC,

Whippany, New Jersey, USA). Dose of contrast medium

was 2 ml/kg. Flow rate and delayed scanning time for

arterial phase was adjusted by patient body weight in

order to obtain late arterial phase. Flow rate 3 cc/min

and delayed time of 40 sec for patient body weight < 50

kg, ow rate 3.5 cc/min and delayed time of 38 sec for

patient body weight 50-70 kg and ow rate 4 cc/min

and delayed time of 35 sec for patient body weight >70

kg. Portovenous phase was obtained at a xed delayed

time at 80 seconds aer contrast medium injection.

e computed monochromatic images at 70 keV were

generated for arterial phase of CCTI at post-processing

workstation. en, the iodinated material density images

were created by processing of the 70 keV computed

monochromatic image using mono material density

compare technique of GE workstation.

Data collection and interpretation

Two CT imaging sets were independently reviewed

by two radiologists who had experience of 13 years for

reader 1 and 5 years for reader 2. CCTI set included pre-

contrast phase, arterial phase computed monochromatic

image at 70 keV and portovenous phase. For IMDI set,

post-processing iodinated material density images were

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

209

Original Article

SMJ

used for arterial phase. Two radiologists reviewed each

imaging set at time interval about 8 weeks to exclude

recognition bias.

e number of tumor, tumor size, and reading

time of two radiologists for each imaging set, radiation

dose and type of follow-up imaging were recorded.

Five-point performance score was used to evaluate post

TACE response.

Score 1: Dense iodized oil uptake with or without

a thin marginal rim enhancement.

Score 2: Suggestive of a non-viable tumor with a

mildly thickened, smooth marginal rim enhancement,

but without nodular enhancement.

Score 3: Suspicious for viable tumor seen as equivocal

nodular enhancement or an irregularly thickened marginal

rim enhancement.

Score 4: Suggestive of viable tumor with more

prominent abnormal ndings

Score 5: Denite viable tumor

e discordant performance score for each imaging

set was consensus by two radiologists and undetected

lesion was rated as score 0.

To compare the diagnostic performance of both

imaging sets, the present study used imaging follow up

with hepatic angiogram, liver MRI or liver CT until 6

months as gold standard. A viable tumor was dened as

hypervascularized and neovascularized tumor staining

on hepatic angiogram, or a lesion that demonstrated

arterial enhancement or portovenous washout on liver

CT/MRI. Non-viable tumor was dened as lesion without

hypervascularized and neovascularized staining on hepatic

angiogram, or dense lipiodol staining lesion without

arterial enhancement or portovenous washout on liver

CT/ MRI.

Statistical analyses

Agreement between two radiologists for each imaging

set were determined using weighted kappa (quadratic

weight, K) which was classied as; K of 0.00-0.20, 0.21-

0.40, 0.41-0.60, 0.61-0.80 and 0.81-1.00 for poor, fair,

moderate, good and excellent agreement, respectively. To

calculate the sensitivity and specicity for each modality,

lesions assigned to score 4 or 5 were regarded as positive

for the presence of HCC and lesions assigned to score 1

or 2 were regarded as negative for viable tumor. Lesions

assigned to score 3 was regarded as uncertain diagnostic

lesions. McNemar’s test was used to compare the sensitivity

and specicity between CCTI and IMDI. A paired t-test

was applied to compare mean reading time between

CCTI and IMDI. e radiation dose was reported using

descriptive statistics. All statistical data analyses were

performed using SPSS 18.0. P-value of less than 0.05

indicated a statistically signicant dierence.

RESULTS

A total of 21 patients, 17 patients (81%) were male

and 4 patients (19%) were female with mean age 61.8

± 10.2 years old (range 42-82 years). At the time of the

TACE, the mean serum alfa-fetoprotein (AFP) level was

about 165.9 ± 498.9 IU/ml (Max= 2248 and Min= 2.3

IU/ml). Episodes of TACE treatment were 1

time in

7 patients (33.3%), 2

-4

times in 12 patients (57.1%)

and ≥ 5

times in 2 patients (9.5%). Number of lesions

treated with TACE was single lesion in 8 patients (38.0%),

2-5 lesions in 11 patients (52.4%) and > 5 lesions in 2

patients (9.6%). Mean duration of CT aer TACE was

about 6.57 ± 3.27 weeks. ere were 66 lesions in these

21 patients. Tumor size ranged from 0.5-16.3 cm., mean

2.71 ± 2.97 SD.

At 6 months follow-up, 14 patients underwent

conventional liver CT, 3 patients underwent hepatic

angiogram with TACE, 3 patients underwent both of

conventional liver CT and hepatic angiogram with TACE

and only one patient underwent liver MRI with Primovist.

ere were 35 viable HCCs lesions and 31 non-viable

HCCs lesions.

Table 1 showed diagnostic 5-point performance score

of overall ethiodized oil-laden lesions and viable HCCs.

e lesion detection rate of overall ethiodized oil-laden

lesions and viable HCCs were excellent (97.1% - 100%) by

both imaging sets. e inter-observer agreement between

both radiologists for overall ethiodized oil-laden lesions

were excellent. However, the inter-observer agreement

for viable HCC lesions by CCTI was excellent (K =

0.931), but the inter-observer agreement by IMDI was

moderate (K =0.534).

Table 2 showed diagnostic 5-point performance

score of overall ethiodized oil-laden lesions of both

imaging sets aer consensus by two radiologists. e

iodinated material density image detected more viable

tumor (score 4 and 5, n=35 vs. n=31) but less uncertain

diagnosis (score 3, n=2 vs. n=4) and non-viable tumor

(score 1 and score 2, n= 29 vs. n= 30) than conventional

CT image.

Of the total 35 viable HCC lesions, IMDI correctly

dened as viable tumor in all lesions (score 4 and 5, n =

9 and 26; sensitivity = 100%) whereas CCTI dened as

viable tumor in 31/35 lesions (score 4 and 5, n = 6 and 25;

sensitivity = 88.6%). ere was one missed viable tumor

(Fig 1) and three uncertain diagnostic lesions (score 3)

by CCTI (Fig 2). McNemar p-value cannot be computed

to compare the sensitivity between IMDI and CCTI due

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

210

Pengwan et al.

TABLE 1. Diagnostic 5-point performance score of overall ethiodized oil-laden lesions and viable HCCs.

Type of lesion Imaging set Score Lesion Weighted

detection rate K value

0 1 2 3 4 5

Overall ethiodized CCTI Reader 1 1 20 11 5 3 26 98.5% 0.968

oil-laden lesions Reader 2 1 21 6 7 7 24 98.5%

(n=66) IMDI Reader 1 0 23 6 7 2 28 100% 0.942

Reader 2 0 28 0 1 13 24 100%

CCTI Reader 1 1 0 1 4 3 26 97.1% 0.931

Viable HCCs Reader 2 1 0 0 3 7 24 97.1%

(n=35) IMDI Reader 1 0 0 0 5 2 28 100% 0.534

Reader 2 0 0 0 0 12 23 100%

TABLE 2. Diagnostic 5-point performance score of overall ethiodized oil-laden lesions (n= 66) of both imaging

sets aer consensus by two radiologists.

IMDI score

Total

CCTI score 0 1 2 3 4 5

0 0 0 0 0 1 0 1

1 0 22 0 0 0 0 22

2 0 3 4 1 0 0 8

3 0 0 0 1 3 0 4

4 0 0 0 0 3 3 6

5 0 0 0 0 2 23 25

Total 0 25 4 2 9 26 66

Fig 1. Demonstrated missed viable tumor by CCTI but could detected by IMDI.

A. Unenhanced CT image showed a tiny ethiodized oil-laden lesion near liver dome.

B. Arterial phase computed monochromatic image at 70 keV showed no denite arterial enhancement (score 0)

C. Arterial phase iodinated material density image showed nodular arterial enhancement (arrow) surrounding ethiodized oil-laden

lesion (score 4).

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

211

Original Article

SMJ

Fig 2. Demonstrated uncertain diagnostic lesion by CCTI but dened as viable tumor by IMDI.

A. Arterial phase computed monochromatic image at 70 keV showed a partial ethiodized oil-laden lesion with equivocal nodular

enhancement (arrow); score 3.

B. Arterial phase iodinated material density image showed nodular arterial enhancement (arrow); score 4. Another viable HCC

was also seen at hepatic segment VI (score 5).

to 100% sensitivity of IMDI. Among 31 non-viable HCC

lesions, IMDI was dened as non-viable tumor in 29/31

lesions (score 1 and 2, n= 25 and 4; specicity=93.5%)

and uncertain diagnosis (score 3) in 2/31 lesions. CCTI

dened as non-viable tumor in 30/31 lesions (score 1

and 2, n= 22 and 8; specicity=96.8%). e remaining

one case was dened as uncertain diagnosis (score 3).

Fig 3 showed a non-viable HCC lesion which was dened

as uncertain diagnosis (score 3) by both imaging sets.

ere was no statistically signicant dierence of the

specicity between IMDI and CCTI (McNemar p-value

= 1.000).

e overall mean reading time of two radiologists

for CCTI was 151.2 ± 134.7 seconds and 123.2 ± 126.8

seconds for IMDI (p-value = 0.048).

Table 3 showed the mean radiation dose of dynamic

liver CT. Mean total radiation dose was 1194.22 ± 179.44

mGycm. Mean value of the CTDI Vol were 12.17 ± 2.09

mGy, 13.33 mGy, and 12.17 ± 2.06 mGy for unenhanced,

arterial and portovenous phases, respectively.

Fig 3. Demonstrated a non-viable HCC lesion which was dened as uncertain diagnosis (score 3) by both imaging sets.

A. Arterial phase computed monochromatic image at 70 keV showed a partial ethiodized oil-laden lesion with equivocal nodular

enhancement (arrow) at central part of lesion.

B. Arterial phase iodinated material density image also showed equivocal nodular enhancement (arrow) at central part of lesion.

Aer 6 months follow-up, this lesion was conrmed a non-viable tumor. All of other remaining lesions seen on both imageswere

correctly dened as viable tumors (score 5).

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

212

Pengwan et al.

TABLE 3. Mean radiation dose of dynamic liver CT.

Mean ± SD

Phase CTDI Vol (mGy) DLP (mGy cm)

Unenhanced 12.17 ± 2.09 384.21 ± 79.49

Arterial 13.33 423.39 ± 33.76

Portovenous 12.17 ± 2.06 386.63 ± 77.46

Total DLP 1194.22 ± 179.44

DISCUSSION

Due to lack of MRI availability, conventional CT

of liver is usually used to assess therapeutic response of

HCC aer TACE. However, it has only 43% accuracy, 36%

sensitivity and 57% specicity for evaluation of tumor

viability aer TACE.

DECT has potential benet to detect

hypervascular hepatic lesions including HCC. Based on

the fact that contrast material has higher attenuation at

lower peak voltage

, computed monochromatic images

obtained from ssDECT at lower keV levels can provide

greater conspicuity of hypervascular hepatic lesions with less

noise than polychromatic images from conventional CT.

However, evaluation of viable HCC aer TACE is usually

dicult because ethiodized oil in the chemotherapeutic

agent used in TACE contains iodine which can mimic

focal hepatic enhancement on iodinated material density

image.

erefore, unenhanced images must be obtained

and interpreted in conjunction with enhanced images.

9, 10

The present study showed that IMDI had only

moderate inter-observer agreement. is could be from

both readers had little experience in IMDI. It would be

better if the third radiologist with high experience was

assigned to judge a discordant performance score. e

reading time of IMDI was reduced by 28 seconds when

compare with CCTI (p-value = 0.048). IMDI had sensitivity

of 100% and specicity of 93.5% for detection of viable

HCC aer TACE while the sensitivity and the specicity

of CCTI were 88.6% and 96.8%, respectively. Calculation

of the sensitivity and the specicity was done by assigning

the score 3 lesions as uncertain diagnosis. If the authors

assigned the score 1 or 2 lesions as negative for viable

tumor and lesions with score 3, 4, or 5 as positive for

the presence of HCC, the sensitivity and the specicity

of CCTI will be 97.1% and 96.8%, respectively while

the sensitivity and the specicity of MDCI will remain

unchanged. CCTI in the present study had much higher

sensitivity and specicity than prior study

because it

used computed monochromatic image at 70 keV during

arterial phase instead of polychromatic images from

conventional CT. e possible explanation of very high

sensitivity and specicity in the present study could

be that almost all of viable lesions (34/35 lesions) had

area of ethiodized oil staining < 90%. is resulted in

untroubled dierentiation between viable tumor and

ethiodized oil.

Radiation dose is a concerned issue of DECT. Radiation

dose minimizing is possible if obviating unenhanced CT

acquisition.

4,5

However, unenhanced CT is essential for

assessing therapeutic response of HCC aer TACE. e

present study shown that mean value of the CTDI Vol

of arterial phase obtained from ssDECT (13.33 mGy)

was slightly higher than the CTDI Vol of unenhanced

and portovenous phases performed by single energy CT

(12.17 ± 2.09 mGy and 12.17 ± 2.06 mGy). Prior study

tried to develop a method to discriminate viable HCC

from ethiodized oil by limiting the window setting of the

color-coded iodine map of DECT without unenhanced

images.

Result showed that the color-coded iodine CT

is comparable to conventional CT for detection of viable

HCC aer TACE, while it allows a reduction in radiation

dose. However, the range of Hounseld unit (HU) in

viable HCC is partially overlapped with normal hepatic

parenchyma. A further study is needed.

e present study had some limitations. First, it was

a preliminary study with a small number of population.

Second, the readers had little experience in interpretation

of the material density images and there was only moderate

inter-observer agreement between both readers. It is

required to have more experience in the interpretation

skill of DECT images. ird, there was no pathological

conrm of viable HCC.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

213

Original Article

SMJ

CONCLUSION

IMDI has higher sensitivity for detection of viable

HCCs aer TACE with less consumed reading time

than CCTI. DECT including unenhanced and enhanced

acquisitions has high sensitivity and specicity to detect

viable HCC aer TACE with slightly higher radiation

dose than conventional liver CT. Further research is

needed to develop a method for radiation dose reduction.

ACKNOWLEDGMENTS

The authors (VS, AC) were supported by

Chalermphrakiat Grant, Faculty of Medicine Siriraj

Hospital, Mahidol University. e authors wish to thank

Dr. Chulaluk Komoltri for the statistical analysis.

REFERENCES

1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C,

Rebelo M, et al. Cancer incidence and mortality worldwide:

sources, methods and major patterns in GLOBOCAN 2012.

Int J Cancer 2015;136:E359-86.

2. Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular

carcinoma incidence, mortality, and survival trends in the

United States from 1975 to 2005. J Clin Oncol 2009;27:1485-

91.

3. Shari MI, Cox IJ, Gomaa AI, Khan SA, Gedroyc W, Taylor-

Robinson SD. Hepatocellular carcinoma: current trends in

worldwide epidemiology, risk factors, diagnosis and therapeutics.

Expert Rev Gastroenterol Hepatol 2009;3:353-67.

4. Silva AC, Morse BG, Hara AK, Paden RG, Hongo N, Pavlicek

W. Dual energy (Spectral) CT: applications in abdominal

imaging. Radio Graphics 2011;31:1031-46.

5. Ho LM, Yoshizumi TT, Hurwitz LM, Nelson RC, Marin D,

Toncheva G, et al. Dual energy versus single energy MDCT:

measurement of radiation dose using adult abdominal imaging

protocols. Acad Radiol 2009;16:1400-7.

6. Lee JA, Jeong WK, Kim Y, Song SY, Kim J, Heo JN, et al. Dual-

energy CT to detect recurrent HCC aer TACE: initial experience

of color-code iodine CT image. Eur J Radiol 2013;82:569-76.

7. Hunt SJ, Yu W, Weintraub J, Prince MR, Kothary N. Radiologic

monitoring of hepatocellular carcinoma tumor viability aer

transhepatic arterial chemoembolization: estimating the accuracy

of contrast-enhanced cross-sectional imaging with histopathologic

correlation. J Vasc Interv Radiol 2009;20:30-8.

8. Yeh BM, Shepherd JA, Wang ZJ, Teh HS, Hartman RP, Prevrhal

S. Dual energy and low-kVp CT in the abdomen. AJR Am J

Roentgenol 2009;193:47-54.

9. Kim HC, Kim AY, Han JK, Chung JW, Lee JY, Park JH. Hepatic

arterial and portal venous phase helical CT in patients treated

with transcatheter arterial chemoembolization for hepatocellular

carcinoma: added value of unenhanced images. Radiology

2002;225:773-80.

10. Kim SH, Lee WJ, Lim HK, Lim JH. Prediction of viable tumor

in hepatocellular carcinoma treated with transcatheter arterial

chemoembolization: usefulness of attenuation value measurement

at quadruple-phase helical computed tomography. J Comput

Assist Tomogr 2007;31:198-203.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

214

Prapapin Siripohn, HN, M.Sc.*, Porntita Visavajarn, R.N., M.Sc.*, Ueamphon Suwannatrai, M.Ed.**, Supakij

Suwannatrai, M.Sc.**, Peamruetai Butdapan, BATM.**, Monchai Ruangchainikom, M.D.***

*Department of Nursing, Siriraj Hospital, **Center of Applied ai Traditional Medicine, ***Department of Orthopaedic Surgery, Faculty of Medicine

Siriraj Hospital, Mahidol University, Bangkok 10700, ailand.

The Effects of the Thai Traditional Medicine of

Abdominal Massage on Defecation in Post Lumbar

Laminectomy Patients

Corresponding author: Monchai Ruangchainikom

E-mail: monchai.ortho@gmail.com

Received 2 March 2018 Revised 18 April 2019 Accepted 22 April 2019

ORCID ID: http://orcid.org/0000-0003-0525-6390

http://dx.doi.org/10.33192/Smj.2019.33

ABSTRACT

Objective: is prospective study examined the defecation enhancement eects in post-lumbar laminectomy

patients who received ai traditional medicine of abdominal massage (TTMAM) in combination with standard

nursing care, compared with patients receiving only standard nursing care.

Methods: is prospective, randomized, controlled trial was conducted at Siriraj Hospital between 2011 and 2015.

Eighty-eight patients with spinal stenosis scheduled for lumbar laminectomy with or without fusion were enrolled.

e patients were randomly assigned to two groups: the rst group underwent standard nursing care combined

with TTMAM (the TTMAM group), and the second group underwent standard nursing care (the non-TTMAM

group). e clinical outcomes regarding the rst defecation within 3 days aer surgery, abdominal distension, and

patient satisfaction with defecation care were evaluated.

Results: When comparing the rst defecation within 3 days aer surgery, no signicant dierences were found in

the number of patients between the two groups. e number of the patients who had their rst defecation within

3 days aer surgery was higher in the TTMAM group (46.5%) than the non-TTMAM group (27.3%). ere was

signicantly less abdominal distension on the third day aer surgery in the TTMAM group than in the non-

TTMAM group. Moreover, the mean score of patient satisfaction of the TTMAM group was higher than that of

the non-TTMAM group.

Conclusion: ai traditional medicine of abdominal massage tends to help defecation in post-lumbar laminectomy

patients as it relieves abdominal distension and increases satisfaction with defecation care. erefore, the use of

TTMAM with other bowel care methods could provide additional benet for lumbar laminectomy patients.

Keywords: ai traditional medicine of abdominal massage; defecation; post lumbar laminectomy patient (Siriraj

Med J 2019;71: 214-219)

INTRODUCTION

Lumbar laminectomy is a surgical procedure to enlarge

the spinal canal and relieve pressure on the spinal cord

or nerve roots caused by spinal stenosis.

Constipation

is a common problem for many people recovering from

back surgery.

2,3

Phataranavic et al. suggested that 9% of

*is study was supported by Siriraj Research Development Fund (Managed by Routine to Research: R2R)

postoperative orthopedic patients have constipation.

Even though constipation is not life-threatening, the

absence of any treatment may cause discomfort, abdominal

distention, abdominal pain, and the loss of appetite, with

the possibility of fever, vomiting, and delirium.

5,6,7

Siripohn et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

215

Original Article

SMJ

e use of the common constipation treatments

(stool soeners, laxatives, and enemas) sometimes leads

to harmful side-eects like abdominal distention, nausea,

uid and electrolyte loss, and defecation-reex loss,

particularly with patients with chronic diseases.

ere

have been studies on constipation prevention programs

that have utilized high ber foods and the drinking

of water.

9,10

However, such programs require careful

administration in the case of elderly patients with heart,

lung, or kidney diseases in order to avoid water and

electrolyte imbalances.

e use of complementary approaches like abdominal

massage to relieve constipation has been suggested since

the 19

century.

Several studies on patients with spinal

injuries found that abdominal massage reduced the colonic

transit time and abdominal distention, increased the

frequency of defecation, and improved continence.

13,14,15

e Center of Applied ai Traditional Medicine,

Faculty of Medicine Siriraj Hospital, Mahidol University

has much experience with the administration of a range

of traditional healing approaches. e ai traditional

medicine of abdominal massage (TTMAM) is one of the

treatments which is normally administered to patients

with constipation, most of whom had improved defecation

as a result. However, to our knowledge, there is no data

or research available relating to the eects of TTMAM

on defecation in post lumbar laminectomy patients.

e present study was designed to examine the eects

of TTMAM in post lumbar laminectomy patients in

terms of defecation.

MATERIALS AND METHODS

This single-center, prospective, randomized,

controlled trial was conducted during the 2011 to 2015

study period. e Siriraj Institutional Review Board

(SIRB), Faculty of Medicine Siriraj Hospital, Mahidol

University, approved the study protocol (Si. 095/2011).

e enrolled subjects were spinal stenosis patients who

were scheduled to undergo a decompressive laminectomy

with or without fusion. Patients were excluded if they

had any of the following conditions: abdominal aortic

aneurysm; aortic dissection; palpable pulsatile intra-

abdominal mass; previous abdominal surgery; preexisting

medical diseases which could interfere with defecation,

such as hypothyroidism, delirium, and stroke; or the

need to be placed in the ICU post-operatively.

Patients were randomized into two groups (44

patients per group) using simple randomization. e

control group (non-TTMAM) consisted of patients who

received standard nursing care only. e intervention

group (the TTMAM group) was comprised of patients

who were provided with the TTMAM in addition to

standard nursing care. Aer being provided with verbal

and written information regarding the procedure, 88

patients were accepted to participate in this study. Written

informed consent was obtained from all 88 participants.

Postoperatively, the non-TTMAM group received

standard nursing care. is consisted of a deep breathing

exercise every 4 hours, and at least 100 times per day;

turning the patients every 2 hours; an ankle pumping

exercise at least 100 times per day; and the drinking of

at least 1,000 cc of water per day.

By comparison, the TTMAM group received standard

nursing care combined with the TTMAM on Days 1 to

3 postoperatively; twenty minutes of the TTMAM was

performed two hours aer dinner. e TTMAM was

conducted by certied, applied-ai traditional medicine

therapists from the Center of Applied ai Traditional

Medicine, Faculty of Medicine Siriraj Hospital. e

TTMAM maneuver is described in Fig 1.

e clinical outcomes that were evaluated comprised

the rst defecation within 3 days aer surgery and the

abdominal symptoms after surgery. The latter were

assessed daily using the abdominal distention evaluation

form (modied from Wattanawetch

); belching, atus

excretion, the perception of fullness, bowel sounds, and

increases in abdominal girth were examined. Patient

satisfaction was evaluated by the level of satisfaction with

defecation care, which was determined by questionnaires

administered on the fourth day aer surgery.

Statistical analysis

All statistical analyses were performed using SPSS

Statistics for Windows, version 18. A chi-square test was

used to compare the number of participants in the two

groups who rst defecated within 3 days aer surgery,

and the degree of abdominal distention experienced by

the experimental and control groups. An independent

t-test was used to compare the level of satisfaction with

the defecation care reported by patients in the two groups.

A p-value of 0.05 or less was considered statistically

signicant.

RESULTS

The forty-four patients in the TTMAM group

consisted of thirty females and fourteen males, with an

average age of 62.8 years. e forty-four patients in the

non-TTMAM group, comprised of thirty-ve females

and nine males, had an average age of 63.8 years. e

demographic data are shown in Table 1. All patients

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

216

Fig 1. e ai traditional medicine abdominal massage maneuver. e subject is placed in a supine position. e massage therapist stands

beside the subject and uses the thumb, nger tips and hand to massage along the muscles via 4 motions; the split motion (1A); the pressing

motion (1B); the scooping motion (1C); and the so massage of 5 important abdominal points, to about 70% of the maximum weight (1D).

Fig 1A split motion

Fig 1B pressing motion

Fig 1C scooping motion

Fig 1D massage important abdominal points

completed the study protocol. ere were no statistically

signicant dierences between the two groups, and no

complications were found in either group.

When comparing the number of patients with

a rst defecation within 3 days aer surgery, no signicant

dierences were found in the gures for the two groups.

However, the number was higher for the TTMAM group

(n = 20, 46.5%) than for the non-TTMAM group (n = 12,

27.3%; p = 0.063).

On the other hand, there was a signicant dierence

between the intervention and control groups in terms

of the degree of abdominal distention and abdominal

discomfort on the third day aer surgery (Table 2).

In addition, there was a statistically signicant dierence

in the mean scores for satisfaction with the defecation

care reported by the patients in the two groups (Table 3).

Siripohn et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

217

Original Article

SMJ

TABLE 1. Baseline characteristics of 88 patients with spinal stenosis who randomly received standard nursing care

(non-TTMAM group) versus TTMAM in addition to standard nursing care (TTMAM group).

Non-TTMAM Group TTMAM Group

(n = 44) (n = 44)

Gender (male: female ) 9:35 (20.5%:79.5%) 14:30 (31.8%:68.2%)

Age (years) 63.8 62.8

Laminectomy 14(31.8%) 24(54.5%)

Laminectomy with fusion 30(68.2%) 20(45.5%)

Volumes of drinking water

day after surgery (mL) 1278.6±470.2 1254.3±504.3

day after surgery (mL) 1351.6±496.3 1277.1±462.6

day after surgery (mL) 1305.4±475.3 1381.1±496.0

Morphine 34(77.2%) 30(68.2%)

Abbreviation: TTMAM = ai traditional medicine of abdominal massage

TABLE 2. Comparison of the number and percentage of patients with abdominal distention and of the level of

abdominal distention on the 3

day aer surgery in the control and experimental groups.

Non-TTMAM Group TTMAM Group P-value

(n = 44) (n = 44 )

Belching / 4 hours 0.70

No belching 12 (27.3%) 16 (36.4%)

1-10 times 30 (68.1%) 27 (61.3%)

> 11 times 2 (4.5%) 1 (2.3%)

Flatus excretion 0.92

 Noatusexcretion 1(2.3%) 1(2.3%)

1-6 times 34 (77.3%) 33 (75.0%)

 ≥7times 9(20.5%) 10(22.7%)

Perception of fullness 0.04*

Severe 1 (2.3%) 1 (2.3%)

Moderate 29 (65.9%) 16 (36.4%)

Mild 14 (31.8%) 27 (61.4%)

Bowel sounds 0.66

< 3 times / minute 7 (15.9%) 5 (11.4%)

> 3 times / minute 37 (84.1%) 39 (88.6%)

Increased abdominal girth 0.41

> 3.9 centimeters 16 (36.4%) 11 (25.0%)

< 3.9 centimeters 28 (63.6%) 33 (75.1%)

Degree of abdominal distention 0 .01*

Mild 10 (22.7%) 21 (47.7%)

Moderate 34 (77.3%) 21 (47.7%)

Severe 0 (0.0%) 2 (4.5%)

* = statistical signicance level of ≤0.05

Abbreviation: TTMAM = ai traditional medicine of abdominal massage

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

218

TABLE 3. Comparison of the mean scores for patient satisfaction with defecation care for the non-TTMAM and

TTMAM groups.

Non-TTMAM Group TTMAM Group P-value

(n = 44) (n = 44)

Satisfaction score 2.34 ± 1.92 4.09 ± .86 < 0.001***

*** = statistical signicance level of ≤0.001

Abbreviation: TTMAM = ai traditional medicine of abdominal massage

DISCUSSION

is study found that constipation, dened as a rst

defecation later than 3 days aer surgery, is a common

problem among lumbar laminectomy patients (72.7% in

the standard nursing care, or non-TTMAM, group). Pain

aer surgery encourages patients to remain in bed aer

surgery, which causes the sympathetic nervous system

to become dominant. In turn, this inhibits the bowel

functions, slows bowel movements, aects digestion, causes

poor absorption, and promotes abdominal distention

and constipation.

Moreover, pain aer surgery is oen

treated with opioids, such as morphine, thereby reducing

the patient’s bowel movements.

e results of the present study on the number of

defecations within the rst 3 days aer surgery found that

there was no statistically signicant dierence between

the group that received the TTMAM and the group that

received standard bowel care. Even though previous

studies have reported that the use of the TTMAM has

enhanced defecation, most of those studies were done on

spinal injury patients who had chronic constipation.

13,14

On the other hand, the patients in the present study

were in a dierent situation because of their recent

spinal surgery; they had limited mobility and acute pain,

which led to an acute change in the habit of constipation

rather than to the chronic constipation reported in the

aforementioned studies that had enrolled chronic spinal

cord injury patients.

With regard to abdominal distention on the third

day aer surgery, the present study demonstrated that

the group that had received TTMAM had less severe

abdominal distention than the group that had only

been treated with standard nursing care, with statistical

signicance. is nding is in line with a study on the

eects of abdominal massage on the gastrointestinal

function in patients with spinal injuries

; it found that

abdominal massage improved bowel movements, reduced

the colonic transit time, and reduced abdominal distention,

as massaging increases pressure in the abdomen. Massaging

also stimulates the somato-autonomic reexes, which

in turn reduce the colonic transit time.

Furthermore,

abdominal massage stimulates the parasympathetic system,

which is responsible for the stomach and the intestinal

functions, thereby reducing abdominal distention.

The analysis of the level of patient satisfaction

with defecation care revealed that the group receiving

the TTMAM were more satised than the group given

standard nursing care, with statistical signicance. An

earlier study of the eects of Swedish abdominal massage

on constipation found that patients felt satised and safe

while the massage was being given.

Another study on

the eects of the TTMAM together with a soap rectal

suppository on spinal injury patients determined that

none rejected the massage, they felt relaxed during

the abdominal massage, and there were no feelings of

distention or discomfort.

Aer the TTMAM, those

subjects were able to pass atus for longer durations, had

less abdominal distention and no nausea, and were able

to defecate more easily. ese ndings can be explained

by the fact that abdominal massage is a type of touch

that is meaningful and stimulates a profound feeling.

Massage inhibits the hypothalamic function, which works

with the autonomic system to stimulate the secretion of

norepinephrine and acetylcholine in the sympathetic and

parasympathetic systems. Norepinephrine has a positive

eect on a person’s mood. In addition, massage reduces

the function of the sympathetic system and stimulates

the parasympathetic system, which causes relaxation.

18,19

e limitations of this study are related to uncontrollable

factors, such as the amount of high-ber food eaten, the

degree of patient mobility, and the level of stress arising

from the surgery. Bowel movements and abdominal

pressure were not measured. Moreover, the volume and

consistency of the feces were not evaluated.

Siripohn et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

219

Original Article

SMJ

CONCLUSION

e ai traditional medicine of abdominal massage

tends to help post-laminectomy patients to defecate.

Furthermore, this procedure reduces abdominal distention

and increases patient satisfaction. It should therefore be

employed with other defecation stimulation methods.

REFERENCES

1. Chiengthong K, Bunmaprasert T. Degenerative disease of the

spine. Chiang Mai: Faculty of Medicine, Chiang Mai University;

2007. (In ai)

2. Pamela E. Verkuilen. Preventing Constipation Aer Back

Surgery. (Internet). 2007 (Cited 2017 July 22). Available from:

http://www.spine-health.com/treatment.

3. Cassinelli EH, Eubanks J, Vogt M, Furey C, Yoo J, Bohlman

HH. Risk factors for the development of perioperative complications

in elderly patients undergoing lumbar decompression and

arthrodesis for spinal stenosis. Spine J. 2007;32:230-35.

4. Phataranavic P, Okmaen R, Kuntisomboon S. A study of

symptom disturbances and postoperative complications in

orthopaedic patients. Journal of Orthopaedic Nursing. 2005;10:

85-99. (In ai.)

5. Eberhardie C. Constipation: Identifying the problem. Nurs

Older People. 2003;15:22-6.

6. Khumtaveeporn P. Pathophysiology of movement. In: Unnapirak

L, editor. Pathophysiology in nursing. 8th ed. Bangkok: Boonsiri;

2009. p.170-98. (In ai)

7. Norton C. Constipation in older patients: Eects on quality

of life. Br J Nurs. 2006; 15:188-92.

8. Tack J, Muller-Lissner S. Review Treatment of Chronic

Constipation: current Pharmacologic approaches and future

direction. Clin Gastroenterol Hepato. 2009;7:502–8.

9. Stumm RE, omas MS, Coombes J, Greenhill J, Hay J. Managing

Constipation in Elderly orthopaedic patients using either pear

juice or a high ber supplement. Aust J Nutr Diet. 2001;58:

181-5.

10. Monmai P. e eectiveness of a constipation prevention

program for hospitalized elderly with hip surgery [master’s

thesis]. Bangkok: Mahidol University; 2009.p.154 (In ai)

11. Hinrichs M, Huseboe J. Research-based protocol management

of constipation. J Geronto Nurs. 2001;27:17-28.

12. ai massage restoration project. e manual of ai massage

in primary health care. Bangkok: Ruenkaew; 1992. (In ai)

13. Lämås K,Lindholm L,Stenlund H,Engström B,Jacobsson C.

Eects of abdominal massage in management of constipation—A

randomized controlled trial. Int J Nurs Stud.2009;46:759-67.

14. Ayas S, Leblebici B, Sozay S, Bayramoglu M, Niron EA. e

eect of abdominal massage on bowel function in patients

with spinal cord injury. Am J Phys Med Rehabil. 2006;85:951-5.

15. Vatthakavarn P. Eectiveness of abdominal massage combined

with soap rectal suppository on stimulating bowel movement

in spinal cord injury patients [master’s thesis]. Khon Kaen:

Khon Kaen University; 2002.p.75 (In ai)

16. Wattanawech T. e inuence of selected factors and self-

care behavior on abdominal distention in patients with abdominal

surgery (master’s thesis). Bangkok: Mahidol University; 2002.

p.124 (In ai)

17. Diego MA, Field T. Moderate pressure massage elicits a

parasympathetic nervous system response. Int J Neurosci.

2009;119:630-8.

18. Lamas K, Graneheim UH, Jacobsson C. Experiences of abdominal

massage for constipation. J Clin Nurs; 2012;21:757-65.

19. Boonsawat W. Eects of ai traditional massage on pain

reduction in cancer patients [master’s thesis]. Songkla: Prince

of Songkla University; 2005.p.173 (In ai)

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

220

Supansa Kuntasorn, M.Sc.*, Amornrat Anuwatnonthakate, Ph.D.*, Tawatchai Apidechkul, Dr.P.H.*,**

*School of Health Science, **Center of Excellence for the Hill tribe Health Research, Mae Fah Luang University, Chiang Rai 57000, ailand.

Prevalence and Factors Associated with Abnormal

Cervical Cell among the Hmong and Mien Hill Tribe

Women in Pha Yao Province, Thailand

Corresponding author: Tawatchai Apidechkul

E-mail: Tawatchai.api@mfu.ac.th

Received 22 November 2018 Revised 11 February 2019 Accepted 15 March 2019

ORCID ID: http://orcid.org/0000-0001-8301-2055

http://dx.doi.org/10.33192/Smj.2019.34

ABSTRACT

Objective: To estimate the prevalence and to determine factor associated with abnormal cervical cell among the

Hmong and Mien hill tribe women.

Methods: A cross-sectional study aimed to estimate the prevalence and to determine the factors associated with

abnormal cervical cell among the Hmong and Mien hill tribe women living in Pha Yao province, ailand was

conducted. e data from validated questionnaires and Papanicolaou (Pap) smear test results were collected. Logistic

regression was used to detect the associations between variables and abnormal cervical cell at the signicant level

of alpha = 0.05.

Results: Totally, 450 Hmong and Mien women were recruited into the analysis. e overall prevalence of abnormal

cervical cell was 2.2%; 1.2% were atypical squamous cells of undetermined signicance (ASC-US), 0.4% were atypical

squamous cells-cannot exclude HSIL (ASC-H), 0.4% were cervical intraepithelium neoplasia-I (CIN-I) and 0.2%

were cervical intraepithelium neoplasia-II (CIN-II). Two variables, the number of their sexual partners and the

number of husbands’ sexual partners, were signicantly associated with abnormal cervical cell. e women who

had ≥ 4 sexual partners had a 7.09 times (95%CI=1.85-27.17) more likely to have abnormal cervical cell than those

who had < 4 sexual partners. e women whose husbands had ≥ 4 partners had a 5.63 times (95%CI=1.51-20.90)

more likely to have abnormal cervical cell than those whose husbands had < 4 sexual partners.

Conclusion: e number of sexual partners is signicantly associated with abnormal cervical cell among the Hmong

and Mien hill tribe women. Health interventions regarding safe sex should be promoted in the hill tribe people.

Keywords: Abnormal cervical cell; Hmong; Mien; hill tribe; prevalence (Siriraj Med J 2019;71: 220-227)

INTRODUCTION

Cancer is a major threat to human life in worldwide.

In 2015, there were 17.5 million cases worldwide and

8.7 million deaths.

is number is expected to increase

to 24 million by 2035.

Cervical cancer is the signicant

leading cause of death globally in women including

ailand.

e human papillomavirus (HPV) is the cause

of cervical cancer which involved sexual behavior.

4-6

Consequently, personal suering and economic loss are

the major impacts to an individual health and family.

In 2016, the Ministry of Public Health reported that

cervical cancer was ranked the second overall cause of death

in women in ailand with the prevalence at 608/100,000

population.

e northern region of ailand reported

the highest prevalence and accounted for 12.1% of all

female cancer. e average age-standardized incidence

Kuntasorn et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

221

Original Article

SMJ

rate (ASR) was 17.0 per 100,000.

In 2016, Pha Yao

province was ranked second followed by Chiang Rai

province with the ASR at 25.0/100,000 pop which was

higher than the average ASR of northern ailand.

Besides, the trend of cervical cancer is rising yearly,

and it has become a signicant health problem in Pha

Yao province.

However, only 55.9% of women aged

30-60 were screened for cervical cancer by a Pap smear

test, and less than 20.0% among the hill tribe women in

2015.

A number of the hill tribe people live in Pha Yao

province which is located in northern ailand. Most

hill tribe people living in Pha Yao province are Hmong

and Mien.

ese two tribes have their own culture, and

lifestyles including sexual behaviors.

Most Hmong and

Mien men and women have their rst sexual intercourse

at young age, and get married at early age as well.

Moreover, these tribes have a unique culture of polygamy.

Regarding their economic status, they are living under

the poverty line of ailand.

Hmong and Mien women

did not favor a regular Pap smear test.

erefore, a

few data are available on cervical cancer among the

hill tribe population particularly the Hmong and Mein

women. is study aimed to assess the prevalence and

to determine the factors associated with cervical cancer

among the Hmong and Mien women. e data could

be used to develop public health policy and also health

promotion intervention in the area.

MATERIALS AND METHODS

Study design

A cross sectional study was used to assess the prevalence

and to determine the factors associated with abnormal

cervical cell among the Hmong and Mien women.

Study setting

e study was conducted in 13 Hmong and Mien

villages in Pong, and Chiang Kham districts, Pha Yao

province. Seven villages were selected from Pong district;

Ban Pang Kha, Ban Pang Ma-O, Ban Sip Song Pattana,

Ban Kun Kam Lang, Ban San Ti Suk, Ban Saeng Sai,

and Ban Hwauy Khok Moo villages. Another 6 villages

were selected from Chiang Kham district; Ban Mai Rom

Yen, Ban Pra Cha Pak Dee, Ban Hwauy Poom, Ban Pra

Cha Pattana, Ban Roung San, and Ban Hwauy Diar Doi

Nang villages.

Study population

Hmong and Mien women aged 30-60 years old and

their husbands who lived in the study settings were the

study population.

Inclusion criteria

a) ose that self-identied as Hmong or Mien

tribe women, b) aged between 30 and 60 years old,

c) married, d) lived in the study area for at least 1 year.

Exclusion criteria

a) ose that could not provide essential information

due to any causes such as ability to communicate in ai,

b) women who had a period at the date of Pap smear

test, c) women who were pregnant.

Study sample and sample size calculation

Hmong and Mein women aged 30-60 and their

husbands were the target population. In 2016, there were

2,038 couples living in the 13 villages.

e sample size

was calculated by the following formula

;

n=(Z

P(1-P))/d

At the condence level 95%, d = 0.05, P=12.2%

, at

least 405 samples were required. Adding for any errors

during the study for 10.0%, then, 450 samples were

needed for the analysis.

Research instruments

A validated questionnaire and Pap smear test were

used for data collection in the study. ere were 5 parts

in the questionnaire. Part I asking about the general

information which consisted of ve questions; age, tribe,

education, religion, income, etc. Part II consisted of six

questions regarding the risk factors such as what age

they got married, number of partners, history of sexually

transmitted infections (STIs), history of Pap screening

test previous year, etc. Part III consisted of four questions,

asking about risk behaviors of husband such as number

of partners, history of STIs, etc. Part IV consisted of six

questions regarding health behaviors such as smoking,

alcohol drinking, etc. Part V consisted of thirty short

questions regarding knowledge, attitude, and practice

for cervical cancer prevention.

Questionnaire was developed from the literature

review and consulting with experts in relevant elds.

Questionnaire was tested for validity by Index of Item

Congruence (IOC) method which was assessed by three

external experts. Questions that resulted in IOC score of

less than 0.5 were excluded. Aer that, a pilot test was

done with 30 participants with similar characteristics

with the study sample. e purposes of the pilot test were

to determine the reliability, feasibility, and possibility

of collecting the data from the participants. Questions

in part V were tested for reliability from the pilot test

using Cronbach’s alpha. Questions that had Cronbach’s

alpha less than 0.5 were deleted due to less reliability.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

222

Resulting, the overall Cronbach’s alpha was 0.76. Moreover,

Kuder-Richardson (KR)

was used to detect the quality

of questions regarding the knowledge. e overall KR

score was 0.71.

Pap smear (e Bethesda 2001 Cytology Report) was

used to collect the specimen. e process of collecting the

specimen was done by two trained nurses. All specimens

were sent to Chiang Kham, which has the only standard

institute with medical laboratory in Pha Yao province

for detection the cervical cancer. Abnormal cervical cell

was dened according to the Bethesda system 2001 as;

atypical squamous cells of undetermined signicance

(ASC-US), atypical squamous cells cannot exclude high

grade squamous intraepithelial lesion (ASC-H), low grade

squamous intraepithelial lesion (LSIL) encompassing

human papillomavirus change/cervical intraepithelial

neoplasia I (CIN I), high grade squamous intraepithelial

lesion (HSIL) encompassing cervical intraepithelial

neoplasia II (CIN II)/ cervical intraepithelial neoplasia III

(CIN III)/with feature suspicious for invasive, squamous

cell carcinoma, atypical glandular cell, atypical glandular

cells favor neoplasia, endocervical adenocarcinoma in

situ, adenocarcinoma endocervical cells/endometrials,

other malignants.

Data collection procedures

Aer getting the ethical approval from the Human

Research Committee from Mae Fah Luang University,

Pha Yao Public Health Oce was contacted to request

their approval to conduct the study and also information

regarding the hill tribe villages in Pha Yao province

including the contact number of all health promoting

hospitals in the study area. Four health promoting hospitals

located at the hill tribe villages were contacted; Pang

Kha, Khun Kwaun, Hwauy Khok Mhoo and Rom Yen

health promoting hospitals. Two trained nurses on Pap

smear technique were contacted for to help in collecting

specimen. A one-day training course was provided for

two trained nurses and all health promoting hospitals

sta regarding research objectives and procedures.

All targeted village leaders were contacted and

asked for their cooperation to conduct the study. Lists of

women who met the inclusion criteria were sent to the

researcher who was supported by the village headman.

A simple random sampling was used to select the study

samples. Appointments were made with all the selected

samples at the health promoting hospitals close to their

resident.

On the day of collecting data, all the participants and

their husbands were provided the essential information

and the researcher obtained the informed consent form

from both of them before interview. e interviews were

done separately in a private and condential room.

Each interview lasted for 20 minutes for woman, and

10 minutes for husband. Aer the interview, a trained

nurse collected specimen from the women.

Statistical analysis

Data were coded and double-entered into Microso

Excel 2010. e analysis was conducted by using SPSS

(version 20; IBM, Armonk, NY). Descriptive statistics

was used to explain the characteristics of the participants;

percentage, mean, SD. Logistic regression was used to

detect the associations between variables and abnormal

cervical cell as an outcome at the signicant level α=0.05.

All independent variables were detected the association

with the outcome in simple logistic regression model.

Aerward, all signicant variables in simple logistic

regression model were considered to put into the multivariate

analysis by using “ENTER” mode. Variables remaining a

signicant association with the outcome, were determined

as factors association with abnormal cervical cell in the

nal model.

Ethical considerations

e study was approved by the Ethics Committee

for Human Research, Mae Fah Laung University, Chiang

Rai, ailand (No.REH-60022). All information was

kept in the private and secured code only the researcher

could access. Aer the analysis was complete, data were

deleted including the questionnaire and laboratory results.

A small gi was given to all participants to appreciate

their cooperation. e laboratory results were sent to all

participants with the guideline for future medical care

required particularly those who were abnormal.

RESULTS

Characteristics of women

A total of 450 women were recruited into the analysis.

More than half were Hmong (63.6%), average age was

45 (SD=8), and majority were aged 51-60 years (36.2%).

Most participants graduated primary school (50.0%),

worked as farmers (77.3%), and had monthly income

≤ 3,000 Bath (55.3%). Most participants had free access

to health care. More than half had their rst sexual

intercourse while aged < 18 years (53.8%), and married

while aged < 18 years (52.4%). Almost all the participants

had < 4 sexual partners (90.0%), and only 17.5% were

screened for cervical cancer previous year. A few of the

participants had congenital problem; 13.3% had yellow

or green or oensive odour leucorrhoea, and 8.9% had

a history of genital ulcer. Regarding health behaviors;

Kuntasorn et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

223

Original Article

SMJ

44.0% smoked, and 37.3% drank alcohol. Regarding

the knowledge, attitude, and practice on cervical cancer

prevention; 46.4% had low level of knowledge, 28.0% had

negative, neutral or positive attitude towards cervical

cancer prevention, and 26.4% had incorrect practice of

cervical cancer prevention, respectively (Table 1).

Characteristics of husband

Majority had < 4 partners (76.9%), none of them

had a genital discharge. A few of them had a history of

genital ulcer (3.3%), and some of them had experience

of having sexual intercourse with sex workers (11.6%)

(Table 2).

e overall prevalence of abnormal cervical cell was

2.2%; 1.2% were atypical squamous cells of undetermined

signicance (ASC-US), 0.4% were atypical squamous cells

and cannot exclude high grade squamous intraepithelial

lesion (ASC-H), 0.4% were low grade squamous intraepithelial

lesion (LSIL) encompassing cervical intraepithelial

neoplasia I (CIN I), and 0.2% were high grade squamous

intraepithelial lesion (HSIL) encompassing cervical

intraepithelial neoplasia II (CIN II) (Table 3). ere

were 7 participants positive among 286 Hmong women

(2.5%), and 3 positive participants among 164 Mien

women (1.8%). ere was no statistically signicant

dierence between tribes (χ

=0.17, p-value=0.675).

ree variables were signicantly associated with

abnormal cervical cell in the univariate analysis: women’s

number of partners, husband’s number of sexual partners,

and husband’s history of sexual intercourse with sex

workers (Table 1).

In the multivariate model, two variables were still

significantly associated with abnormal cervical cell;

women’s number of partners, and husband’s number

sexual partners. Women who had ≥ 4 partners had

a 7.09 time (95%CI=1.85-27.17) more likely to have

abnormal cervical cell than those who had < 4 partners.

Women whose husbands had ≥ 4 partners had a 5.63

time (95%CI=1.51-20.90) more likely to have abnormal

cervical cell than those whose husbands had < 4 partners

(Table 1).

DISCUSSION

e study found that Hmong and Mien in Pha Yao

province are living in low socio-economic condition. e

overall prevalence of abnormal cervical cell among our

study subjects was 2.2%. Number of partners both in

women and men are the factors associated with cervical

cancer in the Hmong and Mien women in Pha Yao

province. In our study, it was found that the prevalence

of cervical cancer between Hmong and Mien women

was not statistically dierent. However, a study in Iran

reported some ethnicity related trends in cervical cancer.

e study of Akram Husain

also reported that some

groups of Indian women in the south were at a greater

risk of cervical cancer than women who lived in other

regions in India. In terms of the prevalence of cervical

cancer among these two hill tribe women is higher than

ai national rate at 23/100,000 population.

e rate

of screening for cervical cancer is also lower than ai

targeted women at 60.2%.

In our study we found that women’s number of

partners was a signicant factor associated with abnormal

cervical cancer. Liu, et al

reported that number of

partners was highly associated with cervical cancer from

the meta-analysis. Whereas several studies

25-27

reported

that women’s number of partners and history of STIs

were associated with cervical cancer among the women

in South Africa. However, the study of Obiri-Yeboah

reported that age of women and circumcision status of

main sexual partner were associated with cervical cancer,

but no association was found with number of partners.

We also found that number of partner of husband

related to the occurrence of cervical cancer in women.

is coincides with the study which was conducted in

Shanxi province, China reported that number of partners

of women and her husband were associated with cervical

cancer of women.

Some limitations were found in the study. First,

at the beginning of the interview process, both male

and female participants were interviewed by a female

interviewer. However, upon completing 3 interviews;

it was found that the husbands were not comfortable

to provide information. Aerwards, the process was

adjusted and interviews were conducted by same sex.

Another point is the ability to communicate in ai. It

was found that 3 women were excluded from the study

due to limitation in use of ai. ey could not provide

the essential information to the interviewer. e study

could not use a translator for gathering information

from the participants since all information required are

sensitive. Moreover, 7 selected women were excluded

from the study because 5 were on their period, and 2

were pregnant. However, the researcher believes that it

did not impact the study results since an excess of 20

couples had been selected at the stage of sample selection

by a random method.

CONCLUSION

e hill tribe women are at risk for abnormal cervical

cell. e number of partners of both women and the

number of partners of their husband are identied as the

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

224

Characteristics Total Abnormal Normal OR 95% CI P-value OR

adj

95% CI

P-value

n (%) n (%) n (%)

Tribe

Hmong 286 (63.6) 7 (2.4) 279 (97.6) 1.34 (0.34-5.28) 0.670

Mien 164 (36.4) 3 (1.8) 161 (98.2) 1

Age (years)

30-40 152 (33.8) 4 (2.6) 148 (97.4) 2.17 (0.39-12.05) 0.374

41-50 135 (30.0) 4 (3.0) 131 (97.0) 2.45 (0.44-13.63) 0.303

51-60 163 (36.2) 2 (1.2) 161 (98.8) 1

Education

Illiterate 151 (33.6) 4 (2.6) 147 (97.4) 0.98 (0.17-5.47) 0.981

Primary school 225 (50.0) 4 (1.8) 221 (98.2) 0.65 (0.11-3.63) 0.625

High school 74 (16.4) 2 (2.7) 72 (97.3) 1

Occupation

Farmer 348 (77.3) 6 (1.7) 342 (98.3) 0.39 (0.07-2.01) 0.264

Merchant 55 (12.2) 2 (3.6) 53 (96.4) 0.84 (0.11-6.27) 0.873

Labor 47 (10.5) 2 (4.3) 45 (95.7) 1

Income (bath/month)

≤ 3,000 249 (55.3) 3 (1.2) 246 (98.8) 0.22 (0.04-1.15) 0.075

3,001-5,000 142 (31.6) 4 (2.8) 138 (97.2) 0.54 (0.11-2.49) 0.431

≥ 5001 59 (13.1) 3 (5.1) 56 (94.9) 1

Religion

Buddhist 401(89.1) 9 (2.2) 392 (97.8) 1.10 (0.13-8.88) 0.927

Christian 49 (10.9) 1 (2.0) 48 (98.0) 1

Rights of free access health care

Yes 368 (81.8) 7 (1.9) 361 (98.1) 1 0.338

No 82 (18.2) 3 (3.7) 79 (96.3) 1.95 (0.49-7.74)

Age at rst sexual intercourse (years)

<18 242 (53.8) 3 (1.2) 239 (98.8) 2.77 (0.70-10.86) 0.143

≥18 208 (46.2) 7 (3.4) 201 (96.6) 1

Age at marriage (years)

<18 236 (52.4) 3 (1.3) 233 (98.7) 2.62 (0.67-10.28) 0.166

≥18 214 (47.6) 7 (3.3) 207 (96.7) 1

Number of partners (persons)

<4 405 (90.0) 6 (1.5) 399 (98.5) 1 1

≥4 45 (10.0) 4 (8.9) 41 (91.1) 6.48 (1.75-23.93) 0.005* 7.09 (1.85-27.17) 0.004*

Method of contraception use

None 261 (58.0) 5 (1.9) 256 (98.1) 1

Orally 57 (12.7) 1 (1.8) 56 (98.2) 0.91 (0.10-7.97) 0.935

Injection 58 (12.9) 3 (5.2) 55 (94.8) 2.79 (0.64-12.03) 0.168

Tubal ligation 74 (16.4) 1 (1.4) 73 (98.6) 0.70 (0.08-6.09) 0.748

History of yellow or green or offensive odour leucorrhoea

Yes 62 (13.8) 3 (4.8) 59 (95.2) 2.76 (0.69-11.00) 0.148

No 388 (86.2) 7 (1.8) 381 (98.2) 1

TABLE 1. Univariate and multivariate analyses of factors associated with abnormal cervical cell.

Kuntasorn et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

225

Original Article

SMJ

TABLE 1. Univariate and multivariate analyses of factors associated with abnormal cervical cell.

Characteristics Total Abnormal Normal OR 95% CI P-value OR

adj

95% CI

P-value

n (%) n (%) n (%)

History of genital ulcer

Yes 40 (8.9) 2 (5.0) 38 (95.0) 2.64 (0.54-12.90) 0.229

No 410 (91.1) 8 (2.0) 402 (98.0) 1

Smoking

Yes 198 (44.0) 7 (3.5) 191 (96.5) 3.04 (0.77-11.91) 0.110

No 252 (56.0) 3 (1.2) 249 (98.8) 1

Alcohol use

Yes 168 (37.3) 3 (1.8) 165 (98.2) 0.71 (0.18-2.80) 0.629

No 282 (62.7) 7 (2.5) 275 (97.5) 1

History of cervical cancer of family member

Yes 28 (6.2) 2 (7.1) 26 (92.9) 3.98 (0.80-19.70) 0.090

No 422 (93.8) 8 (1.9) 414 (98.1) 1

Exercise

Yes 203 (45.1) 3 (1.5) 200 (98.5) 1

No 247 (54.9) 7 (2.8) 240 (97.2) 1.94 (0.46-7.61) 0.340

Knowledge

Low 209 (46.4) 5 (2.4) 204 (97.6) 1.05 (0.12-9.25) 0.962

Moderate 197 (43.8) 4 (2.0) 193 (98.0) 0.89 (0.09-8.17) 0.919

High 44 (9.8) 1 (2.3) 43 (97.7) 1

Attitude

Low 126 (28.0) 4 (3.2) 122 (96.8) 2.78 (0.30-25.37) 0.363

Moderate 238 (52.9) 5 (2.1) 233 (97.9) 1.82 (0.21-15.83) 0.586

High 86 (19.1) 1 (1.2) 85 (98.8) 1

Practice

Low 119 (26.4) 2 (1.7) 117 (98.3) 0.82 (0.11-5.93) 0.845

Moderate 233 (51.8) 6 (2.6) 227 (97.4) 1.26 (0.25-6.39) 0.773

High 98 (21.8) 2 (2.0) 96 (98.0) 1

Number of sexual partners of husband (persons)

<4 346 (76.9) 4 (1.2) 342 (98.8) 1 1

≥4 104 (23.1) 6 (5.8) 98 (94.2) 5.23 (1.44-18.92) 0.012* 5.63 (1.51-20.90) 0.010*

Condom use with other women (n=271)

Never 132 (48.7) 5 (3.8) 127 (96.2) 1.65 (0.18-14.55) 0.650

Sometimes 96 (35.4) 4 (4.2) 92 (95.8) 1.82 (0.19-16.83) 0.595

Always 43 (15.9) 1 (2.3) 42 (97.7) 1

Husband’s history of genital ulcer

Yes 15 (3.3) 1 (6.7) 14 (93.3) 3.38 (0,40-28.54) 0.263

No 435 (96.7) 9 (2.1) 426 (97.9) 1

History of sexual intercourse with sex workers

Yes 52 (11.6) 4 (7.7) 48 (92.3) 5.44 (1.48-19.98) 0.011*

No 398 (88.4) 6 (1.5) 392 (98.5) 1

* Signicant level at α =0.05

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

226

TABLE 2. General characteristics of husbands.

TABLE 3. Prevalence of abnormal cervical cancer.

Characteristics n (%)

Number of partners (persons)

<4 346 (76.9)

≥4 104 (23.1)

Condom use while having sex with other women (n=271)

Never 132 (48.7)

Sometimes 96 (35.4)

Always 43 (15.9)

History of genital discharge

Yes 0 (0.0)

No 450 (100.0)

History of genital ulcer

Yes 15 (3.3)

No 435 (96.7)

Sexual intercourse with sex worker

Yes 52 (11.6)

No 398 (88.4)

Characteristics N (%)

Negative for intraepithelial lesion or malignancy (NIL) 345 (76.7)

Organism

Trichomonas spp. 3 (0.7)

Fungus 26 (5.8)

Coccobacilli shift in vaginal ora 32 (7.1)

Others 2 (0.4)

Other non-neoplastic ndings

Inammation 29 (6.4)

Atrophy 3 (0.7)

Epithelial cells abnormalities

Squamous cells 10 (2.2)

Atypical squamous cells of undetermined signicance (ASC-US) 5 (1.2)

Atypical squamous cells-cannot exclude HSIL (ASC-H) 2 (0.4)

Low grade squamous intraepithelial lesion (LSIL)

Cervical Intraepithelium Neoplasia I (CIN-I) 2 (0.4)

High grade squamous intraepithelial lesion (HSIL)

Cervical Intraepithelium Neoplasia II (CIN-II) 1 (0.2)

Kuntasorn et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

227

Original Article

SMJ

factors associated to abnormal cervical cell of Hmong

and Mien women. Public health intervention which is

focused on minimizing the number of partners among

these hill tribe population should be implemented to

reduce the possibility of having abnormal cervical cell.

ACKNOWLEDGMENTS

e authors would like to thank the Hmong and

Mien women who participated in the study. We also would

like to thank the directors of Pang Kha, Khun Kwaun,

Hwauy Khok Mhoo and Rom Yen Health Promoting

Hospitals in Pha Yao province, ailand, for help in

data collection.

REFERENCES

1. Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA,

Brenner H, et al. Global, regional, and national cancer incidence,

mortality, years of life lost, years lived with disability, and

disability-adjusted life-years for 32 cancer groups, 1990 to

2015: A systematic analysis for the global burden of disease

study. JAMA Oncology 2017;3: 524-48.

2. World Cancer Research Fund International (WCRF International).

Cancer facts & gures worldwide data. Available from http://

www.wcrf.org/int/cancer-facts- gures/worldwide- data.

3. World Health Organization (WHO). Cancer situation in SEAR

countries. Available from: http://www.searo.who.int/thailand/

news/cancer-sear/en/

4. Sreedevi A, Javed R, Dinesh A. Epidemiology of cervical cancer

with special focus on India. Int J Women’s Health 2015;7:405-14.

5. Centers for Disease Control and Prevention (CDC). Gynecologic

cancers: cervical cancer. Available from: https:// www.cdc.gov/

cancer/cervical/

6. World Health Organization (WHO). Cervical cancer prevention

and control saves lives in the Republic of Korea. Available from:

http://www.who.int/news-room/feature- stories/detail/cervical-

cancer-prevention-and-control-saves- lives-in-the-republic-

of-korea.

7. Sawatdimongkol S. Annual report of non-communicable diseases

2015. Available from: http://www. thaincd.com/document/

le/download/paper manual/Annual-report-2015.pdf

8. Lampang Cancer Hospital. Cancer incidence in northern

ailand, 2012-2016. Available from: http://www.lpch.go.th/

lpch/lpch_attachment/20151016085144134377.pdf

9. Lampang Cancer Hospital. Cancer incidence in Pha Yao

province. Available from: http://www. lpch.go.th/lpch/lpch_

attachment/20151202100952874252.pdf

10. itibordin B. Reporting system of cancer service plan in Pha

Yao province, ailand. Available from: http:// bie.moph.

go.th/eins59/upload/2559A12103114.doc

11. Pha Yao Provincial Public Health Oce, ailand. Cervical

cancer screening report. Available from: http://203.209.96.247/

chronic/rep_cancer_vagina. php

12. Hill Tribe Development Center of Pha Yao Province, ailand.

Hill tribe population data in 2016-2017. Available from: http://

www.sdc31.go.th/index.php?name=download& le=readdownload

&id=19

13. Apidechkul T. A 20-year retrospective cohort study of TB

infection among the Hill-tribe HIV/AIDS populations, ailand.

BMC Infect Dis 2016;16:72.

14. Kritpetcharat OW, Sirijaichingkul S, Kritpetcharat P. Comparison

of Pap smear screening results between Akha hill tribe and

urban women in Chiang Rai province, ailand. Asian Pac J

Cancer Prev 2012;13:5501-4.

15. awongma S, Maneewan K. Roles of adolescents Hmong

and sexual behavior modication. Hill Tribe’s Health Development

Center, Chiang Mai, ailand. 2006.

16. Apidechkul T, Laingoen O, Suwannaporn S. Inequity in accessing

health care service in ailand in 2015: A case study of the Hill

tribe people in Mae Fah Luang district, Chiang Rai, ailand.

J Health Res 2016;30 67-71.

17. Khirisuntikul S. Development of a health promotion model

for cervical cancer prevention among hill tribe women aged

30-60 years. Available from: https://wwwnno.moph. go.th/

research/index.php/2559/item/274-2559-1

18. Pha Yao Provincial Public Health Oce, ailand. Hill tribe

population in 2016. Pha Yao Provincial Public Health Oce,

Pha Yao, ailand, 2016.

19. Naing L, Winn T, Rusli BN. Practical issues in calculating the

sample size for prevalence studies. Arch Orofac Sci 2006;1:9-14.

20. Mohayza MM, Sulaiman L, Sern LC, Salleh KM. Measuring

the validity and reliability of research instruments. Procedia

Soc Behav Sci 2015;204:164-71.

21. Michaan N, Gortzak-Uzan L, Grisario D, Laskov I. Ethnicity-

related trends in gynecologic malignancies in Israel, 1993-2013.

Int J Gynaecol Obstet 2018;142:176-81.

22. Akram Husain RS, Rajakeerthana R, Sreevalsan A, Prema Jayaprasad P,

Ahmed S, Ramakrishnan V. Prevalence of human papilloma virus

with risk of cervical cancer among south Indian women: A genotypic

study with meta- analysis and molecular dynamics of HPV

E6 oncoprotein. Infect Genet Evol 2018;62:130-40.

23. e HPV Information Center, ailand. Human papilloma

virus and related disease report. Available from: http://www.

hpvcentre.net/statistics/reports/THA.pdf

24. Liu ZC, Liu WD, Liu YH, Ye XH, Chen SD. Multiple sexual

partners as a potential independent risk factor for cervical

cancer: a meta-analysis of epidemiological studies. Asian Pac

J Cancer Prev 2015;16:3893-900.

25. Jolly PE, Mthethwa-Hleta S, Padilla LA, Pettis J, Winston S,

Akinyenmiju TF, et al. Screening, prevalence, and risk factors

for cervical lesion among HIV positive and HIV negative

women in Swaziland. BMC Public Health 2017;17:218.

26. Okunade KS, Nwogu CM, Oluwole AA, Anorlu RI. Prevalence

and risk factors of genital high-risk human papillomavirus

infection among women attending the out-patient clinics of a

university teaching hospital in Lagos, Nigeria. Pan Afr Med J

2017; 28:227.

27. Mbulawa ZZA, van Schalkwyk C, Hu NC, Meiring TL, Barnabas

S, Dabee S, et al. High human papillomavirus (HPV) prevalence

in South Africa adolescents and young women encourages expanded

HPV vaccination campaigns. PLoS One 2018;13(1): e0190166.

28. Obiri-Yeboah D, Akakpo PK, Mutocheluh M, Adje-Danso

E, Allornuvor G, Amoako-Sakyi D, et al. Epidemiology of

cervical human papillomavirus (HPV) infection and squamous

intraepithelial lesion (SIL) among a cohort of HIV-infected

and uninfected Ghanaian women. BMC Cancer 2017;17:688.

29. Shi N, Lu Q, Zhang J, Li L, Zhang J, Zhang F, et al. Analysis

of risk factors for persistent infection of asymptomatic women

with high-risk human papilloma virus. Hum Vaccin Immunother

2017;13:1404-11.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

228

Chonnakarn Jatchavala, M.D., M.Sc., Jarurin Pitanupong M.D.

Department of Psychiatry, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, ailand.

Resilience in Medical Doctors within the Areas of

the Southern Thailand Insurgency

Corresponding author: Chonnakarn Jatchavala

E-mail: jchonnak@gmail.com

Received 20 December 2018 Revised 29 March 2019 Accepted 22 April 2019

ORCID ID: http://orcid.org/0000-0001-9765-2184

http://dx.doi.org/10.33192/Smj.2019.35

ABSTRACT

Objective: is study aimed to examine resilience and its’ associated factors among medical doctors who worked at

hospitals, either in the restive areas of the southern ailand insurgency, or non-restive areas of nearby provinces.

Methods: is cross-sectional study was conducted for all medical doctors who worked at the hospitals located

in the lower southern part of ailand from January to April 2018. All of the participants completed the personal

information and ai resilience questionnaires (ai-RQ) by themselves. e data was analyzed by descriptive

statistics, whilst the factors associated with resilience were analyzed using logistic regression analysis.

Results: From 245 medical doctors, most were female (58.0%), single (50.2%) and worked more than 40 hours

per week (30.2%). e average resilience scores were at a normal level (62.3 ± 7.8) as well as most of them being

(67.3%). e highest section of resilience was coping skills, with the lowest being emotional stability. ere were no

dierences in resilience between those who worked in restive areas, or those who worked in non-restive areas of the

southern ailand insurgency. Perceived sleep/rest quality and family relationships were signicantly associated

with their resilience.

Conclusion: Most of the medical doctors, who worked at hospitals either in the restive or non-restive areas of the

southern ailand insurgency, were at normal levels of resilience. No dierence of resilience was found between

these two areas. e factors associated with resilience were perception of sleep/rest quality and family relationships.

Keywords: Resilience; medical doctor; south ailand insurgency (Siriraj Med J 2019;71: 228-233)

INTRODUCTION

Since 2004, the ailand’s southern insurgency,

which is a part of a complicated political conict, has

continuingly deteriorated, generating violence in the

3 provinces of southern ailand: Patani, Yala and Narathi,

in addition to some parts of Songkhla province, which

the ai media has dubbed as the SBP (Southern border

Providences) of ailand.

From the 1

of January 2004 to the 31

of August

2018; 19,993 violent situations were ocially reported

with; 6,848 people killed and another 13,443 injured

in total.

Local people, including medical professionals

working in these areas, have to live under these ongoing,

stressful circumstances and embody a substantial escalation

in psychological distresses.

ey are at risk of many

mental illnesses; not only burnout syndrome which is

commonly found among health care professionals, but

also more severe psychiatric disorders, such as; post-

traumatic stress disorder.

However, Charoenwong and the co-authors

found

that most, local people in the restive areas represented

as having normal levels of stress. Even a survey among

widows whose husbands died due to the violent situations

in the SBP, revealed stable stress management, spiritual

and physical strength.

Jatchavala et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

229

Original Article

SMJ

e remarkable question is: ‘Exactly how do they live

under these continuing stressful conditions?’ Especially

medical doctors, who normally already work in demanding

settings as is the nature of their profession. the researchers

focused on the medical doctors ‘resilience’, as this is

the capacity to recover quickly from any diculties.

Within Thailand’s context, resilience and resilience

assessment were conceptually based on 3 sources of: “I AM”,

“I HAVE” and “I CAN”. erefore, the ai version of

resilience quotient was divided into 3 parts: emotional

stability, will power and coping skills.

Previous studies of

resilience promotion reported that; the extrinsic factors

that are associated to the level of resilience were quality

of family relationship and governmental/social support.

As well as which intrinsic factors were self- esteem, faith

and high cognitive functionality, however; physical

illnesses could interfere with resilience, particularly

among patients with an abnormal cortisol level, which

is also related to stress.

For these reasons, the researchers emphasized both

resilience and associating factors among medical doctors,

who work in government hospitals in the restive areas

of SBP, and the other 4 southern provinces of ailand

for comparison. is was in order for the collection of

principal data for promoting mental health among ai

health care professionals, and to develop psychological

support systems for public health organizations in ailand.

MATERIALS AND METHODS

is study was a cross-sectional survey; designed

to determine the level of resilience and its’ associated

factors among medical doctor, working at secondary and

tertiary-care hospitals in the restive areas of Narathiwas,

Patani, Yala, and 4 the non-restive provinces of Songkhla,

Satun, Trang and Phatthalung, from January to April

2018. Additionally, this research also compared resilience

between the restive areas of the ailand’s southern

insurgency, and the non-restive areas in 4 nearby provinces.

Aer the research proposal was endorsed by the ethic

committee of Prince of Songkla University (REC number:

60-262-03-1), the researchers contacted human resource

ocers at each secondary and tertiary hospitals in both the

restive and non-restive areas of the ailand’s southern

insurgency. Upon contact, we asked for permission from

the directors of each hospital for help in the administration

all of the sealed envelopes of the self-administered

questionnaires: ai resilience questionnaires (ai-

RQ)

, to all medical doctors, who were employed at

that time. Consensus to participate in the study had to

be individually agreed upon.

Whilst the estimated size of our target population

is at least 320 medical doctors

, according to region 12,

from the Ministry of Public health records, there are 1,592

physicians on duty.

en, the data were performed

using the R soware package, and were analyzed by using

descriptive statistics. e primary results were presented

as: frequency, percentage, average and standard deviation.

erefore, associated factors of resilience were analyzed

by using logistic regression.

RESULTS

Of the 245 medical doctors, who participated

in this study (19.3% responded from a total of 1270

questionnaires); 55.9% of them worked in restive areas

of the SBP. Participants were mostly females (58.0%)

Buddhist (80.0%), healthy (74.7%) and single (50.2%).

The mean age±SD was 35.9±9.5 years old, with the

mean±SD amount of working hours per week being

63.0±26.4. Around half of the participants reported

that they perceived adequate rest and sleep, but more

of them perceived this to be inadequate (48.6% and

49.0% respectively). Most of them revealed that the most

important reason in the choice of their workplace location

was so as to be near their homes, and families (55.1%).

ey also assessed their own family relationships as

being good or excellence (48.6% and 40.0% respectively).

However, 86.9 % of them reported that they perceived

considerable stress form their work. (Table 1)

Regarding levels of resilience (Table 2), no signicant

dierence was found between medical doctors who worked

in either the restive or non-restive areas of ailand’s

southern insurgency. Only 15.7% of the medical doctors

in restive areas, and 14.7% of those who worked in

non-restive ones, had less levels of resilience than that

of a normal population. Whilst the domain showed, the

highest prevalence of normal to above average levels of

resilience, was coping skills (91.7% in restive areas, and

88.2% in non-restive areas). e domain of emotional

stability represented the lowest prevalence; as 14.8% in

restive areas and 15.4% in non-restive area, were reported

as lower levels of resilience than normal people. (Table 3)

On the subject of associated factors to resilience

(Table 4), perception of sleeping/rest quality (p -value=0.067)

and family relationships (p-value<0.001) were found

to be statistically signicantly associated to the levels

of resilience among medical doctors, working in both

the restive and non-restive areas of ailand’s southern

insurgency. According to Table 5, both groups of medical

doctors, who perceived adequate rest/sleep, showed 2.5

greater levels of resilience than those who perceived this

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

230

Demographic characteristics Number (%)

Gender

Male 103 (42.0)

Female 142 (58.0)

Age (year)

Mean±S.D.(min-max) 35.9±9.5 (24-60)

Hometown

3 southern border provinces 89 (36.3)

Other southern provinces 124 (50.6)

Others provinces 31 (12.7)

Missing valued 1 (0.4)

Religion

Buddhism 196 (80.0)

Islam 44 (18.0)

Christianity 2 (0.8)

Others 3 (1.2)

Marital status

Single 123 (50.2)

Married/couple 115 (46.9)

Divorced /widow 3 (1.2)

Missing value 4 (1.6)

Hospitallocation

Non-SBP 137 (55.9)

SBP 108 (44.1)

Work hour (per week)

Mean±S.D. (min-max) 63.0±26.4 (6-120)

 ≤40 74(30.2)

41-60 62 (25.3)

61-80 36 (14.7)

>80 55 (22.4)

Missing value 18 (7.3)

Perceived quality of resting or sleeping

Adequate 119 (48.6)

Not adequate 120 (49.0)

Not sure 1 (0.4)

Missing valued 5 (2.0)

Perceived work stress

No 30 (12.2)

Yes 213 (86.9)

Missing value 2 (0.8)

History of physical illness

No 183 (74.7)

Yes 59 (24.1)

Missing value 3 (1.2)

Family relationship

Excellent 98 (40.0)

Good 119 (48.6)

Fair 26 (10.6)

Missing value 2 (0.8)

Initial reasons of working in the hospital

Near home 135 (55.1)

Reimbursement education fund 39 (15.9)

Follow couple or family 20 (8.2)

Have a chance for study programming 15 (6.1)

Others 33 (13.5)

Missing value 3 (1.2)

TABLE 1. Demographic characteristics (n=245).

Abbreviations: S.D. = standard deviation, GPA = grade point average

Jatchavala et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

231

Original Article

SMJ

TABLE 2. Level of resilience categorized by working area.

Resilience Quotient Total (%) Non-restive (%) Restive (%) Chi2

screening test n=136 n=108 P-value

Level of resilience 0.675

Less than normal range (<55) 37 (15.1) 20 (14.7) 17 (15.7)

Normal range (55-69) 165 (67.3) 90 (66.2) 75 (69.4)

Higher than Normal range (>69) 42 (17.1) 26 (19.1) 16 (14.8)

Mean±S.D. (min-max) 62.3±7.8 (40-80) 62.5±7.8 (42-80) 61.9±7.8 (40-78)

TABLE 3. ree domain of Resilience Quotient by working area (n=244).

Domain of resilience

Total (%) Non-restive (%) Restive (%) Chi2

n=137 n=108 P-value

Emotional stability 0.721

Less than normal range 37 (15.1) 21 (15.4) 16 (14.8)

Normal range (27-34) 173 (70.6) 94 (69.1) 79 (73.1)

Higher than normal range 34 (13.9) 21 (15.4) 13 (12.0)

Mean±S.D. (min-max) 30.2±4.1 (19-40) 30.3±4.2 (20-40) 30.1±3.9 (19-38)

Will power 0.501

Less than normal range 27 (11.0) 13 (9.6) 14 (13.0)

Normal range (14-19) 177 (72.2) 98 (72.1) 79 (73.1)

Higher than normal range 40 (16.3) 25 (18.4) 15 (13.9)

Mean±S.D. (min-max) 16.7±2.5 (10-20) 16.8±2.4 (10-20) 16.6±2.5 (10-20)

Coping skill 0.462

Less than normal range 25 (10.2) 16 (11.8) 9 (8.3)

Normal range (13-18) 197 (80.4) 106 (77.9) 91 (84.3)

Higher than normal range 22 (9.0) 14 (10.3) 8 (7.4)

Mean±S.D. (min-max) 15.4±2.3 (9-20) 15.5±2.3 (9-20) 15.2±2.2 (9-20)

to be inadequate (95%CI=1.1,5.8). Whereas, those who

appraised their family relationship as being excellence,

were found to have resiliency levels 6.5 higher than those

who did not (95%CI=2.1,19.9).

DISCUSSION

Previous studies of mental health, in the SBP of

ailand, mostly focused on mental diculties and

psychiatric diseases, in valuable populations, such as;

patients with substance dependence.

However, it is

questionable as to why some groups of people can produce

positive consequences in specic situations at risk, for

example; medical doctors in the areas of ailand’s southern

insurgency as well as nearby provinces. Compared with

a study among patients with substance-related disorders

in the restive areas of SBP, 15.7% of medical doctors who

worked in the same area were found to have lower levels

of resilience than that of a normal population. Whereas,

28.3% of these patients reported the same level.

e

dierent results may clarify the phenomenon of dierent

social and occupational functioning. Oppositely, dissimilar

physical and mental strength between the two groups

of the population may explain the dierence on the

outcomes of resilience.

However, the authors found that 99.6% of the same

group of medical doctors were suering from burnout

syndrome.

is survey of resilience, which found 84.4%

of the total medical doctors, and 84.2% of those who

worked in the restive areas had normal to higher than

normal levels of resilience, and this may explain the

reason why these medical doctors could work as per usual

in situations with surrounding violence, while suering

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

232

TABLE 4. Association between demographic variables and level of resilience.

Level of resilience Chi2

Demographic characteristics <55 >=55 P-value

(n=37) (n=207)

Gender 0.161

Male 20 (54.1) 83 (40.1)

Female 17 (45.9) 124 (59.9)

Age (year) 0.579

<30 13 (35.1) 58 (28.2)

30-40 14 (37.8) 96 (46.6)

41-60 10 (27.0) 52 (25.2)

Religion 0.679

Buddhism 31 (83.8) 164 (79.2)

Islam/Christianity 6 (16.2) 43 (20.8)

Marital status 0.175

Single/ divorced / widow 23 (63.9) 102 (50.0)

Married/couple 13 (36.1) 102 (50.0)

Work hours (per week) 0.131

 ≤40 6(18.2) 68(35.1)

41-60 8 (24.2) 54 (27.8)

61-80 8 (24.2) 28 (14.4)

>80 11 (33.3) 44 (22.7)

Perceived quality of resting or sleeping 0.067

Adequate 12 (34.3) 107 (52.7)

Not adequate 23 (65.7) 96 (47.3)

Perceived work stress 0.271

No 2 (5.7) 28 (13.5)

Yes 33 (94.3) 179 (86.5)

History of physical illness 0.977

No 27 (77.1) 155 (75.2)

Yes 8 (22.9) 51 (24.8)

Family relationship <0.001

Excellent 8 (22.9) 90 (43.5)

Good 17 (48.6) 101 (48.8)

Fair 10 (28.6) 16 (7.7)

= p-value from Fisher’s exact test

Level of resilience <55 = below average

>=55 = average and above average

TABLE 5. Analyzed Factors associated with resilience (n=221).

Factors

Crude OR Adjusted OR (95%CI) P

(95%CI) LR-test

Perceived quality of resting or sleeping 0.021

Not adequate 1 1

Adequate 2.9 (1.3, 6.3) 2.5 (1.1, 5.8)

Family relationship 0.005

Fair 1 1

Excellent 7.3 (2.4, 22.1) 6.5 (2.1, 19.9)

Good 3.5 (1.4, 9.1) 3.3 (1.3, 8.8)

Abbreviations: OR= Odds ratio, LR = Likelihood Ratio

Jatchavala et al.

Volume 71, No.3: 2019 Siriraj Medical Journal

www.smj.si.mahidol.ac.th

233

Original Article

SMJ

from burnout syndrome. In so saying, a secondary data

analysis study for correlation should be undertaken.

Regarding the associated factors of resilience, quality

of rest/sleep and family relationships showed to have a

signicant association. To promote resilience in medical

doctors, especially those who work in situations at risk;

policy makers should emphasize the working hours,

work-load and work-place location, so as to provide for

adequate rest/sleep and non-disturbance of such family

relationships. Additionally, medical doctors themselves

should be aware of their quality of sleep/rest, family

relationships along with other resources to face both

the mental and physical diculties from their work.

Strength and limitation

Even though this study was the rst study of resilience

among ai medical doctors, especially in the restive areas

of southern ailand’s insurgency, the response rate was

below 20.0%. However, the sample size determination

for nite populations was 320 medical doctors; therefore,

245 participants were 76.5% of calculated sample size,

which is adequate for this resilience study.

e design of this study was that of a cross-sectional

survey; the results could not summarize the process of

medical doctors’ adaptation in spite of adversities. us, a

cohort coupled with long-term, follow-up studies in this

group of the population should be conducted. Moreover,

the data came from a quantitative designed research, which

explains only individual traits of the participants could

also be tabled. To understand the paradigm of resilience,

we have to study contextual interactions between their

inner strengths and contributions within the environment,

therefore; a qualitative- designed study is required.

CONCLUSION

Most medical doctors, who worked at secondary

and tertiary-care hospitals in both the restive areas of

ailand’s southern insurgency as well as the non-restive

areas of nearby provinces, were at normal or higher than

normal levels of resilience. No dierence of resilience was

found between the restive and the non-restive areas of the

ailand’s southern insurgency. e factors associated

to resilience were: perception of sleeping/rest quality

and family relationships. Medical doctors who perceived

adequate rest/sleep showed a 2.5 greater level of resilience,

while those who estimated excellent family relationships

were found to have a resiliency level of 6.5 higher.

ACKNOWLEDGMENTS

is study was fully granted by the Faculty of Medicine,

Prince of Songkla University, ailand. Authors feel

very thankful for cooperation from all hospitals which

participated in our study. We also appreciate Mrs. Nisan

Werachattawanand and Ms. Kruewan Jongborwanwiwat for

their absolute helpful data-analyzing and administration.

Conict of Interest: No conict of interest was declared

by the corresponding author, on behalf of all authors.

REFERENCES

1. Deep South watch. Summary of incidents in Southern ailand,

august 2018 [Internet]. Deepsouthwatch.org. 2018 [cited 2018

Oct 3]. Available from: https://deepsouthwatch.org/en/node/

11862

2. Charoenwong S, Kongsuwan V, Taogani M. Stress and

psychological self-care behaviors of the people in the unrest

area of Narathiwat Province, ailand. Bangkok: Mental Health

in the City; 2007.

3. Maslach C, Jackson S. Burnout in health professions: a social

psychological analysis. In: Sanders G, Suls J, editors. Social

psychology of health and illness. New Jersey: Lawrence Erlbaum;

1982. p. 227-51.

4. Udomlapsakul S, Intanon T, Suttharangsee W. Mental health

promotion of widows from situation of unrest in the three

southernmost provinces, ailand. PNU J 2011; 3:29-40.

5. Oxford University Press. Resilience | Denition of resilience

in English by Oxford Dictionaries [Internet]. Oxford

Dictionaries | English. 2018 [cited 2018 Oct 4]. Available from:

https://en.oxforddictionaries.com/denition/resilience

6. Maneerat S, Isaramalai S- arun, Boonyasopun U. A conceptual

structure of resilience among ai elderly. e Journal of

Behavioral Science [Internet]. 2011 [cited 2018 Oct 5];6(1):

24-40. Available from: https://www.tci-thaijo.org/index.php/

IJBS/article/view/514

7. Rutter M. Psychosocial resilience and protective mechanisms.

Am J Orthopsychiat 1987; 57(3):316-31.

8. Simeon D, Yehuda R, Cunill R, Knutelska M, Putnam F, Smith

L. Factors associated with resilience in healthy adults.

Psychoneuroendocrinology 2007; 32:1149-52.

9. Mental Health Center Region 10. Mental health screening tool

[Internet]. Ubon Ratchathani: Mental Health Center Region

10; 2018 [cited 2018 Dec 4]. Available from: http://www.mhc10.

go.th/evaluation.php

10. Yamane, Taro. Statistics, An Introductory Analysis, 2

ed.,

New York: Harper and Row, 1967.

11. Ministry of public health, ailand. Information of stas

[Internet]. Sasuk12.com. 2017 [cited 5 August 2017]. Available

from: http://www.sasuk12.com/index3.php

12. Jatchavala C, Vittayanont A. Post-traumatic stress disorder

symptoms among patients with substance-related disorders

in the restive areas of south ailand insurgency. Songkla Med

J 2017; 35(2):121-32.

13. Jatchavala C, Ngamkajornwiwat A. Resilience among patients

with substance-related disorders in the restive area of south

ailand insurgency. J Psychiatr Assoc ailand 2016; 61(4):307-18.

14. Pitanupong J, Jatchavala C. A study on the comparison of

burnout syndrome, among medical doctors in the restive areas

and non-restive areas of the South ailand Insurgency. J

Health Sci Med Res 2018; 36(4):279-89.