Siriraj Medical Journal

SMJ

Volume 73, Number 11, November 2021

E-ISSN 2228-8082

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ORIGINAL ARTICLE

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Siriraj Medical Journal

SMJ

Volume 73, Number 11, November 2021

ORIGINAL ARTICLE

727 Pure Flat Epithelial Atypia of the Breast on Core Needle Biopsy: No Need for Surgical

Excision

Warapan Numprasit, et al.

732 Sacral Neuromodulation in the Treatment of Non-Neurogenic Female Lower Urinary Tract

Dysfunction; First Case-series and Systematic Review of Literature

Patkawat Ramart, et al.

738 Temporal Bone Landmarks of the Transverse-sigmoid Sinus Junction:An Anatomical

Study in Dried Human Skulls

Thanawan Supawannawiwat, et al.

744 Speech Outcome Analysis after Primary Cleft Palate Repair: Interim Siriraj Hospital Audit

Sunisa Thongprayoon et al.

752 Clinical Efficacy Test of Polyester Dressing Containing Herbal Extracts and Silver

Sulfadiazine Cream Compared with Silver Sulfadiazine Cream in Healing Burn Wounds:

A Prospective Randomized Controlled Trial

Suttipong Tianwattanatada, et al.

758 Intraoperative Problems and Solutions in Pneumovesicum Laparoscopic Cross-trigonal

Ureteral Reimplantation in Children by a Beginner Surgeon

Thawatchai Mankongsrisuk, et al.

763 Outcomes and Prognostic Factors in Patients with Malignant Peripheral Nerve Sheath

Tumor

Chindanai Hongsaprabhas, et al.

772 Role of Laparoscopy in Diagnosis and Treatment of Endometriosis Associated with

Infertility: A Prospective Analysis

Ankita Ratan, et al.

ORIGINAL ARTICLE

635 Effect of Diabetes Self-Management Education (DSME) with and without Motivational

Interviewing (MI) on Glycemic Control among Children and Adolescents with Type 1

Diabetes Mellitus: A Randomized Controlled Trial

Ornsuda Lertbannaphong, et al.

644 Vaginal Suppository of Metronidazole (750 mg) plus Miconazole Nitrate (200 mg) versus

Oral Metronidazole (2 g) for Bacterial Vaginosis: A Randomized Controlled Trial

Manopchai Thamkhantho, et al.

652 Prevalence and Factors Associated with Antepartum Depression: A University

Hospital-Based

Pavarisa Choosuk, et al.

661 The Perceptions of Roles and Understanding about Forensic Evidence and Crime Scene

Preservation of Thai Paramedics

Thongpitak Huabbangyang, et al.

672 The Predictive Factors Associated with Longer Operative Time in Single-Incision

Laparoscopic Cholecystectomy

Weerayut Thowprasert, et al.

680 Clinical Outcomes of Extracranial Germ Cell Tumors: A Single Institute’s Experience

Kamala Laohverapanich, et al.

687 Renal Outcomes of Childhood IgA Nephropathy and Henoch Schönlein Purpura Nephritis

Thanaporn Chaiyapak, et al.

695 Effects of Physical Exercise Program on Physical Mobility of Patients with Cranial Surgery

Jittima Panyasarawut, et al.

702 Leak-Testing of an Endoscopic Aerosol Box for Preventing SARS-CoV-2 Infection during

Upper Gastrointestinal Endoscopy

Taya Kitiyakara, et al.

REVIEW ARTICLE

710 Operating Room and Flight Deck: What Do These Places Have in Common?

Pattarachat Maneechaeye, et al.

721 Access to Healthcare as a Fundamental Right or Privilege?

Tengiz Verulava

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SMJ

Volume 73, No.11: 2021 Siriraj Medical Journal

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727

Original Article

SMJ

Warapan Numprasit, M.D.*, Norasate Samarnthai, M.D.**, Tichakorn Srianujata, M.D.***

*Department of Surgery, **Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ***anyarak Breast Center,

Siriraj Hospital, Bangkok 10700, ailand.

Pure Flat Epithelial Atypia of the Breast on Core

Needle Biopsy: No Need for Surgical Excision

ABSTRACT

Objective: From previous data, pure at epithelial atypia (FEA) of the breast demonstrated on core needle biopsy

(CNB) was related to malignant upgrading. However, FEA itself is not an independent factor for developing breast

cancer; therefore, the necessity of subsequent surgical excision is controversial. is study aimed to evaluate the

upgrade rate of FEA aer surgical excision and to demonstrate the necessity of surgical excision in FEA lesions

identied on CNB.

Materials and Methods: is retrospective study involved a review of the clinical features, mammographic and

ultrasound ndings, and pathological reports of patients with pure FEA found from CNB specimens between

January 2010 to January 2019. FEA accompanied with atypical ductal hyperplasia, atypical lobular hyperplasia,

ductal carcinoma in situ (DCIS), and invasive cancer (IC) in ipsilateral breast were excluded. FEA upgrade is dened

as patients with in situ or invasive cancer presented in surgical excision specimens. e breast imaging results of

pure FEA and FEA upgrade subsets were compared.

Results: In total, 45 pure FEA specimens were revealed from CNB; of which, 6 of the pure FEA (13.33%) did not

undergo further surgical excision, however, they showed no recurrence during follow-up (median follow-up time:

2.68 years). e majority of FEA cases were detected by mammography in 39 patients (86.67%). Of the 45 patients,

32 were classied into BI-RADS 4B (71.11%), 11 as BI-RADS 4A (24.44%), and 2 as BI-RADS 4C (4.44%). One

patient was upgraded to DCIS (2.7%). BI-RADS classication did not dier between upgrade FEA and non-upgrade

FEA groups (p=0.49).

Conclusion: Only a 2.7% upgrade rate, omitting the surgical excision of pure FEA from CNB, was possible. Even

though our study could not demonstrate a correlation between FEA upgrade and radiological ndings, BIRADS

4A was less likely to carry the malignant cells. Furthermore, segmental microcalcication tended to be associated

with upgraded lesions, but not signicantly.

Keywords: Breast cancer; at epithelial atypia (FEA); upgrade rate (Siriraj Med J 2021; 73: 727-731)

Corresponding author: Warapan Numprasit

E-mail: gi_warapan@gmail.com

Received 5 November 2020 Revised 11 May 2021 Accepted 12 May 2021

ORCID ID: https://orcid.org/0000-0001-9027-7406

http://dx.doi.org/10.33192/Smj.2021.93

INTRODUCTION

In recent decades, the diagnosis of at epithelial

atypia (FEA) has been increasing. Previously, FEA was

known as intraepithelial neoplasia, albeit with an unclear

exact pathological description. In 2003, the World Health

Organization (WHO) coined the term “at epithelial

atypia” to describe a lesion where native ductal cells

are replaced by atypical columnar or cuboidal cells.

e incidence of upgrading to malignancy, in which

atypical cells occur concomitantly with malignancy (in

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728

situ or invasive carcinoma) in larger specimens, aer

FEA has been diagnosed in core needle biopsy (CNB)

specimens as varying from 0 - 42%.

2-4

erefore, the

current standard treatment for FEA aer CNB is surgical

excision. However, FEA itself is not an independent factor

for developing breast cancer. Previous studies found

no risk of breast cancer in FEA lesions aer 13 years

follow-up.

5,6

As a result, the necessity for subsequent

surgical excision is controversial. is study aimed to

evaluate the upgrading rate of FEA aer surgical excision

and to evaluate FEA patients identied by CNB who

have the potential to avoid surgical excision.

MATERIALS AND METHODS

is study involved a retrospective analysis of medical

records and was approved by the Ethics Committee of the

Siriraj Institutional Review Board, Faculty of Medicine

Siriraj Hospital (Si 482/2019). All pathological reports

from CNB specimens diagnosed as FEA from January

2010 to January 2019 were reviewed. Pure FEA from core

needle biopsy specimens, dened as only FEA or FEA

concomitantly occurring with other non-proliferative

or benign proliferative epithelial lesions, were included.

All patients had mammography (MMG) and breast

ultrasound (US) performed followed by core needle

biopsy at Siriraj Hospital. FEA accompanied with atypical

ductal hyperplasia (ADH), atypical lobular hyperplasia

(ALH), ductal carcinoma in situ (DCIS), and invasive

cancer (IC) in ipsilateral breast were excluded. However,

pure FEA from CNB in one breast with contralateral

ADH, ALH, DCIS, and IC were included. All patients

underwent excisional biopsy, otherwise in the case of

patients for whom surgical excision was not performed,

they needed to undergo surveillance at Siriraj Hospital.

Clinical presentation, mammographic and

ultrasonographic ndings, and pathological reports were

collected. For core needle tissue sampling, suspicious

microcalcifications were biopsied by stereotactic-

guided biopsy using a 14-gauge core-biopsy needle

(BARD®MAGNUM®), 14- or 9-gauge vacuum-assisted

device (Eviva®, Hologic), and if a mass was targeted,

ultrasound guidance with a 14-gauge needle (BARD®,

MAGNUM®). e average was obtained from ve cores.

A radiographic clip was placed in some patients for

facilitating follow-up.

Statistical analyses were performed using SPSS

soware version 21 (IBM SSPS, Chicago, IL). Categorical

data was reported as the median with the interquartile

range, mean with SD, or as a percentage. e chi-square

test was used to examine the association between upgrade

to malignancy, the morphology, and the distribution of

the microcalcications. Student’s t-test or Mann–Whitney

U-test was applied to analyze the continuous data. For

the categorical data, the

-test or Fisher-exact test were

used to analyze for statistical signicance. A p-value

less than 0.05 was considered statistically signicant

throughout this study.

RESULTS

During January 2010 to January 2019, 45 pure

FEA lesions diagnosed from CNB were identied. e

baseline characteristics of the patients are described in

Table 1. Of these 45 lesions, 39 were surgically removed.

Six lesions (13.3%) were observed with no following

surgery; however, they showed no recurrence during

surveillance (median follow-up, 2.7 years; range, 29–2844

days). In this study, only one lesion was found upgraded

to DCIS. e median age at diagnosis was 49 years old. Of

the 45 patients, 5 (11.1%) had a history of benign breast

disease at the index breast, while no-one had a family

history of breast or ovarian cancer. e majority of FEA

were detected by mammography (39 lesions; 86.7%);

whereas, 6 lesions were detected by ultrasonography.

When classifying according to BI-RADS classication

(Breast Imaging Reporting and Data System, established

by the American College of Radiology), 11 lesions were

categorized into BI-RADS 4a (24.4%), 32 into BI-RADS

4b (71.1%), and only 2 into BI-RADS 4c (4.4%). All 45

lesions were biopsied; 73.3% stereotactic-guided, 13.3%

vacuum assisted, and 13.3% by US-guided (Table 1).

In cases in which surgical excision was done, FEA

from CNBs were found as pure FEA in the nal surgical

specimens in 26 of 39 patients (66.7%) and coexisted with

either ADH, IDC, or DCIS in 13 patients (33.3%) (Table 2).

Of these latter 13 patients, 1 patient was upgraded to

DCIS (2.6% of total pure FEA from CNB), while no-one

was associated with invasive cancer, and 1 patient had

FEA with ALH (2.6%); meanwhile, 11 patients had FEA

accompanied with ADH (28.2%): 8 found with ADH

and 3 found with ADH, ALH, or LCIS.

Regarding the radiological ndings of the 26 patients

whose nal surgical specimens had conrmed FEA,

8 of the 26 patients were BIRADS 4a (30.8%), 17 were

BIRADS 4b (65.4%), and 1 was BIRADS 4c (3.9%).

Four lesions were detected by US and 22 by MMG. e

mammographic ndings of pure FEA presented with

microcalcication (MC) were as described. In terms

of the shape, 19 were amorphous, 2 punctate, and 1

round. In terms of the distribution, there were 9 clusters,

8 groups, 4 regional, and 1 linear.

ere were 12 lesions for which the nal pathological

report from the surgical excisional specimen demonstrated

Numprasit et al.

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TABLE 1. Baseline characteristics of pure FEA from CNB patients.

Characters CNB pure FEA (n = 45)

Age (years)

Range 37–61

Median 49.0

Detected lesions

 Microcalcication 39

Mass 5

 Microcalcicationwithmass 1

BIRADS

1–3 0

4a 11

4b 32

4c 2

5 0

Target lesion sampling

 Microcalcication 39

 Stereotactic 33

 Vacuumassisted 6

Mass

USG-guided 6

 Residualcalcication

Yes 16

No 18

 Unknown 5

Surgery after FEA identied from CNB

Yes 39

No 6

Histology of excision specimens

Pure FEA 26

 FEAwithAH 12

 FEAwithcancer 1

Abbreviations: AH: atypical hyperplasia, CNB: core needle biopsy, FEA: at epithelial atypia

TABLE 2. Radiographic ndings according to the nal histological results.

Group Total Pure FEA FEA with AH FEA with DCIS P-value

Factor n = 39, (%) n = 26, (%) n = 12, (%) n = 1, (%)

Detectionmethods

MMG 35 22 12 1

US 4 4 0 0

BI-RADS

4A 9 8 (30.8) 1 (8.3) 0 0.49

4B 28 17 (65.4) 10 (83.3) 1 (100)

4C 2 1 (3.9) 1 (8.3) 0

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730

FEA combined with high-risk benign breast lesion. Of these

12 lesions, 10 were BIRADS 4b (83.3%), 1 was BIRADS

4a (8.3%), and 1 was BIRADS4c (8.3%). In terms of the

shape of the microcalcications in these 12 lesions, 10

were amorphous, 1 was ne linear, and 1 was punctuate.

Interestingly, 1 patient whose nal surgical excision

specimen showed DCIS was categorized into BIRADS

4b with segmental amorphous microcalcication. When

comparing the BIRADS classications, no dierence

was observed between the pure and combined FEA

subgroups (p = 0.49).

DISCUSSION

Overall, 1 lesion in our study was upgraded to DCIS

(2.6%) and none of the lesions were invasive carcinoma.

In addition, breast cancer did not occur whether omitting

the surgical group or following surgery in the group

without the upgrading. Despite the risk of subsequent

breast cancer of FEA being unclear, just as in previous

studies, this could not be proven conclusively

5,7

, but

FEA itself tended to not increase the risk of subsequent

cancer. Said et al. found no increasing long-term breast

cancer events when FEA was found concomitantly with

either atypical hyperplasia (AH) or proliferative lesions

(PL): [AH + FEA 4.74 vs. AH 4.23; p = 0.59] and [PL +

FEA 2.04 vs. PL 1.90; p = 0.76], respectively.

In the case

of pure FEA aer surgical excision, de Mascarel et al.

also found that none of the pure FEA patients in their

study had breast cancer during 10-year follow-ups.

e ndings from our study were similar in terms of

the rarity of events following upgrading to malignancy

in FEA lesions diagnosed on CNB.

In practice, pure FEA from CNB should be followed

by surgical removal. is relies on previous evidence,

which demonstrated a 10-40% combination of FEA

with other malignant lesions (either in situ or invasive

carcinoma) from CNB specimens.

2-4,9

However, when

emphasizing cancer upgrading (DCIS or invasive cancer),

the possibility of FEA accompanying these malignant cells

is low (7.5%) compared to its co-incidence with other

high-risk lesions (18.6%).

When vacuum-assisted core

needle biopsy (VCNB) was rst introduced, the rate of

upgrading decreased dramatically. Recent investigations

using VCNB reported decreasing histologic upstaging at

0 - 3%.

10,11

However, even our practices did not routinely

use VCNB in all microcalcication-detected cases, and

our upgrading rate was only 2.6%. The necessity of

surgical excision, therefore, is controversial.

Despite the low incidence of malignant upgrading,

the rate of combining ADH was high (30.7%). In addition,

our study could not demonstrate the correlation between

FEA upgrading and radiologic ndings. Even though most

patients presented with suspicious microcalcications

detected by mammography and were classied into

BIRADS 4b, the study population was too small to

specify the signicance of the imaging classication to

discriminate whether the lesion was pure or mixed FEA.

In the case of mammographic abnormalities, amorphous

microcalcications were more commonly identied in

30 of 39 specimens (76.9%) than other shapes and the

majority were distributed as clusters. In 1 lesion with

DCIS upgrading, the patient presented with segmental

amorphous microcalcication, which was the only case

where the microcalcication was distributed as a segmental

shape. Likewise, previous studies failed to identify the

specic radiographic characters for FEA upstaging

3,12

which tended to be clustered or segmental amorphous

microcalcications.

3,13

Although, no distinctive breast

imaging was noted, FEA diagnosed as BIRADS 4a was

less likely to be upgraded, and occurred in only one of

9 patients (11.1%), meanwhile, FEA also occurred with

BIRADS 4b (11 of 28; 39.3%) or 4c (1 of 2; 50%); therefore,

BIRADS classication was not a good independent predictor

for selecting patients to observe instead of performing

surgery. Among one of several studies, Alencherry et al.

recently reported that one of the independent risk factors

to upstaging was a history of cancer in individuals or

rst-degree relatives

13,14

, but no patients in our cohort

had a family history of breast cancer.

However, there were some limitations in our study

to note. As the pathological denition of FEA has only

recently been introduced in the past few decades, there may

have been interobserver variabilities of the interpretation

among pathologists and it might have been reported

as columnar cell change in some cases, thus causing a

smaller number to be included in the study population,

especially as we could not review all the slide specimens.

Another shortcoming, because of the higher cost of

vacuum-assisted devices, is that in our hospital, core

needle biopsy with a 14-gauge needle rather than VCNB

is the most practised technique, which might be less

accurate.

CONCLUSION

Flat epithelial atypia is a marker of carrying a high

risk lesion rather than for upgrading to breast cancer.

Even though the histological nding may show atypical

cells, the risk of subsequent breast cancer is very low

compared to ADH. Surgical excision may be omitted

particularly in cases of pure FEA from core needle biopsy.

Numprasit et al.

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Needle Biopsy. Mayo Clin Proc. 2014;89(4):536-47.

8. de Mascarel I, MacGrogan G, Mathoulin-Pélissier S, Vincent-

Salomon A, Soubeyran I, Picot V, et al. Epithelial atypia in

biopsies performed for microcalcications. practical considerations

about 2,833 serially sectioned surgical biopsies with a long

follow-up. Virchows Arch. 2007;451(1):1-10.

9. Lavoue V, Roger CM, Poilblanc M, Proust N, Monghal-Verge

C, Sagan C, et al. Pure at epithelial atypia (DIN 1a) on core

needle biopsy: study of 60 biopsies with follow-up surgical

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10. Chan PMY, Chotai N, Lai ES, Sin PY, Chen J, Lu SQ, et al.

Majority of at epithelial atypia diagnosed on biopsy do not

require surgical excision. Breast. 2018;37:13-17.

11. Hugar SB, Bhargava R, Dabbs DJ, Davis KM, Zuley M, Clark

BZ. Isolated Flat Epithelial Atypia on Core Biopsy Specimens

Is Associated With a Low Risk of Upgrade at Excision. Am J

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Patkawat Ramart, M.D., Phadungsak Sangsoad, M.D.

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

Sacral Neuromodulation in the Treatment of

Non-Neurogenic Female Lower Urinary Tract

Dysfunction; First Case-series and Systematic

Review of Literature

ABSTRACT

Objective: To demonstrate which types of non-neurogenic female lower urinary tract dysfunction (LUTD) respond

to sacral neuromodulation (SNM) aer the failure of all non-invasive treatments.

Materials and Methods: Female LUTD performed SNM between 2017 and 2019 were retrospectively reviewed. A case

with anatomical or neurological abnormalities were excluded by thorough physical examination and investigations.

e specic type of LUTD, including midurethral obstruction (MUO), was diagnosed by videourodynamics

(VUDS). Clinical diagnoses, including idiopathic urinary retention (IUR), voiding dysfunction (VD) and refractory

overactive bladder (OAB), were used instead of VUDS diagnosis when the result was normal or inconclusive. e

International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) in ai version

were used to compare between pre and post-treatment. Responder was dened as an IPSS and/or OABSS decreased

more than 50% from baseline.

Results: Total 21 cases were performed SNM. e average age was 49.6 (24–80) years. e average pre-treatment

IPSS and OABSS were 23.4 and 6.4 as well as average post-treatment IPSS and OABSS were 13.7 and 3.8. Only 9

out of 21 cases (42.9%) showed improvement aer SNM. e responders included 7 out of 11 MUO (63.6%), 1 out

of 4 IUR (25.0%), and 1 out of 3 OAB (33.3%). None of the VD cases responded to SNM.

Conclusions: SNM is another option for female patients with LUTD who have failed to respond to conservative

treatments. Aer completely excluding anatomical and neurological abnormalities, the types of LUTD having a

chance to respond to SNM are MUO, IUR, and OAB.

Keywords: Lower urinary tract dysfunction, Female, Sacral neuromodulation (Siriraj Med J 2021; 73: 732-737)

Corresponding author: Patkawat Ramart

E-mail: patkawat.ram@mahidol.ac.th

Received 6 September 2021 Revised 14 October 2021 Accepted 14 October 2021

ORCID ID: https://orcid.org/0000-0003-0452-367x

http://dx.doi.org/10.33192/Smj.2021.94

Abbreviation

LUTD : Lower urinary tract dysfunction

SNM : Sacral neuromodulation

VUDS : Videourodynamics

BOO : Bladder outlet obstruction

MUO : Midurethral obstruction

DU : Detrusor underactivity

IUR : Idiopathic urinary retention

VD : Voiding dysfunction

OAB : Overactive bladder

Ramart et al.

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INTRODUCTION

Lower urinary dysfunction (LUTD) is a functional

problem that mainly causes lower urinary symptoms in

women and usually aects their quality of life. Functional

abnormalities in each patient may consist of bladder and/or

outlet dysfunction. Because LUTD is a dynamic abnormality

and changes over time, the appropriate management

for LUTD should be conservative treatment and/or

medication. However, lower urinary tract symptoms may

not properly be alleviated by non-invasive treatment; while

invasive surgery will rarely be considered due to the risk

of a permanent change of function. Neuromodulation, a

treatment using electrical stimulation directly to the nerve

in order to modulate the reexes that inuence the bladder,

sphincters, bowel, and pelvic oor

to restore normal

lower urinary tract function, has been widely accepted

for treating LUTD and is considered as a non-invasive

procedure. Nowadays, there are many neuromodulation

procedures that have been used for treating LUTD, but

the most popular one is sacral neuromodulation (SNM),

which has supported from many scientic studies. e US

FDA has approved the use of InterStim™ or SNM for the

treatment of urgency-frequency syndrome, urinary urge

incontinence, and non-obstructive urinary retention.

In ailand, neuromodulation has been used in many

neurological conditions but there has never had a study

of neuromodulation for treating LUTD. Consequently,

this study aims to demonstrate our experience and to

provide the LUTD characteristics of patients who have

a chance to obtain a benet from SNM.

MATERIALS AND METHODS

We retrospectively reviewed the medical records

of 21 female patients with non-neurogenic LUTD who

were performed SNM between 2017 and 2019 in our

hospital. is study was approved by our institute IRB,

number 714/2562(IRB2)

Patient selection

e inclusion criteria were female patients with

LUTD who had not responded or had an unsatisfactory

response to all conservative treatments for more than 6

months. All cases would like to try SNM aer counselling

and understanding the risks and benets of procedure.

Further, physical and neurological examination must reveal

no signicant anatomical or neurological abnormality that

could probably be a cause of the LUTD. All the cases had

videourodynamics (VUDS) performed followed by the

International Continence Society (ICS) recommendation

in order to diagnose a type of functional abnormality

and to get a clear urodynamic diagnosis before SNM was

performed. Because surface electromyography during

VUDS was unreliable, the result was not considered as

a part of diagnosis and uoroscopic imaging was used

instead of it. In cases of normal or inconclusive result

due to situational inability to void, clinical diagnosis was

used for the grouping instead of urodynamic diagnosis.

Denitions

According to ICS terminology 2010, the denition of

characteristics of LUTD consist of an overactive bladder

(OAB), dened as urinary urgency, usually accompanied

by frequency and nocturia, with or without urgency

urinary incontinence, in the absence of urinary tract

infection or other obvious pathology; voiding dysfunction

(VD), dened as an abnormally slow and/or incomplete

micturition; detrusor underactivity (DU), dened as a

detrusor contraction of reduced strength and/or duration,

resulting in prolonged bladder emptying and/or a failure

to achieve complete bladder emptying within a normal

time span; and bladder outlet obstruction (BOO), dened

as a reduced urine ow rate and/or presence of a raised

post-void residual urine and an increased detrusor

pressure.

e urodynamic criteria for the diagnosis of

female BOO were described in Blaivas’s study.

In this

group, the point of obstruction could be demonstrated

by uoroscopic examination on VUDS so that specic

term, including midurethral obstruction (MUO), was used

instead of BOO. Urethral stricture must be excluded by

cystourethroscopy in all BOO cases. In cases of normal

or inconclusive VUDS, the clinical diagnosis consisted

of voiding dysfunction (VD), dened as a maximal urine

ow rate equal to or less than 12 ml/sec with or without

post-void residual urine; idiopathic urinary retention

(IUR), dened as a past or current inability to void; and

refractory overactive bladder (OAB), dened as OAB

which had failed to respond to conservative treatment

and medications or led to intolerable adverse events.

Responders were dened as being cured or showed an

improvement aer SNM.

Measurement

e validated questionnaires in the ai language,

including the International Prostate Symptom Score (IPSS)

and Overactive Bladder Symptom Score (OABSS)

, were

used as a symptom measurement tool. Cure was dened

as an IPSS and/or OABSS improvement of more than

80% from baseline, while improvement was dened as an

IPSS and/or OABSS improvement of between 50% and

80% from baseline within 7-30 days aer implantation

and the last follow-up for the response cases. Responder

was dened as a case who was cure or improvement aer

SNM.

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Ramart et al.

Procedure

Sacral neuromodulation (SNM) is usually performed

in two stages: a test phase and a phase with implantation

of an implantable pulse generator (IPG) by using the

InterStim II® system (Medtronic). e test phase utilized

two techniques: temporary lead implantation, called

percutaneous nerve evaluation (PNE), and permanent

tined lead implantation, composed of four leads and a

hook. e full SNM system consisted of a permanent

tined lead and IPG. Lead implantation was performed

in the prone position, in a well-prepared sterile eld and

under local anesthesia with light sedation. Fluoroscopic

guidance was used to identify the 3

sacral foramen in

two-dimensions, in the anteroposterior and lateral views.

A 20-gauge needle in the set of SNM was used to make a

puncture at 2 cm cephalad to the 3rd sacral foramen in

the anteroposterior view and at the 45°–60° axis in the

lateral view. e needle was passed through the foramen

and stopped at the anterior surface. e proximal end of

the needle was connected to an external pacemaker and

then electrical stimulation was given. e proper position

of the needle was dened by the patient reporting feeling

a tickling sensation at the perianal area, anus, and/or

vagina, called a sensory response and demonstrating anal

contraction, called a motor response. If the selected site

did not demonstrate any response, the procedure would

be repeated at the contralateral site in the same step. e

needle stylet was then removed. Either a temporary lead

or permanent lead was inserted via the needle and placed

in a proper position by checking the sensory and motor

responses. For PNE, the lead was xed directly at the

puncture site using a transparent medical dressing. For

the permanent lead, a subcutaneous tunnel was created by

a trocar with a plastic tube from the puncture site to the

subcutaneous pocket at the right buttock and the lead was

connected to an extended wire to directly connect to an

external pacemaker in order to prevent contamination.

Due to the easy displacement of the PNE lead, some

cases reporting no response might repeat either PNE or

permanent tined lead implantation if the patient agrees.

During the test phase, the external pacemaker was used

as an electrical generator and the implanted patient

could adjust the intensity of the electrical stimulation by

monitoring their feeling in the perianal area, anus, and

vagina. If the feeling was too much, electrical stimulation

could be reduced by remote control. For evaluation, if

a patient reported symptoms improvement of more

than 50% from baseline by IPSS and OABSS, full SNM

system implantation would be performed within 1-4

weeks. Because of the high cost of full SNM system

implantation, PNE was considered as a rst step in all

cases who had unsuccessful VUDS or where there were

doubts about the benet of SNM. All cases of full SNM

system implantation were supported by the high cost

treatment project of our hospital foundation.

Statistics

e results were presented using descriptive statistics

as a frequency and percentage for categorical data, as

well as average for continuous data.

RESULTS

In total, 21 cases of female LUTD who had SNM

performed. e average age was 49.6 (24 – 80) years.

e types of LUTD consisted of MUO 11 cases, IUR 4

cases, VD 3 cases, and OAB 3 cases. MUO and VD cases

were treated by non-invasive management including

behavioral therapy, pelvic oor muscle rehabilitation

and oral medications. IUR cases were initially treated by

indwelling catheter and then performed clean intermittent

catheterization. OAB cases were treated step by step

including rst - single oral bladder relaxant, second -

combination of oral high dose bladder relaxant and last

- 100 unit of intradetrusor botulinum toxin A injection.

e average pre-treatment IPSS and OABSS were 23.4

and 6.4 as well as the average post-treatment IPSS and

OABSS were 13.7 and 3.8. (Table 1) Only 9 out of 21

cases (42.9%) were cured or improved aer SNM. e

responders included 7 out of 11 MUO (63.6%), 1 out

of 4 IUR (25.0%), and 1 out of 3 OAB (33.3%). None of

the VD cases responded to SNM. Twelve of 21 cases had

complete VUDS successfully performed. (Table 2) Only

8 out of 9 responders had fully implanted SNM and the

average follow-up was 15.4 (4.4 – 32.4) months, while the

average IPSS and OABSS were 8.4 and 2.7, respectively.

One case decided not to continue with SNM because of

an awareness of the foreign body and fear of the long-

term consequences (Table 3). In total, 6 out of 8 cases

reported and considered themselves cured. No adverse

events were reported in all cases.

DISCUSSION

Female LUTD without anatomical and neurologic

abnormality is a challenging condition. Importantly, it

is not a life-threatening condition but always aects the

patient’s quality of life. Because of the dynamic changes

that can occur, the most appropriate treatment, including

conservative and medical treatment, should be reversible

over time, meaning that invasive surgery is not an ideal

option. However, while most patients are properly treated

by conservative and medical treatment, some patients

may not achieve their goal. SNM is another treatment

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TABLE 1. Comparison between average pre- and post-treatment IPSS and OABSS in each type of LUTD.

TABLE 2. Case number, diagnosis and videourodynamics parameters in each case.

Type of LUTD No.

IPSS OABSS

Pre-treatment Post-treatment Pre-treatment Post-treatment

MUO

Responder 7 23.7 5.4 6.0 1.9

Non-responder 4 18.3 15.0 3.5 2.6

IUR

Responder 1 34.0 6.0 6.0 3.0

Non-responder 3 27.3 22.7 4.0 2.7

Responder 0 - - - -

Non-responder 3 25.3 23.3 8.3 8.3

OAB

Responder 1 15.0 0 9.0 0

Non-responder 2 15.5 15.5 11.0 11.0

Free

Urodynamic parameters

Case

Age Dx Group VV PVR uroow

no.

Qmax

Catheter Pdet at Fluoroscopic

Qmax Qmax ndings

1 35 MUO Responder 178 0 12.9 - - Mid

2 54 MUO Responder 115 155 - 4.2 80 Mid

3 41 MUO Non-responder 67 0 13.8 4.8 51.5 Mid

4 54 MUO Responder 40 205 - 2.1 57.5 Mid

5 68 MUO Responder 81 154 25 4.3 23 Mid

6 53 MUO Responder 376 0 16 16.4 26.5 Mid

7 53 MUO Non-responder 144 0 - 10.3 61.2 Mid

8 38 MUO Non-responder 210 0 18.8 - - Mid

9 24 MUO Responder 65 0 - 8.8 24 Mid

10 76 MUO Responder 80 96 - 5 25 Mid

11 80 MUO Non-responder 274 63 11 8.8 37.2 Mid

12 42 IUR Non-responder 199 202 11.6 - - -

13 45 IUR Non-responder 161 80 6.9 - - -

14 31 IUR Non-responder 126 150 10.2 - - -

15 36 IUR Responder 70 600 4 - - -

16 38 VD Non-responder 592 0 12 - - -

17 34 VD Non-responder 233 200 10 - - -

18 65 VD Non-responder 256 0 11.5 - - -

19 76 OAB Responder 491 0 - 21.9 17.1 No BOO

20 41 OAB Non-responder 420 0 - 25.5 30 No BOO

21 59 OAB Non-responder 180 0 - 24.2 28.2 No BOO

Abbreviations: Dx : diagnosis, VV : voided volume (ml), PVR : post-void residual urine (ml), Qmax : maximal urine ow rate (ml/sec),

Pdet@Qmax : detrusor pressure at maximal urine ow rate (cmH2O), Mid : midurethral obstruction, BOO : bladder outlet obstruction

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Ramart et al.

TABLE 3. Comparison between pre- and post-treatment IPSS and OABSS in responder group at the last follow up.

Case Age Follow time

IPSS OABSS

no. (year)

Diagnosis

(month)

Pre- Post- Pre- Post- Status

treatment treatment treatment treatment

1 35 MUO 32.4 31 0 3 0 Cure

2 54 MUO 21.2 40 1 15 1 Cure

4 54 MUO 7.1 22 11 6 2 Improvement

5 68 MUO 13.0 20 8 4 3 Improvement

6 53 MUO 12.7 15 0 2 2 Cure

9 24 MUO - 19 - 11 - Notperform

10 76 MUO 4.4 19 1 1 1 Cure

15 36 IUR 7.3 34 4 6 2 Cure

19 76 rOAB 25.2 15 5 9 4 Cure

option and is appropriate for LUTD. In our study, we

categorized female LUTD into 4 types based on rstly

urodynamic and lastly clinical diagnosis, including MUO,

IUR, DV, and OAB.

For female BOO, common locations of obstruction

are the bladder neck and midurethral. Bladder neck

obstruction is usually treated by an alpha-adrenergic

antagonist or transurethral incision bladder neck. On

the other hand, most MUO cases are usually treated and

respond to SNM. Soumendra et al. reported a 10-year

experience of SNM for females with urinary retention

secondary to external urethral sphincter overactivity or

Fowler’s syndrome. e overall success was 72% and

the results revealed that females with normal urethral

sphincter activity had worse outcomes than those with

an abnormal urethral sphincter activity.

In our study,

female BOO was diagnosed by VUDS according to the

criteria in Blaivas’s study

and we found 11 cases were

MUO. In total, 7 out of 11 (63.6%) MUO cases responded

to SNM and the success rate was comparable.

In our study, both IUR and DV were clinical

diagnoses because of inconclusive VUDS result, such

that they might be detrusor acontractility (DAC), DU,

BOO, or combined abnormalities. Rademakers et al.

performed a study in 18 men with DU, dened as a

measurement value less than the 25

percentile in the

linear interpolation of a Maastricht–Hannover nomogram,

and reported that 50% of the cases responded to SNM.

Chan et al. performed a study in 50 women and 19 men

with DU, dened as having a bladder contractility index

(BCI = Pdet at Qmax + 5Qmax) of less than 100, and

reported that 51% of cases had a favorable response to

the trial phase, dened by at least a 50% improvement

in symptoms, PVR, and voided volume bladder diary.

Interestingly, 6 of 18 cases with detrusor acontractility,

dened by an absent contractility with failure to empty

and absence of EMG abnormalities, had a favorable

response to the trial phase. ey concluded that patients

with preserved detrusor contractility were more likely

to respond to SNM.

In our study, only one of our IUR

cases successfully responded to SNM, which probably

meant this patient had enough detrusor contractility or

BOO.

Noblett et al. performed a study in patients with

OAB, conrmed on a consecutive three-day voiding diary

with a minimum of two involuntary leaking episodes

in 72 hours and/or ≥ 8 voids per day, where success

at 12 months was dened as a ≥50% improvement in

average leaks/day or ≥50% improvement in voids/day or

a return to normal voiding frequency (<8 voids/day). e

responder rate was 85% in overall OAB symptoms. Only

37% of OAB cases with UUI had complete continence.

In our study, 1 of our 3 OAB cases gained continence

and was cured.

A key strength of our study study is that we tried to

identify dysfunctional causes in each case by VUDS in

order to make it clear which type of LUTD would benet

from SNM. However, urodynamic diagnosis should be

a key tool to predict SNM response, as VUDS could not

be successfully performed for most cases. Because the

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test is in an unnatural setting, we even tried to perform

it in a similar way to mimic a patient’s lower urinary

tract function. Importantly, strict urodynamic criteria

for diagnosing female BOO and DU are inconclusive and

dicult to draw conclusions, so that the SNM results of

many studies highly depend on patient selection. Lastly,

the limitations of this study to note are its small sample

size and retrospective design, which prompt the need

for further research.

CONCLUSION

SNM is another option for female patients with

non-neurogenic LUTD who have failed to respond to all

conservative treatments. In our study, aer completely

excluding anatomical abnormalities, the type of LUTD

having the highest chance to respond to SNM was found

to be midurethral obstruction (MUO). For idiopathic

urinary retention (IUR) and refractory overactive bladder

(OAB), only one-third of cases responded. No voiding

dysfunction (VD) cases responded to SNM. is information

may help urologists to better select patients for SNM.

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2. Liberman D, Ehlert MJ, Siegel SW. Sacral Neuromodulation

in Urological Practice. Urology. 2017;99:14-22.

3. Rosier P, Schaefer W, Lose G, Goldman HB, Guralnick M,

Eustice S, et al. International Continence Society Good Urodynamic

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and pressure-ow study. Neurourol Urodyn. 2017;36(5):1243-

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4. Haylen BT, de Ridder D, Freeman RM, Swi SE, Berghmans B,

Lee J, et al. An International Urogynecological Association

(IUGA)/International Continence Society (ICS) joint report

on the terminology for female pelvic oor dysfunction. Neurourol

Urodyn. 2010;29(1):4-20.

5. Blaivas JG, Groutz A. Bladder outlet obstruction nomogram

for women with lower urinary tract symptomatology. Neurourol

Urodyn. 2000;19(5):553-64.

6. Nontakaew K, Kochakarn W, Kijvika K, Viseshsindh W,

Silpakit C. Reliability of a ai version of the International

Prostate Symptom Score (IPSS) for the ai population. Journal

of the Medical Association of ailand = Chotmaihet thangphaet.

2014;97(6):615-20.

7. Bunyavejchevin S. Reliability of Thai-Version Overactive

Bladder Symptom Scores (OABSS) Questionnaire and the

Correlations of OABSS with Voiding Diary, International

Prostate Symptom Score (IPSS), and Patient Perception of

Bladder Condition (PPBC) Questionnaires. Journal of the Medical

Association of ailand = Chotmaihet thangphaet. 2015;98(11):

1064-74.

8. Datta SN, Chaliha C, Singh A, Gonzales G, Mishra VC, Kavia

RB, et al. Sacral neurostimulation for urinary retention: 10-

year experience from one UK centre. BJU Int. 2008;101(2):192-6.

9. Rademakers KL, Drossaerts JM, van Kerrebroeck PE, Oelke M,

van Koeveringe GA. Prediction of sacral neuromodulation

treatment success in men with impaired bladder emptying-time

for a new diagnostic approach. Neurourol Urodyn. 2017;36(3):

808-10.

10. Chan G, Qu LG, Gani J. Evaluation of pre-operative bladder

contractility as a predictor of improved response rate to a staged

trial of sacral neuromodulation in patients with detrusor

underactivity. World J Urol. 2020.

11. Noblett K, Siegel S, Mangel J, Griebling TL, Sutherland SE,

Bird ET, et al. Results of a prospective, multicenter study

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anawan Supawannawiwat, M.D., Chottiwat Tansirisithikul, M.D., BunpotSitthinamsuwan, M.D.,M.Sc.

Division of Neurosurgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, MahidolUniversity, Bangkok 10700, ailand

Temporal Bone Landmarks of the Transverse-

sigmoid Sinus Junction: An Anatomical Study in

Dried Human Skulls

ABSTRACT

Objective: To investigate the accuracy in localization of the anterosuperior margin of TSSJ by using the intersection

point between the squamosal and parietomastoid sutures (A point) and the intersection of the squamosal suture

and supramastoid crest (B point) as bony landmarks.

Materials and Methods: e A and B points were marked on the inner surface of a skull by using the transillumination

technique. e anatomical relationship between the projected A point, B point, and groove of TSSJ was investigated

in 60 dried ai human skulls (120 sides).

Results: Of the 120 sides, the projected A points were located exactly on the anterosuperior margin of the TSSJ in

38 (31.7%) instances and adjacent (above and below) the anterosuperiormargin in 82 (68.3%) cases. Of the 118

sides with identiable supramastoid crests, the projected B points were located precisely on the anterosuperior

margin of TSSJ in 60 (50.8%) cases and above the anterosuperior margin of the TSSJ in 57 (48.3%) cases.Hence,

the projected B point was a more reliable bony landmark for localizing the anterosuperior margin of the TSSJ when

compared with the projected A point (p = 0.003, OR 2.2, and 95% CI =1.3-3.8).

Conclusion: e B point is a more reliable temporal bone landmark for localization of the TSSJ than the A point.

In temporal craniotomy, an initial burr hole at the B point is relatively safe and carries a very low risk of inadvertent

venous sinus injury.

Keywords: Relationship; transverse-sigmoid sinus junction; squamosal suture; parietomastoid suture; supramastoidcrest;

temporal craniotomy; middle cranial fossa (Siriraj Med J 2021; 73: 738-743)

Corresponding author: Chottiwat Tansirisithikul

E-mail: tansirichok@hotmail.co.th

Received 21 January 2021 Revised 20 April 2021 Accepted 31 May 2021

ORCID ID: https://orcid.org/0000-0001-6562-0671

http://dx.doi.org/10.33192/Smj.2021.95

INTRODUCTION

In neurosurgical practice, temporal craniotomy

is one of the most common surgical approaches for

dealing with lesions that involve the middle cranial

fossa. is procedure is also the key component for

more aggressive lateral skull base approaches such asthe

transpetrosalapproach. e posterior boundary of this

approach is dened by the transverse-sigmoid sinus

junction (TSSJ). In order to maximize craniotomy size

and to avoid inadvertent venous sinus injury, localization

of this major venous sinus is crucial during planning for

craniotomy.

1-9

Although the neuronavigation system is

extremely useful nowadays, it is not generally available in

a resource-limited public hospital or emergency situation.

As a result, anatomical landmarks are still important

for neurosurgeons, especially when performing initial

burr hole placement.

1-9

e temporal bone is known

for its complexity with various bony landmarkssuch

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as the squamosal suture,parietomastoidsuture,and

supramastoidcrest. ere has been controversy in previous

anatomical studies regarding the best bony landmark of

TSSJ in which the intersection between the squamosal

andparietomastoidsutures and the intersection between

the squamosal suture andsupramastoidcrest have been

mentioned.

1,6-9

Both intersections have been commonly

used as the bony landmark of TSSJ. Additionally, race-

based dierences of the skull may also aect the surgical

approach and make one bony landmark suitable for

one race but unreliable for another.

10-11

e authors of

this study used dried human skulls to investigate the

relationship between the temporal bone landmarks and

TSSJ.

MATERIALS AND METHODS

One hundred twenty temporal bones from 60

dried ai adult human skulls were evaluated in this

study. e squamosal sutures, parietomastoid sutures,

andsupramastoidcrest were identied at the outer

surface of the skull. On the inner surface, the grooves of

the transverse sinuses and sigmoid sinuses and TSSJ were

identied. For practicality issues, if there was variation in

sutures such as presence of sutural bone causing multiple

sutures, the most conspicuous suture line would be used.

Aer identifying these key structures, a point on the

intersection between the squamosal and parietomastoid

sutures was labeled as the “Apoint”, and the intersection

between the squamosal suture andsupramastoidcrest

was determined to be the “Bpoint”. Both points were then

marked on the outer surface of the skull (Fig1). e A and

B points were then projected onto the inner surface of the

skull and traced via a transillumination technique using

a laser pointer positioned perpendicular to the skull’s

surface (Fig 2). e projected points A and B were then

evaluated according to whether they were situated on

TSSJ (Fig 3). If conrmed, it would be further classied

as the projected points would be positioned exactly at the

anterosuperior margin or other areas of the TSSJ. Also,

the relationship betweenthe anterosuperiormargin of

TSSJ and projectedA and B point was described and a

distance between these landmarks was measured along

the horizontal (X) and vertical (Y) axis.

is study was ethically approved bythe Institutional

Review Board (IRB) at Siriraj Hospital, Mahidol University

(Si 717/2561 (Exempt)).

Statistical analysis

A statistical analysis was performed using PASW

version 22.0 (SPSS, Chicago, IL, USA). Descriptive

statistics were used to investigate characteristics of the

study sample, including median, range, and percentage

for numerical data. Accuracy of the projected A point

and B point for predicting the location of the TSSJ was

analyzed using Pearson’s chi-squared test. A p-value of

less than 0.05 was considered statistically signicant.

Odds ratio (OR) and 95% condence interval (CI) was

estimated from Pearson’s chi-squared test.

Fig 1. Key points on the outer surface

of the skull. (A): “Apoint” (arrow),

dened as the point of intersection

between the squamosal (arrowhead)

and parietomastoid sutures (double

arrowheads); (B): “Bpoint” (arrow),

dened as the point of intersection

between squamosal suture

(arrowhead) and supramastoid crest

(double arrowheads); MP refers to

mastoid process.

Fig 2. Transillumination technique using a laser

pointer perpendicular to the outer surface of the

skull and marking of the projected point (arrow)

on the inner surface of the skull.

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740

Fig 3. Measurement of distance between the projected

A point (arrow) and the anterosuperior margin of

TSSJ (arrowhead) in vertical (a) and horizontal (b)

directions.

RESULTS

Demographic characteristics

e mean age of the skull specimens was 38 ± 11.1

years (range 18-60 years). Of the sixty skulls, 30 (50%)

were male, and 29 (48.3%) were female. e remaining

skull (1.7%) belonged to an unknown gender.

e relationship between the projected A point and

anterosuperior margin of the TSSJ

e projected A points were located exactly on

the anterosuperior margin of the TSSJ in 38 out of

120 cases (31.7%). In 82 out of 120 cases (68.3%), the

projected A points were not exactly located on the sinus

margin but situated adjacent (either above or below)

theanterosuperiormargin of the TSSJ (Fig 4A).e

distance from the projected A point to the anterosuperior

margin of the TSSJ ranged from -16 to 12 mm (median

0 mm) on the X-axis and -14 to 17 mm (median 0 mm)

on the Y-axis.

e relationship between the projected B point and

anterosuperior margin of the TSSJ

Of the 60 human skulls, one was excluded due to its

unidentiable bilateral supramastoid crest. e projected

B points were located exactly on the anterosuperior

margin of the TSSJ in 60 of the remaining 118 sides

(50.8%). In cases where the projected B points were not

exactly located on the sinus margin, almost all of the

points were situated above the anterosuperior margin

of the TSSJ (57 of 118 sides or 48.3%). e projected B

point of the remaining one side was positioned within

the TSSJ below the anterosuperior margin (Fig 4B). e

distance from the projected B point to the anterosuperior

margin of the TSSJ ranged from -14 to 9 mm (median

0 mm) on the X-axis and -4 to 28 mm (median 0 mm)

on the Y-axis.

Fig 4. e distribution of the projected A (a) and B points (b) related to the location of the transverse sigmoid sinus junction (TSSJ). In both

gures, the intersection between the X- and Y-axis indicate the anterosuperior margin of the TSSJ; SS, sigmoid sinus; TS, transverse sinus.

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Comparison between the accuracy of the projected

A and B points for predicting the location of the

anterosuperior margin of the TSSJ

Sixty out of one-hundred and eighteen sides (50.8%)

of the projected B points were located exactly on the

anterosuperior margin of the TSSJ whereas the projected

A points were located on the anterosuperior margin in

38 of 120 cases (31.7%). is dierence in accuracy was

statistically signicant (p = 0.003, OR 2.2, and 95% CI

=1.3-3.8).

Comparison between the accuracy of A and B points

for predicting the location of the TSSJ (excluding the

anterosuperior margin of the sinus)

e projected A points were located within the

TSSJ in 21 of 120 sides (17.5%) while the projected B

point was located with the TSSJ in only one out of 118

sides (0.8%). is dierence of accuracy was statistically

signicant (p < 0.001, OR 24.8, 95% CI = 3.3-187.8).

e eect of gender on anatomical relationships

When a subgroup analysis with gender was

done, the pattern of relationship between projected

A points, B points and the anterosuperior margin

of the TSSJ was the same as above in both genders.

Between genders, there was no signicant dierence

in relationship between the projected A point, B point

and the anterosuperior margin of the TSSJ (p=0.291 for

A point, p=0.475 for B point)

In both genders, the projected B point was signicantly

more accurate in predicting the location of the TSSJ

(excluding the anterosuperior margin of the sinus) than

the A point (p < 0.001). When predicting the location of

the anterosuperior margin of the TSSJ, the projected B

point was signicantly more accurate than the A point

in females (p=0.004, OR 2.8) but not signicant in males

(p=0.267, OR 1.5).

DISCUSSION

In dealing with surgical lesions in the middle cranial

fossa, temporal craniotomy is the key procedure. However,

it is also used as the major component of more aggressive

skull base approaches such asthe transpetrosalapproach.

In order to perform an eective craniotomy, neurosurgeons

should create an appropriately-sized cranial opening

while avoiding injury of the adjacent major venous

sinuses.

1-10

Since the posterior boundary of temporal

craniotomy is determined using the position of TSSJ, precise

identication of this major venous structure, especially

the anterosuperior margin of the venous junction, is

crucial.Moreover, despite technological advancements

in the neuronavigation system, which helps facilitate

safer and faster surgery

, it is not usually available in a

resource-limited public hospital or emergency situation.

erefore, anatomical bony landmarks are still essential

for neurosurgeons in the initial burr hole process before

beginning temporal craniotomy.

e temporal bone is one of the most complex in the

human body as it is full of various anatomicallandmarks,

such as squamosal suture, parietomastoid suture,

supramastoidcrest, etc. e point of intersection between

the squamosal andparietomastoidsutures (A point) and

the point of intersection between the squamosal suture

andsupramastoidcrest (B point) are commonly used as

the surface landmark to help locate TSSJ.

1,6-10

However,

previous anatomical and clinical studies reported

heterogeneous results and no direct comparison between

both the bony landmarks was studied.

UcerlerandGosvanoted that theasterionwas a

reliable bony landmark for TSSJ, however, when itwas

not exactly supercial, it was mostly inferior to TSSJ.

is

meant that the asterion was a suitable bony landmark for

posterior cranial fossa approachesbut not for temporal

craniotomy, in which the location of the craniotomy is

superior to TSSJ. RazaandQuinones-Hinojosaproposed a

surgical technique for the extendedretrosigmoidapproach

that includes an initial burr hole that encompasses TSSJ,

however, it was slightlysupratentorial.

Despite this, they

did not mention the exact landmark of the burr hole.

Ribas et al. also studied dried human skulls and found

thatthe meeting point between the parietomastoidand

squamous sutures could be easily identied and were

related to the superior margin of the transverse sinus or

oor of the middle cranial fossa.

However, this study

did not mention TSSJ directly. Studies by Bozbugaet al and

Day et al used an imaginary line connecting thesquamosal-

parietomastoidsuture junction and mastoid tip to the

identify sigmoid sinus trajectory but they did not directly

study the relationship between this line and the TSSJ.

6-7

Goto and his coworkers also described their

technique for the safe exposure of the sigmoid sinus

in presigmoidapproaches. ey used the intersection

between the supramastoidcrest and squamosal suture as

a landmark for the anterior margin of TSSJ in this large

case series.

Li et al. studied anatomical landmarks of

the anterosuperiorpoint of the TSSJ using dried human

skulls. ey compared the location of the squamosal-

parietomastoidsuture junction with their coordinate

system and concluded it was more accurate in localization

of the venous sinus junction.

Additionally, a radiological study of cranial surface

landmarks and the venous sinus was conducted bySheng

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742

and colleagues. ey used computerized tomography

angiography and found that 89% ofthe squamosal-

parietomastoidsuture junctions werelocated superior

and anterior to TSSJ.

In our opinion, the use of a

3-dimensional anatomical study is more accurate than

a 2-dimensional radiological study.

ere are also studies showing that how the size,

shape, and structure of the cranium could be dierent

across ethnic groups.

ese dierences can be large

enough to aect surgical approaches. Low et al. found that

Europeans had a greater petrous angle than Chinese people

and therefore they recommended a larger craniotomy size

in Europeans.

For this reason, our study was specic

to the ai population.Duangthongpon et al. studied

supramastoid crest as a surgical landmark for temporal

craniotomy and found that the supramastoid crest is easy

to identify and safe from injury. However, they did not

compare it with other available landmarks.

In our study, three major anatomical landmarks,

including the squamosal and parietomastoid sutures, and

supramastoid crest, were consistently identiable in almost

all specimens. It was only in one specimen (0.8%) that

thesupramastoidcrest could not be identied bilaterally.

Comparing the accuracy of the projected A and B points

in predicting the location of the anterosuperior margin

of the TSSJ, B point was relatively more accurate when

it came to bony landmarks (p = 0.003, OR 2.2, 95% CI

1.3-3.8).

Following the exclusion of the anterosuperior

margin of TSSJ, a signicantly greater proportion of

the projected A point was located within the TSSJ when

compared with the projected B point (p < 0.001, OR

24.8, 95% CI 3.3-187.8). is result implied that using

the B point as a bony landmark for the initial burr hole

in temporal craniotomy carries less risk of major venous

sinus injury.

Moreover, when the projected A and B point were

not located at the anterosuperior margin or within the

TSSJ, the projected B point had a greater accuracy in

localization of initial burr hole and was also able to

avoid inadvertent venous sinus injury. Almost all of the

remaining projected B points were positioned above

theanterosuperiormargin of the TSSJ (48.3%) compared

with the remaining projected A points which were mostly

positioned around (above or below) the anterosuperior

margin of the TSSJ (68.3%).

Our results suggest that when performing temporal

craniotomy in ais, the B point or the intersection

between the squamosal suture andsupramastoidcrest,

is a more reliable temporal bone landmark for localizing

the anterosuperior margin of the TSSJ than the A

point, which is the intersection between the squamosal

andparietomastoidsutures. is is due to the B point

consistent higher accuracy in correct identication, better

predictable relationship, and lower risk of venous sinus

injury.

In order to explain our results, we have to understand

the controversy whether sutural landmarks such as

the asterion are reliable or not.

14-16

In general, sutural

landmarks can be used to “estimate” the location of

major venous sinuses but with caution of individual

variations.

One factor that makes sutural landmarks less

accurate is the presence of additional, irregular sutural

(Wormian) bones which make sutures more varied.

is

presence of sutural bone is used to classify the asterion

into type I (with sutural bone) and II.

18-19

However,

the prevalence of type I asterion was round 10-20%

and generally not mentioned in anatomical studies for

surgical purposes.

1-7,9-10,15-16

Since the aim of our study was

practical usage, we used only conspicuous suture lines.

e prevalence of this bone is highest in the lambdoid

suture followed by posteriorly located sutures such as

parieto-mastoid suture.

is might explain our result

that show how using 2 sutures is less reliable compared

to the landmark which uses only 1 suture.

ere are three factors that are known to aect skull

size and shape and they may have impacted our results.

e rst factor is race, however, comparing races was

not our goal. As our study population included only

ais, our results are very race-specic and might not

be suitable for other ethnic groups.

e second factor is gender. However, Johnson

et al. showed that the dierence between races is larger

than the dierence between gender within the same race.

Moreover, gender dierences are also unique in each

race.

We used equal proportions of both genders in

our study to prevent selection bias. Our results showed

that there were no statistically signicant dierence

between gender regarding relationship between both

skull landmarks and the anterosuperior margin of TSSJ.

Last but not least, the third factor is age. In early

life, the human skull size and shape can change rapidly

but there is minimal growth aer 15 years.

In adults,

bone resorption from increasing age can change cranial

morphology.

However, this change might not be clinically

signicant. A study of cranial morphometry by Nikita

showed that unlike gender, changes in cranial shape

due to increasing age is not statistically signicant and

therefore it was justiable to pool dierent age groups

in a bioarcheological analyses.

Gapert and colleagues

also studied the age eect on sexual dimorphism of adult

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SMJ

foramen magnum. ey found no signicant age eect,

suggesting that a separation by age is not necessary.

From all this evidence, it is reasonable to generalize our

results for ai adults without age stratication.

CONCLUSION

e intersection between the squamosal suture

andsupramastoidcrest serves as a more reliable temporal

bone landmark for localizing the anterosuperior margin

of TSSJ than the intersection between the squamosal and

parietomastoid sutures. Most points with greater reliability

were located at/or superior to the anterosuperior margin

of the TSSJ.



We have no conict of interest to disclose.

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

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Thongprayoon et al.

Sunisa ongprayoon, M.D.*, Kanokwan Liadprathom, B.Sc.**, Apirag Chuangsuwanich, M.D., FRCST*,

Mark H. Moore, MBChB, FRACS***, Sarut Chaisrisawadisuk, M.D., FRCST*,***

*Division of Plastic Surgery, Department of Surgery, **Division of Speech erapy, Department of Rehabilitation Medicine, Faculty of Medicine

Siriraj Hospital, Mahidol University, Bangkok 10700, ailand., ***Cle and Craniofacial South Australia, Women’s and Children’s Hospital, North

Adelaide, South Australia, Australia.

Speech Outcome Analysis after Primary Cleft

Palate Repair: Interim Siriraj Hospital Audit

ABSTRACT

Objective: To evaluate the speech outcomes aer primary cle palate repair in a single tertiary medical institution

of ailand.

Materials and Methods: A prospective cohort study was performed. Patients who had cle palate with/without cle

lip and underwent primary cle palate repair were included. Speech assessment was performed using the Pittsburgh

weighted speech score (PWSS) by a speech-language pathologist.

Results: Forty patients (21 males and 19 females) who underwent primary cle palate repair at Siriraj Hospital

were included. e median age at the time of speech evaluation was 7 years. e median age at primary cle palate

surgery was 12 months. e predominant cle palate type was Veau 3 (47.5%). Oronasal stula occurred 40%.

Two-ap palatoplasty and intravelar veloplasty were the most common procedures. Median PWSS was 7, in which

the competence velopharyngeal mechanism was found 5%, borderline competence 10%, borderline incompetence

32.5%, and incompetence velopharyngeal mechanism 52.5%. Among the velopharyngeal incompetence group,

articulation disorder was the most common disorder with median score of 3. Besides, the median scores for nasality,

nasal emission, phonation, and facial grimace disorder were 1, 2, 0 and 0, respectively. ere was no statistically

signicant association between velopharyngeal incompetence and cle types, age at primary surgery, type of operation,

the width of cle palate and prevalence of postoperative oronasal stula or otitis media eusion.

Conclusion: Velopharyngeal incompetence has been commonly identied aer cle palate repair in our institute.

e articulation disorder is the most common characteristic.

Keywords: Cle palate; speech outcome; velopharyngeal insuciency; craniofacial abnormalities (Siriraj Med J

2021; 73: 744-751)

Corresponding author: Sarut Chaisrisawadisuk

E-mail: sarut.cha@mahidol.ac.th; drsarut@gmail.com

Received 28 May 2021 Revised 3 May 2021 Accepted 12 September 2021

ORCID ID: https://orcid.org/0000-0001-6040-0784

http://dx.doi.org/10.33192/Smj.2021.96

INTRODUCTION

Cle lip and/or cle palate (CLP) are common

craniofacial anomalies in ailand. Chuangsuwanich

et al., in 1998, reported that the incidence of patients

with CLP was around 1 in 600 per live births at Siriraj

Hospital.

Recently, Chowchuen et al. also reported a

prevalence of CLP of 1.93 per 1000 live births in the

northeast region of ailand.

Patients with CLP have

cosmetic and functional concerns, which typically require

comprehensive multidisciplinary team (MDT) care

and long-term follow-up, starting with cle lip repair

at around 3-6 months and cle palate repair between

6-18 months of age.

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Cle palate (CP) repair aims to create an anatomically

intact and functional palate to improve feeding, achieve

normal speech, and minimize maxillary growth restriction

and middle ear infection.

In order to produce normal

speech, a child must have velopharyngeal competence,

dened as the ability to completely close the velopharyngeal

sphincter, which separates the oro- and nasopharynx.

e absence of this ability is termed velopharyngeal

insuciency.

e primary eects of velopharyngeal

insuciency are nasal air escape and hypernasality. A

wide range of postoperative velopharyngeal insuciency

cases requiring secondary operation have been reported

(15%–50%).

4-5

e phonemic system in the ai language is dierent

from English. A ai syllable consists of an initial, a

vocalic nucleus, a nal, and a tone.

e ai language

is a tonal language with sentences typically comprising a

subject, verb, and object in order. e subject is usually not

obviously stated but contextually assumed, similar to the

case with the object. e verb has no declensions, tense,

or conjugations.

According to this, if cle palate patients

have a decreased intelligibility of speech expression or

are especially prone to articulation errors, it may disturb

their communication skills, resulting in dicult social

circumstances and communications.

Perceptual evaluation of speech by an experienced

speech-language pathologist remains a widely accepted

standard tool.

8-9

e Pittsburgh weighted speech score

(PWSS), originally described by McWilliams and

Phillips

, is one of the key standardized methods used

for a perceptual speech assessment. is tool rates the

severity of velopharyngeal incompetency (VPI) by

evaluating ve speech components: nasality/resonance,

nasal air emission, facial grimace, phonation/voice, and

articulation.

Due to the lack of postoperative speech outcomes

aer CP repair in our centre, we conducted this study

using PWSS to evaluate the postoperative speech outcomes

aer primary palatal repair.

MATERIALS AND METHODS

Patient enrollment

is research involved a prospective cohort study.

Ethical approval was granted by the Institutional Review

Board committee, Faculty of Medicine Siriraj Hospital,

Mahidol University (Si 382/2018(EC2)). Informed consent

was obtained. Patients who were diagnosed with CP

with/without CL and underwent primary CP repair at

Siriraj Hospital were enrolled. Exclusion criteria were

syndromic patients with associated anomalies and patients

who had follow-up time less than 3 years (co-operable

assessment issue). Aer reviewing medical records, the

eligible patients were contacted via telephone and invited

for study participation.

Speech outcome assessment

The speech evaluation was conducted between

October 2019 and 2020. Perceptual speech outcome

assessments using PWSS were conducted face-to-face

by a qualied speech-language pathologist (K.L.) (Fig 1).

Five components were investigated: nasal air emission,

facial grimace, nasality/resonance, phonation/voice,

and articulation. e sum of scores equal to 0 indicated

velopharyngeal competency, 1-2 indicated borderline

velopharyngeal competency, 3-6 indicated borderline

VPI, and ≥7 indicated VPI.

Data collection

e patients’ medical records were reviewed to

collect the following data: age and weight at primary

palatoplasty, gender, cle palate type based on Veau

classication

, cle gap, techniques used in hard/so

palate procedures, the use of Vomerine ap, operation

time, estimated blood loss, hospital length of stay, and

the incidence of postoperative oronasal stula (ONF) and

otitis media eusion (OME). e Veau classication

categorizes cle palate into four groups: Veau 1 (defects

involving the so palate only), Veau 2 (defects involving

the hard and so palate), Veau 3 (defects involving the

so palate to the alveolus, usually with lip involvement),

and Veau 4 (complete bilateral cle palate). Intraoral

examination and photography were performed to identify

postoperative ONF, dened as an abnormal connection or

hole between the oral and nasal cavities, while intentionally

unrepaired anterior hard palate and lingual–alveolar or

labial–alveolar stulas were not dened as this particular

condition.

Statistical analysis

As appropriate, continuous variables were summarized

using Mean ± standard deviation (SD) or Median (range).

Categorical variables were summarized using counts

with the percentage. e clinical and peri-operative

characteristics between patients with and without VPI

were compared using the Student’s t-test or Mann-

Whitney U test for continuous variables, while Pearson

chi-square, Yates’ continuity correction or Fisher’s exact

test was used for categorical variables, as appropriate.

P-value of ≤0.05 was considered statistically signicant.

Statistical analyses were performed using PASW Statistics

for Windows, Version 18.0. Chicago: SPSS Inc.

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Fig 1. Perceptual speech evaluation form adapted from the Weighted Values for Speech Symptoms Associated with Velopharyngeal

Incompetence of the Cle Palate Center of the University of Pittsburgh

Nasal Emission: Facial Grimace: ____2

Not present _____0

_____1

Nasality:

Inconsistent, Visible Normal ____0

Consistent, Visible _____2 Mild Hypernasality ____1

Nasal escape on nasals appropriate _____0

_____0

Moderate Hypernasality ____2-3

Reduced Severe Hypernasality ____4

Absent Hypo-Hypernasality ____ 2

Audible _____3 Cul de sac resonance ____2

Nasal Turbulence _____3 Hyponasality ____ 0

******Summary: Nasal emission scores: _____* ******Summary: Facial grimace

and nasality scores: ____*

Phonation: Articulation:

Normal ____0 Normal ____0

Hoareseness or Breathiness Development errors ____0

Mild ____1 Errors from other causes not related to VPI ____0

Moderate ____2 Errors related to anterior dentition ____0

Severe ____3 Reduced intraoral pressure for sibila nts ____1

Reduced Loudness ____2 Reduced intraoral pressure for other fricatives ____2

Tension in system ____3 Reduced intraoral pressure for plosives ____3

Other__________________ Omission of fricatives or plosives ____2

******Summary: Phonation scores: ____* Omission of fricatives or plosives plus

hard glottal attacks for vowels ____3

Lingual-palatal sibilants ____2

Pharyngeal fricatives, snorts,inhalation or

exhalation substitutions ____3

Glottal stops ____3

Nasal substitutions for pressure sounds ____4

******Summary: Articulation scores: ____*

******TOTAL SCORE (from all sections above): ____

Speech Indicates:

____0 Competent Velopharyngeal Mechanism

____1-2 Competent to Borderline Competent

____3-6 Borderline to Boderline Incompetent

____7 Incompetent Velopharyngeal Mechanism

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RESULTS

Forty patients (21 males and 19 females) with CP

between 3-15 years of age who underwent primary cle

palate repair in Siriraj Hospital were included in the study.

e median age at primary palatoplasty was 12 months

old (range 8-40). Veau type 3 was found in 47.5% of

patients, while Veau type 4, type 2, and type 1 were found

in 30%, 15%, and 7.5%, respectively. e mean cle gap

width was 12.3 mm. e Bardach two-ap palatoplasty

technique was performed in 94.6% of patients, while 5.4%

underwent Veau-Wardill-Kilner palatoplasty for hard

palate surgery. Intravelar veloplasty was performed in

82.5% of patients, while 2.5% underwent radical intravelar

veloplasty, and 12.5% underwent Furlow z-plasty for so

palate surgery. One patient (2.5%) has unknown detail

of the so palate procedure. e vomerine ap was used

in 42.5% of patients. e mean operation time was 127

min. Table 1 summarizes the patients’ demographic

data.

At the time of speech evaluation, the median age

was 7 years (range 3-15 years). Among 40 patients, 21

(52.5%) had VPI, while 13 (32.5%) had borderline VPI,

and 4 (10%) had borderline velopharyngeal competency,

and 2 (5%) had velopharyngeal competency. e median

total PWSS score was 7.0 (0-18). Median score for nasal

emission was 2 (0-3), phonation was 0 (0-5), facial grimace

was 0 (0-2), nasality was 1 (0-4), and articulation was

3 (0-10) (Table 2). ere was no signicant dierence

in age at primary palatoplasty, or for the type and width

of cle palate, type of surgery for hard and so palate,

or incidence of postoperative ONF and OME between

patients with or without VPI (data shown in Table 3).

Overall, 16 patients (40%) had postoperative ONF. All

of those underwent stula closure operations. However,

8 patients had recurrence stula at the time of speech

evaluation. e median interval between primary CP

surgery and ONF occurrence was 22 months (range

3-40 months). OME was found in 30 patients (75%).

DISCUSSION

We present interim data on the perceptual speech

outcomes aer primary cle palate repair from a tertiary

referral centre in ailand. We found over half of our

patients with CP had postoperative VPI aer primary

CP repair at around 7 years of age. Moreover, making

articulation errors was the most common characteristic

aecting achieving a higher PWSS.

Normal speech achievement is one of the most

important goals of CP surgery. Perceptual evaluation

(i.e., listening) is the “gold standard” clinical assessment

method for speech and voice disorders in the cle palate

population, and has been used in several previous studies.

8,12-16

In this study, VPI was identied by perceptual speech

evaluation using PWSS in 53% of patients. is rate is

higher than those reported in prior studies, ranging

from 15% to 45%.

4-5

Articulation errors were found to

be the most common speech distortions in our series.

Pratanee et al., in 2016, found that articulation errors

were the most common speech and language defects in

ai cle palate patients.

Oopanasak et al. organized

a case-control study of ai children aged 6-13 years

old and found that patients with CLP had signicantly

higher articulation defects than normal children, with

velar and trill errors the most common articulation

patterns.

Another study in Saudi Arabic-speaking

children aged between 6-15 years old by Albustanji et

al. found speech abnormalities, including articulation,

hypernasality, and resonance, in 74% of patients aer

CP repair.

A study from Korea reported that 20% of

patients had postoperative VPI and 50% demonstrated

articulation decits.

Recently, a study of Arabic-speaking

Egyptian children between 3-9 years old demonstrated

that articulation disorders, especially substitution, were

the most common errors in CP patients with VPI.

ere are many factors involved in articulation.

Every element of the speech apparatus, including the lips,

teeth, palate, tongue, velum, and larynx, are engaged in

producing intelligible sounds.

Patients in our study were

evaluated at 7 years old, which is in the mixed dentition

phase. Abnormal dental alignment (e.g., severe crowding),

including transverse maxillary collapse during this time,

maybe a causative factor in articulatory disorders in cle

palate patients. Another factor, including the prevalence

of remaining alveolar cle during this particular phase,

may interfere with the incidence of articulation errors.

Signicantly, most children with CP in our study did

not receive any regular long-term speech therapy aer

surgery. Although speech therapy in ailand is oered

to cle palate patients free of charge due to our universal

health care program, regular long-term speech therapy

can be burdensome. Ideally, patients are required to

attend 30-minute speech therapy sessions at least every

2-3 months for several years. Further, the speech therapy

service is only available in a restricted number of tertiary

referral hospitals. In addition, as the patients are children,

their parents need to accompany them to the hospital

for the service. is would cost them transportation

expenses and a need to miss work, resulting in reduced

income. erefore, access to and take-up speech therapy

in our patients is limited, especially when considering the

long distance to the service and socioeconomic status of

many of our patients’ families.

23-24

Unsurprisingly, many

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TABLE 1. Demographic data of 40 patients with cle palate who underwent primary cle palate repair.

Characteristics (Total=40)

Genders, number (%)

Male 21 (52.5%)

Female 19(47.5%)

Surgeons

Attendingstaff 33(82.5%)

Trainees 7 (17.5%)

Age at primary palatoplasty (months), Median (range) 12 (8-40)

Age at speech assessment (years), Median (range) 7 (3-15)

Cleft types, number (%)

VeautypeI 3(7.5%)

VeautypeII 6(15%)

VeautypeIII 19(47.5%)

VeautypeIV 12(30%)

Cleft gap width (mm.), Mean ± SD 12.3 ± 4.1

Type of hard palate procedure, number (%) Total37

Two-appalatoplasty 35(94.6%)

Veau–Wardill–Kilnerpalatoplasty 2(5.4%)

Type of soft palate procedure, number (%) Total40

Intravelarveloplasty 33(82.5%)

Radicalintravelarveloplasty 1(2.5%)

FurlowZ-plasty 5(12.5%)

Unknowndetailoftheprocedure 1(2.5%)

Vomerine ap use, number (%) 17 (42.5%)

Blood loss (ml.), Median (range) 20 (1-150)

Surgery duration (minute), Mean ± SD 127 ± 49

Hospital stay (days), Mean ± SD 4 ± 1

Presence of oronasal stula, number (%) 16 (40%)

Presence of otitis media effusion, number (%) 30 (75%)

Speech indicates, number (%)

 Velopharyngealcompetency 2(5%)

 Borderlinevelopharyngealcompetency 4(10%)

Borderline VPI 13 (32.5%)

VPI 21 (52.5%)

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TABLE 2. Modied weighted values for speech symptoms associated with velopharyngeal incompetence of the Cle

Palate Center of the University of Pittsburgh by perceptual evaluation.

TABLE 3. Various parameters and the association with VPI.

Modality Score

Total:Median(range) 7(0-18)

Articulation:Median(range) 3(0-10)

Nasality:Median(range) 1(0-4)

Nasalemission:Median(range) 2(0-3)

Phonation:Median(range) 0(0-5)

Facialgrimace:Median(range) 0(0-2)

Parameter

PWSS < 7 PWSS ≥ 7

(n= 19) (n= 21)

P-value

Age at primary palatoplasty, Median (range) (months) 12 (8-40) 12 (9-39) 0.539

Cleft types, number (%)

VeautypeI 3(15.8) 0(0) 0.238

VeautypeII 3(15.8) 3(14.3)

VeautypeIII 7(36.8) 12(57.1)

VeautypeIV 6(31.6) 6(28.6)

Cleft gap width, Mean ± SD (mm.) 12.2 ± 3.4 12.3 ± 4.7 0.909

Type of hard palate procedure, number (%)

Two-appalatoplasty 16(84.2) 19(90.5) 0.495

Veau–Wardill–Kilnerpalatoplasty 0(0) 2(9.5)

Type of soft palate procedure, number (%)

Intravelarveloplasty 13(68.4) 20(95.2) 0.130

Radicalintravelarveloplasty 1(5.3) 0(0)

FurlowZ-plasty 4(21.1) 1(4.8)

Vomerine ap use, number (%) 7 (36.8) 10 (47.6) 0.713

Presence of oronasal stula, number (%) 6 (31.6) 10 (47.6) 0.477

Presence of otitis media effusion, number (%) 15 (78.9) 15 (71.4) 1.000

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factors, not only velopharyngeal anatomical deciencies,

are associated with VPI in our patients in this centre.

Our study revealed no signicant association between

age at primary surgery, types and width of cle palate,

type of CP surgery, or incidence of postoperative ONF,

OME, and severity of VPI. ese data are consistent with

a previous study from a tertiary university hospital in

Northeast ailand.

Postoperative ONFs in cle palate have been reported

in 9%-50% of cases.

26-27

e ONF rate in the present study

was 40%, which is consistent with previous literature.

28-31

A large case series from Khon Kaen University, ailand,

revealed that ONF formation was signicantly associated

with higher types of Veau classication, syndromic cle

patients, and a cle width more than 11.5 mm.

In our

series, we found that the majority of patients had Veau type

3 or 4 (77%), and the mean cle gap was 12.3 mm. From

our study, 48% of patients with VPI had postoperative

ONF. Although an ONF closure procedure was performed

in all these patients, 50% still had residual stula at the

time of the study. In the borderline VPI group, 38% of

patients had ONF. Also, 60% of those still had residual

ONF at the time of the study despite a stula closure

procedure having been performed. ere were no ONF

cases in the velopharyngeal competency and borderline

velopharyngeal competency group. ONF might be the

cause for this, producing a higher hypernasality score

in the PWSS.

OME is common in CLP, oen resulting in hearing

loss, speech delay, and learning disabilities. If untreated,

chronic otitis media or cholesteatoma may occur, leading

to permanent middle ear damage. In our hospital, the

prevalence of OME was reported by Ungkanont et al.

to be around 50%–80%.

ey also found a signicant

improvement in the audiograms aer palatoplasty. In

this series, we found 75% of patients had OME. is

condition might be another confounding factor that

aected the poor speech outcomes in this study, despite

the statistical analysis suggesting no signicant association

between OME and speech outcomes in this study. Further

subgroup analysis should be performed to conrm this

outcome.

We realize that one of the signicant limitations

of our study was the small population sample. We had

previously planned to enrol a study population of 200

by calculating the predicted sample size using nQuery

Advisor (San Diego, CA) and by assuming the rate of

velopharyngeal incompetency as 37.5% with condence

interval of 95%. However, due to the COVID-19 pandemic

in ailand during 2020, we, unfortunately, could only

enrol 40 patients to take part in face-to-face speech

evaluation. Ongoing speech evaluations are continuing

for a complete long-term speech outcome assessment.

is interim study should, however, be of benet

for our hospital and can reinforce the need for MDT

care, including cle surgeon, speech pathologist, ear nose

throat surgeon, and dental team, which is mandatory for

all patients with CLP. Objective investigations, such as

nasendoscopy and/or video-uoroscopy, should be further

used in patients who have VPI from initial perceptual

speech evaluation as the diagnostic tools and preoperative

planning before any subsequent correction procedure.

CONCLUSION

Postoperative VPI is common aer cle palate

repair in our hospital. e articulation disorder is the

most common characteristic aecting speech outcomes.

We encourage establishing a cle and craniofacial centre

to deliver MDT care in our hospital to achieve the best

benets in CLP care.

ACKNOWLEDGEMENTS

The authors gratefully thank all the attending

sta in the Division of Plastic Surgery, Department of

Surgery, Faculty of Medicine Siriraj Hospital for their

great contribution to this study and patient management.

Funding: e authors received no nancial support for

this article’s research, authorship, and/or publication.

Conicts of interest: e authors declare no conicts

of interest concerning this article’s research, authorship,

and/or publication.

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12. Persson C, Elander A, Lohmander-Agerskov A, Söderpalm E.

Speech outcomes in isolated cle palate: impact of cle extent

and additional malformations. Cle Palate Craniofac J 2002;39:

397-408.

13. Nyberg J, Westberg LR, Neovius E, Larson O, Henningsson G.

Speech results aer one-stage palatoplasty with or without muscle

reconstruction for isolated cle palate. Cle Palate Craniofac

J 2010;47:92-103.

14. Klintö K, Salameh EK, Svensson H, Lohmander A. e impact

of speech material on speech judgement in children with and

without cle palate. Int J Lang Commun Disord 2011;46(3):348-

60.

15. Britton L, Albery L, Bowden M, Harding-Bell A, Phippen G,

Sell D. A cross-sectional cohort study of speech in ve-year-

olds with cle palate ± lip to support development of national

audit standards: benchmarking speech standards in the United

Kingdom. Cle Palate Craniofac J. 2014;51(4):431-51.

16. Dissaux C, Grollemund B, Bodin F, Picard A, Vazquez MP,

Morand B, et al. Evaluation of 5-year-old children with complete

cle lip and palate: Multicenter study. Part 2: Functional results.

J Craniomaxillofac Surg 2016;44(2):94-103.

17. Prathanee B, Pumnum T, Seepuaham C, Jaiyong P. Five-year

speech and language outcomes in children with cle lip-palate.

J Craniomaxillofac Surg 2016;44(10):1553-60.

18. Ooppanasak N, Makarabhirom K, Chowchuen B, Prathanee

B. Speech Outcomes in Children with Cle and Palate: Srinagarind

Hospital, Khon Kaen University, ailand. J Med Assoc ai

2019;102:10.

19. Albustanji YM, Albustanji MM, Hegazi MM, Amayreh MM.

Prevalence and types of articulation errors in Saudi Arabic-

speaking children with repaired cle lip and palate. Int J Pediatr

Otorhinolaryngol 2014;78(10):1707-15.

20. Ha S, Koh KS, Moon H, Jung S, Oh TS. Clinical Outcomes

of Primary Palatal Surgery in Children with Nonsyndromic

Cle Palate with and without Lip. Biomed Res Int 2015;2015:185459.

21. Abou-Elsaad T, Baz H, Afsah O, Mansy A. e nature of articulation

errors in Egyptian Arabic-speaking children with velopharyngeal

insuciency due to cle palate. Int J Pediatr Otorhinolaryngol

2015;79(9):1527-32.

22. Dorf DS, Curtin JW. Early cleft palate repair and speech

outcome. Plast Reconstr Surg 1982;70(1):74-81.

23. Prathanee B, Dechongkit S, Manochiopinig S. Development

of community-based speech therapy model: for children with

cle lip/palate in northeast ailand. J Med Assoc ai 2006;

89(4):500-8.

24. Setabutr D, Sathavornmanee T, Jitpakdee P, Nudchawong S,

Krergmatukorn P. e Trend of Cle Care at a Children’s

Referral Center in ailand. Cle Palate Craniofac J 2020;57(9):

1100-4.

25. Kaewkumsan N, Chowchuen B, Prathanee B. Clinical outcomes

of primary palatoplasty in preschool-aged cle palate children

in Srinagarind Hospital and comparison with other standard

cle centers. J Med Assoc ai 2014;97(Suppl 10):S37-48.

26. Jackson MS, Jackson IT, Christie FB. Improvement in speech

following closure of anterior palatal stulas with bone gras.Br

J Plast Surg 1976;29(4):295-96.

27. Abyholm FE, Borchgrevink HH, Eskeland G. Palatal stulae

following cle palate surgery.Scand J Plast Reconstr Surg 1979;

13(2):295-300.

28. Murthy AS, Parikh PM, Cristion C, omassen M, Venturi M,

Boyajian MJ. Fistula aer 2-ap palatoplasty: a 20-year review.

Ann Plast Surg 2009;63(6):632-5.

29. Stewart TL, Fisher DM, Olson JL. Modied Von Langenbeck

cle palate repair using an anterior triangular ap: decreased

incidence of anterior oronasal stulas. Cle Palate Craniofac

J 2009;46(3):299-304.

30. Eberlinc A, Koželj V. Incidence of residual oronasal stulas:

a 20-year experience. Cle Palate Craniofac J 2012;49(6):643-8.

31. Hortis-Dzierzbicka M, Radkowska E, Fudalej PS. Speech

outcomes in 10-year-old children with complete unilateral cle

lip and palate aer one-stage lip and palate repair in the rst

year of life. J Plast Reconstr Aesthet Surg 2012;65(2):175-81.

32. Saothonglang K, Punyavong P, Winaikosol K, Jenwitheesuk K,

Surakunprapha P. Risk Factors of Fistula Following Primary

Palatoplasty. J Craniofac Surg 2021 ;32(2):587-90.

33. Ungkanont K, Boonyabut P, Komoltri C, Tanphaichitr A,

Vathanophas V. Surveillance of Otitis Media with Eusion in

ai Children With Cle Palate: Cumulative Incidence and

Outcome of the Management. Cle Palate Craniofac J 2018;

55(4):590-5.

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Suttipong Tianwattanatada, M.D.*, Nantaporn Namviriyachote, Ph.D. *, Kusuma Chinaroonchai, M.D. *,

Natthida Owattanapanich, M.D. *, Harikrishna K.R. Nair, M.D. **, Pornprom Muangman, M.D.*

*Division of Trauma, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

**Wound Care Unit, Dept of Internal Medicine, Kuala Lumpur Hospital, Malaysia.

Clinical Efcacy Test of Polyester Dressing

Containing Herbal Extracts and Silver Sulfadiazine

Cream Compared with Silver Sulfadiazine Cream in

Healing Burn Wounds: A Prospective Randomized

Controlled Trial

ABSTRACT

Objective: e most common method of burn wound care is the application of silver sulfadiazine cream with

sterilized gauze covering. However, conventional gauze fabric with a large pore size may stick to the wound bed

and cause wound trauma, leading to the delay of healing and pain. e non-adherent property of a hydrocolloid

dressing coated with herbal extract (SI-HERB) can promote wound healing as well as reduce pain. us, this study

aims to compare clinical ecacy between a “polyester dressing containing herbal extracts and silver sulfadiazine

cream” and “silver sulfadiazine cream” alone in second degree burn wound healing.

Materials and Methods: is study compared the two methods of burn wound treatment in the same patients, who

were randomly split into a “treatment group”, which were applied both silver sulfadiazine cream and hydrocolloid

dressing, and “control group”, which were applied only silver sulfadiazine cream. e studied outcomes were the

number of days for wound closure, the percentage epithelialization, and the pain score. In total, 24 patients at the

Burn Unit, Siriraj Hospital were enrolled in this study.

Results: e wound areas were initially ranged from 210–220 cm

. e treatment group exhibited signicant results

regarding faster wound healing, referring to the number of days of wound closure (18 days in the control group

vs. 15 days in the experimental group) and the percentage epithelialization compared to the control group. e

average pain score in the experimental group was also lower on days 9, 12, and 15 aer treatment (p < 0.05). No

adverse eects were observed during the study.

Conclusion: e combination of hydrocolloid dressing and silver sulfadiazine cream could reduce the wound shearing

force and wound bed injury, accelerating the rate of wound closure and decreasing the pain during changing the

dressing. is technique could improve upon the standard burn wound treatment.

Keywords: Burn; wound; silver sulfadiazine cream; hydrocolloids dressing (Siriraj Med J 2021; 73: 752-757)

Corresponding author: Pornprom Muangman

E-mail: pornprom.mua@mahidol.ac.th

Received 9 September 2020 Revised 22 September 2021 Accepted 25 September 2021

ORCID ID: https://orcid.org/0000-0001-9828-0060

http://dx.doi.org/10.33192/Smj.2021.97

INTRODUCTION

Wounds involve a breakdown of the protective

function of the skin and the loss of continuity of the

epithelium, with or without the loss of underlying connective

tissue (i.e., muscle, bone, nerves). Although the body

system itself has the ability to heal, there are many factors

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that can aect wound healing, such as age, nutritional

status, immunization status, co-morbidity, and the types

of wound. Wound care aims to accelerate the healing

process and prevent complications that could prolong

the wound healing process and length of hospital stay.

Wide, open wounds, especially burn wounds, can easily

become infected and require a prolonged hospital stay.

is can cause an increase in the cost of burn wound care

by up to 15,000 USD on average per person.

studies have reported a correlation between the area and

depth of the burn wound and the cost of treatment.

2,3

erefore, shortening the healing process may lead to

less complications, a decrease length of hospital stay

and hospital costs, and also better quality of life of the

patients.

Burn wounds are categorized into 3 degrees of burn

according to the depth. A rst degree burn can heal itself

without intervention in a week. A second degree burn

can heal with an epithelialization process; however, it

can turn to a third degree burn if not properly managed.

A third degree burn needs surgical intervention for

promoting the healing process. is study focuses on

second degree burn wounds.

e most common method of burn wound care

in Asia is the application of silver sulfadiazine cream

(SSD) with sterilized gauze covering. SSD is composed

of silver nitrate, which provides a bactericidal eect,

and sodium sulfadiazine for its bacteriostatic property.

SSD has a broad spectrum antimicrobial action with

wound healing nurture.

However in clinical application,

there are various factors that are hard to control, such

as the thickness of the cream and the amount of cream

per area, which are varying in practitioner. Also, the

gauze absorbs the SSD, it can dry up and adhere to the

wound bed. While peeling the gauze out to change the

dressing, this can create a shearing force on the wound

bed, causing wound bed trauma and thus slowing the

wound healing process.

Lipido-colloid dressing was developed to increase the

interval of wound dressing, reduce pain during dressing,

due to the decrease adherence between the wound and

the gauze dressing.

However, the major problem for

this treatment is the cost since these products have to

be imported.

Our previous study investigated a product comprising

a hydrocolloid dressing coated with herbal extract, called

SI-HERB.

is product has absorption capacities, drainage

abilities, and it does not stick to the wound. Furthermore,

it is locally made in ailand and only costs one dollar

per piece. It has no clinical side eects and it has already

been approved by the ai FDA. e herbal extracts in

this material comprise Centella asiatica and Aloe Vera,

which show anti-microbial eects, accelerate wound

healing, moisten the wound, and show anti-inammatory

eects.

8,9

Some studies have indicated that these two

substances can heal a wound faster than SSD.

10,11

Research

from Muangman et al. in 2016 compared SI-HERB with

old fashioned polyester (Bactigras), and showed that

SI-HERB was superior in wound healing and improving

tissue regeneration, with a lower cost of treatment and

less pain during wound care.

Consequently, this study used a hydrocolloid dressing

coated with herbal extract (SI-HERB) combined with

SSD on a dermal burn wound, which had some part of

the eschar remaining on the wound surface, compared

with using SSD alone. We hypothesized that the results

would show better wound healing than using SSD alone.

Objective

e objective of this study was to compare the

clinical ecacy between a “polyester dressing containing

herbal extracts and silver sulfadiazine cream” and “silver

sulfadiazine cream” alone in second degree burn wound

healing regarding the number of days for wound closure,

the percentage epithelialization, and the pain score of

patients.

MATERIALS AND METHODS

Population

In total, 24 patients were included in this study. e

patients, aged between 18 to 60 years old, had at least

two second degree burn wounds. Each patient’s burn

wound was at least 150 cm

in area (approximating to

10% of body surface area by Wallace’s rule of nine). e

patients were ASA class I or II and ECOG 0 before getting

burn wounds. Patients with history of allergy to silver,

sulfadiazine or herbal products were excluded. Pregnant,

breastfeeding, diabetes, or immunocompromised patients

were also excluded from the study.

Study design

is was a single-center, prospective, randomized

controlled study comparing wound dressing with a

polyester dressing containing herbal extracts and silver

sulfadiazine cream with silver sulfadiazine cream alone

in second degree burn wound healing. is study was

conducted at the Burns Unit, Division of Trauma Surgery

Department of Surgery, Faculty of Medicine Siriraj

Hospital, Mahidol University, Bangkok. e data were

obtained between January 2019 and June 2020.

e second degree burn wounds of at least 150 cm

with some areas of eschar in the recruited patients were

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754

randomly allocated to one of two treatment groups. In

each patient, aer an accurate debridement and cleaning

of the burn wound with appropriate steriled normal

saline solution, each burn wound size was evaluated by

a registered nurse uninvolved with the dressing wound

team. Photos of the burn wound were taken and evaluated

in terms of size using the Image J program. Burn wound

dressing was performed according to the treatment

group. In the experimental group, patients were covered

with SSD and a polyester dressing containing the herbal

extracts. In the control group, they were covered with

SSD. All the burn wounds were covered with steriled

gauze, gamgee, and tape.

Evaluation was done every 3 days. Photos of each

burn wound were taken and the size evaluated using

the Image J program. Pain was evaluated by using the

visual analog scale (VAS) range 0-10. Complications

and other intervention needs were assessed by medical

doctors. e evaluation and assessment team were not

involved in the dressing procedure.

Wound healing was measured as the %epithelialization

calculated by the formula below.

e dierences between the treatment groups were

evaluated using the paired t-test or Wilcoxon signed ranks

test. e dierence at each point in time was analyzed by

repeated-measure ANOVA. For the qualitative variables,

we used Pearson’s Chi-square test or Fisher’s exact test.

All the statistical tests for ecacy were two-sided, with

an alpha level = 0.05.

RESULTS

ere were 24 second degree burn wound patients

eligible for this study. Most were male patients (62.5%).

e average age of the patients was 40.13 ± 14.20 years

old. e total burn surface area was 35.35% in average.

e average hospital stay was 41.96 ± 22.39 days. e

most common cause of the burn wounds was scald burns

in 35.35 ± 17.49% of cases, as shown in Table 1.

(Area of initial wound

Area of wound at exam

date)

___________________

Area of initial wound

%Epithelialization =

x 100

Ethics and material safety

Written informed consent was obtained from each

patient or relatives prior to their participation in this

study. e study was conducted in accordance with

the international code of medical ethics. Patients could

withdraw their consent whenever they felt uncomfortable

and wished to nish the trial. e trial protocol and

subsequent amendments including ethical approval

were reviewed and approved by the Human Research

Protection Unit, Siriraj Institutional Review Board (SIRB),

ailand.

is product, the polyester dressing containing

herbal extracts, is already approved by the ai FDA.

ere was no clinical side eects in the previous study

utilizing this product.

Statistical analysis

Demographic data are described with descriptive

statistics. Quantitative data are described in terms of

the mean ± standard deviation, or median (P25, P75).

Quantitative data are described in frequency (percentage)

TABLE 1. Demographic data of the burn wound patients

included in the study.

Demographic data

Malepatients 15(62.50%)

Age(year) 40.13±14.20

Burnpercentage(%) 35.35±17.49

Hospitalstay(day) 41.96±22.39

Causes

 Flameburn 9(37.50%)

Scald burn 14 (58.33%)

 Electricalburn 1(4.17%)

Underlyingdiseases

 Hypertension 4(16.67)

 Hypercholesterolemia 1(4.17)

e burn wounds of each patient were randomly

assigned in both treatment groups. e experimental

group was applied polyester dressing containing the

herbal extracts and silver sulfadiazine cream. e control

group was applied silver sulfadiazine cream alone. e

initial burn wound area was not statistically signicantly

dierent between the two treatment groups: 219.15 ±

52.09 and 211.04 ± 46.18 cm

in the experimental and

control group, respectively.

e percentage epithelialization calculated using

the formula above is shown in Graph 1. e percentage

epithelialization was similar in both groups at day 3 aer

treatment, at 10%. Aer that, the percentage epithelialization

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rose, especially in the experimental group, as shown in

Graph 1. e dierences in the percentage epithelialization

were statistically dierent at days 12, 15, and 18 (p<0.05).

e wounds were more than 90% healed aer 12 days

and 15 days in the experimental group and control group,

respectively. e wounds in the experimental group were

completely healed in 15.04 ± 3.76 days on average. is

was signicantly faster than in the control group, which

took 18.04 ± 3.74 days to heal on average (p < 0.05).

Graph 1. Percentage epithelialization and days for treatment comparing

the experimental group and the control group.

e pain scores were rated by each patient every

three days of the experiment and the scores are shown

Graph 2. Pain scores every three days of treatment comparing the

experimental group and the control group.

Some examples of burn wound patients and the

wound healing progression are shown in Figs 1-6. ese

pictures show the progression of the burn wound from

initial of treatment until completely heal.

in Graph 2. e initial pain scores were not dierent in

the experimental group and the control group (6.0 ± 1.0

and 6.1 ± 1.0, sequentially). e pain score decreased as

time goes on. e experimental group had signicantly

lower pain scores on days 9, 12, and 15 (p<0.05).

Fig 1. Example photos of the

rst patient in the control group

Fig 2. Example photos of the

rst patient in the experimental

group

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Fig 3. Example photos of the second patient

in the control group

Fig 4. Example photos of the second patient

in the experimental group

Fig 6. Example photos of the third patient

in the experimental group

Fig 5. Example photos of the third patient

in the control group

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DISCUSSION

is study showed that wound dressing with polyester

dressing containing herbal extracts and SSD had a better

outcome compared to SSD alone in terms of the days

taken for wound closure, the percentage epithelialization,

and the pain scores of the patients. is was due to the

non-adhesive properties of the dressing to the wound,

causing less trauma to the newly generated epithelium.

is study showed similar results for the days taken

for wound closure as our previous study in 2016, which

reported an average of 15 days for wound closure, which

was 2 days faster than the group with the wound not

covered with the polyester dressing containing herbal

extracts.

e herbal extracts in this product, namely Centella

asiatica and Aloe vera, had antimicrobial properties. Such

an antimicrobial property has previously been reported in

an Aloe vera-containing dressing (Barkat et al., 2017 and

Khorasani et al., 2009) and Centella asiatica-containing

dressing, with both showing signicant ecacy.

e limitation of this study to note is that the study

was not double-blinded. Patients inevitably knew the

treatment of each burn wound. Another limitation is the

pain scores that were rated by the patients. Sometimes

it can be dicult to distinguish pain from each burn

wound part in the body.

CONCLUSION

is study can conclude that for second degree

burn wounds with some degree of eschar on top of

the wounds, the use of a polyester dressing containing

herbal extracts combined with silver sulfadiazine cream

can promote better wound healing and cause less pain

without any clinical side eects.

is treatment strategy might be included in the

standard burn wound care protocol in the future to improve

burn wound care. Further cost-analysis research might

be helpful in future implementation of this treatment

in the protocol.

REFERENCES

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acute burn patients treated in a burn centre: the Gulhane

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2. Sanchez JL, Pereperez SB, Bastida JL, Martinez MM. Cost-utility

analysis applied to the treatment of burn patients in a specialized

center. Arch Surg 2007; 142(1): 50-7; discussion 7.

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dos Santos Barbeira CB. Analysis of cost of dressings in the

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5. Moncrief JA. Burns. N Engl J Med 1973; 288(9): 444-54.

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Reconstr Surg 1984; 18(1): 119-26.

7. Ma KK, Chan MF, Pang SM. e eectiveness of using a

lipido-colloid dressing for patients with traumatic digital

wounds. Clin Nurs Res 2006; 15(2): 119-34.

8. Khorasani G, Ahmadi A, Jalal Hosseinimehr S, Ahmadi A, Taheri

A, Fathi H. e Eects of Aloe Vera Cream on Split-thickness

Skin Gra Donor Site Management: A Randomized, Blinded,

Placebo-controlled Study. Wounds 2011; 23(2): 44-8.

9. Shetty BS, Udupa SL, Udupa AL, Somayaji SN. Eect of Centella

asiatica L (Umbelliferae) on normal and dexamethasone-

suppressed wound healing in Wistar Albino rats. Int J Low

Extrem Wounds 2006; 5(3): 137-43.

10. Shahzad MN, Ahmed N. Eectiveness of Aloe Vera gel compared

with 1% silver sulphadiazine cream as burn wound dressing

in second degree burns. J Pak Med Assoc 2013; 63(2): 225-30.

11. Saeidinia A, Keihanian F, Lashkari AP, et al. Partial-thickness

burn wounds healing by topical treatment: A randomized

controlled comparison between silver sulfadiazine and centiderm.

Medicine (Baltimore) 2017; 96(9): e6168.

12. Muangman P, Praditsuktavorn B, Chinaroonchai K, Chuntrasakul

C. Clinical Ecacy Test of Polyester Containing Herbal Extract

Dressings in Burn Wound Healing. Int J Low Extrem Wounds

2016; 15(3): 203-12.

13. Chuntrasakul C, Muangman, P., Benjathanung, R., Suvanchote, S.,

Boonpamee, S., Jantarapakdee, S., & Kittidacha, S. Clinical

Experience of ActicoatTM Treatment in Extensive Burn Wounds.

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14. Lohsiriwat V, Siripoon C, Kitmanee M, Vongviriyangkoon T.

Laser Doppler Analysis of Blood Perfusion in Burn Wounds.

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awatchai Mankongsrisuk, M.D.*, Jad A. Degheili, M.D.**, Bansithi Chaiyaprasithi, M.D.*

*Division of Urology, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand, **Division of Pediatric

Urology, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.

Intraoperative Problems and Solutions in

Pneumovesicum Laparoscopic Cross-trigonal

Ureteral Reimplantation in Children by a Beginner

Surgeon

ABSTRACT

Objective: Many beginner surgeons feel anxious when rst doing the procedure. Some may encounter many

intraoperative diculties or problems, resulting in abandoning the technique. We will demonstrate our methods

and the solutions to major intraoperative problems.

Materials and Methods: A beginner surgeon performed the operation on 13 children with VUR (20 ureters) who

met the indications for surgery between October 2016 and August 2017. Age ranged from 2 to 7 years. Each operation

comprised 2 main steps: anchoring the urinary bladder wall to the anterior abdominal wall under cystoscopic

vision, followed by a cross-trigonal ureteral reimplantation under pneumovesicum laparoscopy. e intraoperative

problems, postoperative care, and follow-up periods were recorded to identify surgical outcomes.

Results: Most signicant, intraoperative problems were air leakage, bleeding, tear of the bladder mucosa above the

tunnel, and inability to insert a tube into the ureter pre- and post-reimplantation. Most problems could be managed.

Only one case had to be converted to open reimplantation due to uncontrolled air leakage. Postoperatively, 2 patients

had hydroureteronephrosis at 4 weeks, but it eventually spontaneously regressed. One patient had cystitis, treated

with oral antibiotics. Between the 1-year and 4-year follow-up, no patients had hydroureteronephrosis or urinary

tract infections (UTI).

Conclusion: Pneumovesicum laparoscopic ureteral reimplantation is a feasible technique for beginner surgeons.

Although many intraoperative problems may be encountered, most can be managed, resulting in the completion

of the laparoscopic procedure.

Keywords: Vesicoureteral reux; pneumovesicum laparoscopic ureteral reimplantation; vesicoscopic ureteral

reimplantation; beginner surgeon (Siriraj Med J 2021; 73: 758-762)

Corresponding author: awatchai Mankongsrisuk

E-mail: thawatchai.man@mahidol.ac.th

Received 21 May 2021 Revised 1 October 2021 Accepted 5 October 2021

ORCID ID: https://orcid.org/0000-0001-9459-0870

http://dx.doi.org/10.33192/Smj.2021.98

INTRODUCTION

Although many of the patients diagnosed with

vesicoureteral reux (VUR) may recover spontaneously

with conservative treatment, a large number meet the

indications for anti-reux interventions. Injection therapy

is now more popular because of its endoscopic approach

that can be done in an outpatient setting and is more

cost-eective than open ureteral reimplantation, especially

for low-grade VURs.

1,2

In contrast, for high-grade VURs,

ureteral reimplantation is considered a suitable option due

to the lower success rate of injection therapy.

In many

countries, including ailand, no injection materials are

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used due to high cost. Consequently, ureteral reimplantation

remains the option of choice for VUR treatment.

Like many other operations, ureteral reimplantation

can be performed using open and/or laparoscopic methods.

Based on our experience, laparoscopic surgery, in general,

is associated with less pain, shorter lengths of hospital stay,

rapid recovery, and better cosmesis than open approach.

e same applies to the ureteral reimplantation procedure.

Laparoscopic ureteral reimplantation employs 2 techniques:

an extravesical and an intravesical approach. Because

of concerns about postoperative voiding dysfunction,

extravesical ureteral reimplantation is considered inferior

to the intravesical technique, especially for bilateral

reimplantation. A novel technique, transvesicoscopic

Cohen ureteral reimplantation under carbon dioxide

bladder insuation, was rst reported by Yeung et al.

in 2005.

ey demonstrated a high success rate for this

method (96%), which is comparable with the conventional

open intravesical Cohen cross-trigonal technique. is

technique is currently in widespread use and is still

employed to treat VUR.

For young pediatric urologists, laparoscopic

procedures in children are hard to perform and require

more learning than those for adults. is is not only

because of the very small working space available in a

little body, but also due to relatively few cases. Many

beginner surgeons therefore face a steep learning curve.

Compared to a pneumoperitoneum, a pneumovesicum

has much less working space, resulting in more diculty

in performing a vesicoscopic ureteral reimplantation.

is paper describes the experience gained in performing

this operation by a beginner surgeon, the intraoperative

problems encountered, and the solutions developed.

e content should enable other beginner surgeons to

undertake this operation with a degree of condence

and encourage them to perform further laparoscopic

surgeries in children.

MATERIALS AND METHODS

Patients

From October 2016 to August 2017, a urologist,

who recently nished his residency training in June

2016, carried out pneumovesicum laparoscopic ureteral

reimplantation in 20 ureters of 13 patients with VUR.

eir ages ranged from 2 to 7 years at the time of surgery.

ey all were followed until mid-2021.

Surgical technique

Cystoscopy. Aer general anesthesia was administered,

each patient was placed in the lithotomy position. e

abdomen and external genitalia were prepared and

draped in a sterile fashion. Transurethral cystoscopy

with a 30-degree lens and normal saline irrigation was

performed. e bladder was carefully inspected, and

both sides of the ureteral orices were identied before

the bladder capacity was measured. Normal saline was

lled in the bladder again until maximum anesthetic

capacity was reached.

Bladder wall anchoring and ports placement. e next step

was to anchor the bladder wall to the anterior abdominal

wall. is procedure prevented bladder collapse during

the operation. Under cystoscopic vision, two, 24-gauge,

Medi-Cut needles were passed into the bladder at the

midline of the suprapubic site, which corresponded

to the most anterior part of the bladder wall that had

been observed from the cystoscopy. In this step, there

is a need to be aware of the peritoneal recess, which

may go down to cover the superior part of the anterior

bladder wall. Number 1 nylon was rst inserted into one

Medi-Cut needle. Grasping forceps for cystoscopy were

subsequently inserted into the other needle in order to

grasp the end of the nylon, pull it up, and tie both ends of

the nylon together, thereby anchoring the bladder wall.

Using the same technique, two other anchoring stitches

were sequentially placed on the Langer’s at Langer line,

just lateral to the site where the working ports would be

placed. A 5-mm camera port was placed below the midline

anchoring stitch using an open technique. Another two,

5-mm working ports were placed under laparoscopic

vision on the Langer line (Fig 1). Placing the working

ports on the Langer’s line facilitated the later dissection

of the ureter and creation of the submucosal tunnel. e

bladder was then drained and insuated with carbon

dioxide at a pressure of 10–12 mmHg via a camera port

at the bladder dome.

Ureteral dissection and tunnel creation. A size 5 to 6 Fr

feeding tube was inserted into the ureteral orice. is

tube facilitated the visualization of the ureter’s contour

and its serosa. e medial side of the ureteral orice was

hung with 4–0 chromic catgut or Vicryl. Dissection of

the ureter was performed with the hook. Blood vessels

on the serosa of the ureter were clearly visualized under

the laparoscope. When the ureter was freely dissected,

a cross-trigonal submucosal tunnel was created with

sharp scissors. e ureter was mobilized through the

tunnel and xed into position with 4–0 Vicryl. e gap

of the muscular layer at the ureteral hiatus was sutured

to prevent the future formation of a diverticulum. e

ureter serosa was xed to the hiatus before the bladder

mucosa was closed. e feeding tube was placed in the

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(range: 200 to 450 mL). e mean operative time (from

cystoscopy to wound closure) was 176 minutes (range:

140 to 205 minutes) for the unilateral reimplantations and

240 minutes (range: 180 to 371 minutes) for the bilateral

reimplantations. Table 1 details the demographic data

and operative times of all 13 cases. In our experience,

the intraoperative problems were air leakage (4 cases),

bleeding (3 cases), tear of the bladder mucosa over the

tunnel (2 cases), and inability to insert the ureteral stent

(1 case). e whole operation managed to be performed

for almost all of the patients. e procedure for only

one patient (who was the youngest, aged 1 year and 10

months) had to be converted to an open reimplantation

because of uncontrolled air leakage into the extravesical

space and severe bladder collapse.

No patient had signicant postoperative complications.

ey occasionally had gross hematuria for only a few

days. ey could start ambulating on postoperative day

1. Bladder spasm was minimal with no anti-muscarinic

administration. e ureteral stent was le in the reimplanted

ureter for 7 days. e urethral catheter was removed

one day aer the ureteral catheter removal, following

which the patients were discharged home. A follow-up

was conducted 4 weeks later. A urinalysis and kidney

ultrasonography were carried out on all patients. If both

tests were normal and the patients had no abnormal

symptoms, they were scheduled for a further follow-up

3 months postoperatively. One patient was found to have

dysuria, frequent urination, and pyuria at the initial two

follow-ups. She received oral antibiotics and recovered

fully during the following 2 weeks. Two patients with

grade 5 VUR were found to have hydronephrosis in the

rst follow-up. However, the degree of hydronephrosis

had improved by the next 4-week follow-up. Between

the 1-year and 4-year follow-up visits, none of the 13

patients exhibited a dilated ureter or hydronephrosis in

an ultrasound examination, and there were no signs or

symptoms of urinary tract infections.

DISCUSSION

A minimally invasive technique for intravesical

cross-trigonal ureteral reimplantation was reported by

Gill et al. in 2001.

ey used a transurethral endoscope,

and 2 working balloon-ports were placed at the suprapubic

area. However, this technique had some limitations,

such as not being suitable for bilateral reimplantations

and problems with the original ureteral hiatus. In 2005,

Yeung et al. reported the rst series of transvesicoscopic

Cohen ureteral reimplantations; these had a high success

rate that was comparable with that achieved with open

cross-trigonal ureteral reimplantations.

ey placed

Fig 1. Position of all ports

ureter to enable splinting via the working port. e

working port was removed, but the feeding tube was

le and xed to the skin with Number 3 nylon. A Foley

catheter was placed. e camera port was removed, and

cystoplasty was performed using an absorbable suture.

e anchoring stitches were removed, and the abdominal

sheath and skin were closed.

Postoperative care and follow-up. General routine

postoperative care was conducted. A ureteral stent was

used for about 6 to 7 days, and the Foley catheter was

removed 1 day aer the ureteral stent removal. Without

any catheter, the patient could then be discharged from

the hospital. e patient was scheduled for a urinalysis and

kidney-bladder sonography at 4 weeks postoperatively.

If no abnormal symptoms or ndings were found at

that time, the patient was rescheduled to see us every

3 months postoperatively in the rst year and every year

with ultrasound aerwards. Voiding cystourethrography

would be repeated in case of persistent hydronephrosis

or febrile UTI. Prophylactic antibiotics was discontinued

at 6 months aer surgery if the patient had improved

hydronephrosis and no febrile UTI.

RESULTS

e mean age of the patients was 4 years 6 months

(range: 1 year 10 months to 6 years 5 months). Six patients

had unilateral VUR, while seven had bilateral VUR; a total

of 20 ureters were reimplanted without tapering of the

ureters. e mean bladder anesthetic capacity was 302 mL

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a camera port at the dome of the bladder instead of using

transurethral endoscopy, resulting in a better forward

intravesical view. Moreover, they used carbon dioxide

to distend the bladder instead of glycine, which resulted

in much better intravesical vision. e largest series of

this technique was reported by Valla et al. in 2009.

eir

success rate was 92%–95%, and the conversion rate was

6%. e cause of the conversions was an inability to

maintain pneumovesicum, which mostly occurred in

patients aged under 2 years.

From our series and experience, there are four main

problems which occur during the operation. e methods

to solve or to prevent those problems are described below.

Air leakage and port problem. is is an important

problem that forces surgeons to convert to open surgery.

Air from the inated bladder may leak through to the

urethra, the ureteral hiatus, or the port sites. e Foley

catheter placement and traction can prevent air leakage

through the urethra. Air leakage through the hiatus aer

the ureteral dissection can be solved by the immediate

suturing of the defect aer the ureteral dissection, and by

the subsequent insertion of a small feeding tube into the

prevesical space beside the ports to release the air. From

the series of Mohan et al., another method to solve air

leakage from the hiatus is to reduce the pressure.

ey

reduced the intravesical pressure from 14 to 8 mmHg,

and air leakage did not recur. Air leakage through the

port sites into the extravesical space can be prevented

by anchoring the bladder to the abdominal wall and by

assuring the stability of the working ports by xing them

the skin with suture material or using a balloon port

instead. We observed that younger patients had a port

problem more than older patients. Port displacement

is also an important problem that is associated with air

leakage. One patient in our series had to be converted

because of severe bladder collapse from uncontrolled air

leakage into the extravesical space. According to the series

from Yeung et al.,

out of 16 patients had this problem,

and 1 patient had to be converted to open surgery.

Canon et al. also reported a port problem.

One out of

52 patients in their series had to be converted to open

surgery due to poor port placement and an equipment

malfunction. ey also reported air leakage into the

peritoneal cavity, which caused pneumoperitoneum.

However, transumbilical Veress needle placement was

used to release the air in the abdominal cavity. In our

series, no pneumoperitoneum occurred. is may be the

result of using a dierent technique for the placement

of the camera port at the dome of bladder. We used the

open technique, whereas Canon et al. placed the camera

port under cystoscopy. Port placement with the open

technique can denitely avoid entering the peritoneum

TABLE 1. Demographic data and operative times.

Gender Age Side Grade of VUR Bladder capacity (mL) Operative-time

(Lt/Rt) (mL) (minutes)

Male 5yr.2mo. Left 4 350 193

Female 5yr.10mo. Both 3/3 350 190

Female 5yr.3mo. Both 5/1 260 371

Male 2yr.4mo. Left 4 200 205

Male 6yr.1mo. Left 4 350 140

Female 5yr.7mo. Left 3 320 180

Female 6yr.5mo. Left 3 300 180

Male 4yr.3mo. Both 5 300 270

Male 3yr.1mo. Both 5/4 250 205

Female 4yr.5mo. Left 3 450 160

Female 3yr.9mo. Both 3/4 300 275

Male 4yr.11mo. Both 4/5 300 180

Male 1yr.10mo. Both 4/4 200 190

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via the peritoneal recess. In Valla’s study, 4 out of 72

patients had to be converted owing to a port placement

problem, and 6 patients had pneumoperitoneum, which

could be corrected using a Veress needle.

Bleeding. e laparoscopic approach resulted in a

higher chance of serosal blood vessel preservation than

the open reimplantation technique because of better

visualization. However, it is possible to have a bleeding

from the detrusor muscle or the serosa of the ureter

during a ureteral dissection. Although bleeding in this

operation is usually minimal, it will cause diculty with

the visualization of the plane between the ureter and the

bladder muscle. is problem can be solved by careful

electrocoagulation at the bleeding point. However, extensive

electrocoagulation may cause long term complications,

such as ureteral stricture due to ischemia or heat eect.

Tear of bladder mucosa over the tunnel. If this

problem occurs, it can be easily corrected by suturing

the tear mucosa. is problem mainly stems from an

inappropriate scissor curve and working-port angle. e

working ports should be placed on the Langer’s line. We

observed that the ureteral orices and the interureteric bar

are usually underneath the Langer’s line. Consequently,

we can create a submucosal tunnel in a direction that will

not cause a mucosal tear. In addition, we recommend

placing the working ports laterally as far as possible

to make the angle of the port more parallel with the

posterior bladder wall. However, one should be aware

of the injury to the iliac and inferior epigastric vessels.

To prevent inferior epigastric vessel injury during the

working-port placement, which may result in abdominal

wall bleeding or hematoma, the light from the cystoscopy

shining through the abdominal wall greatly facilitates

the identication of the position of these vessels.

Inability to insert the feeding tube. e feeding

tube in the ureter allows us to clearly identify the contour

of the ureter and the plane between the ureter and the

detrusor muscle. An inability to insert the feeding tube

may be caused by 2 factors: either the tube is too big, or

the angulation of the ureterovesical junction is dicult.

e later can be solved by inserting the guidewire rst,

followed by railroading the feeding tube over the guidewire.

Alternatively, a smaller tube can be chosen for insertion

into the ureter.

From our series, the average operative time was

longer than the series of Yeung et al., Canon et al.,

and Valla for both the unilateral and bilateral ureteral

reimplantations.

4,6,8

is may reect the level of experience

of the surgeon with laparoscopic surgery. Moreover, we

found that the operative time is inversely associated with

bladder capacity, with no statistical signicance (Pearson

correlation coecient: -0.347; p-value: 0.25). erefore,

it would be easier for beginner surgeons to perform this

operation on patients with a large bladder capacity.

CONCLUSION

Ureteral reimplantation is still a crucial operation

for pediatric urologists. Pneumovesicum laparoscopic

cross-trigonal ureteral reimplantation is a better option

than open technique for reducing postoperative pain, the

incidence of bladder spasms, and the lengths of hospital

stay, and for achieving better cosmesis. Because of the

many problems that may occur during the operation,

this procedure may be hard to perform, but it is not

impossible to learn and acquire the necessary skills.

Despite there being a steep learning curve, we rmly

believe that every beginner surgeon is able to carry it

out eectively and safely with good outcomes.

ACKNOWLEDGEMENTS

I express my sincere gratitude to my advisor,

Dr. Kittipong Phinthusophon, for continuously supporting

my work and related research, and for his patience,

motivation, and immense knowledge. His guidance

helped me throughout the research and operations.

I also thank Ms. Jitsiri Chaiyatho for her kind help with

the proofreading and publishing of this paper.

REFERENCES

1. Benoit RM, Peele PB, Docimo SG. e Cost-Eectiveness of

Dextranomer/Hyaluronic Acid Copolymer for the Management

of Vesicoureteral Reux. 1: Substitution for Surgical Management.

J Urol. 2006;176(4):1588–92.

2. Raju GA, Marks AJ, Benoit RM, Docimo SG. Models of care

for vesicoureteral reux with and without an end point of reux

resolution: A computer cost analysis. J Urol. 2013;189(6):2287–92.

3. Esposito C, Escolino M, Lopez M. Surgical Management of

Pediatric Vesicoureteral Reux: A Comparative Study Between

Endoscopic, Laparoscopic, and Open Surgery. J Laparoendosc

Adv Surg Tech A. 2016;26(7):574–80.3

4. Yeung CK, Sihoe JD, Borzi PA. Endoscopic cross-trigonal

ureteral reimplantation under carbon dioxide bladder insuation:

a novel technique. J Endourol 2005;19:295e9.

5. Gill IS, Ponsky LE, Desai M, Kay R, Ross JH. Laparoscopic

cross-trigonal Cohen ureteroneocystostomy: novel technique.

J Urol. 2001;166(5):1811–4.

6. Valla JS. Transvesicoscopic cohen ureteric reimplantation for

vesico-ureteral reux in children. Pediatr Endourol Tech. 2007;

5(6):39–46.

7. Abraham MK, Viswanath N, Bindu S, Kedari P, Ramakrishnan P,

Naaz A, et al. A simple and safe technique for trocar positioning in

vesicoscopic ureteric reimplantation. Pediatr Surg Int. 2011;27(11):

1223–6.

8. Canon SJ, Jayanthi VR, Patel AS. Vesicoscopic Cross-Trigonal

Ureteral Reimplantation: A Minimally Invasive Option for

Repair of Vesicoureteral Reux. J Urol. 2007;178(1):269–73.

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Chindanai Hongsaprabhas, M.D.*, Sorranart Muangsomboon, M.D.***, Chandhanarat Chandhanayingyong,

M.D.**, Rapin Phimolsarnti, M.D.**, Saranatra Waikakul, M.D.**, Apichat Asavamongkolkul, M.D.**

*Department of Orthopaedics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ailand, **Department of Orthopaedic Surgery,

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

Outcomes and Prognostic Factors in Patients with

Malignant Peripheral Nerve Sheath Tumor

ABSTRACT

Objective: To investigate and report the clinical proles, treatment patterns, and oncologic outcomes in malignant

peripheral nerve sheath tumor (MPNST) patients, and to identify the prognostic factors that signicantly aect survival.

Materials and Methods: Patients diagnosed with and treated for histologically conrmed MPNST at our institute

during the January 1997 to June 2018 study period were included. Patient medical records and surgical specimens

were reviewed, and study-related data was extracted and analyzed.

Results: ere were 27 males and 32 females with a mean age of 44 years. Most patients presented with mass and

most patients were AJCC stage III. Twenty-nine percent of patients had MPNST that was associated with NF-1. At

a median follow-up time, 18 patients (30.51%) suered from local disease recurrence. Two-year and 5-year overall

survival was 72% and 46%, respectively. In univariate analysis, chemotherapy treatment and positive tumor margin

were adverse prognostic factors for disease-free survival. In multivariate analysis, chemotherapy treatment (hazard

ratio (HR): 3.415, 95% CI: 1.367-16.021; p=0.013) and positive tumor margin (HR: 4.680, 95% CI 1.828-10.314;

p=0.014) were found to be independent prognostic factors for disease-free.

Conclusion: Chemotherapy treatment and positive tumor margin were identied as independent adverse prognostic

factors for disease-free and overall survival, respectively. Accordingly, early detection and appropriate treatment

are essential for improved patient outcome.

Keywords: Malignant peripheral nerve sheath tumor; MPNST; prognostic factors; outcomes; survival (Siriraj Med

J 2021; 73: 763-771)

Corresponding author: Apichat Asavamongkolkul

E-mail: apichat.asa@mahidol.ac.th

Received 24 June 2021 Revised 28 September 2021 Accepted 5 October 2021

ORCID ID: https://orcid.org/0000-0002-7868-7426

http://dx.doi.org/10.33192/Smj.2021.99

INTRODUCTION

Malignant peripheral nerve sheath tumor (MPNST)

is a rare and aggressive malignant so-tissue tumor that

is characterized by high risk of local recurrence and

distant metastasis.

ere is a widely held misconception

that curative treatment for MPNST is complete tumor

removal, with adjuvant chemotherapy and radiotherapy

recommended only in large lesions or lesions with high-

grade histology.

Whether treatment for MPNST involves

extensive surgery alone or surgery combined with adjuvant

therapies, the prognosis for patients with this condition

remains poor.

Several studies have reported 5-year

overall survival rates that vary from 16% to 52%, and

5-year disease-free survival rates that range from 26%

to 49%.

4-13

Neurobromatosis type 1 (NF-1) or disease

recurrence when associated with MPNST were found

and reported to be adverse prognostic factors.

10,14

e aim of this study was to investigate and report

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Hongsaprabhas et al.

the clinical proles, treatment patterns, and oncologic

outcomes in MPNST patients. e secondary objective

was to identify the prognostic factors that signicantly

aect survival.

MATERIALS AND METHODS

Seventy-one patients were diagnosed with and

treated for histologically conrmed MPNST during

the January 1997 to June 2018 study period. Of the 12

patients that were excluded, 3 were denied denitive

operative treatment and 9 were lost to follow-up prior

to 6 months aer commencement of treatment. e

remaining 59 patients were enrolled and included in

the nal analysis. Aer the protocol for this study was

approved by the Institutional Review Board, patient

medical records and surgical specimens were reviewed,

and study-related data was extracted and analyzed.

A wide excision of tumor was attempted in all MPNST

patients (Fig 1A-D). Radiation therapy with high-dose

regimen ranging from 45 to 65 Gy was considered in

patients with greater risk of recurrence based on operative

and pathologic ndings. ere were, however, no absolute

indications for radiation therapy at our center during

the study period. Adjuvant chemotherapy, consisting of

doxorubicin and ifosfamide, was considered in patients

with high-grade disease and distant metastasis. Each

patient was discussed at our weekly multidisciplinary

musculoskeletal tumor board meeting to determine the

most appropriate modality treatment.

Statistical analysis

Descriptive statistics were used to analyze demographic

data. Cause-specic mortality, local recurrence, and distant

metastasis were the clinical endpoints in this study. Data

analysis were performed using statistical package Stata

version 14 (StatCorp, College Station, TX, USA) and

program R version 4.0.2 for windows. Shapiro-Wilk test

and histogram were used to evaluate normal distribution.

To summarize the data studied mean (sd) and median

(range) were reported for continuous variables when

appropriate, frequency and percentage for categorical

variables. Kaplan-Meier method and Cox proportional

hazard model was used to determine prognostic factors

for two events, disease free survival and overall survival.

Time to occurrence of event was calculated from the

date of surgery to the date when the event occurred, or

censored at the date of the last follow-up, death from

other cause. Variables of interesting were gender, tumor

Fig 1. A 19-year-old male with MPNST with right pelvic bone destruction who underwent internal hemipelvectomy without reconstruction:

A) Initial plain x-ray; B) Coronal view of T1-weighted MRI; C) Tumor mass aer en-bloc resection; D) Postoperative plain x-ray

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depth, NF-1, primary tumor, chemotherapy, radiotherapy,

tumor site, tumor size, surgery technique, margin and

severity. In this study, the variables with a univariate

signicance level of 0.25 or less were selected to perform

multivariable Cox regression. We also included other

variables from the literature which were reported clinically

relevant and eligible for using in the model. Backward

elimination technique was employed to select variables

into the model. Proportional hazard (PH) assumption was

evaluated using PH test based on Schoenfeld residuals and

in survival curves plot. Variance ination factor (VIF)

was determined whether there was multi-collinearity

among the variables. Candidate variables with VIF > 4

were excluded from data analysis. Goodness of t was

examined for lack of t using graphical approach; the

Cox-Snell residuals against the Nelson-Aalen cumulative

hazard function plot. Data analysis was 2-tailed test with

signicant level 0.05.

RESULTS

e mean age at presentation was 44 years, with an age

range of 13 to 86 years. Twenty-seven males and 32 females

were included. Demographic and clinical characteristics

of 59 study patients are shown in Table 1. Most patients

presented with only one symptom (66.1%) and mass was

the most frequent complaint (89.8%), followed by pain

(28.8%) and neuropathy (15.3%). Twenty-one patients

had been treated at other hospitals before being referred

aer presenting with local tumor recurrence. Most patients

in this study were American Joint Committee on Cancer

(AJCC) stage III (47.5%). Twenty-nine percent (17/59)

of patients had MPNST that was associated with NF-1.

Limb sparing surgeries could be performed in 48 patients

(81.3%), with amputation required in the remaining 11

patients. Negative tumor margin could be achieved in

34 patients (57.6%), with 14 patients (23.7%) emerging

from surgery with positive margins. irty-four patients

(57.6%) received adjuvant radiation therapy, 3 patients

(5.1%) received only adjuvant chemotherapy, and 11

patients (18.6%) received both adjuvant treatments.

At a median follow-up time of 48 months, 18 patients

(30.5%) suered from local recurrence of the disease.

Twenty-nine patients (58%) developed metastasis, and

9 of those had multiple sites metastasis. Pulmonary

metastasis was the most common site (44.1%), followed

by bone, brain, and other organ at percentages of 11.9%,

3.4%, and 6.8%, respectively. Complications occurred in

15 patients (25.4%), as follows: wound dehiscence (6.8%),

supercial wound infection (3.4%), phantom limb pain

(5.1%). Two-year and 5-year overall survival was 72%

and 46%, respectively. Median overall survival time was

58 months (Fig 2A). Median disease-free survival was 32

months based on analysis of 50 initially non-metastatic

patients. Two-year and 5-year disease-free survival was

52% and 40%, respectively (Fig 2B).

Subgroup survival analysis was performed for

NF-1 and type of disease presentation. Median overall

survival of patients with and without NF-1 was 38 months

(95% CI: 13.5-62.5) and 58 months (95% CI: 5.1-11.9),

respectively, with no signicant dierence found between

groups (p=0.648). Similarly, no signicant dierence was

observed between patients with recurrent and primary

tumor (p=0.978). Median overall survival of patients

with recurrent tumor was 46 months (95% CI: 21.7-

70.3), while patients with primary tumor had a median

survival time of 58 months (95% CI: 0.0-121.2).

In univariate analysis in Table 2, chemotherapy

treatment (hazard ratio (HR): 3.176, 95% CI 1.464-6.891;

p=0.003) and positive tumor margin (hazard ratio (HR):

4.342, 95% CI 1.828-10.314; p=0.010) were shown to

be adverse prognostic factors for disease-free survival

(Fig 3A-B). Radiation therapy and type of surgery and

AJCC stages III and IV had a non-signicantly negative

impact on overall survival (Table 3). Of note, AJCC

staging could not be calculated as a prognostic factor

for disease-free survival, because some of our patients

had metastasis initially.

In multivariate analysis, only chemotherapy treatment

(hazard ratio (HR): 3.415, 95% CI: 1.367-16.021; p=0.013)

and positive tumor margin (hazard ratio (HR): 4.680, 95%

CI 1.828-10.314; p=0.014) were found to be independent

prognostic factors for disease-free and overall survival,

respectively.

DISCUSSION

MPNST is widely known to be a rare and aggressive

malignant so-tissue tumor. ey account for approximately

10% of all so tissue sarcomas.

1,3

e symptoms of MPNST

are non-specic. Painless mass is a common chief complaint

and most patients suer from nerve-related symptoms

that are caused by tumor compression.

13,15

Our ndings

revealed mass to be the most common presenting symptom,

while weakness and radicular pain were the least common

presenting symptoms. e most widely recognized risk

factor for MPNST development is NF-1, given that

10-30% of NF-1 patients will develop MPNST during

their lifetime.

In our series, 28.8% of MPNST developed

in NF-1 patients, which is comparable to the incidence

reported from other studies.

4,5,11

Asavamongkolkul,

et al. reported 2 cases of MPNST associated with NF-1,

both of whom died shortly aer diagnosis with distant

metastases.

Data from survival meta-analyses reported

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TABLE 1. Patient demographic and clinical characteristics.

Characteristic Overall Disease free

(n=59) (n=50)

Gender(Female) 32(54.2) 28(56.0)

Meanage(year) 44 45

Followup(months) 48(24–178)* 51.5(24–178)*

Numberofchiefcomplaint 

One 39 (66.1) 35 (70.0)

 Two 18(30.5) 14(28.0)

 Three 2(3.4) 1(2.0)

Chiefcomplaint 

Mass 53 (89.8) 46 (92.0)

Pain 17 (28.8) 13 (26.0)

 Neuropathy 9(15.3) 5(10.0)

 Others 2(3.4) 2(4.0)

Presentation(Primarycase) 37(62.7) 30(61.2)

Visit(Referredcase) 45(76.3) 38(76.0)

Tumorsite 

 Neckandtrunk 16(27.1) 13(26.0)

 Extremity 42(71.2) 36(72.0)

 NeckandExtremity 1(1.7) 1(2.0)

Size(Morethan5cm.) 40(67.8) 33(66.0)

Depth(Deep) 53(89.8) 44(88.0)

Grading

 Low 7(11.9) 7(14.0)

 Intermediate 12(20.3) 10(20.0)

 High 40(67.8) 33(66.0)

AJCCstaging 

I 5 (8.5) 5 (11.9)

II 11 (18.6) 11 (26.2)

III 28 (47.5) 26 (61.9)

IV 7 (11.9) 0 (0.0)

Marginstatus 

 Negative 34(57.6) 29(58.0)

Closed 7 (11.9) 6 (12.0)

 Positive 14(23.7) 12(24.0)

NF-1 (Yes) 17 (28.8) 13 (26.0)

Distantmetastases** 29(58.0) 29(58.0)

Radiationtherapy(Yes) 34(57.6) 29(58.0)

Chemotherapy(Yes) 14(23.7) 12(24.0)

Dealth 24(40.7)

NF-1, neurobromatosis type 1; AJCC, American Joint Committee on Cancer.

*Median (range). ** nine cases have event before begin study.

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Fig 2. Survival rate of overall survival (A) and disease-free survival (B)

TABLE 2. Univariate and multivariate Cox proportional hazard regression for disease free survival (n=50).

Variables Univariate analysis Multivariate analysis

HR p value HR p value

(95 % CI) (95 % CI)

Gender:(Female) 1.159 0.697 - -

(0.551-2.435)

Tumordepth:(Deep) 1.263 0.702 0.552 0.416

(0.381-4.190) (0.132-2.310)

NF-1:(No) 1.134 0.785 - -

(0.459-2.799)

Presentation:(Recurrence) 1.510 0.286 - -

(0.708-3.222)

Chemotherapy:(Yes) 3.176 0.003 3.415 0.013

(1.464-6.891) (1.293-9.022)

Radiotherapy:(Yes) 1.548 0.259 0.509 0.235

(0.725-3.305) (0.167-1.551)

Site:(extremity) 1.065 0.887 2.465 0.092

(0.449-2.525) (0.862-7.049)

Size:(>5cm.) 1.229 0.608 1.136 0.787

(0.559-2.702) (0.450-2.873)

Surgery:(limbsalvage) 2.649 0.114 3.481 0.092

(0.791-8.866) (0.817-14.836)

Margin*:

Close 4.342 0.010 4.680 0.014

(1.828-10.314) (1.367-16.021)

Negative 0.571 0.458 0.570 0.481

(0.130-2.505) (0.120-2.718)

Grade:(High) 1.902 0.124 1.094 0.858

(0.838-4.318) (0.408-2.930)

AJCCStaging:(III+IV) 1.468 0.355 - -

(0.651-3.308)

* Positive qualied reference group.

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Hongsaprabhas et al.

Fig 3. Disease free survival rate related to chemotherapy treatment (A) and tumor margin (B)

TABLE 3. Univariate and multivariate Cox proportional hazard regression for overall survival (n=59).

Variables Univariate analysis Multivariate analysis

HR p value HR p value

(95 % CI) (95 % CI)

Gender:(Female) 1.406 0.420 - -

(0.614-3.217)

Tumordepth:(Deep) 1.139 0.861 - -

(0.265-4.890)

NF-1:(Yes) 1.228 0.648 - -

(0.508-2.968)

Presentation:(Primary) 1.021 0.978 - -

(0.442-2.317)

Chemotherapy:(Yes) 1.644 0.255 - -

(0.699-3.867)

Radiotherapy:(Yes) 1.918 0.148 2.095 0.119

(0.793-4.638) (0.826-5.312)

Site:(extremity) 1.152 0.780 1.528 0.425

(0.427-3.112) (0.540-4.324)

Size:(>5cm.) 1.386 0.469 1.660 0.305

(0.573-3.355) (0.631-4.370)

Surgery:(limbsalvage) 1.678 0.406 - -

(0.495-5.687)

Margin*:

Close 1.952 0.164 1.669 0.314

(0.762-5.001) (0.616-4.519)

 Negative 0.573 0.462 0.474

(0.130-2.526) (0.103-2.182) 0.338

Grade:(High) 2.430 0.079 1.799 0.267

(0.903-6.544) (0.638-5.069)

AJCCStaging:(III+IV) 2.251 0.107 - -

(0.838-6.048)

* Positive qualied reference group.

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a lower odds ratio for survival in MPNST patients associated

with NF-1; however, the prognosis for these patients has

improved in studies published in recent years.

Magnetic resonance imaging (MRI) is a valuable

investigation prior to histo-pathologic study. e main

objective is to dierentiate MPNST from benign peripheral

nerve sheath tumor using criteria that includes peripheral

enhancement, mass dimension, perilesional edema,

and intratumoral cystic lesion. e presence of two or

more of these features is suggestive of malignancy with a

specicity of 90%.

In contrast, target sign is also helpful

in dierentiating benign neurobroma from MPNST.

Fluorodeoxyglucose positron emission tomography (FDG-

PET) has been reported as being able to dierentiate

MPNST and forecast patient prognosis.

2,4

Most patients in our series were in the advance stage

– predominantly AJCC stage III (47.5%) e aggressive

nature of the tumors in our study was reected, as follows:

67.8% of tumors were high grade, 89.8% were deeply located,

and 67.8% were larger than 5 cm in diameter, which was

comparable to data reported from other studies.

8,10,11,13,18

e number of patients who received isolated adjuvant

radiation therapy, isolated adjuvant chemotherapy, and

combined adjuvant treatments was 43%, 4%, and 20%,

respectively, which was comparable to data from other

studies.

8-11,13

Adjuvant radiation therapy is recommended

for tumors with high grade, large size, tumor recurrence,

and closed margin. Alternatively, adjuvant chemotherapy

is considered in tumors with high grade, large size, and

metastasis. Although MPNST has relatively low sensitivity

to radiation, adjuvant irradiation to doses more than 60

Gy is still associated with improved local control, but not

with overall disease survival.

2,6

Carbon ion irradiation

is becoming more popular due to its higher biological

eectiveness compared to photons or protons, but a

study in MPNST treatments revealed that it provided

short-term benets, especially in patients with gross

residual or unresectable tumor.

Local recurrence is common in MPNST. Incidence

of recurrence ranges from 32% to 65%.

2,8-11,13

ere were

18 patients (30.5%) who developed local recurrence in this

study. However, we were not able to correlate recurrence

with initial presentation from survival analysis.

Twenty-nine patients (50.8%) developed metastasis,

and 9 of those had multiple sites metastasis. Pulmonary

metastasis was the most common site (44.1%), followed

by bone, brain, and other locations at percentages of

11.9%, 3.4%, and 6.8%, respectively, and these rates are

comparable to rates published in other reports.

6,8-11,13

Five-year overall survival and disease-free survival in

this study was 46% and 40%, respectively. Our survival

rates are comparable to rates from other studies that

described 5-year overall survival rates that varied from

16% to 52%, and 5-year disease-free survival rates that

ranged from 26% to 49%.

4-13

A variety of signicant favorable prognostic factors

have been reported from several studies. (Table 4) In

the present study, chemotherapy treatment and positive

tumor margin was shown to be an adverse prognostic

factor for disease-free survival. Cashen, et al. identied

Musculoskeletal Tumor Society (MSTS) Rating Scale

as an adverse prognostic outcome.

MPNST with

rhabdomyoblastic dierentiation or malignant triton

tumor (MTT) was reported to be associated with poor

prognosis and more aggressive tumor behavior.

Brekke,

et al. reported that p53-positive MPNST patients are a

high-risk group and they are candidates for adjuvant

treatment.

Chemotherapy for so-tissue sarcoma is limited in

benet and in variety. Chemotherapy options that include

vincristine, doxorubicin, ifosfamide, and etoposide have

a positive eect among metastatic MPNST patients,

but not in non-metastatic patients.

A positive trend

for adjuvant radiation, but not for chemotherapy, was

observed for disease-free survival and overall survival.

13,23,24

Interestingly, we found chemotherapy treatment to be

an adverse prognostic factor for disease-free survival.

Targeted therapy is becoming a compelling treatment

option for patients with MPNST (e.g., erlotinib, sorafenib);

however, some targeted therapy studies are still ongoing

and some have shown no clinical response.

Moreover,

there are studies that have demonstrated the feasibility

of anti-survivin and oncolytic measles virus as a novel

treatment for MPNST patients that should be studied

in future clinical trials, especially in the NF-1-related

group.

25-27

is study has some mentionable limitations. First

and consistent with the retrospective nature of this

study, some patient data may have been incomplete.

Second, the size of the study population was relatively

small. As a result, our study may have lacked sucient

power to identify all signicant associations. ird, the

patients enrolled in this study were from a single center,

the largest tertiary referral hospital. Most patients were

referred to our institute with complicated and intransigent

conditions.

CONCLUSION

Patients with MPNST in this series had survival

rates that are comparable to those reported in other

studies. Chemotherapy treatment and positive tumor

margin were identied as independent adverse prognostic

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Hongsaprabhas et al.

factors for disease-free and overall survival, respectively.

Accordingly, early detection and appropriate treatment

are essential for improved patient outcome.

ACKNOWLEDGEMENTS

e authors gratefully acknowledge Miss Krabkaew

Soparat, M.Sc and Miss Nichakorn Khomawut for assistance

with data analysis and research coordination.

Conict of interest declaration: e authors hereby

declare no personal or professional conicts of interest

regarding any aspect of this study.

TABLE 4. Signicant favorable prognostic factors.

Publications Year Number of cases Signicant favorable prognostic factors

Anghileri

 2005 205 -smallertumorsize

    -lackoflocalrecurrence

    -extremitylocated

Stucky

 2012 175 -tumorsize<5cm

    -lackoflocalrecurrence

    -lowhistologicgrade

    -extremitylocated

Zou

  2009 140 -tumorsize<10cm

    -lowintensityp53staining

Wong

 1998 134 -smallertumorsize

    -lowhistologicgrade

    -perineuralhistologicsubtype

Lafemina

 2012 105 -tumorsize<5cm

    -lowhistologicgrade

    -lackoflocalrecurrence

    -extremitylocated

Cashen

 2004 80 -anatomicallocation

    -MSTSstaging

    -lowerpartoflowerextremity

Brekke

 2009 64 -tumorsize<8cm

    -completesurgicalresection

    -lowerintensityp53staining

Okada

 2007 56 -tumorsize<7cm

    -lackofmetastasis

Baehring

 2003 54 -tumorsize<5cm,completesurgical

    resection,youngage,radiationtherapy, 

    lackofchemotherapy

Thisstudy 2021 51 -lackofchemotherapy,negativetumormargin

MSTS, Musculoskeletal Tumor Society; AJCC, American Joint Committee on Cancer

Funding disclosure: is was an unfunded study.

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prognostic impact of rhabdomyoblastic dierentiation (malignant

triton tumors), neurobromatosis 1 status and location. Eur

J Surg Oncol 2013;39:46-52.

21. Brekke HR, Kolberg M, Skotheim RI, Hall KS, Bjerkehagen B,

Risberg B, et al. Identication of p53 as a strong predictor of

survival for patients with malignant peripheral nerve sheath

tumors. Neuro Oncol 2009;11:514-28.

22. Okada K, Hasegawa T, Tajino T, Hotta T, Yanagisawa M,

Osanai T, et al. Clinical relevance of pathological grades of

malignant peripheral nerve sheath tumor: a multi-institution

TMTS study of 56 cases in Northern Japan. Ann Surg Oncol 2007;

14:597-604.

23. Longhi A, Errani C, Magagnoli G, Alberghini M, Gambarotti

M, Mercuri M, et al. High grade malignant peripheral nerve

sheath tumors: outcome of 62 patients with localized disease

and review of the literature. J Chemother 2010;22:413-8.

24. Zehou O, Fabre E, Zelek L, Sbidian E, Ortonne N, Banu E, et al.

Chemotherapy for the treatment of malignant peripheral nerve

sheath tumors in neurobromatosis 1: a 10-year institutional

review. Orphanet J Rare Dis 2013;8:127.

25. Ghadimi MP, Young ED, Belousov R, Zhang Y, Lopez G, Lusby

K, et al. Survivin is a viable target for the treatment of malignant

peripheral nerve sheath tumors. Clin Cancer Res 2012;18:2545-

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26. Deyle DR, Escobar DZ, Peng KW, Babovic-Vuksanovic D.

Oncolytic measles virus as a novel therapy for malignant

peripheral nerve sheath tumors. Gene 2015;565:140-5.

27. Widemann BC, Italiano A. Biology and management of

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Ankita Ratan, PG*, Sujata Pradhan, M.D.**, Pradip Kumar Panigrahi, M.D.***, Manisha Sahu, MS*, Pratyasha

Peepal, PG*, Somadatta Das, MA****

*Department of Obstetrics and Gynaecology, IMS & SUM Hospital, SOA Deemed to be University, Bhubaneswar, Odisha, India, **Center for Human

Reproduction, Department of Obstetrics & Gynaecology, IMS & SUM Hospital, Siksha ‘O’ Anusandhan Deemed to be University, Bhubaneswar,

Odisha, India, ***Department of Obstetrics and Gynaecology, Sparsh Hospital and critical care, Bhubaneswar, Odisha, India, ****Central Research

Laboratory, IMS & SUM Hospital, SOA Deemed to be University, Bhubaneswar, Odisha, India.

Role of Laparoscopy in Diagnosis and Treatment of

Endometriosis Associated with Infertility:

A Prospective Analysis

ABSTRACT

Objective: Endometriosis is oen considered as an enigma due to its varied clinical presentation and challenges in

diagnosis. e objective of this study is to evaluate the role of laparoscopy in diagnosis and treatment of endometriosis

associated with infertility.

Materials and Methods: Infertile females diagnosed to have endometriosis during or before undergoing laparoscopic

surgery from August 2018 to February 2020 were followed up for spontaneous conception for 6 months following

laparoscopy. Revised American Fertility Society (r-AFS) scoring system was used to score endometriosis and stage

the disease (stage I-IV). Surgical interventions were done on individual case basis following ESHRE guidelines.

Results: Fiy infertile females diagnosed with endometriosis during or before laparoscopy were recruited for the

study. Mean age of patients was 28.58 (±4.21) years. irty-four (68%) patients had primary infertility and 16 (32%)

has secondary infertility. Mean duration infertility was 3.33 (±1.43) years. Only 37 patients (74%) had evidence

of endometriosis in pre-operative ultrasonography. During the follow up period of rst 6 months aer surgery 34

(68%) patients conceived spontaneously. Lower mean endometriosis score (p=0.00) and early stages of endometriosis

(p=0.00) were associated with higher chances of conception. But, female age, duration and type infertility, USG

ndings and type of surgical interventions did not aect pregnancy rate.

Conclusion: Laparoscopy helps in diagnosis of endometriosis. Laparoscopic therapeutic interventions for endometriosis

increase the probability of spontaneous conception in infertile females. Lower surgical score and early stages of

endometriosis are associated with higher chance of conception.

Keyword: Laparoscopy; endometriosis; infertility; diagnosis (Siriraj Med J 2021; 73: 772-776)

Corresponding author: Sujata Pradhan

E-mail: dr.suzzane@gmail.com

Received 21 March 2021 Revised 18 September 2021 Accepted 5 October 2021

ORCID ID: https://orcid.org/0000-0002-3082-0494

http://dx.doi.org/10.33192/Smj.2021.100

INTRODUCTION

Endometriosis is the cause of infertility in 5-15%

of women in reproductive age group.

It is diagnosed in

35 to 50 % of women with chronic pelvic pain, infertility

or both.

But diagnosis is oen postponed for several

years after symptoms onset.

There is no definitive

imaging modality or serum marker for the diagnosis

of endometriosis. While transvaginal scan (TVS) has

recently gained popularity as a rst-line imaging modality

for non-invasive diagnosis of endometriosis,

diagnostic

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laparoscopy is required for conrmation of diagnosis

and staging of the disease.

A systematic review and

meta-analysis of 13 studies on pelvic endometriosis also

revealed non-invasive imaging modalities particularly

transvaginal ultrasonography to be of lesser accuracy

compared to laparoscopy.

Excision and ablation of endometriotic lesions

in mild to severe disease using laparoscopic surgery

enhances fertility.

Surgery improves the probability of

conception by restoring the anatomical distortion caused

by the disease and removing the endometriotic implants,

thereby reducing the inammatory peritoneal response.

Existing literature shows diversities regarding the benecial

eect of therapeutic laparoscopy in infertile females with

dierent stages of the disease. In a retrospective cohort

study, patients with severe endometriosis were followed up

for natural as well as assisted conceptions.

Reproductive

outcomes in infertile women with advanced endometriosis

and repeated IVF failures were also observed.

9,10

In a

retrospective study by Ekine et al. infertility patients

with all stages of endometriosis were followed up for

pregnancy following surgery.

But the pregnancies

resulted from IUI and ART were also included. e

current study was intended to determine the ecacy of

laparoscopic surgery for diagnosis as well as treatment

of pelvic endometriosis in infertile females. It observes

the chances of spontaneous conception for all stages of

endometriosis.

MATERIALS AND METHODS

is prospective study was carried out in a teaching

hospital of Odisha, India. Institutional Ethical Committee

approval was obtained for the study. For all the patients

attending infertility clinic, detail history taking and relevant

clinical examinations were performed. As a part of routine

infertility evaluation, baseline transvaginal ultrasonography,

thyroid function test and male partner’s semen analysis

were done. Patients with clinical and /or ultrasonographic

features of endometriosis without previous history of

surgery for endometriosis were planned for laparoscopy.

Dysmenorrhoea, dyspareunia and chronic pelvic pain

were considered as relevant symptoms for diagnosis of

endometriosis. Similarly, presence of endometriotic cyst in

one or both ovaries or features suggestive of utero-ovarian

adhesions in transvaginal ultrasonography were presumed

to be features of endometriosis. Revised AFS scoring

system was used for scoring and staging endometriosis

during surgery. Chromopertubation was done for all

the patients. erapeutic interventions were done as

per ESHRE guidelines for endometriosis management.

Complete cystectomy was preferred to partial cystectomy

or cyst drainage for ovarian endometriomas. Supercial

endometriotic lesions were fulgurated. Adhesiolysis

was done for pelvic adhesions for restoration of tubo-

ovarian relationship. Surgical specimens were sent for

histopathological conrmation of endometriosis.

Patients with laparoscopic features suggestive of

endometriosis were considered for the study. Females aged

more than 37 years, with polycystic ovarian syndrome

(PCOS) or decreased ovarian reserve were excluded.

Similarly, patients with abnormal male factors and bilateral

tubal block as observed during laparoscopy were also

excluded from the study. Diagnosis of PCOS was done

as per Rotterdam criteria. Similarly, decreased ovarian

reserve was dened as antral follicle count (AFC) < 7

combined in both ovaries or anti-Mullerian hormone

(AMH) < 1.1 ng/ml. Abnormal semen parameters were

dened by sperm concentration < 10 million/ml and /

or progressive motility < 10%.

e study subjects were followed up for 6 months

post-intervention for spontaneous conception. Clinical

pregnancy was considered as the outcome measure of the

study. It was dened by the presence of ultrasonographic

evidence of gestational sac with or without fetal pole at

week of amenorrhoea.

Considering the total number of patients attending

infertility clinic in our hospital and the prevalence of

endometriosis in infertile females, the sample size was

decided to be at least 50 as this is a part of post-graduate

level dissertation with a xed duration for the study.

Data analysis

The data obtained were tabulated in Microsoft

Excel. Statistical analysis was carried out with the aid

of statistical programme SPSS 20.0. Quantitative data

were expressed in mean and standard deviation. e

percentages and proportions were used to express the

categorical results. A Chi-square test was performed to

compare the proportion in two groups for a categorical

variable. An independent t-test was performed to look

for the dierence in the means of two groups with a

quantitative variable, p-value of 0.05 was considered to

be the degree of statistical signicance.

RESULTS

During the study period, y infertile patients

with endometriosis were followed up for spontaneous

conception aer laparoscopy. Mean age of participants

was 28.5 (±4.21) years. Mean duration of infertility was

3.33 (±1.43) years. Majority of them had primary infertility

(68%). Pre-Operative ultrasonography showed evidence

of endometriosis only in 37 (74%) patients. Among the

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Ratan et al.

patients who had ultrasonographic abnormalities, the

most common nding was a right ovarian chocolate cyst

(26%) followed by bilateral chocolate cysts (24%).

Intraoperatively, the minimum r-AFS score was 2

and the maximum score was 88 with mean (±SD) score

of 23.76 (±19.9). Stage III endometriosis was observed in

majority of these patients followed by stage I endometriosis

(20%). Unilateral cystectomy was the most common

intervention done in 48% of the patients, followed by

bilateral cystectomy (24%) and adhesiolysis alone (12%).

Other interventions were fulguration of endometriotic

spots (8%), myomectomy (6%), and oophorectomy (2%).

irty-four patients (68%) conceived spontaneously

at the end of 6 months and 16(32%) patients failed to

conceive. General characteristics of these patients are

compared and represented (Table 1). e mean age

of patients with successful pregnancies was similar to

those who failed to conceive (27.82±4.71 vs 30.18±3.35,

p=0.06). Similarly, there was no dierence in duration

of infertility in these patients (Mean ± SD 3.35±1.45 vs

3.28±1.46, p=0.88). Among 34 patients with primary

infertility, 24 (70.5%) conceived and 10 (62.5%) patients

with secondary infertility conceived in the predened

postoperative period. ere was, however, no statistically

signicant association of infertility type with the status

of conception within 6 months (p=0.56).

Ultrasonographic and operative characteristics of

the patients were compared and represented (Table 2).

Ultrasonography ndings did not aect the chances of

conception (p=0.86). Majority of patients in both categories

had unilateral endometriomas (15/34 vs 15/16) followed

by bilateral endometriomas (9/34 vs 3/16). e mean

score of endometriosis in the conceived patients was

signicantly lower compared to the patients who failed

to conceive spontaneously (16.94±10.58 vs 38.25±26.93,

p=0.00). A similar observation was also noted for stage

of endometriosis. e proportion of study participants

getting pregnant at the end of 6 months was higher

in patients with lower stages of endometriosis than

those with the higher stage (p=0.00). All the participants

with stage-II endometriosis conceived and 80% with

stage-I endometriosis conceived at the end of 6 months.

Similarly, 76.7% of patients with stage-III endometriosis

conceived but, none with stage-IV endometriosis. Out of

24 patients undergoing unilateral cystectomy, 15 (62.5%)

patients conceived. Five out of 6 patients conceived

where adhesiolysis was done. Successful conception

was observed in all four patients aer fulguration of

endometriotic spots. However, there was no statistically

signicant association between the type of intervention

done and the conception status of the study subjects

(p=0.35).

DISCUSSION

In our study, 74% of patients with laparoscopically

conrmed endometriosis had a preoperative diagnosis of

endometriosis through transvaginal 2D ultrasonography

indicating 74% sensitivity for detection of endometriosis.

A similar observation was noted in a prospective study

where transvaginal ultrasonography had a sensitivity

of 75% for detection of endometrioma.

About 68%

of the participants conceived spontaneously following

laparoscopic intervention within 6 months. A similar

spontaneous pregnancy rate (65%) was also observed

in a study by Fuchs F 2007, over a follow-up period of

8.5 months. In this study, assisted conceptions were also

observed.

e follow-up period also varied from one

to two years in dierent studies.

15,16

TABLE 1. Comparison of general characteristics.

Characteristics Status of conception in 6 months Total (n=50) p-value

Not Conceived Conceived

n=16, (%) n=34, (%)

Age (Years) 30.18 ± 3.35 27.82 ± 4.41 28.58 ± 4.21 0.06

(Mean ± SD)

Year of infertility (Years) 3.28 ± 1.46 3.35 ± 1.45 3.33 ± 1.43 0.88

(Mean ± SD)

Infertility type

 Primary 10(29.4) 24(70.5) 34 0.56

 Secondary 6(37.5) 10(62.5) 16

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TABLE 2. Comparison of USG and Operative characteristics.

Characteristics Category Status of conception in 6 months Total n=50 p-value

No Conceived Conceived

n=16 (%) n=34 (%)

 B/Lchocolatecyst 3(25) 9(75) 12 0.63

 Leftchocolatecyst 4(36.4) 7(63.6) 11

USG Findings Myoma 1(33.3) 2(66.7) 3

 Noabnormality 2(20) 8(80) 10

 Rightchocolatecyst 5(38.5) 8(61.5) 13

 Righttubo-oyarianmass, 1(100) 0 1

Score of endometrioses (Mean ± SD) 38.25 ± 26.93 16.94 ± 10.58 23.76 ± 19.95 0.00

I 2 (20.0%) 8 (80.0%) 10 0.00

Endometriosis stage

II 0 (0.0%) 3 (100.0%) 3

III 7 (23.3%) 23 (76.7%) 30

IV 7 (100.0%) 0 (0.0%) 7

 Unilateral 09(37.5%) 15(62.5%) 24 0.35

 Cystectomy

 B/LCystectomy 5(41.6%) 7(58.3%) 12

 Adhesiolysis 1(16.6%) 5(83.3%) 6

Interventions done Fulguration 0(0.0%) 4(100%) 4

 Myomectomywith 1(25%) 2(75%) 3

 adhesiolysis

 Rightoophorectomy 0(0.0%) 1(100%) 1

 withadhesiolysis

Baseline characteristics of patients with and without

successful spontaneous conception were similar. ere

was no dierence in the age of females, type of infertility,

duration of infertility and preoperative ultrasonographic

ndings making the comparison more logical and acceptable.

is eliminates the probability of bias due to eect of

major confounders like age on pregnancy rate.

In the present study, pregnancy rate aer laparoscopy

was lower in patients higher r-AFS score and advanced

stages of endometriosis. is reects the adverse eect of

severity of endometriosis on the probability of spontaneous

conception aer therapeutic surgery. e implications of

this study will help the clinicians to counsel the patients with

advanced endometriosis regarding the poor prognosis for

spontaneous conception following laparoscopy. It agrees

with the study by Fuchs et al. 2007 where the incidence

of pregnancy was signicantly higher in patients with

stage I /II disease than stage III/IV (89% vs 56%). In

contrast, staging and scoring of endometriosis, had no

association with pregnancy rate in the study by Porpora

et al. 2002.

In that study, adnexal adhesion and tubal

condition inuenced the chances of conception.

e current study was undertaken at a single centre.

e study followed up only cases with spontaneous

conception and excluded methods of assisted reproduction

as in the later cases, direct benet of laparoscopic surgery

on chances of conception would have been dicult to

demonstrate. e sample size of the study was limited

to only 50 patients and the follow-up duration of study

participants was only 6 months which was less as compared

to other studies of this nature. e limited-time period

for follow-up is considered for the study as this is part

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of a post-graduate dissertation that has to be completed

in a limited time frame. us, there is a need for further

studies with a larger sample size and long duration follow-

up to support the observations of our study and ensure

generalisability of the study for the overall population

of infertile females with endometriosis.

CONCLUSION

Laparoscopy helps in the diagnosis of pelvic

endometriosis especially in patients without ultrasonographic

abnormalities. In infertile females with endometriosis

undergoing laparoscopy, individualized surgical interventions

are warranted for better fertility outcomes. Successful

spontaneous conception following surgery depends

on the r-AFS score, and stage of endometriosis. Lower

score and early stage of endometriosis are associated

with higher chances of conception.

Ethical consideration: e study was approved by the

Institutional ethical committee (IEC).

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