Effect of Thermoablation with pH Change on Giant Cell Tumor of Bone: An In Vitro Study

Adisak Wongkajornsilpa; Rapin Phimolsarnti; Chandhanarat Chandhanayingyong; Saranatra Waikakul; Pojchong Chotiyarnwong

doi:10.33192/smj.v76i6.266988

Authors

Adisak Wongkajornsilpa Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Rapin Phimolsarnti Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Chandhanarat Chandhanayingyong Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Saranatra Waikakul Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Pojchong Chotiyarnwong Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand

DOI:

https://doi.org/10.33192/smj.v76i6.266988

Keywords:

Thermoablation, pH, giant cell tumor of bone, in vitro

Abstract

Objective: To evaluate the effect of pH on the apoptosis and necrosis rate of giant cell tumor of bone (GCTB) cells during thermoablation.

Materials and Methods: GCTB tissues were collected from 15 patients. Cells were incubated at 25 ºC , 37 ºC, 45 ºC, and 50 ºC, with the variation of the pH at 4.7, 5.6, 6.5, 7.4, 8.3, and 9.2 for 20 minutes (in triplicate for each condition). The effect of thermoablation and pH variation on GCTB cells death was evaluated by staining with Annexin V-FITC and propidium iodide solution after 3 days of incubation. The fluorescence intensity was evaluated by flow cytometry to evaluate the percentage of tumor cells death.

Results: Thermoablation alone increased the percentage of tumor cells death. However, when combined with an increase in pH, the percentage of GCTB cells death increased more. Conversely, lowering the pH did not increase the tumor cells death compared with thermoablation treatment alone, while changing the pH alone had only a low effect on increasing the percentage of GCTB cells death.

Conclusion: Thermoablation the temperature between 37 ºC and 45 ºC plus a pH level slightly higher than physiologic pH (between 7.4 and 8.3) for 20 minutes increased GCTB cell death. However, determining the optimum condition to kill tumor cells while causing minimal harm to normal cells requires more study.

References

Athanasou NA, Bansal M, Forsyth R, Reid RP, Sapi Z. Giant cell tumour of bone. In: Fletcher CD, Bridge JA, Hogendoorn PC, editors. WHO Classification of Tumours of Soft Tissue and Bone: Lyon, France: IARC Press; 2013. p. 321-4.

Cowan RW, Singh G. Giant cell tumor of bone: a basic science perspective. Bone. 2013;52(1):238-46.

Vaishya R, Pokhrel A, Agarwal AK, Vijay V. Current status of bone cementing and bone grafting for giant cell tumour of bone: a systemic review. Ann R Coll Surg Engl. 2019;101(2):79-85.

Liu YP, Li KH, Sun BH. Which treatment is the best for giant cell tumors of the distal radius? A meta-analysis. Clin Orthop Relat Res. 2012;470(10):2886-94.

Chakarun CJ, Forrester DM, Gottsegen CJ, Patel DB, White EA, Matcuk GR, Jr. Giant cell tumor of bone: review, mimics, and new developments in treatment. Radiographics. 2013;33(1):197-211.

Szendröi M. Giant-cell tumour of bone. J Bone Joint Surg Br. 2004;86(1):5-12.

Jones KB, DeYoung BR, Morcuende JA, Buckwalter JA. Ethanol as a local adjuvant for giant cell tumor of bone. Iowa Orthop J. 2006;26:69-76.

Quint U, Müller RT, Müller G. Characteristics of phenol. Instillation in intralesional tumor excision of chondroblastoma, osteoclastoma and enchondroma. Arch Orthop Trauma Surg. 1998;117(1-2):43-6.

Namazi H. Botulinum toxin: a novel adjuvant for giant cell tumor. Ann Surg Oncol. 2008;15(7):2066-7.

Namazi H. Raloxifene can reduce giant cell tumor recurrence: a new adjuvant therapy. Ann Surg Oncol. 2008;15(6):1783-4.

Lewis VO, Wei A, Mendoza T, Primus F, Peabody T, Simon MA. Argon beam coagulation as an adjuvant for local control of giant cell tumor. Clin Orthop Relat Res. 2007;454:192-7.

Waikakul S, Asavamongkolkul A, Phimolsarnti R. Use of warm Ringer's lactate solution in the management of locally advanced giant cell tumor of bone. Int J Clin Oncol. 2016;21(1):177-85.

van der Heijden L, van der Geest IC, Schreuder HW, van de Sande MA, Dijkstra PD. Liquid nitrogen or phenolization for giant cell tumor of bone?: a comparative cohort study of various standard treatments at two tertiary referral centers. J Bone Joint Surg Am. 2014;96(5):e35.

Ruggieri P, Mavrogenis AF, Ussia G, Angelini A, Papagelopoulos PJ, Mercuri M. Recurrence after and complications associated with adjuvant treatments for sacral giant cell tumor. Clin Orthop Relat Res. 2010;468(11):2954-61.

Tsukamoto S, Mavrogenis AF, Kido A, Errani C. Current Concepts in the Treatment of Giant Cell Tumors of Bone. Cancers (Basel). 2021;13(15).

Schoutens C, Verspoor FG. Heat treatment for giant cell tumors of bone: A systematic review. J Orthop Surg (Hong Kong). 2023;31(3):10225536231202157.

Balke M, Campanacci L, Gebert C, Picci P, Gibbons M, Taylor R, et al. Bisphosphonate treatment of aggressive primary, recurrent and metastatic Giant Cell Tumour of Bone. BMC Cancer. 2010;10:462.

van der Heijden L, Dijkstra PDS, Blay JY, Gelderblom H. Giant cell tumour of bone in the denosumab era. Eur J Cancer. 2017;77:75-83.

Shi M, Chen L, Wang Y, Wang W, Zhang Y, Yan S. Effect of bisphosphonates on local recurrence of giant cell tumor of bone: a meta-analysis. Cancer Manag Res. 2019;11:669-80.

Setsu N, Kobayashi E, Asano N, Yasui N, Kawamoto H, Kawai A, et al. Severe hypercalcemia following denosumab treatment in a juvenile patient. J Bone Miner Metab. 2016;34(1):118-22.

Uday S, Gaston CL, Rogers L, Parry M, Joffe J, Pearson J, et al. Osteonecrosis of the Jaw and Rebound Hypercalcemia in Young People Treated With Denosumab for Giant Cell Tumor of Bone. J Clin Endocrinol Metab. 2018;103(2):596-603.

Errani C, Tsukamoto S, Mavrogenis AF. How safe and effective is denosumab for bone giant cell tumour? Int Orthop. 2017;41(11):2397-400.

Phimolsarnti R, Charoenlap C, Ariyaboonsiri B, Wongkajornsilpa A, Waikakul S. In vitro effects of thermoablation on apoptosis of giant cell tumor of bone: a preliminary report. J Med Assoc Thai. 2012;95 Suppl 9:S138-45.

Pimolsanti R, Wongkajornsilpa A, Chotiyarnwong P, Asavamongkolku A, Waikakul S. Effects of thermoablation with or without caffeine on giant cell tumour of bone. J Orthop Surg (Hong Kong). 2015;23(1):95-9.

Matsuyama S, Reed JC. Mitochondria-dependent apoptosis and cellular pH regulation. Cell Death Differ. 2000;7(12):1155-65.

Matsubara T, Diresta GR, Kakunaga S, Li D, Healey JH. Additive Influence of Extracellular pH, Oxygen Tension, and Pressure on Invasiveness and Survival of Human Osteosarcoma Cells. Front Oncol. 2013;3:199.

Kok HP, Cressman ENK, Ceelen W, Brace CL, Ivkov R, Grüll H, et al. Heating technology for malignant tumors: a review. Int J Hyperthermia. 2020;37(1):711-41.

Browning JA, Wilkins RJ. Mechanisms contributing to intracellular pH homeostasis in an immortalised human chondrocyte cell line. Comp Biochem Physiol A Mol Integr Physiol. 2004;137(2):409-18.

Choi JUA, Kijas AW, Lauko J, Rowan AE. The Mechanosensory Role of Osteocytes and Implications for Bone Health and Disease States. Front Cell Dev Biol. 2021;9:770143.

Nordström T, Rotstein OD, Romanek R, Asotra S, Heersche JN, Manolson MF, et al. Regulation of cytoplasmic pH in osteoclasts. Contribution of proton pumps and a proton-selective conductance. J Biol Chem. 1995;270(5):2203-12.

Cheng H, Clymer JW, Po-Han Chen B, Sadeghirad B, Ferko NC, Cameron CG, et al. Prolonged operative duration is associated with complications: a systematic review and meta-analysis. J Surg Res. 2018;229:134-44.