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Histopathological changes in gall bladder mucosa in relation to the number, and size of gallstones, and analysis of the findings in the context of age distribution of the patients: A perspective

  • Received : 2023.01.17
  • Accepted : 2023.04.05
  • Published : 2023.08.31

Abstract

Backgrounds/Aims: To study histopathological changes in gall bladder mucosa in cholelithiasis patients, and analyse their relation to the number and size of gallstones. These findings were evaluated in the context of age distribution of the study population. Methods: One hundred cases of cholecystectomy were part of the study, which was conducted in collaboration with the pathology department. The time period of the study was January 2020 to June 2021. Results: Maximum cases had multiple stones (69.0%), while one third cases (31.0%) had solitary stones. While initial univariate analysis showed age (odds ratio [OR], 6.882; p = 0.043), gallstone number (OR, 9.1; p = 0.050), gallstone size (OR, 17.111; p = 0.013), and duration of symptom (OR, 34.125; p = 0.001) to be significant risk factors associated with gallbladder carcinoma, multivariate analysis found none of these variables to be significant. However, conditional multivariate analysis for the duration of symptom (p = 0.008; OR, 21.118) yielded significant p-value. With histopathological diagnoses, 5% of cases had gallbladder cancer. Conclusions: This study shed light on the rising incidence of cholelithiasis in the young population and the high rate of gallbladder carcinoma in Punjab, India. Although gall stone characteristics (size, number) and patient age appeared to be significant risk factors when their individual relation with gallbladder carcinoma was studied, multivariate analysis, could not prove that. Conditional multivariate analysis showed the duration of symptom to be the only significant risk factor associated with gallbladder carcinoma. Further research with larger sample size is needed to study the rising incidence of gallbladder carcinoma, and the risk factors associated with it.

Keywords

References

  1. Rakesh Tendon. Diseases of gallbladder and biliary tract. In: Siddharth N Shah, ed. API text of Medicine. 7th ed. Association physicians india, 2003:642-644. 
  2. Narang S, Goyal P, Bal MS, Bandlish U, Goyal S. Gall stones size, number, biochemical analysis and lipidogram-an association with gall bladder cancer: a study of 200 cases. Int J Cancer Ther Oncol 2014;2:0203103. 
  3. Bansal A, Akhtar M, Bansal AK. A clinical study: prevalence and management of cholelithiasis. International Surgery Journal. 2014;1:134-9.  https://doi.org/10.5455/2349-2902.isj20141105
  4. Tyagi SP, Tyagi N, Maheshwari V, Ashraf SM, Sahoo P. Morphological changes in diseased gall bladder: a study of 415 cholecystectomies at Aligarh. J Ind Med Assoc 1992;90:178-181. 
  5. Koebnick C, Smith N, Black MH, Porter AH, Richie BA, Hudson S, et al. Pediatric obesity and gallstone disease: results from a cross-sectional study of over 510,000 youth. J Ped Gastroenterol Nutr 2012;55:328-333.  https://doi.org/10.1097/MPG.0b013e31824d256f
  6. Shafique MS, Ahmad R, Ahmad SH, Hassan SW, Khan JS. Gallstones in young population. J Ulutas Med 2018;4:131-138.  https://doi.org/10.5455/umj.20180324011035
  7. Rakesh BH, Rajendra GC. A prospective clinicopathological study of 50 cases of chronic calculous cholecystitis in the local population. Journal of Evolution of Medical and Dental Sciences 2013;2:6706-6717.  https://doi.org/10.14260/jemds/1197
  8. Khan MK, Jalil MA, Khan MS. Oral contraceptives in gall stone diseases. Mymensingh Med J 2007;16(2 Suppl):S40-45. 
  9. Graewin SJ, Kiely JM, Lee KH, Svatek CL, Nakeeb A, Pitt HA. Nonobese diabetic mice have diminished gallbladder motility and shortened crystal observation time. J Gastrointe Surg 2004;8:824-829;discussion 829-830.  https://doi.org/10.1016/j.gassur.2004.06.014
  10. Agunloye AM, Adebakin AM, Adeleye JO, Ogunseyinde AO. Ultrasound prevalence of gallstone disease in diabetic patients at Ibadan, Nigeria. Nigerian J Clin Pract 2013;16:71-75.  https://doi.org/10.4103/1119-3077.106770
  11. Gupta A, Gupta S, Siddeek RA, Chennatt JJ, Singla T, Rajput D, et al. Demographic and clinicopathological profile of gall bladder cancer patients: study from a tertiary care center of the Sub-Himalayan region in Indo-Gangetic Belt. J Carcinog 2021;20:6. 
  12. Rathore A, Pathak A, Ranjan S, Sud R, Shivshankara MS, Pandaya T, et al. A clinicoepidemiological and management profile of metastatic carcinoma gallbladder in the northeast part of Indian patients in a tertiary care center. J Cancer Res Ther 2022;18(Supplement):S428-S433.  https://doi.org/10.4103/jcrt.JCRT_1213_20
  13. Batra Y, Pal S, Dutta U, Desai P, Garg PK, Makharia G, et al. Gallbladder cancer in India: a dismal picture. J Gastroenterol Hepatol 2005;20:309-314.  https://doi.org/10.1111/j.1440-1746.2005.03576.x
  14. Dutta U, Garg PK, Kumar R, Tandon RK. Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder. Am J Gastroenterol 2000;95:784-787.  https://doi.org/10.1111/j.1572-0241.2000.01860.x
  15. Valdivieso V, Covarrubias C, Siegel F, Cruz F. Pregnancy and cholelithiasis: pathogenesis and natural course of gallstones diagnosed in early puerperium. Hepatology 1993;17:1-4.  https://doi.org/10.1002/hep.1840170102
  16. Nakagaki M, Nakayama F. Effect of female sex hormones on lithogenicity of bile. Jap J Surg 1982;12:13-18.  https://doi.org/10.1007/BF02469009
  17. Dutta U, Nagi B, Garg PK, Sinha SK, Singh K, Tandon RK. Patients with gallstones develop gallbladder cancer at an earlier age. Eur J Cancer Prev 2005:14:381-385.  https://doi.org/10.1097/00008469-200508000-00011
  18. Konstantinidis IT, Deshpande V, Genevay M, Berger D, Fernandez-del Castillo C, Tanabe KK, et al. Trends in presentation and survival for gallbladder cancer during a period of more than 4 decades: a single-institution experience. Arch Surg 2009;144:441-447.  https://doi.org/10.1001/archsurg.2009.46
  19. Gupta P, Agarwal A, Gupta V, Singh PK, Pantola C, Amit S. Expression and clinicopathological significance of estrogen and progesterone receptors in gallbladder cancer. Gastrointest Cancer Res 2012;5:41-47. 
  20. Goyal S, Singla S, Duhan A. Correlation between gallstones characteristics and gallbladder mucosal changes: a retrospective study of 313 patients. Clin Cancer Investig J 2014;3:157-161.  https://doi.org/10.4103/2278-0513.130215
  21. Nair B, Malhotra K, Kaundal AK, Malhotra A. A study of chemical composition of gall stones in a tertiary care hospital. J Evol Med Dent Sci 2020;9:2422-2427.  https://doi.org/10.14260/jemds/2020/527
  22. Alshoabi S. Gallstones: site, size, number, prevalence and complications by ultrasonography. Int J Med Ima 2016;4:52-56. 
  23. Mathur SK, Duhan A, Singh S, Aggarwal M, Aggarwal G, Sen R, et al. Correlation of gallstone characteristics with mucosal changes in gall bladder. Trop Gastroenterol 2012;33:39-44.  https://doi.org/10.7869/tg.2012.6
  24. Khanna R, Chansuria R, Kumar M, Shukla HS. Histological changes in gallbladder due to stone disease. Indian J Surg 2006;1;68:201-204. 
  25. Seretis C, Lagoudianakis E, Gemenetzis G, Seretis F, Pappas A, Gourgiotis S. Metaplastic changes in chronic cholecystitis: implications for early diagnosis and surgical intervention to prevent the gallbladder metaplasia-dysplasia-carcinoma sequence. J Clin Med Res 2014;6:26-29.  https://doi.org/10.4021/jocmr1689w
  26. Phadke PR, Mhatre SS, Budukh AM, Dikshit RP. Trends in gallbladder cancer incidence in the high-and low-risk regions of India. Ind J Med Paediatr Oncol 2019;40:90-3.  https://doi.org/10.4103/ijmpo.ijmpo_164_18
  27. Nandakumar A. National cancer registry programme. Consolidated report of the population based cancer registries. Indian Council of Medical Research, 1990:96. 
  28. Yaqub F. Punjab's cancer awareness campaign. Lancet Oncol 2013;14:e92. 
  29. Aggarwal R, Manuja KA, Aditya K, Singh GP. Pattern of cancer in a tertiary care hospital in Malwa region of Punjab, in comparison to other regions in India. J Clin Diagn Res 2015;9:XC05-XC07.  https://doi.org/10.7860/JCDR/2015/11171.5685
  30. Budukh AM, Chaudhary D, Sancheti S, Dora T, Goel AK, Singla A, et al. Determinants of completion of cancer directed treatment: an experience from a rural cancer centre, Sangrur, Punjab state, India. Ecancermedicalscience 2021;15:1313. 
  31. Hundal R, Shaffer EA. Gallbladder cancer: epidemiology and outcome. Clin Epidemiol 2014;6:99-109.  https://doi.org/10.2147/CLEP.S37357
  32. Mishra G, Conway JD. Endoscopic ultrasound in the evaluation of radiologic abnormalities of the liver and biliary tree. Current Gastroenterol Rep 2009;11:150-154.  https://doi.org/10.1007/s11894-009-0023-5
  33. Siegel RL, Torre LA, Soerjomataram I, Hayes RB, Bray F, Weber TK, et al. Global patterns and trends in colorectal cancer incidence in young adults. Gut 2019;68:2179-2185.  https://doi.org/10.1136/gutjnl-2019-319511
  34. Roa I, Ibacache G, Roa J, Araya J, de Aretxabala X, Munoz S. Gallstones and gallbladder cancer-volume and weight of gallstones are associated with gallbladder cancer: a case-control study. J Surg Oncol 2006;93:624-628.  https://doi.org/10.1002/jso.20528
  35. Diehl AK. Gallstone size and the risk of gallbladder cancer. JAMA 1983;250:2323-2326.  https://doi.org/10.1001/jama.1983.03340170049027
  36. Lowenfels AB, Walker AM, Althaus DP, Townsend G, Domellof L. Gallstone growth, size, and risk of gallbladder cancer: an interracial study. Int J Epidemiol 1989;18:50-54.  https://doi.org/10.1093/ije/18.1.50
  37. Csendes A, Becerra M, Rojas J, Medina E. Number and size of stones in patients with asymptomatic and symptomatic gallstones and gallbladder carcinoma: a prospective study of 592 cases. J Gastrointest Sur 2000;4:481-485.  https://doi.org/10.1016/S1091-255X(00)80090-6
  38. Andrea C, Enzo A. Cholesterol gallstones larger than 3 cm appear to be associated with gallbladder cancer: identification of a high risk group of patients that could benefit from preventive cholecystectomy. Ann Surg 2016;263:e56. 
  39. Vitetta L, Sali A, Little P, Mrazek L. Gallstones and gall bladder carcinoma. Aust N Z J Surg 2000;70:667-673.  https://doi.org/10.1046/j.1440-1622.2000.01926.x
  40. Moerman CJ, Lagerwaard FJ, Bueno de Mesquita HB, van Dalen A, van Leeuwen MS, Schrover PA. Gallstone size and the risk of gallbladder cancer. Scand J Gastroenterol 1993;28:482-486.  https://doi.org/10.3109/00365529309098253
  41. Verma GR, Bose SM, Wig JD. Pericholecystic adhesions in single v multiple gallstones and their consequences for laparoscopic cholecystectomy. J Laparoendoscop Adv Surg Tech A 2001;11:275-27 9.  https://doi.org/10.1089/109264201317054555
  42. Mukhopadhyay S, Landas SK. Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens. Arch Pathol Lab Med 2005;129:386-390.  https://doi.org/10.5858/2005-129-386-PPOGDA
  43. Rao I, Araya JC, Valiaseca M, De Aretxabala X, Riedemann P, Endoh K, et al. Preneoplastic lesions and gallbladder cancer: an estimate of the period required for progression. Gastroenterology 1976;111 :232-236.  https://doi.org/10.1053/gast.1996.v111.pm8698204
  44. Mishra K, Behari A, Shukla P, Tsuchiya Y, Endoh K, Asai T, et al. Risk factors for gallbladder cancer development in northern India: a gallstones-matched, case-control study. Indian J Med Res 2021;154:699-706.  https://doi.org/10.4103/ijmr.IJMR_201_19
  45. Serra I, Calvo A, Baez S, Yamamoto M, Endoh K, Aranda W. Risk factors of gallbladder cancer. An international collaborative case-contol study. Cancer 1996;78:1515-1517.  https://doi.org/10.1002/(SICI)1097-0142(19961001)78:7<1515::AID-CNCR21>3.0.CO;2-1
  46. Scott TE, Carroll M, Cogliano FD, Smith BF, Lamorte WW. A case-control assessment of risk factors for gallbladder carcinoma. Dig Dis Sci 1999;44:1619-1625.  https://doi.org/10.1023/A:1026675329644
  47. Sharma M, Singh R. Carcinoma of the gall bladder: 8 year experience from a tertiary care centre, Punjab, India. International Surgery Journal. 2019 May 28;6:1912-6.  https://doi.org/10.18203/2349-2902.isj20192059
  48. Narula MK. Chandigarh: hope for gallbladder cancer patients not eligible for surgery [Internet]. 2023 [cited Mar 19]. Available from: https://www.hindustantimes.com/cities/chandigarh-news/chandigarhhope-for-gallbladder-cancer-patients-not-eligible-for-surgery-101679182426962.html.