|Year : 2018 | Volume
| Issue : 1 | Page : 3-6
Carcinoma of gall bladder: Demographic and clinicopathological profile in Indian patients
AP Dubey1, Kavita Rawat1, Nikhil Pathi2, S Viswanath2, Anvesh Rathore2, Rajan Kapoor2, Abhishek Pathak2
1 Department of Medical Oncology and Haematology, Shanti Mukand Hospital, New Delhi, India
2 Department of Medical Oncology and Haematology, Army Hospital, Research and Referral, New Delhi, India
|Date of Web Publication||23-Mar-2018|
Department of Medical Oncology, Army Hospital Research and Referral, Delhi Cantt, New Delhi - 110 010
Source of Support: None, Conflict of Interest: None
Aim of the Study: The aim of this study is to evaluate the demographic and clinicopathological profile of the patients with gallbladder cancer (GBC). Materials and Methods: A total of 68 diagnosed cases of GBC were taken in the study during the study period from January 2016 to December 2017. A detail questionnaire was filled through the counseling to take demographic profile including socioeconomic status, nonclinical characteristics, dietary, and other risk factors apart from clinicopathological profile of patients. Results: We found most of the patients were females with median age 51.8 years. More than half of them were postmenopausal (56.60%), and high parity was seen in 39.62% of females. Obesity was associated factor mainly in females (28/53), and none of the males were obese. Nearly 83.82% (57/68) of patients had advanced stage disease, with metastatic disease in 72.06% (49/68) patients. Majority of the patients had at least two sites of metastasis (73.47%), with liver (57.14%), omentum (40.82%), and nonregional lymph nodes (53.06%) being common sites of dissemination. Bony metastasis, being rare in literature, was found in 6 (12.24%) of patients, most of them developed it later during the disease course. Conclusion: Majority of the patients was female within the age group of 41–60 years, associated with gallstones and had advanced disease. We did not find greater impact of diet on the incidence as vegans and nonvegans were almost equally divided in our study. A high index of suspicion and health education seems to be the only answers available for early detection and improvement of survival.
Keywords: Clinicopathological factors, demographic profiles, gallbladder carcinoma, risk factors
|How to cite this article:|
Dubey A P, Rawat K, Pathi N, Viswanath S, Rathore A, Kapoor R, Pathak A. Carcinoma of gall bladder: Demographic and clinicopathological profile in Indian patients. Oncol J India 2018;2:3-6
|How to cite this URL:|
Dubey A P, Rawat K, Pathi N, Viswanath S, Rathore A, Kapoor R, Pathak A. Carcinoma of gall bladder: Demographic and clinicopathological profile in Indian patients. Oncol J India [serial online] 2018 [cited 2018 Apr 25];2:3-6. Available from: http://www.ojionline.org/text.asp?2018/2/1/3/228322
| Introduction|| |
Gallbladder cancer (GBC) is the most common biliary tract malignancy accounting for 80%–95% of the cases. Its incidence is significantly higher in the Indian population as compared to global statistics altogether. It has unique, significant and striking gender, geographic, and ethnic variation in its incidence worldwide. The highest rates of GBC are found in northern part of India and Pakistan, East Asia (Korea and Japan), Eastern Europe, and South America (Columbia and Chile). Rates may vary even within a region or a country and genders of those regions. GBC is the most common gastrointestinal malignancy in women in northern part of India. Incidence of GBC in females in northern part of India is as high as 9/100,000 per year as compared to as low as 1/100,000 per year in western and southern regions.
Most of the patients with GBC are diagnosed at an advanced stage and have dismal prognosis. Median overall survival after a diagnosis of advanced disease is around 6 months with 5-year survival rate of around 5%. Diagnosis at an advanced stage may be attributed to the fact that the symptoms mimic that of gallstone disease or acid peptic disease that are often neglected, complicated by difficulty in diagnosis of early GBC at an early stage with routine investigations such as abdominal ultrasonography.
Although various epidemiological reviews have reported that GBC is rare in India, with incidence rates of 0.5 and 1.3/100000 population in men and women, respectively, reported from Mumbai in Western India; however, the incidence rates are as high as 9/100,000 in northern part of India. In Delhi, GBC (incidence rate 6.6/100,000) is the fourth most common cancer (following cervix, breast and ovary) and the most common gastrointestinal cancer in women (more common than esophagus, stomach, and colon). In Jammu, GBC is reported as the third most common cancer (after cervix and breast) in women. In Lucknow, GBC is reported the most common cause of malignant obstructive jaundice. GBC is prevalent in other countries in the northern part of the Indian subcontinent including Pakistan and Bangladesh.
| Materials and Methods|| |
We studied demographic characteristics, risk factors, and clinical profile of 68 patients diagnosed as GBC from January 2016 to December 2017. The demographic characteristics include age, sex, and socioeconomic status. Nonclinical risk factor includes parity, obesity, menstrual status, and use of contraceptive pills among premenopausal female. Diagnosis of gallstone, serum level of triglycerides, total cholesterol, and diabetes were taken as clinical risk factor. Use of vegetarian diet and nonvegetarian diet was included in dietary habit. Clinical profile included performance status, presenting symptoms, duration of symptoms, presence of jaundice, stage and extent of disease, number and sites of metastasis, and pathological features.
Interview technique was used to collect the information about demographic characteristics, nonclinical characteristics, and dietary habit. A questionnaire developed specially for the study was used for the interview. Socioeconomic status was determined as per the modified Kuppuswamy's socioeconomic scale. Documentation of clinical features was done by history, physical examination, and imaging features. GBC and stone were confirmed by the ultrasound and computed tomography (CT) scan report.
| Results|| |
The demographic profile of patients is illustrated in [Table 1]. Majority of the patients (88.23%) were more than 40 years of age. All the patients belonged to northern and northeastern (Bihar) part of India, with the majority of patients (29.41%) from Uttar Pradesh followed by Bihar (20.59%) and Delhi (20.59%). There were 53 females and 15 males in the study. As most of the subjects were female, we also focused on the menopausal status, parity, and use of oral contraceptive pills (OCPs) among premenopausal females as nonclinical risk factors. Postmenopausal status was present in 30 (56.6%) females whereas the rest 23 was premenopausal.
[Table 2] illustrates the clinicopathological profile of patients. Nearly 57(83.82%) patients in study group had advanced disease (Stage 3 or 4) at presentation. The pain was the most common symptom, present in all patients studied. Jaundice was present in half of the patients (51.47%). Interventional biliary drainage was required in 14.70% of the patients. Poorly differentiated adenocarcinoma was the predominant histology seen (41.18%). Liver, nonregional lymph nodes, and omentum were the common sites of metastasis. Majority of the stage 4 patients had metastases to at least two organs (73.47%).
| Discussion|| |
In this study, we evaluated demographic and clinicopathological profile of 68 patients of gallbladder carcinoma. Gallbladder carcinoma is relatively infrequent disease, with marked geographic, ethnic, and socioeconomic variation. All patients in our study belonged to northern part of India, with majority from Uttar Pradesh and Delhi. The incidence of GBC increases with age, and the median age at diagnosis is 51.8 years in the present study. In the previous studies, the mean age of GBC at diagnosis is 64–69.4 years.,, The median age of presentation was 67 years in a Memorial Sloan–Kettering report of 435 GBC patients. The incidence of GBC is more in female (2–6 times) in comparison to male worldwide, especially in northern part of India, Pakistan, and in American-Indian females, and in the present study, the female to male ratio is 3.53:1., In the present study, 77.94% of the patients were females supporting the literatures. In northern part of India, GBC is the most common gastrointestinal tract malignancy among women and also, the most common cause of malignant surgical obstructive jaundice. In the present study, 75% (51) of patients belonged to either lower-middle or lower socioeconomic class, which commensurate with the study by Dwivedi et al. where 67.07% of the patients are in the same group.
The process of carcinogenesis in GBC follows a consequence of metaplasia followed by dysplasia, carcinoma in situ, and invasive cancer. Various risk factors have been implicated in the pathogenesis of GBC which includes female sex, gallstones, obesity, diabetes mellitus, and infections among which cholelithiasis is most common associated factor, frequently associated with GBC in 69%–85% cases independent of age and sex. Gallstones cause local mucosal irritation and chronic inflammation resulting local production of carcinogens, such as secondary bile acids and eventually may results in carcinogenesis after a long duration. Nervi et al. reported an increasing risk of GBC with increasing age in women with gallstones. We found the history of gall stones in 61.76% patients (42/68), of which 29/42 (69.05%) patients were more than 50 years of age. Although the mechanism underlying this association is unclear, both gallstones and GBC predominate in females and are associated with obesity, multiparity, and use of OCPs, implicating alteration of endogenous estrogen role in the pathogenesis of gallstones and GBC.,, In the present study, 41.18% (28/68) of patients were obese, and all were female, with high parity and history of OCP use noticed in 39.62% (21/53) and 37.74% (20/53) females, respectively. Diabetes is a risk factor for stone formation and the risk of developing GBC in diabetes mellitus exists, even in the absence of gallstones. In the present study, 14.71% of the patients are having diabetes mellitus.
The previous results showed that nonvegetarians (such as red meat and consumption of carcinogenic impurities in mustard oil) were more prone to GBC rather than vegetarians., However, in our study, we had almost equal number of vegetarians (32/68) and nonvegetarians (36/68), thus implicating that role of other important risk factors is more important than dietary factors alone in pathogenesis of GBC.
Deeper invasion of the tumor increases the metastatic rates such as progression from T2 to T4 tumors increases the possibility of distant metastasis from 16% to 79% and nodal involvement from 33% to 69%. The prognosis of patients with GBC is dismally poor, as majority of them presents with advanced disease. The presentation at an advanced stage can be attributed to multiple factors including lack of knowledge and education in patients predominantly belonging to lower class, inability to differentiate symptoms of early GBC from those of gallstone disease and poor response to available chemotherapy options. In the present study, 16.18% of the patient had an early stage disease (Stage 1 and 2), and the rest 83.82% of the patients had advanced/metastatic disease. A previous Indian study by Batra et al. has reported slightly lower incidence of early-stage disease (approximately 5%) in comparison to the present study, and the rest 95% patients either locally advanced or metastatic. Early stage GBC is typically diagnosed incidentally because of inflammatory symptoms which are related to coexistence of cholelithiasis or cholecystitis. A review of the literature has reported 0.19% to 3.3% of the patients who underwent cholecystectomies for presumed benign diseases were found to have carcinomas of the gallbladder.,,
In the present study, 41.18% and 35.29% of the cases are poorly and moderately differentiated, respectively, and supported by Lau et al., where it was 42.5% and 38.2%, respectively. GBC metastasizes more commonly to liver, lymph nodes, and peritoneum. Among the metastatic sites, liver and nonregional lymph nodes were the most common sites of metastasis in our study, seen in 57.14% (28/49) and 53.06% (26/49) of patients, respectively. Omental deposits and lung involvement were noticed in 20 (40.82%) and 14 (28.57%) of patients, respectively. Skeletal metastases in carcinoma gallbladder are very rare, with only few case reports of bone metastasis in carcinoma gall bladder at the time of presentation. We had 06/49 (12.24%) patients with skeletal metastasis, with only one patient presenting it at onset, the rest five patients developed bony disease after progression on chemotherapy. One autopsy series has reported about 10% incidence for skeletal metastasis, which may indicate that the carcinoma gallbladder does metastasize to bone, perhaps in advanced stages.
| Conclusion|| |
Although previous studies have documented its incidence more so in postmenopausal women, aged 50–60 years, we found substantial portion of patients (45.59%) below 50 years of age, and premenopausal (43.40%). We did not find greater impact of diet on the incidence as vegans and nonvegans were almost equally divided in our study. The limited number of studies and their contradictory results give rise to a need of more studies in this direction. Majority of the patients had advanced disease, and liver, nonregional lymph nodes, and omentum are the common sites of distant metastasis. A high index of suspicion and health education seems to be the only answers available for early detection and improvement of survival.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Hundal R, Shaffer EA. Gallbladder cancer: Epidemiology and outcome. Clin Epidemiol 2014;6:99-109.
National Cancer Registry Programme. Two-year Report of the Population Based Cancer Registries 1997–1998. New Delhi: Indian Council of Medical Research; 2002.
Sikora SS, Kapoor R, Pradeep R, Kapoor VK, Saxena R, Kaushik SP, et al
. Palliative surgical treatment of malignant obstructive jaundice. Eur J Surg Oncol 1994;20:580-4.
Kapoor VK, Pradeep R, Haribhakti SP, Sikora SS, Kaushik SP. Early carcinoma of the gallbladder: An elusive disease. J Surg Oncol 1996;62:284-7.
Diehl AK. Epidemiology of gallbladder cancer: A synthesis of recent data. J Natl Cancer Inst 1980;65:1209-14.
Kapoor R, Goswami KC, Kapoor B, Dubey VK. Pattern of cancer in Jammu region (hospital based study 1978-87). Indian J Cancer 1993;30:67-71.
Hassan TJ, Zuberi SJ, Maqsood R. Carcinoma of gall bladder. J Pak Med Assoc 1978;28:33-4.
Cavallaro A, Piccolo G, Di Vita M, Zanghì A, Cardì F, Di Mattia P, et al
. Managing the incidentally detected gallbladder cancer: Algorithms and controversies. Int J Surg 2014;12 Suppl 2:S108-19.
Fuks D, Regimbeau JM, Le Treut YP, Bachellier P, Raventos A, Pruvot FR, et al
. Incidental gallbladder cancer by the AFC-GBC-2009 study group. World J Surg 2011;35:1887-97.
Duffy A, Capanu M, Abou-Alfa GK, Huitzil D, Jarnagin W, Fong Y, et al
. Gallbladder cancer (GBC): 10-year experience at memorial Sloan-Kettering Cancer Centre (MSKCC). J Surg Oncol 2008;98:485-9.
Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: Geographical distribution and risk factors. Int J Cancer 2006;118:1591-602.
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;144:441-7.
Dwivedi S, Madeshiya A, Singh D, Singh S, Krishna A. Gall bladder cancer and some epidemiological factors: A cross sectional study. Biomed Res 2013;24:83-7.
Lau CS, Zywot A, Mahendraraj K, Chamberlain RS. Gallbladder carcinoma in the United States: A Population based clinical outcomes study involving 22,343 patients from the surveillance, epidemiology, and end result database (1973-2013). HPB Surg 2017;2017:1532835.
Nervi F, Duarte I, Gómez G, Rodríguez G, Del Pino G, Ferrerio O, et al
. Frequency of gallbladder cancer in Chile, a high-risk area. Int J Cancer 1988;41:657-60.
Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: Cholelithiasis and cancer. Gut Liver 2012;6:172-87.
Wolin KY, Carson K, Colditz GA. Obesity and cancer. Oncologist 2010;15:556-65.
Lai HC, Chang SN, Lin CC, Chen CC, Chou JW, Peng CY, et al
. Does diabetes mellitus with or without gallstones increase the risk of gallbladder cancer? Results from a population-based cohort study. J Gastroenterol 2013;48:856-65.
Pandey M, Shukla VK. Diet and gallbladder cancer: A case-control study. Eur J Cancer Prev 2002;11:365-8.
Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncol 2003;4:167-76.
Boutros C, Gary M, Baldwin K, Somasundar P. Gallbladder cancer: Past, present and an uncertain future. Surg Oncol 2012;21:e183-91.
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;20:309-14.
Zhang WJ, Xu GF, Zou XP, Wang WB, Yu JC, Wu GZ, et al
. Incidental gallbladder carcinoma diagnosed during or after laparoscopic cholecystectomy. World J Surg 2009;33:2651-6.
Shrestha R, Tiwari M, Ranabhat SK, Aryal G, Rauniyar SK, Shrestha HG, et al
. Incidental gallbladder carcinoma: Value of routine histological examination of cholecystectomy specimens. Nepal Med Coll J 2010;12:90-4.
Sujata J, S R, Sabina K, Hassan MJ, Jairajpuri ZS. Incidental gall bladder carcinoma in laparoscopic cholecystectomy: A report of 6 cases and a review of the literature. J Clin Diagn Res 2013;7:85-8.
Dwivedi AN, Jain S, Dixit R. Gall bladder carcinoma: Aggressive malignancy with protean loco-regional and distant spread. World J Clin Cases 2015;3:231-44.
Gupta N, Goswami B, Mahajan N, Dey S. Vertebral metastasis in gallbladder carcinoma – An unusual site. Int J Case Rep Med 2012;2012:3.
Singh S, Bhojwani R, Singh S, Bhatnagar A, Saran RK, Agarwal AK, et al
. Skeletal metastasis in gall bladder cancer. HPB (Oxford) 2007;9:71-2.
[Table 1], [Table 2]