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| ORIGINAL ARTICLE |
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| Year : 2020 | Volume
: 1
| Issue : 1 | Page : 4-7 |
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Clinical spectrum of carcinoma of the gallbladder in the Indian states of Uttarakhand and Western Uttar Pradesh: A retrospective study from a tertiary care hospital of Northern India
Navin Kumar, Deepak Rajput, Amit Gupta, Varun Popuri, Tanuj Singla, Ashikesh Kundal, Jyoti Sharma, Bhargav Gajula
Department of General Surgery, AIIMS, Rishikesh, Uttarakhand, India
| Date of Submission | 14-Jun-2020 |
| Date of Decision | 18-Jun-2020 |
| Date of Acceptance | 23-Jun-2020 |
| Date of Web Publication | 20-Jul-2020 |
Correspondence Address:
Dr. Navin Kumar
Department of General Surgery, AIIMS, Rishikesh - 249 203, Uttarakhand
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/JME.JME_78_20
Background: North India has a very high incidence of Carcinoma gallbladder (GBC). The aim of the study was to identify the hotspot regions and relationship of gallstones to GBC in two northern states of India. Materials and Methods: It was a retrospective, observational, hospital-based cohort study. The data of patients with locally advanced (LA) or metastatic GBC from January 2019 to December 2019 were evaluated for geographical distribution of cases, and their clinical spectrum was compared with the presence or absence of associated cholelithiasis. Statistical analysis was performed using R Statistical software version 3.6.2. Results: Forty-two patients were enrolled in our study. A high burden of GBC was observed from Western Uttar Pradesh (District Bijnor 12(29%) and Muzaffarnagar 7(17%)) and Uttarakhand (District Haridwar 7(17%), whereas the remaining 16(38%) patients were residents of other districts of Uttarakhand (UK) and Western Uttar Pradesh (UP). In our study, only 17(40.5%) patients had associated cholelithiasis. Metastatic disease at presentation was seen in nearly 59% of patients with cholelithiasis and 52% of patients without cholelithiasis. Jaundice was the most common presentation in 12(70.6%) patients, followed by pain in 9(nearly 53%) patients with GBC associated with gallstones. Whereas in patients with GBC without gallstones, loss of appetite and loss of weight was the most common presentation in 16(64%) followed by jaundice in 13(52%). Conclusion: Most cases with LA or metastatic GBC in the present study were not associated with cholelithiasis. Clinical spectrum of either LA or metastatic GBC is similar, irrespective of presence or absence of gallstones.
Keywords: Cholelithiasis and gallbladder cancer, epidemiology of gallbladder cancer, hotspot region for gallbladder cancer
How to cite this article:
Kumar N, Rajput D, Gupta A, Popuri V, Singla T, Kundal A, Sharma J, Gajula B. Clinical spectrum of carcinoma of the gallbladder in the Indian states of Uttarakhand and Western Uttar Pradesh: A retrospective study from a tertiary care hospital of Northern India. J Med Evid 2020;1:4-7 |
How to cite this URL:
Kumar N, Rajput D, Gupta A, Popuri V, Singla T, Kundal A, Sharma J, Gajula B. Clinical spectrum of carcinoma of the gallbladder in the Indian states of Uttarakhand and Western Uttar Pradesh: A retrospective study from a tertiary care hospital of Northern India. J Med Evid [serial online] 2020 [cited 2022 Nov 30];1:4-7. Available from: http://www.journaljme.org/text.asp?2020/1/1/4/290145 |
| Introduction | |  |
Carcinoma gallbladder (GBC) is the most common and aggressive neoplasm of the biliary tract. The clinical presentation of GBC is often vague or delayed relative to pathologic progression, contributing to delayed diagnosis and poor 5-year survival.[1],[2],[3] Majority of the GBCs have gallstones as the predisposing risk factor, but still many cases develop this pathology even without cholelithiasis. The aim of the study was to differentiate the epidemiology of GBC with respect to the presence or absence of associated cholelithiasis and to identify the spatial variation in the occurrence of gallbladder cancers, so that screening of these regions can be done to pick GBC at early stage.
| Materials and Methods | | |
This was an analytical cohort study of retrospectively collected data of consecutive patients diagnosed with either locally advanced (LA) or metastatic carcinoma gallbladder presenting and registered at Hepato–Pancreato–Biliary Unit of the Department of General Surgery at All India Institute of Medical Sciences, Rishikesh, from January 2019 to December 2019. It was a time-bound, observational study. Convenience sampling technique was employed to collect primary data using case study method. Inclusion criteria were patients aged more than 18 years with a diagnosis of LA or metastatic GBC on the evaluation with contrast-enhanced computed tomography (CECT) scan of the abdomen and chest. Patients in whom CECT scan of the abdomen and chest was not done were excluded from the study. STROBE guidelines were used for this observational study. Ethics approval was taken from the Institute Ethics Committee of AIIMS Rishikesh and patient's data being deidentified. The total number of cases with LA or metastatic GBC during the study period was 49, of which 42 cases were enrolled in the study after excluding the cases with missing data. The data were collected on a spreadsheet from the hospital records of the individual patients, which included age, gender, residential address, presence or absence of associated cholelithiasis, symptoms and signs at presentation, blood parameters such as total bilirubin and alkaline phosphatase (ALP) and the CECT scan findings. Patients' residential regions were recorded to find the geographical distribution of GBC. Cases with GBC were divided into two groups on the basis of presence or absence of cholelithiasis. One group comprised the presence of cholelithiasis and other without cholelithiasis. CECT scan identified the mass in the gallbladder, lymph node enlargement, liver invasion, adjacent organ infiltration, vascular encasement and distant metastasis. On the basis of local extension of the tumour and presence of metastasis on CECT scan, GBC was staged into LA and metastatic disease (M). Patients in both the groups were compared regarding clinical spectrum of presentation including age, symptoms, signs, mean of total bilirubin and ALP level and stage of disease according to CECT scan findings. Statistical analyses were performed using R Statistical software version 3.6.2. (R Core Team (2019). Methodology Reference Indicator codes: CSI 019, WAT 002, R Foundation for Statistical Computing, Vienna, Austria, URL: http://www.r-project.org/index.html). The Wilcoxon–Mann–Whitney U non-parametric test was used for comparison of data between the two groups, and Fisher's exact test was used, because of small sample size, to calculate the P value and t-test to compare the mean values of the two datasets. The Chi-square test was applied to find the association of cholelithiasis with LA and M stage of GBC.
| Results | | |
Most of the patients with GBC in our study came mainly from UP (districts of Bijnor 29% (12) followed by Muzaffarnagar 17% (07)) and UK (Haridwar) 17% (07), whereas the remaining 16 (38%) patients were from other districts of Western UP and UK [Figure 1]. | Figure 1: Map of India showing regions of Uttarakhand and Western UP with carcinoma gallbladder
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Out of 42 patients enrolled in the study [Table 1], 33 (78.6%) were female and 9 (21.4%) were male. The mean age at presentation of GBC with cholelithiasis was 5 years earlier (50 years) than cases without cholelithiasis (55 years).
Twenty-three (54.8%) patients had metastatic carcinoma gallbladder at presentation, whereas the remaining 19 (45.2%) patients had LA stage. In the LA group of 19 patients, cholelithiasis was found in 7 (36.8%) and 12 (63.2%) had no gallstones. Out of the 23 patients in the M group, 10 (43.5%) had associated gallstones and 13 (56.5%) had no gallstones. Hence, out of total 42 patients with LA or metastatic carcinoma gallbladder in our study, only 17 (40.5%) had associated cholelithiasis.
Jaundice was the most common presentation in 12 (70.6%) patients, followed by pain in 9 (nearly 53%) patients with carcinoma gallbladder associated with gallstones. Whereas in patients with GBC without gallstones, loss of appetite and loss of weight was the most common presentation in 16 (64%) followed by jaundice in 13 (52%). The mean values of serum total bilirubin and ALP were higher in GBC with cholelithiasis than without cholelithiasis.
The presence of jaundice and loss of appetite and weight was an indicator of advanced disease, irrespective of the presence or absence of cholelithiasis. Liver 16 (38%), lymph node 41 (98%), omentum 23 (55%) and lungs 5 (12%) were the common sites of metastasis, irrespective of the presence or absence of gallstones.
| Discussion | | |
There is a marked geographical variation of the incidence of GBC. The incidence of GBC is very high in the American–Indian, Chilean–Mapuche populations and the North Indian females.[4],[5] GBC is a relatively rare neoplasm and is more common in females than males. The ratio of female to male in our study was 3.7:1, which is consistent with previous studies.[4],[6] The mean age at diagnosis in the present study was 52.71 years, which is similar to the previous studies where it was 52.50 years.[6] The incidence in North India (Delhi) is 10.6/100,000, whereas it is 0.8/100,000 in South India (Chennai).[7] A report from Memorial Sloan Kettering Cancer Center shows the median age of 67 years.[8] The early age of onset in the Indian population is because of higher incidence of gallstones and lower socioeconomic status.[9]
It is a well-known fact that cholelithiasis is the most important risk factor for the development of GBC, as it has been proven to be associated in approximately 70%–90% of the cases with GBC and the overall risk of GBC in persons with cholelithiasis is <3%.[9],[10],[11],[12] Family history of cholelithiasis increases the incidence of GBC.[9] The findings of the current study show an incidence of 40.5% in GBC with associated cholelithiasis. The incidence of GBC with cholelithiasis in certain populations has been reported much higher than this. The incidence of GBC in Pima Indian females is 21/100,000 population and 27/100,000 population in Chilean Mapuche Indian females, whereas the prevalence of cholelithiasis in these populations is 75.8% and 49.4%, respectively.[13],[14] Genetic risk with cholelithiasis is responsible in approximately 25% of cases with GBC.[15] Cholelithiasis produces chronic inflammation in the gallbladder mucosa, which subsequently produces carcinogens.[16] Chronic inflammation causes damage to deoxyribonucleic acid and releases cytokines which are the predisposing factors for GBC.[17]
Environmental exposure of heavy metals (nickel, cadmium, etc.) has been hypothesised in the causation of GBC.[18] Tobacco consumption is another risk factor.[19] Obesity with BMI (body mass index) >30 kg/m2 also increases the risk of GBC.[20]
Our study showed nearly 55% of patients with metastatic disease and 45% with LA disease at presentation, which is close to a previous study (89%) from India.[6] The authors had observed jaundice in 25 (59.5%) cases as the most common presentation followed by loss of appetite and weight in 23 (54.8%), whereas another study from India reported pain as the most common presentation followed by jaundice in 51.47%.[6] The most common site of metastasis in GBC is liver, lymph node and peritoneum.[21] In our study, liver, lymph node, omentum and lungs were the common sites of metastasis, which is almost similar to the previous studies.[6]
GBC is diagnosed by CECT scan of the abdomen, which also identifies the lymph node, liver invasion, metastasis and vascular encasement. On the basis of these findings, it can be staged as early, LA and metastatic GBC.[22] It helps in deciding the resectability of the tumour. Surgical resection is the only potentially curative therapy of GBC. Early GBC is resected with curative intent, LA tumours require major resection and metastatic GBC requires only palliative therapy.
| Conclusion | | |
Risk of GBC is very high in North Indian females and mostly the disease presents as LA or metastatic stage. Population of certain districts of UK and Western UP have higher risk of development of GBC even without cholelithiasis. Clinical spectrum of either LA or metastatic carcinoma gallbladder in the presence or absence of associated cholelithiasis is almost similar in relation to age, gender and symptoms and signs at presentation.
Limitation
It was a single-centre, short-duration study with limited number of patients. Further, long-term and multicentric studies are required with large number of patients to identify the spatial variation and occurrence of gallbladder cancer in this part of the world.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Hu L, Wang B, Liu X, Lv Y. Unsuspected gallbladder cancer: A clinical retrospective study. Arch Iran Med 2013;16:631-5.  |
| 2. | Peng HH, Zhang YD, Gong LS, Liu WD, Zhang Y. Increased expression of microRNA-335 predicts a favorable prognosis in primary gallbladder carcinoma. Onco Targets Ther 2013;6:1625-30. |
| 3. | Liu TY, Tan ZJ, Jiang L, Gu JF, Wu XS, Cao Y, et al. Curcumin induces apoptosis in gallbladder carcinoma cell line GBC-SD cells. Cancer Cell Int 2013;13:64. |
| 4. | Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: Geographical distribution and risk factors. Int J Cancer 2006;118:1591-602. |
| 5. | Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncol 2003;4:167-76. |
| 6. | Dubey AP, Rawat K, Pathi N, Viswanath S, Rathore A, Kapoor R, et al. Carcinoma of gall bladder: Demographic and clinicopathological profile in Indian patients. Oncol J India 2018;2:3-6. [Full text] |
| 7. | Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108. |
| 8. | 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. |
| 9. | 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;14:381-5. |
| 10. | Zatonski WA, Lowenfels AB, Boyle P, Maisonneuve P, Bueno de Mesquita HB, Ghadirian P, et al. Epidemiologic aspects of gallbladder cancer: A case-control study of the SEARCH Program of the International Agency for Research on Cancer. J Natl Cancer Inst 1997;89:1132-8. |
| 11. | 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. |
| 12. | Shukla VK, Khandelwal C, Roy SK, Vaidya MP. Primary carcinoma of the gall bladder: A review of a 16-year period at the University Hospital. J Surg Oncol 1985;28:32-5. |
| 13. | Sampliner RE, Bennett PH, Comess LJ, Rose FA, Burch TA. Gallbladder disease in Pima Indians. Demonstration of high prevalence and early onset by cholecystography. N Engl J Med 1970;283:1358-64. |
| 14. | Singh V, Trikha B, Nain C, Singh K, Bose S. Epidemiology of gallstone disease in Chandigarh: A community-based study. J Gastroenterol Hepatol 2001;16:560-3. |
| 15. | Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: Cholelithiasis and cancer. Gut Liver 2012;6:172-87. |
| 16. | Shaffer EA. Gallbladder cancer: The basics. Gastroenterol Hepatol ( N Y) 2008;4:737-41. |
| 17. | Rashid A, Ueki T, Gao YT, Houlihan PS, Wallace C, Wang BS, et al. K-ras mutation, p53 overexpression, and microsatellite instability in biliary tract cancers: A population-based study in China. Clin Cancer Res 2002;8:3156-63. |
| 18. | Pandey M. Environmental pollutants in gallbladder carcinogenesis. J Surg Oncol 2006;93:640-3. |
| 19. | Jain K, Sreenivas V, Velpandian T, Kapil U, Garg PK. Risk factors for gallbladder cancer: A case-control study. Int J Cancer 2012;132:1660-6. |
| 20. | Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortlity from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003;348:1625-38. |
| 21. | 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. |
| 22. | Kumaran V, Gulati MS, Paul SB, Kumar Pande G, Sahni P, Chattopadhyay TK. The role of dual-phase helical CTin assessing resectability of carcinoma of the gallbladder. Eur Radiol 2002;12:1993-9. |
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