Gall Bladder Cancers in India: A Report from Population Based Cancer Registries (1982-2010)

This report discusses the incidence rates of gall bladder cancers in various regions worldwide, focusing on India. It highlights the significant disparity in rates across different countries and regions. The data analysis includes age-adjusted incidence rates from specific districts in India, as well as a comparison of incidence rates between different areas and gender groups. Additionally, the report presents the relative proportion of gall bladder cancers to all types of cancers over a specified time period. The information provided sheds light on the prevalence and distribution of gall bladder cancers, offering valuable insights for further research and healthcare strategies.

• Gall Bladder Cancers
• Population Based Cancer Registries
• Incidence Rates
• India
• Data Analysis

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1. Gall Bladder Cancers in India : A report from Population Based Cancer Registries(1982-2010) Dr. Meesha Chaturvedi Indian Council of Medical Research 7/30/2024 NCDIR-ICMR 1

2. USA (Hispanics) & Western Europe (France, Norway, UK) Extreme High High Eastern & Central Europe Moderate (Hungary, Poland, Germany) Low Asia (Republic of Korea, Japan, Bangladesh, China, India) South America (Chile, Bolivia, Peru, Ecuador, Colombia, Brazil) GBC incidence rates in the World. Worldwide incidence of GBC in both genders has been mentioned in age standardized rate per 100,000 (www.globocan.iarc.fr). Chile 9.7; Bolivia 8.1; Peru 4.0; Ecuador 4.0; Colombia 2.8; Brazil 1.9; China 2.8; Japan 4.7; India 1.8; Republic of Korea 6.5; Bangladesh 4.2; Germany 2.3; Hungary 2.9; Poland 2.9; USA- 1.6; UK 0.5; France 1.6; Norway 1.6. 2 7/30/2024 NCDIR-ICMR

3. Cancer Atlas in India- Gall Bladder cancers & Ganges River Course 7/30/2024 NCDIR-ICMR 3

4. National Cancer Registry Programme Data INDIA A Synopsis 7/30/2024 NCDIR-ICMR 4

5. Comparison of Age Adjusted Incidence Rates (AARs) of All PBCRs (2012-2014) GALLBLADDER (ICD-10: C23-C24) Kamrup Urban District 17.1 Kamrup Urban District 8.8 Delhi 11.8 Delhi 5.3 5.2 Cachar District Papumpare District Dibrugarh District 10.2 10.2 Cachar District Dibrugarh District 4.1 8.6 Kolkata 3.3 Kolkata 7.7 Imphal West District Tripura State 2.8 2.6 2.6 2.4 2.4 2.2 2.2 2.2 1.8 1.8 1.7 1.7 1.7 1.4 1.4 1.4 1.4 1.3 1.3 1.2 1.2 1.2 1.1 East Khasi Hills District Sikkim State Imphal West District 7.1 6.7 6.6 6.4 Bhopal Nagaland Bhopal Aizawl District Mumbai Aizawl District Tripura State Meghalaya Mumbai Manipur State (MR) Mizoram State (MZ) Naharlagun (NH) Patiala District MR-Excl.Imphal West MZ-Excl.Aizawl 5.8 5.3 5.0 East Khasi Hills District Sikkim State 4.1 3.8 3.6 3.4 3.2 3.0 Chennai Mizoram State (MZ) Manipur State (MR) Meghalaya Naharlagun (NH) Ahmedabad Urban Kollam District Patiala District MR-Excl.Imphal West Males Females 2.1 2.0 1.8 1.8 1.5 1.4 1.3 1.1 1.0 0.7 Bangalore Ahmedabad Urban NH-Excl.Papumpare Nagpur Chennai Nagpur Pune MZ-Excl.Aizawl Thi'puram District Bangalore Wardha District Thi'puram District Kollam District Wardha District Pune 0 4 8 12 16 20 0 2 4 6 8 10 Rate per 100,000 Rate per 100,000 7/30/2024 NCDIR-ICMR 5

6. Fig: Relative Proportion (%) of GALL BLADDER (ICD-10: C23- C24) cancers to ALL TYPE of Cancers - (Pooled Data 1982-2010) Males Females 1.7 3.0 97.0 98.3 7/30/2024 NCDIR-ICMR 6

7. Proportion (%) and Rank of Gall Bladder Cancers in PBCRs featured in top 10 leading sites Registry Proportion (%) Tripura- Females Cachar- Females Dibrugarh- Females Delhi - Females Kamrup- Females Manipur State-Females Kolkata- Males Sikkim State- Females Bhopal - Females Meghalaya- Females East Khasi hills- Females Cachar- Males Dibrugarh- Males NCDIR-ICMR Rank 4 4 4 5 5 5 5 7 7 7 7 9 10 9.0 10.6 9.1 6.2 8.4 6.0 6.0 5.1 3.8 3.8 3.6 3.3 2.7 7/30/2024 7

8. Trends in Gall Bladder Cancers PBCRs (1982-2010) 7/30/2024 NCDIR-ICMR 8

9. Gall Bladder (ICD-10 : C23-C24)-Females Trends Over Time in AAR(1982-2011) Five Year Trend 10 Bangalore Bhopal Chennai Delhi Mumbai 8 AAR per 100,000 persons 6 4 2 0 Year 7/30/2024 NCDIR-ICMR 9

10. Gall Bladder (ICD-10 : C23-C24)-Females Trends Over Time (2003 -2011) in AAR(Range of Years) - Joinpoint regression-NEWER PBCRs 16 Dibrugarh Kamrup Imphal West Sikkim 14 12 10 AAR 8 6 4 2 0 2003 2004 2005 2006 2007 Year 2008 2009 2010 2011 7/30/2024 NCDIR-ICMR 10

11. Changes in Broad Age Groups Females (Bangalore) 12 10 0-24 AAR per 100000 25-34 8 35-44 6 45-54 55-64 4 65+ 2 0 1982-1986 1987-1991 1992-1996 1997-2001 2002-2006 2007-2009 Year 7/30/2024 NCDIR-ICMR 11

12. Changes in Broad Age Groups Females (Bhopal) 35 30 25 AAR per 100000 0-24 25-34 20 35-44 15 45-54 55-64 10 65+ 5 0 1988-1992 1993-1997 1998-2002 2003-2007 2008-2010 Year 7/30/2024 NCDIR-ICMR 12

13. Changes in Broad Age Groups Females (Chennai) 7/30/2024 NCDIR-ICMR 13

14. Table: Projected Cases at India level (2015 and 2020)* Gall Bladder and Extra Hepatic Ducts (ICD-10: C23-24) 2020 Establishment of Population Based Cancer Registries in the Gangetic Belt in Allahabad (the land of Kumbh Mela),Aligarh and Patna India. Males Females Both Sexes All Cancers % to All cancers 36046 55141 91187 1734886 5.2 *Three-year Report of the PBCRs: 2012-2014, Bengaluru, 2016 7/30/2024 NCDIR-ICMR 14

15. Hospital Based Cancer Registry on Gall Bladder Cancers (1984-2010) 7/30/2024 NCDIR-ICMR 15

16. Proportion (%) of Gall Bladder Cancers (ICD10: C23 - 24) according to Method of Diagnosis (1984 2010) 0.8 3.5 3.5 0.6 1.0 1.8 14.7 15.2 Imaging Techniques Imaging techniques Microscopic Microscopic 78.9 80.0 Microscopic Clincial Unknown All Imaging Techniques Others Males Females *Data from HBCR Reports 1984 to 2010 7/30/2024 NCDIR-ICMR 16

17. Proportion (%) of Microscopically Diagnosed Gall Bladder Patients (ICD10: C23 - 24) (1984 2010) 24.3 20.9 60.5 13.0 56.2 13.6 6.0 5.6 Primary Histology Secondary Histology Cytology of Primary Cytology of Metastasis *Data from HBCR Reports 1984 to 2010 Males Females 7/30/2024 NCDIR-ICMR 17

18. Number (#) and Proporation (%) of Gall Bladder Cancer patients (ICD10: C23 - 24) according to Clinical Extent of Disease (Excludes Patients Previously Treated) Males Females Clincial Extent of Disease # 526 % 16.7 # 481 % 12.7 Localised (L) Regional (R) 769 24.4 772 20.5 L + R 1295 41.2 1253 33.2 Distant 1489 47.3 2059 54.6 Others 62 2.0 92 2.4 Unknown 300 9.5 370 9.8 Total 3146 100.0 3774 100.0 7/30/2024 NCDIR-ICMR 18 *Data from HBCR Reports 1984 to 2010

19. Number (#) and Proportion (%) of Gall Bladder Cancer patients (ICD10: C23 - 24) according to Type of Treatment Given at Reporting Institution (1984 2010) Males Females Type of Treatment # % # % Surgery (S) 495 55.3 392 43.4 Radiotherapy (R) 45 5.0 56 6.2 Chemotherapy (C) 223 24.9 273 30.2 S + R 27 3.0 32 3.5 S + C 69 7.7 114 12.6 R + C 12 1.3 19 2.1 S + R + C 11 1.2 5 0.6 Others 13 1.5 13 1.4 Total 895 100.0 904 100.0 7/30/2024 NCDIR-ICMR 19 *Data from HBCR Reports 1984 to 2010

20. Morphologies for Cancer Gall Bladder (23-C24) Rank 1 ADENOCARCINOMA (8140 ) 2 MALIGNANCY (8000 ) 3 CARCINOMA (8010 ) 4 CHOLANGIOCARCINOMA(C22.1,C24.0) (8160 ) 5 PAPILLARY ADENOCARCINOMA (8260 ) 6 SQUAMOUS CELL CARCINOMA (8070 ) 7 ADENOSQUAMOUS CARCINOMA (8560 ) 8 MUCIN-PRODUCING ADENOCARCINOMA (8481 ) 9 NEUROENDOCRINE CARCINOMA (8246 ) 10 MUCINOUS ADENOCARCINOMA (8480 ) 11 SIGNET RING CELL CARCINOMA (8490 ) 12 TUMOR CELLS, MALIGNANT (8001 ) 13 CARCINOMA, UNDIFFERENTIATED (8020 ) 14 SMALL CELL CARCINOMA (8041 ) Total Cases PHM % 60.8 24.4 6.1 1.7 1.1 0.9 0.5 0.5 0.4 0.4 0.3 0.2 0.1 0.1 100.0

21. Risk Factors 7/30/2024 NCDIR-ICMR 21

22. Risk Factors for Gall Bladder Disease/Cancers Age. Female. Diet factors Obesity. Patient Demography Geographic Pathology Genetic Predisposition Heavy Metals. Medications. Oral Contraceptives Infections i.e. Salmonella, Helicobactor Patient Exposure Xanthogranulomatous GB. Porcelain Gall Bladder. Incidental Carcinoma Detection on Cholecystectomy for Cholelithiasis. Gall Bladder Abnormality 7/30/2024 NCDIR-ICMR 22

23. Missed Opportunities- CLINICAL - Gall Bladder Cancers Surgical Removal for Cholelithiasis. General Surgeons performing Cholecystectomy.(ideally expertise for extended cholecystectomy should be available) Incidental finding Resembles Carcinoma at surgery. Forms a tumour like mass in inflammatory Gall Bladder. Xanthogranulomatous Cholecystitis Extensive Calcium encrustation of GB wall. Occurrence of gallbladder carcinoma as a complication of Porcelain Gall Bladder. NCDIR-ICMR Porcelain Gall Bladder 7/30/2024 23

24. Missed Opportunities- DIAGNOSTIC - Gall Bladder Cancers no biochemical tests of importance. Tumor markers CEA and CA 19-9 - no role in diagnosis. FNAC is not indicated (seeding of biliary tracts) Early Detection detect structural changes that include intraluminal polyp, parietal thickening. lumen filled by a mass. Imaging Tools Surgical Removal conditions ressemble Ca GB Porcelain Gall Bladder Xanthogranulomatous Cholecystitis . NCDIR-ICMR Histopathology 7/30/2024 24

25. Missed Opportunities- STAGING & SURVIVAL- Gall Bladder Cancers Inappropriate/No dedicated staging system. Staging Laparoscopy is indicated. Staging Limited studies on Disease free survival. Difficulty in conducting survival studies. Survival Difficult for registry staff to assign - Histology code most valid basis of diagnosis. Others 7/30/2024 NCDIR-ICMR 25

26. To identify environmental high risk regions for gall bladder cancer and correlation with ground water arsenic in the state of Assam, India. Incidental Gall Bladder Cancer and Other Pre malignant Gall Bladder Condition in India towards early Detection of Gall Bladder Cancer Patterns of Care and Survival Studies Gall Bladder Cancers. 7/30/2024 NCDIR-ICMR 26

27. Roadmap Forward (1/2) Synchronization between Registry and clinical practice. Consensus on aspects of staging and treatment for Gall Bladder cancers. Specific studies on preventable risk factors, early diagnostic and prognostic markers . 7/30/2024 NCDIR-ICMR 27

28. Roadmap Forward (2/2) Disease Free survival for cases with Ca Gall Bladder Special registries on Gall Bladder Cancer : customized to scientific requirement (Geographic pathology needs to be revisited). Long term benefit in planning screening programmes in future. 7/30/2024 NCDIR-ICMR 28

29. Acknowledgements Population based Cancer Registries Hospital Based Cancer Registries NCDIR-NCRP Indian Council of Medical Research (ICMR) 7/30/2024 NCDIR-ICMR 29

30. International Classification of Diseases for International Classification of Diseases for Oncology (ICD Oncology (ICD- -O) O) C23 Gallbladder C23.9 Gallbladder C24 Other and Unspecified Parts of Biliary Tract C24.0 Extrahepatic Bile Duct Bile Duct, NOS Biliary Duct, NOS Choledochal Duct Common Bile Duct Common Duct Cystic Bile Duct Cystic Duct Hepatic Bile Duct Hepatic Duct Sphincter of Oddi C24.1 Ampulla of Vater Periampullary C24.8 Overlapping lesion of biliary tract (Note: Neoplasms involving both intrahepatic and extrahepatic bile ducts) C24.9 Biliary Tract, NOS 7/30/2024 NCDIR-ICMR 30

31. Schematic representation of factors contributing to GBC pathogenesis Exposure to certain chemicals and heavy metals, age, female gender, family history, obesity, cholelithiasis, chronic cholecystitis, porcelain gallbladder, polyps, and chronic infection by Salmonella species Genes of Drug Metabolism pathway, Hormonal pathway, Inflammatory pathway, DNA Repair pathway, Hedgehog pathway, Apoptotic pathway, Wnt signaling pathway, miRNA and some other Gallbladder Cancer Pathogenesis Environmental Factors Genetic Factors 7/30/2024 NCDIR-ICMR 31

32. 7/30/2024 NCDIR-ICMR 32

33. Number (#) and Proportion (%) of Gall Bladder Cancers (ICD10: C23 - 24) by Five Year Age Groups (1984 2010) Males # 00-04 - 05-09 - 10-14 - 15-19 3 20-24 21 25-29 57 30-34 133 35-39 281 40-44 436 45-49 544 50-54 629 55-59 641 60-64 508 65-69 422 70-74 221 75+ 122 Unknown 3 Females Age Group % # % - - - - - - - 1 5 0.0 0.1 0.5 1.3 3.5 7.8 12.7 16.6 17.2 13.6 13.0 7.6 3.9 2.2 0.0 0.1 0.5 1.4 3.3 7.0 10.8 13.5 15.6 15.9 12.6 10.5 5.5 3.0 0.1 25 68 186 412 673 877 911 721 689 404 204 115 1 *Data from HBCR Reports 1984 to 2010 4021 100.0 5292 100.0 All Ages 7/30/2024 NCDIR-ICMR 33

34. To identify environmental high risk regions for gall bladder cancer and correlation with ground water arsenic in the state of Assam, India. Life Style Behavior, Dietary Habits, Reproductive factors and risk of Gall Bladder Cancer in Upper Assam A multidisciplinary case control study on Gall bladder cancer -Identification of modifiable risk factors and risk reduction. 7/30/2024 NCDIR-ICMR 34