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Xiao YX, Chen J, Li ZY, Zou YX, Zhou XH, Zhang W, Li HL, Bischof EY, Xiang YB. Global trends in gallbladder cancer survival: A 30-year analysis of cancer registry data. Heliyon 2025; 11:e42853. [PMID: 40070950 PMCID: PMC11894304 DOI: 10.1016/j.heliyon.2025.e42853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 02/17/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Background Gallbladder cancer has historically been characterized with a poor prognosis. This study aims to describe the global patterns and temporal trends in gallbladder cancer survival using data from cancer registries. Methods We conducted a systematic review by searching six databases-PubMed, Web of Science, EMBASE, SEER, CNKI, and Wanfang-for using of registry-based data published before January 1, 2024. Survival data were carefully extracted and analyzed from the final set of included studies. Results Among the 55 studies included, more than 320,000 people, suggest that survival improvements for gallbladder cancer have stagnated over the past three decades. No significant improvements in 5-year relative survival rates were observed worldwide. After age standardization, the highest 5-year relative survival rate is 30.6 % (Changzhou, China, 2011-2013 and Korea, 2013-2019), while the lowest is 6.0 % (Austria, 1990). The 5-year relative survival rate for gallbladder cancer was generally higher in Asian populations than in other regions. Survival rates were more favorable in younger individuals, with no differences in survival observed between the sexes. Conclusions Over the past 30 years, the prognosis of patients with gallbladder cancer has not improved significantly worldwide. There is an urgent need for new treatments for gallbladder cancer as well as simple and effective screening methods to improve the survival rate of gallbladder cancer.
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Affiliation(s)
- Yu-Xuan Xiao
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Jun Chen
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Zhuo-Ying Li
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Fudan University, Shanghai, 200025, China
| | - Yi-Xin Zou
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Fudan University, Shanghai, 200025, China
| | - Xiao-Hui Zhou
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Wei Zhang
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Hong-Lan Li
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Evelyne Y. Bischof
- Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China
| | - Yong-Bing Xiang
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
- School of Public Health, Fudan University, Shanghai, 200025, China
- Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China
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Palepu J, Endo I, Chaudhari VA, Murthy GVS, Chaudhuri S, Adam R, Smith M, de Reuver PR, Lendoire J, Shrikhande SV, De Aretxabala X, Sirohi B, Kokudo N, Kwon W, Pal S, Bouzid C, Dixon E, Shah SR, Maroni R, Nervi B, Mengoa C, Patil S, Ebata T, Maithel SK, Lang H, Primrose J, Hirano S, Guevara OA, Ohtsuka M, Valle JW, Sharma A, Nagarajan G, Núñez Ju JJ, Arroyo GF, Torrez SL, Erdmann JI, Butte JM, Furuse J, Lee SE, Gomes AP, Park SJ, Jang JY, Oddi R, Barreto SG, Kijima H, Ciacio O, Gowda NS, Jarnagin W. 'IHPBA-APHPBA clinical practice guidelines': international Delphi consensus recommendations for gallbladder cancer. HPB (Oxford) 2024; 26:1311-1326. [PMID: 39191539 DOI: 10.1016/j.hpb.2024.07.411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/12/2024] [Accepted: 07/16/2024] [Indexed: 08/29/2024]
Abstract
BACKGROUND The Delphi consensus study was carried out under the auspices of the International and Asia-Pacific Hepato-Pancreato-Biliary Associations (IHPBA-APHPBA) to develop practice guidelines for management of gallbladder cancer (GBC) globally. METHOD GBC experts from 17 countries, spanning 6 continents, participated in a hybrid four-round Delphi consensus development process. The methodology involved email, online consultations, and in-person discussions. Sixty eight clinical questions (CQs) covering various domains related to GBC, were administered to the experts. A consensus recommendation was accepted only when endorsed by more than 75% of the participating experts. RESULTS Out of the sixty experts invited initially to participate in the consensus process 45 (75%) responded to the invitation. The consensus was achieved in 92.6% (63/68) of the CQs. Consensus covers epidemiological aspects of GBC, early, incidental and advanced GBC management, definitions for radical GBC resections, the extent of liver resection, lymph node dissection, and definitions of borderline resectable and locally advanced GBC. CONCLUSIONS This is the first international Delphi consensus on GBC. These recommendations provide uniform terminology and practical clinical guidelines on the current management of GBC. Unresolved contentious issues like borderline resectable/locally advanced GBC need to be addressed by future clinical studies.
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Affiliation(s)
- Jagannath Palepu
- Continental Cancer Centre, Continental Hospitals, Hyderabad, India; Dept. of Surgical Oncology Lilavati Hospital & Research Centre and SL Raheja Hospital, Mumbai, India.
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Vikram Anil Chaudhari
- GI and HPB Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - G V S Murthy
- PRASHO Foundation, Hyderabad, India; London School of Hygiene and Tropical Medicine, London, UK
| | | | - Rene Adam
- Department of Hepatobiliary Surgery, Cancer and Transplantation, AP-HP Hôpital Paul Brousse / Univ Paris-Saclay, Centre Hépato-Biliaire, Villejuif, France
| | - Martin Smith
- Surgery, University of the Witwatersrand Johannesburg, Johannesburg, South Africa
| | | | - Javier Lendoire
- HPB & Liver Transplantation, Instituto de Trasplantes y Alta Complejidad (ITAC), Buenos Aires, Argentina
| | - Shailesh V Shrikhande
- GI and HPB Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | | | - Bhawna Sirohi
- Medical Oncology, Vedanta Medical Research foundation (Balco Medical Centre), Raipur, India
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Sujoy Pal
- Deptt of GI Surgery and Liver transplantation, All India Institute of Medical Sciences, New Delhi, India
| | - Chafik Bouzid
- HPB and Digestive Oncology Surgery, Dept. of Surgical Oncology, DBK anti cancer center, Mouloud Mammeri University, Tizi Ouzou, Algeria
| | - Elijah Dixon
- Department of Surgery, University of Calgary, Calgary, Canada
| | | | - Rodrigo Maroni
- Head of Program of Surgery, Hospital Papa Francisco, Salta, Argentina
| | - Bruno Nervi
- Chief Department, Department of Hematology and Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Claudio Mengoa
- Surgery, Instituto Regional de Enfermedades Neoplasicas, Arequipa, Peru
| | | | - Tomoki Ebata
- Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shishir K Maithel
- Professor of Surgery, Department of Surgery, Emory University, Atlanta, USA
| | - Hauke Lang
- Visceral- and Transplantation Surgery, Universitätsmedizin Mainz, Mainz, Germany
| | - John Primrose
- Department of Surgery, University of Southampton, Southampton, UK
| | - Satoshi Hirano
- Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Oscar A Guevara
- Surgery, Universidad Nacional de Colombia / Instituto Nacional de Cancerologia, Bogota, Colombia
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Juan W Valle
- Chief Medical Officer, Research Department, Cholangiocarcinoma Foundation, Herriman, UT, USA
| | - Atul Sharma
- Medical Oncology, Max Institute Of Cancer Care, New Delhi, India
| | - Ganesh Nagarajan
- Surgical oncology ( GI and HPB), Nanavati Max hospital mumbai, Mumbai, India
| | - Juan Jose Núñez Ju
- HPB General Surgery Service, Hospital Nacional Guillermo Almenara, Lima, Peru
| | | | | | | | - Jean M Butte
- Surgery, Instituto Oncologico FALP, Santiago, Chile
| | - Junji Furuse
- Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan
| | - Seung Eun Lee
- Department of surgery, Chung-Ang University College of Medicine, Seoul, South Korea
| | - António Pedro Gomes
- Surgery Department, Hospital Vila Franca de Xira, Vila Franca de Xira, Portugal
| | - Sang-Jae Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang-si, South Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Ricardo Oddi
- Center for Clinical Medical Education and Research (CEMIC), Buenos Aires, Argentina
| | - Savio George Barreto
- HPB and Liver Transplant Unit, Flinders Medical Centre, Flinders University, Austraila
| | - Hiroshi Kijima
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Oriana Ciacio
- Centre Hépato-Biliaire, AP-HP - Hôpital Paul Brousse / Paris-Saclay University, Villejuif, France
| | - Nagesh S Gowda
- Institute of Gastroenterology and Organ Transplantation, Bengaluru, India
| | - William Jarnagin
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, USA
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Rajput M, Pandey M, Dixit R, Shukla VK. Is cross-species horizontal gene transfer responsible for gallbladder carcinogenesis. World J Surg Oncol 2024; 22:201. [PMID: 39080678 PMCID: PMC11287962 DOI: 10.1186/s12957-024-03492-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 07/19/2024] [Indexed: 08/03/2024] Open
Abstract
BACKGROUND Cross-species horizontal gene transfer (HGT) involves the transfer of genetic material between different species of organisms. In recent years, mounting evidence has emerged that cross-species HGT does take place and may play a role in the development and progression of diseases. METHODS Transcriptomic data obtained from patients with gallbladder cancer (GBC) was assessed for the differential expression of antisense RNAs (asRNAs). The Basic Local Alignment Search Tool (BLAST) was used for cross-species analysis with viral, bacterial, fungal, and ancient human genomes to elucidate the evolutionary cross species origins of these differential asRNAs. Functional enrichment analysis and text mining were conducted and a network of asRNAs targeting mRNAs was constructed to understand the function of differential asRNAs better. RESULTS A total of 17 differentially expressed antisense RNAs (asRNAs) were identified in gallbladder cancer tissue compared to that of normal gallbladder. BLAST analysis of 15 of these asRNAs (AFAP1-AS1, HMGA2-AS1, MNX1-AS1, SLC2A1-AS1, BBOX1-AS1, ELFN1-AS1, TRPM2-AS, DNAH17-AS1, DCST1-AS1, VPS9D1-AS1, MIR1-1HG-AS1, HAND2-AS1, PGM5P4-AS1, PGM5P3-AS1, and MAGI2-AS) showed varying degree of similarities with bacterial and viral genomes, except for UNC5B-AS1 and SOX21-AS1, which were conserved during evolution. Two of these 15 asRNAs, (VPS9D1-AS1 and SLC2A1-AS1) exhibited a high degree of similarity with viral genomes (Chikungunya virus, Human immunodeficiency virus 1, Stealth virus 1, and Zika virus) and bacterial genomes including (Staphylococcus sp., Bradyrhizobium sp., Pasteurella multocida sp., and, Klebsiella pneumoniae sp.), indicating potential HGT during evolution. CONCLUSION The results provide novel evidence supporting the hypothesis that differentially expressed asRNAs in GBC exhibit varying sequence similarity with bacterial, viral, and ancient human genomes, indicating a potential shared evolutionary origin. These non-coding genes are enriched with methylation and were found to be associated with cancer-related pathways, including the P53 and PI3K-AKT signaling pathways, suggesting their possible involvement in tumor development.
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Affiliation(s)
- Monika Rajput
- Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India
| | - Manoj Pandey
- Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
| | - Ruhi Dixit
- Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India
| | - Vijay K Shukla
- Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India
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MAP kinase and mammalian target of rapamycin are main pathways of gallbladder carcinogenesis: results from bioinformatic analysis of next generation sequencing data from a hospital-based cohort (NCT05404347). Mol Biol Rep 2022; 49:10153-10163. [PMID: 36018415 DOI: 10.1007/s11033-022-07874-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 08/16/2022] [Indexed: 10/15/2022]
Abstract
BACKGROUND Gallbladder Cancer (GBC) is one of the most common cancers of the biliary tract and the third commonest gastrointestinal (GI) malignancy worldwide. The disease is characterized by the late presentation and poor outcome despite treatment, and hence, newer therapies and targets need to be identified. METHODS The current study investigated various functionally enriched pathways in GBC pathogenesis involving the genes identified through Next Generation Sequencing (NGS) in a hospital-based cohort. The Pathway enrichment analysis and Gene Ontology (GO) were carried out after NGS, followed by the construction of the protein-protein interaction (PPI) network to discover associations among the genes. RESULTS Of the thirty-three patients with GBC who were screened through next-generation sequencing (NGS), 27somatic mutations were identified. These mutations involved a total of 14 genes. The p53 and KRAS were commonly found to be mutated, while mutations in other genes were seen in one case each, the mean number of mutations were 1.2, and maximum mutation in a single case (eight) was seen in one case. The bioinformatics analysis identified MAP kinase, PI3K-AKT, EGF/EGFR, and Focal Adhesion PI3K-AKT-mTOR signaling pathways and cross-talk between these. CONCLUSION The results suggest that the complex crosstalk between the mTOR, MAPK, and multiple interacting cell signaling cascades can promote GBC progression, and hence, mTOR-MAPK targeted treatment will be an attractive option.
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Environmental and Lifestyle Risk Factors in the Carcinogenesis of Gallbladder Cancer. J Pers Med 2022; 12:jpm12020234. [PMID: 35207722 PMCID: PMC8877116 DOI: 10.3390/jpm12020234] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 11/08/2021] [Accepted: 12/23/2021] [Indexed: 02/01/2023] Open
Abstract
Gallbladder cancer (GBC) is an aggressive neoplasm that in an early stage is generally asymptomatic and, in most cases, is diagnosed in advanced stages with a very low life expectancy because there is no curative treatment. Therefore, understanding the early carcinogenic mechanisms of this pathology is crucial to proposing preventive strategies for this cancer. The main risk factor is the presence of gallstones, which are associated with some environmental factors such as a sedentary lifestyle and a high-fat diet. Other risk factors such as autoimmune disorders and bacterial, parasitic and fungal infections have also been described. All these factors can generate a long-term inflammatory state characterized by the persistent activation of the immune system, the frequent release of pro-inflammatory cytokines, and the constant production of reactive oxygen species that result in a chronic damage/repair cycle, subsequently inducing the loss of the normal architecture of the gallbladder mucosa that leads to the development of GBC. This review addresses how the different risk factors could promote a chronic inflammatory state essential to the development of gallbladder carcinogenesis, which will make it possible to define some strategies such as anti-inflammatory drugs or public health proposals in the prevention of GBC.
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Lin Z, Li Y, Shao R, Hu Y, Gao H. LncRNA TTN-AS1 acts as a tumor promoter in gallbladder carcinoma by regulating miR-107/HMGA1 axis. World J Surg Oncol 2021; 19:163. [PMID: 34090483 PMCID: PMC8180155 DOI: 10.1186/s12957-021-02279-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/28/2021] [Indexed: 12/13/2022] Open
Abstract
Background The incidence of gallbladder carcinoma (GBM) in China has increased in recent years. Here, the functional mechanism of lncRNA TTN-AS1 in GBC was preliminary elucidated. Methods The expression levels of lncRNA TTN-AS1, miR-107, and HMGA1 in tissues and cell lines were assessed by RT-qPCR. Cell proliferation was measured by MTT assays. Cell invasion and migration abilities were evaluated by Transwell assays. The relationship between miR-107 and lncRNA TTN-AS1 or HMGA1 was confirmed by luciferase reporter assay. Results Upregulation of lncRNA TTN-AS1 and downregulation of miR-107 were detected in GBC. Furthermore, the expressions between TTN-AS1 and miR-107 were mutually inhibited in GBC. Functionally, lncRNA TTN-AS1 promoted cell viability and motility in GBC by sponging miR-107. In addition, miR-107 directly targets HMGA1. And HMGA1 can be positively regulated by lncRNA TTN-AS1 in GBC. Furthermore, HMGA1 promoted GBC progression by interacting with lncRNA TTN-AS1/miR-107 axis. Conclusion LncRNA TTN-AS1 acted as a tumor promoter in GBC by sponging miR-107 and upregulating HMGA1.
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Affiliation(s)
- Zhaoxia Lin
- Department of Clinical Laboratory, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Shandong Province, Jinan, 250013, China
| | - Yaosheng Li
- Imaging Department, The People's Hospital of Zhangqiu Area, Shandong Province, Jinan, 250200, China
| | - Rongfeng Shao
- Department of Hepatobiliary Vascular Surgery, Qingdao Central Hospital, Qingdao University, Shandong Province, Qingdao, 266000, China
| | - Yuqing Hu
- Department of Endocrinology, The People's Hospital of Zhangqiu Area, Shandong Province, Jinan, 250200, China
| | - Han Gao
- Department of Pathology, Qingdao Municipal Hospital, No. 5 Donghai Middle Road, Shandong Province, Qingdao, 266071, China.
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Mahananda B, Vinay J, Palo A, Singh A, Sahu SK, Singh SP, Dixit M. SERPINB5 Genetic Variants rs2289519 and rs2289521 are Significantly Associated with Gallbladder Cancer Risk. DNA Cell Biol 2021; 40:706-712. [PMID: 33691472 DOI: 10.1089/dna.2021.0056] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Serine protease inhibitor b5 (SERPINB5) is a tumor suppressor gene that plays a critical role in various cellular processes. In gallbladder cancer (GBC), SERPINB5's aberrant expression is reported but its role in genetic predisposition is not known. We enrolled 270 cases and 296 controls and genotyped them for single nucleotide polymorphisms (SNPs) using direct DNA sequencing, followed by genotype-phenotype analysis in GBC and other cancer cell lines. Luciferase assay was done to determine the role of rs2289521 SNP on expression regulation. We found that two SERPINB5 variants rs2289519 and rs2289521 are significantly associated with GBC and contribute to genetic predisposition. The TT genotype of variant rs2289519 was found to be significantly associated (p = 0.008) with GBC in a recessive model. C allele of rs2289521 increased the risk for GBC significantly at genotypic (CT, p = 0.026) and allelic (p = 0.04) levels. In silico analysis and luciferase assay uncovered the probable regulatory role of the rs2289521 variant on expression. Genotype-phenotype correlation in GBC and breast cancer cell lines showed reduced expression of SERPINB5 in the presence of C allele that was consistent with the result of luciferase assay. Overall, our study reveals the genetic association of two SERPINB5 variants with GBC and rs2289521's possible role in the regulation of expression.
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Affiliation(s)
- Biswaheree Mahananda
- School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, India.,Homi Bhabha National Institute, Mumbai, India
| | - J Vinay
- School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, India.,Homi Bhabha National Institute, Mumbai, India
| | - Ananya Palo
- School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, India.,Homi Bhabha National Institute, Mumbai, India
| | - Ayaskanta Singh
- Department of Gastroenterology and Hepato-Biliary Sciences, IMS & SUM Hospital, Sikshya O Anusandhan University, Bhubaneswar, India
| | - Saroj Kanta Sahu
- Department of Gastroenterology and Hepato-Biliary Sciences, IMS & SUM Hospital, Sikshya O Anusandhan University, Bhubaneswar, India
| | - Shivaram Prasad Singh
- Department of Gastroenterology, Sriram Chandra Bhanja Medical College and Hospital, Cuttack, India
| | - Manjusha Dixit
- School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, India.,Homi Bhabha National Institute, Mumbai, India
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Mhatre S, Rajaraman P, Chatterjee N, Bray F, Goel M, Patkar S, Ostwal V, Patil P, Manjrekar A, Shrikhande SV, Badwe R, Dikshit R. Mustard oil consumption, cooking method, diet and gallbladder cancer risk in high- and low-risk regions of India. Int J Cancer 2020; 147:1621-1628. [PMID: 32142159 DOI: 10.1002/ijc.32952] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 02/20/2020] [Accepted: 02/24/2020] [Indexed: 03/25/2024]
Abstract
The current study aimed to investigate the role of cooking with mustard oil and other dietary factors in relation to gallbladder cancer (GBC) in high- and low-incidence regions of India. A case-control study was conducted including 1,170 histologically confirmed cases and 2,525 group-matched visitor controls from the largest cancer hospital in India. Dietary data were collected through a food frequency questionnaire. For oil consumption, we enquired about monthly consumption of 11 different types of cooking oil per family and the number of individuals usually sharing the meal to estimate per-individual consumption of oil. Information about method of cooking was also requested. Odds ratios (ORs) and 95% confidence intervals (CIs) quantifying the association of GBC risk consumption of different types of oil, method of cooking, and dietary food items, were estimated using logistic regression models, after adjusting for potential confounders. High consumption of mustard oil was associated with GBC risk in both high- and low-risk regions (OR = 1.33, 95% CI = 0.99-1.78; OR = 3.01, 95% CI = 1.66-5.45), respectively. An increased risk of GBC was observed with deep frying of fresh fish in mustard oil (OR = 1.57, 95% CI = 0.99-2.47, p-value = 0.052). A protective association was observed with consumption of leafy vegetables, fruits, onion and garlic. No association was observed between consumption of meat, spicy food, turmeric, pulses or with any other oil as a cooking medium. The effect of high consumption of mustard oil on GBC risk, if confirmed, has implications for the primary prevention of GBC, via a reduced consumption.
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Affiliation(s)
- Sharayu Mhatre
- Centre for Cancer Epidemiology, Tata Memorial Centre, Kharghar, Navi Mumbai, India
- Homi Bhabha national institute (HBNI), Mumbai, India
| | - Preetha Rajaraman
- Office of Global Affairs, Department of Health and Human Services, Washington, District of Columbia, USA
| | - Nilanjan Chatterjee
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
- Department of Biostatistics, Bloomberg School of Public Health, John Hopkins University, Baltimore, Maryland, USA
- Department of Oncology, School of Medicine, John Hopkins University, Baltimore, Maryland, USA
| | - Freddie Bray
- Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
| | - Mahesh Goel
- Homi Bhabha national institute (HBNI), Mumbai, India
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Shraddha Patkar
- Homi Bhabha national institute (HBNI), Mumbai, India
- Department of Clinical Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Vikas Ostwal
- Homi Bhabha national institute (HBNI), Mumbai, India
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Prachi Patil
- Homi Bhabha national institute (HBNI), Mumbai, India
- Department of Medical Gastroenterology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Ankita Manjrekar
- Centre for Cancer Epidemiology, Tata Memorial Centre, Kharghar, Navi Mumbai, India
| | - Shailesh V Shrikhande
- Homi Bhabha national institute (HBNI), Mumbai, India
- Division of Cancer Surgery, GI & HPB Surgical Services, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Rajendra Badwe
- Homi Bhabha national institute (HBNI), Mumbai, India
- Tata Memorial Centre-Surgical Oncology, Mumbai, Maharashtra, India
| | - Rajesh Dikshit
- Centre for Cancer Epidemiology, Tata Memorial Centre, Kharghar, Navi Mumbai, India
- Homi Bhabha national institute (HBNI), Mumbai, India
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Sharma P, Caldwell TS, Rivera MN, Gullapalli RR. Cadmium exposure activates Akt/ERK Signaling and pro-inflammatory COX-2 expression in human gallbladder epithelial cells via a ROS dependent mechanism. Toxicol In Vitro 2020; 67:104912. [PMID: 32512147 DOI: 10.1016/j.tiv.2020.104912] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 05/11/2020] [Accepted: 06/03/2020] [Indexed: 02/06/2023]
Abstract
Gallbladder cancer (GBC) is the commonest biliary tract cancer with an ill-defined etiology. We examined the role of Cd+2 exposures in a primary human gallbladder (GB) cell line model in this study. Cd+2 exposures induced decreased cell viability, reactive oxygen species (ROS) generation, altered Akt/ERK signaling pathway activation, PGE2 and COX-2 expression in a human primary gallbladder epithelial cell model. Pharmacological inhibitors were used to determine the key drivers of elevated COX-2 expression due to Cd+2 exposure. Our results show Cd+2 causes a dose-dependent reduction in GB cell viability (EC50 value - 18.6 μM). Dose-dependent activation of phospho-Akt and phospho-ERK signaling pathways via increased phosphoprotein expression was observed due to Cd+2. Signaling activation of Akt and ERK was prevented by 5 mM N-Acetyl Cysteine (NAC), establishing the role of ROS as a key driver in the activation process. Importantly, we observed Cd+2 also caused a dose dependent change in the COX-2 and PGE2 expression levels. PI3K-Akt and NF-kB signaling pathways play a key role in Cd+2 exposure induced COX-2 activation in the gallbladder epithelial cells. In conclusion, our study measures the toxicological effects of Cd+2 exposures on human GB epithelial cells for the first time and establishes the role of Cd+2 as a possible driver of the Akt/ERK pathway overactivity and chronic inflammation in gallbladder carcinogenesis.
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Affiliation(s)
- Priyanka Sharma
- University of New Mexico, Department of Pathology Albuquerque, NM, USA
| | - Trevar S Caldwell
- University of New Mexico, Department of Pathology Albuquerque, NM, USA
| | - Megan N Rivera
- University of New Mexico, Department of Pathology Albuquerque, NM, USA
| | - Rama R Gullapalli
- University of New Mexico, Department of Pathology Albuquerque, NM, USA; University of New Mexico, Department of Chemical and Biological Engineering Albuquerque, NM, USA.
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10
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Ayuso-Álvarez A, García-Pérez J, Triviño-Juárez JM, Larrinaga-Torrontegui U, González-Sánchez M, Ramis R, Boldo E, López-Abente G, Galán I, Fernández-Navarro P. Association between proximity to industrial chemical installations and cancer mortality in Spain. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2020; 260:113869. [PMID: 31991345 DOI: 10.1016/j.envpol.2019.113869] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 12/17/2019] [Accepted: 12/20/2019] [Indexed: 06/10/2023]
Abstract
It is likely that pollution from chemical facilities will affect the health of any exposed population; however, the majority of scientific evidence available has focused on occupational exposure rather than environmental. Consequently, this study assessed whether there could have been an excess of cancer-related mortality associated with environmental exposure to pollution from chemical installations - for populations residing in municipalities in the vicinity of chemical industries. To this end, we designed an ecological study which assessed municipal mortality due to 32 types of cancer in the period from 1999 to 2008. The exposure to pollution was estimated using distance from the facilities to the centroid of the municipality as a proxy for exposure. In order to assess any increased cancer mortality risk in municipalities potentially exposed to chemical facilities pollution (situated at a distance of ≤5 km from a chemical installation), we employed Bayesian Hierarchical Poisson Regression Models. This included two Bayesian inference methods: Integrated Nested Laplace Approximations (INLA) and Markov Chain Monte Carlo (MCMC, for validation). The reference category consisted of municipalities beyond the 5 km limit. We found higher mortality risk (relative risk, RR; estimated by INLA, 95% credible interval, 95%CrI) for both sexes for colorectal (RR, 1.09; 95%CrI, 1.05-1.15), gallbladder (1.14; 1.03-1.27), and ovarian cancers (1.10; 1.02-1.20) associated with organic chemical installations. Notably, pleural cancer (2.27; 1.49-3.41) in both sexes was related to fertilizer facilities. Associations were found for women, specifically for ovarian (1.11; 1.01-1.22) and breast cancers (1.06; 1.00-1.13) in the proximity of explosives/pyrotechnics installations; increased breast cancer mortality risk (1.10; 1.03-1.18) was associated with proximity to inorganic chemical installations. The results suggest that environmental exposure to pollutants from some types of chemical facilities may be associated with increased mortality from several different types of cancer.
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Affiliation(s)
- Ana Ayuso-Álvarez
- National Center of Tropical Medicine, Network Collaborative Research in Tropical Diseases (RICET), Carlos III Institute of Health, Avda. Monforte de Lemos, 5, 28029 Madrid, Spain; Department of Preventive Medicine and Public Health, School of Medicine, Autonomous University of Madrid, Calle del Arzobispo Morcillo 4, PC, 28029, Madrid, Spain
| | - Javier García-Pérez
- Cancer and Environmental Epidemiology Unit, Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Avda. Monforte de Lemos, 5, 28029 Madrid, Spain; Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública - CIBERESP), Spain
| | | | - Unai Larrinaga-Torrontegui
- Medicina Preventiva OSI Debabarrena, Hospital de Mendaro, Calle Mendarozabal Kalea, s/n, 20850 Mendaro Gipuzkoa, Spain
| | - Mario González-Sánchez
- Cancer and Environmental Epidemiology Unit, Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Avda. Monforte de Lemos, 5, 28029 Madrid, Spain
| | - Rebeca Ramis
- Cancer and Environmental Epidemiology Unit, Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Avda. Monforte de Lemos, 5, 28029 Madrid, Spain; Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública - CIBERESP), Spain
| | - Elena Boldo
- Cancer and Environmental Epidemiology Unit, Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Avda. Monforte de Lemos, 5, 28029 Madrid, Spain; Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública - CIBERESP), Spain
| | - Gonzalo López-Abente
- Cancer and Environmental Epidemiology Unit, Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Avda. Monforte de Lemos, 5, 28029 Madrid, Spain; Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública - CIBERESP), Spain
| | - Iñaki Galán
- Department of Chronic Diseases. Nacional Center for Epidemiology, Institute of Health Carlos III, Avda. Monforte de Lemos, 5, 28029 Madrid, Spain; School of Medicine, Autonomous University of Madrid/IdiPAZ (Instituto de Investigación del Hospital Universitario La Paz/La Paz University Teaching Hospital Research Institute), Calle del Arzobispo Morcillo 4, PC 28029, Madrid, Spain
| | - Pablo Fernández-Navarro
- Cancer and Environmental Epidemiology Unit, Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Avda. Monforte de Lemos, 5, 28029 Madrid, Spain; Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública - CIBERESP), Spain.
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11
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Abou-Alfa GK, Jarnagin W, El Dika I, D'Angelica M, Lowery M, Brown K, Ludwig E, Kemeny N, Covey A, Crane CH, Harding J, Shia J, O'Reilly EM. Liver and Bile Duct Cancer. ABELOFF'S CLINICAL ONCOLOGY 2020:1314-1341.e11. [DOI: 10.1016/b978-0-323-47674-4.00077-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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12
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Nemunaitis JM, Brown-Glabeman U, Soares H, Belmonte J, Liem B, Nir I, Phuoc V, Gullapalli RR. Gallbladder cancer: review of a rare orphan gastrointestinal cancer with a focus on populations of New Mexico. BMC Cancer 2018; 18:665. [PMID: 29914418 PMCID: PMC6006713 DOI: 10.1186/s12885-018-4575-3] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 06/01/2018] [Indexed: 12/18/2022] Open
Abstract
Gallbladder cancer is a rare malignancy of the biliary tract with a poor prognosis, frequently presenting at an advanced stage. While rare in the United States overall, gallbladder cancer has an elevated incidence in geographically distinct locations of the globe including Chile, North India, Korea, Japan and the state of New Mexico in the United States. People with Native American ancestry have a much elevated incidence of gallbladder cancer compared to Hispanic and non-Hispanic white populations of New Mexico. Gallbladder cancer is also one of the few bi-gendered cancers with an elevated female incidence compared to men. Similar to other gastrointestinal cancers, gallbladder cancer etiology is likely multi-factorial involving a combination of genomic, immunological, and environmental factors. Understanding the interplay of these unique epidemiological factors is crucial in improving the prevention, early detection, and treatment of this lethal disease. Previous studies have failed to identify a distinct genomic mutational profile in gallbladder cancers, however, work to identify promising clinically actionable targets is this form of cancer is ongoing. Examples include, interest in the HER2/Neu signaling pathway and the recognition that chronic inflammation plays a crucial role in gallbladder cancer pathogenesis. In this review, we provide a comprehensive overview of gallbladder cancer epidemiology, risk factors, pathogenesis, and treatment with a specific focus on the rural and Native American populations of New Mexico. We conclude this review by discussing future research directions with the goal of improving clinical outcomes for patients of this lethal malignancy.
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Affiliation(s)
- Jacklyn M Nemunaitis
- Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, USA.,Department of Internal Medicine, Division of Hematology and Oncology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Ursa Brown-Glabeman
- Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, USA.,Department of Internal Medicine, Division of Hematology and Oncology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Heloisa Soares
- Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, USA.,Department of Internal Medicine, Division of Hematology and Oncology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Jessica Belmonte
- Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, USA.,Department of Internal Medicine, Division of Hematology and Oncology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Ben Liem
- Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, USA.,Department of Internal Medicine, Division of Hematology and Oncology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Itzhak Nir
- Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, USA.,Department of Surgery, Division of Surgical Oncology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Victor Phuoc
- Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, USA.,Department of Surgery, Division of Surgical Oncology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Rama R Gullapalli
- Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, USA. .,Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. .,Department of Chemical and Biological Engineering, University of New Mexico, Room 333A, MSC08-4640, Albuquerque, NM, 87131, USA.
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13
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Sharma A, Sharma KL, Gupta A, Yadav A, Kumar A. Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update. World J Gastroenterol 2017; 23:3978-3998. [PMID: 28652652 PMCID: PMC5473118 DOI: 10.3748/wjg.v23.i22.3978] [Citation(s) in RCA: 250] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2016] [Revised: 02/01/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023] Open
Abstract
Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine PubMed (http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines (http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.
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14
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Kakaei F, Beheshtirouy S, Nejatollahi SM, Zarrintan S, Mafi MR. Surgical treatment of gallbladder carcinoma: a critical review. Updates Surg 2015; 67:339-51. [PMID: 26563387 DOI: 10.1007/s13304-015-0328-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 09/10/2015] [Indexed: 12/13/2022]
Abstract
Gallbladder carcinoma is a relatively uncommon cancer of gastrointestinal (GI) tract. Medical literature is full of nihilistic reports about the treatment of gallbladder carcinoma, especially due to its resistance to current radiotherapeutic or chemotherapeutic treatment modalities and difficult surgical approach for complete resection of these tumors. Herein, we review current diagnostic and therapeutic approaches to this rare GI cancer.
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Affiliation(s)
- Farzad Kakaei
- Section of Organ Transplantation, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of General & Vascular Surgery, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Samad Beheshtirouy
- Department of Cardiothoracic Surgery, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Sina Zarrintan
- Department of General & Vascular Surgery, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Mohammad Reza Mafi
- Department of General & Vascular Surgery, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
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15
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Rakić M, Patrlj L, Kopljar M, Kliček R, Kolovrat M, Loncar B, Busic Z. Gallbladder cancer. Hepatobiliary Surg Nutr 2014; 3:221-6. [PMID: 25392833 PMCID: PMC4207839 DOI: 10.3978/j.issn.2304-3881.2014.09.03] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Accepted: 09/02/2014] [Indexed: 02/05/2023]
Abstract
Gallbladder cancer is the fifth most common cancer involving gastrointestinal tract, but it is the most common malignancy of the biliary tract, accounting for 80-95% of biliary tract cancers. This tumor is a highly lethal disease with an overall 5-year survival of less than 5% and mean survival mere than 6 months. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis. The percentage of patients diagnosed to have gallbladder cancer after simple cholecystectomy for presumed gallbladder stone disease is 0.5-1.5%. Patients with preoperative suspicion of gallbladder cancer should not be treated by laparoscopy. Epidemiological studies have identified striking geographic and ethnic disparities-inordinately high occurrence in American Indians, elevated in Southeast Asia, yet quite low elsewhere in the Americas and the world. Environmental triggers play a critical role in eliciting cancer developing in the gallbladder, best exemplified by cholelithiasis and chronic inflammation from biliary tract and parasitic infections. Improved imaging modalities and improved radical aggressive surgical approach in the last decade has improved outcomes and helped prolong survival in patients with gallbladder cancer. The overall 5-year survival for patients with gallbladder cancer who underwent R0 curative resection was from 21% to 69%. In the future, the development of potential diagnostic markers for disease will yield screening opportunities for those at risk either with ethnic susceptibility or known anatomic anomalies of the biliary tract.
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Affiliation(s)
- Mislav Rakić
- Department of Hepatobiliary Surgery, University Hospital Dubrava, Zagreb, Croatia
| | - Leonardo Patrlj
- Department of Hepatobiliary Surgery, University Hospital Dubrava, Zagreb, Croatia
| | - Mario Kopljar
- Department of Hepatobiliary Surgery, University Hospital Dubrava, Zagreb, Croatia
| | - Robert Kliček
- Department of Hepatobiliary Surgery, University Hospital Dubrava, Zagreb, Croatia
| | - Marijan Kolovrat
- Department of Hepatobiliary Surgery, University Hospital Dubrava, Zagreb, Croatia
| | - Bozo Loncar
- Department of Hepatobiliary Surgery, University Hospital Dubrava, Zagreb, Croatia
| | - Zeljko Busic
- Department of Hepatobiliary Surgery, University Hospital Dubrava, Zagreb, Croatia
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16
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Abstract
Gallbladder cancer, though generally considered rare, is the most common malignancy of the biliary tract, accounting for 80%-95% of biliary tract cancers. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis, often proving fatal. Its carcinogenesis follows a progression through a metaplasia-dysplasia-carcinoma sequence. This comprehensive review focuses on and explores the risks, management, and outcomes for primary gallbladder carcinoma. Epidemiological studies have identified striking geographic and ethnic disparities - inordinately high occurrence in American Indians, elevated in Southeast Asia, yet quite low elsewhere in the Americas and the world. Age, female sex, congenital biliary tract anomalies, and a genetic predisposition represent important risk factors that are immutable. Environmental triggers play a critical role in eliciting cancer developing in the gallbladder, best exemplified by cholelithiasis and chronic inflammation from biliary tract and parasitic infections. Mortality rates closely follow incidence; those countries with the highest prevalence of gallstones experience the greatest mortality from gallbladder cancer. Vague symptoms often delay the diagnosis of gallbladder cancer, contributing to its overall progression and poor outcome. Surgery represents the only potential for cure. Some individuals are fortunate to be incidentally found to have gallbladder cancer at the time of cholecystectomy being performed for cholelithiasis. Such an early diagnosis is imperative as a late presentation connotes advanced staging, nodal involvement, and possible recurrence following attempted resection. Overall mean survival is a mere 6 months, while 5-year survival rate is only 5%. The dismal prognosis, in part, relates to the gallbladder lacking a serosal layer adjacent to the liver, enabling hepatic invasion and metastatic progression. Improved imaging modalities are helping to diagnose patients at an earlier stage. The last decade has witnessed improved outcomes as aggressive surgical management and preoperative adjuvant therapy has helped prolong survival in patients with gallbladder cancer. In the future, the development of potential diagnostic markers for disease will yield screening opportunities for those at risk either with ethnic susceptibility or known anatomic anomalies of the biliary tract. Meanwhile, clarification of the value of prophylactic cholecystectomy should provide an opportunity for secondary prevention. Primary prevention will arrive once the predictive biomarkers and environmental risk factors are more clearly identified.
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Affiliation(s)
- Rajveer Hundal
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Eldon A Shaffer
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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17
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Abstract
Gallbladder cancer, though generally considered rare, is the most common malignancy of the biliary tract, accounting for 80%-95% of biliary tract cancers. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis, often proving fatal. Its carcinogenesis follows a progression through a metaplasia-dysplasia-carcinoma sequence. This comprehensive review focuses on and explores the risks, management, and outcomes for primary gallbladder carcinoma. Epidemiological studies have identified striking geographic and ethnic disparities - inordinately high occurrence in American Indians, elevated in Southeast Asia, yet quite low elsewhere in the Americas and the world. Age, female sex, congenital biliary tract anomalies, and a genetic predisposition represent important risk factors that are immutable. Environmental triggers play a critical role in eliciting cancer developing in the gallbladder, best exemplified by cholelithiasis and chronic inflammation from biliary tract and parasitic infections. Mortality rates closely follow incidence; those countries with the highest prevalence of gallstones experience the greatest mortality from gallbladder cancer. Vague symptoms often delay the diagnosis of gallbladder cancer, contributing to its overall progression and poor outcome. Surgery represents the only potential for cure. Some individuals are fortunate to be incidentally found to have gallbladder cancer at the time of cholecystectomy being performed for cholelithiasis. Such an early diagnosis is imperative as a late presentation connotes advanced staging, nodal involvement, and possible recurrence following attempted resection. Overall mean survival is a mere 6 months, while 5-year survival rate is only 5%. The dismal prognosis, in part, relates to the gallbladder lacking a serosal layer adjacent to the liver, enabling hepatic invasion and metastatic progression. Improved imaging modalities are helping to diagnose patients at an earlier stage. The last decade has witnessed improved outcomes as aggressive surgical management and preoperative adjuvant therapy has helped prolong survival in patients with gallbladder cancer. In the future, the development of potential diagnostic markers for disease will yield screening opportunities for those at risk either with ethnic susceptibility or known anatomic anomalies of the biliary tract. Meanwhile, clarification of the value of prophylactic cholecystectomy should provide an opportunity for secondary prevention. Primary prevention will arrive once the predictive biomarkers and environmental risk factors are more clearly identified.
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Affiliation(s)
- Rajveer Hundal
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Eldon A Shaffer
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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18
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Abstract
Gallbladder cancer, though generally considered rare, is the most common malignancy of the biliary tract, accounting for 80%–95% of biliary tract cancers. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis, often proving fatal. Its carcinogenesis follows a progression through a metaplasia–dysplasia–carcinoma sequence. This comprehensive review focuses on and explores the risks, management, and outcomes for primary gallbladder carcinoma. Epidemiological studies have identified striking geographic and ethnic disparities – inordinately high occurrence in American Indians, elevated in Southeast Asia, yet quite low elsewhere in the Americas and the world. Age, female sex, congenital biliary tract anomalies, and a genetic predisposition represent important risk factors that are immutable. Environmental triggers play a critical role in eliciting cancer developing in the gallbladder, best exemplified by cholelithiasis and chronic inflammation from biliary tract and parasitic infections. Mortality rates closely follow incidence; those countries with the highest prevalence of gallstones experience the greatest mortality from gallbladder cancer. Vague symptoms often delay the diagnosis of gallbladder cancer, contributing to its overall progression and poor outcome. Surgery represents the only potential for cure. Some individuals are fortunate to be incidentally found to have gallbladder cancer at the time of cholecystectomy being performed for cholelithiasis. Such an early diagnosis is imperative as a late presentation connotes advanced staging, nodal involvement, and possible recurrence following attempted resection. Overall mean survival is a mere 6 months, while 5-year survival rate is only 5%. The dismal prognosis, in part, relates to the gallbladder lacking a serosal layer adjacent to the liver, enabling hepatic invasion and metastatic progression. Improved imaging modalities are helping to diagnose patients at an earlier stage. The last decade has witnessed improved outcomes as aggressive surgical management and preoperative adjuvant therapy has helped prolong survival in patients with gallbladder cancer. In the future, the development of potential diagnostic markers for disease will yield screening opportunities for those at risk either with ethnic susceptibility or known anatomic anomalies of the biliary tract. Meanwhile, clarification of the value of prophylactic cholecystectomy should provide an opportunity for secondary prevention. Primary prevention will arrive once the predictive biomarkers and environmental risk factors are more clearly identified.
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Affiliation(s)
- Rajveer Hundal
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Eldon A Shaffer
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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19
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Yadav R, Jain D, Mathur SR, Sharma A, Iyer VK. Gallbladder carcinoma: An attempt of WHO histological classification on fine needle aspiration material. Cytojournal 2013; 10:12. [PMID: 23858322 PMCID: PMC3709381 DOI: 10.4103/1742-6413.113627] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2013] [Accepted: 05/23/2013] [Indexed: 12/13/2022] Open
Abstract
Background: Carcinoma of the gallbladder (CaGB) is common in India and its prognosis depends primarily on the extent of the disease and histological type. We aim to study the role of guided fine needle aspiration cytology (FNAC) for diagnosis of CaGB and to evaluate the feasibility of applying world health organization (WHO) classification on fine needle aspiration (FNA) material to predict the outcome of the tumor. Materials and Methods: Retrospective cytomorphologic analysis was performed in all cases of CaGB diagnosed by ultrasound (US) guided FNAC over a period of 2 years. A specific subtype was assigned according to WHO classification based on characteristic cytologic features. These included papillary or acinar arrangement, intra and extracellular mucin, keratin, rosettes and columnar, signet ring, atypical squamous, small, clear, spindle and giant cells. Correlation with histopathology was performed when available. Results: A total of 541 aspirations with clinical or radiological suspicion of primary CaGB were studied. Of these, 54 aspirates were unsatisfactory. Fifty cases were negative for malignancy. Remaining 437 aspirates were positive for carcinoma. Histopathologic diagnosis was available in 32 cases. Adenocarcinoma was the most frequent diagnosis in 86.7% of cases. Mucinous, signet ring, adenosquamous, squamous, small cell, mixed adenoneuroendocrine and undifferentiated carcinoma including spindle and giant cell subtypes were diagnosed identifying specific features on FNAC. Correlation with histopathology was present in all, but one case giving rise to sensitivity of 96.8%. No post-FNA complications were recorded. Conclusions: US guided FNAC is a safe and effective method to diagnose CaGB. Although, rare, clinically and prognostically significant variants described in WHO classification can be detected on cytology.
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Affiliation(s)
- Rajni Yadav
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
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20
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Murakami S, Ajiki T, Ueno K, Sawa H, Tsuchida S, Otsubo I, Yoshida Y, Shinozaki K, Okazaki T, Matsumoto I, Fukumoto T, Ku Y. Curative resection of hilar cholangiocarcinoma in a 25-year-old woman: report of a case. Surg Today 2013; 44:1350-4. [PMID: 23580078 DOI: 10.1007/s00595-013-0574-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2012] [Accepted: 01/16/2013] [Indexed: 10/27/2022]
Abstract
A 25-year-old woman was referred to our hospital with persistent upper abdominal pain. Preoperative imaging studies revealed a hilar bile duct stricture with portal venous encasement, and the patient underwent curative resection involving extended left hepatectomy and segmental portal vein resection. The pathological findings demonstrated a well-differentiated tubular adenocarcinoma of the bile duct with regional lymph node metastasis (stage IIIB according to the UICC TNM classification), as well as the overexpression of p53 proteins and the K-ras gene mutation in tumor cells. The patient has shown no evidence of recurrence in the 10 months since the operation. Although there are several reports of relatively young adults with cholangiocarcinoma, the majority of such patients demonstrate either an anomalous arrangement of the pancreaticobiliary duct system or primary sclerosing cholangitis. The absence of any morphological abnormalities in this patient's biliary system implicates de novo carcinogenesis as the most likely cause of the cholangiocarcinoma.
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Affiliation(s)
- Sae Murakami
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan,
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21
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Chhabra D, Oda K, Jagannath P, Utsunomiya H, Takekoshi S, Nimura Y. Chronic Heavy Metal Exposure and Gallbladder Cancer Risk in India, a Comparative Study with Japan. Asian Pac J Cancer Prev 2012; 13:187-90. [DOI: 10.7314/apjcp.2012.13.1.187] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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22
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Srivastava K, Srivastava A, Sharma KL, Mittal B. Candidate gene studies in gallbladder cancer: a systematic review and meta-analysis. Mutat Res 2011; 728:67-79. [PMID: 21708280 DOI: 10.1016/j.mrrev.2011.06.002] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2011] [Revised: 06/11/2011] [Accepted: 06/13/2011] [Indexed: 12/16/2022]
Abstract
Gallbladder cancer (GBC) is the most frequent biliary tract malignancy. Wide variations in GBC incidence and familial and epidemiological data suggest involvement of a genetic component in its etiopathogenesis. A systematic review of genetic association studies in GBC was performed by applying a meta-analysis approach and systematically reviewing PubMed database using appropriate terms. Odds ratios (ORs) and 95% confidence intervals (CIs) were appropriately derived for each gene-disease association using fixed and random effect models. Meta-regression with population size and genotyping method was also performed. Study quality was assessed using a 10-point scoring system designed from published guidelines. Following a review of 44 published manuscripts and one unpublished report, 80 candidate gene variants and 173 polymorphisms were analyzed among 1046 cases and 2310 controls. Majority of studies were of intermediate quality. Four polymorphisms with >3 separate studies were included in the meta-analysis [OGG1 (rs1052133), TP53 (rs1042522), CYP1A1 (rs1048943) and GSTM1 null polymorphism]. The meta-analysis demonstrated no significant associations of any of the above polymorphisms with GBC susceptibility except TP53 (rs1042522) polymorphism. To conclude, existing candidate gene studies in GBC susceptibility have so far been insufficient to confirm any association. Future research should focus on a more comprehensive approach utilizing potential gene-gene, gene-environment interactions and high-risk haplotypes.
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Affiliation(s)
- Kshitij Srivastava
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
| | - Anvesha Srivastava
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, UP, India
| | - Kiran Lata Sharma
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, UP, India
| | - Balraj Mittal
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, UP, India.
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Abstract
Gallbladder cancer (GBC) shows a marked geographical variation in its incidence, with the highest figures being seen in India and Chile and relatively low levels in many Western countries. Risk factors for its development include the presence of gallstones, infection and the presence of an anomalous pancreatobiliary ductal junction. It can arise from either a pathway involving metaplasia or dysplasia or one in which there is a pre-existing adenoma. The former is the more common and, because it is often not associated with a macroscopically recognizable lesion, leads to the recommendation that all gallbladders need to be examined microscopically. Accurate staging of invasive cancers is essential to determine prognosis and treatment, and this requires extensive tumour sampling. A number of genetic alterations have been identified in the preinvasive and invasive stages of GBC and they support the morphological evidence of there being two pathways by which tumours develop. Some of these genetic changes are associated with particular risk factors. For example, cases with anomalous pancreatobiliary ductal junction show a higher frequency of K-ras mutations. Some changes are associated with differences in prognosis. For example, cancers without expression of p21 but with expression for p27 have a better prognosis, whereas those that express c-erb-B2 have a worse one. Work has also been done on identifying clinical, imaging and other factors that indicate that patients have a higher risk of having GBC. This is particularly important in high-incidence areas in which GBC is a significant public health problem.
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Affiliation(s)
- Robert David Goldin
- Department of Histopathology, Imperial College Faculty of Medicine at St Mary's, London, UK.
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Li L, Yang H, Chen D, Cui C, Dou QP. Disulfiram promotes the conversion of carcinogenic cadmium to a proteasome inhibitor with pro-apoptotic activity in human cancer cells. Toxicol Appl Pharmacol 2008; 229:206-14. [PMID: 18304598 DOI: 10.1016/j.taap.2008.01.022] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2007] [Revised: 01/16/2008] [Accepted: 01/18/2008] [Indexed: 11/28/2022]
Abstract
The ubiquitin-proteasome system is involved in various cellular processes, including transcription, apoptosis, and cell cycle. In vitro, in vivo, and clinical studies suggest the potential use of proteasome inhibitors as anticancer drugs. Cadmium (Cd) is a widespread environmental pollutant that has been classified as a human carcinogen. Recent study in our laboratory suggested that the clinically used anti-alcoholism drug disulfiram (DSF) could form a complex with tumor cellular copper, resulting in inhibition of the proteasomal chymotrypsin-like activity and induction of cancer cell apoptosis. In the current study, we report, for the first time, that DSF is able to convert the carcinogen Cd to a proteasome-inhibitor and cancer cell apoptosis inducer. Although the DSF-Cd complex inhibited the chymotrypsin-like activity of a purified 20S proteasome with an IC(50) value of 32 micromol/L, this complex was much more potent in inhibiting the chymotrypsin-like activity of prostate cancer cellular 26S proteasome. Inhibition of cellular proteasome activity by the DSF-Cd complex resulted in the accumulation of ubiquitinated proteins and the natural proteasome substrate p27, which was followed by activation of calpain and induction of apoptosis. Importantly, human breast cancer MCF10DCIS cells were much more sensitive to the DSF-Cd treatment than immortalized but non-tumorigenic human breast MCF-10A cells, demonstrating that the DSF-Cd complex could selectively induce proteasome inhibition and apoptosis in human tumor cells. Our work suggests the potential use of DSF for treatment of cells with accumulated levels of carcinogen Cd.
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Affiliation(s)
- Lihua Li
- The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA
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Venniyoor A. Cholesterol gallstones and cancer of gallbladder (CAGB): molecular links. Med Hypotheses 2007; 70:646-53. [PMID: 17855001 DOI: 10.1016/j.mehy.2007.06.040] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2007] [Accepted: 06/19/2007] [Indexed: 01/11/2023]
Abstract
There is a known association between cholesterol gallstones and cancer of gall bladder (CAGB). However, the exact relation is not clear. It is proposed they are linked at molecular level by the activity of the orphan nuclear receptors (ONRs) and ABC transporter pumps involved in cholesterol and xenobiotic efflux from the liver into bile. There is evidence that these two pathways are closely interlinked and influence each other. Genetic and environmental factors that upregulate these systems can lead to the simultaneous pumping of cholesterol (which precipitate as gallstones) and a food carcinogen into the bile in gall bladder; the latter causes malignant transformation. Aflatoxin B, a potent hepatocarcinogen, could be the culprit in endemic regions such as South America and North India.
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Affiliation(s)
- Ajit Venniyoor
- Department of Medicine and Medical Oncology, INHS Asvini, Near RC Church, Colaba, Mumbai Bombay, Maharastra 400 005, India.
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