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Tian B, Xia X, Li Q, Qin J. Advances in BRAF mutated colorectal cancer-could deoxycholic acid be the culprit? Biochim Biophys Acta Rev Cancer 2025; 1880:189347. [PMID: 40339670 DOI: 10.1016/j.bbcan.2025.189347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 05/02/2025] [Accepted: 05/05/2025] [Indexed: 05/10/2025]
Abstract
BRAF mutated colorectal cancer (CRC) often demonstrates distinct molecular profiles characterized by a high methylator phenotype with two different microsatellite statuses (MSI and MSS) and corresponding methylation spectra. Prognostic disparities between these two different BRAF mutated CRC arise from divergent carcinogenic pathways, with BRAF-mutated MSS CRC exhibiting particularly unfavorable clinical outcomes. The underlying mechanism of these phenomena stems from epigenetic heterogeneity in methylation landscapes. Emerging evidences linking cholelithiasis and deoxycholic acid (DCA) to BRAF-mutated CRC pathogenesis warrant systematic investigation into their potential mechanistic relationships. Elucidating these connections could unravel novel pathogenetic pathways and inform targeted strategies for risk mitigation, molecular diagnostics, and therapeutic intervention of BRAF-mutated CRC.
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Affiliation(s)
- Binle Tian
- Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Xin Xia
- Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Qi Li
- Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
| | - Jian Qin
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
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2
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Jeon HJ, Yoon SK, Park B, Kim HS, Chae H, Kim H, Shin SH, Han IW, Heo JS, Lee O, Yoon SJ. Development and External Validation of a Nomogram Predicting Early Recurrence of Gallbladder Cancer Using Preoperatively Available Prognosticators: A Korean Multicenter Retrospective Study. Cancers (Basel) 2025; 17:1450. [PMID: 40361377 PMCID: PMC12071069 DOI: 10.3390/cancers17091450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2025] [Revised: 04/23/2025] [Accepted: 04/24/2025] [Indexed: 05/15/2025] Open
Abstract
Background: Gallbladder cancer (GBC) is a rare and aggressive malignancy with poor prognosis and high recurrence rates, even after curative surgical resection. Early recurrence, defined as recurrence within one year after surgery, remains a major clinical concern. This study aimed to identify preoperative prognostic factors and develop a predictive model for early recurrence and overall survival in resected GBC patients. Methods: We retrospectively analyzed data from 251 patients who underwent curative-intent resection for GBC between 2008 and 2017. Logistic regression was used to identify preoperative factors associated with early recurrence. Significant variables were used to construct a nomogram, which was externally validated using a cohort of 176 patients from three independent tertiary centers. Results: The independent predictors of early recurrence included male sex, chronic liver disease, preoperative symptoms, elevated carcinoembryonic antigen (CEA), sarcopenic obesity, clinical T3 or higher stage, and suspected metastatic lymph nodes. The nomogram demonstrated strong predictive performance with an AUC of 0.872 (95% CI: 0.817-0.927) in internal validation and 0.703 (95% CI: 0.613-0.793) in external validation. Conclusions: We developed and externally validated a novel nomogram that predicts early recurrence in GBC using only preoperative factors. This model may support individualized risk assessment and aid surgeons and patients in shared decision-making prior to high-risk surgery.
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Affiliation(s)
- Hyun Jeong Jeon
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu 41404, Republic of Korea
| | - So Kyung Yoon
- Department of Surgery, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea
| | - Boram Park
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea;
- College of Medicine, Inha University, Incheon 22332, Republic of Korea
| | - Hyeong Seok Kim
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
| | - Hochang Chae
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
| | - Hongbeom Kim
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
| | - Sang Hyun Shin
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
| | - In Woong Han
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
| | - Jin Seok Heo
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
| | - Okjoo Lee
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea
| | - So Jeong Yoon
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; (H.S.K.)
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Kim J, Lee YS, Lee JC, Hwang JH. Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study. BMC Gastroenterol 2025; 25:138. [PMID: 40045214 PMCID: PMC11883955 DOI: 10.1186/s12876-025-03746-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 02/28/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND Choledocholithiasis has been reported to be associated with the occurrence of cholangiocarcinoma (CCA); however, the association has not yet been sufficiently demonstrated. This study aimed to evaluate the association between choledocholithiasis (common bile duct stones) and CCA. METHODS This nationwide retrospective cohort study used the Health Insurance Review and Assessment database of individuals diagnosed with choledocholithiasis between 2008 and 2009 in South Korea. Individuals were stratified by age, and CCA was categorized into extrahepatic CCA (ECA) and intrahepatic CCA (ICA). The standardized incidence ratio (SIR) was calculated to compare CCA incidence between patients with choledocholithiasis and the general population. RESULTS The study enrolled 20,808 patients with choledocholithiasis (52.35% men and 47.65% women; male-to-female ratio: 1.09:1). Over a 10-year follow-up period, CCA occurred in 548 (2.64%) patients, comprising 238 (1.14%) ECA cases and 310 (1.48%) ICA cases. The SIR was 25.23 (95% confidence interval [CI]: 21.98-28.85) for ECA and 24.64 (95% CI: 21.87-27.73) for ICA. Statistical significance persisted even after excluding cases within the first 2 years from the index date, with an SIR of 18.63 (95% CI: 16.23-21.28) for ICA and 12.73 (95% CI: 10.50-15.30) for ECA. The SIRs peaked in patients diagnosed with choledocholithiasis at the age of 70-79 years (SIR 16.61, 95% CI: 11.83-22.69) for ECA and 60-69 years (SIR 29.27, 95% CI: 23.53-36.03) for ICA. CONCLUSION Our study demonstrated a significant association between choledocholithiasis and cholangiocarcinoma, particularly those in their 70s for ECA and 60s for ICA. However, causation cannot be established due to the retrospective design.
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Affiliation(s)
- Jaihwan Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Yoon Suk Lee
- Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, 170, Juhwa-ro, Ilsanseo-gu, Goyang, South Korea.
| | - Jong-Chan Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
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Geng W, Ma K, Jiang Y, Peng S, Wang X. Association between gallbladder disease and colorectal neoplasia: a meta-analysis. Sci Rep 2025; 15:6276. [PMID: 39979467 PMCID: PMC11842739 DOI: 10.1038/s41598-025-91002-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Accepted: 02/17/2025] [Indexed: 02/22/2025] Open
Abstract
Although studies are available on the impact of gallbladder disease on the risk of colorectal neoplasia (CRN), the results are still debatable. We conducted a meta-analysis to summarize the correlation between gallbladder diseases and CRN. Eligible studies up to June 2024 were screened and retrieved using PubMed and Web of Science as well as by performing a manual review of references. Subgroup analyses stratified by region, location, and pathology of CRN were performed. Subgroup analyses stratified by classification and size of gallbladder disease were also performed. The pooled odd ratios (ORs) with 95% confidence intervals (CIs) were calculated. Sensitivity analyses were also performed. Begg's test was conducted to determine the publication bias. A total of twenty studies were included. The results showed that gallbladder disease significantly increased the risk of CRN (OR = 1.20, 95%CI, 1.11-1.29, P < 0.001). Subgroup analyses showed that subjects with gallstones (OR = 1.14, 95%CI, 1.05-1.25, P = 0.003) or gallbladder polyps (OR = 1.23, 95%CI, 1.15-1.31, P < 0.001) had a significantly higher risk of developing CRN. Asians (OR = 1.21, 95%CI, 1.11-1.31, P < 0.001) with gallstones were more likely to develop CRN. Patients with larger gallbladder polyps (≥ 0.5 cm) were at a greater risk of developing CRN (OR = 1.96, 95%CI, 1.41-2.73, P < 0.001). Gallbladder polyps and gallstones increase the risk of CRN. Therefore, colonoscopy should be performed in patients with gallbladder disease, especially in those of Asian descent, as well as in people with large gallbladder polyps.
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Affiliation(s)
- Wenbin Geng
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, 68 Gehu middle road, Wujing District, Changzhou, 213000, Jiangsu Province, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Kai Ma
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, 68 Gehu middle road, Wujing District, Changzhou, 213000, Jiangsu Province, China
- The Third Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yizhou Jiang
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, 68 Gehu middle road, Wujing District, Changzhou, 213000, Jiangsu Province, China
- The Third Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Shiyu Peng
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
- Department of Gastroenterology, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region, China
| | - Xiaoyong Wang
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, 68 Gehu middle road, Wujing District, Changzhou, 213000, Jiangsu Province, China.
- The Third Affiliated Hospital of Nanjing Medical University, Nanjing, China.
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Zhu Y, Shen L, Huo Y, Wan Q, Qin Y, Hu R, Shi L, Su Q, Yu X, Yan L, Qin G, Tang X, Chen G, Xu Y, Wang T, Zhao Z, Gao Z, Wang G, Shen F, Gu X, Luo Z, Chen L, Li Q, Ye Z, Zhang Y, Liu C, Wang Y, Wu S, Yang T, Deng H, Chen L, Zeng T, Zhao J, Mu Y, Wang W, Ning G, Lu J, Xu M, Bi Y, Hu W. Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study. Front Med 2025; 19:79-89. [PMID: 39722067 DOI: 10.1007/s11684-024-1111-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 09/18/2024] [Indexed: 12/28/2024]
Abstract
This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
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Affiliation(s)
- Yuanyue Zhu
- Department of Geriatrics, Medical Center on Aging, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Linhui Shen
- Department of Geriatrics, Medical Center on Aging, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Yanan Huo
- Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, 330006, China
| | - Qin Wan
- The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Yingfen Qin
- The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China
| | - Ruying Hu
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, China
| | - Lixin Shi
- Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China
| | - Qing Su
- Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Xuefeng Yu
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Li Yan
- Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Guijun Qin
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Xulei Tang
- The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Gang Chen
- Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350003, China
| | - Yu Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Tiange Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Zhiyun Zhao
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Zhengnan Gao
- Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian, 116033, China
| | - Guixia Wang
- The First Hospital of Jilin University, Changchun, 130021, China
| | - Feixia Shen
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Xuejiang Gu
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Zuojie Luo
- The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China
| | - Li Chen
- Qilu Hospital of Shandong University, Jinan, 250012, China
| | - Qiang Li
- The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China
| | - Zhen Ye
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, China
| | - Yinfei Zhang
- Central Hospital of Shanghai Jiading District, Shanghai, 201899, China
| | - Chao Liu
- Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, 210028, China
| | - Youmin Wang
- The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Shengli Wu
- Karamay Municipal People's Hospital, Karamay, 834000, China
| | - Tao Yang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Huacong Deng
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Lulu Chen
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tianshu Zeng
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jiajun Zhao
- Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250012, China
| | - Yiming Mu
- Chinese People's Liberation Army General Hospital, Beijing, 100853, China
| | - Weiqing Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Guang Ning
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Jieli Lu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Min Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
- Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Yufang Bi
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
- Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Weiguo Hu
- Department of Geriatrics, Medical Center on Aging, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
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Zhu L, He J, Yang Z, Huang X, Hong J, Zhou X, Chen Y, Li G. Endoscopic retrograde cholangiopancreatography combined with extracorporeal shock wave lithotripsy for the removal of large gallbladder stones: a pilot study. BMC Gastroenterol 2025; 25:9. [PMID: 39789423 PMCID: PMC11715249 DOI: 10.1186/s12876-025-03590-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 01/03/2025] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Endoscopic gallbladder-preserving cholecystolithotomy (EGPC) has become an alternative option for treating cholecystolithiasis. However, developing a new method of EGPC in which the gallbladder wall is not damaged remains a challenge. This study introduced a new EGPC method called endoscopic retrograde cholangiopancreatography (ERCP) combined with extracorporeal shock wave lithotripsy (ESWL), which preserves the integrity of the gallbladder wall in the treatment of cholecystolithiasis complicated with choledocholithiasis. METHODS In total, six patients (aged 23-72 years, 3 males and 3 females, Han ethnicity) who had large gallbladder stones (diameter ≥ 1 cm) complicated with common bile duct (CBD) stones and who underwent ERCP combined with ESWL at the First Affiliated Hospital of Nanchang University from July 2022 to December 2022 were enrolled. The patients' clinical characteristics, endoscopic treatment and follow-up data were analyzed. A paired t test was performed to compare the differences in the main serological indicators before and after EGPC. RESULTS Of the six patients, five completed EGPC, and one failed due to intolerable abdominal pain during ESWL and was subsequently transferred to surgery. With respect to post-EGPC adverse events, one patient developed mild post-ERCP pancreatitis, and no other adverse events occurred. Both the technical success rate and clinical success rate of ERCP combined with ESWL were 83.3% and the incidence of adverse events was 16.7%. The six patients were followed up for an average of 24 months, during which only one patient experienced a recurrence of gallbladder stones at the 3-month follow-up, but no gallbladder stones were found at the 6-month follow-up after oral administration of ursodeoxycholic acid. CONCLUSIONS ERCP combined with ESWL is a potentially safe and effective treatment for large gallbladder stones. TRIAL REGISTRATION This study was registered at the Chinese Clinical Trial Registry site. [Registration number: ChiCTR2200060927 ( http://www.chictr.org.cn/ ); registration date: June 14, 2022].
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Affiliation(s)
- Liang Zhu
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, China
| | - Jinli He
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, China
| | - Zhenzhen Yang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, China
| | - Xi Huang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, China
| | - Junbo Hong
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, China
| | - Xiaojiang Zhou
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, China
| | - Youxiang Chen
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, China.
| | - Guohua Li
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, China.
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7
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Kim YA, Kim HJ, Kang MJ, Han SS, Park HM, Park SJ. Increased diagnosis of hepato-biliary-pancreatic cancer after cholecystectomy: a population-based study. Sci Rep 2025; 15:411. [PMID: 39747399 PMCID: PMC11696006 DOI: 10.1038/s41598-024-84781-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 12/26/2024] [Indexed: 01/04/2025] Open
Abstract
Given the increasing trend of cholecystectomy, it is imperative to reassess surgical and surveillance strategies in consideration of the potential long-term risks for digestive tract cancers. The objective of this study was to assess the risk of gastrointestinal (GI) and hepato-biliary-pancreatic (HBP) cancer incidence after cholecystectomy. The data for this cohort study was obtained from the National Health Insurance Service database in Korea. 715,872 patients who underwent cholecystectomy between 2004 and 2020 were compared to 1,431,728 individuals who did not underwent cholecystectomy after age, sex, and year of cholecystectomy was matched. The overall incidence rate ratio (IRR) for all GI and HBP cancers was 1.08 (95% C.I., 1.06-1.10). Specifically, the risk of diagnosis of extrahepatic bile duct cancer (IRR 1.92), intrahepatic bile duct cancer (1.78), hepatocellular carcinoma (1.22), and pancreatic cancer (1.13) was significantly increased in the cholecystectomy group. The highest IRR was observed within the 1-3 years following cholecystectomy. Subsequently, the risk of diagnosis gradually decreased and returned to a level comparable to that of the matched control group after 5 to 10 years. In conclusion, hepato-biliary-pancreatic cancer are frequently diagnosed subsequent to cholecystectomy. Too short period of post-cholecystectomy follow-up may hinder monitoring of hepato-biliary-pancreatic cancer occurrence.
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Affiliation(s)
- Young Ae Kim
- Division of Cancer Control & Policy, National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea
| | - Hak Jun Kim
- Division of Cancer Control & Policy, National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea
- Department of Artificial Intelligence Convergence, Hallym University Graduate School, Chuncheon, Republic of Korea
| | - Mee Joo Kang
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea.
- Division of Cancer Registration and Surveillance, National Cancer Control Institute, National Cancer Center, 323 Ilsan-ro Ilsandong-gu, Goyang, 10408, Republic of Korea.
| | - Sung-Sik Han
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Hyeong Min Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Sang-Jae Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea
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8
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Wang Q, Zhou Y. Correlation Between Cholecystectomy and the Risk of Gastric Cancer. Am J Gastroenterol 2024:00000434-990000000-01500. [PMID: 39729293 DOI: 10.14309/ajg.0000000000003232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2024]
Affiliation(s)
- Qin Wang
- West China Hospital, Chengdu, Sichuan, China
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9
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Zhou X, Xu L, Zhang Q, Chen W, Xie H. The impact of long-term (≥5 years) cholecystectomy on gut microbiota changes and its influence on colorectal cancer risk: based on 16S rDNA sequencing analysis. Eur J Gastroenterol Hepatol 2024; 36:1288-1297. [PMID: 39012652 DOI: 10.1097/meg.0000000000002827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/17/2024]
Abstract
BACKGROUND Colorectal cancer (CRC) continues to be a major global health concern. Recent advances in molecular biology have highlighted the gut microbiota's role in CRC. This study investigates long-term (≥5 years) gut microbiota changes in patients postcholecystectomy, comparing them with CRC patients and healthy controls to assess their impact on CRC development. METHODS Sixty participants were divided into three groups: 20 healthy controls, 20 postcholecystectomy (PCE) patients, and 20 CRC patients. Demographic data and stool samples were collected. Gut microbiota composition, abundance, and diversity were analyzed using high-throughput 16S rDNA sequencing. RESULTS Significant differences in microbial community, α-diversity ( P < 0.05) and β-diversity ( P = 0.006), were observed among the three groups. At the phylum level, Firmicutes abundance was significantly reduced in PCE and CRC groups compared with the control group ( P = 0.002), while changes in other phyla were not significant ( P >0.05). At the genus level, Bacteroides , Dialister , and Parabacteroides increased progressively from control to PCE to CRC groups ( P = 0.004, 0.001, and 0.002). Prevotella decreased across these groups ( P = 0.041). Faecalibacterium and Roseburia abundances were reduced in PCE and CRC groups compared with controls ( P = 0.001 and 0.003). The Random Forest algorithm identified Parabacteroides , Bacteroides , Roseburia , and Dialister as key distinguishing genera. CONCLUSION The gut microbiota of long-term (≥5 years) PCE patients significantly differs from that of controls and resembles that of CRC patients, suggesting a potential link between cholecystectomy and CRC development through key microbial changes.
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Affiliation(s)
- Xiecheng Zhou
- Department of General Surgery, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Liang Xu
- Department of General Surgery, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Qixing Zhang
- Department of Pediatrics, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Wenqi Chen
- Department of General Surgery, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Hongwei Xie
- Department of General Surgery, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
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10
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Kim M, Han KD, Ko SH, Woo Y, Han JH. Effect of smoking on the risk of gastrointestinal cancer after cholecystectomy: A national population-based cohort study. World J Gastrointest Surg 2024; 16:2796-2807. [PMID: 39351570 PMCID: PMC11438817 DOI: 10.4240/wjgs.v16.i9.2796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 07/04/2024] [Accepted: 07/31/2024] [Indexed: 09/18/2024] Open
Abstract
BACKGROUND The role of smoking in the incidence of colorectal cancer (CRC) or gastric cancer (GC) in populations undergoing cholecystectomy has not been investigated. AIM To evaluate the effect of smoking on CRC or GC development in cholecystectomy patients. METHODS A total of 174874 patients who underwent cholecystectomy between January 1, 2010 and December 31, 2017 were identified using the Korean National Health Insurance Service claims database. These patients were matched 1:1 with members of a healthy population according to age and sex. CRC or GC risk after cholecystectomy and the association between smoking and CRC or GC risk in cholecystectomy patients were evaluated using adjusted hazard ratios (HRs) and 95%CIs. RESULTS The risks of CRC (adjusted HR: 1.15; 95%CI: 1.06-1.25; P = 0.0013) and GC (adjusted HR: 1.11; 95%CI: 1.01-1.22; P = 0.0027) were significantly higher in cholecystectomy patients. In the population who underwent cholecystectomy, both CRC and GC risk were higher in those who had smoked compared to those who had never smoked. For both cancers, the risk tended to increase in the order of non-smokers, ex-smokers, and current smokers. In addition, a positive correlation was observed between the amount of smoking and the risks of both CRC and GC. CONCLUSION Careful follow-up and screening should be performed, focusing on the increased risk of gastrointestinal cancer in the cholecystectomy group, particularly considering the individual smoking habits.
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Affiliation(s)
- Minseob Kim
- Department of Surgery, Graduate School of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Kyung-Do Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul 06978, South Korea
| | - Seung-Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, South Korea
| | - Yoonkyung Woo
- Division of Hepatobiliary-Pancreas Surgery and Liver Transplantation, Department of Surgery, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, South Korea
| | - Jae Hyun Han
- Division of Hepatobiliary-Pancreas Surgery and Liver Transplantation, Department of Surgery, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, South Korea
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11
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Amaral Raposo M, Sousa Oliveira E, Dos Santos A, Guadagnini D, El Mourabit H, Housset C, Lemoinne S, Abdalla Saad MJ. Impact of cholecystectomy on the gut-liver axis and metabolic disorders. Clin Res Hepatol Gastroenterol 2024; 48:102370. [PMID: 38729564 DOI: 10.1016/j.clinre.2024.102370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 04/28/2024] [Accepted: 05/05/2024] [Indexed: 05/12/2024]
Abstract
Cholecystectomy is considered as a safe procedure to treat patients with gallstones. However, epidemiological studies highlighted an association between cholecystectomy and metabolic disorders, such as type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (MASLD), independently of the gallstone disease. Following cholecystectomy, bile acids flow directly from the liver into the intestine, leading to changes in the entero-hepatic circulation of bile acids and their metabolism. The changes in bile acids metabolism impact the gut microbiota. Therefore, cholecystectomized patients display gut dysbiosis characterized by a reduced diversity, a loss of bacteria producing short-chain fatty acids and an increase in pro-inflammatory bacteria. Alterations of both bile acids metabolism and gut microbiota occurring after cholecystectomy can promote the development of metabolic disorders. In this review, we discuss the impact of cholecystectomy on bile acids and gut microbiota and its consequences on metabolic functions.
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Affiliation(s)
- Mariana Amaral Raposo
- Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas - São Paulo, Brazil; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA) and Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Emília Sousa Oliveira
- Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas - São Paulo, Brazil
| | - Andrey Dos Santos
- Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas - São Paulo, Brazil
| | - Dioze Guadagnini
- Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas - São Paulo, Brazil
| | - Haquima El Mourabit
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA) and Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Chantal Housset
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA) and Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Sara Lemoinne
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA) and Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, European Reference Network on Hepatological Diseases (ERN Rare-Liver), Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France.
| | - Mário José Abdalla Saad
- Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas - São Paulo, Brazil.
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Wang K, Xu Q, Xia L, Sun J, Shen K, Liu H, Xu L, Li R. Gallbladder polypoid lesions: Current practices and future prospects. Chin Med J (Engl) 2024; 137:1674-1683. [PMID: 38420780 PMCID: PMC11268823 DOI: 10.1097/cm9.0000000000003019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Indexed: 03/02/2024] Open
Abstract
ABSTRACT Gallbladder polypoid lesions (GPLs) refer to any elevated lesion of the mucosal surface of the gallbladder wall, and the prevalence is estimated to be between 0.9% and 12.1%. GPLs include benign polyps and malignant polyps. Benign polyps are further classified as non-neoplastic polyps and neoplastic polyps. Cholesterol polyps are the most common benign polyps and adenocarcinoma is the main type of malignant polyp. Hepatitis B virus infection, liver function abnormalities, dyslipidemia, and obesity are the main risk factors for GPLs. Studies of biological mechanisms have focused on malignant gallbladder polyps, the development of which is regulated by hormone levels in vivo , gut microbiota, inflammation, oxidative stress, Salmonella typhimurium , and related molecules. Diagnostic modalities include chemical examination and imaging examination, with imaging examination currently being the mainstay. Treatment of patients with GPLs is based on the presence or absence of symptoms, age, size of the polyps, tendency of the polyp to increase, and risk factors for symptomatic malignancy to determine whether surgery should be performed.
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Affiliation(s)
- Kun Wang
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215026, China
| | - Qingpeng Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215026, China
| | - Lu Xia
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215026, China
| | - Jianing Sun
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215026, China
| | - Kanger Shen
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215026, China
| | - Haoran Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215026, China
| | - Linning Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215026, China
| | - Rui Li
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215026, China
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13
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Huang Y, Cai Y, Chen Y, Zhu Q, Feng W, Jin L, Ma Y. Cholelithiasis and cholecystectomy increase the risk of gastroesophageal reflux disease and Barrett's esophagus. Front Med (Lausanne) 2024; 11:1420462. [PMID: 39091288 PMCID: PMC11292949 DOI: 10.3389/fmed.2024.1420462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 06/20/2024] [Indexed: 08/04/2024] Open
Abstract
Background Cholelithiasis or cholecystectomy may contribute to the development of gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) through bile reflux; however, current observational studies yield inconsistent findings. We utilized a novel approach combining meta-analysis and Mendelian randomization (MR) analysis, to assess the association between them. Methods The literature search was done using PubMed, Web of Science, and Embase databases, up to 3 November 2023. A meta-analysis of observational studies assessing the correlations between cholelithiasis or cholecystectomy, and the risk factors for GERD, BE, and EACwas conducted. In addition, the MR analysis was employed to assess the causative impact of genetic pre-disposition for cholelithiasis or cholecystectomy on these esophageal diseases. Results The results of the meta-analysis indicated that cholelithiasis was significantly linked to an elevated risk in the incidence of BE (RR, 1.77; 95% CI, 1.37-2.29; p < 0.001) and cholecystectomy was a risk factor for GERD (RR, 1.37; 95%CI, 1.09-1.72; p = 0.008). We observed significant genetic associations between cholelithiasis and both GERD (OR, 1.06; 95% CI, 1.02-1.10; p < 0.001) and BE (OR, 1.21; 95% CI, 1.11-1.32; p < 0.001), and a correlation between cholecystectomy and both GERD (OR, 1.04; 95% CI, 1.02-1.06; p < 0.001) and BE (OR, 1.13; 95% CI, 1.06-1.19; p < 0.001). After adjusting for common risk factors, such as smoking, alcohol consumption, and BMI in multivariate analysis, the risk of GERD and BE still persisted. Conclusion Our study revealed that both cholelithiasis and cholecystectomy elevate the risk of GERD and BE. However, there is no observed increase in the risk of EAC, despite GERD and BE being the primary pathophysiological pathways leading to EAC. Therefore, patients with cholelithiasis and cholecystectomy should be vigilant regarding esophageal symptoms; however, invasive EAC cytology may not be necessary.
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Affiliation(s)
- Yu Huang
- Department of Cardiothoracic Surgery, Third Xiangya Hospital of Central South University, Changsha, China
| | - Yicong Cai
- Department of Gastrointestinal Surgery, Third Xiangya Hospital of Central South University, Changsha, China
| | - Yingji Chen
- Department of Cardiothoracic Surgery, Third Xiangya Hospital of Central South University, Changsha, China
| | - Qianjun Zhu
- Department of Cardiothoracic Surgery, Third Xiangya Hospital of Central South University, Changsha, China
| | - Wei Feng
- Department of Cardiothoracic Surgery, Third Xiangya Hospital of Central South University, Changsha, China
| | - Longyu Jin
- Department of Cardiothoracic Surgery, Third Xiangya Hospital of Central South University, Changsha, China
| | - Yuchao Ma
- Department of Cardiothoracic Surgery, Third Xiangya Hospital of Central South University, Changsha, China
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Wang Y, Jiang ZH, Zhou YW, Qiu TT, Wang H, Zhu MS, Chen X, Zhang XN. Gallbladder dysfunction caused by MYPT1 ablation triggers cholestasis-induced hepatic fibrosis in mice. Hepatol Commun 2024; 8:e0473. [PMID: 38934703 PMCID: PMC11213606 DOI: 10.1097/hc9.0000000000000473] [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: 10/27/2023] [Accepted: 04/19/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown. METHODS Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF). RESULTS Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide-resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF. CONCLUSIONS We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.
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Affiliation(s)
- Ye Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
| | - Zhi-Hui Jiang
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
| | - Yu-Wei Zhou
- Jiangsu Key Laboratory of Molecular Medicine, Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Tian-Tian Qiu
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
| | - Han Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
| | - Min-Sheng Zhu
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
| | - Xin Chen
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
| | - Xue-Na Zhang
- State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, China
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jinling Pharmaceutical Co., Ltd., Nanjing, China
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15
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Pan SY, Zhou CB, Deng JW, Zhou YL, Liu ZH, Fang JY. The effects of pks + Escherichia coli and bile acid in colorectal tumorigenesis among people with cholelithiasis or cholecystectomy. J Gastroenterol Hepatol 2024; 39:868-879. [PMID: 38220146 DOI: 10.1111/jgh.16462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 11/20/2023] [Accepted: 12/11/2023] [Indexed: 01/16/2024]
Abstract
BACKGROUND AND AIM Patients with cholelithiasis (CL) or cholecystectomy (CE) would have more chances of getting colorectal adenoma (CRA) or cancer (CRC). We aimed to figure out the effects of gut microbiota and bile acid on colorectal neoplasm in CL and CE patients. METHODS This was a retrospective observational study that recruited 514 volunteers, including 199 people with normal gallbladders (normal), 152 CL, and 163 CE patients. Discovery cohort was established to explore the difference in gut microbiota through 16S rRNA and metagenomics sequencing. Validation cohort aimed to verify the results through quantitative polymerase chain reaction (qPCR). RESULTS Significant enrichment of Escherichia coli was found in patients with cholelithiasis or cholecystectomy both in the discovery cohort (16S rRNA sequencing, PNormal-CL = 0.013, PNormal-CE = 0.042; metagenomics sequencing, PNormal-CE = 0.026) and validation cohort (PNormal-CL < 0.0001, PNormal-CE < 0.0001). Pks+ E. coli was found enriched in CL and CE patients through qPCR (in discovery cohort: PNormal-CE = 0.018; in validation cohort: PNormal-CL < 0.0001, PNormal-CE < 0.0001). The differences in bile acid metabolism were found both through Tax4Fun analysis of 16S rRNA sequencing (Ko00120, primary bile acid biosynthesis, PNormal-CE = 0.014; Ko00121, secondary bile acid biosynthesis, PNormal-CE = 0.010) and through metagenomics sequencing (map 00121, PNormal-CE = 0.026). The elevation of serum total bile acid of CE patients was also found in validation cohort (PNormal-CE < 0.0001). The level of serum total bile acid was associated with the relative abundance of pks+ E. coli (r = 0.1895, P = 0.0012). CONCLUSIONS E. coli, especially pks+ species, was enriched in CL and CE patients. Pks+ E. coli and bile acid metabolism were found associated with CRA and CRC in people after cholecystectomy.
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Affiliation(s)
- Si-Yuan Pan
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Institute of Digestive Disease, Shanghai, China
- State Key, Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Disease, Shanghai, China
| | - Cheng-Bei Zhou
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Institute of Digestive Disease, Shanghai, China
- State Key, Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Disease, Shanghai, China
| | - Jia-Wen Deng
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Institute of Digestive Disease, Shanghai, China
- State Key, Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Disease, Shanghai, China
| | - Yi-Lu Zhou
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Institute of Digestive Disease, Shanghai, China
- State Key, Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Disease, Shanghai, China
| | - Zhu-Hui Liu
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Institute of Digestive Disease, Shanghai, China
- State Key, Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Disease, Shanghai, China
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Institute of Digestive Disease, Shanghai, China
- State Key, Laboratory for Oncogenes and Related Genes, NHC Key Laboratory of Digestive Disease, Shanghai, China
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Wang CC, Huang JY, Weng LH, Hsu YC, Sung WW, Huang CY, Lin CC, Wei JCC, Tsai MC. Association between Cholecystectomy and the Incidence of Pancreaticobiliary Cancer after Endoscopic Choledocholithiasis Management. Cancers (Basel) 2024; 16:977. [PMID: 38473337 PMCID: PMC10930920 DOI: 10.3390/cancers16050977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 02/18/2024] [Accepted: 02/26/2024] [Indexed: 03/14/2024] Open
Abstract
(1) Background: Previous studies have raised concerns about a potential increase in pancreaticobiliary cancer risk after cholecystectomy, but few studies have focused on patients who undergo cholecystectomy after receiving endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. This study aims to clarify cancer risks in these patients, who usually require cholecystectomy, to reduce recurrent biliary events. (2) Methods: We conducted a nationwide cohort study linked to the National Health Insurance Research Database, the Cancer Registry Database, and the Death Registry Records to evaluate the risk of pancreaticobiliary cancers. All patients who underwent first-time therapeutic ERCP for choledocholithiasis from 2011 to 2017 in Taiwan were included. We collected the data of 13,413 patients who received cholecystectomy after endoscopic retrograde cholangiopancreatography and used propensity score matching to obtain the data of 13,330 patients in both the cholecystectomy and non-cholecystectomy groups with similar age, gender, and known pancreaticobiliary cancer risk factors. Pancreaticobiliary cancer incidences were further compared. (3) Results: In the cholecystectomy group, 60 patients had cholangiocarcinoma, 61 patients had pancreatic cancer, and 15 patients had ampullary cancer. In the non-cholecystectomy group, 168 cases had cholangiocarcinoma, 101 patients had pancreatic cancer, and 49 patients had ampullary cancer. The incidence rates of cholangiocarcinoma, pancreatic cancer, and ampullary cancer were 1.19, 1.21, and 0.3 per 1000 person-years in the cholecystectomy group, all significantly lower than 3.52 (p < 0.0001), 2.11 (p = 0.0007), and 1.02 (p < 0.0001) per 1000 person-years, respectively, in the non-cholecystectomy group. (4) Conclusions: In patients receiving ERCP for choledocholithiasis, cholecystectomy is associated with a significantly lower risk of developing pancreaticobiliary cancer.
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Affiliation(s)
- Chi-Chih Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan; (C.-C.W.); (L.-H.W.); (C.-C.L.)
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (J.-Y.H.); (W.-W.S.)
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
| | - Jing-Yang Huang
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (J.-Y.H.); (W.-W.S.)
- Center for Health Data Science, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Li-Han Weng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan; (C.-C.W.); (L.-H.W.); (C.-C.L.)
| | - Yao-Chun Hsu
- Center for Liver Diseases and Center for Clinical Trials, E-Da Hospital, Kaohsiung, Taiwan;
- School of Medicine, I-Shou University, Kaohsiung 84001, Taiwan
| | - Wen-Wei Sung
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (J.-Y.H.); (W.-W.S.)
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
| | - Chao-Yen Huang
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
- Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Chun-Che Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan; (C.-C.W.); (L.-H.W.); (C.-C.L.)
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (J.-Y.H.); (W.-W.S.)
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
| | - James Cheng-Chung Wei
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (J.-Y.H.); (W.-W.S.)
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
- Department of Allergy, Immunology, and Rheumatology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan; (C.-C.W.); (L.-H.W.); (C.-C.L.)
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; (J.-Y.H.); (W.-W.S.)
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
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17
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Shukla R, Chadha M, Shekh R, Tiwari RK. Role of probiotics in gallstone treatment. GALLSTONE FORMATION, DIAGNOSIS, TREATMENT AND PREVENTION 2024:169-187. [DOI: 10.1016/b978-0-443-16098-1.00006-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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18
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Chen Z, Yu C, Li Z. The effect of cholecystectomy on the risk of colorectal cancer: A systematic review and meta-analysis. LAPAROSCOPIC, ENDOSCOPIC AND ROBOTIC SURGERY 2023; 6:134-141. [DOI: 10.1016/j.lers.2023.11.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025] Open
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19
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Sun N, Wang X, Wei J. Gallstones, cholecystectomy and the risk of pancreatic cancer: an updated systematic review and meta-analysis of cohort studies. Eur J Gastroenterol Hepatol 2023; 35:1313-1323. [PMID: 37823406 PMCID: PMC10756705 DOI: 10.1097/meg.0000000000002652] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 09/02/2023] [Indexed: 10/13/2023]
Abstract
The effect of gallstones and cholecystectomy on the development of pancreatic cancer has recently prompted many population-based studies. However, the results are controversial. We conducted an updated systematic review and meta-analysis to explore the causality among gallstones, cholecystectomy and pancreatic cancer. Cohort studies published in the PubMed, Web of Science, Embase, and Cochrane Library databases up to May 2023 were retrieved. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were analyzed using a random-effects model. We screened 1391 articles and included 16 studies. Gallstones were not associated with an increased risk of pancreatic cancer ( P = 0.082), with only the Asian population ( P = 0.011) showing an increased risk in the subgroup analysis. A markedly higher risk of pancreatic cancer was observed among patients with cholecystectomy (RR = 1.23; 95% CI, 1.07-1.41; P = 0.004; I 2 = 74.4%). The association remained significant in the Asian population ( P = 0.004), in the subgroup analyses stratified by sex, lag period, and time interval since cholecystectomy, and when the models were adjusted for diabetes, smoking, and BMI. Interestingly, cholecystectomy due to gallstones (RR = 1.30; 95% CI, 1.14-1.48; P < 0.001; I 2 = 30.8%), rather than for unspecified reasons ( P = 0.116), markedly increased the risk of pancreatic cancer. In conclusion, cholecystectomy due to gallstones, rather than gallstone formation, conferred an increased risk for pancreatic cancer. There was a higher risk for the Asian population for both gallstones and cholecystectomy.
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Affiliation(s)
- Na Sun
- Department of Human Morphology, School of Health and Life Sciences, University of Health and Rehabilitation Sciences
| | - Xudong Wang
- Minimally Invasive Interventional Therapy Center, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital)
| | - Jichao Wei
- Department of Hepatobiliary Surgery, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, Shandong Province, China
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20
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Polychronidis G, Siddiqi H, Ali Ahmed F, Papatheodorou S, Giovannucci EL, Song M. Association of gallstone disease with risk of colorectal cancer: a systematic review and meta-analysis of observational studies. Int J Epidemiol 2023; 52:1424-1434. [PMID: 37071919 DOI: 10.1093/ije/dyad042] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 04/04/2023] [Indexed: 04/20/2023] Open
Abstract
BACKGROUND Numerous studies have assessed the association of gallstones or cholecystectomy (CE) with risk of colorectal cancer (CRC). However, the findings are mixed. OBJECTIVE To systematically review and meta-analyse the association between the presence of gallstone disease (GD), or CE and the incidence of CRC. Secondary endpoints were the risk based on type of exposure, study design, tumour subsites and sex. METHODS PubMed and EMBASE were searched from September 2020 to May 2021. The protocol was registered on the Open Science Foundation Platform. We identified and classified studies according to their design into prospective cohort, population-based case-control, hospital-based case-control and necropsy studies reporting CRC incidence among individuals with diagnosed GD or after CE (or both). Among 2157 retrieved studies, 65 (3%) met the inclusion criteria. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were extracted by two independent reviewers. We evaluated the quality of the study according to the Newcastle-Ottawa Scale and only studies with a score of 6 and above were included in the final analyses. We pooled log-transformed odds ratios/risk ratios from the available adjusted models to estimate a summary relative risk (RR) and 95% confidence interval (CI) in a random-effects model. The primary outcome was overall CRC incidence. We also conducted secondary analyses according to sex and CRC subsites (proximal colon, distal colon and rectum). The outcome was measured by RRs with 95% CIs. RESULTS The overall association of GD and/or CE with CRC was RR = 1.15 (1.08; 1.24), primarily driven by hospital-based case-control studies [RR = 1.61 (1.29; 2.01)], whereas a more modest association was found in population-based case-control and cohort studies [RR = 1.10 (1.02; 1.19)]. Most hospital-based case-control and necropsy studies reported estimates that were adjusted for age and sex only, leaving room for residual confounding; therefore we restricted to population-based case-control and cohort studies for our subsequent analyses. Similar associations were found for women [RR = 1.21 (1.05; 1.4) and men (RR = 1.24 (1.06; 1.44)]. When assessed by CRC subsites, GD and CE were primarily associated with higher risk of proximal colon cancer [RR = 1.16 (1.07; 1.26)] but not distal colon cancer [RR = 0.99 (0.96; 1.03)] or rectal cancer [RR = 0.94 (0.89; 1.00)]. CONCLUSIONS Gallstones are associated with a modestly increased risk of colon cancer, primarily in the proximal colon.
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Affiliation(s)
- Georgios Polychronidis
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Department of General Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Study Centre of the German Surgical Society, University of Heidelberg, Heidelberg, Germany
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Haziq Siddiqi
- Department of Internal Medicine, University of California, San Francisco, CA, USA
| | - Fasih Ali Ahmed
- Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | | | - Edward L Giovannucci
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
| | - Mingyang Song
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
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21
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Sun M, Ma T, Yuan H. Association between history of cholecystectomy and risk of gastric cancer: a meta-analysis of epidemiological studies. BMJ Open 2023; 13:e057138. [PMID: 37640459 PMCID: PMC10462960 DOI: 10.1136/bmjopen-2021-057138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 02/22/2023] [Indexed: 08/31/2023] Open
Abstract
PURPOSE Evidence from previous studies on the association between cholecystectomy and risk of gastric cancer are still inconsistent. We aimed at conducting a meta-analysis of epidemiological studies to evaluate this association. METHODS Researchers searched three databases (PubMed, Embase and Web of Science) through January 2021 for eligible studies. Relative risks (RRs) and 95% CIs in each included studies were pooled by random-effects models. Patients and the public were not involved in our study. RESULTS Eight studies were identified. Four studies reported significantly positive association between history of cholecystectomy and risk of gastric cancer, and the remaining studies reported null association. The pooled RR of these eight studies showed that a history of cholecystectomy was associated with a 11% higher risk of gastric cancer (pooled RR=1.11, 95% CI: 1.03 to 1.20). Moderate heterogeneity across the studies was detected (p=0.117, I2=37.8%). The pooled RRs were 1.12 (95% CI: 1.01 to 1.24) for five cohort studies and 0.95 (95% CI: 0.66 to 1.38) for three case-control studies. Compared with the risk in Europe and the USA, the pooled RR was higher for two studies conducted in Asia. Six studies were assessed as high-quality studies with the pooled RR of 1.12 (95% CI: 1.02 to 1.23). The pooled results were robust by sensitivity analyses, and no indication of publication bias was detected. CONCLUSION This meta-analysis suggests that a history of cholecystectomy may be associated with an increased risk of gastric cancer.
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Affiliation(s)
- Mei Sun
- Department of Gastroenterology, Dalian Municipal Central Hospital, Dalian, Liaoning, China
| | - Tianyi Ma
- Department of Gastroenterology, Dalian Municipal Central Hospital, Dalian, Liaoning, China
| | - Huawei Yuan
- Department of Gastroenterology, Dalian Municipal Central Hospital, Dalian, Liaoning, China
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22
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Tian B, Chen G, Shi X, Jiang L, Jiang T, Li Q, Yuan L, Qin J. Preliminary exploration of the effects of environmental factors on the microsatellite status of BRAF-mutated colorectal cancer. World J Surg Oncol 2023; 21:264. [PMID: 37620872 PMCID: PMC10463889 DOI: 10.1186/s12957-023-03106-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Accepted: 07/12/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND To investigate the expression of EBV products and frequency of gallstone disease (GD) among different microsatellite status in colorectal cancer (CRC) with BRAFV600E mutation. METHODS We collected 30 CRC patients with BRAFV600E mutation and 10 BRAF ( -) CRC patients as well as 54 healthy subjects. Tumor tissue samples were collected to detect the mutation of BRAF, KRAS, and TP53. Microsatellite status was determined by immunohistochemistry and PCR. EBER in situ hybridization was performed to detect EBV. In addition, we also collected clinical information about the patients. RESULTS We found that although EBV products were detected in CRC, there were no significant differences in the EBV distribution between the different BRAF groups. Our study demonstrated that BRAFV600E mutation and BRAFV600E with MSI were significantly more frequent in the right CRC. Furthermore, the KRAS mutation rate in the BRAF-wild-type group was proved to be significantly higher than that in the BRAF mutation group. In addition, we revealed that BRAF mutation and MSI were independent risk factors of TNM stage. The frequency of GD was higher in CRC patients than in general population, and although there was no significant difference between CRC with or without BRAFV600E mutation, the highest frequency of GD was found in MSS CRC with BRAFV600E mutation. CONCLUSIONS EBV plays a role in CRC, but is not a determinant of different microsatellite status in CRC with BRAFV600E mutation. The frequency of GD in MSS CRC with BRAFV600E mutation is significantly higher than that in the general population.
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Affiliation(s)
- Binle Tian
- Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China
| | - Guiming Chen
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China
| | - Xiaoqin Shi
- Pathology Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China
| | - Liren Jiang
- Pathology Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China
| | - Tao Jiang
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China
| | - Qi Li
- Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China
| | - Lin Yuan
- Pathology Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China.
| | - Jian Qin
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China.
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Kharazmi E, Scherer D, Boekstegers F, Liang Q, Sundquist K, Sundquist J, Fallah M, Lorenzo Bermejo J. Gallstones, Cholecystectomy, and Kidney Cancer: Observational and Mendelian Randomization Results Based on Large Cohorts. Gastroenterology 2023; 165:218-227.e8. [PMID: 37054756 DOI: 10.1053/j.gastro.2023.03.227] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 02/17/2023] [Accepted: 03/25/2023] [Indexed: 04/15/2023]
Abstract
BACKGROUND & AIMS Gallstones (cholelithiasis) constitute a major health burden with high costs related to surgical removal of the gallbladder (cholecystectomy), generally indicated for symptomatic gallstones. The association between gallstones and cholecystectomy and kidney cancer is controversial. We comprehensively investigated this association, considering age at cholecystectomy and time from cholecystectomy to kidney cancer diagnosis, and assessed the causal effect of gallstones on kidney cancer risk by Mendelian randomization (MR). METHODS We compared the risk of kidney cancer in cholecystectomized and noncholecystectomized patients (16.6 million in total) from the Swedish nationwide cancer, census, patient, and death registries using hazard ratios (HRs). For 2-sample and multivariable MR, we used summary statistics based on 408,567 UK Biobank participants. RESULTS During a median follow-up of 13 years, 2627 of 627,870 cholecystectomized Swedish patients developed kidney cancer (HR, 1.17; 95% CI, 1.12-1.22). Kidney cancer risk was particularly increased in the first 6 months after cholecystectomy (HR, 3.79; 95% CI, 3.18-4.52) and in patients cholecystectomized before age 40 years (HR, 1.55; 95% CI, 1.39-1.72). MR results based on 18,417 patients with gallstones and 1788 patients with kidney cancer from the United Kingdom revealed a causal effect of gallstones on kidney cancer risk (9.6% risk increase per doubling in gallstone prevalence; 95% CI, 1.2%-18.8%). CONCLUSIONS Both observational and causal MR estimates based on large prospective cohorts support an increased risk of kidney cancer in patients with gallstones. Our findings provide solid evidence for the compelling need to diagnostically rule out kidney cancer before and during gallbladder removal, to prioritize kidney cancer screening in patients undergoing cholecystectomy in their 30s, and to investigate the underlying mechanisms linking gallstones and kidney cancer in future studies.
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Affiliation(s)
- Elham Kharazmi
- Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany; Risk Adapted Prevention Group, Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - Dominique Scherer
- Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany
| | - Felix Boekstegers
- Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany
| | - Qunfeng Liang
- Risk Adapted Prevention Group, Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany
| | - Kristina Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden; Departments of Family Medicine and Community Health and Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York; Center for Community-Based Healthcare Research and Education, Department of Functional Pathology, School of Medicine, Shimane University, Izumo, Japan
| | - Jan Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden; Departments of Family Medicine and Community Health and Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York; Center for Community-Based Healthcare Research and Education, Department of Functional Pathology, School of Medicine, Shimane University, Izumo, Japan
| | - Mahdi Fallah
- Risk Adapted Prevention Group, Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Center for Primary Health Care Research, Lund University, Malmö, Sweden; Institute of Primary Health Care, University of Bern, Bern, Switzerland
| | - Justo Lorenzo Bermejo
- Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany; Department of Biostatistics for Precision Oncology, Institut de Cancérologie Strasbourg Europe, Strasbourg, France.
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24
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Yu L, Liu W, Yan Y, Jiang Y, Gao X, Ruan S. No association between cholecystectomy and risk of colorectal cancer: a meta-analysis of cohort studies. Int J Colorectal Dis 2023; 38:179. [PMID: 37368048 DOI: 10.1007/s00384-023-04463-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2023] [Indexed: 06/28/2023]
Abstract
OBJECTIVE Cohort studies have reported an association between colorectal cancer and cholecystectomy. However, the conclusions are inconsistent. Thus, this meta-analysis will quantify the risk of colorectal cancer following cholecystectomy. METHODS PubMed, EMBASE and Cochrane Library databases were searched for relevant cohort studies. The quality of individual observational studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. The relative risk of colorectal cancer after cholecystectomy was calculated using STATA 14.0 software. Subgroup and sensitivity analyses were used to examine the source of heterogeneity. Funnel plots and Egger's test were finally performed to assess the publication bias. RESULTS This meta-analysis included 14 studies comprising 2,283,616 subjects. Pooled analysis indicated that cholecystectomy was not a risk factor for colorectal cancer (Colorectal: RR 1.06; 95% CI 0.75-1.51, p = 0.739 Colon: RR 1.30; 95% CI 0.88-1.93, p = 0.182 Rectal: RR 0.99; 95% CI 0.74-1.32, p = 0.932). Subgroup showed that patients are at an increased risk of sigmoid colon following cholecystectomy (RR 1.42; 95% CI 1.27-1.58, p = 0.000). Furthermore, it was shown that both females and males undergoing cholecystectomy may have higher risks of colon cancer (Female: RR = 1.47, 95% CI 1.01-2.14, P = 0.042 Male: RR = 1.32; 95% CI 1.07-1.63, P = 0.010), which is similarly observed in the right colon (Female: RR 1.99; 95% CI 1.31-3.03, p = 0.001, P = 0.017 Male: RR 1.68; 95% CI 0.81-3.49, p = 0.166). CONCLUSIONS No clear evidence to support the association between cholecystectomy and an increased risk of colorectal cancer. For patients with valid indications, timely cholecystectomy could be performed without the risk of colorectal cancer.
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Affiliation(s)
- Lulin Yu
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Wenjing Liu
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yici Yan
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yu Jiang
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xin Gao
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shanming Ruan
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
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Dong Z, Shi R, Li P, Song X, Dong F, Zhu J, Wu R, Liang Z, Du M, Wang J, Yang Z. Does postcholecystectomy increase the risk of colorectal cancer? Front Microbiol 2023; 14:1194419. [PMID: 37426004 PMCID: PMC10324655 DOI: 10.3389/fmicb.2023.1194419] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 05/31/2023] [Indexed: 07/11/2023] Open
Abstract
With the increasing number of cholecystectomy and the high proportion of colorectal cancer in malignant tumors, the question of whether cholecystectomy is a risk factor for colorectal disease has been widely concerned. After reviewing the literature at home and abroad, the authors will summarize the research progress of the correlation between the occurrence of colorectal tumors after cholecystectomy, in order to provide help for the prevention and treatment of colorectal tumors.
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Affiliation(s)
- Zhenyu Dong
- Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China
- Baotou Medical College, Baotou, Inner Mongolia, China
| | - Ruixian Shi
- Department of Neurology, Baotou Central Hospital, Baotou, Inner Mongolia, China
- Inner Mongolia Medical University, Hohhot, Inner Mongolia, China
| | - Pengda Li
- Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China
- Baotou Medical College, Baotou, Inner Mongolia, China
| | - Xiaobiao Song
- Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China
| | - Fan Dong
- Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China
| | - Jianmin Zhu
- Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China
| | - Riga Wu
- Department of General Surgery, The Second Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, China
| | - Zhi Liang
- Baotou Medical College, Baotou, Inner Mongolia, China
| | - Mingyue Du
- Baotou Medical College, Baotou, Inner Mongolia, China
| | - Jijun Wang
- Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China
| | - Zhigang Yang
- Department of Urology, Baotou Central Hospital, Baotou, Inner Mongolia, China
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Luo D, Chen XP, Dai Y, Kuang F, Kang MJ, Li B, Su S. Cholecystectomy and risk of liver disease: a systematic review and meta-analysis of 27 million individuals. Int J Surg 2023; 109:1420-1429. [PMID: 36999804 PMCID: PMC10389609 DOI: 10.1097/js9.0000000000000332] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 03/07/2023] [Indexed: 04/01/2023]
Abstract
BACKGROUND There is still a lack of knowledge on the association between cholecystectomy and liver disease. This study was conducted to summarize the available evidence on the association of cholecystectomy with liver disease and quantify the magnitude of the risk of liver disease after cholecystectomy. METHODS PubMed, Embase, Web of Science, and Cochrane Library were searched systematically from database inception to January 2023 to identify eligible studies that evaluated the association between cholecystectomy and the risk of liver disease. Meta-analysis was conducted to obtain a summary odds ratio (OR) and 95% confidence interval (CI) using a random-effects model. RESULTS We identified 20 studies with a total of 27 320 709 individuals and 282 670 liver disease cases. Cholecystectomy was associated with an increased risk of liver disease (OR: 1.63, 95% CI: 1.34-1.98). In particular, cholecystectomy was found to be significantly associated with a 54% increased risk of nonalcoholic fatty liver disease (OR: 1.54, 95% CI: 1.18-2.01), a 173% increased risk of cirrhosis (OR: 2.73, 95% CI: 1.81-4.12), and a 46% increased risk of primary liver cancer (OR: 1.46, 95% CI: 1.18-1.82). CONCLUSIONS There is an association between cholecystectomy and the risk of liver disease. Our results suggest that strict surgical indications should be implemented to reduce unnecessary cholecystectomy. Additionally, the routine assessment of liver disease is necessary for patients with a history of cholecystectomy. More prospective large-sample studies are required for better estimates of the risk.
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Affiliation(s)
- De Luo
- Department of General Surgery (Hepatopancreatobiliary Surgery)
- Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Sichuan
| | - Xin-Pei Chen
- Department of Hepatobiliary Surgery, People’s Hospital of Deyang City, Deyang
| | - Yang Dai
- Department of General Surgery, The First People’s Hospital of Xiangyang, Xiangyang, People’s Republic of China
| | - Fei Kuang
- Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Mao-Ji Kang
- Department of General Surgery (Hepatopancreatobiliary Surgery)
- Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Sichuan
| | - Bo Li
- Department of General Surgery (Hepatopancreatobiliary Surgery)
- Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Sichuan
| | - Song Su
- Department of General Surgery (Hepatopancreatobiliary Surgery)
- Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Sichuan
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27
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Li H, Wei L, Zhu M, Zeng Z, Qu W, Zhu Z. A novel approach of intraoperative cholangiography in laparoscopic left lateral sectionectomy in living donor liver transplantation. Surg Endosc 2023:10.1007/s00464-023-10066-1. [PMID: 37081244 DOI: 10.1007/s00464-023-10066-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 04/01/2023] [Indexed: 04/22/2023]
Abstract
BACKGROUND Accurate division of bile duct during laparoscopic donor hepatectomy in living donor liver transplantation is essential. We here present a novel approach to achieve cholangiography via the bile duct stump of segment IV (B4 stump) during laparoscopic donor hepatectomy in adult-to-pediatric living donor liver transplantation. PATIENTS AND METHODS Donors who underwent laparoscopic left lateral sectionectomy (LLLS) from January 2022 to April 2022 in our liver transplant center were retrospectively analyzed. A total of 32 donors were eventually enrolled into this study. Cholangiography via the B4 stump was performed in 11 donors (B4 group) while indocyanine green (ICG) fluorescence guiding was performed in 21 donors (ICG group). Perioperative data were collected and compared between groups. RESULTS Cholangiography by catheterizing the B4 stump was successfully performed in all 11 donors in the B4 group. The mean time of this procedure was 12.82 ± 9.11 min. Compared to the ICG group, it was more likely to acquire single bile duct orifice on graft in the B4 group (B4: 10/11, 90.91% vs ICG: 9/21, 42.86%) and it was significantly different (p = 0.030). The donors' complications (Clavien-Dindo grade III-IV) were not significantly different. There was one donor developed intraperitoneal effusion in B4 group, while two donors (one bile leakage and one biliary stricture) developed biliary tract related complications in the ICG group. A Roux-en-Y was performed to solve the biliary stricture in the ICG group. The recipients' outcomes were not significantly different between groups. CONCLUSIONS Cholangiography via the B4 stump catheterization is feasible and safe in identifying the bifurcation of bile duct during LLLS.
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Affiliation(s)
- Hongyu Li
- Department of Liver Transplantation, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Lin Wei
- Department of Liver Transplantation, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Mingyue Zhu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Zhigui Zeng
- Department of Liver Transplantation, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Wei Qu
- Department of Liver Transplantation, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Zhijun Zhu
- Department of Liver Transplantation, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
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Luo X, Yang W, Joshi AD, Wu K, Simon TG, Yuan C, Jin L, Long L, Kim MN, Lo CH, Liu X, Abrams TA, Wolpin BM, Chan AT, Giovannucci EL, Zhang X. Gallstones and risk of cancers of the liver, biliary tract and pancreas: a prospective study within two U.S. cohorts. Br J Cancer 2022; 127:1069-1075. [PMID: 35715632 PMCID: PMC9470543 DOI: 10.1038/s41416-022-01877-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 05/12/2022] [Accepted: 05/31/2022] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Gallstones may result in inflammation, altered bile flow, and changes in metabolic hormone levels, thereby increasing cancer risk. However, previous studies for gallstones and cancers of the liver, biliary tract and pancreas in the U.S. were relatively limited. METHODS We followed 115,036 women from the Nurses' Health Study (1982-2012) and 49,729 men from the Health Professionals Follow-up Study (1986-2012). History of gallstones, including with or without performed cholecystectomy, was reported at baseline and updated through biennial questionnaires. The Cox proportional hazard regression model was used to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS During up to 30-year follow-up, we identified 204 incidents of liver cancer, 225 biliary tract cancer and 1147 pancreatic cancer cases. Compared to those without gallstones diagnosis, the multivariable HRs for individuals with gallstones (untreated or with cholecystectomy) were 1.60 for liver cancer (95% CI: 1.14-2.26), 4.79 for biliary tract cancer (95% CI: 3.02-7.58), and 1.13 for pancreatic cancer (95% CI: 0.96-1.32). The multivariable HRs for individuals with cholecystectomy were 1.33 for liver cancer (95% CI: 0.90-1.95) and 1.15 for pancreatic cancer (95% CI: 0.98-1.36). CONCLUSIONS Gallstones were associated with a higher risk of cancers of the liver, biliary tract and possibly pancreas.
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Affiliation(s)
- Xiao Luo
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Health Statistics, School of Public Health, China Medical University, Shenyang, Liaoning, P. R. China
| | - Wanshui Yang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- School of Public Health, Anhui Medical University, Hefei, Anhui, P. R. China
| | - Amit D Joshi
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Tracey G Simon
- Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA
| | - Chen Yuan
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Lina Jin
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology and Biostatistics, Jilin University School of Public Health, Changchun, Jilin, P. R. China
| | - Lu Long
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Sichuan, P. R. China
| | - Mi Na Kim
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
- Laboratory of Clinical Epidemiology in Hepatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Chun-Han Lo
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA
| | - Xing Liu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, P. R. China
| | | | - Brian M Wolpin
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Andrew T Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA
| | - Edward L Giovannucci
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Xuehong Zhang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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Shabanzadeh DM, Martinussen T, Sørensen LT. Development of upper gastrointestinal cancer in patients with symptomatic gallstones, cholecystectomy, and sphincterotomy: A nationwide cohort study. Scand J Surg 2022; 111:39-47. [PMID: 36000728 DOI: 10.1177/14574969221116941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND AND OBJECTIVE Exposures of gallstones and treatments thereof in relation to development of cancer have not been explored before in long-term follow-up studies. Our objective was to determine whether symptomatic gallstones, cholecystectomy, or sphincterotomy were associated with development of upper gastrointestinal cancers. METHODS This is a nationwide cohort study of persons born in Denmark 1930-1984 included from age 30 years with long-term follow-up (1977-2014). Exposures were hospital admissions with gallstones, cholecystectomy, and sphincterotomy. Time-varying covariates were included in analyses to allow the impact of exposures to change with time. Follow-up periods were 2-5 and > 5 years. Hazard ratios (HR) with 95% confidence intervals (CI) were reported. RESULTS A total of 4,465,962 persons were followed. We found positive associations between sphincterotomy and biliary (>5 years HR 4.34, CI [2.17-8.70]), gallbladder (2-5 years HR 20.7, CI [8.55-50.1]), and pancreatic cancer (2-5 years HR 3.68, CI [2.09-6.49]). Cholecystectomy was positively associated with duodenal (2-5 years HR 2.94, CI [1.31-6.58]) and small bowel cancer (2-5 years HR 2.75, CI [1.56-4.87]). Inverse associations were seen for cholecystectomy and biliary (>5 years HR 0.60, CI [0.41-0.87]), pancreatic (>5 years HR 0.45 CI [0.35-0.57]), esophageal (>5 years HR 0.57, CI [0.43-0.74]), and gastric cancer (>5 years HR 0.68, CI [0.55-0.86]) and for gallstones and pancreatic cancer (>5 years HR 0.66, CI [0.47-0.93]). Gallstones were positively associated with gallbladder (>5 years HR 3.51, CI [2.02-6.10]) and small bowel cancer (2-5 years HR 3.21, CI [1.60-6.45]). CONCLUSIONS A positive association between sphincterotomy and biliary cancer was identified. Cholecystectomy seems to be inversely associated with biliary, pancreatic, esophageal, and gastric cancer. Associations should be explored in similar large cohorts.
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Affiliation(s)
- Daniel M Shabanzadeh
- Research Unit, Digestive Disease Center, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Torben Martinussen
- Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Lars T Sørensen
- Digestive Disease Center, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark Institute for Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Xu J, Ren X, Liu Y, Zhang Y, Zhang Y, Chen G, Huang Q, Liu Q, Zhou J, Liu Y. Alterations of Fungal Microbiota in Patients With Cholecystectomy. Front Microbiol 2022; 13:831947. [PMID: 35633725 PMCID: PMC9132483 DOI: 10.3389/fmicb.2022.831947] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 03/31/2022] [Indexed: 11/17/2022] Open
Abstract
Increasing evidence suggests a high risk of gastrointestinal postoperative comorbidities (such as colorectal cancer) in patients with postcholecystectomy (PC). Although previous studies implicated the role of fungi in colon carcinogenesis, few reports focused on the fungal profile in patients with PC. We enrolled 104 subjects, including 52 patients with PC and 52 non-PC controls (CON), for fecal collection to detect the fungal composition by an internal transcribed spacer (ITS) 1 rDNA sequencing. Data showed that Candida (C.) glabrata and Aspergillus (A.) Unassigned were enriched, and Candida albicans was depleted in patients with PC. In addition, postoperative duration was the main factor to affect the fungal composition. Machine learning identified that C. glabrata, A. Unassigned, and C. albicans were three biomarkers to discriminate patients with PC from CON subjects. To investigate the fungal role in colon carcinogenesis, the subjects of the PC group were divided into two subgroups, namely, patients with PC without (non-CA) and with precancerous lesions or colorectal cancer (preCA_CRC), by histopathological studies. C. glabrata was found to be gradually accumulated in different statuses of patients with PC. In conclusion, we found fungal dysbiosis in patients with cholecystectomy, and the postoperative duration was a potent factor to influence the fungal composition. The accumulation of C. glabrata might be connected with carcinogenesis after cholecystectomy.
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Affiliation(s)
- Jun Xu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
| | - Xinhua Ren
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yun Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
| | - Yuanyuan Zhang
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
| | - Yiwen Zhang
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
| | - Guodong Chen
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
| | - Qing Huang
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
| | - Qing Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
| | - Jianhua Zhou
- Institute of Clinical Molecular Biology and Central Laboratory, Peking University People's Hospital, Beijing, China
| | - Yulan Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
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Choi YJ, Jin EH, Lim JH, Shin CM, Kim N, Han K, Lee DH. Increased Risk of Cancer after Cholecystectomy: A Nationwide Cohort Study in Korea including 123,295 Patients. Gut Liver 2022; 16:465-473. [PMID: 35502586 PMCID: PMC9099388 DOI: 10.5009/gnl210009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 05/23/2021] [Accepted: 06/14/2021] [Indexed: 11/04/2022] Open
Abstract
Background/Aims Contradictory findings on the association between cholecystectomy and cancer have been reported. We aimed to investigate the risk of all types of cancers or site-specific cancers in patients who underwent cholecystectomy using a nationwide dataset. Methods Subjects who underwent cholecystectomy from January 1, 2007, to December 31, 2014, who were older than 20 years and who underwent an initial baseline health check-up within 2 years were enrolled. Those who were diagnosed with any type of cancer before the enrollment or within 1 year after enrollment were excluded. Ultimately, patients (n=123,295) who underwent cholecystectomy and age/sex matched population (n=123,295) were identified from the database of the Korean National Health Insurance Service. The hazard ratio (HR) and 95% confidence interval (CI) for cancer were estimated, and Cox regression analysis was performed. Results The incidence of cancer in the cholecystectomy group was 9.56 per 1,000 personyears and that in the control group was 7.95 per 1,000 person-years. Patients who underwent cholecystectomy showed an increased risk of total cancer (adjusted HR, 1.19; 95% CI, 1.15 to 1.24; p<0.001), particularly leukemia and malignancies of the colon, liver, pancreas, biliary tract, thyroid, pharynx, and oral cavity. In the subgroup analysis according to sex, the risk of developing cancers in the pancreas, biliary tract, thyroid, lungs and stomach was higher in men than in women. Conclusions Physicians should pay more attention to the possibility of the occurrence of secondary cancers among patients who undergo cholecystectomy.
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Affiliation(s)
- Yoon Jin Choi
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Hyo Jin
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
| | - Joo Hyun Lim
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Ahn HS, Kim HJ, Kang TU, Park SM. Cholecystectomy reduces the risk of cholangiocarcinoma in patients with complicated gallstones, but has negligible effect on hepatocellular carcinoma. J Gastroenterol Hepatol 2022; 37:669-677. [PMID: 34907591 DOI: 10.1111/jgh.15759] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 11/08/2021] [Accepted: 12/05/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Gallstones have been reported to be positively associated with hepatobiliary cancers. However, risks of these cancers by cholecystectomy or in patients with complicated gallstones are controversial. We studied the effect of cholecystectomy on the risk of cholangiocarcinoma (CCA) or hepatocellular carcinoma (HCC) in patients with gallstones and subgroup of complicated gallstones. METHODS Patients with gallstone disease (n = 958 677) and age-matched and sex-matched controls (n = 9 586 770) were identified using the Korean National Health Insurance database. Complicated gallstones were defined as gallstones associated with acute cholecystitis or acute cholangitis. Adjusted hazard ratios (adjusted hazard ratios, 95% confidence interval) of CCA and HCC incidences were evaluated in patients with gallstones who received cholecystectomy compared to the controls. We also analyzed these effects in patients with complicated gallstones. RESULTS Patients with gallstones showed increased risks of CCA (1.80, 1.67-1.93) and HCC (1.03, 1.00-1.07) compared with controls. Cholecystectomy had minimal effects on the risks of CCA (1.94, 1.76-2.14) and HCC (0.93, 0.87-0.99) compared with those without cholecystectomy. However, patients with complicated gallstones showed highly increased CCA risk (5.62, 4.89-6.46) and a 30% risk reduction after cholecystectomy (3.91, 3.43-4.46). Risk reduction by cholecystectomy was greater for extrahepatic CCA than for intrahepatic CCA or ampulla of Vater cancer. However, the risk of HCC was not different in patients with complicated gallstones and those who underwent cholecystectomy compared to controls. CONCLUSION The risk of CCA was markedly increased in patients with complicated gallstones and was partially reduced by cholecystectomy. The risk change of HCC was minimal with gallstones or cholecystectomy.
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Affiliation(s)
- Hyeong Sik Ahn
- Department of Preventive Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Hyun Jung Kim
- Department of Preventive Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Tae Uk Kang
- Health and Wellness College, Sungshin Women's University, Seoul, South Korea
| | - Seon Mee Park
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, South Korea
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Xu Y, Jing H, Wang J, Zhang S, Chang Q, Li Z, Wu X, Zhang Z. Disordered Gut Microbiota Correlates With Altered Fecal Bile Acid Metabolism and Post-cholecystectomy Diarrhea. Front Microbiol 2022; 13:800604. [PMID: 35250923 PMCID: PMC8894761 DOI: 10.3389/fmicb.2022.800604] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 01/17/2022] [Indexed: 12/12/2022] Open
Abstract
Post-cholecystectomy diarrhea (PCD) is a common complication of gallbladder removal, and gut microbiota changes have been determined in PCD patients. Bile acid diarrhea (BAD) is supposed to be the main pathogenic factor for PCD due to the disrupted fecal bile acid metabolism in diarrheal patients. However, the profiling of bile acid metabolite alteration in PCD is unclear and whether changed gut microbiota and fecal bile acid metabolism are correlated is also underdetermined. The fecal bile acid metabolites from fecal samples were profiled by targeted UPLC/MS (ultra-high-performance liquid chromatography coupled with a triple-quadrupole mass spectrometer) and the composition of fecal bile acid metabolites in PCD patients was demonstrated to be distinct from those in Non-PCD and HC groups. In addition, the quantification of bile acid excretion in feces of diarrheal patients was significantly elevated. Furthermore, 16S rRNA sequencing results revealed that PCD patients had the lowest operational taxonomic units (OTU) and significant reduction in microbial richness and evenness. Bacterial composition was remarkably shifted in PCD patients, which mainly lay in dominated phyla Firmicutes and Bacteroidota. Besides, the co-abundance network among genus bacteria declined in PCD. Among the genera, Prevotella, Enterococcus, and Erysipelotrichaceae_UCG-003 were enriched, but Alistipes, Bacteroides, Ruminococcus, and Phascolarctobacterium were reduced. Moreover, these disease-linked genera were closely associated with several diarrheal phenotypes. Notably, changed bile acid metabolites exhibited strong correlations with gut microbiota as well. Conclusively, this study reveals associations between PCD-linked microbes and bile acid metabolites, which may synergistically correlate to postoperative diarrhea.
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Affiliation(s)
- Yayun Xu
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Hui Jing
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Jianfa Wang
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
| | - Shilong Zhang
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qimeng Chang
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
| | - Zhanming Li
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
- Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Xubo Wu
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
- *Correspondence: Xubo Wu,
| | - Ziping Zhang
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
- Ziping Zhang,
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Yang Y, Liu MH, Li Y. Association Between Cholecystectomy and Gastric Cancer Risk: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:667736. [PMID: 35174075 PMCID: PMC8841561 DOI: 10.3389/fonc.2022.667736] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 01/05/2022] [Indexed: 01/07/2023] Open
Abstract
Objectives Although several epidemiological studies have attempted to evaluate the relationship between cholecystectomy and gastric cancer risk, the findings have been controversial. This study aimed to carry out a systematic review and meta-analysis following the reporting guidelines to comprehensively analyze and quantify the evidence of the aforementioned association. Methods Studies were identified by searching the Medline (PubMed), Embase, and Web of Science from inception to November 30, 2020, with only studies published in English being considered. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random-effects models. Results Eight studies (five cohort studies and three case–control studies) with a total of 26,063 gastric cancer patients and 848,081 participants were included. The summarized RR of the relationship between cholecystectomy and gastric cancer risk was 1.11 (95%CI: 1.03–1.20), with low heterogeneity (P = 0.117, I2 = 37.8%). These positive findings were consistent in most subgroup analyses like region in Asia, number of cases ≥200, cohort study design, sex in male, low risk of bias, exposure collection by database, and adjustments made for age, gender, calendar year. Of note, we also observed positive association between cholecystectomy and non-cardia of gastric cancer risk (RR = 1.17, 95%CI: 1.04–1.33). No publication bias was present. Conclusions The aforementioned evidence suggested that a history of cholecystectomy was associated with a slightly elevated risk of gastric cancer. Results of most subgroup analyses also supported the main findings. More prospective studies are warranted to further validate these findings.
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Wang B, Huang A, Jiang M, Li H, Bao W, Ding K, Jiang Z, Zhao G, Hu H. Risk Factors for Early Recurrence of Gallstones in Patients Undergoing Laparoscopy Combined With Choledochoscopic Lithotomy: A Single-Center Prospective Study. Front Surg 2021; 8:759390. [PMID: 34901141 PMCID: PMC8651707 DOI: 10.3389/fsurg.2021.759390] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 10/12/2021] [Indexed: 01/07/2023] Open
Abstract
Objective: For patients with gallstones, laparoscopy combined with choledochoscopic lithotomy is a therapeutic surgical option for preservation rather than the removal of the gallbladder. However, postoperative recurrence of gallstones is a key concern for both patients and surgeons. This prospective study was performed to investigate the risk factors for early postoperative recurrence of gallstones. Methods: The clinical data of 466 patients were collected. Each patient was followed up for up to 2 years. The first follow-up visit occurred 4 months after the operation, and a follow-up visit was carried out every 6 months thereafter. The main goal of each visit was to confirm the presence or absence of gallbladder stones. The factors associated with gallstone recurrence were analyzed by univariate analysis and Cox regression. Results: In total, 466 eligible patients were included in the study, and 438 patients (180 men and 258 women) completed the 2-year postoperative follow-up. The follow-up rate was 94.0%. Recurrence of gallstones was detected in 5.71% (25/438) of the patients. Univariate analysis revealed five risk factors for the recurrence of gallstones. Multivariate Cox regression analysis showed that multiple gallstones, a gallbladder wall thickness of ≥4 mm, and a family history of gallbladder stones were the three predictive factors for postoperative recurrence of gallstones (P < 0.05). Conclusion: The overall 2-year recurrence rate of gallstones after the operation was 5.71%. Multiple gallstones, a gallbladder wall thickness of ≥4 mm, and a family history of gallstones were the three risk factors associated with early postoperative recurrence of gallstones.
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Affiliation(s)
- Bo Wang
- Center of Gallbladder Diseases, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Anhua Huang
- Center of Gallbladder Diseases, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Min Jiang
- Center of Gallbladder Diseases, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Haidong Li
- Center of Gallbladder Diseases, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wenqing Bao
- Center of Gallbladder Diseases, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Kan Ding
- Center of Gallbladder Diseases, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zhaoyan Jiang
- Center of Gallbladder Diseases, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Gang Zhao
- Center of Gallbladder Diseases, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Hai Hu
- Center of Gallbladder Diseases, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
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Zarnescu N, Zarnescu E, Dumitrascu I, Chirca A, Sanda N, Iliesiu A, Costea R. Synchronous biliary gallstones and colorectal cancer: A single center analysis. Exp Ther Med 2021; 23:138. [PMID: 35069819 PMCID: PMC8756434 DOI: 10.3892/etm.2021.11061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 11/17/2021] [Indexed: 11/29/2022] Open
Abstract
Gallstones and colorectal cancer (CRC) are two common disorders that may develop simultaneously. In such situations, there is a significant chance of missing one of the conditions due to the primary clinical presentation. Late detection, diagnosis and treatment can be especially problematic in the case of unrecognized CRC. In the present study, the medical charts were retrospectively reviewed for all consecutive patients who were treated in the Second Department of Surgery, University Emergency Hospital Bucharest (Romania) between February 2015 and December 2017 following a diagnosis of CRC and/or biliary stones. There were 203 patients with CRC, 433 with biliary gallstones and 19 patients with both conditions. There were 125 men (61.6%) in the CRC group and 138 men (31.9%) in the gallstone group. The average age was 54.1±15.9 years in the gallstone group and 66.1±11.6 years in the CRC group. Obesity was observed in 96 patients (22.2%) with gallstones and in 14 (6.9%) patients in the CRC group. In the CRC group, 80 patients had medical comorbidities (39.4%), while in the gallstone group 126 patients (29.1%) had medical comorbidities. Bivariate analysis comparing gallstone only vs. gallstone and CRC identified age (P=0.001), male sex (P=0.001) and thyroid disease (P=0.001) as significant factors associated with synchronous diagnosis. The multivariable logistic regression of factors predicting CRC in patients with gallstones identified age (OR, 1.06; 95% CI, 1.023-1.105; P=0.002) and thyroid diseases (OR, 11.15; 95% CI, 2.532-49.06; P=0.001) as independent factors. There were significant differences regarding the location of the tumor between the CRC-only group and the gallstone and CRC group (P=0.001): Rectum (39.7 vs. 5.3%), left colon (26.6 vs. 21.1%), transverse colon (13 vs. 26.3%) and right colon (20.7 vs. 47.4%). The study concluded that, in patients with gallstones, age and thyroid conditions were significantly associated with CRC. Patients with a synchronous diagnosis of gallstones and CRC had significantly more right-sided CRC compared with regular CRC.
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Affiliation(s)
- Narcis Zarnescu
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Eugenia Zarnescu
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Ioana Dumitrascu
- Second Department of Surgery, University Emergency Hospital, 050098 Bucharest, Romania
| | - Alexandru Chirca
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Nicoleta Sanda
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Andreea Iliesiu
- Department of Pathology, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Radu Costea
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
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Aurif F, Kaur H, Chio JPG, Kittaneh M, Malik BH. The Association Between Cholecystectomy and Colorectal Cancer in the Female Gender. Cureus 2021; 13:e20113. [PMID: 34984153 PMCID: PMC8720289 DOI: 10.7759/cureus.20113] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Accepted: 12/02/2021] [Indexed: 11/25/2022] Open
Abstract
Colorectal carcinoma (CRC) has been of great interest among researchers, and multiple causes have been proposed and accepted; however, cholecystectomy (CMY) as a potential cause for CRC, particularly in the female gender has not been studied in detail, despite multiple evidence suggesting a positive association. This review is directed at investigating the association between CMY and CRC in the female gender and aims at finding a potential cause for this association. CRC involves cancer of the sigmoid and rectum. The composition of the bile acids is altered in patients after CMY, and the resultant secondary bile acids (BA) without a functioning gall bladder are exposed directly to the intestines, which could lead to cancer. An increase in fecal secondary bile acids is also described as high in the CMY population and has been linked to cancer. Right-sided GI cancers were attributed to CMY, although many earlier studies did not find this to be true. It is interesting to note a strong association between CRC and CMY in the female western population.
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Chen Y, Wang Q, Gao W, Ma B, Xue D, Hao C. Changes and Correlations of the Intestinal Flora and Liver Metabolite Profiles in Mice With Gallstones. Front Physiol 2021; 12:716654. [PMID: 34489732 PMCID: PMC8416897 DOI: 10.3389/fphys.2021.716654] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 08/02/2021] [Indexed: 12/12/2022] Open
Abstract
There is increasing appreciation for the roles of the gut-liver axis in liver and gall diseases. Specific gut microbes are associated with susceptibility to gallstone diseases, while the relationship between intestinal flora and liver metabolism in the formation of gallstones remains unclear. In this study, an experimental group of model mice was given a lithogenic diet, and a control group was given a normal diet. Both groups were fed for 8 weeks. Integrating 16S rRNA gene sequencing and non-targeted metabolomics to explore the impact of the lithogenic diet on intestinal flora and liver metabolism, Spearman correlation analysis reveals the network of relationships between the intestine and liver. Our findings showed that the gut microbiome and liver metabolome compositions of the test group were significantly changed compared with those of the normal group. Through our research, biomarkers of gallstones were identified at the phylum (5), class (5), order (5), family (7), and genus levels. We predicted the function of the differential flora. We analyzed the liver metabolism of mice with gallstones paired with their flora, and the results showed that there were 138 different metabolites between the two groups. The metabolic pathways enriched by these differential metabolites are highly consistent with the functions of the disordered flora. We focused on an analysis of the relationship between deoxycholic acid, asymmetric dimethylarginine, glucosamine, tauroursodeoxycholic acid, and the disordered flora. This provides a basis for the establishment of the intestine-liver axis in gallstone disease. This research provides a theoretical basis for the research and development of probiotics and prebiotics.
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Affiliation(s)
- Yang Chen
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.,Department of General Surgery, Heilongjiang Provincial Hospital, Harbin, China
| | - Qiang Wang
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Wenqi Gao
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Biao Ma
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dongbo Xue
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Chenjun Hao
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
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Wang CC, Tseng MH, Wu SW, Yang TW, Chen HY, Sung WW, Su CC, Wang YT, Chen WL, Lai HC, Lin CC, Tsai MC. Symptomatic cholelithiasis patients have an increased risk of pancreatic cancer: A population-based study. J Gastroenterol Hepatol 2021; 36:1187-1196. [PMID: 32881083 DOI: 10.1111/jgh.15234] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Revised: 08/20/2020] [Accepted: 08/25/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM Pancreatic cancer is a fatal disease; currently, the risk factor survey is not suitable for sporadic pancreatic cancer, which has neither family history nor the genetic analysis data. The aim of the present study was to evaluate the roles of cholelithiasis and cholelithiasis treatments on pancreatic cancer risk. METHODS Symptomatic adult patients with an index admission of cholelithiasis were selected from one million random samples obtained between January 2005 and December 2009. The control group was matched with a 1:1 ratio for sex, age, chronic pancreatitis, and pancreatic cystic disease. Subsequent pancreatic cancer, which we defined as pancreatic cancer that occurred ≥ 6 months later, and total pancreatic cancer events were calculated in the cholelithiasis and control groups. The cholelithiasis group was further divided into endoscopic sphincterotomy/endoscopic papillary balloon dilatation, cholecystectomy, endoscopic sphincterotomy/endoscopic papillary balloon dilatation and cholecystectomy, and no-intervention groups for evaluation. RESULTS The cholelithiasis group and the matched control group included 8265 adults. The cholelithiasis group contained 86 cases of diagnosed pancreatic cancer, and the control group contained 8 cases (P < 0.001). The incidence rate ratio (IRR) of subsequent pancreatic cancer was significantly higher in the cholelithiasis group than in the control group (IRR: 5.28, P < 0.001). The IRR of subsequent pancreatic cancer was higher in the no-intervention group comparing with cholecystectomy group (IRR = 3.21, P = 0.039) but was similar in other management subgroups. CONCLUSION Symptomatic cholelithiasis is a risk factor for pancreatic cancer; the risk is similar regardless of the intervention chosen for cholelithiasis.
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Affiliation(s)
- Chi-Chih Wang
- Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- Division of Gastroenterology and Hepatology, Chung Shan Medical University Hospital, Taichung City, Taiwan
| | - Ming-Hseng Tseng
- Department of Medical Informatics, Chung Shan Medical University, Taichung City, Taiwan
| | - Sheng-Wen Wu
- Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- Division of Nephrology, Chung Shan Medical University Hospital, Taichung City, Taiwan
| | - Tzu-Wei Yang
- Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- Division of Gastroenterology and Hepatology, Chung Shan Medical University Hospital, Taichung City, Taiwan
| | - Hsuan-Yi Chen
- School of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- Division of Gastroenterology and Hepatology, Chung Shan Medical University Hospital, Taichung City, Taiwan
| | - Wen-Wei Sung
- Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- Department of Internal Medicine, Department of Urology, Chung Shan Medical University Hospital, Taichung City, Taiwan
| | - Chang-Cheng Su
- Division of Gastroenterology and Hepatology, Chung Shan Medical University Hospital, Taichung City, Taiwan
| | - Yao-Tung Wang
- Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- Division of Pulmonary Medicine, Chung Shan Medical University Hospital, Taichung City, Taiwan
| | - Wei-Liang Chen
- Division of Gastroenterology and Hepatology, Chung Shan Medical University Hospital, Taichung City, Taiwan
| | - Hsueh-Chou Lai
- Digestive Medicine Center, China Medical University Hospital, Taichung City, Taiwan
- School of Chinese Medicine, China Medical University Hospital, Taichung City, Taiwan
| | - Chun-Che Lin
- Digestive Medicine Center, China Medical University Hospital, Taichung City, Taiwan
- School of Medicine, China Medical University, Taichung City, Taiwan
| | - Ming-Chang Tsai
- Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- Division of Gastroenterology and Hepatology, Chung Shan Medical University Hospital, Taichung City, Taiwan
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Pang Y, Lv J, Kartsonaki C, Guo Y, Yu C, Chen Y, Yang L, Bian Z, Millwood IY, Walters RG, Li X, Zou J, Holmes MV, Chen J, Chen Z, Li L. Causal effects of gallstone disease on risk of gastrointestinal cancer in Chinese. Br J Cancer 2021; 124:1864-1872. [PMID: 33772150 PMCID: PMC8144569 DOI: 10.1038/s41416-021-01325-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 02/05/2021] [Accepted: 02/19/2021] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Gallstone disease (GSD) is associated with a higher risk of gastrointestinal (GI) cancer. However, it is unclear whether the associations are causal. METHODS The prospective China Kadoorie Biobank (CKB) recorded 17,598 cases of GI cancer among 510,137 participants without cancer at baseline during 10 years of follow-up. Cox regression was used to estimate hazard ratios (HRs) for specific cancer by GSD status and duration. Mendelian randomisation was conducted to assess the genetic associations of GSD with specific cancer. RESULTS Overall 6% of participants had symptomatic GSD at baseline. Compared with those without GSD, individuals with symptomatic GSD had adjusted HRs of 1.13 (1.01-1.29) for colorectal, 2.01 (1.78-2.26) for liver, 3.70 (2.88-4.87) for gallbladder, 2.31 (1.78-3.07) for biliary tract, and 1.38 (1.18-1.74) for pancreatic cancer. Compared with participants without GSD, the risks of colorectal, liver, gallbladder, biliary tract, and pancreatic cancer were highest during 0 to <5 years following disease diagnosis. There was evidence of genetic associations of GSD with these cancers, with odds ratios per 1-SD genetic score of 1.08 (1.05-1.11) for colorectal, 1.22 (1.19-1.25) for liver, 1.56 (1.49-1.64) for gallbladder, 1.39 (1.31-1.46) for biliary tract, and 1.16 (1.10-1.22) for pancreatic cancer. When meta-analysing the genetic estimates in CKB and UK Biobank, there was evidence of causal associations of GSD with colon cancer, gallbladder and biliary tract cancer (GBTC), and total GI cancer (RR per 1-SD: 1.05 [0.99-1.11], 2.00 [1.91-2.09], and 1.09 [1.05-1.13]). CONCLUSIONS GSD was associated with higher risks of several GI cancers, warranting future studies on the underlying mechanisms.
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Affiliation(s)
- Yuanjie Pang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China
| | - Jun Lv
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China
- Peking University Center for Public Health and Epidemic Preparedness & Response (PKU-PHEPR), Peking University, 38 Xueyuan Road, Beijing, 100191, China
| | - Christiana Kartsonaki
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, Big Data Institute Building, Roosevelt Drive, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Yu Guo
- Chinese Academy of Medical Sciences, Beijing, China
| | - Canqing Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China
- Peking University Center for Public Health and Epidemic Preparedness & Response (PKU-PHEPR), Peking University, 38 Xueyuan Road, Beijing, 100191, China
| | - Yiping Chen
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, Big Data Institute Building, Roosevelt Drive, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Ling Yang
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, Big Data Institute Building, Roosevelt Drive, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Zheng Bian
- Chinese Academy of Medical Sciences, Beijing, China
| | - Iona Y Millwood
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, Big Data Institute Building, Roosevelt Drive, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Robin G Walters
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, Big Data Institute Building, Roosevelt Drive, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Xiaojun Li
- Jili Street Community Health Service Center, Liuyang, China
| | - Ju Zou
- Jili Street Community Health Service Center, Liuyang, China
| | - Michael V Holmes
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, Big Data Institute Building, Roosevelt Drive, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, UK
- National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital, Oxford, UK
| | - Junshi Chen
- National Center for Food Safety Risk Assessment, Beijing, China
| | - Zhengming Chen
- Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, Big Data Institute Building, Roosevelt Drive, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Liming Li
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
- Peking University Center for Public Health and Epidemic Preparedness & Response (PKU-PHEPR), Peking University, 38 Xueyuan Road, Beijing, 100191, China.
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De Novo Cancer Incidence after Cholecystectomy in Korean Population. J Clin Med 2021; 10:jcm10071445. [PMID: 33916209 PMCID: PMC8037442 DOI: 10.3390/jcm10071445] [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: 01/09/2021] [Revised: 02/08/2021] [Accepted: 03/22/2021] [Indexed: 12/21/2022] Open
Abstract
Background: Cancer development after cholecystectomy remains debatable. We estimated the major cancer incidence rates after cholecystectomy stratified by age and sex. Methods: The records of 408,769 subjects aged >20 years were extracted from the National Health Insurance database from 2008 to 2016. The risks of major cancers were compared between the cholecystectomy and general populations using standardised incidence ratios (SIR). Results: The overall cancer incidence was comparable between cholecystectomy patients and the general population. However, patients aged <65 years who underwent cholecystectomy had a higher cancer risk than those aged ≥65 years and the general population (SIR 2.62; 95% confidence interval [CI] 2.15–3.08; SIR 1.36, 95% CI 1.32–1.40; and SIR 0.90, 95% CI 0.87–0.92 in men and SIR 1.91; 95% CI 1.71–2.10; SIR 1.07; 95% CI 1.03–1.10; and SIR 0.90; 95% CI 0.87–0.94 in women aged 20–34, 35–64, and ≥65 years at cholecystectomy). Colorectal and liver cancer incidences after cholecystectomy were higher than those in the general population regardless of age group and sex (SIR, 1.55 for colorectal cancer in men and women; SIR, 1.25 and 1.51 for liver cancer in men and women, respectively). However, for other major cancers, the risk was higher in patients who underwent cholecystectomy at a younger age than in those who underwent cholecystectomy at an age ≥65 years. Conclusion: Patients with cholecystectomy, especially those undergoing cholecystectomy at a younger age, need preventive strategies based on the cancer type.
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Culliford R, Cornish AJ, Law PJ, Farrington SM, Palin K, Jenkins MA, Casey G, Hoffmeister M, Brenner H, Chang-Claude J, Kirac I, Maughan T, Brezina S, Gsur A, Cheadle JP, Aaltonen LA, Dunlop MG, Houlston RS. Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis. Br J Cancer 2021; 124:1169-1174. [PMID: 33414539 PMCID: PMC7961009 DOI: 10.1038/s41416-020-01211-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 10/09/2020] [Accepted: 11/25/2020] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND Epidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we examine the relationship between these potential risk factors and CRC using Mendelian randomisation (MR). METHODS We used two-sample MR to examine the relationship between genetic liability to gallstone disease and circulating levels of bilirubin with CRC in 26,397 patients and 41,481 controls. We calculated the odds ratio per genetically predicted SD unit increase in log bilirubin levels (ORSD) for CRC and tested for a non-zero causal effect of gallstones on CRC. Sensitivity analysis was applied to identify violations of estimator assumptions. RESULTS No association between either gallstone disease (P value = 0.60) or circulating levels of bilirubin (ORSD = 1.00, 95% confidence interval (CI) = 0.96-1.03, P value = 0.90) with CRC was shown. CONCLUSIONS Despite the large scale of this study, we found no evidence for a causal relationship between either circulating levels of bilirubin or gallstone disease with risk of developing CRC. While the magnitude of effect suggested by some observational studies can confidently be excluded, we cannot exclude the possibility of smaller effect sizes and non-linear relationships.
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Affiliation(s)
- Richard Culliford
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
| | - Alex J Cornish
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
| | - Philip J Law
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
| | - Susan M Farrington
- Cancer Research UK Edinburgh Centre and Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Kimmo Palin
- Medicum and Genome-Scale Biology Research Program, Research Programs Units, Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland
| | - Mark A Jenkins
- Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, VIC, Australia
| | - Graham Casey
- Centre for Public Health Genomics, University of Virginia, Virginia, VA, USA
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany
- German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany
| | - Jenny Chang-Claude
- Unit of Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany
- Cancer Epidemiology Group, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Hamburg, Germany
| | - Iva Kirac
- Department of Surgical Oncology, University Hospital for Tumours, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia
| | - Tim Maughan
- Department of Oncology, University of Oxford, Oxford, UK
| | - Stefanie Brezina
- Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Andrea Gsur
- Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Jeremy P Cheadle
- Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff, UK
| | - Lauri A Aaltonen
- Medicum and Genome-Scale Biology Research Program, Research Programs Units, Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland
| | - Malcom G Dunlop
- Cancer Research UK Edinburgh Centre and Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Richard S Houlston
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
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Alexander C, Cross TWL, Lee AH, Ly LK, Vieson MD, Ridlon JM, Nelson ER, Swanson KS. Development of a novel model of cholecystectomy in subsequently ovariectomized mice and characterization of metabolic and gastrointestinal phenotypes: a pilot study. BMC Gastroenterol 2021; 21:62. [PMID: 33573601 PMCID: PMC7879663 DOI: 10.1186/s12876-021-01648-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 01/20/2021] [Indexed: 11/29/2022] Open
Abstract
Background Cholecystectomy (XGB) is the most common abdominal surgery performed in the United States and is associated with an increased post-surgery incidence of metabolic and gastrointestinal (GI) diseases. Two main risk factors for XGB are sex (female) and age (40–50 yr), corresponding with onset of menopause. Post-menopausal estrogen loss alone facilitates metabolic dysfunction, but the effects of XGB on metabolic and GI health have yet to be investigated in this population. Study objectives were to (1) identify possible short-term effects of XGB and (2) develop a novel murine model of XGB in human menopause via subsequent ovariectomy (OVX) and assess longitudinal effects of OVX on metabolism, GI physiology, and GI microbiota in XGB mice. Methods Female C57BL/6 mice were utilized in two parallel studies (S1&S2). In S1, XGB mice were compared to a non-XGB baseline group after six wk. In S2, mice were XGB at wk0, either sham (SHM) or OVX at wk6, and sacrificed at wk12, wk18, and wk24. Body composition assessment and fresh fecal collections were conducted periodically. Serum and tissues were collected at sacrifice for metabolic and GI health endpoints. Results Compared to baseline, XGB increased hepatic CYP7A1 and decreased HMGCR relative expression, but did not influence BW, fat mass, or hepatic triglycerides after six wk. In S2, XGB/OVX mice had greater BW and fat mass than XGB/SHM. Cecal microbiota alpha diversity metrics were lower in XGB/OVX mice at wk24 compared the XGB/SHM. No consistent longitudinal patterns in fasting serum lipids, fecal microbial diversity, and GI gene expression were observed between S2 groups. Conclusions In addition to developing a novel, clinically-representative model of XGB and subsequent OVX, our results suggest that OVX resulted in the expected phenotype to some extent, but that XGB may modify or mask some responses and requires further investigation.
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Affiliation(s)
- Celeste Alexander
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1207 W Gregory Dr, Urbana, IL, 61801, USA.
| | - Tzu-Wen L Cross
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1207 W Gregory Dr, Urbana, IL, 61801, USA
| | - Anne H Lee
- Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - Lindsey K Ly
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1207 W Gregory Dr, Urbana, IL, 61801, USA
| | - Miranda D Vieson
- College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - Jason M Ridlon
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1207 W Gregory Dr, Urbana, IL, 61801, USA.,Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.,Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, USA.,Carl R. Woese Institute for Genomic Biology, Anticancer Discovery from Pets to People Theme, University of Illinois Urbana-Champaign, IL, Urbana, USA
| | - Erik R Nelson
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1207 W Gregory Dr, Urbana, IL, 61801, USA.,Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, USA.,Carl R. Woese Institute for Genomic Biology, Anticancer Discovery from Pets to People Theme, University of Illinois Urbana-Champaign, IL, Urbana, USA.,Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.,University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, USA
| | - Kelly S Swanson
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1207 W Gregory Dr, Urbana, IL, 61801, USA. .,Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
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44
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Kim SB, Kim KO, Kim TN. Prevalence and Risk Factors of Gastric and Colorectal Cancer after Cholecystectomy. J Korean Med Sci 2020; 35:e354. [PMID: 33140590 PMCID: PMC7606888 DOI: 10.3346/jkms.2020.35.e354] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 09/08/2020] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Previous studies on the relationship between gastrointestinal (GI) cancer and cholecystectomy remain inconclusive. We aimed to evaluate this relationship, albeit particularly between cholecystectomy and gastric cancer or colorectal cancer (CRC), and the risk factors of cancer among individuals who have undergone cholecystectomy in Korea. METHODS In total, 4,222 patients who underwent laparoscopic or open cholecystectomy at our institution between January 2006 and December 2013 were included. Patients who underwent cholecystectomy for gallbladder cancer or were undergoing surgery for GI, hepatic, or pancreatobiliary cancers were excluded, as were those who developed stomach cancer or CRC within a year of their cholecystectomy. The included patients were followed until July 20, 2020. The standardized incidence ratio (SIR) was used to calculate the relative risk of GI cancer in cholecystectomy patients. RESULTS The median patient age (n = 3,588) at the time of cholecystectomy was 54.0 (range, 19-95) years, and the male-to-female ratio was 1:1.04. The median follow-up period after cholecystectomy was 15.0 (range, 0-146) months. We found a 108% greater risk of CRC (SIR, 2.08; 95% confidence interval [CI], 1.28-3.17) and 154% increased risk of CRC in females (SIR, 2.54; 95% CI, 1.16-4.84). Based on multivariate analysis, an age of > 60 years was a significant risk factor for GI cancer in cholecystectomy patients. CONCLUSION Cholecystectomy may increase risk of CRC, especially in females. Age was considered a risk factor of GI cancers in patients with history of cholecystectomy.
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Affiliation(s)
- Sung Bum Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Kyeong Ok Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.
| | - Tae Nyeum Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
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45
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Huang D, Lee J, Song N, Cho S, Choe S, Shin A. Gallstones, Cholecystectomy and the Risk of Hepatobiliary and Pancreatic Cancer: A Nationwide Population-based Cohort Study in Korea. J Cancer Prev 2020; 25:164-172. [PMID: 33033710 PMCID: PMC7523037 DOI: 10.15430/jcp.2020.25.3.164] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 09/21/2020] [Accepted: 09/21/2020] [Indexed: 11/03/2022] Open
Abstract
Several epidemiological studies suggest a potential association between gallstones or cholecystectomy and hepatobiliary and pancreatic cancers (HBPCs). The aim of this study was to evaluate the risk of HBPCs in patients with gallstones or patients who underwent cholecystectomy in the Korean population. A retrospective cohort was constructed using the National Health Insurance Service-National Sample Cohort (NHIS-NSC). Gallstones and cholecystectomy were defined by diagnosis and procedure codes and treated as time-varying covariates. Hazard ratios (HRs) in relation to the risk of HBPCs were estimated by Cox proportional hazard models. Among the 704,437 individuals who were included in the final analysis, the gallstone prevalence was 2.4%, and 1.4% of individuals underwent cholecystectomy. Between 2002 and 2015, 487 and 189 individuals developed HBPCs in the gallstone and cholecystectomy groups, respectively. A significant association was observed between gallstones and all HBPCs (HR 2.16; 95% CI 1.92-2.42) and cholecystectomy and all HBPCs (HR 2.03; 95% CI 1.72-2.39). However, when 1-, 3-, and 5-year lag periods were applied, the HBPC and subsites risk approached zero. A significant association was observed between cholecystectomy and intrahepatic bile duct cancer (IBDC) (HR 2.68; 95% CI 1.63-4.40). When 1-, 3- and 5-year lag periods were applied, the IBDC risk after cholecystectomy was 2.86-fold (95% CI 1.68-4.85), 2.92-fold (95% CI 1.51-5.64), and 4.08-fold (95% CI 1.94-8.61) higher, respectively, than that in the comparison group. In conclusion, gallstone diagnosis and cholecystectomy seem to correlate with HBPCs, especially cholecystectomy and IBDC.
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Affiliation(s)
- Dan Huang
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.,Division of Cancer Control and Policy, National Cancer Control Institute, National Cancer Center, Goyang, Korea
| | - Joonki Lee
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.,Division of Cancer Control and Policy, National Cancer Control Institute, National Cancer Center, Goyang, Korea
| | - Nan Song
- Cancer Research Institute, Seoul National University, Seoul, Korea.,Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Sooyoung Cho
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Sunho Choe
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Aesun Shin
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.,Cancer Research Institute, Seoul National University, Seoul, Korea
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46
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Liu T, Siyin ST, Yao N, Xu G, Chen YT, Duan N, Li W, Qu J, Liu S. Risk of primary liver cancer associated with gallstones and cholecystectomy: A competing risks analysis. Medicine (Baltimore) 2020; 99:e22428. [PMID: 32991479 PMCID: PMC7523846 DOI: 10.1097/md.0000000000022428] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Previous research has revealed a positive relationship between GSD, cholecystectomy and primary liver cancer (PLC). However, previous studies had several limitations including the retrospective design, narrow assessment of potential confounders and lack of competing risk models in time-to-event analyses. We conducted a large prospective cohort study to explore the relationship between GSD, cholecystectomy and PLC. A total of 95,021 participants who had not been diagnosed with PLC previously were enrolled from the Kailuan Cohort study. Demographic characteristics and biochemical parameters were recorded at baseline for all participants. We used Cox regression models and competing risk regression models to evaluate the association of GSD and cholecystectomy with the risk PLC. A total of 306 incidental PLC cases were identified during a median follow-up of 9.05 (8.75-9.22) years per participant. Compared with the normal group, the multivariable HRs (95%CI) for the association of GSD and cholecystectomy with PLC were 1.77 (1.05-2.94), 5.25 (1.95-14.17). In the CS model, the multivariable HRs (95%CI) was 1.76 (1.05-2.94) for the association of GSD and cholecystectomy with PLC and 5.25 (1.95-14.17) for GSD and cholecystectomy. Similar results were also obtained in the SD model with corresponding multivariate HRs (95%CI) of 1.75 (1.01-3.00), 5.22 (1.90-14.07) in the GSD group and cholecystectomy group, respectively. GSD and cholecystectomy were associated with an elevated risk of PLC.Registration number: ChiCTR-TNRC-11001489.
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Affiliation(s)
- Tong Liu
- Department of General Surgery, Aerospace Center Hospital
| | - Sarah Tan Siyin
- Department of General Surgery, Beijing Children's Hospital, National Center for Children's Health
| | - Nan Yao
- Department of General Surgery, Aerospace Center Hospital
| | - Guoshuai Xu
- Department of General Surgery, Aerospace Center Hospital
| | - Yi-Tsun Chen
- Department of Clinic Medicine, Peking University Health Science Center, Beijing
| | - Ning Duan
- Department of General Surgery, Aerospace Center Hospital
| | - Wenqiang Li
- Department of General Surgery, Aerospace Center Hospital
| | - Jun Qu
- Department of General Surgery, Aerospace Center Hospital
| | - Siqing Liu
- Department of Hepatobiliary Surgery, Kailuan General Hospital, Tangshan, China
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Singh A, Koenen B, Kirby DF. Bariatric Surgery and Its Complications in Inflammatory Bowel Disease Patients. Inflamm Bowel Dis 2020; 26:1155-1165. [PMID: 31626698 DOI: 10.1093/ibd/izz246] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Indexed: 12/14/2022]
Abstract
Recent data have suggested that bariatric procedures, especially laparoscopic sleeve gastrectomy (SG), are safe and effective weight loss measures in patients with inflammatory bowel disease (IBD). But most of the studies have looked at short-term outcomes, and there is a general lack of awareness of underlying disease processes and baseline comorbidities in IBD patients undergoing bariatric procedures. Postbariatric issues in IBD patients including diarrhea from dumping syndrome, choleretic diarrhea, a high prevalence of small intestinal bacterial overgrowth, gastroesophageal reflux disease, Barrett's esophagus, stomal ulcerations, stenosis, and renal and gallstones can complicate the natural history of IBD. This could lead to unnecessary hospitalizations, change of medical therapy, and poor surgical and quality of life outcomes. In this review, we will discuss major complications after common bariatric procedures (SG, Roux-en-Y gastric bypass, and gastric banding) and suggest possible management strategies.
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Affiliation(s)
- Amandeep Singh
- Department of Gastroenterology, Hepatology & Nutrition, Center for Human Nutrition, Center for Gut Rehabilitation and Intestinal Transplantation, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Brian Koenen
- Department of Gastroenterology, Hepatology & Nutrition, Center for Human Nutrition, Center for Gut Rehabilitation and Intestinal Transplantation, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Donald F Kirby
- Department of Gastroenterology, Hepatology & Nutrition, Center for Human Nutrition, Center for Gut Rehabilitation and Intestinal Transplantation, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
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48
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Zhao X, Wang N, Sun Y, Zhu G, Wang Y, Wang Z, Zhang Y, Cheng K, Wang G, Wu S, Wang L. Screen-detected gallstone disease and risk of liver and pancreatic cancer: The Kailuan Cohort Study. Liver Int 2020; 40:1744-1755. [PMID: 32250535 DOI: 10.1111/liv.14456] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 03/17/2020] [Accepted: 03/28/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Few studies have examined the risk of gastrointestinal cancers in screen-detected gallstone disease. This study aimed to investigate the association between screen-detected gallstone disease and gastrointestinal cancers using the Kailuan cohort, a population-based prospective cohort initiated in 2006. METHODS A total of 79 809 men who underwent gallbladder ultrasonography, were free of cancers in 2006 and did not have gastrointestinal cancers within one year were enrolled. A Cox proportional hazards model with age as the timescale was used to evaluate the association between screen-detected gallstone disease and gastrointestinal cancers. RESULTS We identified 1264 cases with gastrointestinal cancers, including 303 cases with liver cancer and 94 cases with pancreatic cancer. Screen-detected gallstone disease increased the risk of liver cancer, with an HR of 2.28 [95% confidence interval (CI): 1.20-4.33, P = .012]. The association was modified by the hepatitis B surface antigen status. A non-significant positive association was observed between pancreatic cancer and gallstone disease (HR 2.19, 95% CI: 0.95-5.05, P = .065). However, the HR became significant after those individuals with diabetes were excluded (HR 2.60, 95% CI: 1.12-6.01, P = .026). CONCLUSION Screen-detected gallstone disease may predict the risk for liver and pancreatic cancer.
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Affiliation(s)
- Xinyu Zhao
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
| | - Na Wang
- Department of cardiology, the second hospital of Qinhuangdao, Qinhuangdao, China
| | - Yuanyuan Sun
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
| | - Guoling Zhu
- Department of Gastroenterology, Kailuan General Hospital, Tangshan, China
| | - Yanhong Wang
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
| | - Zhenyu Wang
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
| | - Yanmin Zhang
- Department of Gastroenterology, Kailuan General Hospital, Tangshan, China
| | - Kailiang Cheng
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
| | - Guodong Wang
- Department of Employee Health Protection, Tangshan, China
| | - Shouling Wu
- Department of cardiology, Kailuan General Hospital, Tangshan, China
| | - Li Wang
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
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Grigor’eva IN, Romanova TI. Gallstone Disease and Microbiome. Microorganisms 2020; 8:E835. [PMID: 32498344 PMCID: PMC7356158 DOI: 10.3390/microorganisms8060835] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 05/28/2020] [Accepted: 05/30/2020] [Indexed: 12/12/2022] Open
Abstract
Gallstone disease (GSD) has, for many years, remained a high-cost, socially significant public health problem. Over the past decade, a number of studies have been carried out-both in humans and in animal models-confirming the role of the microbiota in various sections of the gastrointestinal tract as a new link in the etiopathogenesis of GSD. The microbiome of bile correlates with the bacterial composition of saliva, and the microbiome of the biliary tract has a high similarity with the microbiota of the duodenum. Pathogenic microflora of the oral cavity, through mechanisms of immunomodulation, can affect the motility of the gallbladder and the expression of mucin genes (MUC1, Muc3, MUC4), and represent one of the promoters of stone formation in the gallbladder. The presence of H. pylori infection contributes to the formation of gallstones and affects the occurrence of complications of GSD, including acute and chronic cholecystitis, cholangitis, pancreatitis. Intestinal bacteria (Clostridium, Bifidobacterium, Peptostreptococcus, Bacteroides, Eubacterium, and Escherichia coli) participating in the oxidation and epimerization of bile acids can disrupt enterohepatic circulation and lead to the formation of gallstones. At the same time, cholecystectomy due to GSD leads to the further transformation of the composition of the microbiota in various parts of the gastrointestinal tract, increasing the risk of developing stomach cancer and colorectal cancer. Further research is required to determine the possibility of using the evaluation of the composition of the microbiota of the gastrointestinal and biliary tracts as an early diagnostic marker of various gastroenterological diseases.
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Affiliation(s)
| | - Tatyana I. Romanova
- Laboratory of Gastroenterology, Research Institute of Internal and Preventive Medicine-Branch of The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of Russian Academy of Sciences, Novosibirsk 630089, Russia;
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50
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Chen CH, Lin CL, Kao CH. The Effect of Cholecystectomy on the Risk of Colorectal Cancer in Patients with Gallbladder Stones. Cancers (Basel) 2020; 12:cancers12030550. [PMID: 32120781 PMCID: PMC7139669 DOI: 10.3390/cancers12030550] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 02/15/2020] [Accepted: 02/24/2020] [Indexed: 12/24/2022] Open
Abstract
To evaluate the risk of colorectal cancer (CRC) after cholecystectomy for gallbladder stones (GBS). METHODS This nationwide population-based cohort study analyzed the inpatient data from the Taiwan National Health Insurance Research Database. The study cohort comprised of 83,963 patients aged 20 years undergoing cholecystectomy for GBS between 2000 and 2010. The control cohort comprised the GBS patients without cholecystectomy, who were propensity matched with the study cohort at a 1:1 ratio based on age, sex, comorbidities, and the index date for cholecystectomy. RESULTS The cumulative incidence of CRC within 6 months of follow-up was higher in the cholecystectomy cohort than that in the non-cholecystectomy cohort (aHR (adjusted hazard ratio) = 7.90, 95% confidence interval (CI) = 6.27-9.94; log-rank test, p < 0.001). The cumulative incidence of CRC after 6 months of follow-up was lower in the cholecystectomy cohort than that in the non-cholecystectomy cohort (aHR = 0.66, 95% CI = 0.60-0.73; log-rank test, p < 0.001), but the reduced risk of CRC for the cholecystectomy cohort was statistically significant only in rectal cancer after separately considering females (aHR = 0.64, 95% CI = 0.46-0.88) and males (aHR = 0.59, 95% CI = 0.44-0.79). CONCLUSIONS The positive association between cholecystectomy and the CRC risk within the first 6 months after cholecystectomy might be due to a detection bias or pre-existing CRC. However, cholecystectomy is associated with a decreased risk of rectal cancer, rather than proximal or distal colon cancer, after more than 6 months of follow-up.
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Affiliation(s)
- Chien-Hua Chen
- Digestive Disease Center, Changbing Show-Chwan Memorial Hospital, Lukang Township, Changhua County 500, Taiwan;
- Digestive Disease Center, Show-Chwan Memorial Hospital, Changhua 500, Taiwan
- Department of Food Science and Technology, Hungkuang University, Taichung 433, Taiwan
- Chung Chou University of Science and Technology, Yuanlin Township, Changhua County 500, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung 404, Taiwan;
- College of Medicine, China Medical University, Taichung 404, Taiwan
| | - Chia-Hung Kao
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan
- Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung 404, Taiwan
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung 404, Taiwan
- Center of Augmented Intelligence in Healthcare, China Medical University Hospital, Taichung 404, Taiwan
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taichung 40447, Taiwan
- Correspondence: or ; Tel.: +886-422-052-121 (ext. 7412); Fax: +886-422-336-174
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