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Rosales RS, Ruettermann M. How to conduct a meta-analysis in hand surgery. Part II: heterogeneity and publication bias. J Hand Surg Eur Vol 2025:17531934251317837. [PMID: 39939133 DOI: 10.1177/17531934251317837] [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] [Indexed: 02/14/2025]
Abstract
This is the second part of a two-part article on pitfalls in meta-analysis in hand surgery. The purpose of this second part is to introduce the concepts of heterogeneity and publication bias and to describe how these problems should be analysed and addressed when conducting meta-analyses in hand surgery. Statistical heterogeneity, which occurs when the variability in the observed effect cannot be explained by sampling variability alone, may be caused by clinical heterogeneity, methodological heterogeneity or both. A common error in hand surgery meta-analyses is the failure to adequately investigate the sources of heterogeneity. Heterogeneity is also associated with publication bias. Understanding heterogeneity in published meta-analyses would help in the understanding of the available evidence in Hand Surgery.
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Affiliation(s)
| | - Mike Ruettermann
- University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands
- HPC, Oldenburg Institute for Hand and Plastic Surgery, Poststrasse 1, 26122 Oldenburg, Germany
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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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Muñoz RA, Ramos AA, Miranda FJ, De La Rosa JE, Muñoz AE, Ramírez AA, Chavez EP, Gallardo G, Pizarro S. Cholecystectomy Is a Risk Factor for Proximal Colon Cancer That May Also Relate to its Aggressiveness. J Surg Res 2024; 304:152-161. [PMID: 39547064 DOI: 10.1016/j.jss.2024.10.018] [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: 04/26/2024] [Revised: 09/22/2024] [Accepted: 10/15/2024] [Indexed: 11/17/2024]
Abstract
INTRODUCTION There are studies with mixed conclusions about the role cholecystectomy plays as a risk factor for proximal colorectal cancer (CRC). METHODS We performed a multicenter retrospective cohort study where the records of patients with CRC were reviewed. Data was collected regarding affected colon subsegment (cecum, ascending, transverse, descending, sigmoid, or rectum, which were also combined into proximal or distal colon), history and time since cholecystectomy, histopathology reports (TNM classification and clinical stage), and KRAS, NRAS, and BRAF mutation analysis. Univariate and multivariate analysis adjusting for age, smoking history, body mass index, sex, and family history of cancer were performed. Logistical regression for statistical analysis was used to estimate the odds ratio for the association between cholecystectomy and tumor location. RESULTS Four hundred four cases were obtained, of which 52 previously had cholecystectomy. The date of surgery was recorded in 43 patients, with a 5 y median and an interquartile range of 1.5-14 y prior to CRC diagnosis. Both crude and adjusted odds ratio (2.86 and 2.42, respectively) confirmed an associated risk for developing proximal CRC after cholecystectomy. When proximal CRC cases with previous cholecystectomy were directly compared against proximal CRC without cholecystectomy and distal CRC cases, the former had a higher distribution of prevalence for T3, T4b, N1b, M1a, and M1c. KRAS mutation also presented its highest prevalence in this group with 33%. CONCLUSIONS Cholecystectomy was related to the development of proximal CRC in all its subsegments, seemingly associated with higher stages at diagnosis. Close surveillance should be considered in patients who undergo cholecystectomy.
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Affiliation(s)
- Raymundo A Muñoz
- Department of Research and Medical Education, Hospital Angeles Chihuahua, Chihuahua, Mexico; Faculty of Medicine and Biomedical Sciences, Autonomous University of Chihuahua (UACH), Chihuahua, Mexico.
| | - Andrei A Ramos
- Department of General Surgery, Christus Muguerza Hospital del Parque, Chihuahua, Mexico
| | - Francisco J Miranda
- Department of Oncologic Surgery, Christus Muguerza Hospital del Parque, Chihuahua, Mexico
| | - José E De La Rosa
- Medical Program Coordination Office, Faculty of Medicine and Biomedical Sciences, UACH, Chihuahua, Mexico
| | - Alfonzo E Muñoz
- College Of Science, University of Texas at El Paso (UTEP), El Paso, Texas
| | - Aáron A Ramírez
- Department of General Surgery, Christus Muguerza Hospital del Parque, Chihuahua, Mexico
| | - Eva P Chavez
- Plastic Surgery, Private Practice, El Paso, Texas
| | - Guillermo Gallardo
- Department of General Surgery & Endoscopy, Hospital Angeles Chihuahua, Chihuahua, Mexico
| | - Salvador Pizarro
- Department of Rheumatology, Hospital Angeles Chihuahua, Chihuahua, Mexico
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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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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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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: 0] [Impact Index Per Article: 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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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: 0] [Impact Index Per Article: 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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Chen L, Fan Z, Sun X, Qiu W, Mu W, Chai K, Cao Y, Wang G, Lv G. Associations of cholecystectomy with the risk of colorectal cancer: a Mendelian randomization study. Chin Med J (Engl) 2023; 136:840-847. [PMID: 37027252 PMCID: PMC10150870 DOI: 10.1097/cm9.0000000000002612] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Indexed: 04/08/2023] Open
Abstract
BACKGROUND Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown. METHODS We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. RESULTS The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy. CONCLUSIONS The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.
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Affiliation(s)
- Lanlan Chen
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin 130021, China
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Jiang X, Jiang Z, Cheng Q, Sun W, Jiang M, Sun Y. Cholecystectomy promotes the development of colorectal cancer by the alternation of bile acid metabolism and the gut microbiota. Front Med (Lausanne) 2022; 9:1000563. [PMID: 36213655 PMCID: PMC9540502 DOI: 10.3389/fmed.2022.1000563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 09/06/2022] [Indexed: 12/24/2022] Open
Abstract
The incidence and mortality of colorectal cancer (CRC) have been markedly increasing worldwide, causing a tremendous burden to the healthcare system. Therefore, it is crucial to investigate the risk factors and pathogenesis of CRC. Cholecystectomy is a gold standard procedure for treating symptomatic cholelithiasis and gallstone diseases. The rhythm of bile acids entering the intestine is altered after cholecystectomy, which leads to metabolic disorders. Nonetheless, emerging evidence suggests that cholecystectomy might be associated with the development of CRC. It has been reported that alterations in bile acid metabolism and gut microbiota are the two main reasons. However, the potential mechanisms still need to be elucidated. In this review, we mainly discussed how bile acid metabolism, gut microbiota, and the interaction between the two factors influence the development of CRC. Subsequently, we summarized the underlying mechanisms of the alterations in bile acid metabolism after cholecystectomy including cellular level, molecular level, and signaling pathways. The potential mechanisms of the alterations on gut microbiota contain an imbalance of bile acid metabolism, cellular immune abnormality, acid-base imbalance, activation of cancer-related pathways, and induction of toxin, inflammation, and oxidative stress.
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Affiliation(s)
- Xi Jiang
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Zhongxiu Jiang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Qi Cheng
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Wei Sun
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Min Jiang
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yan Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- *Correspondence: Yan Sun,
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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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Kharazmi E, Sundquist K, Sundquist J, Fallah M, Bermejo JL. Risk of Gynecological Cancers in Cholecystectomized Women: A Large Nationwide Cohort Study. Cancers (Basel) 2022; 14:cancers14061484. [PMID: 35326635 PMCID: PMC8946708 DOI: 10.3390/cancers14061484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 03/03/2022] [Accepted: 03/07/2022] [Indexed: 12/10/2022] Open
Abstract
Background: Gallstones affect women more frequently than men, and symptomatic gallstones are increasingly treated with surgical removal of the gallbladder (cholecystectomy). Breast, endometrial, and ovarian cancer share several risk factors with gallstones, including overweight, obesity, and exposure to female sex hormones. We intended to assess the association between cholecystectomy and female cancer risk, which has not been comprehensively investigated. Methods: We investigated the risk of female cancers after cholecystectomy leveraging the Swedish Cancer, Population, Patient, and Death registries. Standardized incidence ratios (SIRs) adjusted for age, calendar period, socioeconomic status, and residential area were used to compare cancer risk in cholecystectomized and non-cholecystectomized women. Results: During a median follow-up of 11 years, 325,106 cholecystectomized women developed 10,431 primary breast, 2888 endometrial, 1577 ovarian, and 705 cervical cancers. The risk of ovarian cancer was increased by 35% (95% confidence interval (CI) 2% to 77%) in the first 6 months after cholecystectomy. The exclusion of cancers diagnosed in the first 6 months still resulted in an increased risk of endometrial (19%, 95%CI 14% to 23%) and breast (5%, 95%CI 3% to 7%) cancer, especially in women cholecystectomized after age 50 years. By contrast, cholecystectomized women showed decreased risks of cervical (-13%, 95%CI -20% to -7%) and ovarian (-6%, 95%CI -10% to -1%) cancer. Conclusions: The risk of ovarian cancer increased by 35% in a just short period of time (6 months) following the surgery. Therefore, it is worth ruling out ovarian cancer before cholecystectomy. Women undergoing cholecystectomy showed an increased risk of breast and endometrial cancer up to 30 years after surgery. Further evaluation of the association between gallstones or gallbladder removal on female cancer risk would allow for the assessment of the need to intensify cancer screening in cholecystectomized women.
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Affiliation(s)
- Elham Kharazmi
- Institute of Medical Biometry, University of Heidelberg, 69120 Heidelberg, Germany;
- Risk Adapted Prevention Group, Division of Preventive Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;
- Center for Primary Health Care Research, Lund University, 202 13 Malmö, Sweden; (K.S.); (J.S.)
| | - Kristina Sundquist
- Center for Primary Health Care Research, Lund University, 202 13 Malmö, Sweden; (K.S.); (J.S.)
- Department of Family Medicine and Community Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Center for Community-Based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Izumo 693-8501, Japan
| | - Jan Sundquist
- Center for Primary Health Care Research, Lund University, 202 13 Malmö, Sweden; (K.S.); (J.S.)
- Department of Family Medicine and Community Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Center for Community-Based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Izumo 693-8501, Japan
| | - Mahdi Fallah
- Risk Adapted Prevention Group, Division of Preventive Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;
- Center for Primary Health Care Research, Lund University, 202 13 Malmö, Sweden; (K.S.); (J.S.)
- Institute of Primary Health Care (BIHAM), University of Bern, 3012 Bern, Switzerland
| | - Justo Lorenzo Bermejo
- Institute of Medical Biometry, University of Heidelberg, 69120 Heidelberg, Germany;
- Correspondence: ; Tel.: +49-6221-56-4195
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12
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Ma Y, Qu R, Zhang Y, Jiang C, Zhang Z, Fu W. Progress in the Study of Colorectal Cancer Caused by Altered Gut Microbiota After Cholecystectomy. Front Endocrinol (Lausanne) 2022; 13:815999. [PMID: 35282463 PMCID: PMC8907136 DOI: 10.3389/fendo.2022.815999] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 02/01/2022] [Indexed: 12/26/2022] Open
Abstract
Epidemiological studies have found an increased incidence of colorectal cancer (CRC) in people who undergo cholecystectomy compared to healthy individuals. After cholecystectomy, bile enters the duodenum directly, unregulated by the timing of meals. Disruption of the balance of bile acid metabolism and increased production of primary bile acids, which in turn affects the composition and abundance of intestinal microorganisms. The link among cholecystectomy, the gut microbiota, and the occurrence and development of CRC is becoming clearer. However, due to the complexity of the microbial community, the mechanistic connections are less well understood. In this review, we summarize the changes of gut microbiota after cholecystectomy and illuminate the potential mechanisms on CRC, such as inflammation and immune regulation, production of genotoxins, metabolism of dietary ingredients, activation of signaling pathways, and so on. By reviewing these, we aimed to unravel the interactions between the gut microbiota and its host and be better positioned to develop treatments for CRC after cholecystectomy.
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Affiliation(s)
- Yanpeng Ma
- Department of General Surgery, Peking University Third Hospital, Beijing, China
- Cancer Center, Peking University Third Hospital, Beijing, China
| | - Ruize Qu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
- Cancer Center, Peking University Third Hospital, Beijing, China
| | - Yi Zhang
- Department of General Surgery, Peking University Third Hospital, Beijing, China
- Cancer Center, Peking University Third Hospital, Beijing, China
| | - Changtao Jiang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China
- Key Laboratory of Molecular Cardiovascular Science (Peking University), Ministry of Education, Beijing, China
- Center of Basic Medical Research, Institute of Medical Innovation and Research, Third Hospital, Peking University, Beijing, China
- Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing, China
| | - Zhipeng Zhang
- Department of General Surgery, Peking University Third Hospital, Beijing, China
- Cancer Center, Peking University Third Hospital, Beijing, China
- *Correspondence: Zhipeng Zhang, ; Wei Fu,
| | - Wei Fu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
- Cancer Center, Peking University Third Hospital, Beijing, China
- *Correspondence: Zhipeng Zhang, ; Wei Fu,
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13
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Chin Y, Yang KS, Chang SH, Cheng-Chung Wei J, Yip HT, Hung YM, Chang R. Risk of non-typhoidal Salmonella infection in patients with cholecystectomy: Results from a nationwide matched cohort study in Taiwan. Int J Clin Pract 2021; 75:e14787. [PMID: 34534394 DOI: 10.1111/ijcp.14787] [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: 07/19/2020] [Revised: 04/02/2021] [Accepted: 09/02/2021] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND The current study was designed to investigate the association between cholecystectomy and the risk of non-typhoidal Salmonella (NTS) infection. METHODS We obtained claims-based data from the Taiwan National Health Insurance Research Database (NHIRD) to perform a nationwide cohort study. A propensity score (PS)-matching analysis was performed with a ratio of 1:2 in the cholecystectomy cohort and cholecystectomy-free group to reduce selection bias. Both groups were followed until NTS diagnosis, a dropout from the insurance programme or the end of 2013. Cox proportional hazard regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of NTS infection between the cholecystectomy and cholecystectomy-free groups. RESULTS Our study enrolled 197 444 patients who had undergone cholecystectomy and 394 888 patients who did not receive cholecystectomy. The adjusted HR (aHR) of NTS infection was 1.34 (95% CI, 1.13-1.58; P < .001) for the cholecystectomy group after adjusting for demographical characteristics and relevant comorbidities. The study population is predominantly female patients (55%) and older (58% older than 50 years). The subgroup analysis revealed that both sexes and notably, patients aged >50, who underwent cholecystectomy had a higher risk of NTS infection than the matched controls. Follow-up of patients who underwent cholecystectomy showed that they had a significantly higher risk of NTS infection for more than 6 months after the procedure. CONCLUSIONS Our study showed that cholecystectomy might be an independent risk factor for subsequent NTS infection.
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Affiliation(s)
- Yen Chin
- Department of Internal Medicine, Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan
- Division of Chest Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Kai-Shan Yang
- School of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shu-Han Chang
- Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - James Cheng-Chung Wei
- Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
| | - Hei-Tung Yip
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Yao-Min Hung
- Department of Internal Medicine, Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan
- Division of Chest Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- College of Health and Nursing, Meiho University, Pingtung, Taiwan
| | - Renin Chang
- Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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Ali H. Future incidence and mortality of colorectal carcinoma in the United States: an updated overview of risk factors and preventative measures. EXPLORATION OF MEDICINE 2021. [DOI: 10.37349/emed.2021.00063] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
According to the Global Cancer Observatory (GLOBOCAN) 2020, colorectal carcinoma (CRC) was the second leading cause of cancer death globally. Current literature utilizes reported databases such as Surveillance, Epidemiology, and End Results (SEER) to better understand the epidemiology of CRC. The global cancer observatory’s “Cancer Tomorrow” data visualization tools was used to predict the future incidence and mortality of colorectal cancers until 2030 as a guided tool to look over ways to reduce incidence by controlling risk factors of CRC. The total number of CRC is expected to rise by 2030, with a percent change of 17.3%. The expected percent change in colon cancer is more than rectal cancer (19.8% vs. 11.6%). The estimated number of deaths secondary to CRC is expected to increase in 2030, an estimated percent change of 22.2%. The incidence and mortality rate was higher in men vs. women; however, the gap seems to be closing on trend analysis. Major risk factors for CRC include familial syndromes, family history, race, gender, obesity, diet, alcohol, and smoking. Risk can be reduced by exercise and dietary changes, fiber intake, vitamin D, calcium, and minerals. Individualized screening based on age, gender, and additional risk factors could be an option that needs further comparative data to propose a definitive benefit over established screening guidelines.
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Affiliation(s)
- Hassam Ali
- Department of Internal Medicine, East Carolina University/Vidant Medical Center, Greenville, NC 27834, USA
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15
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Uchiyama K, Naito Y, Yagi N, Mizushima K, Higashimura Y, Hirai Y, Dohi O, Okayama T, Yoshida N, Katada K, Kamada K, Ishikawa T, Takagi T, Konishi H, Kuriu Y, Nakanishi M, Otsuji E, Honda A, Itoh Y. Identification of colorectal neoplasia by using serum bile acid profile. Biomarkers 2021; 26:462-467. [PMID: 33926316 DOI: 10.1080/1354750x.2021.1917663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 04/05/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Colonoscopy is the gold standard for detecting earlier stages of CRC, although screening of patients is difficult because of invasiveness, low compliance and procedural health risks. Therefore, the need for new screening methods for CRC is rising. Previous studies have demonstrated the diagnostic ability of serum BAs; however, the results have been inconsistent. In this study, we conducted a comprehensive analysis of serum BAs from patients with CRC and verified their diagnostic ability to detect CRC. METHODS A total of 56 CRC patients (n = 14 each of stages I-IV), 59 patients with colonic adenoma and 60 healthy controls were included. Age and sex were matched for each group. Serum BA compositions were measured by LC-MS/MS and serum concentration of 30 types of BAs were analysed by discriminant analysis with multidimensional scaling method. RESULTS Free CA, 3epi-DCA&CDCA, 3-dehydro CA, GCA and TCA were extracted as principal component (PC) 1 and free 3-dehydroDCA as PC 2 by canonical discriminant function coefficients. The verification of discriminability using cross-validation method revealed that the correct classification rate was 66.3% for original data and 52.6% for cross-validation data. CONCLUSIONS A combined analysis using comprehensive serum BA concentration can be an efficient method for screening CRC.
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Affiliation(s)
- Kazuhiko Uchiyama
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yuji Naito
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Endoscopy and Ultrasound Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Nobuaki Yagi
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Gastroenterology, Asahi University Hospital, Asahi University, Gifu, Japan
| | - Katsura Mizushima
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yasuki Higashimura
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yasuko Hirai
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Osamu Dohi
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tetsuya Okayama
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Naohisa Yoshida
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kazuhiro Katada
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kazuhiro Kamada
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeshi Ishikawa
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tomohisa Takagi
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department for Medical Innovation and Translational Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hideyuki Konishi
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshiaki Kuriu
- Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masayoshi Nakanishi
- Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Eigo Otsuji
- Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akira Honda
- Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan
| | - Yoshito Itoh
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Coelho LGV, Coelho MCF. Helicobacter pylori and colorectal neoplasms: a concise review. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:114-119. [PMID: 33909789 DOI: 10.1590/s0004-2803.202100000-19] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 09/17/2020] [Indexed: 12/16/2022]
Abstract
Helicobacter pylori is the main etiological agent of all malignant tumors caused by an infectious disease. It is a major, at times dominant, factor in the pathogenesis of a large spectrum of diseases such as acute and chronic gastritis, gastric and duodenal ulcers, gastric carcinoma, and lymphoma. Epidemiological and experimental studies suggest that H. pylori chronic infection may be related to different extragastric diseases, including colorectal neoplasms. This concise review aims to explore the association of H. pylori infection with colorectal cancer and adenoma, including the recent epidemiological findings, the diagnostic methods employed to detect H. pylori and virulent factors, and the potentially involved mechanisms. Furthermore, is attempted to establish the current data integration for causal inference using the Bradford-Hill causality criteria. The weak, although global, strength of the epidemiological positive association between H. pylori infection and colonic neoplasms associated to new mechanisms postulated to explain this interaction, including intestinal dysbiosis, should stimulate future studies. Prospective confirmatory studies to establish the role of H. pylori eradication in the process of carcinogenic transformation of the colonic epithelium may define its eventual role in the treatment and prevention of colonic neoplasms.
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Affiliation(s)
- Luiz Gonzaga Vaz Coelho
- Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil
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He YG, Gao MF, Li J, Peng XH, Tang YC, Huang XB, Li YM. Cystic duct dilation through endoscopic retrograde cholangiopancreatography for treatment of gallstones and choledocholithiasis: Six case reports and review of literature. World J Clin Cases 2021; 9:736-747. [PMID: 33553415 PMCID: PMC7829737 DOI: 10.12998/wjcc.v9.i3.736] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 11/11/2020] [Accepted: 11/29/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Choledocholithiasis removal via endoscopic retrograde cholangiopancreatography (ERCP) then followed by laparoscopic cholecystectomy (LC) has gradually become the principal method in the treatment of gallstones and choledocholithiasis. We use ERCP through the cystic duct to treat gallstones combined with choledocholithiasis, with the aim to preserve the normal function of the gallbladder while simultaneously decreasing risk of biliary tract injury. CASE SUMMARY A total of six cases of patients diagnosed with gallstones and choledocholithiasis were treated with ERCP. The efficacy was evaluated via operation success rate, calculus removal rate, postoperative hospital stay and average hospitalization costs; the safety was evaluated through perioperative complication probability, gallbladder function detection and gallstones recrudesce. The calculus removal rate reached 100%, and patients had mild adverse events, including 1 case of postoperative acute cholecystitis and another of increased blood urinary amylase; both were relieved after corresponding treatment, the remaining cases had no complications. The average hospital stay and hospitalization costs were 6.16 ± 1.47 d and 5194 ± 696 dollars. The 3-11 mo follow-up revealed that gallbladder contracted well, without recurrence of gallstones. CONCLUSION This is the first batch of case reports for the treatment of gallstones and choledocholithiasis through ERCP approached by natural cavity. The results and effects of six reported cases proved that the new strategy is safe and feasible and is worthy of further exploration and application.
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Affiliation(s)
- Yong-Gang He
- Department of Hepatobiliary, The Second Affiliated Hospital, Army Medical University, Chongqing 400037, China
| | - Ming-Fa Gao
- Department of Hepatobiliary, North-Kuanren General Hospital, Chongqing 401121, China
| | - Jing Li
- Department of Hepatobiliary, The Second Affiliated Hospital, Army Medical University, Chongqing 400037, China
| | - Xue-Hui Peng
- Department of Hepatobiliary, The Second Affiliated Hospital, Army Medical University, Chongqing 400037, China
| | - Yi-Chen Tang
- Department of Hepatobiliary, The Second Affiliated Hospital, Army Medical University, Chongqing 400037, China
| | - Xiao-Bing Huang
- Department of Hepatobiliary, The Second Affiliated Hospital, Army Medical University, Chongqing 400037, China
| | - Yu-Ming Li
- Department of Hepatobiliary, The Second Affiliated Hospital, Army Medical University, Chongqing 400037, China
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18
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Qin JM. Causes of misdiagnosis and missed diagnosis and therapeutic and preventive strategies for unexpected gallbladder carcinoma. Shijie Huaren Xiaohua Zazhi 2020; 28:1167-1176. [DOI: 10.11569/wcjd.v28.i23.1167] [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] [Indexed: 02/06/2023] Open
Abstract
Laparoscopic cholecystectomy (LC) has been widely used in the treatment of gallbladder diseases. Since the indications for operation are constantly expanding, the intraoperative or postoperative incidence of unexpected gallbladder carcinoma (UGC) is gradually increasing. The incidence of UGC in LC and open cholecystectomy is 2.09% and 0.91%, respectively. Because gallbladder carcinoma is often accompanied by gallstones or inflammation and lacks specific clinical manifestations, imaging features, and specific serum tumor markers, the preoperative diagnostic rate of gallbladder carcinoma is only 30%, and 30% of cases of gallbladder carcinoma are diagnosed intraoperatively or postoperatively. Pathological T stage, lymph node metastasis, and gallbladder rupture are independent risk factors for the prognosis of patients with UGC. Preoperative imaging combined with serological tumor markers, intraoperative careful exploration, and rapid pathological examination are important measures to reduce the misdiagnosis and missed diagnosis of UGC. For patients with benign gallbladder diseases with a high potential of canceration, performing cholecystectomy in time and strictly grasping the indications for preserving gallbladder for benign gallbladder diseases are important preventive measures to reduce the incidence of UGC.
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Affiliation(s)
- Jian-Min Qin
- Department of General Surgery, The Third Hospital Affiliated to Naval Military Medical University, Shanghai 201805, China
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19
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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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20
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Osadchuk MA, Svistunov AA, Mironova ED, Vasil'eva IN, Kireeva NV. [Diseases of biliary tract in the context of association with oncological diseases of the digestive system]. TERAPEVT ARKH 2019; 91:98-104. [PMID: 32598596 DOI: 10.26442/00403660.2019.12.000455] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 12/16/2022]
Abstract
Cancers of the gastrointestinal tract are widespread among the population and cause significant damage to the health care system. In order to improve the strategy of preventive measures and the detection of oncological diseases at the early stages, it is necessary to provide timely impact on possible risk factors contributing to the onset and progression of malignant neoplasms. This review demonstrates the association between the pathology of the biliary tract and oncological diseases of the digestive system, discusses the possible mechanisms of the influence of cholelithiasis and cholecystectomy on the development of malignant neoplasms of various parts of the gastrointestinal tract.
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Affiliation(s)
- M A Osadchuk
- Sechenov First Moscow State Medical University (Sechenov University)
| | - A A Svistunov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - E D Mironova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - I N Vasil'eva
- Sechenov First Moscow State Medical University (Sechenov University)
| | - N V Kireeva
- Sechenov First Moscow State Medical University (Sechenov University)
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21
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Kamarudin MNA, Sarker MMR, Zhou JR, Parhar I. Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects. J Exp Clin Cancer Res 2019; 38:491. [PMID: 31831021 PMCID: PMC6909457 DOI: 10.1186/s13046-019-1495-2] [Citation(s) in RCA: 117] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Accepted: 11/28/2019] [Indexed: 02/07/2023] Open
Abstract
Growing evidence showed the increased prevalence of cancer incidents, particularly colorectal cancer, among type 2 diabetic mellitus patients. Antidiabetic medications such as, insulin, sulfonylureas, dipeptyl peptidase (DPP) 4 inhibitors and glucose-dependent insulinotropic peptide (GLP-1) analogues increased the additional risk of different cancers to diabetic patients. Conversely, metformin has drawn attention among physicians and researchers since its use as antidiabetic drug exhibited beneficial effect in the prevention and treatment of cancer in diabetic patients as well as an independent anticancer drug. This review aims to provide the comprehensive information on the use of metformin at preclinical and clinical stages among colorectal cancer patients. We highlight the efficacy of metformin as an anti-proliferative, chemopreventive, apoptosis inducing agent, adjuvant, and radio-chemosensitizer in various colorectal cancer models. This multifarious effects of metformin is largely attributed to its capability in modulating upstream and downstream molecular targets involved in apoptosis, autophagy, cell cycle, oxidative stress, inflammation, metabolic homeostasis, and epigenetic regulation. Moreover, the review highlights metformin intake and colorectal cancer risk based on different clinical and epidemiologic results from different gender and specific population background among diabetic and non-diabetic patients. The improved understanding of metformin as a potential chemotherapeutic drug or as neo-adjuvant will provide better information for it to be used globally as an affordable, well-tolerated, and effective anticancer agent for colorectal cancer.
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Affiliation(s)
- Muhamad Noor Alfarizal Kamarudin
- Brain Research Institute Monash Sunway (BRIMS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Selangor Malaysia
| | - Md. Moklesur Rahman Sarker
- Department of Pharmacy, State University of Bangladesh, 77 Satmasjid Road, Dhanmondi, Dhaka, 1205 Bangladesh
- Health Med Science Research Limited, 3/1 Block F, Lalmatia, Mohammadpur, Dhaka, 1207 Bangladesh
| | - Jin-Rong Zhou
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 USA
| | - Ishwar Parhar
- Brain Research Institute Monash Sunway (BRIMS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Selangor Malaysia
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You DD, Cho SJ, Kim OH, Song JS, Hwang KS, Lee SC, Kim KH, Choi HJ, Hong HE, Seo H, Hong TH, Park JH, Lee TY, Ahn J, Jung JK, Jung KY, Kim SJ. Superior gallstone dissolubility and safety of tert-amyl ethyl ether over methyl-tertiary butyl ether. World J Gastroenterol 2019; 25:5936-5952. [PMID: 31660031 PMCID: PMC6815801 DOI: 10.3748/wjg.v25.i39.5936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 08/19/2019] [Accepted: 09/11/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The use of methyl-tertiary butyl ether (MTBE) to dissolve gallstones has been limited due to concerns over its toxicity and the widespread recognition of the safety of laparoscopic cholecystectomy. The adverse effects of MTBE are largely attributed to its low boiling point, resulting in a tendency to evaporate. Therefore, if there is a material with a higher boiling point and similar or higher dissolubility than MTBE, it is expected to be an attractive alternative to MTBE. AIM To determine whether tert-amyl ethyl ether (TAEE), an MTBE analogue with a relatively higher boiling point (102 °C), could be used as an alternative to MTBE in terms of gallstone dissolubility and toxicity. METHODS The in vitro dissolubility of MTBE and TAEE was determined by measuring the dry weights of human gallstones at predetermined time intervals after placing them in glass containers with either of the two solvents. The in vivo dissolubility was determined by comparing the weights of solvent-treated gallstones and control (dimethyl sulfoxide)-treated gallstones, after the direct infusion of each solvent into the gallbladder in both hamster models with cholesterol and pigmented gallstones. RESULTS The in vitro results demonstrated a 24 h TAEE-dissolubility of 76.7%, 56.5% and 38.75% for cholesterol, mixed, and pigmented gallstones, respectively, which represented a 1.2-, 1.4-, and 1.3-fold increase in dissolubility compared to that of MTBE. In the in vitro experiment, the 24 h-dissolubility of TAEE was 71.7% and 63.0% for cholesterol and pigmented gallstones, respectively, which represented a 1.4- and 1.9-fold increase in dissolubility compared to that of MTBE. In addition, the results of the cell viability assay and western blot analysis indicated that TAEE had a lower toxicity towards gallbladder epithelial cells than MTBE. CONCLUSION We demonstrated that TAEE has higher gallstone dissolubility properties and safety than those of MTBE. As such, TAEE could present an attractive alternative to MTBE if our findings regarding its efficacy and safety can be consistently reproduced in further subclinical and clinical studies.
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Affiliation(s)
- Dong Do You
- Department of Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul 16247, South Korea
| | - Suk Joon Cho
- College of Pharmacy, Chungbuk National University, Cheongju 28644, South Korea
| | - Ok-Hee Kim
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
- Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
| | - Jin Sook Song
- Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, South Korea
| | - Kyu-Seok Hwang
- Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, South Korea
| | - Sang Chul Lee
- Department of Surgery, Daejeon St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul 34943, South Korea
| | - Kee-Hwan Kim
- Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul 11765, South Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
| | - Ha-Eun Hong
- Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
- Department of Biomedicine and Health Science, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
| | - Haeyeon Seo
- Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
- Department of Biomedicine and Health Science, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
| | - Tae Ho Hong
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
| | - Jung Hyun Park
- Department of Surgery, Eunpyeong St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul 03312, South Korea
| | - Tae Yoon Lee
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
| | - Joseph Ahn
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
| | - Jae-Kyung Jung
- College of Pharmacy, Chungbuk National University, Cheongju 28644, South Korea
| | - Kwan-Young Jung
- Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, South Korea
- Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, Daejeon 34113, South Korea
| | - Say-June Kim
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
- Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, the Catholic University of Korea, Seoul 06591, South Korea
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Yang F, Xu YL, Zhu RF. Helicobacter pylori infection and the risk of colorectal carcinoma: a systematic review and meta-analysis. Minerva Med 2019; 110:464-470. [PMID: 31368293 DOI: 10.23736/s0026-4806.19.05942-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Helicobacter pylori is a gram-negative bacterium that is colonized in the stomach. H. pylori infection can lead to a series of stomach diseases. However, the relationship between H. pylori infection and colorectal cancer is currently controversial. Therefore, we performed this meta-analysis to further understand the relationship between H. pylori infection and colorectal cancer. EVIDENCE ACQUISITION We conducted a comprehensive retrieval from electronic databases, included the PubMed, Medline, China National Knowledge Infrastructure (CNKI), and China Wanfang Data Knowledge Service Platform databases (Wanfang Databases) through May 1st, 2018. We used the search terms H. pylori and colorectal cancer or colorectal carcinoma and collected all relevant studies to explore the association between H. pylori infection and colorectal cancer. EVIDENCE SYNTHESIS Twenty-seven studies including 14357 cases were included. H. pylori infection was associated with an increased risk of colorectal cancer. A pooled odds ratio (OR) of 1.27 with a 95% CI of 1.17-1.37 (P<0.001) was calculated by using a fixed-effects model (I2=45.5%, P=0.006). The subgroup analysis revealed that H. pylori infection was associated with an increased risk of colorectal cancer in the subgroups of Western countries (OR=1.34, 95% CI: 1.14-1.57) (P<0.001), serological testing (OR=1.20, 95% CI: 1.08-1.34) (P=0.001), multiple methods of testing (OR=2.63, 95% CI: 1.09-6.31) (P=0.031), cross-sectional studies (OR=1.92, 95% CI: 1.17-3.16) (P=0.010) and case-control studies (OR 1.26, 95% CI: 1.16-1.36) (P<0.001). CONCLUSIONS The present meta-analysis provides evidence suggests that a positive association between H. pylori infection and the risk of colorectal cancer.
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Affiliation(s)
- Fan Yang
- Department of Intensive Care, Sixth People's Hospital of Nantong, Nantong, China
| | - Ying-Lu Xu
- Department of General Surgery, Third People's Hospital of Nantong, Nantong, China
| | - Ren-Fei Zhu
- Department of General Surgery, Third People's Hospital of Nantong, Nantong, China -
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24
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Choi HJ, Cho SJ, Kim OH, Song JS, Hong HE, Lee SC, Kim KH, Lee SK, You YK, Hong TH, Kim EY, Park JH, Na GH, Do You D, Han JH, Park JW, Kwak BJ, Lee TY, Ahn J, Lee HH, Kang SK, Hwang KS, Jung JK, Jung KY, Kim SJ. Efficacy and safety of a novel topical agent for gallstone dissolution: 2-methoxy-6-methylpyridine. J Transl Med 2019; 17:195. [PMID: 31182117 PMCID: PMC6558798 DOI: 10.1186/s12967-019-1943-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 05/30/2019] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Although methyl-tertiary butyl ether (MTBE) is the only clinical topical agent for gallstone dissolution, its use is limited by its side effects mostly arising from a relatively low boiling point (55 °C). In this study, we developed the gallstone-dissolving compound containing an aromatic moiety, named 2-methoxy-6-methylpyridine (MMP) with higher boiling point (156 °C), and compared its effectiveness and toxicities with MTBE. METHODS The dissolubility of MTBE and MMP in vitro was determined by placing human gallstones in glass containers with either solvent and, then, measuring their dry weights. Their dissolubility in vivo was determined by comparing the weights of solvent-treated gallstones and control (dimethyl sulfoxide)-treated gallstones, after directly injecting each solvent into the gallbladder in hamster models with cholesterol and pigmented gallstones. RESULTS In the in vitro dissolution test, MMP demonstrated statistically higher dissolubility than did MTBE for cholesterol and pigmented gallstones (88.2% vs. 65.7%, 50.8% vs. 29.0%, respectively; P < 0.05). In the in vivo experiments, MMP exhibited 59.0% and 54.3% dissolubility for cholesterol and pigmented gallstones, respectively, which were significantly higher than those of MTBE (50.0% and 32.0%, respectively; P < 0.05). The immunohistochemical stains of gallbladder specimens obtained from the MMP-treated hamsters demonstrated that MMP did not significantly increase the expression of cleaved caspase 9 or significantly decrease the expression of proliferation cell nuclear antigen. CONCLUSIONS This study demonstrated that MMP has better potential than does MTBE in dissolving gallstones, especially pigmented gallstones, while resulting in lesser toxicities.
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Affiliation(s)
- Ho Joong Choi
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea
| | - Suk Joon Cho
- College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea
| | - Ok-Hee Kim
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea
- Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Sook Song
- Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, 141, Gajeong-ro, Yuseong-gu, Daejeon, 34114 Republic of Korea
| | - Ha-Eun Hong
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea
- Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sang Chul Lee
- Department of Surgery, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kee-Hwan Kim
- Department of Surgery, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sang Kuon Lee
- Department of Surgery, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Young Kyoung You
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea
| | - Tae Ho Hong
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea
| | - Eun Young Kim
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea
| | - Jung Hyun Park
- Department of Surgery, St. Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Gun Hyung Na
- Department of Surgery, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dong Do You
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jae Hyun Han
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jae Woo Park
- Department of Surgery, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Bong Jun Kwak
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea
| | - Tae Yun Lee
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea
| | - Joseph Ahn
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea
| | - Hwan Hee Lee
- Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, 141, Gajeong-ro, Yuseong-gu, Daejeon, 34114 Republic of Korea
| | - Seung Kyu Kang
- Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, 141, Gajeong-ro, Yuseong-gu, Daejeon, 34114 Republic of Korea
| | - Kyu-Seok Hwang
- Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, 141, Gajeong-ro, Yuseong-gu, Daejeon, 34114 Republic of Korea
| | - Jae-Kyung Jung
- College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea
| | - Kwan-Young Jung
- Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, 141, Gajeong-ro, Yuseong-gu, Daejeon, 34114 Republic of Korea
- Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, Daejeon, Republic of Korea
| | - Say-June Kim
- Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea
- Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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25
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Peng Z, Chen J, Drachenberg CB, Raufman JP, Xie G. Farnesoid X receptor represses matrix metalloproteinase 7 expression, revealing this regulatory axis as a promising therapeutic target in colon cancer. J Biol Chem 2019; 294:8529-8542. [PMID: 30967475 DOI: 10.1074/jbc.ra118.004361] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Revised: 04/03/2019] [Indexed: 12/13/2022] Open
Abstract
The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of bile acid-activated transcription factors and an important regulator of cell proliferation, apoptosis, and Wnt signaling. Down-regulated expression of FXR plays an important role in some malignancies such as colon cancer, and in rodent models of intestinal neoplasia, FXR knockout increases the size and number of colon tumors. These previous observations implicate FXR as a tumor suppressor, but the underlying molecular mechanisms are unclear. Employing complementary experimental approaches and using human colon cancer specimens, human and murine colon cancer cell lines, and FXR transgenic mice, here we identified an additional, potentially important role for FXR. We observed an inverse relationship between the expression of FXR and matrix metalloproteinase-7 (MMP7), a collagenase and signaling molecule consistently associated with colon cancer progression. We noted that FXR gene ablation increases MMP7 expression. Consistent with this finding, FXR overexpression and a dominant-negative FXR mutation reduced and augmented, respectively, MMP7 expression. Of note, MMP7 was the only MMP gene family member whose expression was down-regulated after FXR activation. FXR-mediated regulation of MMP7 transcription did not require heterodimerization with the retinoid X receptor (RXR), indicating that FXR represses MMP7 expression independently of RXR. Last, we uncovered that FXR suppresses MMP7 transcription by binding to a negative FXR-responsive element in the 5' MMP7 promoter, an event that inhibited colon cancer cell proliferation and invasion. These findings identify the FXR-MMP7 axis as a potential therapeutic target for managing colon cancer.
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Affiliation(s)
- Zhongsheng Peng
- Veterans Affairs Maryland Healthcare System, Department of Medicine, Division of Gastroenterology and Hepatology, and Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201
| | - Jiayan Chen
- Veterans Affairs Maryland Healthcare System, Department of Medicine, Division of Gastroenterology and Hepatology, and Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201
| | - Cinthia B Drachenberg
- Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201
| | - Jean-Pierre Raufman
- Veterans Affairs Maryland Healthcare System, Department of Medicine, Division of Gastroenterology and Hepatology, and Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201
| | - Guofeng Xie
- Veterans Affairs Maryland Healthcare System, Department of Medicine, Division of Gastroenterology and Hepatology, and Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201.
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26
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Wang S, Dong W, Liu L, Xu M, Wang Y, Liu T, Zhang Y, Wang B, Cao H. Interplay between bile acids and the gut microbiota promotes intestinal carcinogenesis. Mol Carcinog 2019; 58:1155-1167. [PMID: 30828892 PMCID: PMC6593857 DOI: 10.1002/mc.22999] [Citation(s) in RCA: 94] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 02/13/2019] [Accepted: 02/18/2019] [Indexed: 12/21/2022]
Abstract
The gut microbiota and the bile acid pool play pivotal roles in maintaining intestinal homeostasis. Bile acids are produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. Gut dysbiosis has been reported to be associated with colorectal cancer. However, the interplay between bile acid metabolism and the gut microbiota during intestinal carcinogenesis remains unclear. In the present study, we investigated the potential roles of bile acids and the gut microbiota in the cholic acid (CA; a primary bile acid)‐induced intestinal adenoma‐adenocarcinoma sequence. Apcmin/+ mice, which spontaneously develop intestinal adenomas, were fed a diet supplemented with 0.4% CA for 12 weeks. Mice that were fed a normal diet were regarded as untreated controls. In CA‐treated Apcmin/+ mice, the composition of the gut microbiota was significantly altered, and CA was efficiently transformed into deoxycholic acid (a secondary bile acid) by the bacterial 7α‐dehydroxylation reaction. The intestinal adenoma‐adenocarcinoma sequence was observed in CA‐treated Apcmin/+ mice and was accompanied by an impaired intestinal barrier function and IL‐6/STAT3‐related low‐grade inflammation. More importantly, microbiota depletion using an antibiotic cocktail globally compromised CA‐induced intestinal carcinogenesis, suggesting a leading role for the microbiota during this process. Overall, our data suggested that the crosstalk between bile acids and the gut microbiota mediated intestinal carcinogenesis, which might provide novel therapeutic strategies against intestinal tumor development.
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Affiliation(s)
- Sinan Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Wenxiao Dong
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Li Liu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Mengque Xu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China.,Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yu Wang
- Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, National Clinical Research Center of Cancer, Tianjin, China
| | - Tianyu Liu
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Yujie Zhang
- Department of Pathology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China
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27
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Lee J, Choe S, Park JW, Jeong SY, Shin A. The Risk of Colorectal Cancer After Cholecystectomy or Appendectomy: A Population-based Cohort Study in Korea. J Prev Med Public Health 2018; 51:281-288. [PMID: 30514058 PMCID: PMC6283741 DOI: 10.3961/jpmph.18.105] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Accepted: 10/09/2018] [Indexed: 12/15/2022] Open
Abstract
Objectives We investigated the association between cholecystectomy or appendectomy and the subsequent risk of colorectal cancer (CRC) in the Korean population. Methods A retrospective cohort study was conducted with the National Health Insurance Service–National Sample Cohort of Korea; this sample was followed up from January 1, 2002, until the date of CRC incidence, loss to follow-up, or December 31, 2015. The exposure status of cholecystectomy and appendectomy was treated as a time-varying covariate. The calculated risk of CRC was stratified by follow-up period, and the association between these surgical procedures and CRC was investigated by a Cox regression model applying appropriate lag periods. Results A total of 707 663 individuals were identified for analysis. The study population was followed up for an average of 13.66 years, and 4324 CRC cases were identified. The hazard ratio (HR) of CRC was elevated in the first year after cholecystectomy (HR, 1.71; 95% confidence interval [CI], 1.01 to 2.89) and in the first year and 2-3 years after appendectomy (HR, 4.22; 95% CI, 2.87 to 6.20; HR, 2.34; 95% CI, 1.36 to 4.03, respectively). The HRs of CRC after applying 1 year of lag after cholecystectomy and 3 years of lag after appendectomy were 0.80 (95% CI, 0.57 to 1.13) and 0.77 (95% CI, 0.51 to 1.16), respectively. Conclusions The risk of CRC increased in the first year after cholecystectomy and appendectomy, implying the possibility of bias. When appropriate lag periods after surgery were applied, no association was found between cholecystectomy or appendectomy and CRC.
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Affiliation(s)
- Joonki Lee
- 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
| | - Ji Won Park
- Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.,Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Seung-Yong Jeong
- Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.,Cancer Research Institute, Seoul National University, 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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28
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Delgado-Rodríguez M, Sillero-Arenas M. Systematic review and meta-analysis. Med Intensiva 2018; 42:444-453. [PMID: 29169792 DOI: 10.1016/j.medin.2017.10.003] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 10/09/2017] [Accepted: 10/13/2017] [Indexed: 01/08/2023]
Abstract
In this review the usual methods applied in systematic reviews and meta-analyses are outlined. The ideal hypothesis for a systematic review should be generated by information not used later in meta-analyses. The selection of studies involves searching in web repertories, and more than one should be consulted. A manual search in the references of articles, editorials, reviews, etc. is mandatory. The selection of studies should be made by two investigators on an independent basis. Data collection on quality of the selected reports is needed, applying validated scales and including specific questions on the main biases which could have a negative impact upon the research question. Such collection also should be carried out by two researchers on an independent basis. The most common procedures for combining studies with binary outcomes are described (inverse of variance, Mantel-Haenszel, and Peto), illustrating how they can be done using Stata commands. Assessment of heterogeneity and publication bias is also illustrated with the same program.
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Affiliation(s)
- M Delgado-Rodríguez
- Catedrático de Medicina Preventiva y Salud Pública, Universidad de Jaén, Jaén, Spain; Director Científico, CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
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29
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Halldorsson MO, Hauptmann M, Snaebjornsson P, Haraldsdóttir KH, Aspelund T, Gudmundsson EF, Gudnason V, Jonasson JG, Haraldsdottir S. The risk of developing a mismatch repair deficient colorectal cancer after undergoing cholecystectomy. Scand J Gastroenterol 2018; 53:972-975. [PMID: 30010450 DOI: 10.1080/00365521.2018.1481997] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Mismatch repair deficient (dMMR) colorectal cancer (CRC) is caused by inactivation of the MMR DNA repair system, most commonly via epigenetic inactivation of the MLH1 gene, and these tumors occur most frequently in the right colon. The objective was to determine whether cholecystectomy (CCY) increases the risk of a dMMR CRC by comparing CCY incidence in patients with dMMR CRC and proficient MMR (pMMR) CRC to unaffected controls. MATERIALS AND METHODS All patients diagnosed with CRC in Iceland from 2000 to 2009 (n = 1171) were included. They had previously been screened for dMMR by immunohistochemistry (n = 129 were dMMR). Unaffected age- and sex-matched controls (n = 17,460) were obtained from large Icelandic cohort studies. Subjects were cross-referenced with all pathology databases in Iceland to establish who had undergone CCY. Odds ratios were calculated using unconditional logistic regression. RESULTS Eighteen (13.7%) dMMR CRC cases and 90 (8.7%) pMMR CRC cases had undergone CCY compared to 1532 (8.8%) controls. CCY-related odds ratios (OR) were 1.06 (95% CI 0.90-1.26, p = .577) for all CRC, 1.16 (95% CI 0.66-2.05 p = .602) for dMMR CRCand 1.04 (95% CI 0.83-1.29, p = .744) for pMMR CRC. Furthermore, OR for dMMR CRC was 0.51 (95% CI 0.16-1.67, p = .266), 2.04 (95% CI 0.92-4.50, p = .080) and 1.08 (95% CI 0.40-2.89, p = .875) <10 years, 10-20 years and >20 years after a CCY, respectively. CONCLUSIONS There was no evidence of increased risk of developing dMMR CRC after CCY although a borderline significantly increased 2-fold risk was observed 10-20 years after CCY. Larger studies are warranted to examine this further.
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Affiliation(s)
| | - Michael Hauptmann
- b Department of Epidemiology and Biostatistics , The Netherlands Cancer Institute , Amsterdam , The Netherlands
| | - Petur Snaebjornsson
- c Department of Pathology , The Netherlands Cancer Institute , Amsterdam , The Netherlands
| | | | - Thor Aspelund
- e University of Iceland , Reykjavík , Iceland.,f Icelandic Heart Association , Kópavogur , Iceland
| | | | - Vilmundur Gudnason
- a Faculty of Medicine , University of Iceland , Reykjavík , Iceland.,f Icelandic Heart Association , Kópavogur , Iceland
| | - Jon Gunnlaugur Jonasson
- a Faculty of Medicine , University of Iceland , Reykjavík , Iceland.,d Landspitali University Hospital Iceland , Reykjavík , Iceland.,g Department of Pathology , Landspitali-University Hospital , Iceland
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30
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Di Ciaula A, Wang DQH, Molina-Molina E, Lunardi Baccetto R, Calamita G, Palmieri VO, Portincasa P. Bile Acids and Cancer: Direct and Environmental-Dependent Effects. Ann Hepatol 2017; 16:s87-s105. [PMID: 29080344 DOI: 10.5604/01.3001.0010.5501] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Accepted: 09/06/2017] [Indexed: 02/05/2023]
Abstract
Bile acids (BAs) regulate the absorption of fat-soluble vitamins, cholesterol and lipids but have also a key role as singalling molecules and in the modulation of epithelial cell proliferation, gene expression and metabolism. These homeostatic pathways, when disrupted, are able to promote local inflammation, systemic metabolic disorders and, ultimately, cancer. The effect of hydrophobic BAs, in particular, can be linked with cancer in several digestive (mainly oesophagus, stomach, liver, pancreas, biliary tract, colon) and extra-digestive organs (i.e. prostate, breast) through a complex series of mechanisms including direct oxidative stress with DNA damage, apoptosis, epigenetic factors regulating gene expression, reduced/increased expression of nuclear receptors (mainly farnesoid X receptor, FXR) and altered composition of gut microbiota, also acting as a common interface between environmental factors (including diet, lifestyle, exposure to toxics) and the molecular events promoting cancerogenesis. Primary prevention strategies (i.e. changes in dietary habits and lifestyle, reduced exposure to environmental toxics) mainly able to modulate gut microbiota and the epigenome, and the therapeutic use of hydrophilic BAs to counterbalance the negative effects of the more hydrophobic BAs might be, in the near future, part of useful tools for cancer prevention and management.
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Affiliation(s)
| | - David Q-H Wang
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Emilio Molina-Molina
- Clinica Medica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, Bari, Italy
| | - Raquel Lunardi Baccetto
- Clinica Medica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, Bari, Italy
| | - Giuseppe Calamita
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari. Italy
| | - Vincenzo O Palmieri
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari. Italy
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, Bari, Italy
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Zhang Y, Liu H, Li L, Ai M, Gong Z, He Y, Dong Y, Xu S, Wang J, Jin B, Liu J, Teng Z. Cholecystectomy can increase the risk of colorectal cancer: A meta-analysis of 10 cohort studies. PLoS One 2017; 12:e0181852. [PMID: 28771518 PMCID: PMC5542607 DOI: 10.1371/journal.pone.0181852] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 07/07/2017] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE This study aimed to elucidate the effects of cholecystectomy on the risk of colorectal cancer (CRC) by conducting a meta-analysis of 10 cohort studies. METHODS The eligible cohort studies were selected by searching the PubMed and EMBASE databases from their origination to June 30, 2016, as well as by consulting the reference lists of the selected articles. Two authors individually collected the data from the 10 papers. When the data showed marked heterogeneity, we used a random-effects model to estimate the overall pooled risk; otherwise, a fixed effects model was employed. RESULTS The final analysis included ten cohort studies. According to the Newcastle-Ottawa Scale (NOS), nine papers were considered high quality. After the data of these 9 studies were combined, an increased risk of CRC was found among the individuals who had undergone cholecystectomy (risk ratio (RR) 1.22; 95% confidence interval (CI) 1.08-1.38). In addition, we also found a promising increased risk for colon cancer (CC) (RR 1.30, 95% CI 1.07-1.58), but no relationship between cholecystectomy and rectum cancer (RC) (RR 1.09; 95% CI 0.89-1.34) was observed. Additionally, in the sub-group analysis of the tumor location in the colon, a positive risk for ascending colon cancer (ACC) was found (RR 1.18, 95% CI 1.11-1.26). After combining the ACC, transverse colon cancer (TCC), sigmoid colon cancer (SCC) and descending colon cancer (DCC) patients, we found a positive relationship with cholecystectomy (RR 1.18, 95% CI 1.11-1.26). Furthermore, after combining the ACC and DCC patients, we also found a positive relationship with cholecystectomy (RR 1.28; 95% CI 1.11-1.26) in the sub-group analysis. In an additional sub-group analysis of patients from Western countries, there was a positive relationship between cholecystectomy and the risk of CRC (RR 1.20; 95% CI 1.05-1.36). Furthermore, a positive relationship between female gender and CRC was also found (RR 1.17; 95% CI 1.03-1.34). However, there was no relationship between gender and CC or RC. Furthermore, no publication bias was observed, and the sensitivity analysis indicated stable results. CONCLUSIONS This meta-analysis of 10 cohort studies revealed that cholecystectomy is associated with an increased risk for CRC, CC and ACC, particularly in Western countries. No relationship between cholecystectomy and RC was observed. There was no relationship between gender and either CC or RC, but a positive relationship between female gender and CRC was observed.
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Affiliation(s)
- Yong Zhang
- Department of General Surgery, The 6th Affiliated Hospital of Kunming Medical University, The People’s Hospital of Yuxi City, Yuxi, Yunnan, China
| | - Hao Liu
- Department of General Surgery, The 6th Affiliated Hospital of Kunming Medical University, The People’s Hospital of Yuxi City, Yuxi, Yunnan, China
| | - Li Li
- Department of General Surgery, The 6th Affiliated Hospital of Kunming Medical University, The People’s Hospital of Yuxi City, Yuxi, Yunnan, China
| | - Min Ai
- School of Public Health, Dali University, Dali, Yunnan, China
| | - Zheng Gong
- Department of General Surgery, The 6th Affiliated Hospital of Kunming Medical University, The People’s Hospital of Yuxi City, Yuxi, Yunnan, China
| | - Yong He
- Department of General Surgery, The 6th Affiliated Hospital of Kunming Medical University, The People’s Hospital of Yuxi City, Yuxi, Yunnan, China
| | - Yunlong Dong
- Department of General Surgery, The 6th Affiliated Hospital of Kunming Medical University, The People’s Hospital of Yuxi City, Yuxi, Yunnan, China
| | - Shuanglan Xu
- Department of Respiratory Medicine, The Affiliated Yanan Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Jun Wang
- Department of General Surgery, The 6th Affiliated Hospital of Kunming Medical University, The People’s Hospital of Yuxi City, Yuxi, Yunnan, China
| | - Bo Jin
- Department of General Surgery, The 6th Affiliated Hospital of Kunming Medical University, The People’s Hospital of Yuxi City, Yuxi, Yunnan, China
| | - Jianping Liu
- Department of Science and Education, The 6th Affiliated Hospital of Kunming Medical University, The People’s Hospital of Yuxi City, Yuxi, Yunnan, China
| | - Zhaowei Teng
- Department of Orthopedic Surgery, The 6th Affiliated Hospital of Kunming Medical University, The People’s Hospital of Yuxi City, Yuxi, Yunnan, China
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Bile acids and colon cancer: Is FXR the solution of the conundrum? Mol Aspects Med 2017; 56:66-74. [DOI: 10.1016/j.mam.2017.04.002] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Revised: 03/20/2017] [Accepted: 04/07/2017] [Indexed: 02/07/2023]
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Lee JY, Park HW, Choi JY, Lee JS, Koo JE, Chung EJ, Chang HS, Choe J, Yang DH, Myung SJ, Jung HY, Yang SK, Byeon JS. Helicobacter pylori Infection with Atrophic Gastritis Is an Independent Risk Factor for Advanced Colonic Neoplasm. Gut Liver 2017; 10:902-909. [PMID: 27458180 PMCID: PMC5087929 DOI: 10.5009/gnl15340] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Revised: 11/05/2015] [Accepted: 02/02/2016] [Indexed: 12/14/2022] Open
Abstract
Background/Aims Helicobacter pylori is a major risk factor for atrophic gastritis (AG) and gastric cancer. The correlation between H. pylori, AG and colorectal neoplasm (CRN) has only been examined in a limited number of studies, and findings have been inconclusive. We aimed to investigate the association between H. pylori infection status, AG and advanced CRN. Methods This cross-sectional study investigated the relationship between the presence of serum anti-H. pylori IgG antibodies, AG, and advanced CRN in 6,351 consecutive asymptomatic subjects who underwent a screening colonoscopy. Results A total of 316 participants (5.0%) had advanced CRN. H. pylori seropositivity was 61.3%. In a univariate analysis, the presence of H. pylori infection was associated with advanced CRN (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17 to 1.91; p=0.001). H. pylori infection was associated with an increased risk of advanced CRN after adjusting for clinically relevant confounders (OR, 1.34; 95% CI, 1.04 to 1.72; p=0.023). H. pylori-related AG was significantly associated with the risk of advanced CRN (OR, 1.40; 95% CI, 1.03 to 1.91; p=0.030), whereas H. pylori infection without AG was not. Conclusions H. pylori infection increased the risk of advanced CRN, especially when it was combined with AG. Strict colonoscopy screening and surveillance may be warranted in those with H. pylori-positive AG.
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Affiliation(s)
- Ji Young Lee
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hye Won Park
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Young Choi
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jong-Soo Lee
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ja Eun Koo
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Ju Chung
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hye-Sook Chang
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jaewon Choe
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Jae Myung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong-Sik Byeon
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Xiong J, Wang Y, Huang H, Bian J, Wang A, Long J, Zheng Y, Sang X, Xu Y, Lu X, Zhao H. Systematic review and meta-analysis: cholecystectomy and the risk of cholangiocarcinoma. Oncotarget 2017; 8:59648-59657. [PMID: 28938668 PMCID: PMC5601764 DOI: 10.18632/oncotarget.19570] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2017] [Accepted: 07/19/2017] [Indexed: 12/15/2022] Open
Abstract
Studies have reported that cholecystectomy may increase the risk of cholangiocarcinoma. However, this association is controversial. Thus, we conducted a systematic review and meta-analysis to explore the relationship between cholecystectomy and the risk of cholangiocarcinoma. Relevant studies were identified by searching PubMed, EMBASE, ISI Web of Science published before February 2017. We used the random effects model proposed by DerSimonian and Laird to quantify the relationship between cholecystectomy and risk of cholangiocarcinoma. Publication bias was evaluated using funnel plots, Begg's and Egger's tests. Subgroup and sensitivity analyses were performed to validate the stability of the results. 16 articles, comprising 220,376 patients with cholecystectomy and 562,392 healthy controls, were included in our research. Our meta-analysis suggested that the risk of cholangiocarcinoma was significantly higher in the cholecystectomized patients in comparison with healthy controls, with heterogeneity among studies (summary odds ratio [OR] = 0.72; confidence interval [CI] = 0.55-0.90; I2 = 69.5%). Additionally, this association was also observed in cohort studies (OR = 0.83; 95% CI = 0.73-0.94) and case-control studies (OR = 0.60; 95% CI = 0.40-0.80). However, When the intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma were analyzed separately, the present study only indicated cholecystectomy was associated with increased the risk of extrahepatic cholangiocarcinoma (OR = 1.19; 95% CI = 0.32-2.05), rather than intrahepatic cholangiocarcinoma (OR = 1.19; 95% CI = 0.32-2.05). In conclusion, cholecystectomy was associated with a significant 54% increase in the risk of cholangiocarcinoma, especially in the extrahepatic cholangiocarcinoma.
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Affiliation(s)
- Jianping Xiong
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Yaqin Wang
- Department of Interventional Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Hanchun Huang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Jin Bian
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Anqiang Wang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Junyu Long
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Ying Zheng
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macau SAR, China
| | - Xinting Sang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Yiyao Xu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Xin Lu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
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Ryu S, Chang Y, Yun KE, Jung HS, Shin JH, Shin H. Gallstones and the Risk of Gallbladder Cancer Mortality: A Cohort Study. Am J Gastroenterol 2016; 111:1476-1487. [PMID: 27575712 DOI: 10.1038/ajg.2016.345] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Accepted: 07/02/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Despite epidemiologic data, definitive evidence for the role of gallstones as a cause for gallbladder cancer is lacking. The goal of this study was to evaluate the association between gallstones, determined by ultrasound, and the risk of gallbladder cancer mortality in a large study of Korean men and women. In addition, the association between gallstones and cholecystectomy, and risk of hepatobiliary cancer mortality was investigated. METHODS A cohort study was performed for 396,720 South Korean men and women who underwent a health checkup from 2002 to 2012. Hazard ratios for mortality outcomes were estimated using Cox-proportional hazards regression analysis. Vital status and cause of death assignment were based on linkage to the National Death Index of death certificate records. RESULTS From a total of 2,158,906.2 person-years of follow-up (median follow-up of 5.4 years), we identified 224 deaths from hepatobiliary cancer, comprising 174 cases of liver/intrahepatic bile ducts cancer, 20 cases of gallbladder cancer, and 30 cases of biliary tract cancer. Gallstones were significantly associated with increased risk of hepatobiliary cancer mortality, especially liver/intrahepatic biliary cancer, and gallbladder cancer mortality. The multivariable-adjusted hazard ratios (95% confidence intervals) for hepatobiliary cancer, liver/intrahepatic biliary cancer, and gallbladder cancer mortality comparing subjects having gallstones with those without gallstone disease were 2.74 (1.83-4.10), 2.34 (1.45-3.77), and 7.35 (2.60-20.8), respectively. Cholecystectomy was not significantly associated with hepatobiliary cancer mortality. CONCLUSIONS In this large cohort study, gallstones were associated with increased risk of hepatobiliary cancer mortality, especially liver/intrahepatic cancer, and gallbladder cancer mortality independent of potential confounders. Future studies with longer follow-up periods that include data on incident cancer cases should provide a more comprehensive view of the role of gallstones in cancer development.
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Affiliation(s)
- Seungho Ryu
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
| | - Yoosoo Chang
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
| | - Kyung Eun Yun
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hyun-Suk Jung
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jun Ho Shin
- Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hocheol Shin
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Housset C, Chrétien Y, Debray D, Chignard N. Functions of the Gallbladder. Compr Physiol 2016; 6:1549-77. [PMID: 27347902 DOI: 10.1002/cphy.c150050] [Citation(s) in RCA: 114] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The gallbladder stores and concentrates bile between meals. Gallbladder motor function is regulated by bile acids via the membrane bile acid receptor, TGR5, and by neurohormonal signals linked to digestion, for example, cholecystokinin and FGF15/19 intestinal hormones, which trigger gallbladder emptying and refilling, respectively. The cycle of gallbladder filling and emptying controls the flow of bile into the intestine and thereby the enterohepatic circulation of bile acids. The gallbladder also largely contributes to the regulation of bile composition by unique absorptive and secretory capacities. The gallbladder epithelium secretes bicarbonate and mucins, which both provide cytoprotection against bile acids. The reversal of fluid transport from absorption to secretion occurs together with bicarbonate secretion after feeding, predominantly in response to an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent pathway triggered by neurohormonal factors, such as vasoactive intestinal peptide. Mucin secretion in the gallbladder is stimulated predominantly by calcium-dependent pathways that are activated by ATP present in bile, and bile acids. The gallbladder epithelium has the capacity to absorb cholesterol and provides a cholecystohepatic shunt pathway for bile acids. Changes in gallbladder motor function not only can contribute to gallstone disease, but also subserve protective functions in multiple pathological settings through the sequestration of bile acids and changes in the bile acid composition. Cholecystectomy increases the enterohepatic recirculation rates of bile acids leading to metabolic effects and an increased risk of nonalcoholic fatty liver disease, cirrhosis, and small-intestine carcinoid, independently of cholelithiasis. Among subjects with gallstones, cholecystectomy remains a priority in those at risk of gallbladder cancer, while others could benefit from gallbladder-preserving strategies. © 2016 American Physiological Society. Compr Physiol 6:1549-1577, 2016.
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Affiliation(s)
- Chantal Housset
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.,Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Centre de Référence Maladies Rares (CMR) des Maladies Inflammatoires des Voies Biliaires (MIVB), Service d'Hépatologie, Paris, France
| | - Yues Chrétien
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.,Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Centre de Référence Maladies Rares (CMR) des Maladies Inflammatoires des Voies Biliaires (MIVB), Service d'Hépatologie, Paris, France
| | - Dominique Debray
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.,Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants Malades, Medical-Surgical Center, Hepatology and Transplantation, Paris, France
| | - Nicolas Chignard
- Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
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Velidedeoğlu M, Çitgez B, Arıkan AE, Ayan F. Is it necessary to perform prophylactic cholecystectomy for all symptomatic gallbladder polyps diagnosed with ultrasound? Turk J Surg 2016; 33:25-28. [PMID: 28740946 DOI: 10.5152/ucd.2015.3259] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2015] [Accepted: 10/04/2015] [Indexed: 11/22/2022]
Abstract
OBJECTIVE The main aim of this study is to determine the necessity of cholecystectomy in patients with ultrasound diagnosed symptomatic polypoid lesions of the gallbladder. MATERIAL AND METHODS The data of 82 patients with polypoid lesions of the gallbladder who had cholecystectomy between 2000 and 2012 were analyzed retrospectively with preoperative ultrasound and histopathology results. RESULTS The mean age was 48.05±11.18 years (range 25-74 years). All patients underwent preoperative ultrasound examination. Eighteen (22%) of the 82 patients were asymptomatic; their polypoid lesions of the gallbladder were detected with ultrasound during a check-up or other reasons. In 45 (55%) of cases pathology reported no polypoid lesions of the gallbladder. Right upper quadrant or epigastric pain was the most common symptom (41.46%) that led to hepatobiliary ultrasound, the other symptom was dyspepsia (36.59%). On preoperative ultrasound evaluation, 22 patients had multiple polyps, and 9 of these 22 patients had at least 3 polyps. CONCLUSION There is an inaccuracy of ultrasound to detect polypoid lesions of the gallbladder. After diagnosing polypoid lesions of the gallbladder by using standard ultrasound, further pre-operative diagnostic tests are needed to help discriminating benign lesions from malignant ones, which may prevent unnecessary surgery regardless of symptoms.
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Affiliation(s)
- Mehmet Velidedeoğlu
- Department of General Surgery, İstanbul University Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Bülent Çitgez
- Clinic of General Surgery, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul, Turkey
| | - Akif Enes Arıkan
- Department of General Surgery, İstanbul University Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Fadıl Ayan
- Department of General Surgery, İstanbul University Cerrahpaşa School of Medicine, İstanbul, Turkey
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Hong SN, Lee TY, Yun SC. The Risk of Colorectal Neoplasia in Patients with Gallbladder Diseases. J Korean Med Sci 2015; 30:1288-94. [PMID: 26339169 PMCID: PMC4553676 DOI: 10.3346/jkms.2015.30.9.1288] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2015] [Accepted: 06/03/2015] [Indexed: 01/06/2023] Open
Abstract
Cholecystectomy is associated with an increased risk of colorectal cancer, but little is known about the relationship between gallbladder disease and colorectal adenoma. Gallbladder polyps and colorectal neoplasia (CRN) share several risk factors such as obesity, diabetes and metabolic syndrome, which might account for their association. In this study, we investigated whether asymptomatic patients with gallbladder disease are at increased risk of CRN and identified the factors to their association. The study population consisted of 4,626 consecutive, asymptomatic individuals drawn from a prospective health check-up cohort who underwent both ultrasonography and colonoscopy screening. The prevalence of CRNs in patients with gallbladder polyps or gallstones was significantly higher than that in the control group (32.1% vs. 26.8%; P = 0.032, 35.8% vs. 26.9%; P = 0.020). A multivariate regression analysis showed that gallbladder polyps were an independent risk factor for CRN [adjusted odds ratio (OR): 1.29; 95% confidence interval (CI); 1.03-1.62] whereas gallstones were not (adjusted OR: 1.14; 95% CI: 0.79-1.63). The adjusted OR for the risk of CRN was 1.12 for gallbladder polyps < 5 mm (95% CI, 0.85-1.46) and 1.79 for gallbladder polyps ≥ 5 mm (95% CI, 1.15-2.77). The prevalence of CRN increased with increasing polyp size (P trend = 0.022). Our results suggest that colorectal neoplasia is significantly related to gallbladder polyps, especially those ≥ 5 mm.
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Affiliation(s)
- Sung Noh Hong
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tae Yoon Lee
- Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Sung-Cheol Yun
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Liu Y, He Y, Li T, Xie L, Wang J, Qin X, Li S. Risk of primary liver cancer associated with gallstones and cholecystectomy: a meta-analysis. PLoS One 2014; 9:e109733. [PMID: 25290940 PMCID: PMC4188756 DOI: 10.1371/journal.pone.0109733] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2014] [Accepted: 09/09/2014] [Indexed: 12/14/2022] Open
Abstract
Background Recent epidemiological evidence points to an association between gallstones or cholecystectomy and the incidence risk of liver cancer, but the results are inconsistent. We present a meta-analysis of observational studies to explore this association. Methods We identified studies by a literature search of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and relevant conference proceedings up to March 2014. A random-effects model was used to generate pooled multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Between-study heterogeneity was assessed using Cochran’s Q statistic and the I2. Results Fifteen studies (five case-control and 10 cohort studies) were included in this analysis. There were 4,487,662 subjects in total, 17,945 diagnoses of liver cancer, 328,420 exposed to gallstones, and 884,507 exposed to cholecystectomy. Pooled results indicated a significant increased risk of liver cancer in patients with a history of gallstones (OR = 2.54; 95% CI, 1.71–3.79; n = 11 studies), as well as cholecystectomy (OR = 1.62; 95% CI, 1.29–2.02; n = 12 studies), but there was considerable heterogeneity among these studies. The effects estimates did not vary markedly when stratified by gender, study design, study region, and study quality. The multivariate meta-regression analysis suggested that study region and study quality appeared to explain the heterogeneity observed in the cholecystectomy analysis. Conclusions Our results suggest that individuals with a history of gallstones and cholecystectomy may have an increased risk of liver cancer.
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Affiliation(s)
- Yanqiong Liu
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Yu He
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Taijie Li
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Li Xie
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Jian Wang
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Xue Qin
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Shan Li
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
- * E-mail:
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Gadaleta RM, Cariello M, Sabbà C, Moschetta A. Tissue-specific actions of FXR in metabolism and cancer. Biochim Biophys Acta Mol Cell Biol Lipids 2014; 1851:30-9. [PMID: 25139561 DOI: 10.1016/j.bbalip.2014.08.005] [Citation(s) in RCA: 82] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Revised: 08/08/2014] [Accepted: 08/11/2014] [Indexed: 12/25/2022]
Abstract
The nuclear Farnesoid X Receptor (FXR) is a transcription factor critically involved in metabolic homeostasis in the gut-liver axis. FXR activity is mediated by hormonal and dietary signals and driven by bile acids (BAs), which are the natural FXR ligands. Given the great physiological importance in BA homeostasis, as well as in the regulation of glucose and lipid metabolism, FXR plays a pivotal role in the pathogenesis of a wide range of disease of the liver, biliary tract and intestine, including hepatic and colorectal cancer. In the last years several studies have shown the relative FXR tissue-specific importance, highlighting synergism and additive effects in the liver and intestine. Gain- and loss-of-FXR-function mouse models have been generated in order to identify the biological processes and the molecular FXR targets. Taking advantage of the knowledge on the structure-activity relationship of BAs for FXR, semi-synthetic and synthetic molecules have been generated to obtain more selective and powerful FXR activators than BAs. This article is part of a Special Issue entitled: Linking transcription to physiology in lipodomics.
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Affiliation(s)
- Raffaella Maria Gadaleta
- Division of Cancer, Imperial Centre for Translational and Experimental Medicine, Imperial College London, UK
| | - Marica Cariello
- National Cancer Research Center, IRCCS Istituto Oncologico "Giovanni Paolo II", Bari, Italy
| | - Carlo Sabbà
- Clinica Medica Frugoni, Department of Interdisciplinary Medicine, University of Bari, Italy
| | - Antonio Moschetta
- National Cancer Research Center, IRCCS Istituto Oncologico "Giovanni Paolo II", Bari, Italy; Clinica Medica Frugoni, Department of Interdisciplinary Medicine, University of Bari, Italy.
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Chen YK, Yeh JH, Lin CL, Peng CL, Sung FC, Hwang IM, Kao CH. Cancer risk in patients with cholelithiasis and after cholecystectomy: a nationwide cohort study. J Gastroenterol 2014; 49:923-31. [PMID: 23807230 DOI: 10.1007/s00535-013-0846-6] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2013] [Accepted: 06/03/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND This study examined the association of cholelithiasis post-cholecystectomy with subsequent cancers and evaluated the risk of cancer in patients with both cholelithiasis and cholecystectomy. METHODS The Taiwanese National Health Insurance Research Database was used to identify 15545 newly diagnosed cholelithiasis patients from 2000 to 2010, and 62180 frequency-matched non-cholelithiasis patients. A total of 5850 (37.6 %) with cholelithiasis patients received a cholecystectomy. The risk of developing cancer after cholecystectomy was measured using the Cox proportional-hazards model. RESULTS The incidence of developing cancer in the cholelithiasis cohort was 1.52-fold higher than that in the comparison cohort (p < 0.001). Compared with patients aged 20-34 years, patients in older age groups had a higher risk of developing cancer. The hazard ratio (HR) for developing gallbladder, extrahepatic bile duct, pancreatic, liver, stomach, and colorectal cancer was 59.3, 10.7, 3.12, 1.90, 1.71, and 1.36-fold higher for patients with cholelithiasis, respectively. After a cholecystectomy, the HR for developing stomach and colorectal cancer was 1.81-fold and 1.56-fold, respectively. The incidence rate ratio was higher for the first 5 years and over 5 years (5.05 and 4.46, respectively) (95 % confidence interval 4.73-5.39 and 4.11-4.84, respectively) in proximal colon and stomach cancer patients with cholecystectomies. CONCLUSIONS Cholelithiasis patients have a higher risk of gastrointestinal cancer, particularly of gallbladder and extrahepatic bile duct cancer. Post-cholecystectomy patients have a risk of colorectal and stomach cancer within the first 5 years and persisting after 5 years, respectively. This paper proposes strategies for preventing gastrointestinal cancer.
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Affiliation(s)
- Yen-Kung Chen
- Department of Nuclear Medicine and PET Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
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Ford K, Davenport M. Letter to the editor. J Pediatr Surg 2014; 49:664. [PMID: 24726134 DOI: 10.1016/j.jpedsurg.2013.12.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2013] [Accepted: 12/30/2013] [Indexed: 10/25/2022]
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Nogueira L, Freedman ND, Engels EA, Warren JL, Castro F, Koshiol J. Gallstones, cholecystectomy, and risk of digestive system cancers. Am J Epidemiol 2014; 179:731-9. [PMID: 24470530 DOI: 10.1093/aje/kwt322] [Citation(s) in RCA: 90] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Gallstones and cholecystectomy may be related to digestive system cancer through inflammation, altered bile flux, and changes in metabolic hormone levels. Although gallstones are recognized causes of gallbladder cancer, associations with other cancers of the digestive system are poorly established. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2005), which includes 17 cancer registries that cover approximately 26% of the US population, to identify first primary cancers (n = 236,850) occurring in persons aged ≥66 years and 100,000 cancer-free population-based controls frequency-matched by calendar year, age, and gender. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis, adjusting for the matching factors. Gallstones and cholecystectomy were associated with increased risk of noncardia gastric cancer (odds ratio (OR) = 1.21 (95% confidence interval (CI): 1.11, 1.32) and OR = 1.26 (95% CI: 1.13, 1.40), respectively), small-intestine carcinoid (OR = 1.27 (95% CI: 1.01, 1.60) and OR = 1.78 (95% CI: 1.41, 2.25)), liver cancer (OR = 2.35 (95% CI: 2.18, 2.54) and OR = 1.26 (95% CI: 1.12, 1.41)), and pancreatic cancer (OR = 1.24 (95% CI: 1.16, 1.31) and OR = 1.23 (95% CI: 1.15, 1.33)). Colorectal cancer risk associated with gallstones and cholecystectomy decreased with increasing distance from the common bile duct (P-trend < 0.001). Hence, gallstones and cholecystectomy are associated with the risk of cancers occurring throughout the digestive tract.
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Abstract
OBJECTIVE To investigate the risk of intestinal cancer in a cohort of people who had undergone cholecystectomy for gallstones, and in a cohort of people who had been hospitalized for gallbladder disease but had not undergone cholecystectomy. BACKGROUND Some investigators have suggested that cholecystectomy increases the risk of intestinal cancer. Despite extensive study, the evidence remains inconclusive. If there is doubt about safety, the question arises of whether patients considering the operation should be told of a possible risk. It is also increasingly clear that there are noncausal associations between gallstones and intestinal cancer. METHOD Analysis of record-linked hospital admission and mortality statistics for England from 1998 to 2008; calculation of ratio of rates of cancers in the cholecystectomy cohort and the gallbladder disease cohort compared with a control cohort. RESULTS : In the first year after cholecystectomy, the rate ratios for cancer of the small intestine, colon, and rectum were significantly high at, respectively, 4.6 (95% confidence interval 3.9-5.5), 2.0 (1.9-2.1), and 1.7 (1.6-1.9). Rates of these cancers were also significantly high in people with gallstones without cholecystectomy. By 8 to 10 years after cholecystectomy, rate ratios had declined to nonsignificant levels. CONCLUSIONS These cancers are associated with gallstones. The highest elevation of risk of cancer after cholecystectomy was at the shortest time interval after operation. Thereafter, the level of risk in the cholecystectomy and control cohorts gradually converged. The association in this study, between cholecystectomy and intestinal cancer, is very unlikely to be causal. Intestinal cancers are, on occasion, initially misdiagnosed as gallbladder disease.
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Inoue I, Kato J, Yoshimura N, Maeda Y, Moribata K, Shingaki N, Deguchi H, Enomoto S, Maekita T, Ueda K, Iguchi M, Tamai H, Fujishiro M, Yamamichi N, Takeshita T, Ichinose M. Elevated risk of recurrent colorectal neoplasia with Helicobacter pylori-associated chronic atrophic gastritis: A follow-up study of patients with endoscopically resected colorectal neoplasia. Mol Clin Oncol 2012; 1:75-82. [PMID: 24649126 DOI: 10.3892/mco.2012.22] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2012] [Accepted: 08/17/2012] [Indexed: 12/19/2022] Open
Abstract
In a previous population-based case-control study, we demonstrated an elevated risk of colorectal neoplasia with Helicobacter pylori (H. pylori) infection. The present study investigated the effects of H. pylori-associated chronic gastritis on the development of colorectal neoplasia by analyzing the recurrence of colorectal neoplasia subsequent to endoscopic resection. Ninety-nine patients who had undergone endoscopic resection of colorectal neoplasia were monitored under colonoscopy, and the recurrence of colorectal neoplasia was prospectively investigated. The stage of H. pylori-associated chronic gastritis in each subject was evaluated using a combination of two serum tests: H. pylori antibody and pepsinogen. In the present cohort, colorectal neoplasia recurred at a rate of 15,296/100,000 person-years during the study period. After adjusting for the confounding factors, chronic atrophic gastritis (CAG) was identified as an independent risk factor [adjusted hazard ratio (HR), 2.72; 95% confidence interval, 1.33-5.57], while H. pylori-infected non-atrophic gastritis was not identified as an independent risk factor for recurrent colorectal neoplasia. Colorectal neoplasia recurred earlier and was significantly more frequent in patients with CAG (22,573/100,000 person-years) compared to patients without CAG (11,089/100,000 person-years; P=0.029, log-rank test). Patients with more extensive CAG showed a higher risk of recurrence. These results demonstrated a significant elevation of the risk of recurrent colorectal neoplasia with the establishment and progression of CAG, indicating the involvement of H. pylori infection in the development of colorectal neoplasia. The two serum tests were useful clinical markers for noninvasively evaluating the risk of each individual for recurrent colorectal neoplasia subsequent to endoscopic resection.
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Affiliation(s)
- Izumi Inoue
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama 641-0012
| | - Jun Kato
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama 641-0012
| | | | - Yoshimasa Maeda
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama 641-0012
| | - Kosaku Moribata
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama 641-0012
| | - Naoki Shingaki
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama 641-0012
| | - Hisanobu Deguchi
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama 641-0012
| | - Shotaro Enomoto
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama 641-0012
| | - Takao Maekita
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama 641-0012
| | - Kazuki Ueda
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama 641-0012
| | - Mikitaka Iguchi
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama 641-0012
| | - Hideyuki Tamai
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama 641-0012
| | - Mitsuhiro Fujishiro
- Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655
| | - Nobutake Yamamichi
- Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655
| | - Tatsuya Takeshita
- Department of Public Health, School of Medicine, Wakayama Medical University, Wakayama 641-0012, Japan
| | - Masao Ichinose
- Department of Gastroenterology, School of Medicine, Wakayama Medical University, Wakayama 641-0012
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Abstract
BACKGROUND Increased levels of secondary bile acids after gallstone disease and cholecystectomy are believed to increase the risk of colorectal cancer. It remains unclear whether there is a similar risk of developing adenomas. The aim of this meta-analysis was to determine the risk of developing colonic adenomas following gallstone disease or cholecystectomy. METHODS The study was based on a systematic search of PubMed, MEDLINE, EMBASE, and Current Contents (1950-2012). Selection criteria were developed to sort for studies exploring the relationship between cholelithiasis, cholecystectomy, and colonic adenoma in an adult population. A random-effects model was used to generate pooled odds ratios (OR) and 95 % confidence intervals (CI). Publication bias and heterogeneity were assessed. RESULTS Of the 1,276 studies identified, 14 were suitable for final analysis. There were 253,059 subjects in total, 42,543 of whom were diagnosed with colonic adenoma, and 28,281 of whom had gallstones or underwent cholecystectomy. There was a significant risk of developing colonic adenoma if gallstones were present (OR = 2.26; 95 % CI = 1.83-2.81). A risk was also seen with cholecystectomy (OR = 1.15; 95 % CI = 1.04-1.26), but this risk was negated when only adjusted odds were selected (OR = 1.01; 95 % CI = 0.91-1.12). No publication bias and only low levels of heterogeneity existed. CONCLUSIONS Gallstones increase the risk of colonic adenoma. No association exists with cholecystectomy.
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Affiliation(s)
- Corinna Chiong
- The Whiteley-Martin Research Centre, Discipline of Surgery, The University of Sydney, Nepean Hospital, Level 5, South Block, P.O. Box 63, Penrith, NSW 2751, Australia
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Risk factors for colon cancer in 150,912 postmenopausal women. Cancer Causes Control 2012; 23:1599-605. [DOI: 10.1007/s10552-012-0037-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2012] [Accepted: 07/18/2012] [Indexed: 01/08/2023]
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Tavani A, Rosato V, Di Palma F, Bosetti C, Talamini R, Dal Maso L, Zucchetto A, Levi F, Montella M, Negri E, Franceschi S, La Vecchia C. History of cholelithiasis and cancer risk in a network of case-control studies. Ann Oncol 2012; 23:2173-2178. [PMID: 22231026 DOI: 10.1093/annonc/mdr581] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND We analyzed the relationship between cholelithiasis and cancer risk in a network of case-control studies conducted in Italy and Switzerland in 1982-2009. METHODS The analyses included 1997 oropharyngeal, 917 esophageal, 999 gastric, 23 small intestinal, 3726 colorectal, 684 liver, 688 pancreatic, 1240 laryngeal, 6447 breast, 1458 endometrial, 2002 ovarian, 1582 prostate, 1125 renal cell, 741 bladder cancers, and 21 284 controls. The odds ratios (ORs) were estimated by multiple logistic regression models. RESULTS The ORs for subjects with history of cholelithiasis compared with those without were significantly elevated for small intestinal (OR=3.96), prostate (OR=1.36), and kidney cancers (OR=1.57). These positive associations were observed ≥10 years after diagnosis of cholelithiasis and were consistent across strata of age, sex, and body mass index. No relation was found with the other selected cancers. A meta-analysis including this and three other studies on the relation of cholelithiasis with small intestinal cancer gave a pooled relative risk of 2.35 [95% confidence interval (CI) 1.82-3.03]. CONCLUSION In subjects with cholelithiasis, we showed an appreciably increased risk of small intestinal cancer and suggested a moderate increased risk of prostate and kidney cancers. We found no material association with the other cancers considered.
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Affiliation(s)
- A Tavani
- Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan.
| | - V Rosato
- Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan
| | - F Di Palma
- Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan
| | - C Bosetti
- Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan
| | - R Talamini
- Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico, Aviano
| | - L Dal Maso
- Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico, Aviano; Department of Occupational Health, University of Milan, Milan, Italy
| | - A Zucchetto
- Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico, Aviano
| | - F Levi
- Cancer Epidemiology Unit and Registre Vaudois des Tumeurs, Institut universitaire de médecine sociale et préventive, Lausanne, Switzerland
| | - M Montella
- Unit of Epidemiology, Istituto Tumori "Fondazione Pascale", Naples, Italy
| | - E Negri
- Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan
| | - S Franceschi
- International Agency for Research on Cancer, Lyon
| | - C La Vecchia
- Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan; Department of Occupational Health, University of Milan, Milan, Italy; International Prevention Research Institute, Lyon, France
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Abstract
Gallstone disease in children is evolving, and for the previous 3 decades, the frequency for surgery has increased greatly. This is in part because of improved diagnostic modalities, but also changing pathology, an increased awareness of emerging comorbidities, such as childhood obesity, and other associated risk factors. This article outlines the pathophysiology, genetics, and predisposing factors for developing gallstones and includes a review of the literature on the current and more novel medical and surgical techniques to treat this interesting disease.
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Affiliation(s)
- Jan Svensson
- Department of Paediatric Surgery, Astrid Lindgren Children's Hospital, Karolinska University Hospital & Karolinska Institutet, Stockholm, Sweden
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Abstract
BACKGROUND Increased levels of secondary bile acids after cholecystectomy and cholelithiasis are believed to increase the risk of colorectal cancer, and several studies have suggested that the risk of colorectal cancer may be the greatest proximally. Numerous conflicting studies have been published and it remains unclear whether the risk is apparent in the rectum. This meta-analysis aims to determine the risk of developing rectal cancer following gallstone disease or cholecystectomy. METHODS The prospective protocol included a literature search of PubMed, MEDLINE, EMBASE, and Current Contents (1950-2011). Selection criteria were developed to sort for studies exploring the relationship between cholelithiasis, cholecystectomy, and rectal cancer in an adult population. A random-effects model was used to generate pooled odds ratios (OR) and 95% confidence intervals (CI). Publication bias and heterogeneity were assessed. RESULTS Of the 2358 studies identified, 42 were suitable for final analysis. There were 1,547,506 subjects in total, 14,226 diagnosed with rectal cancer, and 496,552 with gallstones or cholecystectomy. There was a statistically significant risk of rectal cancer following cholelithiasis (OR = 1.33; 95% CI = 1.02-1.73), though no risk was apparent following cholecystectomy (OR = 1.14; 95% CI = 0.92-1.41). CONCLUSIONS Cholelithiasis increases the risk of rectal cancer. No association exists between cholecystectomy and rectal cancer.
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Affiliation(s)
- Corinna Chiong
- Discipline of Surgery, The Whiteley-Martin Research Centre, The University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia
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