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Zhang X, Yang X, Wang Y, Xu Z, Yi S, Guo T, Liao Y, Tang X, Zhang J, Wang R. A supramolecular nanoprodrug for prevention of gallstone formation. CHINESE CHEM LETT 2025; 36:109854. [DOI: 10.1016/j.cclet.2024.109854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Sung MJ, Han SY, Lee JH, Kim TI, Kim DU, Kwon CI, Cho JH, Choe JW, Hyun JJ, Yang JK, Lee TH, Lee J, Jang SI, Jeong S. Combinatorial Effects of Terpene, Chenodeoxycholic Acid, and Ursodeoxycholic Acid on Common Bile Duct Stone Recurrence and Gallbladder Stone Dissolution. J Clin Med 2024; 13:7414. [PMID: 39685879 DOI: 10.3390/jcm13237414] [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: 10/08/2024] [Revised: 11/26/2024] [Accepted: 12/03/2024] [Indexed: 12/18/2024] Open
Abstract
Background: Ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA) plus UDCA (C&U), and terpene are widely administered to prevent common bile duct (CBD) stone recurrence and dissolve gallbladder (GB) stones. We evaluated and compared the combined effects of these agents on CBD stone recurrence and GB stone resolution. Methods: This study included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) at six referral centers, retrospectively. A total of 940 patients who underwent cholecystectomy before or after CBD stone removal by ERCP were evaluated to assess CBD stone recurrence (the CBD recurrence cohort), and 98 patients with GB stones were assessed by abdominal or endoscopic ultrasonography before and 6 months after ERCP to evaluate GB stone resolution (GB cohort). Patients were divided into no-medication, single-agent treatment (UDCA, C&U, or terpene), or dual-agent treatment (terpene plus UDCA or C&U) groups for the analysis. Results: In the CBD recurrence cohort, baseline characteristics were similar in the three groups. CBD stone recurrence rates were 41.5%, 12.7%, and 9.8% in the no-medication, single-agent, and dual-agent groups, respectively (p < 0.001), and the recurrence rate was significantly lower for those administered C&U plus terpene (5.2% vs. 13.2%, p = 0.002). In the GB cohort, baseline characteristics were also similar in the groups. GB stone resolution rates of >30% were observed in 5.3%, 14.3%, and 34.8% of patients in the no-medication, single-agent, and dual-agent groups, respectively (p = 0.028). Conclusions: C&U plus terpene was significantly more effective for preventing CBD stone recurrence and achieving GB stone resolution than no medication or single agents.
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Affiliation(s)
- Min Je Sung
- Digestive Disease Center, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Republic of Korea
| | - Sung Yong Han
- Department of Internal Medicine, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Jong Hyun Lee
- Department of Internal Medicine, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Tae In Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Dong Uk Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Chang-Il Kwon
- Digestive Disease Center, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Republic of Korea
| | - Jae Hee Cho
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea
| | - Jung Wan Choe
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea
| | - Jong Jin Hyun
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea
| | - Jae Kook Yang
- Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, Cheonan 31151, Republic of Korea
| | - Tae Hoon Lee
- Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, Cheonan 31151, Republic of Korea
| | - Jungnam Lee
- Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, Incheon 22332, Republic of Korea
| | - Sung Ill Jang
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea
| | - Seok Jeong
- Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, Incheon 22332, Republic of Korea
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Lammert F, Wittenburg H. Gallstones: Prevention, Diagnosis, and Treatment. Semin Liver Dis 2024; 44:394-404. [PMID: 39095030 DOI: 10.1055/a-2378-9025] [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] [Indexed: 08/04/2024]
Abstract
Gallstones are common and affect up to 20% of the general adult population and >20% of them will develop symptoms or complications of cholelithiasis. The high risk of gallbladder stone formation can be reduced by ursodeoxycholic acid in the case of significant weight reduction resulting from diet or bariatric surgery. Laparoscopic cholecystectomy is indicated for symptomatic gallstones, as the risk of recurrence or complications increases over the course of the disease. Biliary colic is treated with nonsteroidal anti-inflammatory drugs and spasmolytics; opioids can also be used in cases of severe acute pain. Acute cholecystitis represents a common complication of gallbladder stones and a cholecystectomy should be performed early electively, i.e., within 24 hours of admission to hospital. Symptomatic bile duct stones are primarily treated endoscopically. Immediate anti-infective therapy is mandatory in acute cholangitis. Although knowledge on the genetics and pathophysiology of gallstones has increased, current treatment algorithms remain predominantly invasive, based on interventional endoscopy and surgery. Future efforts should focus on novel strategies to prevent the development of gallstones.
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Affiliation(s)
- Frank Lammert
- Health Sciences, Hannover Medical School (MHH), Hannover, Germany
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Xie L, Xu M, Lei Y, Li J, Xie J. The causal relationship between diet habits and cholelithiasis: a comprehensive Mendelian randomization (MR) study. Front Nutr 2024; 11:1377631. [PMID: 38933877 PMCID: PMC11203601 DOI: 10.3389/fnut.2024.1377631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 05/29/2024] [Indexed: 06/28/2024] Open
Abstract
Background Epidemiological studies show dietary habits can have an impact on the risk of cholelithiasis, but the relationship is still unclear. We used a comprehensive Mendelian randomization (MR) study to explore the relationship between dietary habits and cholelithiasis. Methods The 18 dietary habits were divided into six categories: meat foods, cereals, vegetables, fruits, dairy products, beverages, and condiments. Cholelithiasis data came from a GWAS meta-analysis and the FinnGen consortium. The inverse variance weighted (IVW), the weighted median (WM), and MR-Egger approaches were used as the main MR analysis methods. In addition, multiple sensitivity analysis and meta-analysis were performed to verify the robustness of the results. Results Dried fruit intake [odds ratio (OR) = 0.568; 95% confidence interval (CI), 0.405-0.797; p = 0.001] was discovered to reduce the risk of cholelithiasis. The sensitivity analysis and meta-analysis showed reliable results for the relationship between dried fruit intake and cholelithiasis. Conclusion Our study found that dried fruit intake is a protective factor in the development of cholelithiasis. However, the mechanisms of action need to be further explored.
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Affiliation(s)
- Lin Xie
- The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Mingzhi Xu
- The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Yahan Lei
- The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Juan Li
- The Seventh Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Jiajia Xie
- Shenzhen Bao’an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
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Sakai Y, Tsuyuguchi T, Ohyama H, Kumagai J, Kaiho T, Ohtsuka M, Kato N, Sakai T. Natural history of asymptomatic gallbladder stones in clinic without beds: A long-term prognosis over 10 years. World J Clin Cases 2024; 12:42-50. [PMID: 38292642 PMCID: PMC10824178 DOI: 10.12998/wjcc.v12.i1.42] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 10/31/2023] [Accepted: 12/18/2023] [Indexed: 01/02/2024] Open
Abstract
BACKGROUND Several studies have explored the long-term prognosis of patients with asymptomatic gallbladder stones. These reports were primarily conducted in facilities equipped with beds for addressing symptomatic cases. AIM To report the long-term prognosis of patients with asymptomatic gallbladder stones in clinics without bed facilities. METHODS We investigated the prognoses of 237 patients diagnosed with asymptomatic gallbladder stones in clinics without beds between March 2010 and October 2022. When symptoms developed, patients were transferred to hospitals where appropriate treatment was possible. We investigated the asymptomatic and survival periods during the follow-up. RESULTS Among the 237 patients, 214 (90.3%) remained asymptomatic, with a mean asymptomatic period of 3898.9279 ± 46.871 d (50-4111 d, 10.7 years on average). Biliary complications developed in 23 patients (9.7%), with a mean survival period of 4010.0285 ± 31.2788 d (53-4112 d, 10.9 years on average). No patient died of biliary complications. CONCLUSION The long-term prognosis of asymptomatic gallbladder stones in clinics without beds was favorable. When the condition became symptomatic, the patients were transferred to hospitals with beds that could address it; thus, no deaths related to biliary complications were reported. This finding suggests that follow-up care in clinics without beds is possible.
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Affiliation(s)
- Yuji Sakai
- Department of Gastroenterology, Sakai Clinic, Kimistu 299-1162, Japan
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba 260-8677, Japan
| | - Toshio Tsuyuguchi
- Department of Gastroenterology, Chiba Prefectural Sawara Hospital, Chiba Prefectural Sawara Hospital, Sawara 287-0003, Japan
| | - Hiroshi Ohyama
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba 260-8677, Japan
| | - Junichiro Kumagai
- Department of Gastroenterology, Kimitsu Central Hospital, Kisarazu 292-8535, Japan
| | - Takashi Kaiho
- Department of Surgery, Kimitsu Central Hospital, Kisarazu 292-8535, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8677, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba 260-8677, Japan
| | - Tadao Sakai
- Department of Gastroenterology, Sakai Clinic, Kimistu 299-1162, Japan
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Bhattacharya T, Nandi A, Das A, El-Shazly M. Role of liver in gallstone formation. GALLSTONE FORMATION, DIAGNOSIS, TREATMENT AND PREVENTION 2024:51-70. [DOI: 10.1016/b978-0-443-16098-1.00014-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Fujita N, Yasuda I, Endo I, Isayama H, Iwashita T, Ueki T, Uemura K, Umezawa A, Katanuma A, Katayose Y, Suzuki Y, Shoda J, Tsuyuguchi T, Wakai T, Inui K, Unno M, Takeyama Y, Itoi T, Koike K, Mochida S. Evidence-based clinical practice guidelines for cholelithiasis 2021. J Gastroenterol 2023; 58:801-833. [PMID: 37452855 PMCID: PMC10423145 DOI: 10.1007/s00535-023-02014-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 06/21/2023] [Indexed: 07/18/2023]
Abstract
The Japanese Society of Gastroenterology first published evidence-based clinical practice guidelines for cholelithiasis in 2010, followed by a revision in 2016. Currently, the revised third edition was published to reflect recent evidence on the diagnosis, treatment, and prognosis of cholelithiasis conforming to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Following this revision, the present English version of the guidelines was updated and published herein. The clinical questions (CQ) in the previous version were reviewed and rearranged into three newly divided categories: background questions (BQ) dealing with basic background knowledge, CQ, and future research questions (FRQ), which refer to issues that require further accumulation of evidence. Finally, 52 questions (29 BQs, 19 CQs, and 4 FRQs) were adopted to cover the epidemiology, pathogenesis, diagnosis, treatment, complications, and prognosis. Based on a literature search using MEDLINE, Cochrane Library, and Igaku Chuo Zasshi databases for the period between 1983 and August 2019, along with a manual search of new information reported over the past 5 years, the level of evidence was evaluated for each CQ. The strengths of recommendations were determined using the Delphi method by the committee members considering the body of evidence, including benefits and harms, patient preference, and cost-benefit balance. A comprehensive flowchart was prepared for the diagnosis and treatment of gallbladder stones, common bile duct stones, and intrahepatic stones, respectively. The current revised guidelines are expected to be of great assistance to gastroenterologists and general physicians in making decisions on contemporary clinical management for cholelithiasis patients.
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Affiliation(s)
- Naotaka Fujita
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.
- Miyagi Medical Check-up Plaza, 1-6-9 Oroshi-machi, Wakabayashi-ku, Sendai, Miyagi, 984-0015, Japan.
| | - Ichiro Yasuda
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Itaru Endo
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroyuki Isayama
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takuji Iwashita
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Toshiharu Ueki
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kenichiro Uemura
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Akiko Umezawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Akio Katanuma
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yu Katayose
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yutaka Suzuki
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Junichi Shoda
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Toshio Tsuyuguchi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Toshifumi Wakai
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kazuo Inui
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Michiaki Unno
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshifumi Takeyama
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takao Itoi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Satoshi Mochida
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Cholelithiasis'', The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
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Shenoy R, Kirkland P, Hadaya JE, Tranfield MW, DeVirgilio M, Russell MM, Maggard-Gibbons M. Management of symptomatic cholelithiasis: a systematic review. Syst Rev 2022; 11:267. [PMID: 36510302 PMCID: PMC9743645 DOI: 10.1186/s13643-022-02135-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 11/08/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Symptomatic cholelithiasis is a common surgical disease and accounts for half of the over one million cholecystectomies performed in the USA annually. Despite its prevalence, only one prior systematic review has examined the evidence around treatment strategies and it contained a narrow scope. The goal of this systematic review was to analyze the clinical effectiveness of treatment options for symptomatic cholelithiasis, including surgery, non-surgical therapies, and ED pain management strategies. METHODS Literature search was performed from January 2000 through June 2020, and a narrative analysis was performed as studies were heterogeneous. RESULTS We identified 12 publications reporting on 10 trials (9 randomized controlled trials and 1 observational study) comparing treatment methods. The studies assessed surgery, observation, lithotripsy, ursodeoxycholic acid, electro-acupuncture, and pain-management strategies in the emergency department. Only one compared surgery to observation. CONCLUSION This work presents the existing data and underscores the current gap in knowledge regarding treatment for patients with symptomatic cholelithiasis. We use these results to suggest how future trials may guide comparisons between the timing of surgery and watchful waiting to create a set of standardized guidelines. Providing appropriate and timely treatment for symptomatic cholelithiasis is important to streamline care for a costly and prevalent disease. TRIAL REGISTRATION PROSPERO Protocol Number: CRD42020153153.
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Affiliation(s)
- Rivfka Shenoy
- Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, USA. .,Veterans Health Administration, Greater Los Angeles Healthcare System, Los Angeles, CA, USA. .,National Clinician Scholars Program, UCLA, Los Angeles, CA, USA.
| | - Patrick Kirkland
- Department of Surgery, Los Angeles County Harbor-UCLA Medical Center, Los Angeles, CA, USA
| | - Joseph E Hadaya
- Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, USA
| | - M Wynn Tranfield
- Louise M. Darling Biomedical Library, UCLA Library, University of California, Los Angeles, CA, USA
| | - Michael DeVirgilio
- Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.,Veterans Health Administration, Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| | - Marcia M Russell
- Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.,Veterans Health Administration, Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| | - Melinda Maggard-Gibbons
- Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.,Veterans Health Administration, Greater Los Angeles Healthcare System, Los Angeles, CA, USA.,Rand Corporation, Santa Monica, CA, USA.,Olive View-UCLA Medical Center, Sylmar, CA, USA
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Strohaeker J, Sabrow J, Yurttas C, Königsrainer A, Ladurner R, Hoenes F. Management of Symptomatic Gallstone Disease during COVID-19 Lockdown in a High-Resource Setting: Is There a Need for Treatment Alterations? Visc Med 2022; 38:265-271. [PMID: 36160825 PMCID: PMC9421663 DOI: 10.1159/000519789] [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: 06/29/2021] [Accepted: 09/17/2021] [Indexed: 08/03/2023] Open
Abstract
Introduction Cholecystectomy (CCE) is the treatment of choice of symptomatic gallstones. Due to the SARS-CoV-2 pandemic, operating room (OR) capacities have been reduced. The goal of this study was to evaluate the duration of symptoms of patients presenting with gallstone disease during a lockdown, the surgical management, and the severity grade of their disease. Materials and Methods A cohort study of 353 CCEs performed at a university hospital over two 10-week periods during 2 pandemic lockdowns in Germany compared to corresponding periods in 2018 and 2019. Results During the lockdowns, 101 CCEs were performed compared to 252 in the prior years. The number of elective CCEs was reduced to save OR capacities (p < 0.001), and the most common indication for CCE was acute cholecystitis. The median time to CCE after symptom onset was 3 days in both groups for acute cholecystitis. The severity of cholecystitis was comparable (p = 0.760). The time to CCE after choledocholithiasis was shorter during the lockdowns (median of 4 days vs. 9 days; p = 0.006). Conclusions The incidence and severity of acute cholecystitis during the lockdowns were comparable to the prior years. Acute care surgery was provided at the expense of elective procedures, and there was no need for treatment alterations.
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Affiliation(s)
- Jens Strohaeker
- Department of General, Visceral and Transplantation Surgery, University Hospital of Tuebingen, Tuebingen, Germany
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10
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Haal S, Guman MSS, Boerlage TCC, Acherman YIZ, de Brauw LM, Bruin S, de Castro SMM, van Hooft JE, van de Laar AWJM, Moes DE, Schouten M, Schouten R, van Soest EJ, van Veen RN, de Vries CEE, Fockens P, Dijkgraaf MGW, Gerdes VEA, Voermans RP. Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial. Lancet Gastroenterol Hepatol 2021; 6:993-1001. [PMID: 34715031 DOI: 10.1016/s2468-1253(21)00301-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 08/08/2021] [Accepted: 08/09/2021] [Indexed: 01/12/2023]
Abstract
BACKGROUND Rapid weight loss is a major risk factor for the formation of cholesterol gallstones. Consequently, patients with morbid obesity undergoing bariatric surgery frequently develop symptomatic gallstone disease. This trial assessed the efficacy of ursodeoxycholic acid versus placebo for the prevention of symptomatic gallstone disease after bariatric surgery. METHODS This multicentre, double-blind, randomised, placebo-controlled superiority trial enrolled patients with an intact gallbladder scheduled for laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy in three hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module to receive 900 mg ursodeoxycholic acid daily for 6 months or matched placebo. Randomisation was stratified by the presence of asymptomatic gallstones at baseline and type of surgery. Patients, clinicians, and study staff were masked to treatment allocation. The primary endpoint was symptomatic gallstone disease within 24 months, assessed in the modified intention-to-treat population (all randomly assigned eligible patients with any post-randomisation measurement). Prespecified subgroup analyses were done based on the stratification groups. Safety was assessed in all patients who took at least one dose of the study drug. This trial is registered with the Netherlands Trial Register, NL5954. FINDINGS Between Jan 11, 2017, and Oct 22, 2018, 985 patients were randomly assigned to receive either ursodeoxycholic acid (n=492) or placebo (n=493). 967 patients were included in the modified intention-to-treat population, of whom 959 had data available for primary endpoint assessment. 189 (20%) patients had asymptomatic gallstones at baseline and 78 (8%) received a sleeve gastrectomy. Symptomatic gallstone disease occurred in 31 (6·5%) of 475 patients in the ursodeoxycholic acid group and in 47 (9·7%) of 484 patients in the placebo group (relative risk 0·67, 95% CI 0·43-1·04, p=0·071). Logistic regression showed a significant interaction between ursodeoxycholic acid and the presence of asymptomatic gallstones at baseline (p=0·046), with an effect of ursodeoxycholic acid in patients without (0·47, 0·27-0·84, p=0·0081), and no effect in patients with asymptomatic gallstones at baseline (1·22, 0·61-2·47, p=0·57). The effect was stronger in patients without gallstones at baseline undergoing RYGB (0·37, 0·20-0·71, p=0·0016), whereas the subgroup of patients undergoing sleeve gastrectomy was too small to draw clear conclusions. Adverse events were rare. In the ursodeoxycholic acid group, diarrhoea occurred in four (0·9%) of 444 patients and skin rash in two (0·5%) patients. In the placebo group, diarrhoea occurred in two (0·4%) of 453 patients and skin rash in two (0·4%) patients. The total number of serious adverse events did not significantly differ between the trial groups (75 [17%] in 444 patients in the ursodeoxycholic acid group and 102 [23%] in 453 patients in the placebo group). The most common serious adverse events were abdominal pain and internal hernia. No serious adverse event was attributed to the study drug. INTERPRETATION Ursodeoxycholic acid prophylaxis did not significantly reduce the occurrence of symptomatic gallstone disease in all patients after bariatric surgery. In patients without gallstones before RYGB surgery, ursodeoxycholic acid treatment reduced the occurrence of symptomatic gallstone disease compared with placebo. Further research is needed to assess the efficacy of ursodeoxycholic acid after sleeve gastrectomy. FUNDING The Netherlands Organization for Health Research and Development, Zambon Netherlands BV, Foundation for Clinical Research of the Slotervaart Hospital, the Spaarne Gasthuis Academy, and Amsterdam Gastroenterology Endocrinology Metabolism.
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Affiliation(s)
- Sylke Haal
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, Netherlands; Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, Netherlands
| | - Maimoena S S Guman
- Department of Internal and Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, Netherlands; Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, Netherlands
| | - Thomas C C Boerlage
- Department of Gastroenterology and Hepatology, UMC Utrecht, Utrecht, Netherlands
| | | | | | - Sjoerd Bruin
- Department of Surgery, Spaarne Gasthuis, Hoofddorp, Netherlands
| | | | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, Netherlands
| | | | - Daan E Moes
- Department of Surgery, Dijklander Hospital, Hoorn, Netherlands
| | - Manon Schouten
- Department of Surgery, Flevohospital, Almere, Netherlands
| | - Ruben Schouten
- Department of Surgery, Flevohospital, Almere, Netherlands
| | - Ellert J van Soest
- Department of Gastroenterology and Hepatology, Spaarne Gasthuis, Hoofddorp, Netherlands
| | | | | | - Paul Fockens
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, Netherlands
| | - Marcel G W Dijkgraaf
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, Netherlands
| | - Victor E A Gerdes
- Department of Internal and Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, Netherlands; Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, Netherlands
| | - Rogier P Voermans
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, Netherlands.
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11
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Aapkes SE, de Haas RJ, Bernts LHP, Blijdorp CJ, Dekker SEI, van Gastel MDA, Meijer E, Veldman A, Drenth JPH, Gansevoort RT. Incident Gallstones During Somatostatin Analog Treatment are Associated with Acute Biliary Complications Especially After Discontinuation. Drugs R D 2021; 21:179-188. [PMID: 33779943 PMCID: PMC8206401 DOI: 10.1007/s40268-021-00342-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/10/2021] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION Gallstones are a known adverse effect of somatostatin analogs, but the exact incidence and clinical implications are unknown. OBJECTIVES The aim of this study was to investigate the incidence of gallstones on imaging and related complications in unbiased trial data. METHODS Data from the DIPAK 1 trial, in which 305 polycystic kidney disease patients were randomized to standard of care (SoC) or lanreotide for 120 weeks, were used. Magnetic resonance imaging (MRI) was performed at baseline and end of treatment and was assessed for the presence, number, and size of gallstones. For all patients who had gallstones at the end of the trial, we obtained follow-up after the trial. RESULTS Of 249 patients with data available, 11 patients randomized to lanreotide and four randomized to SoC had gallstones at baseline. During the study, new gallstones were formed in 19/124 patients using lanreotide (15%) and 1/125 patients receiving SoC (1%). The odds ratio for gallstone formation with lanreotide use was 25.9 (95% confidence interval 3.37-198.8; p < 0.001). Gallstones during lanreotide treatment were multiple (> 20 stones in 69% of patients) and small (≤ 3 mm in 63% of patients). Of the 19 patients with incident gallstones during lanreotide treatment, 9 experienced gallstone-associated complications, 8 of whom experienced gallstone-associated complications after discontinuation of treatment (median time after discontinuation 2.5 years). In patients with gallstones at baseline and in patients receiving SoC, no complications occurred. CONCLUSIONS Treatment with a somatostatin analog leads to the formation of multiple, small gallstones that are associated with severe complications, especially after discontinuation of therapy. CLINICAL TRIAL REGISTRY WEBSITE AND TRIAL NUMBER ClinicalTrials.gov ( https://clinicaltrials.gov ); NCT01616927.
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Affiliation(s)
- Sophie E Aapkes
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands
| | - Robbert J de Haas
- Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Lucas H P Bernts
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Charles J Blijdorp
- Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Sosha E I Dekker
- Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Maatje D A van Gastel
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands
| | - Esther Meijer
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands
| | - Abigail Veldman
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands
| | - Joost P H Drenth
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Ron T Gansevoort
- Department of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
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12
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Gao K, Zheng C, Han H, Guo C. A Multicenter Randomized Prospective Study of Early Cholecystectomy for Pediatric Patients with Biliary Colic. J Gastrointest Surg 2021; 25:713-719. [PMID: 32935270 DOI: 10.1007/s11605-020-04700-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 06/11/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND In patients with biliary colic, high-quality prospective data supporting the precise timing of cholecystectomy are lacking. The purpose of this study was to determine the effectiveness of early laparoscopic cholecystectomy in children with biliary colic. METHODS A multicenter, parallel-group, randomized study was conducted in patients with biliary colic at 5 hospitals in China. Pediatric patients with biliary colic were prospectively randomized to either the early cholecystectomy or conservative management strategy. The clinical outcomes within 6 months, including the number of biliary colic-free patients and gallstone-related complications, were compared (register number ChiCTR1900021830). RESULTS During the first 2 months of follow-up, 71 patients (59.2%, 71/120) receiving conservative management and 124 patients (97.6%, 124/127) in the early cholecystectomy group (p < 0.001) reported being entirely colic-free. The GIQLI measures were higher in the early cholecystectomy group than in the conservative management group (p = 0.032). Acute readmissions occurred in 7 (5.5%) of 127 patients in the early cholecystectomy group, compared with 23 (19.2%) of 120 patients in the conservative management group (risk ratio [RR] 0.25; 95% CI [0.10-0.60], p = 0.001) in the 6-month period. CONCLUSIONS Early cholecystectomy is effective in providing beneficial outcomes in terms of both short-term and long-term improvement of symptoms.
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Affiliation(s)
- Kai Gao
- Department of Pediatric General Surgery and Liver Transplantation, Children's Hospital, Chongqing Medical University, 136 Zhongshan 2nd Rd., Chongqing, 400014, People's Republic of China
| | - Chao Zheng
- Department of Orthopedics, Children's Hospital, Chongqing Medical University, Chongqing, 400014, People's Republic of China
| | - Huanli Han
- Department of Pediatric General Surgery and Liver Transplantation, Children's Hospital, Chongqing Medical University, 136 Zhongshan 2nd Rd., Chongqing, 400014, People's Republic of China.
| | - Chunbao Guo
- Department of Pediatric General Surgery and Liver Transplantation, Children's Hospital, Chongqing Medical University, 136 Zhongshan 2nd Rd., Chongqing, 400014, People's Republic of China. .,Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
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13
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Lee YJ, Park YS, Park JH. Cholecystectomy is Feasible in Children with Small-Sized or Large Numbers of Gallstones and in Those with Persistent Symptoms Despite Medical Treatment. Pediatr Gastroenterol Hepatol Nutr 2020; 23:430-438. [PMID: 32953638 PMCID: PMC7481062 DOI: 10.5223/pghn.2020.23.5.430] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 05/01/2020] [Indexed: 12/21/2022] Open
Abstract
PURPOSE We investigated the clinical features and factors affecting the choice of treatment modality and the course of pediatric gallstone (GS) disease. METHODS We retrospectively analyzed the medical records of 65 patients diagnosed with GS using imaging studies between January 2009 and December 2017 were included. RESULTS This study included 65 patients (33 boys and 32 girls; mean age, 8.5±5.3 years; range, 0.2-18 years) who primarily presented with abdominal pain (34%), jaundice (18%), and vomiting (8%). Idiopathic GS occurred in 36 patients (55.4%). The risk factors for GS included antibiotic use, obesity, hemolytic disease, and chemotherapy in 8 (12.3%), 7 (10.8%), 6 (9.2%), and 4 patients (6.2%), respectively. We observed multiple stones (including sandy stones) in 31 patients (47.7%), a single stone in 17 (26.2%), and several stones in 17 (26.2%). GS with a diameter of <5 mm occurred in 45 patients (69.2%). Comorbidities included hepatitis, choledocholithiasis, cholecystitis, and acute pancreatitis in 20 (30.8%), 11 (16.9%), 11 (16.9%), and 4 patients (6.2%), respectively. Ursodeoxycholic acid (UDCA) was administered to 54 patients (83.1%), leading to stone dissolution in 22 patients (33.8%) within 6 months. Cholecystectomy was performed in 18 patients (27.7%) (mean age, 11.9±5.1 years). Most patients treated surgically had multiple stones (83%) and stones measuring <5 mm in size (89%), and 66.7% of patients had cholesterol stones. CONCLUSION Cholecystectomy is feasible in patients with small-sized or large numbers of GS and those with persistent abdominal pain and/or jaundice. UDCA administration with close follow-up is recommended in patients with uncomplicated GS.
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Affiliation(s)
- Yeoun Joo Lee
- Department of Pediatrics, Pusan National University School of Medicine, Yangsan, Korea
| | - Yeh Seul Park
- Department of Pediatrics, Pusan National University School of Medicine, Yangsan, Korea
| | - Jae Hong Park
- Department of Pediatrics, Pusan National University School of Medicine, Yangsan, Korea
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14
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Feng X, Zhu C, Lee S, Gao J, Zhu P, Yamauchi J, Pan C, Singh S, Qu S, Miller R, Monga SP, Peng Y, Dong HH. Depletion of hepatic forkhead box O1 does not affect cholelithiasis in male and female mice. J Biol Chem 2020; 295:7003-7017. [PMID: 32273342 DOI: 10.1074/jbc.ra119.012272] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 04/07/2020] [Indexed: 11/06/2022] Open
Abstract
Cholelithiasis is one of the most prevalent gastroenterological diseases and is characterized by the formation of gallstones in the gallbladder. Both clinical and preclinical data indicate that obesity, along with comorbidity insulin resistance, is a predisposing factor for cholelithiasis. Forkhead box O1 (FoxO1) is a key transcription factor that integrates insulin signaling with hepatic metabolism and becomes deregulated in the insulin-resistant liver, contributing to dyslipidemia in obesity. To gain mechanistic insights into how insulin resistance is linked to cholelithiasis, here we determined FoxO1's role in bile acid homeostasis and its contribution to cholelithiasis. We hypothesized that hepatic FoxO1 deregulation links insulin resistance to impaired bile acid metabolism and cholelithiasis. To address this hypothesis, we used the FoxO1LoxP/LoxP-Albumin-Cre system to generate liver-specific FoxO1-knockout mice. FoxO1-knockout mice and age- and sex-matched WT littermates were fed a lithogenic diet, and bile acid metabolism and gallstone formation were assessed in these animals. We showed that FoxO1 affected bile acid homeostasis by regulating hepatic expression of key enzymes in bile acid synthesis and in biliary cholesterol and phospholipid secretion. Furthermore, FoxO1 inhibited hepatic expression of the bile acid receptor farnesoid X receptor and thereby counteracted hepatic farnesoid X receptor signaling. Nonetheless, hepatic FoxO1 depletion neither affected the onset of gallstone disease nor impacted the disease progression, as FoxO1-knockout and control mice of both sexes had similar gallstone weights and incidence rates. These results argue against the notion that FoxO1 is a link between insulin resistance and cholelithiasis.
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Affiliation(s)
- Xiaoyun Feng
- Division of Endocrinology and Diabetes, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.,Department of Endocrinology & Metabolism, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China
| | - Cuiling Zhu
- Division of Endocrinology and Diabetes, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.,Department of Endocrinology & Metabolism, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Sojin Lee
- Division of Endocrinology and Diabetes, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224
| | - Jingyang Gao
- Division of Endocrinology and Diabetes, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.,Department of Endocrinology & Metabolism, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Ping Zhu
- Division of Endocrinology and Diabetes, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.,Department of Endocrinology and Metabolism, Guangzhou Red Cross Hospital, Medical College of Jinan University, Guangzhou 510220, China
| | - Jun Yamauchi
- Division of Endocrinology and Diabetes, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224
| | - Chenglin Pan
- Division of Endocrinology and Diabetes, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.,Department of Pediatrics, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Sucha Singh
- Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.,Pittsburgh Liver Research Center, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224
| | - Shen Qu
- Department of Endocrinology & Metabolism, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Rita Miller
- Division of Endocrinology and Diabetes, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224
| | - Satdarshan P Monga
- Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.,Pittsburgh Liver Research Center, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224
| | - Yongde Peng
- Department of Endocrinology & Metabolism, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China
| | - H Henry Dong
- Division of Endocrinology and Diabetes, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224 .,Pittsburgh Liver Research Center, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224
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15
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Burdyukov M, Nechipay A. Choledocholithiasis: narrative review. DOKAZATEL'NAYA GASTROENTEROLOGIYA 2020; 9:55. [DOI: 10.17116/dokgastro2020904155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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16
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Gurusamy KS, Davidson BR. Gallstone Disease. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:342-352. [DOI: 10.1002/9781119211419.ch22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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17
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Wilkins T, Agabin E, Varghese J, Talukder A. Gallbladder Dysfunction: Cholecystitis, Choledocholithiasis, Cholangitis, and Biliary Dyskinesia. Prim Care 2017; 44:575-597. [DOI: 10.1016/j.pop.2017.07.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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18
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EASL Clinical Practice Guidelines on the prevention, diagnosis and treatment of gallstones. J Hepatol 2016; 65:146-181. [PMID: 27085810 DOI: 10.1016/j.jhep.2016.03.005] [Citation(s) in RCA: 310] [Impact Index Per Article: 34.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 03/09/2016] [Indexed: 02/06/2023]
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19
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Portincasa P, Di Ciaula A, Grattagliano I. Preventing a Mass Disease: The Case of Gallstones Disease: Role and Competence for Family Physicians. Korean J Fam Med 2016; 37:205-13. [PMID: 27468338 PMCID: PMC4961852 DOI: 10.4082/kjfm.2016.37.4.205] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 04/22/2016] [Accepted: 04/25/2016] [Indexed: 02/05/2023] Open
Abstract
Gallstone formation is the result of a complex interaction between genetic and nongenetic factors. We searched and reviewed the available literature to define how the primary prevention of gallstones (cholesterol gallstones in particular) could be applied in general practice. Electronic bibliographical databases were searched. Prospective and retrospective cohort studies and case-controlled studies were analyzed and graded for evidence quality. The epidemiological data confirmed that genetic factors are estimated to account for only approximately 25% of the overall risk of gallstones, while metabolic/environmental factors are at least partially modifiable in stone-free risk groups, and are thus modifiable by primary prevention measures related to diet, lifestyle, and environmental factors (i.e., rapid weight loss, bariatric surgery, somatostatin or analogues therapy, transient gallbladder stasis, and hormone therapy). There is no specific recommendation for the secondary prevention of recurrent gallstones. Family physicians can contribute to preventing gallstones due to their capability to identify and effectively manage several risk factors discussed in this study. Although further studies are needed to better elucidate the involvement of epigenetic factors that may regulate the effect of environment and lifestyle on gene expression in the primary prevention of gallstone formation, preventive interventions are feasible and advisable in the general practice setting.
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Affiliation(s)
- Piero Portincasa
- Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri", University of Bari Medical School, Bari, Italy
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20
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Ansaloni L, Pisano M, Coccolini F, Peitzmann AB, Fingerhut A, Catena F, Agresta F, Allegri A, Bailey I, Balogh ZJ, Bendinelli C, Biffl W, Bonavina L, Borzellino G, Brunetti F, Burlew CC, Camapanelli G, Campanile FC, Ceresoli M, Chiara O, Civil I, Coimbra R, De Moya M, Di Saverio S, Fraga GP, Gupta S, Kashuk J, Kelly MD, Koka V, Jeekel H, Latifi R, Leppaniemi A, Maier RV, Marzi I, Moore F, Piazzalunga D, Sakakushev B, Sartelli M, Scalea T, Stahel PF, Taviloglu K, Tugnoli G, Uraneus S, Velmahos GC, Wani I, Weber DG, Viale P, Sugrue M, Ivatury R, Kluger Y, Gurusamy KS, Moore EE. 2016 WSES guidelines on acute calculous cholecystitis. World J Emerg Surg 2016; 11:25. [PMID: 27307785 PMCID: PMC4908702 DOI: 10.1186/s13017-016-0082-5] [Citation(s) in RCA: 179] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Accepted: 06/02/2016] [Indexed: 12/12/2022] Open
Abstract
Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of “high risk” patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient.
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Affiliation(s)
- L Ansaloni
- General Surgery I, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy
| | - M Pisano
- General Surgery I, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy
| | - F Coccolini
- General Surgery I, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy
| | - A B Peitzmann
- Department of Surgery, UPMC, University of Pittsburgh School of Medicine, Pittsburgh, PA USA
| | - A Fingerhut
- Department of Surgical Research, Medical Univeristy of Graz, Graz, Austria
| | - F Catena
- Department of Emergency and Trauma Surgery of the University Hospital of Parma, Parma, Italy
| | - F Agresta
- Department of General Surgery, Adria Civil Hospital, Adria (RO), Italy
| | - A Allegri
- General Surgery I, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy
| | - I Bailey
- University Hospital Southampton, Southampton, UK
| | - Z J Balogh
- Department of Traumatology, John Hunter Hospital and University of Newcastle, Newcastle, NSW Australia
| | - C Bendinelli
- Department of Traumatology, John Hunter Hospital and University of Newcastle, Newcastle, NSW Australia
| | - W Biffl
- Acute Care Surgery, Queen's Medical Center, School of Medicine of the University of Hawaii, Honolulu, HI USA
| | - L Bonavina
- Department of Surgery, IRCCS Policlinico San Donato, University of Milan Medical School, Milan, Italy
| | | | - F Brunetti
- Unit of Digestive, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital AP-HP, Université Paris Est-UPEC, Créteil, France
| | - C C Burlew
- Surgical Intensive Care Unit, Department of Surgery, Denver Health Medical Center, University of Colorado School of Medicine, Denver, USA
| | - G Camapanelli
- General Surgery - Day Surgery Istituto Clinico Sant'Ambrogio, Insubria University, Milan, Italy
| | - F C Campanile
- Ospedale San Giovanni Decollato - Andosilla, Civita Castellana, Italy
| | - M Ceresoli
- General Surgery I, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy
| | - O Chiara
- Emergency Department, Trauma Center, Niguarda Hospital, Milan, Italy
| | - I Civil
- Department of Surgery, Auckland City Hospital, Auckland, New Zealand
| | - R Coimbra
- Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, University of California San Diego Health Sciences, San Diego, CA USA
| | - M De Moya
- Harvard University, Cambridge, MA USA
| | - S Di Saverio
- General, Emergency and Trauma Surgery, Maggiore Hospital Trauma Center, Bologna, Italy
| | - G P Fraga
- Division of Trauma Surgery, University of Campinas, Campinas, SP Brazil
| | - S Gupta
- Department of Surgery, Government Medical College, Chandigarh, India
| | - J Kashuk
- Tel Aviv University Sackler School of Medicine, Assia Medical Group, Tel Aviv, Israel
| | - M D Kelly
- Acute Surgical Unit, Canberra Hospital, Canberra, ACT Australia
| | - V Koka
- Surgical Department, Mozyr City Hospital, Mozyr, Belarus
| | - H Jeekel
- Erasmus MC Rotterdam, Rotterdam, Holland Netherlands
| | - R Latifi
- University of Arizona, Tucson, AZ USA
| | | | - R V Maier
- Department of Surgery, Harborview Medical Center, Seattle, WA USA
| | - I Marzi
- Department of Trauma, Hand, and Reconstructive Surgery, University Hospital, Goethe-University Frankfurt, Frankfurt, Germany
| | - F Moore
- Department of Surgery, University of Florida, Gainesville, FL USA
| | - D Piazzalunga
- General Surgery I, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy
| | - B Sakakushev
- First General Surgery Clinic, University Hospital St. George/Medical University, Plovdiv, Bulgaria
| | - M Sartelli
- Department of Surgery, Macerata Hospital, Macerata, Italy
| | - T Scalea
- Shock Trauma Center, Critical Care Services, University of Maryland School of Medicine, Baltimore, MD USA
| | - P F Stahel
- Denver Health Medical Center, Denver, CO USA
| | - K Taviloglu
- Taviloglu Proctology Center, Istanbul, Turkey
| | - G Tugnoli
- General, Emergency and Trauma Surgery, Maggiore Hospital Trauma Center, Bologna, Italy
| | - S Uraneus
- Department of Surgery, Medical University of Graz, Graz, Austria
| | - G C Velmahos
- Emergency Surgery, and Surgical Critical Care, Massachusetts General Hospital, Boston, MA USA
| | - I Wani
- DHS, Srinagar, Kashmir India
| | - D G Weber
- Trauma and General Surgery & The University of Western Australia, Royal Perth Hospital, Perth, Australia
| | - P Viale
- Infectious Disease Unit, Teaching Hospital, S. Orsola-Malpighi Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - M Sugrue
- Letterkenny University Hospital & Donegal Clinical Research Academy, Donegal, Ireland
| | - R Ivatury
- Virginia Commonwealth University, Richmond, VA USA
| | - Y Kluger
- Division of General Surgery, Rambam Health Care Campus, Haifa, Israel
| | - K S Gurusamy
- Royal Free Campus, University College London, London, UK
| | - E E Moore
- Taviloglu Proctology Center, Istanbul, Turkey
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21
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Lammert F, Gurusamy K, Ko CW, Miquel JF, Méndez-Sánchez N, Portincasa P, van Erpecum KJ, van Laarhoven CJ, Wang DQH. Gallstones. Nat Rev Dis Primers 2016; 2:16024. [PMID: 27121416 DOI: 10.1038/nrdp.2016.24] [Citation(s) in RCA: 441] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Gallstones grow inside the gallbladder or biliary tract. These stones can be asymptomatic or symptomatic; only gallstones with symptoms or complications are defined as gallstone disease. Based on their composition, gallstones are classified into cholesterol gallstones, which represent the predominant entity, and bilirubin ('pigment') stones. Black pigment stones can be caused by chronic haemolysis; brown pigment stones typically develop in obstructed and infected bile ducts. For treatment, localization of the gallstones in the biliary tract is more relevant than composition. Overall, up to 20% of adults develop gallstones and >20% of those develop symptoms or complications. Risk factors for gallstones are female sex, age, pregnancy, physical inactivity, obesity and overnutrition. Factors involved in metabolic syndrome increase the risk of developing gallstones and form the basis of primary prevention by lifestyle changes. Common mutations in the hepatic cholesterol transporter ABCG8 confer most of the genetic risk of developing gallstones, which accounts for ∼25% of the total risk. Diagnosis is mainly based on clinical symptoms, abdominal ultrasonography and liver biochemistry tests. Symptoms often precede the onset of the three common and potentially life-threatening complications of gallstones (acute cholecystitis, acute cholangitis and biliary pancreatitis). Although our knowledge on the genetics and pathophysiology of gallstones has expanded recently, current treatment algorithms remain predominantly invasive and are based on surgery. Hence, our future efforts should focus on novel preventive strategies to overcome the onset of gallstones in at-risk patients in particular, but also in the population in general.
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Affiliation(s)
- Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Saarland University, Kirrberger Str. 100, 66424 Hamburg, Germany
| | - Kurinchi Gurusamy
- Royal Free Campus, University College London Medical School, 9th Floor, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK
| | - Cynthia W Ko
- Department of Medicine, Division of Gastroenterology, University of Washington, Seattle, Washington, USA
| | - Juan-Francisco Miquel
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Piero Portincasa
- Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri", University of Bari Medical School, Bari, Italy
| | - Karel J van Erpecum
- Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, The Netherlands
| | - Cees J van Laarhoven
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - David Q-H Wang
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Saint Louis, Missouri, USA
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Portincasa P, Di Ciaula A, de Bari O, Garruti G, Palmieri VO, Wang DQH. Management of gallstones and its related complications. Expert Rev Gastroenterol Hepatol 2016; 10:93-112. [PMID: 26560258 DOI: 10.1586/17474124.2016.1109445] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The majority of gallstone patients remain asymptomatic; however, interest toward the gallstone disease is continuing because of the high worldwide prevalence and management costs and the development of gallstone symptoms and complications. For cholesterol gallstone disease, moreover, a strong link exists between this disease and highly prevalent metabolic disorders such as obesity, dyslipidemia, type 2 diabetes, hyperinsulinemia, hypertriglyceridemia and the metabolic syndrome. Information on the natural history as well as the diagnostic, surgical (mainly laparoscopic cholecystectomy) and medical tools available to facilitate adequate management of cholelithiasis and its complications are, therefore, crucial to prevent the negative outcomes of gallstone disease. Moreover, some risk factors for gallstone disease are modifiable and some preventive strategies have become necessary to reduce the onset and the severity of complications.
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Affiliation(s)
- P Portincasa
- a Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri" , University of Bari Medical School , Bari , Italy
| | - A Di Ciaula
- b Division of Internal Medicine , Hospital of Bisceglie , Bisceglie , Italy
| | - O de Bari
- a Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri" , University of Bari Medical School , Bari , Italy
- d Department of Internal Medicine, Division of Gastroenterology and Hepatology , Saint Louis University School of Medicine , St. Louis , MO , USA
| | - G Garruti
- c Department of Emergency and Organ Transplants, Section of Endocrinology, Andrology and Metabolic Diseases , University of Bari Medical School , Bari , Italy
| | - V O Palmieri
- a Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri" , University of Bari Medical School , Bari , Italy
| | - D Q-H Wang
- d Department of Internal Medicine, Division of Gastroenterology and Hepatology , Saint Louis University School of Medicine , St. Louis , MO , USA
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Cho SM, Park JA, Kim NH, Kim DS, Zhang D, Yi H, Cho HJ, Kim JK, Lee DK, Kim JS, Shin HC. Effect of eicosapentaenoic acid on cholesterol gallstone formation in C57BL/6J mice. Mol Med Rep 2014; 11:362-6. [PMID: 25333303 DOI: 10.3892/mmr.2014.2687] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2013] [Accepted: 05/19/2014] [Indexed: 11/05/2022] Open
Abstract
The present study investigated the preventive effect of ω-3 fatty acids against cholesterol gallstone (CG) formation. CG formation was induced in C57BL/6J mice using a lithogenic diet (LD). The mice were divided into four treatment groups: i) LD, ii) LD plus eicosapentaenoic acid (EPA), iii) LD plus docosahexaenoic acid (DHA) and iv) LD plus EPA plus DHA. Subsequent to feeding the mice the LD for four weeks, EPA and/or DHA (70 mg/kg/day) were orally administered for eight weeks. The mice in the EPA treatment groups exhibited significantly less gallstone formation than those in the LD group. By contrast, DHA treatment only slightly suppressed gallstone formation. The expression of mucin 2, 5AC, 5B and 6 was significantly decreased in the gallbladders of mice in the EPA groups (70-90%) and the LD plus DHA group (30-50%), compared with that in the mice in the LD group. In addition, the mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase was significantly decreased in the livers of mice in the EPA treatment group compared with that in the livers of mice in the LD group. In conclusion, EPA was found to have a dominant anti-lithogenic effect in C57BL/6J mice.
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Affiliation(s)
- Soo-Min Cho
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143‑701, Republic of Korea
| | - Jin-A Park
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143‑701, Republic of Korea
| | - Na-Hyun Kim
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143‑701, Republic of Korea
| | - Dong-Soon Kim
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143‑701, Republic of Korea
| | - Dan Zhang
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143‑701, Republic of Korea
| | - Hee Yi
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143‑701, Republic of Korea
| | - Hee-Jung Cho
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143‑701, Republic of Korea
| | - Ja Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120‑752, Republic of Korea
| | - Dong Ki Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120‑752, Republic of Korea
| | - Jin-Suk Kim
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143‑701, Republic of Korea
| | - Ho-Chul Shin
- Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143‑701, Republic of Korea
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Guarino MPL, Cocca S, Altomare A, Emerenziani S, Cicala M. Ursodeoxycholic acid therapy in gallbladder disease, a story not yet completed. World J Gastroenterol 2013; 19:5029-5034. [PMID: 23964136 PMCID: PMC3746374 DOI: 10.3748/wjg.v19.i31.5029] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2013] [Revised: 07/12/2013] [Accepted: 07/19/2013] [Indexed: 02/06/2023] Open
Abstract
Gallstone disease represents an important issue in the healthcare system. The principal non-invasive non-surgical medical treatment for cholesterol gallstones is still represented by oral litholysis with bile acids. The first successful and documented dissolution of cholesterol gallstones was achieved in 1972. Since then a large number of investigators all over the world, have been dedicated in biochemical and clinical studies on ursodeoxycholic acid (UDCA), demonstrating its extreme versatility. This editorial is aimed to provide a brief review of recent developments in UDCA use, current indications for its use and, the more recent advances in understanding its effects in terms of an anti-inflammatory drug.
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Döring B, Lütteke T, Geyer J, Petzinger E. The SLC10 carrier family: transport functions and molecular structure. CURRENT TOPICS IN MEMBRANES 2013. [PMID: 23177985 DOI: 10.1016/b978-0-12-394316-3.00004-1] [Citation(s) in RCA: 95] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The SLC10 family represents seven genes containing 1-12 exons that encode proteins in humans with sequence lengths of 348-477 amino acids. Although termed solute carriers (SLCs), only three out of seven (i.e. SLC10A1, SLC10A2, and SLC10A6) show sodium-dependent uptake of organic substrates across the cell membrane. These include the uptake of bile salts, sulfated steroids, sulfated thyroidal hormones, and certain statin drugs by SLC10A1 (Na(+)-taurocholate cotransporting polypeptide (NTCP)), the uptake of bile salts by SLC10A2 (apical sodium-dependent bile acid transporter (ASBT)), and uptake of sulfated steroids and sulfated taurolithocholate by SLC10A6 (sodium-dependent organic anion transporter (SOAT)). The other members of the family are orphan carriers not all localized in the cell membrane. The name "bile acid transporter family" arose because the first two SLC10 members (NTCP and ASBT) are carriers for bile salts that establish their enterohepatic circulation. In recent years, information has been obtained on their 2D and 3D membrane topology, structure-transport relationships, and on the ligand and sodium-binding sites. For SLC10A2, the putative 3D morphology was deduced from the crystal structure of a bacterial SLC10A2 analog, ASBT(NM). This information was used in this chapter to calculate the putative 3D structure of NTCP. This review provides first an introduction to recent knowledge about bile acid synthesis and newly found bile acid hormonal functions, and then describes step-by-step each individual member of the family in terms of expression, localization, substrate pattern, as well as protein topology with emphasis on the three functional SLC10 carrier members.
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Affiliation(s)
- Barbara Döring
- SLC10 family research group, Institute of Pharmacology and Toxicology, Justus Liebig University Giessen, Biomedical Research Center (BFS), Giessen, Germany
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Bouwense SA, Besselink MG, van Brunschot S, Bakker OJ, van Santvoort HC, Schepers NJ, Boermeester MA, Bollen TL, Bosscha K, Brink MA, Bruno MJ, Consten EC, Dejong CH, van Duijvendijk P, van Eijck CH, Gerritsen JJ, van Goor H, Heisterkamp J, de Hingh IH, Kruyt PM, Molenaar IQ, Nieuwenhuijs VB, Rosman C, Schaapherder AF, Scheepers JJ, Spanier MBW, Timmer R, Weusten BL, Witteman BJ, van Ramshorst B, Gooszen HG, Boerma D. Pancreatitis of biliary origin, optimal timing of cholecystectomy (PONCHO trial): study protocol for a randomized controlled trial. Trials 2012. [PMID: 23181667 PMCID: PMC3517749 DOI: 10.1186/1745-6215-13-225] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Background After an initial attack of biliary pancreatitis, cholecystectomy minimizes the risk of recurrent biliary pancreatitis and other gallstone-related complications. Guidelines advocate performing cholecystectomy within 2 to 4 weeks after discharge for mild biliary pancreatitis. During this waiting period, the patient is at risk of recurrent biliary events. In current clinical practice, surgeons usually postpone cholecystectomy for 6 weeks due to a perceived risk of a more difficult dissection in the early days following pancreatitis and for logistical reasons. We hypothesize that early laparoscopic cholecystectomy minimizes the risk of recurrent biliary pancreatitis or other complications of gallstone disease in patients with mild biliary pancreatitis without increasing the difficulty of dissection and the surgical complication rate compared with interval laparoscopic cholecystectomy. Methods/Design PONCHO is a randomized controlled, parallel-group, assessor-blinded, superiority multicenter trial. Patients are randomly allocated to undergo early laparoscopic cholecystectomy, within 72 hours after randomization, or interval laparoscopic cholecystectomy, 25 to 30 days after randomization. During a 30-month period, 266 patients will be enrolled from 18 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite endpoint of mortality and acute re-admissions for biliary events (that is, recurrent biliary pancreatitis, acute cholecystitis, symptomatic/obstructive choledocholithiasis requiring endoscopic retrograde cholangiopancreaticography including cholangitis (with/without endoscopic sphincterotomy), and uncomplicated biliary colics) occurring within 6 months following randomization. Secondary endpoints include the individual endpoints of the composite endpoint, surgical and other complications, technical difficulty of cholecystectomy and costs. Discussion The PONCHO trial is designed to show that early laparoscopic cholecystectomy (within 72 hours) reduces the combined endpoint of mortality and re-admissions for biliary events as compared with interval laparoscopic cholecystectomy (between 25 and 30 days) after recovery of a first episode of mild biliary pancreatitis. Trial registration Current Controlled Trials: ISRCTN72764151
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Affiliation(s)
- Stefan A Bouwense
- Department of OR/Evidence Based Surgery, Radboud University Nijmegen Medical Centre, HP 690, PO 9101, Nijmegen HB 6500, the Netherlands
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Portincasa P, Ciaula AD, Bonfrate L, Wang DQ. Therapy of gallstone disease: What it was, what it is, what it will be. World J Gastrointest Pharmacol Ther 2012; 3:7-20. [PMID: 22577615 PMCID: PMC3348960 DOI: 10.4292/wjgpt.v3.i2.7] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2011] [Revised: 09/21/2011] [Accepted: 09/28/2011] [Indexed: 02/06/2023] Open
Abstract
Cholesterol gallstone disease is a common clinical condition influenced by genetic factors, increasing age, female gender, and metabolic factors. Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones, new perspectives regarding medical therapy of cholelithiasis are currently under discussion, also taking into account the pathogenesis of gallstones, the natural history of the disease and the analysis of the overall costs of therapy. A careful selection of patients may lead to successful non-surgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones. The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations, suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe), or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis, might be proposed as additional approaches for treating cholesterol gallstones. In this review we discuss old, recent and future perspectives on medical treatment of cholesterol cholelithiasis.
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Affiliation(s)
- Piero Portincasa
- Piero Portincasa, Leonilde Bonfrate, Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri", University of Bari Medical School, Piazza Giulio Cesare 11, Policlinico, 70124 Bari, Italy
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Veedfald S, Penninga L, Wettergren A, Gluud C. Bile acids for biliary colic. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2011. [DOI: 10.1002/14651858.cd009253] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Affiliation(s)
- Simon Veedfald
- Rigshospitalet, Copenhagen University Hospital; Department of Surgery and Transplantation C2122; Blegdamsvej 9 Copenhagen Denmark DK-2100
| | - Luit Penninga
- Rigshospitalet, Copenhagen University Hospital; Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344,; Blegdamsvej 9 Copenhagen Denmark DK-2100
| | - Andre Wettergren
- Rigshospitalet, Copenhagen University Hospital; Department of Surgery and Transplantation C2122; Blegdamsvej 9 Copenhagen Denmark DK-2100
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital; Cochrane Hepato-Biliary Group; Blegdamsvej 9 Copenhagen Denmark DK-2100
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Abstract
Most asymptomatic gallstone carriers require no therapy. Laparoscopic cholecystectomy is the best definitive therapy for symptomatic gallstone disease. Selective laparoscopic cholecystectomy can provide secondary prevention of symptoms and complications in certain instances (in a complex clinical setting such as sickle cell disease or to prevent gallbladder carcinoma from developing in those at risk with large gallstones or with a calcified gallbladder). Primary prevention is unproven but focuses on early identification and risk alteration to decrease the possibility of developing gallstones. Ursodeoxycholic acid has a limited role for stone dissolution but can prevent stone development in severe obesity during rapid weight reduction with diet or after bariatric surgery. Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy represents the therapeutic cornerstone for managing severe pancreatitis and cholangitis.
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Wittenburg H. Hereditary liver disease: gallstones. Best Pract Res Clin Gastroenterol 2010; 24:747-56. [PMID: 20955975 DOI: 10.1016/j.bpg.2010.07.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2010] [Revised: 07/14/2010] [Accepted: 07/16/2010] [Indexed: 01/31/2023]
Abstract
Gallstones are common in Western countries and due to pain and complications pose a substantial burden on health care systems. In general, cholesterol gallstones are distinguished from bilirubin gallstones. Bilirubin gallstones form if the ion product of unconjugated bilirubin and calcium in gallbladder bile exceeds the solubilisation capacities of mixed micelles and vesicles. Cholesterol gallstones develop if the amount of cholesterol in gallbladder bile exceeds the maximum concentration that is soluble at the given concentration of bile salts and phospholipids. In addition, cholesterol gallstone formation requires hypomotility of the gallbladder and a mucin gel as nucleation matrix for monohydrate crystals. The individual risk of gallstone formation is determined by interactions of lithogenic alleles of gallstone susceptibility genes and multiple environmental factors. For asymptomatic gallstones, expectant management is recommended, whereas an episode of gallstone-associated pain substantially increases the risk of complications such as cholecystitis, cholangitis and pancreatitis and therefore necessitates cholecystectomy.
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Affiliation(s)
- Henning Wittenburg
- University of Leipzig, Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, Liebigstr. 20, 04103 Leipzig, Germany.
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Ali S, Ali H. Treating Abdominal Pain in Children: What Do We Know? CLINICAL PEDIATRIC EMERGENCY MEDICINE 2010. [DOI: 10.1016/j.cpem.2010.06.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Di Ciaula A, Wang DQH, Wang HH, Bonfrate L, Portincasa P. Targets for current pharmacologic therapy in cholesterol gallstone disease. Gastroenterol Clin North Am 2010; 39:245-64, viii-ix. [PMID: 20478485 PMCID: PMC2915454 DOI: 10.1016/j.gtc.2010.02.005] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gallstone disease is a frequent condition throughout the world and, cholesterol stones are the most frequent form in Western countries. The standard treatment of symptomatic gallstone subjects is laparoscopic cholecystectomy. The selection of patients amenable for nonsurgical, medical therapy is of key importance; a careful analysis should consider the natural history of the disease and the overall costs of therapy. Only patients with mild symptoms and small, uncalcified cholesterol gallstones in a functioning gallbladder with a patent cystic duct are considered for oral litholysis by hydrophilic ursodeoxycholic acid, in the hope of achieving cholesterol desaturation of bile and progressive stone dissolution. Recent studies have raised the possibility that cholesterol-lowering agents that inhibit hepatic cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe), or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis, may offer, alone or in combination, additional medical therapeutic tools for treating cholesterol gallstones. Recent perspectives on medical treatment of cholesterol gallstone disease are discussed in this article.
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Affiliation(s)
- Agostino Di Ciaula
- Division of Internal Medicine, Hospital of Bisceglie, via Bovio 279 - 70052 - Bisceglie (Bari), Italy, +39-80-3363271, +39-80-3363232 (fax)
| | - David Q.-H. Wang
- Liver Center and Gastroenterology Division, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School and Harvard Digestive Diseases Center, 330 Brookline Avenue, DA 601, Boston, MA 02215, (617) 667-0561, (617) 975-5071 (fax)
| | - Helen H. Wang
- Department of Medicine, Liver Center and Gastroenterology Division, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, DA 601, Boston, MA 02215, (617) 667-5156, (617) 975-5071 (fax)
| | - Leonilde Bonfrate
- Clinica Medica “A. Murri”, Department of Internal and Public Medicine, University of Bari Medical School, Piazza Giulio Cesare 11, Policlinico, 70124 Bari, Italy. +39-80-5478227, +39-80-5478232 (fax)
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Internal Medicine and Public Medicine, University Medical School, Bari, Italy
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Is complicated gallstone disease preceded by biliary colic? J Gastrointest Surg 2009; 13:312-7. [PMID: 18949524 PMCID: PMC2719723 DOI: 10.1007/s11605-008-0729-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2008] [Accepted: 10/06/2008] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Cholecystectomy in cases of "warning" episodes of biliary colic may prevent biliary pancreatitis. We aimed to determine which proportion of patients with biliary pancreatitis, compared to other complicated and uncomplicated symptomatic gallstone disease, experienced "warning" episodes of colic and why these episodes did not lead to early cholecystectomy. PATIENTS AND METHODS One hundred seventy-five patients with complicated gallstone disease [pancreatitis (n = 53), symptomatic common bile duct (CBD) stones (n = 64), and acute cholecystitis (n = 58)] and 175 patients with symptomatic uncomplicated gallstones were interviewed at admission. RESULTS Fifty-seven percent (100 of 175) of patients with complicated disease (95% confidence interval = 50-65%) experienced "warning" episodes of biliary colic (pancreatitis 58%, CBD stones 67%, cholecystitis 45%) vs 96% (164 of 175) in uncomplicated disease. Eighty-seven percent of patients with "warning" episodes and complicated disease experienced patient's and general practitioner's delays. General practitioner's delay was more frequent if pain was located in the epigastric region compared to the right upper quadrant (51% vs 38%, P = 0.03). CONCLUSIONS Half of patients with biliary pancreatitis experience "warning" episodes of biliary colic, similar to other gallstone complications. In symptomatic patients, complications are often not prevented because of significant delays in diagnosis and treatment.
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Koppisetti S, Jenigiri B, Terron MP, Tengattini S, Tamura H, Flores LJ, Tan DX, Reiter RJ. Reactive oxygen species and the hypomotility of the gall bladder as targets for the treatment of gallstones with melatonin: a review. Dig Dis Sci 2008; 53:2592-603. [PMID: 18338264 DOI: 10.1007/s10620-007-0195-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2007] [Accepted: 12/21/2007] [Indexed: 12/17/2022]
Abstract
Free radical-mediated damage of the gall bladder epithelium predisposes to the development of both gall bladder inflammation and gallstone formation, which often coexist. Melatonin, a pineal and gut secretory product, due to its antioxidant activity along with its effect on the aging gall bladder myocytes, inhibits gallstone formation. Melatonin reduces the biliary levels of cholesterol by inhibiting cholesterol absorption across the intestinal epithelium and by increasing the conversion of cholesterol to bile acids. The incidence of gallstones is increasing and is expected to rise dramatically with the increase in the longevity and the risk factors such as obesity. The change in the prevalence of cholelithiasis is associated with a proportionate rise in the incidence of cholangiocarcinoma. In an attempt to improve the quality of life of the rapidly increasing aging population, this article reviews up-to-date information on the pathophysiology of the gall bladder function and discusses the development of new therapies with potential good patient compliance and lower cost than the current treatments.
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Affiliation(s)
- Sreedevi Koppisetti
- Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
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Jüngst C, Sreejayan N, Zündt B, Müller I, Spelsberg FW, Hüttl TP, Kullak-Ublick GA, del Pozo R, Jüngst D, von Ritter C. Ursodeoxycholic acid reduces lipid peroxidation and mucin secretagogue activity in gallbladder bile of patients with cholesterol gallstones. Eur J Clin Invest 2008; 38:634-9. [PMID: 18837739 DOI: 10.1111/j.1365-2362.2008.01995.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Recently it has been postulated that gallbladder mucin hypersecretion observed in the pathogenesis of cholesterol gallstone disease may be induced by biliary lipid peroxidation. Ursodeoxycholic acid treatment reduces mucin concentration and the formation of cholesterol crystals in the gallbladder bile of patients with cholesterol gallstones and this effect might be mediated by a decrease of biliary lipid peroxidation. MATERIAL AND METHODS In a double-blind, placebo-controlled trial patients with symptomatic cholesterol gallstones received either ursodeoxycholic acid (750 mg daily) (n = 10) or placebo (n = 12) 10-12 days prior to cholecystectomy. As a marker for lipid peroxidation malondialdehyde was measured in bile together with mucin concentration. In addition, the mucin secretagogue activity of the individual bile samples was assessed in cultured dog gallbladder epithelial cells. RESULTS Ursodeoxycholic acid therapy resulted in a significant reduction of lipid peroxidation in bile as determined by the biliary malondialdehyde concentration (1.36 +/- 0.28 vs. 2.05 +/- 0.38 micromol L(-1); P < 0.005) and the malondialdehyde (micromol L(-1))/total bile acid (mmol L(-1)) ratio (0.02 +/- 0.005 vs. 0.06 +/- 0.01; P < 0.001). Furthermore, a decrease in mucin concentrations (0.7 +/- 0.3 vs. 1.3 +/- 0.5 mg mL(-1); P < 0.005) and of the mucin secretagogue activity of gallbladder bile (0.9 +/- 0.2 vs. 2.2 +/- 0.3 times control; P < 0.001) was observed. CONCLUSIONS The reduction of lipid peroxidation and mucin secretagogue activity of gallbladder bile induced by ursodeoxycholic acid treatment may contribute to the beneficial effects of this drug on gallbladder bile composition and symptoms in cholesterol gallstone patients.
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Affiliation(s)
- C Jüngst
- Division of Clinical Pharmacology and Toxicology, University Hospital, Zurich, Switzerland
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37
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Attasaranya S, Fogel EL, Lehman GA. Choledocholithiasis, ascending cholangitis, and gallstone pancreatitis. Med Clin North Am 2008; 92:925-60, x. [PMID: 18570948 DOI: 10.1016/j.mcna.2008.03.001] [Citation(s) in RCA: 112] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Gallstone disease is encountered commonly in clinical practice. The diagnosis of biliary stones has become less problematic with current, less-invasive imaging methods. The relatively invasive endoscopic techniques should be reserved for therapy and not used for diagnosis. Acute cholangitis and gallstone pancreatitis are two major complications that require prompt recognition and timely intervention to limit morbidity and prevent mortality or recurrence. Appropriate noninvasive diagnostic studies, adequate monitoring/supportive care, and proper patient selection for invasive therapeutic procedures are elements of good clinical practice.
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Affiliation(s)
- Siriboon Attasaranya
- Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University Medical Center, 550 N. University Boulevard, UH 4100, Indianapolis, IN 46202, USA
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38
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Abstract
The number of gallstone patients is increasing in ageing populations with a high prevalence of metabolic syndrome and obesity. Recently variants of hepatic ATP binding cassette transporters have been identified as genetic susceptibility factors for gallstone disease, pointing to novel means for risk assessment and prevention. Although laparoscopic cholecystectomy is the mainstay of therapy for symptomatic gallbladder stones, the clinical management of gallstone disease is changing rapidly, with an increase in day case surgery and the advent of transluminal endoscopic surgery. Here, we summarize the molecular and genetic mechanisms of gallstone formation as well as the current evidence-based algorithms for diagnosis and therapy of gallbladder and bile duct stones.
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Affiliation(s)
- Frank Lammert
- Department Internal Medicine II, Saarland University Hospital, Saarland University, Kirrberger Str., 66421 Hamburg/Saar, Germany.
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39
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Portincasa P, Di Ciaula A, Wang HH, Palasciano G, van Erpecum KJ, Moschetta A, Wang DQH. Coordinate regulation of gallbladder motor function in the gut-liver axis. Hepatology 2008; 47:2112-26. [PMID: 18506897 DOI: 10.1002/hep.22204] [Citation(s) in RCA: 91] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Gallstones are one of the most common digestive diseases with an estimated prevalence of 10%-15% in adults living in the western world, where cholesterol-enriched gallstones represent 75%-80% of all gallstones. In cholesterol gallstone disease, the gallbladder becomes the target organ of a complex metabolic disease. Indeed, a fine coordinated hepatobiliary and gastrointestinal function, including gallbladder motility in the fasting and postprandial state, is of crucial importance to prevent crystallization and precipitation of excess cholesterol in gallbladder bile. Also, gallbladder itself plays a physiopathological role in biliary lipid absorption. Here, we present a comprehensive view on the regulation of gallbladder motor function by focusing on recent discoveries in animal and human studies, and we discuss the role of the gallbladder in the pathogenesis of gallstone formation.
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Affiliation(s)
- Piero Portincasa
- Department of Internal Medicine and Public Medicine, Clinica Medica A. Murri, University of Bari Medical School, Bari, Italy.
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40
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Pernas Gómez P, Gómez López L, Moreno Hernando J. Eliminación espontánea de un cálculo biliar en un lactante. An Pediatr (Barc) 2008; 68:73-5. [DOI: 10.1157/13114478] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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41
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Abstract
Ursodeoxycholic acid (UDCA) is used in the treatment of cholestatic liver diseases, gallstone dissolution, and for patients with hepatitis C virus infection to ameliorate elevated alanine aminotransferase levels. The efficacy of UDCA treatment has been debated and the mechanisms of action in humans have still not defined. Suggested mechanisms include the improvement of bile acid transport and/or detoxification, cytoprotection, and anti-apoptotic effects. In this review, we summarize the proposed molecular mechanisms for the action of UDCA, especially in hepatocytes, and also discuss the putative future clinical usage of this unique drug.
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Affiliation(s)
- Tadashi Ikegami
- Division of Gastroenterology and Hepatology, Tokyo Medical University, Kasumigaura Hospital, Ibaraki, Japan
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42
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Affiliation(s)
- Grant Sanders
- Department of Upper Gastrointestinal Surgery, Derriford Hospital, Plymouth.
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43
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Colecchia A, Festi D. Biliary symptoms, gallbladder motility, and cholecystectomy. Hepatology 2007; 45:259-60. [PMID: 17187423 DOI: 10.1002/hep.21454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
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44
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Abstract
With a prevalence of 10-15% in adults in Europe and the USA, gallstones are the most common digestive disease needing admission to hospital in the West. The interplay between interprandial and postprandial physiological responses to endogenous and dietary lipids underscores the importance of coordinated hepatobiliary and gastrointestinal functions to prevent crystallisation and precipitation of excess biliary cholesterol. Indeed, identifying the metabolic and transcriptional pathways that drive the regulation of biliary lipid secretion has been a major achievement in the field. We highlight scientific advances in protein and gene regulation of cholesterol absorption, synthesis, and catabolism, and biliary lipid secretion with respect to the pathogenesis of cholesterol gallstone disease. We discuss the physical-chemical mechanisms of gallstone formation in bile and the active role of the gallbladder and the intestine. We also discuss gaps in our knowledge of the pathogenesis of gallstone formation and the potential for gene targeting in therapy.
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Affiliation(s)
- Piero Portincasa
- Department of Internal and Public Medicine, University Medical School, Bari, Italy.
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45
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Abstract
Several risk factors for cholesterol gallstone formation in the general population have been identified. There is a strongly increased risk of gallstone disease during prolonged fasting, rapid weight loss, total parenteral nutrition, and somatostatin(-analogue) treatment. The annual risk of biliary colic and gallstone complications in asymptomatic gallstone carriers has been investigated sparsely. In asymptomatic and symptomatic gallstone carriers, treatment with the hydrophilic bile salt ursodeoxycholic acid (UDCA) has been claimed to reduce the risk of biliary colic and gallstone complications such as acute cholecystitis and acute pancreatitis. Also, prophylactic cholecystectomy could be beneficial in certain subgroups of asymptomatic gallstone carriers. However, randomized, double-blind, placebo-controlled trials are lacking. In this review, strategies for the prevention of gallstone formation in the general population and in high-risk conditions are dealt with. Also, strategies for the prevention of biliary colic and gallstone complications in asymptomatic and symptomatic gallstone carriers are discussed.
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Affiliation(s)
- Niels G Venneman
- Gastrointestinal Research Unit, Department of Gastroenterology, University Medical Center Utrecht, The Netherlands.
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