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Ponz de Leon Pisani R, Altieri G, Stasio RC, Lazzano P, Reni M, Falconi M, Vanella G, Arcidiacono PG, Capurso G. Gastrointestinal symptoms in the journey of pancreatic cancer patients. Expert Rev Anticancer Ther 2025. [PMID: 40489240 DOI: 10.1080/14737140.2025.2517888] [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: 04/08/2025] [Revised: 06/04/2025] [Accepted: 06/05/2025] [Indexed: 06/11/2025]
Abstract
INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy frequently arising with nonspecific and overlooked gastrointestinal symptoms. Gastroenterologists are typically the first specialists to encounter these patients, positioning them to play a pivotal role not only in early diagnosis, but also in the ongoing management of the disease's complex symptom burden. AREAS COVERED This review explored gastrointestinal symptoms in patients with PDAC (ranging from pain and diarrhea to anorexia, jaundice, and nausea) and outlined both tumor- and treatment-related causes. A literature review based on non-systematic PubMed search updated to April 2025 was conducted to summarize current diagnostic strategies, medical, endoscopic therapies, and multidisciplinary management approaches. In addition, we present original data from a single-center cohort, suggesting that the involvement of gastroenterologists leads to more comprehensive management of gastrointestinal symptom control and supportive care. EXPERT OPINION Collaboration among specialists is essential for optimizing patient outcomes in the multidisciplinary management of PDAC. Gastroenterologists' 'stewardship' significantly contributes to prompt diagnosis, symptom control, quality of life preservation, and prognosis. Future priorities should focus on strengthening integration within care pathways, fostering interdisciplinary coordination, and implementing shared clinical tools to enhance comprehensive patient care. A well-structured team-based approach is key to advancing holistic PDAC management.
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Affiliation(s)
- Ruggero Ponz de Leon Pisani
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gabriele Altieri
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Rosa Claudia Stasio
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Pilar Lazzano
- Gastroenterology and Hepatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Michele Reni
- Oncology Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- "Vita-Salute" San Raffaele University, Milan, Italy
| | - Massimo Falconi
- "Vita-Salute" San Raffaele University, Milan, Italy
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giuseppe Vanella
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- "Vita-Salute" San Raffaele University, Milan, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- "Vita-Salute" San Raffaele University, Milan, Italy
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Mendoza-Domínguez G, Garrido-Santos ZM, Lau C, Balbuena R, Santana-Vargas AD, Schmulson-Wasserman M. Real-world experience with the diagnosis of bile acid malabsorption (BAM) using serum 7-alpha-C4 and 48-hour stool bile acids. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2025:S2255-534X(25)00039-8. [PMID: 40383704 DOI: 10.1016/j.rgmxen.2025.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Revised: 08/10/2024] [Accepted: 08/12/2024] [Indexed: 05/20/2025]
Abstract
INTRODUCTION AND AIMS Bile acid malabsorption (BAM) is responsible for 30% of cases of diarrhea-predominant irritable bowel syndrome (IBS-D) or functional diarrhea and 63.5% of cases of diarrhea following cholecystectomy. 75SeHCAT is the gold standard diagnostic method but is unavailable in Mexico. Alternatively, primary bile acid (PBA) and total bile acid (TBA) determination in 48 h stools and 7αC4 measurement have been proposed as screening tests. OBJECTIVE Our aim was to evaluate the experience with PBAs and/or TBAs and to determine whether 7αC4 is a good screening biomarker for BAM in clinical practice. MATERIAL AND METHODS An ambispective study of patients with chronic diarrhea was conducted. BAM was considered present with 7αC4 > 55 ng/mL (cost $420.00 USD), PBAs ≥ 9.8%, TBAs > 2,337 μmol/48 h, or TBAs > 1,000 μmol/48 h + PBAs > 4% (TBAs + PBAs) ($405.00 USD). However, those tests must be shipped to the US for their analysis (total cost $825.00 USD). Data were compared using the chi-square test and Student's t test, and Spearman's Rho correlations were calculated. RESULTS We analyzed 48 patients with 7αC4 (age: 58.4 ± 16.9, women: 54.2%). BAM was confirmed by 7αC4 in 12.5%, by PBAs in 38.9%; by TBAs in 5.5%, and by TBAs + PBAs in 16.7%. We found elevated 7αC4 in patients with high or normal PBA/TBA levels (correlation with TBAs: 0.542, p = 0.020; PBAs: -0.127, p = 0.605; TBAs + PBAs: -0.200, p = 0.426). Lastly, BAM identified by 7αC4 was more frequent in patients with previous cholecystectomy (22.7%) vs. those without (3.8%). CONCLUSIONS Our study confirms that 7αC4 correlates well with TBAs and is a good biomarker for BAM screening because it can be elevated, despite normal PBA/TBA levels. Additionally, it represents a 49% cost savings in BAM investigation.
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Affiliation(s)
- G Mendoza-Domínguez
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental (UME) Dr. Ruy Pérez Tamayo, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico; Programa de Estudios Combinados en Medicina (PECEM), Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
| | - Z M Garrido-Santos
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental (UME) Dr. Ruy Pérez Tamayo, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico; Programa de Estudios Combinados en Medicina (PECEM), Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
| | - C Lau
- Laboratorios Biomédica de Referencia, Mexico City, Mexico
| | - R Balbuena
- Laboratorios Biomédica de Referencia, Mexico City, Mexico
| | - A D Santana-Vargas
- Departamento de Investigación, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico
| | - M Schmulson-Wasserman
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental (UME) Dr. Ruy Pérez Tamayo, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico; Gastroenterología y Motilidad Gastrointestinal, Clínica Lomas Altas, Mexico City, Mexico.
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Mochizuki Y, Katoh N, Matsushima A, Yazaki M, Kuwabara N, Nakagawa S, Sekijima Y. Involvement of bile acid in diarrhoea and therapeutic effect of colestimide in hereditary ATTR amyloidosis. Amyloid 2025; 32:39-45. [PMID: 39565048 DOI: 10.1080/13506129.2024.2430554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 10/12/2024] [Accepted: 11/12/2024] [Indexed: 11/21/2024]
Abstract
BACKGROUND Diarrhoea is one of the most serious complications in hereditary ATTR (ATTRv) amyloidosis. However, its precise pathomechanism remains unknown. The present study investigated the involvement of bile acid in diarrhoea along with the therapeutic effect of colestimide, a bile acid sequestrant, in ATTRv amyloidosis. METHODS We prospectively enrolled 19 ATTRv amyloidosis patients (9 with refractory diarrhoea and 10 without diarrhoea) and 20 healthy individuals for measurements of serum 7a-hydroxy-4-cholesten-3-one (C4) levels. The patients with diarrhoea were then treated with oral colestimide (1.5 g twice daily) for 28 days. The frequency of diarrhoea and C4 level were evaluated before and after colestimide treatment. RESULTS Mean serum C4 level was significantly higher in ATTRv patients with diarrhoea (62.3 ng/mL) than in ATTRv patients without diarrhoea (24.0 ng/mL, p = 0.03). Colestimide treatment significantly decreased mean diarrhoea frequency (pre-treatment period: 9.1 times/week, colestimide treatment period, 6.6 times/week, p = 0.04) and increased mean C4 level (before treatment: 66.2 ng/mL, after treatment: 187.1 ng/mL, p = 0.02). CONCLUSIONS Bile acid status was significantly associated with diarrhoea in ATTRv amyloidosis. Colestimide and other bile acid sequestrants may reduce diarrhoea frequency in afflicted patients.
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Affiliation(s)
- Yusuke Mochizuki
- Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan
| | - Nagaaki Katoh
- Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan
| | - Akira Matsushima
- Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan
| | - Masahide Yazaki
- Institute for Biomedical Sciences, Shinshu University, Matsumoto, Japan
| | - Naoko Kuwabara
- Laboratory of Functional and Analytical Food Sciences, Faculty of Applied Life Sciences, Niigata University of Pharmacy and Medical and Life Sciences, Niigata, Japan
| | - Saori Nakagawa
- Division of Bio-Analytical Chemistry, Faculty of Medical Technology, Niigata University of Pharmacy and Medical and Life Sciences, Niigata, Japan
| | - Yoshiki Sekijima
- Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan
- Institute for Biomedical Sciences, Shinshu University, Matsumoto, Japan
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Barbara G, Bellini M, Portincasa P, Stanghellini V, Annibale B, Benedetti A, Cammarota G, Fries W, Usai Satta P, Corazziari ES. Bile acid diarrhea in patients with chronic diarrhea. Current appraisal and recommendations for clinical practice. Dig Liver Dis 2025; 57:680-687. [PMID: 39827025 DOI: 10.1016/j.dld.2024.12.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 12/14/2024] [Accepted: 12/23/2024] [Indexed: 01/22/2025]
Abstract
Bile Acid Diarrhea (BAD) is a common cause of chronic diarrhea, often accompanied by urgency, occasional fecal incontinence, abdominal pain, and fatigue. A nationwide survey has shown limited awareness of BAD within the Italian medical community, prompting a panel of experts to develop a Position Paper that outlines the most practical and cost-saving diagnostic investigations and treatments for this frequently overlooked condition. The document provides an overview of the epidemiology, pathophysiology, clinical manifestations, and classification of the different types of Bile Acid Diarrhea (BAD). A key focus is the diagnostic approach to identifying and managing the many undiagnosed BAD patients in both primary care and specialized medical settings. Finally, the paper addresses the optimal therapeutic strategies for BAD, including traditional bile acid sequestrants and newer, promising treatments.
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Affiliation(s)
- Giovanni Barbara
- IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Massimo Bellini
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J)University of Bari Aldo Moro, Bari, Italy
| | - Vincenzo Stanghellini
- IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Bruno Annibale
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Roma, Italy
| | - Antonio Benedetti
- Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ospedali Riuniti-University Hospital, Ancona, Italy
| | - Giovanni Cammarota
- Gastroenterology Unit, Fondazione Policlinico A Gemelli IRCCS, Catholic University of Medicine, Roma, Italy
| | - Walter Fries
- Clinical Unit of Gastroenterology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Ellegaard AM, Kårhus ML, Winther-Jensen M, Knop FK, Kårhus LL. Bile Acid Diarrhea Is Associated With an Increased Incidence of Gastrointestinal Cancers. Am J Gastroenterol 2024; 119:2107-2113. [PMID: 38717021 PMCID: PMC11446519 DOI: 10.14309/ajg.0000000000002859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 05/02/2024] [Indexed: 06/11/2024]
Abstract
INTRODUCTION Bile acid diarrhea (BAD) is an underrecognized and socially debilitating disease caused by high concentrations of bile acids in the colon. Bile acids directly and indirectly promote carcinogenesis. In this article, we investigated whether individuals with BAD have an increased risk of gastrointestinal (GI) cancers. METHODS By using the Danish health registries, adult individuals with BAD were identified by International Classification of Diseases 10th revision code K90.8 or referral to the diagnostic ⁷⁵selenium-homotaurocholic acid test followed by prescription of a bile acid sequestrant within 365 days (n = 5,245). Age- and sex-matched individuals without BAD were included for comparison (n = 52,450). We analyzed the cumulative incidence of GI cancers after BAD diagnosis and the odds ratios (ORs) of GI cancer 8 and 15 years before BAD diagnosis/matching. RESULTS Cumulative incidence of GI cancer 6 years after BAD diagnosis/matching was 1.6% in the BAD group and 1.1% in controls ( P = 0.01). The ORs of total GI cancer 8 and 15 years before BAD diagnosis were 6.16 (5.08-7.48) and 5.19 (4.28-6.29), respectively. Furthermore, 47 individuals with BAD (0.9%) and 250 (0.5%) controls died of GI cancer. DISCUSSION This nationwide cohort study indicates an association between BAD and GI cancers. We found both a higher incidence of GI cancer after BAD diagnosis compared with controls and increased OR of GI cancer before BAD diagnosis. Bearing in mind the underdiagnosis of BAD, the delay of BAD diagnosis, and the carcinogenic effect of bile acids, these findings warrant further investigations of the risk of GI cancer in individuals with BAD.
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Affiliation(s)
- Anne-Marie Ellegaard
- Center for Clinical Metabolic Research, Copenhagen University Hospital–Herlev and Gentofte, Hellerup, Denmark
| | - Martin L. Kårhus
- Center for Clinical Metabolic Research, Copenhagen University Hospital–Herlev and Gentofte, Hellerup, Denmark
| | - Matilde Winther-Jensen
- Center for Clinical Research and Prevention, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Frederiksberg, Denmark
| | - Filip K. Knop
- Center for Clinical Metabolic Research, Copenhagen University Hospital–Herlev and Gentofte, Hellerup, Denmark
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.
- Currently employed at Novo Nordisk A/S, Søborg, Denmark.
| | - Line L. Kårhus
- Center for Clinical Research and Prevention, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Frederiksberg, Denmark
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Sun Y, Zhang Y, Wang Z, Liu Q, Mo J. Efficacy and safety of Chinese herbal medicine in treating postcholecystectomy diarrhea: A systematic review and meta-analysis. Medicine (Baltimore) 2024; 103:e38046. [PMID: 38701312 PMCID: PMC11062710 DOI: 10.1097/md.0000000000038046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 04/05/2024] [Indexed: 05/05/2024] Open
Abstract
BACKGROUND Postcholecystectomy diarrhea (PCD) is among the most distressing and well-known clinical complications of cholecystectomy. Despite various available treatment options, clinical outcomes are greatly limited by unclear pathophysiological mechanisms. Chinese herbal medicine (CHM) is widely used as a complementary and alternative therapy for the treatment of functional diarrhea. Thus, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of CHM for the treatment of PCD. METHODS Electronic database searches were conducted using the Cochrane Library, PubMed, Web of Science, Embase, Wanfang Data, China National Knowledge Infrastructure, and the Chinese Scientific Journal Database. All RCTs on CHMs for managing patients with PCD were included. The meta-analysis was performed using RevMan 5.4 software. RESULTS The present meta-analysis included 14 RCTs published between 2009 and 2021 in China. The primary findings indicated that CHM had a higher total efficacy and cure rate as a monotherapy for PCD (P < .00001). Two trials reported the scores of the main symptoms with statistically significant differences in stool nature (P < .00001), defecation frequency (P = .002), and abdominal pain and bloating (P < .00001). In addition, CHM reduced CD3+ and CD4+ levels more effectively in terms of T lymphocyte subset determination (P < .00001). The main symptoms of PCD in traditional Chinese medicine (TCM) are splenic deficiency and liver stagnation. All treatments were used to strengthen the spleen and (or) soothing the liver. CONCLUSION CHM had a favorable effect on PCD. No adverse events were observed. Larger, high-quality RCTs are warranted to draw definitive conclusions and standardize treatment protocols.
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Affiliation(s)
- Yan Sun
- Guang’an Men Hospital, China Academy of Chinese Medical Sciences, Xicheng District, Beijing, P.R. China
| | - Yong Zhang
- Guang’an Men Hospital, China Academy of Chinese Medical Sciences, Xicheng District, Beijing, P.R. China
| | - Zheng Wang
- Guang’an Men Hospital, China Academy of Chinese Medical Sciences, Xicheng District, Beijing, P.R. China
| | - Quanda Liu
- Guang’an Men Hospital, China Academy of Chinese Medical Sciences, Xicheng District, Beijing, P.R. China
| | - Juefei Mo
- Guang’an Men Hospital, China Academy of Chinese Medical Sciences, Xicheng District, Beijing, P.R. China
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Kim HJ, Kim HJ. [Bile Acid Diarrhea]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 83:133-142. [PMID: 38659249 DOI: 10.4166/kjg.2023.119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/17/2023] [Accepted: 12/18/2023] [Indexed: 04/26/2024]
Abstract
Diarrhea is a very common gastrointestinal symptom, and the presence of higher concentrations of bile acid in the colon leads to bile acid diarrhea (BAD). In BAD patients, a portion of bile from the small intestine that is normally controlled by enterohepatic circulation is present at a high concentration in the lumen of the large intestine, resulting in increased motility and secretion of the large intestine. The prevalence of BAD is estimated to be 1-2% of the general population, and it comprises one-third of the instances of diarrhea-predominant irritable bowel syndrome. The clinical symptoms of BAD include chronic diarrhea, increased frequency of defecation, urgency to defecate, fecal incontinence, and cramping abdominal pain. The pathophysiology of BAD has not yet been fully elucidated. However, recent studies have reported increased intestinal permeability, shortened intestinal transit time, and changes in the intestinal microbial community to be the possible causes of BAD. Although fecal and serum bile acid tests are widely used for diagnosis, new test methods that are non-invasive, inexpensive, and have high sensitivity and specificity are needed at various institutions to facilitate the diagnosis. The selenium homo-tauro-cholic acid (SeHCAT) test is the gold standard for BAD diagnosis and severity assessment. The validation of several other serum markers, such as 7-hydroxy-4-cholesten-3-one (serum 7αC4) and the fibroblast growth factor 19 (FGF19) for use in clinical practice is ongoing. Although bile acid sequestrants are the mainstay of treatment, the development of drugs that are more effective and have better compliance is required. Farnesoid X receptor (FXR) agonists are showing promising results.
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Affiliation(s)
- Hee Jin Kim
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, Korea
| | - Hyun Jin Kim
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, Korea
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Huang RL, Huang WK, Xiao XY, Ma LF, Gu HZR, Yang GP. Diagnosis and treatment of post-cholecystectomy diarrhoea. World J Gastrointest Surg 2023; 15:2398-2405. [PMID: 38111762 PMCID: PMC10725554 DOI: 10.4240/wjgs.v15.i11.2398] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 07/22/2023] [Accepted: 09/22/2023] [Indexed: 11/26/2023] Open
Abstract
The incidence of cholecystitis is relatively high in developed countries and may usually be attributed to gallstones, the treatment for which involves complete surgical removal of the gallbladder (cholecystectomy). Bile acids produced following cholecystectomy continue to flow into the duodenum but are poorly absorbed by the colon. Excessive bile acids in the colon stimulate mucosal secretion of water and electrolytes leading, in severe cases, to diarrhoea. Bile acid diarrhoea (BAD) is difficult to diagnose, requiring a comprehensive medical history and physical examination in combination with laboratory evaluation. The current work reviews the diagnosis and treatment of BAD following cholecystectomy.
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Affiliation(s)
- Rang-Lang Huang
- Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of The Central South University, Changsha 410013, Hunan Province, China
| | - Wen-Kai Huang
- Department of General Medicine, The Third Xiangya Hospital of The Central South University, Changsha 410013, Hunan Province, China
| | - Xiang-Yi Xiao
- The Xiangya School of Medicine, The Central South University, Changsha 410013, Hunan Province, China
| | - Lin-Feng Ma
- The Xiangya School of Medicine, The Central South University, Changsha 410013, Hunan Province, China
| | - He-Zi-Rui Gu
- The Xiangya School of Medicine, The Central South University, Changsha 410013, Hunan Province, China
| | - Guo-Ping Yang
- Department of Clinical Pharmacy, The Third Hospital of The Central South University, Changsha 410013, Hunan Province, China
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Lewinska M, Kårhus ML, Ellegaard AMG, Romero-Gómez M, Macias RIR, Andersen JB, Knop FK. Serum lipidome unravels a diagnostic potential in bile acid diarrhoea. Gut 2023; 72:1698-1708. [PMID: 37072179 PMCID: PMC10423493 DOI: 10.1136/gutjnl-2022-329213] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 03/30/2023] [Indexed: 04/20/2023]
Abstract
OBJECTIVE Bile acid diarrhoea (BAD) is debilitating yet treatable, but it remains underdiagnosed due to challenging diagnostics. We developed a blood test-based method to guide BAD diagnosis. DESIGN We included serum from 50 treatment-naive patients with BAD diagnosed by gold standard 75selenium homotaurocholic acid test, 56 feature-matched controls and 37 patients with non-alcoholic fatty liver disease (NAFLD). Metabolomes were generated using mass spectrometry covering 1295 metabolites and compared between groups. Machine learning was used to develop a BAD Diagnostic Score (BDS). RESULTS Metabolomes of patients with BAD significantly differed from controls and NAFLD. We detected 70 metabolites with a discriminatory performance in the discovery set with an area under receiver-operating curve metric above 0.80. Logistic regression modelling using concentrations of decanoylcarnitine, cholesterol ester (22:5), eicosatrienoic acid, L-alpha-lysophosphatidylinositol (18:0) and phosphatidylethanolamine (O-16:0/18:1) distinguished BAD from controls with a sensitivity of 0.78 (95% CI 0.64 to 0.89) and a specificity of 0.93 (95% CI 0.83 to 0.98). The model was independent of covariates (age, sex, body mass index) and distinguished BAD from NAFLD irrespective of fibrosis stage. BDS outperformed other blood test-based tests (7-alpha-hydroxy-4-cholesten-3-one and fibroblast growth factor 19) currently under development. CONCLUSIONS BDS derived from serum metabolites in a single-blood sample showed robust identification of patients with BAD with superior specificity and sensitivity compared with current blood test-based diagnostics.
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Affiliation(s)
- Monika Lewinska
- Health and Medical Sciences, University of Copenhagen Biotech Research and Innovation Centre, Copenhagen, Denmark
| | - Martin Lund Kårhus
- Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark
| | - Anne-Marie Gade Ellegaard
- Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark
| | - Manuel Romero-Gómez
- Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain
| | - Rocio I R Macias
- HEVEPHARM, Physiology and Pharmacology, IBSAL, CIBERehd, University of Salamanca, Salamanca, Spain
| | - Jesper B Andersen
- Health and Medical Sciences, University of Copenhagen Biotech Research and Innovation Centre, Copenhagen, Denmark
| | - Filip Krag Knop
- Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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The Symptomatic Outcomes of Cholecystectomy for Gallstones. J Clin Med 2023; 12:jcm12051897. [PMID: 36902684 PMCID: PMC10004100 DOI: 10.3390/jcm12051897] [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: 02/07/2023] [Revised: 02/22/2023] [Accepted: 02/26/2023] [Indexed: 03/08/2023] Open
Abstract
Cholecystectomy is the definite treatment for symptomatic gallstones, and rates are rapidly rising. Symptomatic complicated gallstones are generally treated with cholecystectomy, but there is no consensus on the clinical selection of patients with symptomatic uncomplicated gallstones for cholecystectomy. The aim of this review is to describe symptomatic outcomes before versus after cholecystectomy in patients with symptomatic gallstones as reported in prospective clinical studies and to discuss patient selection for cholecystectomy. Following cholecystectomy, resolution of biliary pain is high and reported for 66-100%. Dyspepsia has an intermediate resolution of 41-91% and may co-exist with biliary pain but may also develop following cholecystectomy with an increase of 150%. Diarrhea has a high increase and debuts in 14-17%. Persisting symptoms are mainly determined by preoperative dyspepsia, functional disorders, atypical pain locations, longer duration of symptoms, and poor psychological or physical health. Patient satisfaction following cholecystectomy is high and may reflect symptom alleviation or a change in symptoms. Comparison of symptomatic outcomes in available prospective clinical studies is limited by variations in preoperative symptoms, clinical presentations, and clinical management of post-cholecystectomy symptoms. When selecting patients with biliary pain only in a randomized controlled trial, 30-40% still have persisting pain. Strategies for the selection of patients with symptomatic uncomplicated gallstones based on symptoms alone are exhausted. For the development of a selection strategy, future studies should explore the impact of objective determinants for symptomatic gallstones on pain relief following cholecystectomy.
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11
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Storr M, Gross M, Madisch A, von Arnim U, Mönnikes H, Walters J, Krammer H, Keller J. Chologene Diarrhö, Stiefkind der chronischen Diarrhö
– Prävalenz, Diagnostik und Therapie. AKTUELLE ERNÄHRUNGSMEDIZIN 2022. [DOI: 10.1055/a-1923-0760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Die chologene Diarrhö ist eine der häufigsten nicht
diagnostizierten Ursachen der chronischen Diarrhö, der zahlreiche
verschiedene Pathophysiologien zugrunde liegen können. Auch nach
Ausschlussdiagnostik der häufigeren Ursachen verbleiben bis zu
5% der Bevölkerung von einer ungeklärten chronischen
Diarrhö betroffen. In diesem Kollektiv findet sich in bis zu 50%
als Ursache eine chologene Diarrhö.
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12
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McKenzie YA, Sremanakova J, Todd C, Burden S. Effectiveness of diet, psychological, and exercise therapies for the management of bile acid diarrhoea in adults: A systematic review. J Hum Nutr Diet 2022; 35:1087-1104. [PMID: 35274385 PMCID: PMC9790321 DOI: 10.1111/jhn.13005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 02/23/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Bile acid diarrhoea (BAD) causes chronic diarrhoea and is primarily treated pharmacologically. This systematic review aimed to evaluate the effectiveness of non-pharmacological therapies for evidence-based management of BAD in adults. METHODS A systematic review of the medical literature was performed from 1975 to 13 July 2021 to identify studies on diet, psychological, and exercise therapies that met diagnostic criteria for BAD in adults with diarrhoea. Effectiveness was judged by responder or improvement in diarrhoea at study endpoint according to each study's definition of diarrhoea. Therapeutic effect on abdominal pain and flatulence was also measured. Risk of bias was assessed using the Risk Of Bias In Non-Randomised Studies of Interventions tool. A narrative review was conducted using 'Synthesis Without Meta-analysis' guidance. Certainty of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. RESULTS Eight prospective cohort studies were identified on diet therapies from 2 weeks to over 2 years involving 192 patients. No psychological or exercise therapies were found. Carbohydrate modification (one study, n = 2) in primary BAD, and dietary fat intake reductions (five studies, n = 181) and an exclusive elemental diet therapy (two studies, n = 9) in secondary BAD, showed beneficial directions of effect on diarrhoea, abdominal pain, and flatulence. Risks of bias for each study and across studies for each therapy type were serious. Certainty of the evidence was very low for all outcomes. CONCLUSIONS No conclusions could be drawn on the effectiveness of diet, psychological, or exercise therapies on diarrhoea, abdominal pain, and flatulence for the management of BAD in adults. High-quality randomised controlled trials are needed.
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Affiliation(s)
- Yvonne A. McKenzie
- School of Health Sciences, Faculty of Biology, Medicine and HealthUniversity of ManchesterUK
| | - Jana Sremanakova
- School of Health Sciences, Faculty of Biology, Medicine and HealthUniversity of ManchesterUK
| | - Chris Todd
- School of Health Sciences, Faculty of Biology, Medicine and HealthUniversity of ManchesterUK
- Manchester University NHS Foundation TrustManchesterUK
| | - Sorrel Burden
- School of Health Sciences, Faculty of Biology, Medicine and HealthUniversity of ManchesterUK
- Salford Royal NHS Foundation TrustSalfordUK
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Savarino E, Zingone F, Barberio B, Marasco G, Akyuz F, Akpinar H, Barboi O, Bodini G, Bor S, Chiarioni G, Cristian G, Corsetti M, Di Sabatino A, Dimitriu AM, Drug V, Dumitrascu DL, Ford AC, Hauser G, Nakov R, Patel N, Pohl D, Sfarti C, Serra J, Simrén M, Suciu A, Tack J, Toruner M, Walters J, Cremon C, Barbara G. Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. United European Gastroenterol J 2022; 10:556-584. [PMID: 35695704 PMCID: PMC9278595 DOI: 10.1002/ueg2.12259] [Citation(s) in RCA: 78] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 05/20/2022] [Indexed: 11/23/2022] Open
Abstract
Irritable bowel syndrome with diarrhoea (IBS-D) and functional diarrhoea (FDr) are the two major functional bowel disorders characterized by diarrhoea. In spite of their high prevalence, IBS-D and FDr are associated with major uncertainties, especially regarding their optimal diagnostic work-up and management. A Delphi consensus was performed with experts from 10 European countries who conducted a literature summary and voting process on 31 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation criteria. Consensus (defined as >80% agreement) was reached for all the statements. The panel agreed with the potential overlapping of IBS-D and FDr. In terms of diagnosis, the consensus supports a symptom-based approach also with the exclusion of alarm symptoms, recommending the evaluation of full blood count, C-reactive protein, serology for coeliac disease, and faecal calprotectin, and consideration of diagnosing bile acid diarrhoea. Colonoscopy with random biopsies in both the right and left colon is recommended in patients older than 50 years and in presence of alarm features. Regarding treatment, a strong consensus was achieved for the use of a diet low fermentable oligo-, di-, monosaccharides and polyols, gut-directed psychological therapies, rifaximin, loperamide, and eluxadoline. A weak or conditional recommendation was achieved for antispasmodics, probiotics, tryciclic antidepressants, bile acid sequestrants, 5-hydroxytryptamine-3 antagonists (i.e. alosetron, ondansetron, or ramosetron). A multinational group of European experts summarized the current state of consensus on the definition, diagnosis, and management of IBS-D and FDr.
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Xu Y, Jing H, Wang J, Zhang S, Chang Q, Li Z, Wu X, Zhang Z. Disordered Gut Microbiota Correlates With Altered Fecal Bile Acid Metabolism and Post-cholecystectomy Diarrhea. Front Microbiol 2022; 13:800604. [PMID: 35250923 PMCID: PMC8894761 DOI: 10.3389/fmicb.2022.800604] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 01/17/2022] [Indexed: 12/12/2022] Open
Abstract
Post-cholecystectomy diarrhea (PCD) is a common complication of gallbladder removal, and gut microbiota changes have been determined in PCD patients. Bile acid diarrhea (BAD) is supposed to be the main pathogenic factor for PCD due to the disrupted fecal bile acid metabolism in diarrheal patients. However, the profiling of bile acid metabolite alteration in PCD is unclear and whether changed gut microbiota and fecal bile acid metabolism are correlated is also underdetermined. The fecal bile acid metabolites from fecal samples were profiled by targeted UPLC/MS (ultra-high-performance liquid chromatography coupled with a triple-quadrupole mass spectrometer) and the composition of fecal bile acid metabolites in PCD patients was demonstrated to be distinct from those in Non-PCD and HC groups. In addition, the quantification of bile acid excretion in feces of diarrheal patients was significantly elevated. Furthermore, 16S rRNA sequencing results revealed that PCD patients had the lowest operational taxonomic units (OTU) and significant reduction in microbial richness and evenness. Bacterial composition was remarkably shifted in PCD patients, which mainly lay in dominated phyla Firmicutes and Bacteroidota. Besides, the co-abundance network among genus bacteria declined in PCD. Among the genera, Prevotella, Enterococcus, and Erysipelotrichaceae_UCG-003 were enriched, but Alistipes, Bacteroides, Ruminococcus, and Phascolarctobacterium were reduced. Moreover, these disease-linked genera were closely associated with several diarrheal phenotypes. Notably, changed bile acid metabolites exhibited strong correlations with gut microbiota as well. Conclusively, this study reveals associations between PCD-linked microbes and bile acid metabolites, which may synergistically correlate to postoperative diarrhea.
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Affiliation(s)
- Yayun Xu
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Hui Jing
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Jianfa Wang
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
| | - Shilong Zhang
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qimeng Chang
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
| | - Zhanming Li
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
- Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Xubo Wu
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
- *Correspondence: Xubo Wu,
| | - Ziping Zhang
- Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai, China
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
- Ziping Zhang,
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15
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Farrugia A, Attard JA, Khan S, Williams N, Arasaradnam R. Postcholecystectomy diarrhoea rate and predictive factors: a systematic review of the literature. BMJ Open 2022; 12:e046172. [PMID: 35177439 PMCID: PMC8860059 DOI: 10.1136/bmjopen-2020-046172] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVES Cholecystectomy is one of the most common surgical procedures performed worldwide to treat gallstone-related disease. Postcholecystectomy diarrhoea (PCD) is a well-reported phenomenon, however, the actual rate, predictive factors and mechanism of action have not been well determined. A systematic review was undertaken to determine the rate and predictive factors associated with diarrhoea in the postcholecystectomy setting. METHODS The review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. Databases searched included Medline, Embase, Pubmed, Cochrane and Google Scholar up to 29 September 2020. The inclusion criteria consisted of cohort studies or randomised trials which investigated the rate of PCD and predictive factors. Case reports, case series, conference abstracts and expert opinion pieces were excluded as were other systematic reviews as all the original articles from those reviews were included in this review. Papers that did not include PCD as a separate entity were excluded. Bias assessment was performed using the Newcastle-Ottawa Scale for cohort studies and the Cochrane risk of bias tool for randomised controlled trials as appropriate. Data were extracted by two authors (AF and JAA) and an overall rate of PCD was calculated. Predictive factors were also extracted and compared between studies. RESULTS 1204 papers were obtained and 21 were found to contain relevant information about PCD, including the number of patients developing diarrhoea, method of symptom assessment and time of onset postcholecystectomy. A pooled total of 3476 patients were included across the identified studies with 462 (13.3%) patients developing PCD. Possible predictive factors varied across all studies, with characteristics such as gender, age and weight of patients postulated as being predictive of PCD, with no agreement across studies. DISCUSSION PCD is therefore relatively common (13.3%). This has important implications for patient consent. Patients ought to be investigated early for bile acid diarrhoea in suspected PCD. More studies are required to determine the possible predictive factors for PCD. Limitations of the study included that most studies were not powered for calculation of PCD, and assessment methods between studies varied. PROSPERO REGISTRATION NUMBER CRD42019140444.
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Affiliation(s)
- Alexia Farrugia
- General Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
- Biomedical sciences, University of Warwick, Warwick Medical School, Coventry, UK
| | | | - Saboor Khan
- General Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Nigel Williams
- General Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Ramesh Arasaradnam
- Biomedical sciences, University of Warwick, Warwick Medical School, Coventry, UK
- Gastroenterology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
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16
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Berti G, Rettura F, Lambiase C, Bellini M. Empirical trial or diagnostic tests for bile acid diarrhea? That is the question! J Dig Dis 2021; 22:557-558. [PMID: 34415680 DOI: 10.1111/1751-2980.13044] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 08/16/2021] [Indexed: 12/11/2022]
Affiliation(s)
- Ginevra Berti
- Department of New Technologies and Translational Research in Medicine and Surgery, Gastroenterology Unit, University of Pisa, Pisa, Italy
| | - Francesco Rettura
- Department of New Technologies and Translational Research in Medicine and Surgery, Gastroenterology Unit, University of Pisa, Pisa, Italy
| | - Christian Lambiase
- Department of New Technologies and Translational Research in Medicine and Surgery, Gastroenterology Unit, University of Pisa, Pisa, Italy
| | - Massimo Bellini
- Department of New Technologies and Translational Research in Medicine and Surgery, Gastroenterology Unit, University of Pisa, Pisa, Italy
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17
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Phillips ME, Hopper AD, Leeds JS, Roberts KJ, McGeeney L, Duggan SN, Kumar R. Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000643. [PMID: 34140324 PMCID: PMC8212181 DOI: 10.1136/bmjgast-2021-000643] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/08/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Pancreatic exocrine insufficiency is a finding in many conditions, predominantly affecting those with chronic pancreatitis, pancreatic cancer and acute necrotising pancreatitis. Patients with pancreatic exocrine insufficiency can experience gastrointestinal symptoms, maldigestion, malnutrition and adverse effects on quality of life and even survival.There is a need for readily accessible, pragmatic advice for healthcare professionals on the management of pancreatic exocrine insufficiency. METHODS AND ANALYSIS A review of the literature was conducted by a multidisciplinary panel of experts in pancreatology, and recommendations for clinical practice were produced and the strength of the evidence graded. Consensus voting by 48 pancreatic specialists from across the UK took place at the 2019 Annual Meeting of the Pancreatic Society of Great Britain and Ireland annual scientific meeting. RESULTS Recommendations for clinical practice in the diagnosis, initial management, patient education and long term follow up were developed. All recommendations achieved over 85% consensus and are included within these comprehensive guidelines.
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Affiliation(s)
- Mary E Phillips
- Nutrition and Dietetics, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
| | - Andrew D Hopper
- Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - John S Leeds
- HPB Unit, Freeman Hospital, Newcastle Upon Tyne, Tyne and Wear, UK
| | - Keith J Roberts
- HPB Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Laura McGeeney
- Nutrition and Dietetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Sinead N Duggan
- Department of Surgery, Trinity College Dublin, Dublin, Ireland
| | - Rajesh Kumar
- HPB Surgery, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
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18
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Montenegro A, Andújar X, Fernández-Bañares F, Esteve M, Loras C. Usefulness of endoscopic ultrasound in patients with minilithiasis and/or biliary sludge as a cause of symptoms of probable biliary origin after cholecystectomy. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 45:91-98. [PMID: 34023476 DOI: 10.1016/j.gastrohep.2021.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 03/06/2021] [Accepted: 03/10/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Endoscopic ultrasound (EUS) is a more sensitive technique than transabdominal ultrasound for the diagnosis of gallstones. This greater sensitivity, especially in the diagnosis of microlithiasis/biliary sludge, facilitates the indication of cholecystectomy in patients with symptoms of probable biliary origin but may result in over-indication of this surgery. OBJECTIVES Evaluate the role of EUS in the diagnosis of minilithiasis/biliary sludge in patients with digestive symptoms of probable biliary origin by resolving the symptoms after cholecystectomy. Analyse factors related to the remission of symptoms following cholecystectomy. PATIENTS AND METHODS Retrospective, longitudinal, single-centre study based on a prospective database of 1.121 patients undergoing EUS. Seventy-four patients were identified as meeting inclusion-exclusion criteria (diagnosed with minilithiasis/sludge by EUS after presenting digestive symptoms of probable biliary origin without a history of complicated cholelithiasis). A telephone questionnaire for symptoms was conducted with cholecystectomized patients. Factors related to a good response were analysed with logistic regression analysis. RESULTS Of the 74 patients, 50 were cholecystectomized (67.5%), mean age 49 years (SEM 2.26) (41 women). Seventy percent of patients (35/50) presented remission of symptoms with median follow-up 353.5 days (95% CI, 270-632.2). The only variable associated with remission of symptoms was the presence of typical biliary colic with an OR of 7.8 (95% CI, 1.8-34; p=0.006). No complications associated with EUS were recorded. One patient (2%) suffered haemoperitoneum and 18% (9/50) suffered diarrhoea following cholecystectomy. CONCLUSIONS EUS is a very useful technique for the indication of cholecystectomy in patients with minilithiasis/sludge and typical symptoms of biliary colic.
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Affiliation(s)
- Andrea Montenegro
- Department of Gastroenterology, Hospital Universitari Mútua Terrassa, Fundació per la Recerca Mútua Terrassa, Terrrassa, Catalonia, Spain; Department of Gastroenterology, Hospital Universitari General de Catalunya, Catalonia, Spain
| | - Xavier Andújar
- Department of Gastroenterology, Hospital Universitari Mútua Terrassa, Fundació per la Recerca Mútua Terrassa, Terrrassa, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
| | - Fernando Fernández-Bañares
- Department of Gastroenterology, Hospital Universitari Mútua Terrassa, Fundació per la Recerca Mútua Terrassa, Terrrassa, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
| | - María Esteve
- Department of Gastroenterology, Hospital Universitari Mútua Terrassa, Fundació per la Recerca Mútua Terrassa, Terrrassa, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
| | - Carme Loras
- Department of Gastroenterology, Hospital Universitari Mútua Terrassa, Fundació per la Recerca Mútua Terrassa, Terrrassa, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
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Storr M, Gross M, Madisch A, von Arnim U, Mönnikes H, Walters J, Krammer H, Keller J. [Bile acid diarrhea, stepchild of chronic diarrhea - prevalence, diagnosis and treatment. Update 2021]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:580-591. [PMID: 33634438 DOI: 10.1055/a-1378-9627] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Bile acid diarrhea is one of the most frequently undiagnosed causes of chronic diarrhea. A variety of different pathophysiologic causes can underlie chronic diarrhea. Even after exclusion of the more frequent causes, up to 5 % of the population remains affected by unexplained chronic diarrhea. In up to 50 % within this cohort, bile acid diarrhea is the underlying cause.The various pathophysiologies leading to bile acid diarrhea are well characterized. In this way, bile acid diarrhea can be divided into primary, secondary and tertiary subtypes. Common to all causes is the increased amount of bile acids in the colon and in the faeces and the resulting secretory-osmotic diarrhea, in more severe forms in combination with steatorrhea. The diagnosis of bile acid diarrhea follows a clear algorithm which, in addition to the search for the cause and possibly a therapeutic trial, recognizes the 75SeHCAT test as the reference method for the detection of an increased loss of bile acids. In view of the chronic nature of the symptoms and the need for permanent, lifelong therapy, the use of a one-time, reliable diagnostic test is justified, though the test is currently only available at a few centers. In addition to the treatment of identifiable underlying diseases, the current treatment includes the use of drugs that bind bile acids, with additional nutritional recommendations and vitamin substitutions.The present review article summarizes the pathophysiology and importance of bile acid diarrhea and discusses the current approach towards diagnosis and treatment.
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Affiliation(s)
| | - Manfred Gross
- Internistisches Klinikum München Süd, Klinik für Gastroenterologie, München
| | - Ahmed Madisch
- Klinikum Siloah, Gastroenterologie, interventionelle Endoskopie, Diabetologie und Akutgeriatrie, Hannover
| | - Ulrike von Arnim
- Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum, Magdeburg
| | - Hubert Mönnikes
- Klinik für Innere Medizin, Martin Luther Krankenhaus, Berlin
| | | | - Heiner Krammer
- Praxis für Gastroenterologie und Ernährungsmedizin am Deutschen End- und Dickdarmzentrum Mannheim
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Flores V, Martínez-Lozano H, Bighelli F, Orcajo J, García-Lledó J, Alonso-Farto JC, Menchén L. Prevalence of biliary acid malabsorption in patients with chronic diarrhoea of functional characteristics: a prospective study. BMC Gastroenterol 2021; 21:56. [PMID: 33563227 PMCID: PMC7871394 DOI: 10.1186/s12876-021-01637-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 02/02/2021] [Indexed: 12/22/2022] Open
Abstract
Background Bile acid malabsorption occurs in up to one third of patients with chronic diarrhoea of functional characteristics. The gold standard test for its diagnosis is the 75Selenium homocholic acid taurine (75SeHCAT) test. The aim of this work is to confirm previous data suggesting that bile acid malabsorption, diagnosed by 75Se-HCAT test, is the underlying cause of diarrhoea in a significant proportion of patients previously diagnosed with a functional disorder. In addition, we have analysed the clinical response of bile acid sequestrants in those patients with a bile acid diarrhoea diagnosis. Methods This is a prospective, single-centre study including consecutive adult patients diagnosed with chronic diarrhoea of unknown origin and with functional characteristics; systematic rule out of common causes of chronic diarrhoea was performed before bile acid malabsorption evaluation by 75SeHCAT scanning. A retention percentage less than 10% was considered positive. Clinical response to cholestyramine was further evaluated in those patients with a positive diagnosis of bile acid diarrhoea Results 38 patients (20 male, mean age 37.5 years) were finally included. Twenty (52.6%) patients included had a positive 75SeHCAT test. Median body mass index was significantly higher in those patients. We did not find significant differences in other clinical or biochemical variables 75SeHCAT-positive and 75SeHCAT-negative groups. Only 6 of 17 (35.3%) patients responded to cholestyramine treatment; 10 patients did not have response or withdraw the drug due to adverse events. Logistic regression analysis showed that none of the included variables was a predictor of clinical response to cholestyramine. Conclusions Bile acid malabsorption occurs in a high proportion of patients suffering from chronic diarrhoea with functional characteristics. Systematic investigation of bile acid malabsorption should be included in the diagnostic algorithms of patients with chronic watery diarrhoea in the routine clinical practice. Absence of response to cholestyramine does not rule out bile acid diarrhoea.
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Affiliation(s)
- Virginia Flores
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, C/ Dr. Esquerdo 46, 28007, Madrid, Spain
| | - Helena Martínez-Lozano
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, C/ Dr. Esquerdo 46, 28007, Madrid, Spain
| | - Federico Bighelli
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, C/ Dr. Esquerdo 46, 28007, Madrid, Spain
| | - Javier Orcajo
- Servicio de Medicina Nuclear, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Javier García-Lledó
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, C/ Dr. Esquerdo 46, 28007, Madrid, Spain
| | - Juan Carlos Alonso-Farto
- Servicio de Medicina Nuclear, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Luis Menchén
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, C/ Dr. Esquerdo 46, 28007, Madrid, Spain. .,Departamento de Medicina, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas Y Digestivas (CIBEREHD), Universidad Complutense de Madrid, Madrid, Spain. .,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas Y Digestivas (CIBEREHD), Madrid, Spain.
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Singh A, Koenen B, Kirby DF. Bariatric Surgery and Its Complications in Inflammatory Bowel Disease Patients. Inflamm Bowel Dis 2020; 26:1155-1165. [PMID: 31626698 DOI: 10.1093/ibd/izz246] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Indexed: 12/14/2022]
Abstract
Recent data have suggested that bariatric procedures, especially laparoscopic sleeve gastrectomy (SG), are safe and effective weight loss measures in patients with inflammatory bowel disease (IBD). But most of the studies have looked at short-term outcomes, and there is a general lack of awareness of underlying disease processes and baseline comorbidities in IBD patients undergoing bariatric procedures. Postbariatric issues in IBD patients including diarrhea from dumping syndrome, choleretic diarrhea, a high prevalence of small intestinal bacterial overgrowth, gastroesophageal reflux disease, Barrett's esophagus, stomal ulcerations, stenosis, and renal and gallstones can complicate the natural history of IBD. This could lead to unnecessary hospitalizations, change of medical therapy, and poor surgical and quality of life outcomes. In this review, we will discuss major complications after common bariatric procedures (SG, Roux-en-Y gastric bypass, and gastric banding) and suggest possible management strategies.
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Affiliation(s)
- Amandeep Singh
- Department of Gastroenterology, Hepatology & Nutrition, Center for Human Nutrition, Center for Gut Rehabilitation and Intestinal Transplantation, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Brian Koenen
- Department of Gastroenterology, Hepatology & Nutrition, Center for Human Nutrition, Center for Gut Rehabilitation and Intestinal Transplantation, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Donald F Kirby
- Department of Gastroenterology, Hepatology & Nutrition, Center for Human Nutrition, Center for Gut Rehabilitation and Intestinal Transplantation, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
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22
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Lyutakov I, Ursini F, Penchev P, Caio G, Carroccio A, Volta U, De Giorgio R. Methods for diagnosing bile acid malabsorption: a systematic review. BMC Gastroenterol 2019; 19:185. [PMID: 31726982 PMCID: PMC6854889 DOI: 10.1186/s12876-019-1102-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 10/29/2019] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Bile acid malabsorption (BAM) and bile acid-related diarrhea represent an under-recognized cause of chronic diarrhea mainly because of limited guidance on appropriate diagnostic and laboratory tests. We aimed to perform a systematic review of the literature in order to identify and compare the diagnostic accuracy of different diagnostic methods for patients with BAM, despite a proven gold standard test is still lacking. METHODS A PubMed literature review and a manual search were carried out. Relevant full papers, evaluating the diagnostic accuracy of different methods for BAM, were assessed. Available data were analyzed to estimate the sensitivity and specificity of each published test. RESULTS Overall, more than one test was considered in published papers on BAM. The search strategy retrieved 574 articles; of these, only 16 were full papers (with a total of 2.332 patients) included in the final review. Specifically, n = 8 studies used 75Selenium-homotaurocholic-acid-test (75SeHCAT) with a < 10% retention threshold; n = 8 studies evaluated fasting serum 7-α-hydroxy-4-cholesten-3-one (C4); n = 3 studies involved total fecal bile acid (BA) excretion over 48 h; n = 4 studies assessed fibroblast growth factor 19 (FGF19). 75SeHCAT showed an average sensitivity and specificity of 87.32 and 93.2%, respectively, followed by serum C4 (85.2 and 71.1%) and total fecal BA (66.6 and 79.3%). Fasting serum FGF19 had the lowest sensitivity and specificity (63.8 and 72.3%). All the extracted data were associated with substantial heterogeneity. CONCLUSIONS Our systematic review indicates that 75SeHCAT has the highest diagnostic accuracy for BAM, followed by serum C4 assay. The diagnostic yield of fecal BA and FGF19 assays is still under investigation. Our review reinforces the need for novel biomarkers aimed to an objective detection of BAM and therefore improving the management of this condition.
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Affiliation(s)
- Ivan Lyutakov
- Clinic of Gastroenterology, University Hospital "Tsaritsa Yoanna - ISUL", Sofia, Bulgaria
| | - Francesco Ursini
- Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - Plamen Penchev
- Clinic of Gastroenterology, University Hospital "Tsaritsa Yoanna - ISUL", Sofia, Bulgaria
| | - Giacomo Caio
- Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - Antonio Carroccio
- DiBiMIS University of Palermo, Palermo, Italy.,Internal Medicine, Giovanni Paolo II Hospital, Sciacca (ASP Agrigento), Sciacca, Italy
| | - Umberto Volta
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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Lim SJ, Gracie DJ, Kane JS, Mumtaz S, Scarsbrook AF, Chowdhury FU, Ford AC, Black CJ. Prevalence of, and predictors of, bile acid diarrhea in outpatients with chronic diarrhea: A follow-up study. Neurogastroenterol Motil 2019; 31:e13666. [PMID: 31225936 DOI: 10.1111/nmo.13666] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 06/04/2019] [Accepted: 06/10/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning to rule out bile acid diarrhea (BAD) in patients with chronic diarrhea has a high yield. Our previous study showed that patients with terminal ileal (TI) Crohn's disease, TI resection, or cholecystectomy were highly likely to have an abnormal scan. As a result, we encouraged clinicians to use a therapeutic trial of a bile acid sequestrant in these patients, instead of scanning. This may have reduced diagnostic yield of the test, so we examined this issue, as well as factors predicting an abnormal scan, in a large cohort of patients referred subsequently. METHODS We retrospectively identified 1,071 consecutive patients with chronic diarrhea undergoing SeHCAT scanning at Leeds Teaching Hospitals Trust from 2012 to 2016. We reviewed electronic patient records to obtain information on presenting gastrointestinal symptoms and any proposed risk factors for BAD. BAD was categorized according to subtype and severity. KEY RESULTS As expected, indications for scanning changed between 2012 and 2016, with a significant reduction in referrals with TI Crohn's disease or resection year-on-year (P < 0.001). Despite this, 457 (42.7%) patients had BAD and there was no downward trend in yield of SeHCAT during the 5 year period (P = 0.39). Overall, 51.6% had type II BAD, 36.1% type III, and 12.3% type I. BAD was mild in 31.7%, moderate in 34.4%, and severe in 33.9%. In total, 653 (61.0%) patients had no known risk factors, other than chronic diarrhea, but 233 (35.7%) of these individuals had BAD, and in 143 (61.4%), this was moderate or severe. CONCLUSIONS AND INFERENCES Despite reduced referrals for SeHCAT scanning in those with clear risk factors for BAD, the yield remained > 40%. One-third of those without known risk factors had BAD.
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Affiliation(s)
- Shujing Jane Lim
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - David J Gracie
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - John S Kane
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Saqib Mumtaz
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | | | - Fahmid U Chowdhury
- Department of Nuclear Medicine, St. James's University Hospital, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
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