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Camilleri M. Sex as a biological variable in irritable bowel syndrome. Neurogastroenterol Motil 2020; 32:e13802. [PMID: 31943595 PMCID: PMC7319890 DOI: 10.1111/nmo.13802] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 12/23/2019] [Accepted: 12/26/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND The pathophysiology and mechanisms of irritable bowel syndrome (IBS) involve both central and peripheral mechanisms that result in altered perception, as well as changes in bowel functions. These dysfunctions are associated with motor, sensory, immune, barrier, and intraluminal perturbations, including the microbiota, and their products and endogenous molecules with bioactive properties. There is evidence that these mechanisms are altered in both females and males. However, there is also increasing evidence that sex is a biological variable that impacts a number of aspects of the mechanisms, epidemiology, and manifestations of IBS. PURPOSE The objective of this article is to review the evidence of the differences among genders of the following factors in IBS: the brain-gut axis and sex hormones, epidemiology, diagnostic criteria and prognosis, pain perception, colonic transit, abdominal distension, overlap with urogynecological conditions, psychologic issues, anorexia, fibromyalgia, serotonin, and responsiveness to treatment of IBS. It is important to consider the variations attributable to sex in order to enhance the management of patients with IBS and the research of mechanisms involved in IBS.
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Affiliation(s)
- Michael Camilleri
- Division of Gastroenterology and Hepatology Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) Mayo Clinic Rochester Minnesota
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Holtmann GJ, Talley NJ. Inconsistent symptom clusters for functional gastrointestinal disorders in Asia: is Rome burning? Gut 2018; 67:1911-1915. [PMID: 29921653 DOI: 10.1136/gutjnl-2017-314775] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 04/06/2018] [Accepted: 05/12/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Gerald J Holtmann
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Faculties of Medicine and Health and Behavioural Sciences, University of Queensland and Translational Research Institute (TRI), Brisbane, Queensland, Australia
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
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Chang JY, Almazar AE, Richard Locke G, Larson JJ, Atkinson EJ, Talley NJ, Saito YA. Quantifying Rome symptoms for diagnosis of the irritable bowel syndrome. Neurogastroenterol Motil 2018; 30:e13356. [PMID: 29701271 DOI: 10.1111/nmo.13356] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 03/21/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, diagnosed on symptom-based criteria. Many have reported discrepancies between formal Rome criteria and diagnoses made in clinical practice. The aim of the study was to explore whether a quantitative version of the Rome criteria would better represent a clinical diagnosis of IBS than the current dichotomous criteria for symptom measure. METHODS As part of a large, case-control study, participants completed a validated bowel disease questionnaire. Rome criteria were analyzed based on 15 individual symptoms. Penalized logistic regression model with stepwise selection was used to identify significant symptoms of IBS which were independently associated with case-control status. KEY RESULTS In cases with a clinical diagnosis of IBS, 347 (70%) met Rome criteria for IBS. Increasing number of Rome symptoms were found related to the odds of being diagnosed with IBS. Nearly half of the Rome-negative case group experienced infrequent symptoms suggesting milder disease. Five of 15 Rome symptoms were associated with predicting case-control status in the final model, with 96% correctly classified among Rome-positive cases, 76% for Rome-negative cases, and 91% for controls. CONCLUSIONS AND INFERENCES Irritable bowel syndrome appears to be a spectrum disorder. Quantifying individual symptoms of Rome criteria has greater utility than the current application in representing the degree of IBS affectedness and appears to better reflect a clinical diagnosis of IBS applied by physicians. The use of a quantitative diagnostic Rome "score" may be helpful in clinical practice and research studies to better reflect the degree an individual is affected with IBS.
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Affiliation(s)
- J Y Chang
- Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - A E Almazar
- Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - G Richard Locke
- Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - J J Larson
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - E J Atkinson
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - N J Talley
- Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.,Pro Vice-Chancellor, Global Research, University of Newcastle, New Lambton, NSW, Australia
| | - Y A Saito
- Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Abstract
The symptom-based diagnosis of irritable bowel syndrome (IBS) has not been established in everyday clinical practice, and the diagnosis of this disorder remains one of exclusion. It has been demonstrated that the densities of duodenal chromogranin A, rectal peptide YY and somatostatin cells are good biomarkers for the diagnosis of sporadic IBS, and low-grade mucosal inflammation is a promising biomarker for the diagnosis of postinfectious IBS. Genetic markers are not useful as biomarkers for IBS since the potential risk genes have yet to be validated, and the intestinal microbiota cannot be used because of the lack of an association between a specific bacterial species and IBS. Furthermore, gastrointestinal dysmotility and visceral hypersensitivity tests produce results that are too nonconsistent and noncharacteristic to be used in the diagnosis of IBS. A combination of symptom-based assessment, exclusion of overlapping gastrointestinal diseases and positive biomarkers appears to be the best way to diagnose IBS.
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Affiliation(s)
- Magdy El-Salhy
- a Department of Medicine, Section for Gastroenterology, Stord Hospital, Stord, Norway
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Soubieres A, Wilson P, Poullis A, Wilkins J, Rance M. Burden of irritable bowel syndrome in an increasingly cost-aware National Health Service. Frontline Gastroenterol 2015; 6:246-251. [PMID: 28839818 PMCID: PMC5369587 DOI: 10.1136/flgastro-2014-100542] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Revised: 01/26/2015] [Accepted: 02/04/2015] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The National Health Service (NHS) is faced with increasing cost pressures that make the efficient use of resources paramount. Irritable bowel syndrome (IBS) places a large burden on the NHS as it has been estimated that at least 12% of the UK population is affected. However, poor clinical coding makes accurate assessment of this burden challenging. OBJECTIVE To calculate primary-care prescribing and both hospital outpatient and admission costs associated with the management of IBS in England. DESIGN AND MAIN OUTCOME MEASURES Hospital Episode Statistics data for 2012-2013 for all clinical commissioning groups in England were analysed to calculate the tariff cost of IBS. Prescribing analysis and cost tabulation (PACT) data for this period were also analysed. RESULTS In 2012-2013, there were 1 219 961 outpatient attendances in gastroenterology and colorectal surgery specialties. Despite this, only 1982 patients were recorded with IBS-specific codes, with a total estimated tariff cost of £812 336. In addition, 28 849 patients were recorded with IBS-related symptom codes at a cost of £11 002 874. In 2011-2012, there were 658 698 diagnostic lower gastrointestinal endoscopies at a tariff cost of £16 967 670 4. Of these, 323 752 (49%) had no further follow-up in secondary care over the subsequent 12 months. PACT data indicated that £44 977 959 and £25 582 752, respectively, were spent on selected laxatives and antispasmodics commonly used to treat IBS in primary care. CONCLUSIONS Better diagnosing, through improved clinical coding and standardisation of diagnostic criteria, is required to more accurately assess the true burden and allow optimal management of IBS.
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El-Salhy M, Hatlebakk JG, Hausken T. Reduction in duodenal endocrine cells in irritable bowel syndrome is associated with stem cell abnormalities. World J Gastroenterol 2015; 21:9577-9587. [PMID: 26327765 PMCID: PMC4548118 DOI: 10.3748/wjg.v21.i32.9577] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Revised: 02/09/2015] [Accepted: 04/03/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine whether the decreased density of duodenal endocrine cells in irritable bowel syndrome (IBS) is associated with abnormalities in stem cell differentiation.
METHODS: The study sample comprised 203 patients with IBS (180 females and 23 males with a mean age of 36 years) and a control group of 86 healthy subjects without gastrointestinal complaints (77 females and 9 males with a mean age of 38 years). The patients included 80 with mostly diarrhoea (IBS-D), 47 with both diarrhoea and constipation (IBS-M), and 76 with mostly constipation (IBS-C). Both the patients and controls underwent gastroscopy and four biopsy samples were taken from the descending part of the duodenum, proximal to the papilla of Vater. The biopsy samples were sectioned and immunostained for Musashi 1 (Msi-1), neurogenin 3 (NEUROG3), secretin, cholecystokinin (CCK), gastric inhibitory peptide (GIP), somatostatin and serotonin. Immunostaining was performed with an ultraView Universal DAB Detection Kit (v1.02.0018, Venata Medical Systems, Basal, Switzerland) using the BenchMark Ultra immunohistochemistry/in situ hybridization staining module (Venata Medical Systems). Endocrine cell densities were quantified by computerized image analysis using the Olympus cellSens imaging program.
RESULTS: The densities of Msi-1 and NEUROG3 cells were significantly lower in IBS patients, regardless of the subtype, than in the controls (77 ± 17 vs 8 ± 2; P = 0.0001, and 351 ± 33 vs 103 ± 22; P = 0.00002, respectively). Furthermore, the densities of secretin, and CCK cells were significantly lower in patients with diarrhoea as the predominant IBS symptom (IBS-D) than in the controls (161 ± 11 vs 88 ± 8; P = 0.00007, and 325 ± 41 vs 118 ± 10; P = 0.00006, respectively), but not in patients with constipation as the predominant IBS symptom (IBS-C) or those with both diarrhoea and constipation (IBS-M). The GIP cell density was significantly reduced in both IBS-D (152 ± 12 vs 82 ± 7; P = 0.00003), and IBS-C (152 ± 12 vs 107 ± 8; P = 0.01), but not in IBS-M. The densities of somatostatin cells in the controls and the IBS-total, IBS-D, IBS-M and IBS-C patients were 81 ± 8, 28 ± 3, 20 ± 4, 37 ± 5 and 28 ± 4 cells/mm2 epithelium, respectively. The density of somatostatin cells was lower in IBS-total, IBS-D, IBS-M and IBS-C patients than in the controls (P = 0.00009, 0.00006, 0.009 and 0.00008, respectively). The density of serotonin cells did not differ between IBS patients and controls.
CONCLUSION: The reduction in duodenal endocrine cells in IBS patients found in this study is probably attributable to the reduction in cells expressing Msi-1 and NEUROG3.
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Abstract
BACKGROUND Functional bowel disorders are recognized as being common, but remain very difficult to diagnose accurately and to differentiate from one another, despite their significant impact on the quality of life of patients.The aim of this study was to evaluate whether the clinical sign of 'floating stools' is associated with psychological disorders, colonic transit time, or other specific bowel disorders as defined by the Rome III diagnostic criteria. MATERIALS AND METHODS A total of 1252 consecutive patients, referred for and found to have functional gastrointestinal disorders, filled in a standard clinical questionnaire on the basis of the Rome III diagnostic criteria and were asked to provide information on the presence of floating stools. Overall, 344 of these scored positive for functional bowel disorders and underwent psychometric testing and colonic transit time studies. RESULTS Floating stools were reported by 26% of functional bowel disorder patients and 3% of the other functional gastrointestinal disorder patients (P<0.001). The basic demographic characteristics, psychometric evaluation scores, Bristol stool form scales, and total and segmental colonic transit times were not statistically different according to the presence or not of floating stools in these patients. Logistic regression showed that mixed irritable bowel syndrome was the only functional gastrointestinal disorder associated independently with floating stools (P=0.003). CONCLUSION Floating stools are a characteristic of patients with mixed irritable bowel syndrome.
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El-Salhy M, Hatlebakk JG, Gilja OH, Hausken T. Densities of rectal peptide YY and somatostatin cells as biomarkers for the diagnosis of irritable bowel syndrome. Peptides 2015; 67:12-9. [PMID: 25765365 DOI: 10.1016/j.peptides.2015.02.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Accepted: 02/27/2015] [Indexed: 12/19/2022]
Abstract
Irritable bowel syndrome (IBS) is a common chronic disorder. IBS diagnosis is a diagnosis of exclusion since there are no blood tests, radiological or endoscopic examinations for this disorder. Although several attempts have been made to develop a symptoms-based diagnosis, such systems are not widely used in clinics. Several tests and examinations measuring pathological findings in IBS have been considered for the diagnosis of IBS, but none of them has proved useful as a biomarker. Abnormalities in the cell densities of rectal peptide YY (PYY) and somatostatin cells have been reported in IBS patients. The aim of the present study was to determine the utility of these abnormalities as biomarkers for the diagnosis of IBS. Patients with IBS established according to Rome III criteria (n = 101) were included in this study (71 females and 30 males with a mean age of 35 years; range 18-61 years), and 62 healthy subjects (38 females and 24 males with a mean age of 41 years; range 18-65 years) were recruited as controls. Both the patients and controls underwent colonoscopy during which rectal biopsy samples were taken. The tissue samples were immunostained for PYY and somatostatin, and the number of stained cells was quantified relative to both the area of epithelial cells and per microscopic field. The density of PYY cells was significantly lower in IBS patients than in the healthy controls (P < 0.0001); receiver operator characteristic (ROC) analysis revealed an area under the ROC curve (AUC) of 0.99. The somatostatin cell density in IBS patients was higher than in the controls (P < 0.0001); ROC analysis revealed an AUC of 0.86. The densities of the rectal PYY and somatostatin cells appear to be clinically effective biomarkers for IBS. Furthermore, measurement of these parameters is inexpensive, rapid and does not require considerable experience or sophisticated equipment.
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Affiliation(s)
- Magdy El-Salhy
- Division of Gastroenterology, Department of Medicine, Stord Hospital, Stord, Norway; Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
| | - Jan Gunnar Hatlebakk
- Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
| | - Odd Helge Gilja
- Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
| | - Trygve Hausken
- Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
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Camilleri M, Shin A, Busciglio I, Carlson P, Acosta A, Bharucha AE, Burton D, Lamsam J, Lueke A, Donato LJ, Zinsmeister AR. Validating biomarkers of treatable mechanisms in irritable bowel syndrome. Neurogastroenterol Motil 2014; 26:1677-85. [PMID: 25244349 PMCID: PMC4245393 DOI: 10.1111/nmo.12421] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 08/06/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND A valid biomarker is 'an indicator of normal biologic or pathogenic processes, or pharmacological responses to a therapeutic intervention'. There is no validated biomarker for irritable bowel syndrome (IBS). The aim of the study was to assess ability of three quantitative traits to identify treatable processes to discriminate between IBS-diarrhea (IBS-D) patients, IBS-constipation (IBS-C) patients and healthy volunteers (HV). METHODS In 30 HV, 30 IBS-C patients and 64 IBS-D patients, we characterized bowel symptoms and quantitated pathophysiological mechanisms: bile acid (BA) synthesis (serum C4 and FGF19), fecal BA and fat, colonic transit (CT), and intestinal permeability (IP). We used multiple logistic regression and receiver-operating characteristic (ROCAUC ) to appraise three factors (fecal BA, CT, and IP) individually and in combination to identify discriminant targets for treatment in IBS. KEY RESULTS There were significant associations between the three subgroups and symptoms reflecting bowel function and the quantitative traits. There were significant associations between fecal BA and CT at 48 h (r = 0.43; p < 0.001) and between fecal BA and IP (r = 0.23; p = 0.015). Individually, fecal BA and CT48 (but not IP) were significant independent predictors for distinguishing HV from IBS. In combination, they discriminated HV from IBS-D patients (ROCAUC 0.70), HV from IBS-C patients (ROCAUC 0.73), and IBS-C patients from IBS-D patients (ROCAUC 0.86). Colonic transit and fecal BA excretion together discriminate between healthy volunteers and IBS-C patients or IBS-D patients, or between the IBS subgroups with 75-90% specificity at 60% sensitivity. CONCLUSIONS & INFERENCES Colonic transit and fecal BA individually and together constitute useful biomarkers to identify treatable mechanisms in IBS and to differentiate subgroups of IBS.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Alan Lueke
- Department of Laboratory Medicine and Pathology, Mayo Clinic College
of Medicine, Rochester, Minnesota
| | - Leslie J. Donato
- Department of Laboratory Medicine and Pathology, Mayo Clinic College
of Medicine, Rochester, Minnesota
| | - Alan R. Zinsmeister
- Division of Biomedical Statistics and Informatics, Department of Health
Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota
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Validation of the Rome III criteria and alarm symptoms for recurrent abdominal pain in children. J Pediatr Gastroenterol Nutr 2014; 58:779-85. [PMID: 24866784 DOI: 10.1097/mpg.0000000000000319] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Rome criteria were formulated to define functional gastrointestinal disorders (Rome III criteria, 2006) excluding organic diagnoses when alarm symptoms were absent. The aims of the study were to validate the Rome III criteria as to their capacity to differentiate between organic and functional abdominal pain and to assess the role of alarm symptoms in this differentiation. METHODS During 2 years all of the patients (ages 4-16 years) presenting with recurrent abdominal pain (Apley criteria) and referred to secondary care were included. Clinical diagnoses were based on protocolized evaluation and intervention with 6-month follow-up. Alarm symptoms were registered. Rome III criteria for functional pain syndromes were assigned independently. Descriptive statistical analyses were performed. RESULTS In 200 patients (87 boys, mean age 8.8 years), organic (17%), functional (40%), combined organic and functional (9%), spontaneous recovery (27%), and other (8%) clinical diagnoses were established. Alarm symptoms were found in 57.5% (organic causes 56%, functional causes 61%). The evaluation for Rome symptom clusters revealed symptoms of irritable bowel syndrome in 27%, functional dyspepsia in 15%, functional abdominal pain in 28%, functional abdominal pain syndrome in 14.5%, and no pain syndrome in 15.5%. Rome diagnoses, based on symptoms and absence of alarm symptoms, predicted functional clinical diagnosis with sensitivity 0.35 (95% confidence interval 0.27-0.43), specificity 0.60 (0.46-0.73), positive predictive value 0.71 (0.61-0.82), and negative predictive value of 0.24 (0.17-0.32). CONCLUSIONS The Rome III criteria for abdominal pain are not specific enough to rule out organic causes. Alarm symptoms do not differentiate between organic and functional abdominal pain.
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El-Salhy M, Hatlebakk JG, Gilja OH, Hausken T. Irritable bowel syndrome: recent developments in diagnosis, pathophysiology, and treatment. Expert Rev Gastroenterol Hepatol 2014; 8:435-43. [PMID: 24580043 DOI: 10.1586/17474124.2014.888952] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The diagnosis of irritable bowel syndrome (IBS) remains a diagnosis of exclusion, whereby an extensive investigation is performed to exclude other organic diseases that may explain the symptoms of patients. Attempts to have a positive diagnosis based on symptom assessments failed to achieve widely use in clinical practice. Abnormalities in the gastrointestinal endocrine cells in IBS patients have been reported recently, providing evidence that IBS is an organic disorder, and opening the door to the use of these abnormalities as markers for a positive diagnosis of IBS. New and promising drugs for the treatment of IBS with constipation as the predominant symptom are currently on the market, and the treatment results have been satisfactory thus far.
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Affiliation(s)
- Magdy El-Salhy
- Department of Medicine, Section for Gastroenterology, Stord Hospital, Stord, Norway
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El-Salhy M, Gundersen D, Gilja OH, Hatlebakk JG, Hausken T. Is irritable bowel syndrome an organic disorder? World J Gastroenterol 2014; 20:384-400. [PMID: 24574708 PMCID: PMC3923014 DOI: 10.3748/wjg.v20.i2.384] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 11/05/2013] [Accepted: 11/13/2013] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is generally considered to be functional because there appears to be no associated anatomical defect. Stress and psychological factors are thought to play an important role in IBS. The gut neuroendocrine system (NES), which regulates all functions of the gastrointestinal tract, consists of endocrine cells that are scattered among the epithelial cells of the mucosa, and the enteric nervous system. Although it is capable of operating independently from the central nervous system (CNS), the gut NES is connected to and modulated by the CNS. This review presents evidence for the presence of an anatomical defect in IBS patients, namely in the gastrointestinal endocrine cells. These cells have specialized microvilli that project into the lumen and function as sensors for the luminal content and respond to luminal stimuli by releasing hormones into the lamina propria, which starts a chain reaction that progresses throughout the entire NES. The changes in the gastrointestinal endocrine cells observed in IBS patients are highly consistent with the other abnormalities reported in IBS patients, such as visceral hypersensitivity, dysmotility, and abnormal secretion.
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Abstract
Bile acids (BA) are actively reabsorbed in the terminal ileum by the apical Na(+)-dependent bile salt transporter. This review addresses the epidemiology, pathophysiology, diagnosis and treatment of BA diarrhea (BAD). BAD is typically caused by ileal resection or disease; 25-33% of patients with chronic functional diarrhea or irritable bowel syndrome-diarrhea (IBS-D) have BAD, possibly from deficiency in the ileal hormone, FGF-19, which normally provides feedback inhibition of BA synthesis. Diagnosis of BAD is typically based on reduced BA retention of radiolabeled BA ((75)SeHCAT), increased BA synthesis (serum C4) or increased fecal BA loss. In clinical practice, diagnosis is often based on response to BA sequestrants (e.g., cholestyramine or colesevelam). Diagnostic tests for BA malabsorption (BAM) need to be used more extensively in clinical practice. In the future, farnesoid X receptor agonists that stimulate ileal production of FGF-19 may be alternative treatments of BAD.
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Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, 200 First St. S.W., Charlton Bldg., Rm. 8-110, Rochester, MN 55905, USA
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14
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Abstract
Irritable bowel syndrome (IBS), characterized by abdominal pain or discomfort associated with a change in bowel patterns, is one of the most common functional gastrointestinal disorders. Because no single drug effectively relieves all IBS symptoms, management relies on dietary and lifestyle modifications, as well as pharmacologic and nonpharmacologic therapies. The authors review current approaches to treatment and discuss nursing implications.
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15
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Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Charlton 8-110, 200 First Street SW, Rochester, MN 55905, USA
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Dang J, Ardila-Hani A, Amichai MM, Chua K, Pimentel M. Systematic review of diagnostic criteria for IBS demonstrates poor validity and utilization of Rome III. Neurogastroenterol Motil 2012; 24:853-e397. [PMID: 22632582 DOI: 10.1111/j.1365-2982.2012.01943.x] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND In the absence of a clear biomarker for irritable bowel syndrome (IBS), clinical criteria are used. In this study, we conduct a systematic review to examine the validation and utilization of IBS criteria. METHODS A systematic review was performed in two stages. The first was a review of literature from 1978 validating IBS diagnostic criteria. The second stage of review was to select studies published in IBS between 1992 and 2011. This time period was divided into three segments (Rome I era from 1992 to 1999, Rome II era from 2000 to 2006, and Rome III era from 2007 to 2011). The number and type of study (RCT or other) and criteria used were evaluated for each era. KEY RESULTS The first stage of the systematic review identified only 14 published studies validating diagnostic tests for IBS (with three studies evaluating more than one criterion). There were eight validations for Manning, three validations for Kruis, four validations for Rome I, three validations for Rome II, and no validation for Rome III. In the second review of utilization of Rome criteria, only 25.7% of published IBS papers used Rome III criteria during the Rome III era (Rome II was used most in 64.8% of studies). CONCLUSIONS & INFERENCES This review identified that comparator groups varied widely between studies making comparison of criteria impossible. Manning criteria are the most valid and accurate criteria. More importantly, Rome III is not validated and is poorly adopted in clinical research trial enrollment.
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Affiliation(s)
- J Dang
- GI Motility Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Money ME, Camilleri M. Review: Management of postprandial diarrhea syndrome. Am J Med 2012; 125:538-44. [PMID: 22624684 DOI: 10.1016/j.amjmed.2011.11.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2011] [Revised: 11/11/2011] [Accepted: 11/14/2011] [Indexed: 02/07/2023]
Abstract
Unexpected, urgent, sometimes painful bowel movements after eating are common complaints among adults. Without a clear etiology, if pain is present and resolves with the movements, this is usually labeled "irritable bowel syndrome-diarrhea" based solely on symptoms. If this symptom-based approach is applied exclusively, it may lead physicians not to consider treatable conditions: celiac disease, or maldigestion due to bile acid malabsorption, pancreatic exocrine insufficiency, or an a-glucosidase (sucrase, glucoamylase, maltase, or isomaltase) deficiency. These conditions can be misdiagnosed as irritable bowel syndrome-diarrhea (or functional diarrhea, if pain is not present). Limited testing is currently available to confirm these conditions (antibody screens for celiac disease; fecal fat as a surrogate marker for pancreatic function). Therefore, empirical treatment with alpha amylase, pancreatic enzymes, or a bile acid-binding agent may simultaneously treat these patients and serve as a surrogate diagnostic test. This review will summarize the current evidence for bile acid malabsorption, and deficiencies of pancreatic enzymes or a-glucosidases as potential causes for postprandial diarrhea, and provide an algorithm for treatment options.
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Affiliation(s)
- Mary E Money
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
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18
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Abstract
Rather than being a diagnosis of exclusion, irritable bowel syndrome (IBS) is a diagnosis that can be identified by symptom-based criteria. The collection of these criteria by a meticulous history can be enhanced by using various tools. Once a positive diagnosis is made, using clinical criteria for diagnosis, one should look for alarm or warning symptoms or signs, and should characterize the type of bowel habit. Determining whether the condition is a diarrhea-predominant or a constipation-predominant IBS will direct further diagnostic evaluation and management.
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Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN 55905, USA.
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Money ME, Walkowiak J, Virgilio C, Talley NJ. Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea. Frontline Gastroenterol 2011; 2:48-56. [PMID: 22095308 PMCID: PMC3009417 DOI: 10.1136/fg.2010.002253] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/24/2010] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE: To evaluate the efficacy of pancrealipase (PEZ) compared with placebo in the reduction of postprandial irritable bowel syndrome-diarrhoea (IBS-D). DESIGN: An intention to treat, double blind, randomised, crossover trial comparing PEZ to placebo for reduction of postprandial IBS-D. Patients had to recognise at least two different triggering foods, be willing to consume six baseline 'trigger meals' and again blinded with PEZ and placebo. Patients then chose which drug they preferred for another 25 meals. SETTING: Outpatient internal medicine practice clinic. PATIENTS: 255 patients were screened; 83 met the criteria, including 5 years of symptoms, recognised 'food triggers', no other identifiable cause for the symptoms, either a normal colonoscopy or barium enema while symptomatic and able to discontinue all anticholinergic medications. 69 patients were enrolled, 20 withdrew before randomisation, leaving 49 patients: 14 men, 35 women, mean age 52 years (SD 15.3). Over 60% had experienced symptoms for 11-30 years and 16% for more than 40 years. INTERVENTIONS: After completing six baseline meals, patients were randomised in blocks of four to receive either identical PEZ or a placebo for another six meals, and after a washout period of time received the alternative drug. MAIN OUTCOME MEASURES: The primary analysis was number of patients who chose PEZ over placebo for the extended use. RESULTS: Overall, 30/49 (61%) would have chosen PEZ (p=0.078), with first drug preference for PEZ at 0.002. Among the PEZ subgroup, PEZ use compared with placebo, demonstrated improvement in all symptoms (p≤0.001) for cramping, bloating, borborygami, urge to defecate, global pain and decrease stooling with increase in stool firmness. CONCLUSIONS: PEZ was found in a small group of patients to reduce postprandial IBS-D symptoms and deserves further evaluation.
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Affiliation(s)
- Mary E Money
- Washington County Health Systems, Hagerstown, Maryland, USA
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How reliable are the Rome III criteria for the assessment of functional gastrointestinal disorders in children? Am J Gastroenterol 2010; 105:2697-701. [PMID: 20808296 DOI: 10.1038/ajg.2010.350] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Functional gastrointestinal disorders (FGIDs) are common in children. Diagnosis of these conditions is based on the pediatric Rome criteria. In the past, we have shown that there was low inter-rater reliability (IRR) among pediatric gastroenterologists using the Rome II criteria. Since then, a new version of the criteria has been issued. The reliability of the Rome III criteria has not been established. METHODS A total of 10 pediatric gastroenterologist specialists and 10 pediatric gastroenterology fellows were provided with 20 clinical vignettes and a list of 17 possible diagnoses (all pediatric categories of the Rome criteria plus "none of the above" or "not enough information") and instructed to select one or more diagnosis for each vignette. RESULTS The average percentage of agreement among the raters was 50% for the pediatric gastroenterologists and 45% for the pediatric gastroenterology fellows. The inter-rater percentage of agreement per clinical case was >50% in only 7 out of 20 (35%) vignettes for the gastroenterologists and only 6 out of 20 (30%) cases for the fellows. The inter-rater percentage of agreement was <25% in 2 out of 20 (10%) vignettes for the gastroenterologists and 4 out of 20 (20%) vignettes for the fellows. The κ coefficient was 0.45 for the specialists (P<0.0001) and 0.39 for the fellows (P<0.0001). In a subanalysis of the groups of pain and constipation-related disorders, the inter-rater percentage of agreement per clinical case ranged between 27 and 100% (mean 57%, κ=0.37, P<0.0001) for the gastroenterologists and between 36 and 80% (mean 52%, κ=0.33, P<0.0001) for the fellows in the constipation subgroup. The inter-rater percentage of agreement per clinical case for the pain subgroup ranged between 22 and 80% (mean 48%, κ=0.36, P<0.0001) for the gastroenterologists and 22 and 62% (mean 39%, κ=0.29, P<0.0001) for the fellows in the pain subgroup. The κ coefficient for specialists with expertise in FGIDs was 0.37 (P<0.0001) and for those with expertise in other gastroenterology conditions was 0.53 (P<0.0001). CONCLUSIONS The IRR among pediatric gastroenterologists and fellows was found to be fair to moderate for the Rome III criteria. Only slight to fair agreement between raters existed for important subcategories of pain and constipation. The results from our current study are almost similar to that of the IRR study done for the Rome II criteria. This indicates the need for further refinement of the Rome criteria to make them more encompassing and user friendly.
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Validation of symptom-based diagnostic criteria for irritable bowel syndrome: a critical review. Am J Gastroenterol 2010; 105:814-20; quiz 813, 821. [PMID: 20179688 PMCID: PMC3856202 DOI: 10.1038/ajg.2010.56] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This article reviews the evidence for validity of symptom-based criteria (Manning, Rome I, Rome II, and Rome III) for irritable bowel syndrome (IBS). Two kinds of validations are reported: (i) studies testing whether symptom criteria discriminate patients with structural disease at colonoscopy from patients without structural disease; and (ii) studies testing whether symptom criteria discriminate patients presumed to have IBS by positive diagnosis from healthy subjects or patients with other functional and structural disorders. The first study type addresses an important clinical management question but cannot provide meaningful information on the sensitivity or positive predictive value because IBS is defined only by exclusion of structural disease. Specificity is modest (about 0.7) but can be improved to 0.9 by the addition of red flag signs and symptoms. The second type of study judges validity by whether the symptom criteria consistently perform as predicted by theory. Here, factor analysis confirms consistent clusters of symptoms corresponding to IBS; symptom-based criteria agree reasonably well (sensitivity, 0.4-0.9) with clinical diagnoses made by experienced clinicians; and patients with a clinical diagnosis of IBS who fulfill Rome II criteria have greater symptom severity and poorer quality of life than patients with a clinical diagnosis of IBS who do not fulfill Rome criteria. There are no consistent differences in sensitivity or specificity between Manning, Rome I, and Rome II. Both study types support the validity of symptom-based IBS criteria. Tests of Rome III are needed.
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