Browse
Submit Data
Databases
API
Help

Dataset Information

7 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Etiopathogenetic Mechanisms in Diverticular Disease of the Colon.

ABSTRACT: This article reviews epidemiological evidence of heritability and putative mechanisms in diverticular disease, with greatest attention to 3 recent studies of genetic associations with diverticular disease based on genome-wide or whole-genome sequencing studies in large patient cohorts. We provide an analysis of the biological plausibility of the significant associations with gene variants reported and highlight the relevance of ANO1, CPI-17 (aka PPP1R14A), COLQ6, COL6A1, CALCB or CALCA, COL6A1, ARHGAP15, and S100A10 to colonic neuromuscular function and tissue properties that may result in altered compliance and predispose to the development of diverticular disease. Such studies also identify candidate genes for future studies.

SUBMITTER: Camilleri M

PROVIDER: S-EPMC6881605 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Etiopathogenetic Mechanisms in Diverticular Disease of the Colon.

Camilleri Michael M Sandler Robert S RS Peery Anne F AF

Cellular and molecular gastroenterology and hepatology 20190725 1

This article reviews epidemiological evidence of heritability and putative mechanisms in diverticular disease, with greatest attention to 3 recent studies of genetic associations with diverticular disease based on genome-wide or whole-genome sequencing studies in large patient cohorts. We provide an analysis of the biological plausibility of the significant associations with gene variants reported and highlight the relevance of ANO1, CPI-17 (aka PPP1R14A), COLQ6, COL6A1, CALCB or CALCA, COL6A1, ...[more]

PMID: 31351939

Similar Datasets

Colonic diverticular disease.

Project description:Diverticula are outpouchings of the intestinal wall and are common anatomical alterations detected in the human colon. Colonic diverticulosis (the presence of diverticula in the colon; referred to as diverticulosis) remains asymptomatic in most individuals but ~25% of individuals will develop symptomatic diverticulosis, termed colonic diverticular disease (also known as diverticular disease). Diverticular disease can range in severity from symptomatic uncomplicated diverticular disease (SUDD) to symptomatic disease with complications such as acute diverticulitis or diverticular haemorrhage. Since the early 2000s, a greater understanding of the pathophysiology of diverticulosis and diverticular disease, which encompasses genetic alterations, chronic low-grade inflammation and gut dysbiosis, has led to improvements in diagnosis and management. Diagnosis of diverticular disease relies on imaging approaches, such as ultrasonography, CT and MRI, as biomarkers alone are insufficient to establish a diagnosis despite their role in determining disease severity and progression as well as in differential diagnosis. Treatments for diverticular disease include dietary fibre, pharmacological treatments such as antibiotics (rifaximin), anti-inflammatory drugs (mesalazine) and probiotics, alone or in combination, and eventually surgery. Despite being effective in treating primary disease, their effectiveness in primary and secondary prevention of complications is still uncertain.

| S-EPMC7486966 | biostudies-literature

Predictive value of the Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification on the outcome of diverticular disease of the colon: An international study.

Project description:Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification has been recently developed for patients suffering from diverticulosis and diverticular disease.We assessed retrospectively the predictive value of DICA in patients for whom endoscopic data and clinical follow-up were available.For each patient, we recorded: age, severity of DICA, presence of abdominal pain, C-reactive protein and faecal calprotectin test (if available) at the time of diagnosis; months of follow-up; therapy taken during the follow-up to maintain remission (if any); occurrence/recurrence of diverticulitis; need of surgery.We enrolled 1651 patients (793?M, 858?F, mean age 66.6?±?11.1 years): 939 (56.9%) patients were classified as DICA 1, 501 (30.3%) patients as DICA 2 and 211 (12.8%) patients as DICA 3. The median follow-up was 24 (9-38) months. Acute diverticulitis (AD) occurred/recurred in 263 (15.9%) patients; surgery was necessary in 57 (21.7%) cases. DICA was the only factor significantly associated to the occurrence/recurrence of diverticulitis and surgery either at univariate (?(2?)=?405.029; p?<?0.0001) or multivariate analysis (hazard ratio?=?4.319, 95% confidence interval (CI) 3.639-5.126; p?<?0.0001). Only in DICA 2 patients was therapy effective for prevention of AD occurrence/recurrence with a hazard ratio (95% CI) of 0.598 (0.391-0.914) (p?=?0.006, log rank test). Mesalazine-based therapies reduced the risk of AD occurrence/recurrence and needs of surgery with a hazard ratio (95% CI) of 0.2103 (0.122-0.364) and 0.459 (0.258-0.818), respectively.DICA classification is a valid parameter to predict the risk of diverticulitis occurrence/recurrence in patients suffering from diverticular disease of the colon.

| S-EPMC4971788 | biostudies-literature

Role of cyclooxygenase isoforms in the altered excitatory motor pathways of human colon with diverticular disease.

Project description:Background and purposeThe COX isoforms (COX-1, COX-2) regulate human gut motility, although their role under pathological conditions remains unclear. This study examines the effects of COX inhibitors on excitatory motility in colonic tissue from patients with diverticular disease (DD).Experimental approachLongitudinal muscle preparations, from patients with DD or uncomplicated cancer (controls), were set up in organ baths and connected to isotonic transducers. Indomethacin (COX-1/COX-2 inhibitor), SC-560 (COX-1 inhibitor) or DFU (COX-2 inhibitor) were assayed on electrically evoked, neurogenic, cholinergic and tachykininergic contractions, or carbachol- and substance P (SP)-induced myogenic contractions. Distribution and expression of COX isoforms in the neuromuscular compartment were assessed by RT-PCR, Western blot and immunohistochemical analysis.Key resultsIn control preparations, neurogenic cholinergic contractions were enhanced by COX inhibitors, whereas tachykininergic responses were blunted. Carbachol-evoked contractions were increased by indomethacin or SC-560, but not DFU, whereas all inhibitors reduced SP-induced motor responses. In preparations from DD patients, COX inhibitors did not affect electrically evoked cholinergic contractions. Both indomethacin and DFU, but not SC-560, decreased tachykininergic responses. COX inhibitors did not modify carbachol-evoked motor responses, whereas they counteracted SP-induced contractions. COX-1 expression was decreased in myenteric neurons, whereas COX-2 was enhanced in glial cells and smooth muscle.Conclusions and implicationsIn control colon, COX-1 and COX-2 down-regulate cholinergic motility, whereas both isoforms enhance tachykininergic motor activity. In the presence of DD, there is a loss of modulation by both COX isoforms on the cholinergic system, whereas COX-2 displays an enhanced facilitatory control on tachykininergic contractile activity.

| S-EPMC4128069 | biostudies-literature

Anticipation of thermal pain in diverticular disease.

Project description:BackgroundThe relative importance of peripheral nerve injury or central pain processing in painful diverticular disease (DD) is unclear. Functional magnetic resonance imaging (fMRI) has demonstrated that dysfunctional central pain processing predominates in irritable bowel syndrome (IBS). This study aims to identify anticipatory changes in symptomatic DD (SDD) compared to asymptomatic DD (ADD) and IBS patients.MethodsGastrointestinal symptoms and somatization were evaluated via the Patient Health Question-12 Somatic Symptom and the SDD group divided into low (?6 [LSDD]) and high (?7 [HSDD]) somatization. Cued painful cutaneous thermal stimuli were delivered to the left hand and foot during fMRI. Fixed effect group analysis of the 'cued' anticipatory phase was performed.Key resultsWithin the right posterior insula, greater deactivation was found in the ADD compared to other groups. In emotion processing centers, anterior and middle insula, greater activation was identified in all patient compared to the ADD group, and in LSDD compared to IBS and HSDD groups. In comparison, amygdala deactivation was greater in ADD than the IBS and HSDD groups, and in LSDD vs HSDD groups. Descending nociceptive control centers, such as the superior medial frontal and orbitofrontal cortex, also showed greater deactivation in the ADD and LSDD compared to the HSDD and IBS groups.Conclusions & inferencesThe HSDD group have altered anticipatory responses to thermal pain, similar to IBS group. The LSDD are similar to ADD group. This suggests underlying differences in pain pathophysiology, and the need for individualized treatment strategies to target the cause of their chronic pain.

| S-EPMC4879512 | biostudies-literature

Diverticular disease: A therapeutic overview.

Project description:Formation of colonic diverticula, via herniation of the colonic wall, is responsible for the development of diverticulosis. When diverticulosis becomes symptomatic, it becomes diverticular disease. Diverticular disease is common in Western and industrialized countries, and it is associated with numerous abdominal symptoms (including pain, bloating, nausea, diarrhea, and constipation). Standard medical therapies with antibiotics are currently recommended for patients affected by diverticular disease. However, changing concepts on the pathophysiology of the disease suggest that diverticular disease may share many of the hallmarks of inflammatory bowel diseases. On this basis, the addition of therapies using mesalazine and probiotics may enhance treatment efficacy by shortening the course of the disease and preventing recurrences.

| S-EPMC3091143 | biostudies-other

Diverticular disease and the obese patient.

Project description:Diverticular disease is common in the Western world and is a considerable source of morbidity. Many have proposed an association between diverticular disease, its complications, and obesity. We examine this question through a review of the available literature. While it is likely that an association between diverticular disease and obesity exists, there is no evidence suggesting that obese patients should be managed any differently from the non-obese.

| S-EPMC3311492 | biostudies-other

Crohn's-like reaction in diverticular disease.

Project description:BACKGROUND: Diverticulitis and Crohn's disease affecting the colon occur at similar sites in older individuals, and in combination are said to carry a worse prognosis than either disease in isolation. It is possible that diverticulitis may initiate inflammatory changes which resemble Crohn's disease histologically, but do not carry the clinical implications of chronic inflammatory bowel disease. AIMS: To evaluate histological features and clinical outcome in individuals initially diagnosed histologically as having both Crohn's colitis and diverticulitis. PATIENTS: Eleven consecutive individuals having a colonic resection showing histological features of both Crohn's disease and diverticulitis. METHODS: Retrospective review of histological specimens, case notes, and discharge letters. RESULTS: In nine patients, the Crohn's-like reaction was confined to the segment bearing diverticula. They had no clinical evidence of Crohn's disease. CONCLUSION: A Crohn's-like inflammatory response can be a localised reaction to diverticulitis and does not necessarily indicate chronic inflammatory bowel disease.

| S-EPMC1727035 | biostudies-other

Laparoscopic treatment of complicated colonic diverticular disease: A review.

Project description:Up to 10% of acute colonic diverticulitis may necessitate a surgical intervention. Although associated with high morbidity and mortality rates, Hartmann's procedure (HP) has been considered for many years to be the gold standard for the treatment of generalized peritonitis. To reduce the burden of surgery in these situations and as driven by the accumulated experience in colorectal and minimally-invasive surgery, laparoscopy has been increasingly adopted in the management of abdominal emergencies. Multiple case series and retrospective comparative studies confirmed that with experienced hands, the laparoscopic approach provided better outcomes than the open surgery. This technique applies to all interventions related to complicated diverticular disease, such as HP, sigmoid resection with primary anastomosis (RPA) and reversal of HP. The laparoscopic approach also provided new therapeutic possibilities with the emergence of the laparoscopic lavage drainage (LLD), particularly interesting in the context of purulent peritonitis of diverticular origin. At this stage, however, most of our knowledge in these fields relies on studies of low-level evidence. More than ever, well-built large randomized controlled trials are necessary to answer present interrogations such as the exact place of LLD or the most appropriate sigmoid resection procedure (laparoscopic HP or RPA), as well as to confirm the advantages of laparoscopy in chronic complications of diverticulitis or HP reversal.

| S-EPMC4770167 | biostudies-literature

Role of Inflammation in the Pathogenesis of Diverticular Disease.

Project description:Diverticulosis of the colon is the most common condition in Western societies and it is the most common anatomic alteration of the human colon. Recurrent abdominal pain is experienced by about 20% of patients with diverticulosis, but the pathophysiologic mechanisms of its occurrence are not completely understood. In the last years, several fine papers have showed clearly the role of low-grade inflammation both in the occurrence of symptoms in people having diverticulosis, both in symptom persistence following acute diverticulitis, even if the evidence available is not so strong. We do not know yet what the trigger of this low-grade inflammation occurrence is. However, some preliminary evidence found colonic dysbiosis linked to low-grade inflammation and therefore to symptom occurrence in those patients. The aim of this paper is to summarize current evidences about the role of inflammation in symptom occurrence in symptomatic uncomplicated diverticular disease and in symptom persistence after an episode of acute diverticulitis.

| S-EPMC6437747 | biostudies-literature

Laparoscopy improves short-term outcomes after surgery for diverticular disease.

Project description:Observational studies and small randomized controlled trials have shown that the use of laparoscopy in colon resection for diverticular disease is feasible and results in fewer complications. We analyzed data from a large, prospectively maintained, multicenter database (National Surgical Quality Initiative Program) to determine whether the use of laparoscopy in the elective treatment of diverticular disease decreases rates of complications compared with open surgery, independent of preoperative comorbid factors.The analysis included data from 6970 patients who underwent elective surgeries for diverticular disease from 2005 to 2008. Patients with diverticular disease were identified by International Classification of Diseases, 9th revision codes and then categorized into open or laparoscopic groups based on Current Procedural Terminology codes. Preoperative, intraoperative, and postoperative data were analyzed to determine factors associated with increased risk for postoperative complications.Data were analyzed from 3468 patients who underwent open surgery and 3502 patients who underwent laparoscopic procedures. After correcting for probability of morbidity, American Society of Anesthesiology class, and ostomy creation, overall complications (including superficial surgical site infections, deep incisional surgical site infections, sepsis, and septic shock) occurred with significantly lower incidence among patients who underwent laparoscopic procedures compared with those who received open operations.The use of laparoscopy for treating diverticular disease, in the absence of absolute contraindications, results in fewer postoperative complications compared with open surgery.

| S-EPMC3371380 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data