Role of Dietary Habits in the Prevention of Diverticular Disease Complications: A Systematic Review.

Recent evidence showed that dietary habits play a role as risk factors for the development of diverticular complications. This systematic review aims to assess the effect of dietary habits in the prevention of diverticula complications (i.e., acute diverticulitis and diverticula bleeding) in patients with diverticula disease. PubMed and Scopus databases were searched up to 19 January 2021, 330 records were identified, and 8 articles met the eligibility criteria and were subjected to data extraction. The quality of the studies was evaluated by the Newcastle-Ottawa quality assessment form. No study meets the criteria for being a high-quality study. A high intake of fiber was associated to a decreased risk of diverticulitis or hospitalization due to diverticular disease, with a protective effect for fruits and cereal fiber, but not for vegetable fiber; whereas, a high red meat consumption and a generally Western dietary pattern were associated with an increased risk of diverticulitis. Alcohol use seemed to be associated to diverticular bleeding, but not to recurrent diverticulitis or diverticular complications. Further high-quality studies are needed to better define these associations. It is mandatory to ascertain the role of dietary habits for the development of recurrent acute diverticulitis and diverticular bleeding.

Presentation and anatomical distribution of diverticular disease in four hospitals in Sudan.

INTRODUCTION: diverticular disease (DD) was thought to be more prevalent in the western countries, especially the white populations, but the recent increase in incidence among African and Asian population, was reported. Up to our knowledge, there is no previous study of DD in Sudan. METHODS: this is a descriptive cross-sectional study conducted at the department of endoscopy in four Sudanese hospitals in the period from October 2017 to February 2019. We included all patients who underwent colonoscopy during the study period. The main objective is to study the presentation and the anatomical pattern of diverticular disease among the Sudanese population. RESULTS: prevalence of DD in the included population was 7.5% (104/1393). The mean age was 66.4 ± 12.5 years with the percentage of males in our study is 77.1% and females were 22.9%. Presenting complains were: abdominal pain in all patients, constipation in 78.8% and rectal bleeding in 57.7%. Regarding anatomical distribution: 63.5% have left colonic DD, 19.2% in the right colon and 17.3% involving the entire colon. There was a significant correlation between the left side DD and following clinical presentations: mucus per-rectum (p = 0.015) and weight loss (p = 0.048). Other endoscopic findings of significance were internal pile in 21.2% and colo-rectal polyp in 15.4%. CONCLUSION: the prevalence of DD in the included population, is 7.5% which is consistent with recent literature from the Middle East, Africa and Asia but still less than the prevalence in the western countries and left side colon is predominantly affected.

Colonic diverticular disease.

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.

Pathophysiology of diverticular disease.

INTRODUCTION: Inflammation of diverticula, or outpouchings of the colonic mucosa and submucosa through the muscularis layer, leads to diverticulitis. The development of diverticular disease, encompassing both diverticulosis and diverticulitis, is a result of genetic predisposition, lifestyle, and environmental factors, including the microbiome. Areas covered: Previous reports implicated genetic predisposition, environmental factors, and colonic dysmotility in diverticular disease. Recent studies have associated specific host immune responses and the microbiome as contributors to diverticulitis. To review pertinent literature describing pathophysiological factors associated with diverticulosis or diverticulitis, we searched the PubMed database (March 2018) for articles considering the role of colonic architecture, genetic predisposition, environment, colonic motility, immune response, and the microbiome. Expert commentary: In the recent years, research into the molecular underpinnings of diverticular disease has enhanced our understanding of diverticular disease pathogenesis. Although acute uncomplicated diverticulitis is treated with broad spectrum antibiotics, evaluation of the microbiome has been limited and requires further comprehensive studies. Evidence suggests that a deregulation of the host immune response is associated with both diverticulosis and diverticulitis. Further examining these pathways may reveal proteins that can be therapeutic targets or aid in identifying biological determinants of clinical or surgical decision making.

The correlation between diverticulosis and redundant colon.

BACKGROUND: Diverticulosis and redundant colon are colonic conditions for which underlying pathophysiology, management and prevention are poorly understood. Historical papers suggest an inverse relationship between these two conditions. However, no further attempt has been made to validate this relationship. This study set out to assess the correlation between diverticulosis and colonic redundancy. METHODS: Redundant colon, diverticulosis and patient demographics were recorded during colonoscopy. Multivariate binary logistic regression was performed with redundant colon as the dependent variable and age, gender and diverticulosis as independent variables. Nagelkerke R 2 and a receiver operator curve were calculated to assess goodness of fit and internally validate the multivariate model. RESULTS: Redundant colon and diverticulosis were diagnosed in 31 and 113 patients, respectively. The probability of redundant colon was increased by female gender odds ratio (OR) 8.4 (95% CI 2.7-26, p = 0.00020) and increasing age OR 1.7 (95% CI 1.1-2.6, p = 0.017). Paradoxically, diverticulosis strongly reduced the probability of redundant colon with OR of 0.12 (95% CI 0.42-0.32, p = 0.000039). The Nagelkerke R 2 for the multivariate model was 0.29 and the area under the curve at ROC analysis was 0.81 (95% CI 0.73-0.90 p-value 3.1 × 10-8). CONCLUSIONS: This study found an inverse correlation between redundant colon and diverticulosis, supporting the historical suggestion that the two conditions rarely occur concurrently. The underlying principle for this relationship remains to be found. However, it may contribute to the understanding of the aetiology and pathophysiology of these colonic conditions.

Limited evidence of abnormal intra-colonic pressure profiles in diverticular disease - a systematic review.

AIM: Abnormal colonic pressure profiles and high intraluminal pressures are postulated to contribute to the formation of sigmoid colon diverticulosis and the pathophysiology of diverticular disease. This study aimed to review evidence for abnormal colonic pressure profiles in diverticulosis. METHOD: All published studies investigating colonic pressure in patients with diverticulosis were searched in three databases (Medline, Embase, Scopus). No language restrictions were applied. Any manometry studies in which patients with diverticulosis were compared with controls were included. The Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control studies was used as a measure of risk of bias. A cut-off of five or more points on the NOS (fair quality in terms of risk of bias) was chosen for inclusion in the meta-analysis. RESULTS: Ten studies (published 1962-2005) met the inclusion criteria. The studies followed a wide variety of protocols and all used low-resolution manometry (sensor spacing range 7.5-15 cm). Six studies compared intra-sigmoid pressure, with five of six showing higher pressure in diverticulosis vs controls, but only two reached statistical significance. A meta-analysis was not performed as only two studies were above the cut-off and these did not have comparable outcomes. CONCLUSION: This systematic review of manometry data shows that evidence for abnormal pressure in the sigmoid colon in patients with diverticulosis is weak. Existing studies utilized inconsistent methodology, showed heterogeneous results and are of limited quality. Higher quality studies using modern manometric techniques and standardized reporting methods are needed to clarify the role of colonic pressure in diverticulosis.

Risk factors for severity and recurrence of colonic diverticular bleeding

Background: Colonic diverticular bleeding is the most common cause of lower gastrointestinal bleeding. Risk factors related to severity and repeated bleeding episodes are not completely clearly defined. Objective: To characterize a Portuguese population hospitalized due to colonic diverticular bleeding and to identify the clinical predictors related to bleeding severity and rebleeding. Methods: Retrospective analysis of all hospitalized patients diagnosed with colonic diverticular bleeding from January 2008 to December 2013 at our institution. The main outcomes evaluated were bleeding severity, defined as any transfusion support requirements and/or signs of hemodynamic shock, and 1-year recurrence rate. Results: Seventy-four patients were included, with a mean age of 75.7 ± 9.5 years; the majority were male (62.2%). Thirty-six patients (48.6%) met the criteria for severe bleeding; four independent risk factors for severe diverticular bleeding were identified: low hemoglobin level at admission (≤ 11 g/dL; OR 18.8), older age (≥ 75 years; OR 4.7), bilateral diverticular location (OR 14.2) and chronic kidney disease (OR 5.6). The 1-year recurrence rate was 12.9%. We did not identify any independent risk factor for bleeding recurrence in this population. Conclusion: In this series, nearly half of the patients hospitalized with diverticular bleeding presented with severe bleeding. Patients with low hemoglobin levels, older age, bilateral diverticular location and chronic kidney disease had a significantly increased risk for severe diverticular bleeding. In addition, a small number of patients rebled within the first year after the index episode, although we could not identify independent risk factors associated with the recurrence of diverticular bleeding (AU)

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Diverticular Disease of the Colon: Neuromuscular Function Abnormalities.

Colonic diverticular disease is a frequent finding in daily clinical practice. However, its pathophysiological mechanisms are largely unknown. This condition is likely the result of several concomitant factors occurring together to cause anatomic and functional abnormalities, leading as a result to the outpouching of the colonic mucosa. A pivotal role seems to be played by an abnormal colonic neuromuscular function, as shown repeatedly in these patients, and by an altered visceral perception. There is recent evidence that these abnormalities might be related to the derangement of the enteric innervation, to an abnormal distribution of mucosal neuropeptides, and to low-grade mucosal inflammation. The latter might be responsible for the development of visceral hypersensitivity, often causing abdominal pain in a subset of these patients.

[Prevention of complications of colonic diverticular disease in outpatient practice].

The literature review gives an update on the frequency and risk factors of complications of colonic diverticular disease, the results of recent investigations, which suggest the success and safety of outpatient treatment for uncomplicated acute diverticulitis. It evaluates the efficacy of pharmacological agents from different groups in preventing complications of colonic diverticular disease.

Changes in the response to excitatory antagonists, agonists, and spasmolytic agents in circular colonic smooth muscle strips from patients with diverticulosis.

BACKGROUND: Colonic samples from asymptomatic diverticulosis (DS) patients presented enhanced electrical field stimulation (EFS)-contractions, in an earlier study of ours, suggesting increased endogenous responses. The aim of this study was to explore changes in excitatory neuromuscular transmission and to assess the pharmacodynamics of spasmolytic agents in DS. METHODS: Circular muscle strips from sigmoid colon of DS patients (n = 30; 69.5 ± 14.8 years) and controls (n = 32; 64.7 ± 16.2 years) were studied using organ baths to evaluate the direct effect of excitatory agonists (carbachol, neurokinin A [NKA] and substance P [SP]), and the effect of antagonists (atropine and NK2 antagonist GR94800) and spasmolytic drugs (otilonium bromide [OB] and N-butyl-hyoscine) on the contractions induced by EFS-stimulation of excitatory motorneurons. qRT-PCR was also performed to compare mRNA expression of M2 , M3 , NK2 receptors and L-type calcium channels. KEY RESULTS: Contractions to carbachol (Emax : 663.7 ± 305.6% control vs 2698.0 ± 439.5% DS; p < 0.0005) and NKA (Emax : 387.8 ± 35.6% vs 1102.0 ± 190.1%; p < 0.0005) were higher in DS group, without differences for SP. Higher potency for DS patients was observed in the concentration-response curves for atropine (pIC50  = 8.56 ± 0.15 control vs pIC50  = 9.95 ± 0.18 DS group; p < 0.005) and slightly higher for GR94800 (pIC50  = 7.21 ± 0.18 control vs pIC50  = 7.97 ± 0.32 group; p < 0.0001). Lower efficacy (Emax ) and potency (pIC50 ) was observed for spasmolytic drugs in DS, whereas no differences were found regarding the relative expression of the receptors evaluated between groups. CONCLUSIONS & INFERENCES: The greater response to cholinergic and tachykinergic agonists and greater potency for muscarinic and NK2 antagonists observed in DS might play a role in the spasticity found in diverticular disease.

Colonic diverticular disease. Treatment and prevention.

Diverticular disease represents the most common disease affecting the colon in the Western world. Most cases remain asymptomatic, but some others will have symptoms or develop complications. The aims of treatment in symptomatic uncomplicated diverticular disease are to prevent complications and reduce the frequency and intensity of symptoms. Fibre, probiotics, mesalazine, rifaximin and their combinations seem to be usually an effective therapy. In the uncomplicated diverticulitis, outpatient management is considered the optimal approach in the majority of patients, and oral antibiotics remain the mainstay of treatment. Admission to hospital and intravenous antibiotic are recommended only when the patient is unable to intake food orally, affected by severe comorbidity or does not improve. However, inpatient management and intravenous antibiotics are necessary in complicated diverticulitis. The role of surgery is also changing. Most diverticulitis-associated abscesses can be treated with antibiotics and/or percutaneous drainage and emergency surgery is considered only in patients with acute peritonitis. Finally, patient related factors, and not the number of recurrences, play the most important role in selecting recipients of elective surgery to avoid recurrences.

Association between colonic diverticulosis and bowel symptoms: A case-control study of 1629 Asian patients.

BACKGROUND: It remains unclear whether diverticulosis, absent inflammation, is responsible for chronic bowel symptoms. We examined the association between bowel symptoms and asymptomatic diverticulosis. METHOD: This case-control study included 543 patients with diverticulosis and 1086 age and sex-matched controls (1:2) without diverticulosis on screening colonoscopy. Eleven symptoms (abdominal discomfort, hunger discomfort, borborygmus, abdominal distension, flatus, constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) were evaluated using a gastrointestinal symptoms rating scale (GSRS) at baseline and second questionnaire. Associations between diverticulosis and symptoms were estimated using odds ratios (ORs) and 95 confidence interval (CI). RESULTS: In multivariate analysis, constipation (OR, 0.85 [0.78-0.93]) and hard stools (OR, 0.86 [0.78-0.94]) were negatively associated with diverticulosis. The other nine symptoms showed no association with diverticulosis. Diverticulosis was negatively associated with constipation (OR, 0.93 [0.74-0.93]), hard stools (OR, 0.85 [0.76-0.96]), and incomplete evacuation (OR, 0.88 [0.79-0.99]) in males, and positively associated with diarrhea (OR, 1.39 [1.14-1.69]) and loose stools (OR, 1.28 [1.05-1.55]) in females. No bowel symptoms were positively associated with any of right-sided, left-sided, or bilateral diverticulosis. Test-retest reliability of GSRS (mean interval, 4.4 months) was moderate (Mean Kappa, 0.568) in males and good (Mean Kappa, 0.652) in females. CONCLUSIONS: This large, colonoscopy-based, case-control study demonstrated that neither constipation nor hard stools were associated with an increased risk of diverticulosis, regardless of diverticulum location. In females, but not males, diarrhea and loose stools were positively associated with diverticulosis. Long-term test-retest reliability suggested that these symptoms remain consistent over a given period.

Nitrergic neuro-muscular transmission is up-regulated in patients with diverticulosis.

BACKGROUND: Neuro-transmission impairment could be associated to motility changes observed in patients with diverticular disease. Therefore, the objective was to characterize the inhibitory neuro-muscular transmission and gene expression changes of the enteric inhibitory pathways in patients with diverticulosis (DS). METHODS: Circular muscle strips from sigmoid colon of patients with DS and controls were studied using the organ bath technique to evaluate spontaneous contractility and enteric motor neurons stimulated by electrical field and qRT-PCR to assess the expression of nNOS, iNOS, P2Y1 R and PGP9.5. KEY RESULTS: Patients with DS presented decreased spontaneous rhythmic contractions (SRC) that were significantly enhanced after incubation with L-NNA (1 mM) and TTX (1 µM), and unaffected by the P2Y1 antagonist MRS2500 (1 µM). Stimulation on enteric motor neurons caused an increased duration of the latency of OFF-contractions in DS group (p < 0.001), antagonized by L-NNA and slightly affected by MRS2500 (1 µM). No differences in the IC50 between controls and DS patients were observed on inhibition of SRC for the NO-donor sodium nitroprusside (SNP) and the preferential P2Y agonist ADPßS. Moreover, nNOS relative expression was also up-regulated 2.3-fold in the DS group (p < 0.05) whereas there was no significant difference in relative expression of iNOS, P2Y1 R and the neuronal marker PGP9.5 between groups. CONCLUSIONS & INFERENCES: Patients with DS presented an over-expression of nNOS with increased endogenously NO-mediated responses suggesting enhanced NO-release. Up-regulation in the nitrergic pathway in early stages of the disease might play a role in colonic motor disorders associated to diverticular disease.

New physiopathological and therapeutic approaches to diverticular disease: an update.

INTRODUCTION: Diverticular disease (DD) of the colon is a widespread disease, which shows worldwide increasing incidence and represents a significant burden for National Health Systems. The current guidelines claim that symptomatic uncomplicated DD (SUDD) has to be treated with spasmolithics and high-fiber diet, whereas both uncomplicated and complicated acute diverticulitis has to be treated with antibiotics. However, new physiopathological knowledge suggests that further treatment may be promising. AREAS COVERED: Pathogenetic and treatment studies on SUDD and acute diverticulitis published in PubMed, www.clinicaltrials.gov , and in the main International Congress were reviewed. EXPERT OPINION: Although absorbable antibiotics and 5-aminosalycilic acid seem to be effective in treating SUDD, their role in preventing diverticulitis recurrence is still under debate. Antibiotic use in managing acute diverticulitis is at least questionable, and use of probiotics seems to be promising but need further robust studies to confirm the preliminary results.

The alterations of the sigmoid-rectal junction in diverticular disease of the colon revealed by MR-defecography.

PURPOSE: The sigmoidorectal junction (SRJ) has been defined as an anatomical sphincter with particular physiological behavior that regulates sigmoid and rectum evacuation. Its function in clinical conditions, such as diverticular disease has been advocated. The aim of our study is to identify the SRJ and to compare the morphometric and dynamic features of the SRJ between patients with diverticular disease and healthy subjects using MR-defecography. METHODS: Sixteen individuals, eight with uncomplicated diverticular disease and eight healthy subjects, were studied using MR-defecography to identify the SRJ and to compare the morphometric and dynamic features observed. RESULTS: In each subject studied, MR-defecography was able to identify the SRJ. This resulted in the identification of a discrete anatomical entity with a mean length of 31.23 mm, located in front of the first sacral vertebra (S1) and at a mean distance of 15.55 cm from the anal verge, with a mean wall thickness of 4.45 mm, significantly different from the sigmoid and rectal parietal thickness. The SRJ wall was significantly thicker in patients with diverticular disease than the controls (P = 0.005), showing a unique shape and behavior in dynamic sequences. CONCLUSION: Our findings support the hypothesis that SRJ plays a critical role in patients with symptomatic diverticular disease; further investigation may clarify whether specific SRJ analysis, such as MR-defecography, would predict inflammatory complications of this diffuse and heterogenic disease.

In vitro motor patterns and electrophysiological changes in patients with colonic diverticular disease.

PURPOSE: The underlying mechanism responsible for motility changes in colonic diverticular disease (DD) is still unknown. In the present study, our aim was to investigate the structural and in vitro motor changes in the sigmoid colon of patients with DD. METHODS: Muscle bath, microelectrodes and immunohistochemical techniques were performed with samples obtained from the left and sigmoid colon of patients with DD and compared with those of patients without DD. RESULTS: The amplitude and area under the curve of the spontaneous rhythmic phasic contractions were greatly reduced in patients with DD whereas their frequency and tone remained unaltered. Electrical field stimulation induced a neurally mediated, enhanced ON-contraction (amplitude) in patients with DD and increased the duration of latency of OFF-contractions. The resting membrane potential of smooth muscle cells was hyperpolarized and the amplitude of the inhibitory junction potential was increased in patients with DD. In contrast, no significant histological differences were observed in patients with DD as smooth muscle (circular and longitudinal layers), interstitial cells of Cajal, glial cells and myenteric neurons densities remained unaltered. CONCLUSIONS: Sigmoid strips from patients with asymptomatic DD showed an altered motor pattern with reduced spontaneous motility and enhanced neurally mediated colonic responses involving both excitatory and inhibitory motor pathways. No major neural and muscular structural elements were detected at this stage of the disease. These findings could be valuable in understanding the pathophysiology of this prevalent digestive disease.

Alcohol consumption is a risk factor for colonic diverticulosis.

BACKGROUND AND AIM: The exact factors predisposing to colonic diverticulosis other than age are unknown. METHODS: Cross-sectional study of asymptomatic subjects undergoing screening colonoscopy. A detailed dietary and social questionnaire was completed on all participants. A worldwide review of the literature was performed to further investigate any association between identified risk factors and diverticulosis. RESULTS: Seven hundred forty-six consecutive individuals were enrolled (mean age, 61.1±8.3 y; female: male=0.98). Overall, the prevalence of diverticulosis was 32.8% (95% CI, 29.5-36.2). Diverticula were left-sided, right-sided, or both in 71.5%, 5.8%, and 22.7% of affected subjects, respectively. On univariate analysis, age, sex, adenomatous polyps, advanced neoplasia (adenoma≥1 cm, villous histology, or cancer), aspirin, and alcohol use were significantly associated with diverticulosis. Diet, body mass index, physical activity, and bowel habits were not associated with the disease. On multivariate analysis, increasing age (P<0.001), advanced neoplasia (P=0.021), and alcohol consumption (P<0.001) were significantly associated with diverticulosis. The adjusted odds ratio for diverticulosis in alcohol users was 1.91 (1.36 to 2.69), with increasing prevalence with higher alcohol consumption (P-value for trend=0.001). When the prevalence of diverticulosis reported from 18 countries was analyzed against alcohol use, there was a strong correlation with national per-capita alcohol consumption rates (Pearson correlation coefficient r=0.68; P=0.002). CONCLUSIONS: Alcohol use is a significant risk factor for colonic diverticulosis and may offer a partial explanation for the existing East-West paradox in disease prevalence and phenotype. Further studies are needed to investigate this association and its putative pathophysiological mechanisms.

Pathogenesis of colonic diverticular disease.

PURPOSE: This paper aims to review the current evidence regarding pathogenesis of colonic diverticular disease and its complications, which are a major health problem in the Western world. METHODS: Based on selective Medline searches, relevant literature was indentified regarding pathogenesis of (1) diverticulosis/formation of diverticula, (2) diverticulitis/inflammation of diverticula, (3) complicated diverticulitis/perforation, and (4) diverticular bleeding. RESULTS: Pathogenesis of colonic diverticula is regarded as a multifactorial process, involving dietary factors (Western low-fiber diet), structural changes of the colonic wall (altered musculature, collagen, elastin, etc.) and functional changes (motility disorder, increased intraluminal pressure). Genetic changes are also discussed and aging is also a key factor. Pathogenesis of inflammation (diverticulosis) is regarded as a result of "microperforations" at the fundus of the diverticulum, and not an "abscessed diverticulum" due to an impacted fecolith. Histamine and its receptors do also seem to play a role, corresponding with the promising prophylactic approach with probiotics. Pathogenesis of complicated diverticulitis is characterized by perforation, which is the cardinal feature. Furthermore, an intensive inflammatory infiltrate with macrophages is found in surgical specimens, even after antibiotic pretreatment. Steroid intake and immunosuppression are risk factors and only recently a glucocorticoid-induced tumor necrosis factor-receptor has been suggested to resemble the molecular link. Diverticular bleeding is a distinct disease process-which does usually take place without diverticulitis-and is due to eccentric rupture of the vas rectum. CONCLUSIONS: The pathophysiology of diverticular disease is multifactorial. Some of the current evidence has important implications for clinical practice, e.g., the suggested role of steroid intake and immunosuppression for complicated diverticulitis.