Efficacy of a New Nutraceutical Formulation in Patients with Symptomatic Uncomplicated Diverticular Disease (SUDD): a Prospective Observational Study.

BACKGROUND AND AIM: Symptomatic uncomplicated diverticular disease (SUDD) is characterized by abdominal pain, bloating and altered bowel habits (constipation or diarrhea) attributed to diverticula in the absence of macroscopic mucosal alterations. There is no consensus about management of these patients. DIVER-100®, an association of natural active ingredients may be effective in the treatment of patients with SUDD. The aim was to evaluate the efficacy and safety of DIVER-100® in patients with SUDD. METHODS: We conducted a prospective observational study to evaluate the efficacy of DIVER-100® in consecutive patients with SUDD, confirmed by radiology or endoscopy. All patients were treated with DIVER-100® 2 capsules/day 10 days per month, for 3 months. The primary endpoint was the clinical remission rate, defined as the reduction of abdominal pain and bloating, improvement of bowel habits and prevention of acute diverticulitis (AD). The secondary endpoint was the rate of adverse events. RESULTS: One hundred and one patients were consecutively enrolled at the Internal Medicine and Gastroenterology Unit, Sant'Orsola Hospital, Bologna, Italy. DIVER-100® was effective in inducing remission of symptoms in 12 patients (11.9%) at 3 months and in 10 patients (9.9%) at 6 months. DIVER-100® significantly reduced abdominal pain and bloating in 45.5% and 57.4% of patients respectively (p <0.001) after 3 months. No episodes of AD and no adverse events related to DIVER--100® were recorded at month 6 in the study population. CONCLUSIONS: DIVER-100® is a safe and effective nutraceutical compound in obtaining remission and symptom relief in SUDD patients. Further randomized, placebo-controlled clinical trials are needed to confirm these preliminary data.

Mesalazine to treat symptomatic uncomplicated diverticular disease and to prevent acute diverticulitis occurrence. A systematic review with meta-analysis of randomized, placebo-controlled trials.

BACKGROUND AND AIMS: Symptomatic Uncomplicated Diverticular disease (SUDD) affects about 25% of patients harboring colonic diverticula. We assessed the effectiveness of mesalazine in improving symptoms (namely abdominal pain, primary outcome) and in preventing diverticulitis occurrence (secondary outcome) in patients with SUDD. METHODS: Pertinent studies were selected from the Medline and the Cochrane Central Register of Controlled Trials. Only randomized clinical trials (RCTs) (irrespective of language, blinding, or publication status), which compared mesalazine, irrespective of the dosage assumption, with placebo in SUDD were evaluated. RESULTS: Four RCTs enrolled 379 patients, 197 treated with mesalazine and 182 with placebo. Two studies provided data on symptom relief according to definition: it was achieved in 97/121 (80%) patients in the mesalazine group and in 81/129 (62.7%) patients in the placebo group (OR 0.43; 95% CI 0.24-0.75; p=0.003 in favour of the mesalazine group). Two studies provided information regarding occurrence of diverticulitis during follow-up. It occurred in 23/119 (19.3%) patients in the mesalazine group and in 34/102 (33.3%) patients in the placebo group (OR 0.35; 95% CI 0.17-0.70; p=0.003 in favour of the mesalazine group). CONCLUSIONS: Treatment with mesalazine seems to be effective in achieving symptom relief and in the primary prevention of diverticulitis in patients with SUDD.

Effect of mesalazine on recurrence of diverticulitis in patients with symptomatic uncomplicated diverticular disease: a meta-analysis with trial sequential analysis of randomized controlled trials.

AIM: he aim was to investigate the effect of mesalazine on the recurrence of diverticulitis in patients with symptomatic uncomplicated diverticular disease (SUDD). METHODS: We performed a systematic review and conducted a search of electronic information sources to identify all randomized controlled trials (RCTs) investigating the effect of mesalazine on the recurrence of diverticulitis in patients with SUDD. We used the Cochrane tool to assess the quality of included studies. Random effects models were applied to calculate pooled outcome data. Trial sequential analysis was performed to assess the possibility of type I or II errors and to compute the information size required for conclusive meta-analysis. RESULTS: We identified six RCTs which enrolled a total of 1918 patients. There was no difference in the recurrence of diverticulitis between the mesalazine and placebo groups (OR 1.20, 95% CI 0.96-1.50, P = 0.11). A low level of heterogeneity among the studies existed (I2  = 9%, P = 0.36). When the mesalazine dose was ≤ 2 g/day, there was no difference in recurrence rate between the two groups (OR 1.10, 95% CI 0.79-1.54, P = 0.58). When the mesalazine dose was > 2 g/day, the risk of recurrence was higher in the mesalazine group (OR 1.28, 95% CI 1.02-1.62, P = 0.04). The information size was calculated as 2461 patients. Trial sequential analysis showed that the meta-analysis was conclusive and the risk of type II error was minimal. CONCLUSIONS: Mesalazine does not prevent the recurrence of diverticulitis in patients with SUDD. Further studies are required to investigate the role of mesalazine as an adjunct to other medical agents in the prevention of diverticulitis in patients with SUDD.

Mesalamine (5-ASA) for the prevention of recurrent diverticulitis.

BACKGROUND: Diverticular disease is a common condition that increases in prevalence with age. Recent theories on the pathogenesis of diverticular inflammation have implicated chronic inflammation similar to that seen in ulcerative colitis. Mesalamine, or 5-aminosalicylic acid (5-ASA), is a mainstay of therapy for individuals with ulcerative colitis. Accordingly, 5-ASA has been studied for prevention of recurrent diverticulitis. OBJECTIVES: To evaluate the efficacy of mesalamine (5-ASA) for prevention of recurrent diverticulitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), in the Cochrane Library; Ovid MEDLINE (from 1950 to 9 September 2017); Ovid Embase (from 1974 to 9 September 2017); and two clinical trials registries for ongoing trials - Clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform database (9 September 2017).We also searched proceedings from major gastrointestinal conferences - Digestive Disease Week (DDW), United European Gastroenterology Week (UEGW), and the American College of Gastroenterology (ACG) Annual Scientific Meeting - from 2010 to September 2017. In addition, we scanned reference lists from eligible publications, and we contacted corresponding authors to ask about additional trials. SELECTION CRITERIA: We included randomised controlled clinical trials comparing the efficacy of 5-ASA versus placebo or another active drug for prevention of recurrent diverticulitis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as defined by Cochrane. Three review authors assessed eligibility for inclusion. Two review authors selected studies, extracted data, and assessed methodological quality independently. We calculated risk ratios (RRs) for prevention of diverticulitis recurrence using an intention-to-treat principle and random-effects models. We assessed heterogeneity using criteria for Chi2 (P < 0.10) and I2 tests (> 50%). To explore sources of heterogeneity, we conducted a priori subgroup analyses. To assess the robustness of our results, we carried out sensitivity analyses using different summary statistics (RR vs odds ratio (OR)) and meta-analytical models (fixed-effect vs random-effects). MAIN RESULTS: We included in this review seven studies with a total of 1805 participants. We judged all seven studies to have unclear or high risk of bias. Investigators found no evidence of an effect when comparing 5-ASA versus control for prevention of recurrent diverticulitis (31.3% vs 29.8%; RR 0.69, 95% confidence interval (CI) 0.43 to 1.09); very low quality of evidence).Five of the seven studies provided data on adverse events of 5-ASA therapy. The most commonly reported side effects were gastrointestinal symptoms (epigastric pain, nausea, and diarrhoea). No significant difference was seen between 5-ASA and control (67.8% vs 64.6%; RR 0.98, 95% CI 0.91 to 1.06; P = 0.63; moderate quality of evidence), nor was significant heterogeneity observed (I2 = 0%; P = 0.50). AUTHORS' CONCLUSIONS: The effects of 5-ASA on recurrence of diverticulitis are uncertain owing to the small number of heterogenous trials included in this review. Rates of recurrent diverticulitis were similar among participants using 5-ASA and control participants. Effective medical strategies for prevention of recurrent diverticulitis are needed, and further randomised, double-blinded, placebo-controlled trials of rigorous design are warranted to specify the effects of 5-ASA (mesalamine) in the management of diverticulitis.

Dietary pattern and colonic diverticulosis.

PURPOSE OF REVIEW: To assess the role of dietary pattern on the occurrence of colonic diverticulosis, diverticular disease and acute diverticulitis. RECENT FINDINGS: High-fiber diet does not prevent diverticulosis occurrence, and results about prevention/treatment of diverticular disease and acute diverticulitis are still conflicting.No association was seen between nut, corn or popcorn consumption and occurrence of diverticulosis, diverticular disease and acute diverticulitis.It seems to be a mild association between high alcohol intake and diverticulosis occurrence, whereas alcohol dependence seems to show lower risk of in-hospital mortality due to acute diverticulitis.Higher red-meat consumption shows mild increased risk of acute diverticulitis, especially when consumed as unprocessed red meat (defined as consumption of 'beef or lamb as main dish', 'pork as main dish', 'hamburger' and 'beef, pork or lamb as a sandwich or mixed dish'); higher consumption of poultry (viz. white meat) was not associated with risk of acute diverticulitis.Finally, higher fish intake was associated with reduced risk of diverticulitis in age-adjusted model, but not after further adjustment for other potential confounders. SUMMARY: Current literature data about the role of dietary pattern on the occurrence of colonic diverticulosis, diverticular disease and acute diverticulitis are still too conflicting.

Risk factors for recurrence after acute colonic diverticulitis: a systematic review.

PURPOSE: Several factors may influence the risk of recurrence after an episode of acute colonic diverticulitis. Until now, a comprehensive systematic overview and evaluation of relevant risk factors have not been presented. This review aimed at assembling and evaluating current evidence on risk factors for recurrence after conservatively treated acute colonic diverticulitis. METHODS: PubMed, Embase, and Cochrane databases were searched for studies evaluating risk factors for recurrence after acute diverticulitis treated non-surgically defined as antibiotic treatment, percutaneous abscess drainage, or by observation. Randomized clinical trials and observational studies were included. Analyzed outcome variables were extracted and grouped. No meta-analysis was performed due to low inter-study comparability. Variables were rated according to their likelihood of causing recurrence (no/low, medium, high). RESULTS: Of 1153 screened records, 35 studies were included, enrolling 396,676 patients with acute diverticulitis. A total of 50,555 patients experienced recurrences. Primary diverticulitis with abscess formation and young age increased the risk of recurrence. Readmission risk was higher within the first year after remission. In addition, the risk of subsequent diverticulitis more than doubled after two earlier episodes of diverticulitis and the risk increased further for every episode. CONCLUSIONS: The best treatment strategy for recurrent diverticulitis is undetermined. However, the risk of a new recurrence seemed to increase after each recurrence making elective resection a viable option at some point after multiple recurrences depending on patient risk factors and preferences.

Mesalazine for the Treatment of Symptomatic Uncomplicated Diverticular Disease of the Colon and for Primary Prevention of Diverticulitis: A Systematic Review of Randomized Clinical Trials.

BACKGROUND: Symptomatic uncomplicated diverticular disease (SUDD) is a common gastrointestinal disease, because it affects about one fourth of the patient harboring colonic diverticula. GOAL: To assess the effectiveness of mesalazine in improving symptoms (namely abdominal pain) and in preventing diverticulitis occurrence in patients with SUDD. STUDY: Only randomized clinical trials (irrespective of language, blinding, or publication status) that compared mesalazine with placebo or any other therapy in SUDD were evaluated. The selected endpoints were symptom relief and diverticulitis occurrence at maximal follow-up. Absolute risk reduction (ARR, with 95% confidence interval) and the number needed to treat were used as measures of the therapeutic effect. RESULTS: Six randomized clinical trials enrolled 1021 patients: 526 patients were treated with mesalazine and 495 with placebo or other therapies. Symptom relief with mesalazine was always larger than that with placebo and other therapies. However, absolute risk reduction was significant only when mesalazine was compared with placebo, a high-fiber diet, and low-dose rifaximin. The incidence of diverticulitis with mesalazine was lower than that observed with placebo and other treatments, being significant only when compared with placebo. CONCLUSIONS: Mesalazine is effective in achieving symptom relief and primary prevention of diverticulitis in patients with SUDD.

[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.

A population-based case-control study on statin exposure and risk of acute diverticular disease.

OBJECTIVE: A reduced risk of perforated diverticular disease among individuals with current statin exposure has been reported. The aim of the present study was to investigate whether statins reduce the risk of acute diverticular disease. MATERIAL AND METHODS: A nation-wide population-based case-control study was performed, including 13,127 cases hospitalised during 2006-2010 with a first-time diagnosis of colonic diverticular disease, and 128,442 control subjects (matched for sex, age, county of residence and calendar year). Emergency surgery, assumed to be a proxy for complicated diverticulitis, was performed on 906 of the cases during the index admission, with 8818 matched controls. Statin exposure was classified as "current" or "former" if a statin prescription was last dispensed ≤ 125 days or >125 days before index date, respectively. The association between statin exposure and acute diverticular disease was investigated by conditional logistic regression, including models adjusting for country of birth, educational level, marital status, comorbidities, nonsteroidal anti-inflammatory drug/steroid exposure and healthcare utilisation. RESULTS: A total of 1959 cases (14.9%) and 16,456 controls (12.8%) were current statin users (crude OR 1.23 [95% CI 1.17-1.30]; fully adjusted OR 1.00 [0.94-1.06]). One hundred and thirty-two of the cases subjected to surgery (14.6%), and 1441 of the corresponding controls (16.3%) were current statin users (crude OR 0.89 [95% CI 0.73-1.08]; fully adjusted OR 0.70 [0.55-0.89]). CONCLUSIONS: The results do not indicate that statins affect the development of symptomatic diverticular disease in general. However, current statin use was associated with a reduced risk of emergency surgery for 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.

[Dietary prevention and treatment of diverticular disease of the colon]. / PostEpowanie dietetyczne w profilaktyce i leczeniu choroby uchyLkowej jelita grubego.

Diverticular disease is more often categorized as a civilization disease that affects both women and men, especially at an old age. The pathophysiology remains complex and arises from the interaction between dietary fiber intake, bowel motility and mucosal changes in the colon. Obesity, smoking, low physical activity, low-fiber diet (poor in vegetables, fruit, whole grain products, seeds and nuts) are among factors that increase the risk for developing diverticular disease. Additionally, the colonic outpouchings may be influenced by involutional changes of the gastrointestinal tract. Therefore, the fiber rich diet (25-40 g/day) plays an important role in prevention, as well as nonpharmacological treatment of uncomplicated diverticular disease. The successful goal of the therapy can be achieved by well-balanced diet or fiber supplements intake. Research indicate the effectiveness of probiotics in dietary management during the remission process. Moreover, drinking of appropriate water amount and excluding from the diet products decreasing colonic transit time - should be also applied.

[Prevention and conservative therapy of diverticular disease]. / Prophylaxe und konservative Therapie der Divertikelkrankheit.

Diverticulosis and diverticular disease are a common problem in daily practice and one third of the patients with diverticulosis develop symptoms. Patients with uncomplicated diverticulitis are very often treated with antibiotics. There is growing evidence that antibiotics are not necessary in uncomplicated cases. One problem is the different classification of diverticulitis and diverticular disease. Therefore, it is not easy to compare different studies. The evidence for therapy with antibiotics, mesalamine, probiotics and fibers are initially discussed and secondly therapeutic recommendations are given for the various stages of diverticular disease.

Microencapsulated sodium butyrate administered to patients with diverticulosis decreases incidence of diverticulitis--a prospective randomized study.

BACKGROUND: Microencapsulated sodium butyrate (MSB) has been previously associated with anti-inflammatory and regenerative properties regarding large bowel mucosa. We aimed to examine a role of MSB in patients with diverticulosis, hypothesizing its potential for reduction of diverticulitis episodes and diverticulitis prevention. METHODS: Seventy-three patients with diverticulosis (diagnosed in colonoscopy or/and barium enema or/and CT colography) were recruited for the study and randomized. The investigated group was administered MSB 300 mg daily; the control group was administered placebo. After 12 months, a total of 52 patients completed the study and were subject to analysis (30 subjects and 22 controls). During the study, the number of episodes of diverticulitis (symptomatic diagnosis with acute pain, fever, and leukocytosis), hospitalizations, and surgery performed for diverticulitis were recorded. Additionally, a question regarding subjective improvement of symptoms reflected changes in quality of life during the analysis. RESULTS: After 12 months, the study group noted a significantly decreased number of diverticulitis episodes in comparison to the control group. The subjective quality of life in the study group was higher than in the control group. There were no side effects of the MSB during the therapy. CONCLUSIONS: MSB reduces the frequency of diverticulitis episodes, is safe, and improves the quality of life. It can play a role in the prevention of diverticulitis.

Intermittent versus every-day mesalazine therapy in preventing complications of diverticular disease: a long-term follow-up study.

BACKGROUND: Mesalazine seems to be effective in preventing recurrence of acute uncomplicated diverticulitis (AUD), but the optimal mesalazine scheme to achieve these results is still debated. AIM: To assess the effectiveness of two different mesalazine-based treatments in preventing recurrence of AUD and the occurrence of other complications of diverticular disease (DD) during a long-term follow-up. PATIENTS AND METHODS: We reviewed 311 patients suffer from recent episode of AUD and undergoing to mesalazine treatment: 207 (group A, 105 males, median age 63 years, range 47-74 years) were treated with mesalazine 1.6 g for 10 days each month, whilst 104 (group B, 55 males, median age 65 years, range 50-72 years) were treated with mesalazine 1.6 g every day. Patients were followed-up every 6 months (median 7.5 months, range 5-13 months). RESULTS: Patients were followed-up for a mean time of 3 years (range 12-72 months). Overall, occurrence of complication recurred more frequently in group A than in group B (p = 0.030, log-rank test). Acute diverticulitis recurred in 17 (8.2%) patients in group A and in 3 (2.9%) in group B; diverticular bleeding occurred in 4 (1.9%) patients in group A and in 1 (0.96%) patient in group B; surgery was required in 3 (1.4%) patients in group A and in no (0%) patient in group B. CONCLUSIONS: This is the first study showing that long-term mesalazine treatment is significantly better that intermittent mesalazine treatment in preventing occurrence of DD complications after an attack of acute diverticulitis.

[Medical treatment of sigmoid diverticulitis]. / Traitement médical des diverticulites sigmoïdiennes.

Acute diverticulitis is defined by diverticular and peridiverticular inflammation and infection and is efficiently treated medically in most of the cases. For most patients, outpatient treatment is possible and hospitalization is only indicated if the patient is unable to eat, suffers from an acute attack, has diverticulitis related complications or if symptoms fail to improve despite adequate outpatient therapy The treatment of acute uncomplicated diverticulitis usually consists of broad-spectrum antibiotics covering both aerobic and anaerobic bacteria. Antibiotic therapy is usually administrated for 7 to 10 days but its duration can be longer if any complications occur. If there is no clinical improvement within 2 or 3 days, repeat CT imaging is needed, as this may reveal an abscess, phlegmon or fistula, which may require percutaneous drainage or surgery. The published literature does not support the recommendation of any prophylactic diet or medical treatment for reducing the risk of first or recurrent diverticulitis in patients with diverticulosis.

[Surgical treatment of sigmoid diverticulitis]. / Traitement chirurgical de a diverticulite sigmoïdienne.

Surgery for diverticulitis is usually discussed in two situations: in emergency to treat a diverticulitis related complication or electively to prevent the risk of diverticulitis recurrence (prophylactic colonic resection). Surgical treatment of complicated diverticulitis has gone to changes during the last decade thanks to advances in laparoscopic surgery and interventional radiology (drainage, embolization). Emergency surgery for diverticulitis is mainly indicated (90%) for infectious related complications and more rarely for bleeding or stenosis. Surgery is the standard treatment of peritonitis complicating diverticulitis (Hinchey 3 or 4) and is recommended in Hinchey 1 or 2 diverticulitis after failure of a well conducted medical treatment with or without radiological drainage (for abscesses >or= 5cm). Indications for prophylactic surgery after an episode of uncomplicated diverticulitis is not systematic and should be discussed case by case according to the baseline characteristics of patients. Prophylactic surgery consists in sigmoid resection including the sigmoido-rectal junction with colorectal anastomosis and should be performed under laparoscopy.

[Follow-up and dietary advice after sigmoid diverticulitis]. / Suivi et conseils diét6téques dans la diverticulose colique et ses complications.

Currently published data do not demonstrate the benefit of any medical treatment in the prevention of the onset or the recurrence of colonic diverticular disease. No specific diet can be recommended to patients with colonic diverticula for the prevention of diverticular disease. Non steroidal anti-inflammatory drugs as well as corticosteroids should be used cautiously in patients with diverticular disease since they induce a higher rate of complications, especially diverticular haemorrhage and severe sigmoid diverticulitis. In patients over 50 years old, or if a sigmoidectomy is needed, physicians should perform a colonoscopy in order to rule out colonic polyps or neoplasm.