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.

Prognostic Role of the Endoscopic Classification "DICA".

Diverticular inflammation and complication assessment (DICA) endoscopic classification has been recently developed for patients suffering from diverticulosis and diverticular disease. Its predictive value in those patients was recently retrospectively assessed. For each patient, the following parameters were recorded: age, severity of DICA, presence of abdominal pain, C-reactive protein, fecal 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, and need of surgery. A total of 1651 patients (793 male, 858 female, mean age 66.6±11.1 y) were enrolled: 939 (56.9%) classified as DICA 1, 501 (30.3%) as DICA 2, and 211 (12.8%) as DICA 3. The median follow-up was 24 (9 to 138) months. Acute diverticulitis (AD) occurred/recurred in 263 (15.9%) patients, and surgery was necessary in 57 (21.7%) cases. DICA was the only factor significantly associated with the occurrence/recurrence of diverticulitis and surgery either at univariate (χ=405.029; P<0.0001) or multivariate analysis (hazard ratio=4.319; 95% CI, 3.639-5.126; P<0.0001). Only in DICA 2 patients scheduled therapy was 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 need 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 seems to be a valid parameter to predict the risk of diverticulitis occurrence/recurrence in patients suffering from diverticular disease of the colon.

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.

Treatment of Diverticular Disease With Aminosalicylates: The Evidence.

Colonic diverticulosis is an increasingly common condition in Western industrialized countries. About 20% of patients develop symptoms, including abdominal pain, bloating, changes in bowel habits, and, eventually, diverticulitis or other complications. The management of symptomatic uncomplicated diverticular disease (SUDD) and the prevention of acute diverticulitis remains a challenge for the clinician. The rationale for the use of aminosalicylates, such as mesalazine, is based on the assumption of low-grade inflammation in SUDD and symptoms generation, whereas an overt inflammation may induce diverticulitis in patients with diverticular disease. Clinical scenarios in which the efficacy and safety of mesalazine have been studied include SUDD, prevention of diverticulitis, and of recurrent diverticulitis. Data from uncontrolled studies suggest a benefit of mesalazine on patients with SUDD, whereas data from randomized controlled trials showed some evidence of improvement of symptoms, although contrasting results are reported. The largest study so far published on the efficacy of mesalamine in the prevention of recurrence of diverticulitis showed that mesalamine was not superior to placebo. At this time, the role of mesalazine in the prevention of acute diverticulitis remains to be defined with many issues open and unresolved.

Diverticular disease: changing epidemiology and management.

Diverticulosis is the most common pathological finding in routine colonoscopy. Diverticular disease comprises both diverticulitis and diverticular hemorrhage. This review examines the pathophysiological basis for disease including the importance of the elastin/collagen profile in diverticula formation. It summarizes the latest epidemiological findings with an emphasis on age- and sex-related differences. Risk factors including obesity, medications, hereditary factors, and diet are critically reviewed with the most up-to-date evidence. A detailed appraisal of therapeutic options is provided with special emphasis on 5-aminosalicylate, probiotics, mesalamine, percutaneous abscess drainage, and image-guided embolization. The role of antibiotics and surgery is discussed and compared with guideline recommendations. A more conservative approach, averting admission and even antibiotics, is explored. Finally, a careful review of the data surrounding the utility of colonoscopy in diagnosis and management is provided given the increasing number of reports citing the low incidence of colorectal neoplasia after an episode of diverticulitis. Throughout the review we focus on the older patient with diverticular disease.

Diverticular disease: guidelines of the german society for gastroenterology, digestive and metabolic diseases and the german society for general and visceral surgery.

BACKGROUND: Diverticular disease is one of the most common disorders of the gastrointestinal tract. 28-45% of the population develop colonic diverticula, while about 25% suffer symptoms and about 5% complications. AIM: To create formal guidelines for diagnosis and management. METHODS: Six working groups with 44 participants analyzed key questions in subject areas assigned to them. Following a systematic literature search, 451 publications were included. Consensus was obtained by agreement within the working groups, two Delphi processes and a guideline conference. RESULTS: Targeted management of diverticular disease requires a classificatory diagnosis. A new classification was created. In addition to the clinical examination, intestinal ultrasound or computed tomography is the determining factor. Interval colonoscopy is recommended to exclude comorbidities. A low-fiber diet, obesity, lack of exercise, smoking and immunosuppression have an adverse impact on diverticulosis. This can lead to diverticulitis. Antibiotics are no longer recommended in uncomplicated diverticulitis if no risk factors such as immunosuppression are present. If close monitoring is ensured, uncomplicated diverticulitis can be treated on an outpatient basis. Complicated diverticulitis should be treated in hospital, involving broad-spectrum antibiotic therapy, where necessary abscess drainage, and surgery, if possible laparoscopically. In the case of chronic relapsing diverticulitis, the risk of perforation decreases with each episode, so that surgery is no longer recommended after the second episode but only following individual assessment. CONCLUSIONS: New findings on diverticular disease call into question the overuse of antibiotics and excessive indications for surgery. Targeted treatment requires a precise diagnosis and intensive interdisciplinary cooperation.

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.

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.

Mesalazine in treating diverticular disease of the colon.

Evaluation of: Kruis W, Meier E, Schumacher M, Mickisch O, Greinwald R, Mueller R; German SAG-20 Study Group. Randomised clinical trial: mesalazine (Salofalk granules) for uncomplicated diverticular disease of the colon - a placebo-controlled study. Aliment. Pharmacol. Ther. 37(7), 680-690 (2013). Although diverticular disease (DD) is one of the commonest diseases in the western world, robust evidences about its treatment are lack so far. A recent, placebo-controlled study found mesalazine effective in obtaining pain relief in patients suffering from DD. A brief comment is provided herein in order to assess the rationale of this drug in treating DD.

Randomised clinical trial: mesalazine (Salofalk granules) for uncomplicated diverticular disease of the colon--a placebo-controlled study.

BACKGROUND: Robust evidence regarding medical intervention for symptomatic uncomplicated colonic diverticular disease (DD) is sparse. AIM: To investigate mesalazine (Salofalk granules) in this setting. METHODS: In a double-blind, placebo-controlled, multicentre, 6-week trial, patients were randomised to mesalazine 1000 mg three times daily or placebo. Primary efficacy endpoint was change in lower abdominal pain to week 4 (baseline defined using pain score from 7 days pre-treatment). RESULTS: Median change in lower abdominal pain with mesalazine vs. placebo was -37 (n = 56) vs. -33 (n = 61) [P = 0.374; 95% CI (-11; 4)] in the intent-to-treat (ITT) population, and -41 (n = 40) vs. -33 (n = 51) [P = 0.053; 95% CI (-18; 0)] in the per-protocol (PP) population, i.e. the primary endpoint was not significantly different. Post hoc adjustment for confounding factors ('baseline pain intensity', 'baseline symptom score (Brodribb)', and 'localisation of diverticula in the descending colon') resulted in P = 0.111 [ITT, 95% CI (-15.4; 1.6)] and P = 0.005 [PP, 95% CI (-19.7; -3.5)]. Between-group differences increased using pain score on day 1 as baseline, and reached significance for the PP population [mesalazine -42, placebo -26, P = 0.010; 95% CI (-25; -3)]. Median change in combined symptom score from baseline to week 4 was 257 mm with mesalazine vs. 198 mm with placebo [P = 0.064; 95% CI (-3; 105)]. More placebo-treated patients received analgesic/spasmolytic concomitant medication (34.4% vs. mesalazine 21.4%), indicating improved pain relief with mesalazine (P = 0.119). Safety was comparable. CONCLUSIONS: A daily dose of 3.0 g mesalazine may relieve pain during a symptomatic flare of uncomplicated DD. In this, the first placebo-controlled double-blind trial in acute uncomplicated DD, mesalazine showed promising therapeutic efficacy.

[Multipurpose psyllium monotherapy in patients with diverticular disease].

The purpose of the research was the study of the prebiotic and hypolipidemic effects of 12-week treatment by psillium of patients with uncomplicated diverticular disease and hyperlipidemia. It has been established that the examined medicine has not any by-effects, normalizes intestinal motility and lowers a pain syndrome and flatulence. Prebiotic effect has proved by higher concentration of short-chain fatty acids in faeces and reduction of anaerobic index. Psillium certainly reduces levels of hyperlipidemia and could be recommended as hypolipidemic remedy for monotherapy as long as base datum of cholesterol is less than 6,4 mmol/l.

[Colonic diverticular disease: diagnosis and therapy]. / A diverticularis betegség és kezelése.

Colonic diverticular disease is one of the most common gastrointestinal disorders in the Western world, affecting approximately 50% of the population above the age of 70 years. Symptoms develop only in about one quarter of the affected individuals with complications in one-third of the symptomatic patients. Diagnosis is mostly confirmed by colonoscopy. Abdominal CT is the most sensitive for the diagnosis of complicated severe diverticulitis, while colonoscopy or in severe cases angiography may be performed in bleeding patients. Initial therapy of non-complicated symptomatic diverticulitis includes antibiotics and more recently non-absorbable antibiotics. In complicated cases should be treated with broad spectrum i.v. antibiotics, however surgery may became necessary in a minority of the cases. The proportion of patients needing acute surgical intervention has decreased in the last decades with the advancement of conservative management including medical therapy, endoscopy and imaging techniques and the indication of elective was also changed.

Segmental colitis associated with diverticulosis: systematic evaluation of 486 cases with meta-analysis.

BACKGROUND/AIMS: Segmental colitis associated with colonic diverticulosis is a new and emerging entity. We systematically evaluated 486 cases of this entity and performed qualitative meta-analysis on this information. METHODOLOGY: This diagnosis was made on a 64-year old man by colonoscopic biopsy. His clinical symptoms included hematochezia and crampy lower abdominal pain. PubMed Search using terms such as segmental colitis, colitis associated with diverticulosis was made without language or time barrier. Additional papers were manually added from the reference lists of key articles. Qualitative meta-analysis was done using the well-established methods of qualitative research, e.g. diagramming, theme repetition without serious contradiction, theme saturation and investigator reflexivity. To facilitate qualitative meta-analysis, summary sheets of publications were created. RESULTS: This search produced 486 cases with this entity. The prevalence in patients with diverticulosis is 0.3% to 1.3%. There were 58.7% men. The mean age was 63.6 (range 26-87) years. The most common presenting symptoms were rectal bleeding, diarrhea and abdominal pain. Fever, leucocytosis and rectal involvement were characteristically absent. Endoscopic appearance and histology may resemble ulcerative colitis. Many of these patients have a benign course with spontaneous resolution or may respond to 5-aminosalucylates or steroids. CONCLUSIONS: This is a new and emerging entity. There is male predominance and it occurs in relatively elderly patients. It can be distinguished from acute diverticulitis by clinical, endoscopic and histological features. Most have a benign course.

Diverticular disease: epidemiology and management.

Diverticular disease of the colon is among the most prevalent conditions in western society and is among the leading reasons for outpatient visits and causes of hospitalization. While previously considered to be a disease primarily affecting the elderly, there is increasing incidence among individuals younger than 40 years of age. Diverticular disease most frequently presents as uncomplicated diverticulitis, and the cornerstone of management is antibiotic therapy and bowel rest. Segmental colitis associated with diverticula shares common histopathological features with inflammatory bowel disease and may benefit from treatment with 5-aminosalicylates. Surgical management may be required for patients with recurrent diverticulitis or one of its complications including peridiverticular abscess, perforation, fistulizing disease, and strictures and / or obstruction.

Role of fecal calprotectin in the diagnosis and treatment of segmental colitis associated with diverticulosis.

AIM: Information about fecal calprotectin (FC) in segmental colitis associated with diverticulosis (SCAD) is lacking. We assessed FC in SCAD, comparing it healthy controls (HC), irritable bowel syndrome (IBS), diverticular disease (DD), ulcerative colitis (UC). Moreover, we compared FC levels in different degrees of SCAD and assessed FC SCAD before and after treatment. METHODS: Twenty-seven consecutive patients with a new endoscopic diagnosis of SCAD, and 16 patients for each control group, underwent to FC assessment. FC was assessed by semi-quantitative method. RESULTS: FC was not increased in HC and in IBS patients, whilst it was increased in DD, SCAD, and UC. FC concentration was higher in SCAD and UC than in DD (SCAD vs. DD, P=0.05). No difference was found in FC concentration between SCAD and UC (P=0.213), as well as between different degree of SCAD (P= 0.178). After treatment, FC values decreased to normal values in all patients obtaining remission (P<0.0005). Three patients experienced still symptoms (one SCAD type B and two SCAD type D patients), and in all of them FC was still detectable. CONCLUSION: FC may be useful in differentiating SCAD from functional syndromes. Moreover, it may be useful in assessing response to therapy.