Use of mesalazine in diverticular disease

Diverticular disease includes a spectrum of conditions sharing the underlying pathology of acquired diverticula of the colon: symptomatic uncomplicated diverticular disease, recurrent symptomatic uncomplicated diverticular disease, and complicated diverticular disease. Goals of therapy in diverticular disease should be to improve symptoms and to prevent recurrent attacks in symptomatic uncomplicated diverticular disease, and to prevent the complications of disease such as diverticulitis. Inflammation seems to play a key role in all forms of the disease. This is the rationale for the use of anti-inflammatory drugs such as mesalazine. Inflammation in such diseases seems to be generated by a heightened production of proinflammatory cytokines, reduced anti-inflammatory cytokines, and enhanced intramucosal synthesis of nitric oxide. The mechanisms of action of mesalazine are not yet well understood. It is an anti-inflammatory drug that inhibits factors of the inflammatory cascade (such as cyclooxygenase) and free radicals, and has an intrinsic antioxidant effect. Some recent studies confirm the efficacy of mesalazine in diverticular disease both in relief of symptoms in symptomatic uncomplicated forms and in prevention of recurrence of symptoms and main complications.     

High-fibre diet and Lactobacillus paracasei B21060 in symptomatic uncomplicated diverticular disease

AIM:To investigate in symptomatic uncomplicated diverticular disease the efficacy of symbiotics associated with a high-fibre diet on abdominal symptoms.METHODS:This study was a multicentre,6-mo randomized,controlled,parallel-group intervention with a preceding 4-wk washout period.Consecutive outpatients with symptomatic uncomplicated diverticular disease,aged 40-80 years,evaluated in 4 Gastroenter-ology Units,were enrolled.Symptomatic uncomplicated diverticular disease patients were randomized to two treatment arms A or B.Treatment A(n = 24 patients) received 1 symbiotic sachet Flortec(Lactobacillus paracasei B21060) once daily plus high-fibre diet for 6 mo.Treatment B(n = 21 patients) received high-fibre diet alone for 6 mo.The primary endpoint was regression of abdominal symptoms and change of symptom severity after 3 and 6 mo of treatment.RESULTS:In group A,the proportion of patients with abdominal pain 24 h decreased from 100% at baseline to 35% and 25% after 3 and 6 mo,respectively(P 0.001).In group B the proportion of patients with this symptom decreased from 90.5% at baseline to 61.9% and 38.1% after 3 and 6 mo,respectively(P = 0.001).Symptom improvement became statistically significant at 3 and 6 mo in group A and B,respectively.The proportion of patients with abdominal pain 24 h decreased from 60% to 20% then 5% after 3 and 6 mo,respectively in group A(P 0.001) and from 33.3% to 9.5% at both 3 and 6 mo in group B(P = 0.03).In group A the proportion of patients with abdominal bloating significantly decreased from 95% to 60% after 3 mo,and remained stable(65%) at 6-mo follow-up(P = 0.005) while in group B,no significant changes in abdominal bloating was observed(P = 0.11).After 6 mo of treatment,the mean visual analogic scale(VAS) values of both short-lasting abdominal pain(VAS,mean ± SD,group A:4.6 ± 2.1 vs 2.2 ± 0.8,P = 0.02;group B:4.6 ± 2.9 vs 2.0 ± 1.9,P = 0.03) and abdominal bloating(VAS,mean ± SD,group A:5.3 ± 2.2 vs 3.0 ± 1.7,P = 0.005;group B:5.3 ± 3.2 vs 2.3 ± 1.9,P = 0.006) decreased in both groups,whilst the VAS values of prolonged abdominal pain decreased in the Flortec group,but remained unchanged in the high-fibre diet group(VAS,mean ± SD,group A:6.5 ± 1.5 vs 4.5 ± 2.1,P = 0.052;group B:4.5 ± 3.8 vs 5.5 ± 3.5).CONCLUSION:A high-fibre diet is effective in relievingabdominal symptoms in symptomatic uncomplicated diverticular disease.This treatment may be implemented by combining the high-fibre diet with Flortec.     

Clinical features of symptomatic uncomplicated diverticular disease: a multicenter Italian survey

Purpose

Clinical features of symptomatic uncomplicated diverticular disease are poorly investigated. Abdominal symptoms may be similar to those of irritable bowel syndrome. This survey aimed to assess clinical features associated with symptomatic uncomplicated diverticular disease.

Methods

This multicenter survey included consecutive outpatients with symptomatic uncomplicated diverticular disease to whom a detailed clinical questionnaire regarding demographic, lifestyle, and clinical features was administered. Diagnosis was based on the presence of diverticula and abdominal pain/discomfort. Irritable bowel syndrome and functional dyspepsia were assessed according to Rome III criteria.

Results

A total of 598 patients (50?% female, age 69?years), 71?% with newly diagnosed symptomatic uncomplicated diverticular disease and 29?% with history of colonic diverticula, were recruited. Diverticula were localized in the left colon in 78?% of the patients. Recurrent short-lived abdominal pain (<24?h) was present in 70?% (relieved by evacuation in 73?%), prolonged abdominal pain (>24?h) in 27?%, and recurrent abdominal bloating in 61?% of the patients. Normal, loose, or hard stools were reported by 58, 29, and 13?% of patients, respectively. Irritable bowel syndrome (IBS)-like and functional dyspepsia-like symptoms were recorded in 59 and 7?% of patients, respectively. IBS-like symptoms (odds ratio, 4.3) were associated in patients with prolonged abdominal pain.

Conclusions

Symptomatic uncomplicated diverticular disease is associated with a gender ratio of 1:1 and an unspecific clinical picture mainly characterized by normal stools, short-lived abdominal pain, abdominal bloating, IBS-like symptoms, while functional dyspepsia-like symptoms are not commonly present. These findings suggest that symptomatic uncomplicated diverticular disease often shows similar findings rather than overlaps IBS.     

The effect of non-pathogenic Escherichia coli in symptomatic uncomplicated diverticular disease of the colon

BACKGROUND: The effect of probiotics in symptomatic uncomplicated diverticular disease of the colon has not been followed. DESIGN: Treatment (T1) with an intestinal antimicrobial (dichlorchinolinol) and absorbent (active coal tablets) was compared with the same set-up supplemented with non-pathogenic Escherichia coli(T2) in a prospective open trial. SETTING: The study was performed at the outpatient department of a tertiary centre. PARTICIPANTS: Fifteen subjects (5 males, 10 females) aged 68-91 years (average 74.8 years) presented with abdominal pain, irregular defecation, bloating and excessive flatulence. Diagnosis was established with colonoscopy, double-contrast barium enema, or both. INTERVENTIONS: The T1 regimen was administered for 1 week. In the T2 regimen, the application of E. coli strain Nissle (Mutaflor capsules, 2.5 x 10(10) viable bacteria/capsule) followed immediately after T1 for an average of 5.2 weeks. MAIN OUTCOME MEASURES: The lengths of two successive remissions with the T1 set-up were compared with the length of remission after T2. The intensity of symptoms before and after administration of the probiotic was also evaluated.RESULTS The lengths of two successive remissions after T1 amounted to 2.66 and 2.20 months (average 2.43 months). The average length of remission after T2 was 14.1 months (P < 0.001). All symptoms after T2 decreased significantly (P < 0.001). CONCLUSIONS: Non-pathogenic strain Nissle significantly prolonged the remission period and improved the abdominal syndrome in symptomatic uncomplicated diverticular disease. A randomized, placebo-controlled study is recommended.     

Does uncomplicated diverticular disease produce symptoms?

A questionnaire dealing with bowel symptoms was administered to 97 outpatients referred for air-contrast barium enema. Subsequenlly, the barium enema was interpreted by a radiologist who did not know the results of the questionnaire. Forty-nine had normal x-rays, and 27 had uncomplicated diverticular disease. Weight loss, rectal bleeding, abdominal pain, and pain at night were as common in those with a normal examination as in those with diverticula. Symptoms of colon dysfunction included abdominal pain relieved by defecation, altered stool frequency and consistency with pain onset, abdominal distension, feeling of incomplete evacuation after defecation, and mucus in the stool. These were equally prevalent in both groups. Therefore, no symptoms could be ascribed to the presence of diverticulaSupported by the Ottawa Foundation of Medical Research.     

Effect of mesalazine on epithelial cell proliferation in colonic diverticular disease

Background and aimsIncreased epithelial cell proliferation may be detected in diverticular disease, but antibiotics have failed in reducing it. We assess therefore the effect of mesalazine on epithelial cell proliferation in diverticular disease.MethodsA prospective study was conducted on 20 consecutive patients with a new endoscopic diagnosis of symptomatic uncomplicated diverticular disease. The patients were treated with mesalazine 1.6 mg/day for 1 year. The Ki-67 antigen index of the whole crypt and in the upper third was separately evaluated before and after starting the treatment.ResultsCell proliferation index was higher in diverticular disease patients than healthy controls both in the whole crypt (median 6.7%, range 2–9% vs. median 1.6%, range 1–3%, p = 0.001) and in the upper third of the crypt (median 6.8%, range 2–8% vs. median 1.8%, range 1–3%, p = 0.001).Cell proliferation decreased throughout the follow-up. In the whole crypt it was 6.7% at entry and 3.8% at the end of treatment (p < 0.005), whereas it was 6.8% at entry and 2.9% at the end of treatment in the upper third of the crypt (p < 0.005).ConclusionsWe found mesalazine effective in reducing the colonic cell proliferation in long-term treatment for colonic diverticular disease.     

Mesalazine and/or Lactobacillus casei in maintaining long-term remission of symptomatic uncomplicated diverticular disease of the colon

BACKGROUND/AIMS: Four different therapeutic schedules with mesalazine and/or probiotics were assessed in preventing recurrence of symptomatic diverticular disease (DD) of the colon. METHODOLOGY: A prospective, dose-finding study was conducted on 75 patients, enrolled in an open fashion: mesalazine 800mg/daily (group M1) or mesalazine 1.6gr 10 days/month (group M2); mesalazine 800mg/daily + Lactobacillus casei DG 16 billion/day for 10 day/month (group LM1) or mesalazine 1.6gr + Lactobacillus casei DG 16 billion/day for 10 day/month (group LM2); Lactobacillus casei DG 16 billion/day for 10 day/month (group L). RESULTS: Seventy one patients completed the study (94.66%). Sixty six patients (88%) were symptom-free after the 24th month of treatment: 11 of group M1 (on i-t-t: 84% [CI 95%: 55.5-98.8]), 8 of group M2 (on i-t-t: 80% [CI 95%: 44.39-97.48]), 15 of group LM1 (on i-t-t: 93.75% [CI 95%: 69.77-99.84]), 12 of group LM2 (on i-t-t: 92.30% [CI 95%: 63.97-99.81]), 20 in group L (on i-t-t: 86.95% [CI 95%: 66.41-97.22]) (p-ns). Four patients (5.33%) suspended the treatment during the follow-up: all experienced recurrence of symptoms (100%), and 2 of them developed diverticulitis (50%). CONCLUSIONS: Mesalazine and/or Lactobacillus casei seem to be effective in maintaining remission of DD for long-time. Moreover, we found recurrence of the disease and complications in all patients suspending treatments.     

Efficacy of long term cyclic administration of the poorly absorbed antibiotic Rifaximin in symptomatic, uncomplicated colonic diverticular disease

AIM To comparatively evaluate the long term efficacy of Rifaximin and dietary fibers in reducing symptoms and/or complication frequency in symptomatic, uncomplicated diverticular disease.METHODS 307 patients (118 males, 189 females,age range 40-80 years) were enrolled in the study and randomly assigned to Rifaximin (400 mg bid for 7 d every month) plus dietary fiber supplementation (at least 20 gr/d) or dietary fiber supplementation alone.The study duration was 24 mo; both clinical examination and symptoms' questionnaire were performed every two months.RESULTS Both treatments reduced symptom frequency,but Rifaximin at a greater extent, when compared to basal values. Symptomatic score declined during both treatments, but a greater reduction was evident in the Rifaximin group (6.4 2.8 and 6.2 2.6 at enrollment,P = NS, 1.0 0.7 and 2.4 1.7 after 24 mo, P ＜ 0.001,respectively). Probability of symptom reduction was higher and complication frequency lower (Kaplan-Meyer method) in the Rifaximin group (P ＜ 0.0001 and 0.028,respectively).CONCLUSION In patients with symptomatic,uncomplicated diverticular disease, cyclic administration of Rifaximin plus dietary fiber supplementation is more effective in reducing both symptom and complication frequency than simple dietary fiber supplementation.Long term administration of the poorly absorbed antibiotic Rifaximin is safe and well tolerated by the patients,confirming the usefulness of this therapeutic strategy in the overall management of diverticular disease.     

Long-term outcomes of patients with symptomatic gastroesophageal reflux disease treated with vonoprazan

Objective: The novel potassium-competitive acid blocker, vonoprazan, provides rapid and effective acid suppression. The aim of this study is to evaluate the long-term outcomes of patients with symptomatic gastroesophageal reflux disease (GERD) treated with vonoprazan.

Methods: This retrospective cohort study included 55 patients with symptomatic GERD treated with vonoprazan who have been followed for more than one year. The effectiveness of vonoprazan on gastrointestinal symptoms was evaluated using the Izumo scale, a self-reported questionnaire reflecting quality of life related to various abdominal symptoms.

Results: These 55 patients with symptomatic GERD had non-erosive reflux disease (n?=?30) or erosive esophagitis (n?=?25). Vonoprazan (10?mg) for one month improved GERD symptoms in 89% (responders) and the improvement was maintained at one year in 82% without additional treatment. One-year maintenance therapy resulted in sustained resolution of GERD symptoms in 47%. Of the 49 responders, nine patients had relapse of GERD symptoms and dose escalation of vonoprazan improved the symptoms in six patients. Postprandial distress and the presence of erosive esophagitis before starting vonoprazan were identified as significant negative and positive predictors of sustained resolution of GERD symptoms for one year, respectively. Epigastric pain, postprandial distress, constipation and diarrhea were significantly improved at one-month and maintained at one year. After one-year of treatment, the endoscopic healing rate of erosive esophagitis was 95%.

Conclusion: One-year treatment with vonoprazan significantly improves GERD symptoms and endoscopic healing of erosive esophagitis is satisfactory. The long-term use of vonoprazan is effective and useful to control GERD.     

Therapeutic and prophylactic role of mesalazine (5-ASA) in symptomatic diverticular disease of the large intestine. 4 year follow-up results

In order to evaluate the efficacy and tolerability of mesalazine (5-ASA) in the prophylaxis of symptomatic relapses, of major complications and of microhemorrhagic phenomena in diverticular disease of the large intestine (MDC), prospective clinical study was conducted on patients with light-moderate symptomatic MDC under treatment with sulbactam-ampicillin 1.5 g/12 h i.m. and rifaximine 400 mg/12 h per os for 7 days. Follow-up period of 5 years with seriated checkups and laboratory and instrumentation controls. End points are represented by the relapse on inflammation and/or by the occurrence of major complications. On enrollment, 166 patients were randomized to receive mesalazine (Pentacol tablets--SOFAR S.p.A.) 400 mg b.i.d. per os for 8 weeks (81 patients; group M) or no supplementary treatment (85 patients; group C). After 4 years of follow-up, 44 patients dropped out of the study (9 because of major complications, 3 for massive hemorrhage, and 32 drop outs). Symptomatic relapses occurred in 51 patients (12 M; 39 C), while minor diverticular hemorrhages occurred in 43 patients (12 M; 31 C), with an estimated probability of remaining free respectively from symptomatic relapse (p=0.00005) and from microhemorrhagic phenomena (p=0.001) decisively in favor of the group treated with mesalazine. The duration of abdominal pain due to diverticolitis was also shorter in patients of group M (p=0.0002), while the incidence of major complications and side effects was comparable in the two groups. In conclusion, supplementary treatment with mesalazine in patients affected with MDC--at a follow-up limited to 48 months--proved to be well tolerated and effective in reducing the frequency of symptomatic relapses and microhemorrhagic phenomena and in reducing the duration of abdominal pain.     

Role of endoscopy in patients with diverticular disease

Acute diverticulitis occurs in 10-25% of patients with diverticulosis. Colonoscopy is advised 6 weeks after an attack of acute diverticulitis in order to completely evaluate the colonic lumen and exclude a potential malignancy. We conducted several studies aimed to evaluate the feasibility and safety of early colonoscopy in patients with acute diverticulitis. Consecutive patients hospitalized for acute diverticulitis were included. In the first phase of the study, patients with adjacent peri-diverticular air/fluid on CT were excluded. In the second phase of the study, we included patients with peri-diverticular air/fluid on CT as well. During the first phase of the study, 39 patients underwent uneventful colonoscopy. During the second phase of the study, 40 patients underwent colonoscopy and 1 of 6 patients with peri-diverticular air had perforation of her sigmoid colon. Two patients had a more protracted course and were clearly those who benefited most from the early colonoscopy. Based on our study, we concluded that early colonoscopy in acute diverticulitis is feasible. It should be reserved either for all patients with no air adjacent to diverticuli on CT or just for those with a more protracted course. In the third phase, a prospective randomized study was conducted on patients with acute diverticulitis with no peri-diverticular air. Such patients were randomized into those who underwent early colonoscopy and those who underwent colonoscopy 6 weeks later. Eighty-three patients were included in both groups and in none has a significant lesion been identified (except polyps). It seems therefore that the current abdominal CT with its excellent resolution is enough to exclude colonic cancer. Colonoscopy should be reserved only for patients with a protracted unresolved course of acute diverticulitis.     

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.     

Rifaximin improves symptoms of acquired uncomplicated diverticular disease of the colon

BACKGROUND AND AIMS: We examined the efficacy of cyclic long-term administration of rifaximin, a broad spectrum, poorly absorbable antibiotic, in obtaining symptom relief in a large series of patients with uncomplicated diverticular disease, and compared the incidence of episodes of diverticulitis in the group treated with rifaximin to that in a group receiving fiber supplementation only. PATIENTS AND METHODS: In a multicenter, prospective, open trial, 968 outpatients with uncomplicated symptomatic diverticular disease were randomized to either fiber supplementation with 4 g/day glucomannan plus 400 mg rifaximin twice daily for 7 days every month ( n=558) or 4 g/day glucomannan alone ( n=346). Clinical evaluation was performed on admission and at 4-month intervals for 12 months. RESULTS: After 12 months the group treated with glucomannan + rifaximin showed fewer symptoms (abdominal pain/discomfort, bloating, tenesmus, diarrhea, abdominal tenderness) and a lower global symptomatic score. Overall 56.5% of the patients treated with glucomannan + rifaximin and 29.2% of those treated with glucomannan alone were asymptomatic at 12 months ( P<0.001). The rate of complications (diverticulitis and rectal bleeding) was 1.34% in the rifaximin + glucomannan group and 3.22% in the glucomannan alone group ( P<0.05). CONCLUSION: Cyclic administration of rifaximin is effective in obtaining symptom relief in uncomplicated diverticular disease of the colon. The incidence of episodes of diverticulitis in the group treated with rifaximin was lower than that in the group treated with glucomannan alone.     

Analysis of clinical manifestations of symptomatic acquired jejunoileal diverticular disease

AIM: To analyze systematically our experience over 22 years with symptomatic acquired diverticular disease of the jejunum and ileum, exploring the clinical manifestations and diagnosis of this rare but life-threatening disease. METHODS: The medical records of patients with surgically confirmed symptomatic jejunoileal diverticular disease were retrospectively reviewed. Data collected included demographic data, laboratory results, clinical course (acute or chronic), preoperative diagnosis, and operative findings. Inclusion criteria were as follows: (1) surgical confirmation of jejunoileal diverticular disease and (2) exclusion of congenital diverticula (e.g. Meckel's diverticulum). RESULTS: From January 1982 to July 2004, 28 patients with a total of 29 operations met the study criteria. The male:female ratio was 14:14, and the mean age was 62.6+/-3.5 years. The most common manifestation was abdominal pain. In nearly half of the patients, the symptoms were chronic. Two patients died after surgery. Only four cases were correctly diagnosed prior to surgery, three by small bowel series. CONCLUSION: Symptomatic acquired small bowel diverticular disease is difficult to diagnose. It should be considered in older patients with unexplained chronic abdominal symptoms. A small bowel series may be helpful in diagnosing this potentially life-threatening disease.     

Abnormal colonic cholinergic and nitrergic activities in relation to elastosis in uncomplicated diverticular disease

I read with interest the review on the pathogenesis of diverticular disease by Commane et al in World J Gastroenterol 2009;15(20):2479-2488.However,I would like to discuss several important errors that the authors made whilst citing information from previously published work on the neuromuscular dysfunction in the disease.     

Long-term treatment with mesalazine and rifaximin versus rifaximin alone for patients with recurrent attacks of acute diverticulitis of colon

BACKGROUND/AIMS: To compare efficacy of combined therapy with rifaximin and mesalazine versus rifaximin alone in treatment of patients with recurrent diverticulitis in order to evaluate: 1) rapidity in improvement of symptoms, 2) regulation of bowel attacks, 3) prevention of recurrence of diverticulitis. METHODS: A total of 218 consecutive eligible patients (131 males, 87 females age 64.3 years, range 51-79), affected by diverticulitis were monitored. Of these, 109 patients were treated with rifaximin 400 mg bid plus mesalazine 800 mg tid for 7 days, followed by rifaximin 400 mg bid plus mesalazine 800 mg bid for 7 days/month (group A); 109 patients were treated with rifaximin 400 mg bid for 7 days, followed by rifaximin 400 mg bid for 7 days/month (group B). Colonoscopy was performed after 3, 6 and 12 months of therapy. RESULTS: At end of follow-up, 193 patients were fully compliant to therapy Two patients died during study (1 in group A, 1 in group B), while four patients were lost to follow-up [1 in group A (0.91%) and 3 in group B (2.75%)]. The only side-effects recorded were transient urticaria (1 in group B, 0.91%) and epigastric pain (9 in group A, 8.25%). Severity of symptoms improved significantly in group A vs group B within 3 months (p < 0.005, p < 0.001 and p < 0.0001 and p < 0.0005 at 3, 6, 9 and 12 months, respectively). Bowel habits inproved significantly in group A vs group B within 3 months (p < 0.005, p < 0.0005, p < 0.001 and p < 0.0001 at 3,6,9 and 12 months respectively). Symptomatic recurrence of diverticulitis occurred in 3 patients in group A, while 13 patients showed recurrence of diverticulitis in group B (p < 0.005) during follow-up. CONCLUSIONS: This study clearly shows that rifaximin plus mesalazine are more effective than rifaximin alone in resolution of symptoms and prevention of recurrence of diverticulitis.