European Society of Coloproctology: guidelines for the management of diverticular disease of the colon.

AIM: The goal of this European Society of Coloproctology (ESCP) guideline project is to give an overview of the existing evidence on the management of diverticular disease, primarily as a guidance to surgeons. METHODS: The guideline was developed during several working phases including three voting rounds and one consensus meeting. The two project leads (JKS and EA) appointed by the ESCP guideline committee together with one member of the guideline committee (WB) agreed on the methodology, decided on six themes for working groups (WGs) and drafted a list of research questions. Senior WG members, mostly colorectal surgeons within the ESCP, were invited based on publication records and geographical aspects. Other specialties were included in the WGs where relevant. In addition, one trainee or PhD fellow was invited in each WG. All six WGs revised the research questions if necessary, did a literature search, created evidence tables where feasible, and drafted supporting text to each research question and statement. The text and statement proposals from each WG were arranged as one document by the first and last authors before online voting by all authors in two rounds. For the second voting ESCP national representatives were also invited. More than 90% agreement was considered a consensus. The final phrasing of the statements with < 90% agreement was discussed in a consensus meeting at the ESCP annual meeting in Vienna in September 2019. Thereafter, the first and the last author drafted the final text of the guideline and circulated it for final approval and for a third and final online voting of rephrased statements. RESULTS: This guideline contains 38 evidence based consensus statements on the management of diverticular disease. CONCLUSION: This international, multidisciplinary guideline provides an up to date summary of the current knowledge of the management of diverticular disease as a guidance for clinicians and patients.

Synchronous pathologic findings in patients with colorectal cancer and preoperative incomplete colonoscopy.

BACKGROUND AND PURPOSE: Guidelines recommend perioperative complete colonoscopy in patients with colorectal cancer (CRC) to reduce the risk of metachronous carcinoma. Our aim was to verify these recommendations by examining the residual colon of patients with incomplete preoperative colonoscopy. PATIENTS AND METHODS: This retrospective analysis included patients with the initial diagnosis of CRC and preoperative incomplete or no colonoscopy. Postoperative colonoscopies were investigated to identify synchronous lesions. RESULTS: In two-thirds of the patients, synchronous lesions could be detected. In 78% of the cases, the lesion was located proximal of the endpoint of the initial colonoscopy and therefore undiscovered. Two-thirds of the synchronous lesions were adenomata. CONCLUSIONS: Complete perioperative colonoscopy in patients with CRC should be performed to reduce the rate of metachronous carcinoma. Postoperative completion of preoperative insufficiently colonoscoped patients is recommended.

[Diverticulitis : Domain of conservative or drug therapy?] / Divertikulitis : Domäne der konservativen bzw. medikamentösen Therapie?

Increasing interest in diverticular disease by the scientific community in the last 10-15 years has resulted in an increased number of publications. Among other things, nonevidence-based therapeutic paradigms were tested in randomized, controlled therapy studies. The importance of surgery in the therapy of diverticulitis has diminished in recent years; in particular, it has no role in the treatment of diverticulitis types 1a, 1b, and 2a according to the Classification of Diverticular Disease (CDD) treated successfully by conservative means. Surgery has only a subordinate role in recurrent type 3b diverticulitis according to the CDD. Diverticulitis is therefore increasingly treated using conservative or drug therapy. However, only the classic, established antibiotics are currently available as effective drugs for the treatment of diverticular disease. However, these are also decreasing in significance. Over 90% of patients with type 1a/1b diverticulitis can be safely treated according to current data without the use of antibiotics. It is possible that type 2a diverticulitis will also be successfully treated without antibiotics in the future. Substances such as rifaximin, mesalazine, or probiotics, which were tested above all in patients with chronic recurrent forms (CDD type 3a/3b), have not yet been established.

[Biosimilars in inflammatory bowel disease]. / Biosimilars in der Behandlung chronisch entzündlicher Darmerkrankungen.

After the expiry date of the patent protection for Infliximab in 2013, the biosimilar CT­P13 was approved for indications in Crohn's disease and ulcerative colitis in adults as well as in children. The approval has been based on two randomized clinical studies indicating equivalence for the biosimilar with regard to pharmacokinetics, efficacy, as well as side-effects. The clinical experience since, in addition to multiple non-randomized studies, indicate a comparable efficacy and immunogenicity of the Infliximab biosimilar CT-P13 in inflammatory bowel disease. Thus, the introduction of the biosimilar as primary therapy seems to be justified. Tight monitoring of the safety of biosimilars with regard to efficacy and side effects has to be ensured.

[Current position on Vedolizumab for ulcerative colitis and Crohn's disease]. / Vedolizumab bei Colitis ulcerosa und Morbus Crohn: eine Standortbestimmung.

Vedolizumab, the first drug in the class of anti-integrin molecules, is newly approved for ulcerative colitis and Crohn's disease and can be prescribed in Germany since mid-2014. By a specific receptor binding a relatively gut-selective mode of action was achieved without the known side effects of the systemic immunosuppression of the anti-TNF-alpha antibodies. According to the present data the safety profile of Vedolizumab appears to be more favorable than that of the anti-TNF- alpha therapy. Vedolizumab is suitable for induction therapy in patients with ulcerative colitis and Crohn's disease, however the kinetic of response compared with the anti-TNF-alpha antibodies seems to be slower. For maintenance therapy the Vedolizumab data show a deep and sustained remission in patients initially responding to induction therapy with a lower loss of efficacy in the long-term treatment known from the anti-TNF-alpha therapy. On the basis of currently available data the efficacy of Vedolizumab in ulcerative colitis appears to be slightly better than in Crohn's disease.

Conservative management.

Treatment of diverticulitis comprises at least two options: conservative or surgical management. There is a recent trend to limit surgical treatment of acute diverticulitis and to favor conservative management. This review addresses general aspects of conservative patient care with special focus on the treatment of patients with a first attack of diverticulitis. The presentation does not include a discussion of specific drugs which is given in other sections of this issue.

[Current management of toxic megacolon]. / Management des toxischen Megakolons.

Toxic megacolon is a rare and life-threatening complication of severe colitis, defined as a dilatation of the colon > 6 cm in the absence of distal obstruction in combination with signs of systemic toxicity (major criteria: fever, tachycardia, leukocytosis, anaemia). Various triggers are known and the most common causes are underlying ulcerative colitis and Clostridium difficile. Diagnosis can easily be made by clinical examination, routine laboratory parameters and a plain X-ray of the abdomen. Much more difficult is to decide between non-surgical treatment including intensive care treatment or surgery (mostly subtotal colectomy with terminal ileostomy). Non-surgical therapy includes balancing of electrolytes and fluid volumes, broad-spectrum antibiotics including metronidazole, positioning of patients and probably careful intermittent decompression. In case of ulcerative colitis immunosuppression should be started with corticosteroids and potentially with calcineurin inhibitors. In pseudomembranous colitis vancomycin should be given orally and metronidazole should be given intravenously. As far as possible the patient should be treated in a centre with experience in the field.

[Rational and efficient diagnosis in different stages of Crohn's disease]. / Rationale und rationelle Diagnostik in unterschiedlichen Krankheitsphasen des Morbus Crohn.

The treatment of patients with inflammatory bowel disease has become more complex in recent years through the introduction of various immunosuppressive agents as well as the approval of monoclonal antibodies. Patients receiving such treatment must be carefully monitored. National and international guidelines define a diagnostic and therapeutic context for the practitioner, but can only partially respond to specific questions on the procedure for individual patients. Within the framework of a project initiated by Abbott entitled "IBD ahead" 34 German IBD experts have elaborated concrete proposals for the utility of clinical symptom assessment, endoscopy and the use of laboratory parameters including foecal markers of inflammation. Furthermore, we discuss the significance of conventional X-rays, computed tomography, ultrasound and magnetic resonance tomography. These recommendations are illustrated by case studies from everyday practice in the participating centres.

Successful non-invasive treatment of stricturing fibrosing colonopathy in an adult patient.

OBJECTIVE: Fibrosing colonopathy (FC) is a rare entity associated with cystic fibrosis (CF). Until now, patients with stricturing FC have usually been treated surgically. In this instance, we aimed at avoiding surgery by applying a new conservative approach. - METHODS: Case report on an adult with CF who developed persistent abdominal pain due to a non-passable stricture in the right transverse colon. Histology confirmed fibrosing colonopathy. - RESULTS: Initially we treated the patient with prednisolone pulse therapy and additive antibiotic therapy. For maintenance therapy we administered budesonide. The patient underwent clinical, laboratory and endoscopic follow-up over a three-year period. The stricture healed and was easy to pass. A relapse in the cecum at the ileocecal valve again improved under steroid and antibiotic therapy. - CONCLUSIONS: We present a novel therapeutic approach for advanced stricturing FC in an adult patient which successfully avoided surgery (right hemicolectomy) over a three year follow up.

[IBD ahead 2010--Answering important questions in Crohn's disease treatment]. / IBD ahead 2010--Antworten auf zehn zentrale Fragen in der aktuellen Therapie des Morbus Crohn.

The treatment of patients with inflammatory bowel disease has become more complex in recent years through the introduction of various immunosuppressive agents as well as the approval of monoclonal antibodies against TNF-α and patients receiving such treatment must be carefully monitored. National and international guidelines define a diagnostic and therapeutic context for the practitioner, but can only partially respond to specific questions on the procedure for individual patients. Within the framework of a project initiated by Abbott entitled "IBD ahead" 38 German IBD experts have elaborated concrete proposals for dealing with corticosteroids, immunosuppressants and TNF-α antibodies on the basis of the published literature and their own personal experience in order to close the gap between these guidelines and daily clinical practice. Statements were developed on the choice of correct timing of initiation, dose and duration of the individual substances and on how to proceed with patients exhibiting treatment failure. Moreover, recommendations are also made on drug combination strategies, safety monitoring and the risks regarding the development of infectious complications and malignancies. These recommendations are illustrated by case studies from everyday practice in participating centres.

Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial.

OBJECTIVES: To determine the therapeutic equivalence and safety of once daily (OD) versus three times daily (TID) dosing of a total daily dose of 3 g Salofalk (mesalazine) granules in patients with active ulcerative colitis. DESIGN: A randomised, double-blind, double-dummy, parallel group, multicentre, international, phase III non-inferiority study. SETTING: 54 centres in 13 countries. PATIENTS: 380 patients with confirmed diagnosis of established or first attack of ulcerative colitis (clinical activity index (CAI)>4 and endoscopic index > or =4 at baseline) were randomised and treated. INTERVENTIONS: 8-week treatment with either 3 g OD or 1 g TID mesalazine granules. MAIN OUTCOME MEASURES: Clinical remission (CAI< or =4) at study end. RESULTS: 380 patients were evaluable for efficacy and safety by intention-to-treat (ITT); 345 for per protocol (PP) analysis. In the ITT population, 79.1% in the OD group (n = 191) and 75.7% in the TID group (n = 189) achieved clinical remission (p<0.0001 for non-inferiority). Significantly more patients with proctosigmoiditis achieved clinical remission in the OD group (86%; n = 97) versus the TID group (73%; n = 100; p = 0.0298). About 70% of patients in both treatment groups achieved endoscopic remission, and 35% in the OD group and 41% in the TID group achieved histological remission. About 80% of all patients preferred OD dosing. Similar numbers of adverse events occurred in 55 patients (28.8%) in the OD group and in 61 patients (32.3%) in the TID group, indicating that the two dosing regimens were equally safe and well tolerated. CONCLUSIONS: OD 3 g mesalazine granules are as effective and safe as a TID 1 g schedule. With respect to the best possible adherence of patients to the treatment, OD dosing of mesalazine should be the preferred application mode in active ulcerative colitis.

Safety, feasibility, and tolerability of ileocolonoscopy in inflammatory bowel disease.

BACKGROUND AND STUDY AIMS: Ileocolonoscopy including biopsies is the first-line investigation in the diagnosis, management, and monitoring of inflammatory bowel disease (IBD). However, data on its safety, feasibility, and tolerability, especially in patients with extensive or severe inflammation, are rare. The aim of this study was to assess prospectively the risks of ileocolonoscopy in relation to various disease patterns and to compare possible burdens of the procedure in the endoscopist's and the patient's perception. PATIENTS AND METHODS: We prospectively analyzed a total of 558 consecutive patients, 482 with a confirmed diagnosis of IBD and 76 with suspected IBD. Data were recorded regarding the indication for ileocolonoscopy, sedation, procedure time, completion rate, feasibility of the procedure, patient tolerance, and procedure-related and postprocedure complications. Endoscopic data included the region involved, the nature of the involvement, activity of the disease, and number of biopsies. RESULTS: In 558 endoscopic procedures performed by 14 gastroenterologists no procedure-related deaths occurred. Major complications, defined as bleeding (n = 1) or perforation (n = 3), occurred in 4/558 patients (0.7 %). Minor complications, which included intense flatulence, tachycardia, allergic reaction to a sedation drug, and autonomic symptoms such as nausea, vomiting, and intense perspiration, occurred in 22/558 patients (3.9 %). There was no relationship between the complication rate and the activity of the disease. Mean procedure time was 21.0 minutes and the completion rate, defined by intubation of the terminal ileum, was 94.6 %. We documented a high tolerability independent of the severity of the disease. CONCLUSIONS: Ileocolonoscopy is a safe and feasible procedure in patients with IBD and is well tolerated by patients when carried out by well-trained endoscopists.

Microbial Spectrum of Intra-Abdominal Abscesses in Perforating Crohn's Disease: Results from a Prospective German Registry.

BACKGROUND: Intra-abdominal abscesses [IAAs] are common life-threatening complications in patients with Crohn's disease [CD]. In addition to interventional drainage and surgical therapy, empirical antibiotic therapy represents a cornerstone of treatment, but contemporary data on microbial spectra and antimicrobial resistance are scarce. METHODS: We recruited 105 patients with CD and IAAs from nine German centres for a prospective registry in order to characterize the microbiological spectrum, resistance profiles, antibiotic therapy and outcome. RESULTS: In 92 of 105 patients, microbial investigations of abscess material revealed pathogenic microorganisms. A total of 174 pathogens were isolated, with a median of 2 pathogens per culture [range: 1-6]. Most frequently isolated pathogens were E. coli [45 patients], Streptococcus spp. [28 patients], Enterococci [27 patients], Candida [13 patients] and anaerobes [12 patients]. Resistance to third-generation cephalosporins, penicillins with beta-lactamase inhibitors and quinolones were observed in 51, 36 and 35 patients, respectively. Seven patients had multiple-drug-resistant bacteria. Thirty patients received inadequate empirical treatment, and this was more frequent in patients receiving steroids or immunosuppression [37%] than in patients without immunosuppression [10%: p = 0.001] and was associated with a longer hospital stay [21 days vs 13 days, p = 0.003]. CONCLUSION: Based on antimicrobial resistance profiles, we herein report a high rate of inadequate empirical first-line therapy for IAAs in CD, especially in patients receiving immunosuppression, and this is associated with prolonged hospitalization.

Patient Education in a 14-month Randomised Trial Fails to Improve Adherence in Ulcerative Colitis: Influence of Demographic and Clinical Parameters on Non-adherence.

BACKGROUND AND AIM: Recent observational studies document that non-adherence to mesalamine therapy during remission is frequent. We aimed to investigate patient impact of patient education using objective assessments of adherence. METHODS: A 14-month randomised, prospective clinical trial of adherence to mesalamine was conducted in 248 patients with ulcerative colitis [UC], Colitis Activity Index [CAI] ≤ 9, receiving standard care [n = 122] versus a standardised patient education programme [n = 126]. Primary endpoint was adherence at all visits (5-aminosalicylic acid [5-ASA] urine levels). Secondary endpoints included quality of life (inflammatory bowel disease questionnaise [IBDQ]), disease activity, partial adherence, and self-assessment of adherence. RESULTS: Patient allocation was well balanced. Baseline non-adherence was high in quiescent/mildly active UC [52.4%] without difference between the groups (52.4% of patients in the education group versus 52.5% in the standard care group [p = 0.99]). No difference between the intervention group and standard care was seen in IBDQ, partial adherence, self-assessment of adherence, or therapy satisfaction at all visits. We suggest a model in which individual risks for non-adherence are driven by patients with young age, short disease duration, and low education levels. CONCLUSIONS: Non-adherence is frequent in a population with quiescent/mildly active UC. Although more than 25% of the population was not in remission at the various time points, no relationship between disease activity and adherence was seen over the 14-month observation period. Physicians should maximise their efforts to motivate high-risk patients for adherence. Future trials should use objective exposure assessments to examine the impact of continuous education and consultations on the background of individual risks to develop non-adherence.

Randomised clinical trial: mesalazine versus placebo in the prevention of diverticulitis recurrence.

BACKGROUND: Previous studies have reached conflicting conclusions regarding the efficacy of mesalazine in the prevention of recurrent diverticulitis. AIM: To investigate the efficacy and safety of mesalazine granules in the prevention of recurrence of diverticulitis after acute uncomplicated diverticulitis. METHODS: Two phase 3, randomised, placebo-controlled, double-blind multicentre trials (SAG-37 and SAG-51) investigated mesalazine granules in patients with prior episodes (<6 months) of uncomplicated left-sided diverticulitis. Patients were randomised to receive either 3 g mesalazine once daily or placebo (SAG-37, n=345) or to receive either 1.5 g mesalazine once daily, 3 g once daily or placebo for 96 weeks (SAG-51, n=330). The primary endpoint was the proportion of recurrence-free patients during 48 weeks (SAG-37 and SAG-51) or 96 weeks (SAG-51) of treatment. RESULTS: Mesalazine did not increase the proportion of recurrence-free patients over 48 or 96 weeks compared to placebo. In SAG-37, the proportion of recurrence-free patients during 48 weeks was 67.9% with mesalazine and 74.4% with placebo (P=.226). In SAG-51, the proportion of recurrence-free patients over 48 weeks was 46.0% with 1.5 g mesalazine, 52.0% with 3 g mesalazine and 58.0% with placebo (P=.860 for 3 g mesalazine vs placebo) and over 96 weeks 6.9%, 9.8% and 23.1% respectively (P=.980 for 3 g mesalazine vs placebo). Patients with only one diverticulitis episode in the year prior to study entry had a lower recurrence risk compared to >1 episode. Safety data revealed no new adverse events. CONCLUSION: Mesalazine was not superior to placebo in preventing recurrence of diverticulitis.

Probiotics: do they help to control intestinal inflammation?

There is currently a growing appreciation for the role of the enteric flora in health and disease. In the past years overwhelming evidence has accumulated for the role of commensal gut bacteria in the inflammatory bowel diseases Crohn's disease and ulcerative colitis. Both entities are mainly located in areas with high bacterial concentrations. Reduction of the enteric bacterial concentration by antibiotics, lavage, or surgical bypass results in a mitigation of symptoms, while experimental colitis models depend on the presence of the bacterial flora and the NOD2/CARD15-mutation results in inefficient clearance of invasive bacteria. Those findings helped to bring the concept of probiotic therapy to the forefront, a therapy that had been known for millennia, but had been disregarded by the scientific world. Probiotics are meanwhile established in the maintenance therapy of ulcerative colitis and chronic recurrent or refractory pouchitis. Promising data exist for the primary prevention of pouchitis. Probiotic research at the intersection of gastroenterology, immunology and microbiology is highly dynamic in both the basic and the clinical field. Further understanding of the complex molecular mechanisms leading to the effectiveness of probiotics will also spur the development of more successful probiotic formulations.