Search

Environmental and lifestyle factors play an important role in the natural history of Crohn's disease and ulcerative colitis. A group of international experts from the International Organization for the Study of Inflammatory Bowel Diseases voted on a series of consensus statements to inform the management of inflammatory bowel disease (IBD). The recommendations include avoiding traditional cigarette smoking in patients with Crohn's disease or ulcerative colitis, screening for symptoms of depression, anxiety, and psychosocial stressors at diagnosis and during flares (with referral to mental health professionals when appropriate), and encouraging regular physical activity as tolerated. Patients using dietary approaches for treatment of their IBD should be encouraged to adopt diets that are best supported by evidence and involve monitoring for the objective resolution of inflammation. We recommend formal assessment for obesity and nutritional deficiencies, and patients should be encouraged to maintain a normal body-mass index. A shared decision-making approach to contraception should include the consideration of IBD-related factors, and risk factors for venous thromboembolism. Long-term or frequent use of high-dose non-steroidal anti-inflammatory drugs should be avoided. For primary prevention of disease in the offspring of patients with IBD, we recommend avoiding passive exposure to tobacco, using antibiotics judiciously, and considering breastfeeding when able.

ZusammenfassungDie COVID-19-Pandemie ist ein weltweiter Ausbruch von neu aufgetretenen Infektionen mit dem SARS-CoV-2-Virus, von denen weltweit derzeit mehr als 10.670.000 Menschen erkrankt sind bzw. waren. In Deutschland leiden ca. 450.000 Patienten an einer chronisch entzündlichen Darmerkrankung; diese Patienten benötigen in der Regel eine kontinuierliche und kompetente Betreuung. Vor dem Hintergrund eines rasch zunehmenden Wissenszuwachses haben 68 Experten, die die derzeit gültigen Leitlinien der DGVS zum Morbus Crohn und zur Colitis ulcerosa erstellt haben, im Rahmen einer virtuellen Konferenz aktuelle und praxisnahe Empfehlungen formuliert, um die Versorgung von CED-Patienten zu verbessern. Diese adressieren das Infektionsrisiko einschließlich des Risikos für besondere Gruppen, den möglichen Verlauf der Erkrankung und die Konsequenzen für die medikamentöse und die operative Therapie der Grunderkrankung sowie allgemeine Maßnahmen zur Infektionsprävention und adjuvante Präventions- und Therapiemöglichkeiten.

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.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.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.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.

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.

Summary 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.

After the expiry date of the patent protection for Infliximab in 2013, the biosimilar CT‑P13 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.

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.

Background and Study Aims: Data concerning potential clinically relevant arterial oxygen desaturation (SaO 2

Background and Study Aims: A prerequisite for successful laparoscopic cholecystectomy is the exclusion of potential risks such as cholangiolithiasis or anatomical malformations. As there is no general agreement regarding the appropriate preoperative diagnostic work-up, a comparative study of different diagnostic methods was carried out. Patients and Methods: In 180 consecutive patients admitted to a community hospital for cholecystectomy due to symptomatic cholecystolithiasis, a prospective comparison was carried out of the diagnostic accuracy of patient history, physical examination, laboratory tests, upper gastrointestinal endoscopy, intravenous cholan-giography, ultrasonography, and endoscopic retrograde cholangiopancreatography (ERCP). Results: Measurement of the diameter of the common bile duct was found to be a reliable method as a single noninvasive parameter for diagnosing cholangiolithiasis (sensitivity 100%, specificity 93%), with good predictive power (positive predictive value 0.7, negative predictive value 1.0). The best accuracy achieved noninvasively and without sonography was with a combination of positive patient history and y-glutamyl transferase findings (sensitivity 58%, specificity 84%, positive predictive value 0.37, negative predictive value 0.93). ERCP detected additional cholangiolithiasis in 19 of 139 patients (13.7%) and anatomical malformations in three patients. In all 19 patients, the bile ducts were cleared of stones endoscopically within 24 hours, prior to laparoscopic cholecystectomy. Among the 163 patients primarily assigned to laparoscopic cholecystectomy, the protocol diagnostic work-up, including ERCP, allocated three patients (1.8%) to open surgery. Conversion from laparoscopic cholecystectomy to open cholecystectomy occurred in a further two of 158 patients (1.3%). Conclusions : These results show that routine ultrasonography prior to laparoscopic cholecystectomy can be recommended in order to determine the diameter of the common bile duct. In patients with a ductal diameter of more than 6 mm, ERCP should be performed. Laparoscopic cholecystectomy can be carried out within 24 hours after ERCP and papillotomy.

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.

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.

Toxic megacolon is a rare and life-threatening complication of severe colitis, defined as a dilatation of the colon6 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.

Different oral formulations of 'mesalazine (mesalamine)' may have different efficacy in distal ulcerative colitis.To evaluate the efficacy of mesalazine granules (Salofalk granules) vs. mesalazine tablets (Salofalk tablets) as induction therapy in patients with distinct extensions of ulcerative colitis.A pooled analysis of 705 patients from four prospective, randomised, double-blind phase III trials was performed. The efficacy of 8 weeks' induction with 3 g/day mesalazine granules [3 g once daily (o.d.) or 1 g three times daily (t.d.s)] vs. 3 g/day mesalazine tablets (1 g t.d.s.) was compared in terms of clinical remission (CR: CAI ≤ 4) and endoscopic remission (ER: EI ≤ 3) (both according to Rachmilewitz) in subgroups with pancolitis, left-sided colitis, or proctosigmoiditis.Mesalazine granules were equipotent to mesalazine tablets in pancolitis regarding CR (72% vs. 71%, P = 0.909) and ER (58% vs. 49%, P = 0.338). In left-sided colitis, both mesalazine formulations were equipotent regarding CR (66% vs. 67%; P = 0.843) but mesalazine granules were superior regarding ER (56% vs. 37%; P = 0.025). In proctosigmoiditis, mesalazine granules were significantly more effective than mesalazine tablets regarding CR (78% vs. 55% P0.001) and ER (67% vs. 43% P0.001). Furthermore, o.d. application of mesalazine granules was more effective than t.d.s. dosing in left-sided colitis (CR 73% vs. 62%, P = 0.181; ER 71% vs. 48% P = 0.005) and proctosigmoiditis (CR 86% vs. 73%, P = 0.020; ER 75% vs. 61%, P = 0.021), but not in pancolitis.This pooled analysis supports the hypothesis that mesalazine granules are superior to mesalazine tablets in induction of remission in distal colitis and should be taken once daily.

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.

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.

Comparative data regarding different regimens of oral mesalazine (mesalamine) for maintaining remission in ulcerative colitis are limited.To evaluate whether 3.0 g mesalazine once-daily (OD) is superior to the standard treatment of 0.5 g mesalazine three times daily (t.d.s.) and to prove the therapeutic equivalence of OD vs. t.d.s. dosing of total 1.5 g mesalazine for remission maintenance in patients with ulcerative colitis.A 1-year, multicentre, double-blind, double-dummy study was undertaken in patients with endoscopically and histologically confirmed ulcerative colitis in remission. Patients were randomised to oral mesalazine 3.0 g OD, 1.5 g OD or 0.5 g t.d.s. The primary efficacy endpoint was the proportion of patients still in clinical remission at the final visit, with clinical relapse being defined as CAI score4 and an increase of ≥3 from baseline.The primary efficacy endpoint occurred in 162/217 3.0 g OD patients (75%), 129/212 1.5 g OD patients (61%) and 150/218 0.5 g t.d.s. patients (69%) in the intention-to-treat population, and in 152/177 (86%), 121/182 (67%) and 144/185 (78%) in the per protocol population respectively; 3.0 g OD was superior to both low-dose regimens for the primary endpoint (i.e. P0.001, 3.0 g OD vs. 1.5 g OD; P = 0.024, 3.0 g OD vs. 0.5 g t.d.s.; superiority test, per protocol population). Safety analysis, including comprehensive renal monitoring, revealed no concern in any treatment group.Mesalazine 3.0 g once daily was the most effective dose for maintenance of remission in ulcerative colitis of the three regimens assessed, with no penalty in terms of safety.

To regulate intestinal transit, increased fluid intake, along with fiber is recommended. Considering the usually large volumes of intestinal secretion, this advice is questionable. To demonstrate the effects of adding fluid to fiber, 11 volunteers ingested 15 g of wheat bran twice a day, randomly given without or with 600 mL of additional fluid. Stool weight and frequency were similarly increased in the two settings. Gastric emptying was delayed by bran only when bran was given without additional fluid. Orocecal transit showed no significant changes. Whole gut transit was slightly more accelerated with added fluid (20.6 vs. 13.5%). No test showed significant differences in direct comparison of bran and bran with additional fluid. We conclude that in healthy persons, such effects of wheat bran as acceleration of transit and increase in stool weight and frequency do not depend on an additional intake of fluid.

New concepts are developed in the therapy of diverticular disease. 5-aminosalicylates can be administered in patients with slight forms of diverticulitis. In moderate diverticulitis antibiotics should be applied alternatively or additionally. In cases of severe diverticulitis patients should be kept fasting with parenteral nutrition and intravenous broad spectrum antibiotics. Small abscesses can be treated conservatively while abscesses larger than 4 cm should be drained in a first step and than treated surgically. A free perforation is still an absolute indication for emergency operation. In recurring diverticulitis indication for resection of the affected segment of the bowel should be considered depending on the extent of former attacks.

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.

Functional bowel disorders cause frequent doctor visits. The term comprises various disease entities. Most frequent are the irritable bowel syndrome, functional constipation and functional diarrhea. An exact history plays an outstanding role for the diagnosis of all these entities. History either confirms a positive diagnosis or initiates some complementary investigations. Redundant and dangerous technical procedures should be avoided in the diagnostic work up.

Current data show that probiotics are more effective in preventing the recrudescence of an inflammatory process than in suppressing active disease. This is reflected in the solid evidence for the effect of E. coli Nissle 1917 (Mutaflor) in the maintenance of remission of ulcerative colitis, and of VSL#3 in preventing the recurrence of pouchitis. These indications have since been incorporated in valid guidelines. Initial clinical studies have also provided promising results regarding the efficacy of VSL#3 in preventing pouchitis immediately following proctocolectomy.

In Crohn's disease therapeutic concepts are according to distinct conditions. Course of the disease, the individual disease pattern and the aim of treatment are of particular significance. Care of patients with Crohn's disease requires interdisciplinary cooperation between gastroenterologists and surgeons. Primary therapy in mild to moderate disease comprises aminosalicylates and budesonide. Treatment of refractory or severe cases are corticosteroids. Immunosuppressive therapy is indicated in all kinds of complicated disease. First line immunosuppressants are Azathioprine and 6-Mercaptopurine while Methotrexate, Infliximab, Mycophenolatmofetil and other compounds represent alternative or rescue medications. Maintenance of remission should not be done on a regular basis but rather regarding the individual patients' situation. Risks have to be carefully balanced with possible benefits. The most important aim of treatment is quality of life.

Within a few weeks a 78-year-old woman presented three times in hospital with dramatic blood loss in need of transfusion. At her admission to hospital she complained about general weakness and painless melena. Within the last few years the patient had been treated with aspirin and phenprocoumon for chronic atrial fibrillation and coronary heart disease.Laboratory findings revealed a very low hemoglobin of 6 g/dl when the patient presented at hospital. The esophagogastroduodenoscopy was normal. The first colonoscopy detected diverticula of the left colon and fresh blood in the whole colon. The definitive bleeding site could not be identified. A technetium-colloid scan revealed an increased blood loss in the right colon. A second colonoscopy performed at the same time confirmed a right sided bleeding and an active capillary bleeding in the coecum without any mucosal lesion was identified.As during the patient's first stay at hospital the site of lower gastrointestinal bleeding could not be determined, the patient was treated by transfusion and oral anticoagulation was stopped. The bleeding stopped spontaneously within a few days. At the third rebleeding episode examinations located the bleeding in the right colon, and a right hemicolectomy was performed. After the operation a piece of chicken bone was detected in the wall of the coecum, which had led to a chronic mucosal bleeding after penetration of the colonic wall. After surgery the patient recovered quickly and no rebleeding recurred.Identification of the exact origin of lower gastrointestinal tract bleeding remains difficult. As the mortality rate as well as the re-bleeding rate in blind segmental colectomy is very high, compared to the resection in patients, where bleeding site could be identified, the site of bleeding must found in any case.

A 57-year-old woman complained about increasing pain and weakness in her hips and legs. 7 months earlier active (Crohn's) ileocolitis had been diagnosed. She had received several bouts of steroids and had been in clinical remission for 12 weeks under a dosage of 40 mg/d prednisone.Clinical examination, laboratory work up, x-rays and MRI of the pelvis, bone scan, neurologic examination and muscle biopsy showed unspecific results. THERAPY AN COURSE: Steroides were tapered and replaced by weekly intramuscular methotrexate 20 mg which resulted in long lasting clinical remission. Pain and weakness persisted. 6 months later MRI revealed osteonecrosis of both femoral heads. 4 1/2 years after the initial diagnosis of Crohn's disease the patient complained about pain in her lower legs without evidence of osteonecrosis in MRI. Another 2 years later avascular osteonecrosis was diagnosed by tibial bone biopsy. Now MRI verified patchy osteonecrosis of the tibiae. Further osteonecrosis of the left foot were diagnosed by MRI ten years after initial diagnosis of Crohn's disease in the now 67-year-old patient. She is still in remission on weekly intramuscular 15 mg methotrexate.The long interval between steroid treatment and recurrent avascular bone necrosis as well as the unusual pattern of bone involvement indicate that osteonecrosis is an extraintestinal manifestation of Crohn's disease. More reports and comparative studies are necessary to give more evidence that avascular osteonecrosis is an extraintestinal manifestation of inflammatory bowel disease.

The determinants of the placebo effect are not well established. Goal of this study was to explore likely predictive factors in an already published data set.We re-analysed data from a study in 120 patients with the irritable bowel syndrome (IBS) that were randomly assigned to three arms of the study to receive (double-blind) either a drug (mebeverin) (n = 40) or placebo (n = 40), or (in an open trial) dietary treatment (fibre) (n = 40) for up to 16 week. Treatment was conducted by 3 different doctors (A, B, C) with 44, 27, and 18 patients, resp. A fourth group (n = 31) was treated by different varying physicians. Symptoms were assessed every 4 weeks, and the degree of patient compliance and the number of drop-outs, the number of patients improved/not improved (in %), symptom severity (Kruis Score) at enrolment, and age and gender as covariates were included into the analysis.Drop-out rate was 30 % for placebo, 30 % for mebeverin, and 15 % for the diet. For the patients remaining in the study, average compliance was 75 % with placebo, but 89 % for the drug and 82 % for the diet. Response rates were 39 % for placebo, but 20 % for the drug; response rate for the diet (open trial) was 43 % under all doctors. Response rates for drug and placebo combined were 32 % for doctor A (female,43 years), but 19 % for doctors B and C together (both males, 32 and 40 years)); this effect was not significant. Placebo responders were more often women (47 %) than men (28 %), while age effects were only found with dietary treatment: responders were younger. Placebo responders had an overall lower Kruis Score than non-responders (45 vs 52 points), but this was also true for drug (52 vs. 62 points) and diet responders (56 vs 68 points).The major factors contributing to the placebo response are the treating physician (gender, training), and the patients gender (female). Patients with lower Kruis score (more likely non-functionally disordered) may be prone to higher (placebo) response rates.

Hymecromone (4-methyl-umbiliferone) has been used for more than 20 years for the treatment of functional and obstructive spasms of the biliary tract. Its mode of action however is still largely unknown. We investigated the effect of 4-methyl-umbiliferone p. o. and i. v. on gall bladder and common bile duct motility and studied potentially indirect effects via alterations in bile acid metabolism.Twenty healthy volunteers, aged 25 - 37, 10 males, 10 females, were included into a Placebo-controlled, randomised, cross-over double-blind study. Subjects were treated with 800 mg hymecromone p. o.; in addition a standardized meal (Biloptin, 40 gs) was given. Gall bladder volume and common bile duct diameter were determined by ultrasound. Conjugated and unconjugated bile acids were analysed by gas chromatography. Additionally, in a third open label phase hymecromone was given i. v.Common bile duct diameter was significantly larger after a standard meal with hymecromone given p. o. or i. v. than with placebo (each p0.01). However, alterations in gall bladder volume after a standard meal were not different between placebo and hymecromone (p. o. or i. v.). Unconjugated and conjugated bile acids rose after standard meal in all three groups without significant differences between hymecromone and placebo.Hymecromone was associated with significant dilation of the common bile duct. In contrast to previous reports an effect of hymecromone on gall bladder motility could not be observed. The unchanged values of bile acids in serum after hymecromone compared to placebo, together with the dilatation of the common bile duct after hymecromone, may indicate a bile acid-independent effect of hymecromone on bile secretion.

Alterations in the colon wall, motility disorders, and certain nutritional habits are the essential factors in the development of colon diverticula. Thus, with advancing age this results in a high incidence in Western industrialized countries. The clinical picture is usually one of symptom-free diverticulosis. Diverticular disease can be associated with minor symptoms, but in complicated cases with diverticulitis and diverticular hemorrhage, it is potentially fatal. Further complications include abscess formation, fistula development, and obstruction. Barium double-contrast imaging exhibits the highest diagnostic sensitivity in diverticulosis but is contraindicated in cases of suspected complicated diverticular disease due to the danger of perforation. In these instances, sonography, computed tomography, or magnetic resonance imaging are performed. For diverticular hemorrhage, coloscopy not only represents a possible diagnostic tool but also a therapeutic option for various techniques of hemostasis. Treatment of diverticulitis and its complications requires careful consideration of conservative and surgical approaches and close interdisciplinary cooperation.

Treatment with antibiotics in inflammatory bowel disease has a long tradition and is widely used. The indications for antibiotic therapy are wide ranging, from specific situations such as abscesses or fistulae, to patients with severe disease (as an unspecific 'protective' measure), and to address the hypothesis that the enteric flora as a whole, or specific microorganisms such as mycobacteria, are involved in the pathogenesis of inflammatory bowel disease. The best-studied single antibiotic compound is metronidazole. However, overall, the scientific basis for the use of antibiotics is limited, which may reflect a lack of interest from sponsors within the pharmaceutical industry. Despite this weak evidence base, antibiotics are a globally established therapeutic tool in inflammatory bowel disease. Growing evidence from human and animal studies points towards a pivotal pathogenetic role of intestinal bacteria in inflammatory bowel disease. In view of these experimental findings, clinical trials have been undertaken to elucidate the therapeutic effects of probiotics in inflammatory bowel disease. Probiotics are viable nonpathogenic microorganisms which confer health benefits to the host by improving the microbial balance of the indigenous microflora. So far, of the many candidates, one specific strain (Escherichia coli Nissle 1917) and a mixture of eight different bacteria have demonstrated convincing therapeutic efficacy in controlled studies. Maintenance therapy in ulcerative colitis and prevention therapy, as well as the treatment of pouchitis, have emerged as areas in which probiotic therapy offers a valid therapeutic alternative to current treatments. Further investigations may detect additional clinically effective probiotics and other clinical indications.

The aim of this article is to review potential antineoplastic properties of anti-inflammatory compounds commonly used in various inflammatory diseases such as aminosalicylates, aspirin and other nonsteroidal drugs. Starting from experimental and epidemiologic evidence showing prophylaxis and/or tumor regression/suppression, specific antineoplastic actions especially the inhibition of cyclooxygenase-(COX)dependent and COX-independent steps including the role of transcription factor (NFkappaB) in the cell cycle regulation are reviewed. In addition other mechanisms by which these drugs may exert antitumor effects, also may be important such as induction of apoptosis of cancer cells and/or inhibition of potentially carcinogenic oxidative DNA damage. Based on this knowledge potential clinical implications are discussed.

Recombinant T-cell receptors with antibody-like specificity for tumor-associated antigens are successfully used to direct the cytolytic activity of T cells toward tumor cells. Clinical application, however, needs to comply with the low immunogenicity of the recombinant receptor, efficient gene transfer into peripheral blood T cells, and enrichment of receptor-grafted cells. Here, we address these issues and describe an entirely humanized immune receptor for use in adoptive immunotherapy of colorectal carcinoma. The receptor consists of a single-chain antibody (scFv) binding domain specific for carcinoembryonic antigen (CEA), the IgG hinge and CH2/CH3 (Fc) joining region, and the transmembrane and intracellular CD3 zeta signaling chain. To express the receptor in peripheral blood T cells, both GALV envelope and MuLV 4070A pseudotyped retrovirus turned out to be equally efficient, with transduction efficiencies of about 5% to 40%, depending on the lymphocyte donor. Furthermore, receptor-grafted T cells could be 2- to 6-fold enriched by magnetic activated cell sorting, utilizing an antibody directed to the extracellular IgG domain of the receptor. Upon co-culture with CEA(+) tumor cells, receptor-grafted T cells are specifically and efficiently activated to cytolysis and IFN-gamma secretion, demonstrating their feasibility for the adoptive immunotherapy of CEA(+) carcinomas.

Crohn's disease (CD) and ulcerative colitis (UC) are clinical entities characterized by spontaneous relapses and are thought to be caused in large part by a dysregulated immune response to inflammatory stimuli. Specific infectious agents or antigens inducing or perpetuating inflammation, however, are not known. Recent results in contrast support the hypothesis, that the normal intestinal flora plays a central role in the pathogenesis of both diseases. Studies performed with E. coli Nissle 1917 demonstrated that this bacterium can positively affect the course of disease in UC and CD patients. The clinical efficacy of probiotics can yield valuable information about disease pathogenesis and, as a modification of current standard therapy, opens new and interesting therapeutic alternatives.

Inflammatory bowel disease (IBD) has a definite genetic component as documented by epidemiological and linkage evidence. It shows an earlier onset of disease in children of affected patients than in their parents. This has lead to speculations about genetic anticipation in this disorder. 2,007 IBD patients with sporadic disease and 472 multiplex familial cases (including 103 affected parents and 99 children of affected patients) were evaluated with a multi-item questionnaire as part of a study of inflammatory bowel disease genetics. The Mann-Whitney U-test and the general linear model were used for analysis. Clinical characteristics such as presence of fistulae, stenoses, extraintestinal manifestations, and other parameters, which are related to the severity of the disease, were found to be similar between familial and sporadic cases of IBD (corrected Por = 0.31 for all tests). The mean-age-of onset in children of affected patients was 19.4 years earlier than in their parents. However, the age of the parental cohort was significantly higher (27 years) and the diagnostic interval also longer (1.7 years). If these confounders are corrected in a general linear model, no significant difference is evident for the age-of-onset between the groups (Por = 0.52). There is no evidence for genetic anticipation in inflammatory bowel disease. The absence of genetic anticipation is consistent with the clinical similarity of familial and sporadic inflammatory bowel disease. This finding justifies the primary genetic analysis of familial disease under the assumption that their genetic background will be representative for all presentations of IBD.