[Show abstract][Hide abstract] ABSTRACT: The consistency of endoscopic and histologic findings in patients with ulcerative colitis (UC) has not been elucidated. Choice of assessment may affect study outcomes.
Post hoc analyses were performed using data from 2 randomized, controlled multicenter trials: (1) SAG-26, mesalazine granules for induction of remission in UC (n = 380), and (2) SAG-27, mesalazine granules for maintenance of UC remission (n = 647). Assessments included Clinical Activity Index, Endoscopic Index, modified Disease Activity Index, and Histology Index.
In SAG-26, 52 of 380 patients (13.7%) with clinically (Clinical Activity Index >4) and endoscopically (Endoscopic Index ≥4) active UC showed no histological signs of active inflammation (Histology Index ≤1) at baseline. Among endoscopically and histologically active patients, 246 of 327 (75.2%) reached clinical remission versus 48 of 52 patients (92.3%) with active endoscopy but no inflammation on histology (difference, 17.1%; P = 0.006). The difference in the proportion of patients achieving clinical remission according to endoscopy and histology in clinically inactive (Clinical Activity Index ≤4) patients was 30.8% in SAG-26 (at the study end) and 28.1% in SAG-27 (at baseline). In SAG-27, clinical relapse occurred in 21.2% of patients with endoscopic and histologic remission at baseline and 27.1% of patients with some histological inflammation at baseline (P = 0.111). Using the modified Disease Activity Index ≤1 (mucosal healing) instead of the Endoscopic Index score, the difference was similar (21.2% versus 28.0%, P = 0.073).
Endoscopic and histologic assessments differ in both active and inactive UC. Overdiagnosis of inflammation using endoscopy versus histology can significantly affect outcomes, at least in studies using induction of clinical remission as an endpoint. The assessment criteria for trials in UC should be reconsidered.
[Show abstract][Hide abstract] ABSTRACT: Robust evidence regarding medical intervention for symptomatic uncomplicated colonic diverticular disease (DD) is sparse.
To investigate mesalazine (Salofalk granules) in this setting.
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).
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Appendicitis and diverticulitis are very common entities that show some similarities in diagnosis and course of disease. Both are widely believed to be simple clinical diagnoses, which is in contrast to scientific evidence. An accurate diagnosis has to describe not only the initial detection, but particularly the severity of the disease. It is based mainly on cross-sectional imaging by ultrasound (US) and computed tomography (CT). Appendectomy is the standard treatment for acute appendicitis and is mandatory in complicated cases. Antibiotic therapy is similarly effective in uncomplicated appendicitis, but long-term results are not sufficiently known. Treatment of diverticulitis is related to the disease status. Complications such as perforation and bleeding require intervention. Uncomplicated diverticulitis as graded by US or CT are subject to conservative management, in the form of outpatient or hospital care. It is an unresolved debate as to whether antibiotic treatment offers benefits. Mesalazine seems at least to improve pain. The real challenge is treatment of recurrent diverticulitis. Lifestyle measures such as nutritional habits and physical activity are found to influence diverticular disease. Besides immunosuppression, obesity is a significant risk factor for complicated diverticulitis. Whether any medication such as chronic antibiotics, probiotics or mesalazine offers benefits is unclear. The indication for sigmoid resection has changed; it is no longer given by the number of attacks, but rather by structural changes as depicted by cross-sectional imaging.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Predictive factors for a mild course of Crohn's disease (CD) may have therapeutic consequences, but as yet have not been identified. AIMS: To identify baseline factors that predict mild CD and design a predictive scoring system. METHODS: A retrospective, multicenter study of newly diagnosed CD patients allocated to mild CD (no therapy, mesalazine only, or mesalazine with a single initial short course of low-dose prednisone) or moderate CD (all other patients including resected patients). RESULTS: 162 patients (median follow-up 43months) were analyzed: 47 mild CD and 115 moderate CD. For mild CD versus moderate CD, mean age at first diagnosis was higher (41.1 versus 33.9years, p=0.02), mean C-reactive protein (CRP) concentration was lower (1.6 versus 3.6mg/L, p<0.01), and perianal lesions were less frequent (0% versus 10.4%, p=0.02). The combined incidence of complications (stenosis, any type of fistula, extraintestinal complications or fever) was 21.3% in mild CD versus 35.7% in moderate CD (p=0.07). A scoring system based on age, CRP, endoscopic severity (adapted Rutgeert's score), perianal lesions and combined incidence of complications was developed which can predict a mild prognosis at the initial diagnosis, giving patients the chance of simplified therapy and accelerated step-up in the event of treatment failure. CONCLUSIONS: Approximately a third of CD patients experience a mild disease course and require only basic therapy. A possible scoring system to predict mild CD which may avoid overtreatment and unnecessary risks for the patient and costs is suggested.
Journal of Crohn s and Colitis 11/2012; · 3.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite advances in immunosuppressive therapy, up to 10% of patients with severe Crohn's disease (CD) remain refractory to conventional treatment. Limited evidence from pilot trials suggests that high-dose immunosuppression and autologous peripheral blood stem cell transplantation (autoPBSCT) may induce remission in these patients, but there is substantial controversy regarding the safety and efficacy of this approach.
To address this issue, a monocentre phase I/II trial of autoPBSCT was performed in patients with refractory CD in our hospital.
Here, we report on the outcome of 12 patients with refractory CD treated with autoPBSCT. Briefly, CD34(+) -selected PBSCs were harvested after mobilisation therapy with cyclophosphamide and granulocyte-colony stimulating factor. Later, immunoablative conditioning therapy with high-dose cyclophosphamide followed by autoPBSCT was applied and clinical and endoscopic responses were analysed after a mean follow-up of 3.1 years (range 0.5-10.3 years).
PBSC harvest following mobilisation chemotherapy was successful in 11/12 patients and resulted in a clinical and endoscopic improvement in 7/12 patients. Subsequent conditioning and autoPBSCT were performed in nine patients and were relatively well tolerated. Among those, five patients achieved a clinical and endoscopic remission within 6 months after autoPBSCT. However, relapses occurred in 7/9 patients during follow-up, but disease activity could be controlled by low-dose corticosteroids and conventional immunosuppressive therapy.
Immunoablation by cyclophosphamide and autologous peripheral blood stem cell transplantation is safe and effective to induce remission of refractory Crohn's disease, and should be further evaluated in randomised controlled trials.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND AIMS: The optimal mesalazine dosing strategy for ulcerative colitis (UC) continues to evolve. The current study aimed to explore whether documenting drug use could prompt changes in prescribing habits. METHODS: In a multicenter, prospective, observational study, outpatients with active or quiescent UC were enrolled if they were receiving, or were planned to receive, sustained release mesalazine microgranules (Pentasa®). Clinical and prescribing data were collected at study entry, after 2 and 8weeks. Physician-reported influences on prescribing decisions were recorded at study entry. RESULTS: 360 patients were analyzed (203 active UC, 157 remission). Prior to study entry, the range of oral mesalazine doses was 0.50-6.00g/day in active UC patients, and 0.50-4.00g/day for patients in remission. These changed to 1.50-5.00g/day and 1.00-4.00g/day, respectively, at study entry with little change thereafter. Use of a single daily mesalazine dose increased from 16.7% to 58.0% of active cases during the study, and from 5.9% to 46.8% in remission cases. Gastroenterologists reported that their basis for prescription decision-making was most frequently medical experience (80.8%), followed by guidelines (67.2%), further education or colleagues' recommendations (50.0%) and current study results (20.0%). CONCLUSION: In this analysis of mesalazine dosing in routine clinical practice, there was an improvement in adherence to European Crohn's and Colitis Organisation (ECCO) guidelines and in use of once-daily dosing, consistent with recent trial results, following documentation of dosing regimens. Written reporting of drug dosing schedules should be considered fundamental for chronic, complex diseases such as UC.
Journal of Crohn s and Colitis 08/2012; · 3.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Zeitschrift für Gastroenterologie 07/2012; 50(7):684-93. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Irritable bowel syndrome (IBS) is common in western Europe and North America, and many aspects of its epidemiology, risk factors, and natural history have been described in these regions. Recent data suggest, however, that IBS is also common in the rest of the world and there has been some evidence to suggest some differences in demographics and presenting features between IBS in the west and as it is experienced elsewhere. The World Gastroenterology Organization, therefore, established a Task Force comprising experts on the topic from all parts of the world to examine IBS from a global perspective. IBS does, indeed, seem to be common worldwide though with some significant variations in prevalence rates between regions and countries and there may well be some potentially interesting variations in presenting symptoms and sex distribution. The global map of IBS is far from complete; community-based prevalence data is not available from many areas. Furthermore, while some general trends are evident in terms of IBS impact and demographics, international comparisons are hampered by differences in diagnostic criteria, study location and methodology; several important unanswered questions have been identified that should form the basis for future collaborative research and have the potential to shed light on this challenging disorder.
Journal of clinical gastroenterology 05/2012; 46(5):356-66. · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Zeitschrift für Gastroenterologie 03/2012; 50(3):316-22. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic abdominal pain, bloating, constipation, diarrhea, and stool irregularity are common symptoms in primary care and gastroenterology. A routine diagnostic evaluation fails to reveal any underlying somatic condition in about half of the affected patients, who are therefore said to have a functional bowel disorder. Physicians are often unsure how extensive the work-up must be to exclude a somatic cause.
This review is based on a selective review of the literature, including published guidelines from Germany and abroad.
Functional bowel disorders are diagnosed on the basis of a typical constellation of symptoms and the absence of pathological findings that would adequately explain them (exclusive criteria). The basic diagnostic assessment, consisting of a physical examination, basic laboratory tests, abdominal ultrasonography, and (in women) a gynecological examination, is supplemented by further testing that depends on the patient's symptoms. Colonoscopy is obligatory to rule out underlying pathological abnormalities. By communicating the diagnosis of irritable bowel syndrome to the patient, the physician shows that the patient's symptoms and concerns have been taken seriously. The mainstays of treatment are patient education on the benign course of the disease and the encouragement of a salubrious lifestyle. Further treatment options include dietary measures, time-limited symptomatic treatment with drugs, and psychotherapy.
The diagnosis of a functional bowel disorder is based on a thorough history (positive criteria) and a small battery of diagnostic tests to exclude somatic disease. Both the diagnostic assessment and the treatment should be carried out in accordance with published guidelines.
Deutsches Ärzteblatt International 02/2012; 109(5):83-94. · 3.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: To study the therapeutic effects of probiotic Escherichia coli Nissle 1917 (EcN) in irritable bowel syndrome (IBS) and identify subgroups benefiting most.
Some trials investigating therapeutic effects in irritable bowel syndrome have shown benefits in IBS subgroups only. Probiotic treatment seems to be promising.
Patients with irritable bowel syndrome (120; Rome II) were recruited to a prospective double-blind study and randomized to either EcN (n = 60) or placebo (n = 60) given for 12 weeks. Objectives were to describe efficacy and safety of EcN in different groups of irritable bowel syndrome. Outcome was assessed by 'Integrative Medicine Patient Satisfaction Scale'.
Altogether, the responder rate was higher in the EcN than in the placebo group. However, only after 10 and 11 weeks, the differences were significant (Δ 20.0% points [95% CI 2.6; 37.4], p = 0.01 and Δ 18.3% points [95% CI 1.0; 35.7], p = 0.02, respectively). The best response was observed in the subgroup of patients with gastroenteritis or antibiotics prior to irritable bowel syndrome onset (Δ 45.7% points, p = 0.029). No significant differences were observed in any other subgroup. Both treatment groups showed similar adverse events and tolerance.
Probiotic EcN shows effects in irritable bowel syndrome, especially in patients with altered enteric microflora, e.g. after gastroenterocolitis or administration of antibiotics.
International Journal of Colorectal Disease 12/2011; 27(4):467-74. · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Definition und Diagnosekriterien
Die deutsche RDS-Leitlinie hat sich hinsichtlich der Definition bzw. der Diagnosekriterien von den symptombasierten Diagnosekriterien (Rom-Kriterien) abgewandt und für eine Kombination aus Symptommuster und Ausschlussdiagnostik entschieden.
Danach liegt ein RDS vor, wenn länger als 3 Monate anhaltende Beschwerden bestehen, die von Patient und Arzt auf den Darm bezogen werden, in der Regel mit Stuhlgangsveränderungen einhergehen und begründen, dass der Patient deswegen Hilfe sucht und/oder sich sorgt, und seine Lebensqualität relevant beeinträchtigen. Voraussetzung ist dabei, dass keine für andere Krankheitsbilder charakteristischen Veränderungen vorliegen, die wahrscheinlich für die Symptome verantwortlich sind.
Für die Diagnosestellung sollen Anamnese, Muster und Ausmaß der Beschwerden mit einem Reizdarmsyndrom vereinbar sein. Die „Sicherung“ des Reizdarmsyndroms erfordert darüber hinaus den Ausschluss relevanter Differenzialdiagnosen.
Wenn nach der Diagnosestellung gemäß diesen Kriterien im weiteren Verlauf keine neuen Aspekte auftauchen, soll keine erneute Diagnostik erfolgen.
Die obligate Basisdiagnostik umfasst Anamnese, körperliche Untersuchung, Labor (Blutbild, BSG/CRP, Urinstatus), Ultraschall Abdomen und bei Frauen die gynäkologische Untersuchung. Die weitere Diagnostik hängt von den individuellen Symptomen ab und beinhaltet bei Patienten mit Diarrhö grundsätzlich eine ausführliche Erregerdiagnostik im Stuhl sowie endoskopische (inklusive Stufenbiopsien) und funktionsdiagnostische Untersuchungen.
Die Therapie gliedert sich in allgemeine Therapiemaßnahmen (Eingehen auf psychische Einflussfaktoren, Stressreduktion, individuelle Ernährungsempfehlungen) und die medikamentöse Therapie, die symptomorientiert erfolgen soll.
Bei unzureichendem Therapieerfolg kann es erforderlich sein, sukzessiv unterschiedliche Medikamente einzusetzen.