Perianal fistulodesis - A pilot study of a novel minimally invasive surgical and medical approach for closure of perianal fistulae.

BACKGROUND: Perianal fistulae strongly impact on quality of life of affected patients. AIM: To challenge and novel minimally invasive treatment options are needed. METHODS: Patients with Crohn's disease (CD) in remission and patients without inflammatory bowel disease (non-IBD patients) were treated with fistulodesis, a method including curettage of fistula tract, flushing with acetylcysteine and doxycycline, Z-suture of the inner fistula opening, fibrin glue instillation, and Z-suture of the outer fistula opening followed by post-operative antibiotic prophylaxis with ciprofloxacin and metronidazole for two weeks. Patients with a maximum of 2 fistula openings and no clinical or endosonographic signs of a complicated fistula were included. The primary end point was fistula healing, defined as macroscopic and clinical fistula closure and lack of patient reported fistula symptoms at 24 wk. RESULTS: Fistulodesis was performed in 17 non-IBD and 3 CD patients, with a total of 22 fistulae. After 24 wk, all fistulae were healed in 4 non-IBD and 2 CD patients (overall 30%) and fistula remained closed until the end of follow-up at 10-25 mo. In a secondary per-fistula analysis, 7 out of 22 fistulae (32%) were closed. Perianal disease activity index (PDAI) improved in patients with fistula healing. Low PDAI was associated with favorable outcome (P = 0.0013). No serious adverse events were observed. CONCLUSION: Fistulodesis is feasible and safe for perianal fistula closure. Overall success rates is at 30% comparable to other similar techniques. A trend for better outcomes in patients with low PDAI needs to be confirmed.

Genital Dysplasia and Immunosuppression: Why Organ-Specific Therapy Is Important.

BACKGROUND: Young patients with Crohn's disease (CD) show a high prevalence of human papillomavirus (HPV) which is the main cause of high-grade squamous intraepithelial lesions (HSIL). A major complication for patients undergoing immunocompromising therapy is the development of genital dysplasia. METHODS: We report the case of a 32-year-old patient with recurrent genital dysplasia under long-term therapy for CD with a focus on different drug-related, immunosuppressive mechanisms. RESULTS: Gynecological examination and biopsy revealed high-grade vulvar intraepithelial neoplasia (VIN) positive for HPV 16 treated with laser vaporization. Due to the combination of HPV positivity, intraoperative multilocularity, and CD, follow-up examinations were performed every 6 months. One year later, the patient showed a VIN at a new location and additionally, a cervical intraepithelial neoplasia (CIN), which were surgically treated. Catch-up HPV vaccination was applied accessorily. After the switch from a TNF-α blocker to vedolizumab, which acts as a gut-selective anti-integrin, the subsequent PAP smear, vulvoscopy, and colposcopy showed no more evidence of dysplasia. CONCLUSIONS: This case report highlights that gut-selective immunosuppression with vedolizumab might be favorable in young HPV-positive patients due to a good side effect profile. Regular screening and HPV vaccination are a mainstay of dysplasia prevention and control. The risk for HPV-associated dysplasia in immunosuppressed patients is highly dependent on the choice of immunosuppressive therapy.

Vegetarian or gluten-free diets in patients with inflammatory bowel disease are associated with lower psychological well-being and a different gut microbiota, but no beneficial effects on the course of the disease.

Background: Many inflammatory bowel disease (IBD) patients follow a restrictive diet due to perceived positive effects on their symptoms. We assessed the prevalence of vegetarian (VD) and gluten-free diets (GFDs) in IBD patients, the reasons for following such a diet, and whether nutrition has an impact on disease activity and microbiota composition. Methods: We included 1254 patients from the Swiss Inflammatory Bowel Disease Cohort Study with prospective acquisition of clinical data and psychosocial, disease-related and lifestyle factors between 2006 and 2015. Dietary habits were assessed through a self-report questionnaire. In 92 patients, we analysed intestinal mucosa-associated microbial composition using high-throughput sequencing. Results: Overall, 4.1% (n = 52) of the patients reported following a VD and 4.7% (n = 54) a GFD. No differences regarding disease activity, fistula, hospitalization or surgery rates were observed. Patients on a VD or GFD had significantly higher levels of post-traumatic stress symptoms. Furthermore, GFD patients had significantly higher anxiety and depression symptom levels. The gut microbiota composition in IBD patients following a VD or GFD was significantly different compared to that of omnivores. Conclusions: Although we did not identify a relevant impact of a specific diet on the course of the disease, there was a significant association with lower psychological well-being in VD and GFD patients.

Association of IBD specific treatment and prevalence of pain in the Swiss IBD cohort study.

BACKGROUND: Extraintestinal manifestations (EIM) contribute significantly to the burden of disease in inflammatory bowel disease (IBD). Pain is a leading symptom in IBD and could be seen as an EIM itself. Treatment of IBD associated pain is challenging and insufficiently studied. A better knowledge on the association of pain and IBD specific treatment is warranted to improve the management of IBD patients. METHODS: All patients of the Swiss IBD Cohort Study (SIBDCS) (n = 2152) received a questionnaire regarding pain localization, pain character, and the use of IBD specific medication. RESULTS: 1263 completed questionnaires were received. Twenty-one out of 184 patients (10%) receiving anti-TNF treatment compared to 142 out of 678 patients (21%) not receiving anti-TNF medication reported elbow pain (p = 0.002) while 28 out of 198 patients (14%) receiving steroid treatment significantly more often reported elbow pain compared to 59 from 696 patients (8%) not receiving steroids (p = 0.021). Furthermore, we found significantly more female patients under anti-TNF treatment to report knee/ lower leg pain and ankle/ foot pain compared to their male counterparts (36% vs. 20% and 22% vs. 10%, respectively, p = 0.015 for both comparisons). The frequency of knee, lower leg, ankle and foot pain was especially low in male patients under anti-TNF treatment, indicating a high benefit of male patients from anti-TNF therapy regarding EIM. CONCLUSIONS: The frequency of elbow pain was lower in IBD patients treated with anti-TNF but higher in patients treated with steroids.

ß6 -integrin serves as a novel serum tumor marker for colorectal carcinoma.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify ß6 -integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro- and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non-CRC control patients. A cut-off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6-levels were assessed in 26 CRC patients, pre- and post-surgery, as well as during follow-up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow-up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.

Risk factors for gallstones and kidney stones in a cohort of patients with inflammatory bowel diseases.

BACKGROUND: Gallstones and kidney stones are known complications of inflammatory bowel diseases (IBD). Risk factors have been insufficiently studied and explanatory studies date back up to 30 years. It remains unclear, whether improved treatment options also influenced risk factors for these complications. OBJECTIVES: Identifying risk factors for gallstones and kidney stones in IBD patients. METHODS: Using data from the Swiss Inflammatory Bowel Disease Cohort Study we assessed associations of diseases characteristics with gallstones and kidney stones in univariate and multivariate logistic regression analyses. RESULTS: Out of 2323 IBD patients, 104 (7.8%) Crohn's disease (CD) and 38 (3.8%) ulcerative colitis (UC) patients were diagnosed with gallstones. Significant risk factors for gallstones were diagnosis of CD, age at diagnosis, disease activity and duration, NSAID intake, extra-intestinal manifestations and intestinal surgery. Kidney stones were described in 61 (4.6%) CD and 30 (3.0%) UC patients. Male gender, disease activity, intestinal surgery, NSAID usage and reduced physical activity were significant risk factors. Hospitalization was associated with gallstones and kidney stones. The presence of gallstones increased the risk for kidney stones (OR 4.87, p<0.001). CONCLUSION: The diagnosis of CD, intestinal surgery, prolonged NSAID use, disease activity and duration and bowel stenosis were significantly associated with cholecystonephrolithiasis in IBD.

Long-Term Efficacy and Safety of Certolizumab Pegol in an Unselected Crohn's Disease Population: The FACTS III Survey.

BACKGROUND: Long-term data of certolizumab pegol (CZP) in Crohn's disease (CD) from pivotal registry trials are limited. We therefore aimed to evaluate the long-term efficacy of CZP in clinical practice in Switzerland. METHODS: In the First Approved Certolizumab Therapeutic Experience in Switzerland-III phase IV multicenter cohort, patients receiving CZP were prospectively included all over Switzerland in (non-) academic hospitals and private practice. RESULTS: We included 104 CD patients (52 male; only 22.1% anti-tumor necrosis factor (TNF) naïve, CZP as third anti-TNF agent in 46.2%) with follow-up time between 6 weeks up to 5 years. During treatment with CZP, we observed a significant decrease of the Harvey Bradshaw Index from a median of 7 at baseline (interquartile range 4-11) to 4, 5, 4, 3, 3, and 2 at weeks 6, 26, 52, 78, 104, and 156, respectively. While anti-TNF naïve patients showed a significantly better response at the end of induction, during CZP maintenance therapy response was similar as compared to anti-TNF experienced patients as well as between patients with a short (0-5 years) vs. long duration of disease (>5 years). CONCLUSIONS: CZP is an effective long-term treatment option, including CD patients with long disease duration and prior treatment with 1 or 2 anti-TNF agents.

Patients' views on fecal microbiota transplantation: an acceptable therapeutic option in inflammatory bowel disease?

BACKGROUND: Fecal microbiota transplantation (FMT) represents a new therapeutic option that has been studied in two randomized-controlled trials in ulcerative colitis patients. Our study aimed to identify patients' views on the use of this novel therapeutic approach. METHODS: Using an anonymous questionnaire, we obtained data from 574 inflammatory bowel disease (IBD) patients on their knowledge and willingness to undergo FMT. RESULTS: A large proportion of IBD patients (53.5%) are unaware that FMT is a therapeutic option in Clostridium difficile infection and potentially IBD. More responders preferred FMT (31.5%) to a study with a new medication (28.9%), although the difference was not significant (P=0.37), and the preferred way of transplantation was colonoscopy (49.7%). In all, 38.3% preferred a family member as a donor, but there was fear about the procedure (41.5% mentioned fear of infectious diseases, 26.5% expressed disgust). The knowledge of successful FMT treatment in other patients was important for 82.2% of responders and for 50.7%, a discussion with a specialist would likely change their opinion about FMT. CONCLUSION: FMT represents a therapeutic procedure that is of interest for IBD patients. As FMT has been receiving increasing interest as an alternative treatment in IBD and more studies on FMT in IBD are being carried out, it is important to learn about the knowledge, attitude, and preferences of patients to provide better education to patients on this topic. However, there are reservations because of the fact that data on the benefits of FMT in IBD are controversial and several limitations exist on the use of FMT in IBD.

Risk Factors for the Development of Fistulae and Stenoses in Crohn Disease Patients in the Swiss Inflammatory Bowel Disease Cohort.

BACKGROUND: Fistulae and stenoses represent frequent and severe complications in patients with Crohn disease (CD). Our study aimed to identify risk factors for fistula and stenosis formation in CD patients. SUMMARY: We retrieved data of 1,600 CD patients from the nationwide Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). The risk for fistulae and stenoses in relation to gender, age at diagnosis, smoking status at diagnosis, and ileal involvement at diagnosis were analyzed. In the multivariate analysis, female gender showed a lower risk for developing perianal and any fistula (risk ratio [RR] 0.721, 95% confidence interval [CI] 0.582-0.893, p = 0.003 and RR 0.717, 95% CI 0.580-0.888, p = 0.002, respectively), and older age at diagnosis showed a lower risk for developing perianal fistula (RR 0.661, 95% CI 0.439-0.995, p = 0.047). Furthermore, ileal involvement was associated with a lower risk for perianal fistula (RR 0.713, 95% CI 0.561-0.906, p = 0.006), a lower risk for any fistula (RR 0.709, 95% CI 0.558-0.901, p = 0.005), and a higher risk for stenosis (RR 2.170, 95% CI 1.728-2.725, p < 0.001). KEY MESSAGES: In the nationwide SIBDCS, younger age at diagnosis and male gender were risk factors for developing perianal and nonperianal fistulae. Additionally, ileal involvement was revealed to be a potent risk factor (RR 2.170) for developing a stenosis.

Systematic Evaluation of Diagnostic Delay in Pediatric Inflammatory Bowel Disease.

We evaluated the diagnostic delay (time from first symptoms to diagnosis) in 100 pediatric patients with Crohn disease (CD) and 75 patients with ulcerative colitis (UC). Median (interquartile range) diagnostic delay in patients with CD was 4 (2-8) (range 0-82) months compared with 2 (1-7) (range 0-52) months in patients with UC (P = 0.003). The time interval from first physician visit to inflammatory bowel disease diagnosis was longer in patients with CD and UC when compared to the time interval from symptom onset to first physician visit (CD: median 3 vs 1 months, P < 0.001; UC: median 2 vs 0 months, P < 0.001). No specific risk factors were identified for the length of diagnostic delay. Measures should be taken to reduce diagnostic delay.

Genotype-Phenotype Associations of the CD-Associated Single Nucleotide Polymorphism within the Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 22 in Patients of the Swiss IBD Cohort.

BACKGROUND: Protein tyrosine phosphatase non-receptor type 22 (PTPN22) plays an important role in immune cell function and intestinal homeostasis. The single nucleotide polymorphism (SNP) rs2476601 within the PTPN22 gene locus results in aberrant function of PTPN22 protein and protects from Crohn's disease (CD). Here, we investigated associations of PTPN22 SNP rs2476601 in inflammatory bowel disease (IBD) patients in the Swiss IBD Cohort Study (SIBDCS). METHODS: 2'028 SIBDCS patients (1173 CD and 855 ulcerative colitis (UC) patients) were included. The clinical characteristics were analysed for an association with the presence of the PTPN22 SNP rs2476601 genotypes 'homozygous variant' (AA), 'heterozygous' (GA) and 'homozygous wild-type' (GG). RESULTS: 13 patients (0.6%) were homozygous variant (AA) for the PTPN22 polymorphism, 269 (13.3%) heterozygous variant (GA) and 1'746 (86.1%) homozygous wild-type (GG). In CD, AA and GA genotypes were associated with less use of steroids and antibiotics, and reduced prevalence of vitamin D and calcium deficiency. In UC the AA and GA genotype was associated with increased use of azathioprine and anti-TNF antibodies, but significantly less patients with the PTPN22 variant featured malabsorption syndrome (p = 0.026). CONCLUSION: Our study for the first time addressed how presence of SNP rs2476601 within the PTPN22 gene affects clinical characteristics in IBD-patients. Several factors that correlate with more severe disease were found to be less common in CD patients carrying the A-allele, pointing towards a protective role for this variant in affected CD patients. In UC patients however, we found the opposite trend, suggesting a disease-promoting effect of the A-allele.

Malignancies in Patients with Inflammatory Bowel Disease: A Single-Centre Experience.

BACKGROUND: Gastrointestinal and extraintestinal malignancies are long-term complications in patients with inflammatory bowel disease (IBD), likely as a result of chronic inflammation and the use of immunosuppressive medications used to control inflammation. Here, we assessed the frequency of malignancies in a large tertiary IBD centre at the University Hospital Zurich. METHODS: We performed a retrospective analysis of data from 1,026 patients from our IBD clinic treated between 2007 and 2014. RESULTS: Twenty two of the 1,026 patients developed 28 cases of malignancies, 14 patients were male and 8 patients female. The median latency between IBD diagnosis and first malignancy was 13 years (range 2-27 years). Most common malignancies were non-Hodgkin lymphoma, colorectal cancer (CRC), urothelial carcinoma, cholangiocellular carcinoma (CCC) and prostate cancer. The most common tumour type in Crohn's disease patients (13/22) was lymphoma (5 cases), in ulcerative colitis patients (9/22) CCC (2 cases) and CRC (2 cases). The observed incidence of lymphoma (32.5/100,000), bladder carcinoma (21.7/100,000) and CCC (10.8/100,000) was higher than expected and known from general population. All of the patients that developed a malignancy had received immunosuppressive therapy. Compared to a cohort of 927 IBD patients without malignancies there were no statistical differences regarding gender, antibodies targeting tumour necrosis factor and thiopurine use. CONCLUSION: Our data support the assumption that a long-standing disease course and immunosuppressive therapy increase the risk for developing malignancies in IBD patients.

The Clinical Relevance of the IBD-Associated Variation within the Risk Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 2 in Patients of the Swiss IBD Cohort.

BACKGROUND/AIMS: The single nucleotide polymorphism (SNP) rs1893217 within the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) results in a dysfunctional PTPN2 protein is associated with Crohn's disease (CD) and exists in perfect linkage disequilibrium with the CD- and ulcerative colitis (UC)-associated PTPN2 SNP rs2542151. We investigated associations of PTPN2 SNP rs1893217 and clinical characteristics of inflammatory bowel disease (IBD) patients. METHODS: One thousand seventy three patients with CD and 734 patients with UC from the Swiss IBD Cohort Study (SIBDCS) were included. Epidemiologic, disease and treatment characteristics were analysed for an association with the presence of one of the rs1893217 genotypes 'homozygous wild-type' (TT), 'heterozygous' (CT) and 'homozygous variant' (CC). RESULTS: About 2.88% of IBD patients were identified with CC, 26.8% with CT and 70.4% with TT genotype. The CC-genotype was associated with the existence of gallstones in CD and pancolitis in UC patients. The presence of the C-allele (i.e. either CC or CT genotype) was associated with the onset of uveitis, but protected from aphthous oral ulcers in CD patients. UC patients carrying a C-allele were diagnosed at an older age but required intestinal surgery more often. The presence of the C-allele was associated with a successful treatment with anti-TNF antibodies in both CD and UC patients. CONCLUSION: IBD patients carrying the C-allele of PTPN2 SNP rs1893217 are at greater risk for developing a severe disease course but are more likely to respond to treatment with anti-TNF antibodies. These findings demonstrate a clinical relevance of this PTPN2 risk variant in IBD patients.

[Differential diagnosis of abdominal pain]. / Differenzialdiagnostik abdomineller Schmerzen.

Despite the frequency of functional abdominal pain, potentially dangerous causes of abdominal pain need to be excluded. Medical history and clinical examination must focus on red flags and signs for imflammatory or malignant diseases. See the patient twice in the case of severe and acute abdominal pain if lab parameters or radiological examinations are normal. Avoid repeated and useless X-ray exposure whenever possible. In the case of subacute or chronic abdominal pain, lab tests such as fecal calprotectin, helicobacter stool antigen and serological tests for celiac disease are very useful. Elderly patients may show atypical or missing clinical signs. Take care of red herrings and be skeptical whether your initial diagnosis is really correct. Abdominal pain can frequently be an abdominal wall pain.

Patients' perceptions on the impact of coffee consumption in inflammatory bowel disease: friend or foe?--a patient survey.

BACKGROUND: Environmental factors are an integral component in the pathogenesis of inflammatory bowel disease (IBD). There is an increasing interest in nutritive components. While the potential disease-modifying role of coffee has been intensively investigated in a variety of gastrointestinal diseases, the data on the potential impact on IBD is very limited. We aimed to determine the patients' perspective on coffee consumption in IBD. METHODS: We conducted a questionnaire among IBD patients in Switzerland, assessing key questions regarding coffee consumption. Descriptive statistics including chi square testing were used for analysis of questionnaire data. RESULTS: Among a total of 442 patients 73% regularly consume coffee. 96% of patients attributing a positive and 91% of patients attributing no impact of coffee intake on IBD regularly drink coffee and surprisingly even 49% of those patients that assign a negative impact on disease symptoms. Among those patients refraining from regular coffee intake 62% are convinced that coffee adversely influences intestinal symptoms, significantly more in Crohn's disease (CD) than in ulcerative colitis (UC) (76% vs. 44%, p = 0.002). In total, 38% of all study subjects suppose that coffee has an effect on their symptoms of disease, significantly more in CD (54%) compared to UC patients (22%, p < 0.001). Moreover, while 45% of CD patients feel that coffee has a detrimental influence, only 20% of UC patients share this impression (p < 0.001). CONCLUSION: Two thirds of IBD patients regularly consume coffee. More than twice as many CD compared to UC patients attribute a symptom-modifying effect of coffee consumption, the majority a detrimental one. However, this negative perception does not result in abstinence from coffee consumption.

High Rates of Smoking Especially in Female Crohn's Disease Patients and Low Use of Supportive Measures to Achieve Smoking Cessation--Data from the Swiss IBD Cohort Study.

BACKGROUND AND AIMS: Smoking is a crucial environmental factor in inflammatory bowel disease [IBD]. However, knowledge on patient characteristics associated with smoking, time trends of smoking rates, gender differences and supportive measures to cease smoking provided by physicians is scarce. We aimed to address these questions in Swiss IBD patients. METHODS: Prospectively obtained data from patients participating in the Swiss IBD Cohort Study was analysed and compared with the general Swiss population [GSP] matched by age, sex and year. RESULTS: Among a total of 1770 IBD patients analysed [49.1% male], 29% are current smokers. More than twice as many patients with Crohn's disease [CD] are active smokers compared with ulcerative colitis [UC] [UC, 39.6% vs CD 15.3%, p < 0.001]. In striking contrast to the GSP, significantly more women than men with CD smoke [42.8% vs 35.8%, p = 0.025], with also an overall significantly increased smoking rate compared with the GSP in women but not men. The vast majority of smoking IBD patients [90.5%] claim to never have received any support to achieve smoking cessation, significantly more in UC compared with CD. We identify a significantly negative association of smoking and primary sclerosing cholangitis, indicative of a protective effect. Psychological distress in CD is significantly higher in smokers compared with non-smokers, but does not differ in UC. CONCLUSIONS: Despite well-established detrimental effects, smoking rates in CD are alarmingly high with persistent and stagnating elevations compared with the GSP, especially in female patients. Importantly, there appears to be an unacceptable underuse of supportive measures to achieve smoking cessation.

Severe Sweet's Syndrome with Elevated Cutaneous Interleukin-1ß after Azathioprine Exposure: Case Report and Review of the Literature.

Sweet's syndrome (SS) is a dermatosis with systemic symptoms characterized by tender, red nodules or papules, occasionally covered with vesicles, pustules or bullae, usually affecting the upper limbs, face and neck. SS is frequently observed in patients with leukemia or connective tissue diseases, while it is rather seldom in patients with inflammatory bowel disease. The exact pathogenesis of SS is only partially understood. We report the case of a 50-year-old patient with indeterminate colitis, presenting with a febrile diffuse papulopustular and necrotizing skin eruption that healed with significant scarring and appeared 14 days after onset of treatment with azathioprine. Histological examination revealed the presence of features typical of SS, gene expression analysis very high levels of interleukin-1ß (IL-1ß) mRNA in lesional skin, and immunohistochemistry high levels of IL-1ß at the protein level. SS associated with azathioprine is being increasingly reported and is reviewed herein.

Addressing current treatment challenges in Crohn's disease in real life: a physician's survey.

BACKGROUND: In recent years several trials have addressed treatment challenges in Crohn's disease. Clinical trials however, represent a very special situation. AIMS: To perform a cross-sectional survey among gastroenterologists on the current clinical real life therapeutic approach focussing on the use of biologics. METHODS: A survey including six main questions on clinical management of loss of response, diagnostic evaluation prior to major treatment changes, preference for anti-tumour necrosis factor (TNF) agent, (de-)escalation strategies as well as a basic section regarding personal information was sent by mail to all gastroenterologists in Switzerland (n=318). RESULTS: In total, 120 questionnaires were analysed (response rate 37.7%). 90% of gastroenterologists in Switzerland use a thiopurine as the first step-up strategy (anti-TNF alone 7.5%, combination 2.5%). To address loss of response, most physicians prefer shortening the interval of anti-TNF administration followed by dose increase, switching the biologic and adding a thiopurine. In case of prolonged remission on combination therapy, the thiopurine is stopped first (52.6%) after a mean treatment duration of 15.7 months (biologic first in 41.4%). CONCLUSIONS: Everyday clinical practice in Crohn's disease patients appears to be incongruent with clinical data derived from major trials. Studies investigating reasons underlying these discrepancies are of need to optimize and harmonize treatment.

Risk factors for repetitive ileocolic resection in patients with Crohn's disease: results of an observational cohort study.

BACKGROUND: Surgical recurrence rates among patients with Crohn's disease with ileocolic resection (ICR) remain high, and factors predicting surgical recurrence remain controversial. We aimed to identify risk and protective factors for repetitive ICRs among patients with Crohn's disease in a large cohort of patients. METHODS: Data on 305 patients after first ICR were retrieved from our cross-sectional and prospective database (median follow-up: 15 yr [0-52 yr]). Data were compared between patients with 1 (ICR = 1, n = 225) or more than 1 (ICR >1, n = 80) resection. Clinical phenotypes were classified according to the Montreal Classification. Gender, family history of inflammatory bowel disease, smoking status, type of surgery, immunomodulator, and biological therapy before, parallel to and after first ICR were analyzed. RESULTS: The mean duration from diagnosis until first ICR did not differ significantly between the groups, being 5.93 ± 7.65 years in the ICR = 1 group and 5.36 ± 6.35 years in the ICR >1 group (P = 0.05). Mean time to second ICR was 6.7 ± 5.74 years. In the multivariate logistic regression analysis, ileal disease location (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.02-5.78; P = 0.05) was a significant risk factor. A therapy with immunomodulators at time of or within 1 year after first ICR (OR, 0.23; 95% CI, 0.09-0.63; P < 0.01) was a protective factor. Neither smoking (OR, 1.16; 95% CI, 0.66-2.06) nor gender (male OR, 0.85; 95% CI, 0.51-1.42) or family history (OR, 1.68; 95% CI, 0.84-3.36) had a significant impact on surgical recurrence. CONCLUSIONS: Immunomodulators have a protective impact regarding surgical recurrence after ICR. In contrast, ileal disease location constitutes a significant risk factor for a second ICR.

Smoking cessation alters intestinal microbiota: insights from quantitative investigations on human fecal samples using FISH.

BACKGROUND: There has been a dramatic increase in investigations on the potential mechanistic role of the intestinal microbiota in various diseases and factors modulating intestinal microbial composition. We recently reported on intestinal microbial shifts after smoking cessation in humans. In this study, we aimed to conduct further microbial analyses and verify our previous results obtained by pyrosequencing using a direct quantitative microbial approach. METHODS: Stool samples of healthy smoking human subjects undergoing controlled smoking cessation during a 9-week observational period were analyzed and compared with 2 control groups, ongoing smoking and nonsmoking subjects. Fluorescence in situ hybridization was applied to quantify specific bacterial groups. RESULTS: Intestinal microbiota composition was substantially altered after smoking cessation as characterized by an increase in key representatives from the phyla of Firmicutes (Clostridium coccoides, Eubacterium rectale, and Clostridium leptum subgroup) and Actinobacteria (HGC bacteria and Bifidobacteria) as well as a decrease in Bacteroidetes (Prevotella spp. and Bacteroides spp.) and Proteobacteria (ß- and γ-subgroup of Proteobacteria). CONCLUSIONS: As determined by fluorescence in situ hybridization, an independent direct quantitative microbial approach, we could confirm that intestinal microbiota composition in humans is influenced by smoking. The characteristics of observed microbial shifts suggest a potential mechanistic association to alterations in body weight subsequent to smoking cessation. More importantly, regarding previously described microbial hallmarks of dysbiosis in inflammatory bowel diseases, a variety of observed microbial alterations after smoking cessation deserve further consideration in view of the divergent effect of smoking on the clinical course of Crohn's disease and ulcerative colitis.