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.

A European survey of perendoscopic treatment of biliary complications in patients with alveolar echinococcosis.

BACKGROUND: Biliary complications represent a turning point in the course of Alveolar Echinococcosis (AE). We conducted a European survey to collect data on the current usage and results of perendoscopic interventions (PEIs) for their treatment. METHODS: Patient's characteristics and follow-up until January 31st, 2015 were recorded using an online questionnaire. RESULTS: From 18 centers 129 PEIs were analyzed in 38 patients; 139 plastic stents were inserted during 85 PEIs; median time between stent placements was significantly longer when 3 stents or more were placed. Initial symptoms disappeared in 95% and long-term bile duct patency was obtained in 73% of cases. Cholangitis was a more frequent complication of the PEIs (10%) than in other indications; intensive lavage of the bile ducts may prevent this complication. CONCLUSION: European centers use perendoscopic biliary drainage as an efficient and safe alternative to surgery to treat AE biliary complications. Insertion of multiple plastic stents delays stent occlusion and leads to effective and prolonged bile duct patency.

Cytomegalovirus disease in inflammatory bowel disease: epidemiology and disease characteristics in a large single-centre experience.

BACKGROUND: Patients with inflammatory bowel disease (IBD) show an increased risk of developing cytomegalovirus (CMV) disease because of immunosuppressive medication and malnutrition. Here, we aimed to investigate the prevalence and clinical characteristics of CMV disease in our cohort of IBD patients. PATIENTS AND METHODS: We carried out a retrospective analysis of 1023 IBD patients treated at our IBD clinic at the University Hospital Zurich between 2007 and 2014. CMV disease was defined as a positive immunohistochemistry for CMV and 14 patients were identified. RESULTS: The prevalence of CMV disease in our IBD cohort was 1.37%. Twelve patients had ulcerative colitis and two had Crohn's disease with colonic involvement. All patients who developed CMV disease received immunosuppressive medication or, as in one case, had HIV infection. The most used immunosuppressive medications were steroids and azathioprine. The most common therapeutic strategy was the consecutive use of ganciclovir and valganciclovir. Ten patients recovered and two were treatment refractory; among these, one required colectomy and two had a relapse. CONCLUSION: CMV disease may influence the clinical course of IBD. There is probably an association between CMV disease and IBD-specific medication. Risk factors, epidemiology and therapeutic strategy need to be further investigated.

Better survival in right-sided versus left-sided stage I - III colon cancer patients.

BACKGROUND: The distinction between right-sided and left-sided colon cancer has recently received considerable attention due to differences regarding underlying genetic mutations. There is an ongoing debate if right- versus left-sided tumor location itself represents an independent prognostic factor. We aimed to investigate this question by using propensity score matching. METHODS: Patients with resected, stage I - III colon cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2012). Both univariable and multivariable Cox regression as well as propensity score matching were used. RESULTS: Overall, 91,416 patients (51,937 [56.8 %] with right-sided, 39,479 [43.2 %] with left-sided colon cancer; median follow-up 38 months) were eligible. In univariable analysis, patients with right-sided cancer had worse overall (hazard ratio [HR] = 1.32, 95 % CI:1.29-1.36, P < 0.001) and cancer-specific survival (HR = 1.26, 95 % CI:1.21-1.30, P < 0.001) compared to patients with left-sided cancer. After propensity score matching, the prognosis of right-sided carcinomas was better regarding overall (HR = 0.92, 95 % CI: 0.89 - 0.94, P < 0.001) and cancer-specific survival (HR = 0.90, 95 % CI:0.87 - 0.93, P < 0.001). In stage I and II, the prognosis of right-sided cancer was better for overall (HR = 0.89, 95 % CI:0.84-0.94 and HR = 0.85, 95 % CI:0.81-0.89) and cancer-specific survival (HR = 0.71, 95 % CI:0.64 - 0.79 and HR = 0.75, 95 % CI:0.70-0.80). Right- and left-sided colon cancer had a similar prognosis for stage III (overall: HR = 0.99, 95 % CI:0.95-1.03 and cancer-specific: HR = 1.04, 95 % CI:0.99-1.09). CONCLUSIONS: This population-based analysis on stage I - III colon cancer provides evidence that the prognosis of localized right-sided colon cancer is better compared to left-sided colon cancer. This questions the paradigm from previous research claiming a worse survival in right-sided colon cancer patients.

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.

Meta-Analysis of the Effect of Bowel Preparation on Adenoma Detection: Early Adenomas Affected Stronger than Advanced Adenomas.

BACKGROUND AND AIMS: Low-quality bowel preparation reduces efficacy of colonoscopy. We aimed to summarize effects of bowel preparation on detection of adenomas, advanced adenomas and colorectal cancer. METHODS: A systematic literature search was performed regarding detection of colonic lesions after normal and low-quality bowel preparation. Reported bowel preparation quality was transformed to the Aronchick scale with its qualities "excellent", "good", "fair", "poor", and "insufficient" or "optimal" (good/excellent), "suboptimal" (fair/poor/insufficient), "adequate" (good/excellent/fair) and "inadequate" (poor/insufficient). We identified two types of studies: i) Comparative studies, directly comparing lesion detection according to bowel preparation quality, and ii) repeat colonoscopy studies, reporting results of a second colonoscopy after previous low-quality preparation. RESULTS: The detection of early adenomas was reduced with inadequate vs. adequate bowel preparation (Odds Ratio (OR) 0.53, CI: 0.46-0.62, p<0.001). The advanced adenomas were affected less in comparison (0.74, CI: 0.62-0.87, p<0.001). The large number of subjects considered in the present meta-analysis resulted in smaller confidence intervals compared to earlier studies. Classifying the bowel-preparation quality as suboptimal vs. optimal led to the same qualitative conclusion (OR: 0.81, CI: 0.74-0.89, p<0.001 for early adenomas, OR: 0.94, CI: 0.87-1.01, n.s. for advanced adenomas). Bowel preparation was equally important for right-sided/ flat/ serrated vs. other lesions in most observational studies but more relevant in some repeat colonoscopy studies; data regarding carcinoma detection were insufficient. CONCLUSION: Inadequate bowel preparation affects detection of early colonic lesions stronger than advanced lesions.

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 Impact of Azathioprine-Associated Lymphopenia on the Onset of Opportunistic Infections in Patients with Inflammatory Bowel Disease.

BACKGROUND: Thiopurines are known to cause lymphopenia (<1,500 lymphocytes/µl). As severe lymphopenia (<500C/µl) is associated with opportunistic infections, we investigated severity of thiopurine-related lymphopenia and development of opportunistic infections in our tertiary referral centre. METHODS: We retrospectively screened medical records of 1,070 IBD patients and identified 100 individuals that developed a total of 161 episodes of lymphopenia during thiopurine treatment between 2002 and 2014. Occurrence of opportunistic infections was documented. A control group consisted of IBD patients receiving thiopurines but without developing lymphopenia. RESULTS: Of a total of 161 episodes of lymphopenia, 23% were severe (<500C/µl). In this subgroup, thiopurine dosing was modified in 64% (dosage reduction: 32%, medication discontinued: 32%). We identified 9 cases (5.5%) of opportunistic infections, of which only two occurred during severe lymphopenia. One opportunistic infection (4.5%) was identified in the control group. No association was found between opportunistic infections and severity of lymphopenia. All patients who suffered from opportunistic infections were receiving additional immunosuppressive medication. CONCLUSION: Our patients treated with thiopurines rarely developed severe lymphopenia and opportunistic infections did not occur more often than in the control group. A careful monitoring of lymphocytes and prophylactic adjustment of thiopurine therapy might contribute to this low incidence.

Monitoring colonoscopy withdrawal time significantly improves the adenoma detection rate and the performance of endoscopists.

BACKGROUND AND STUDY AIMS: The recommended minimum withdrawal time for screening colonoscopy is 6 minutes. Adenoma detection rates (ADRs) increase with longer withdrawal times. We aimed to compare withdrawal times and ADRs of endoscopists unaware of being monitored vs. aware. PATIENTS AND METHODS: Seven experienced gastroenterologists prospectively performed 558 screening colonoscopies during a 9-month period in a Swiss University hospital. Colonoscopy withdrawal times were first measured without the gastroenterologists' knowledge of being monitored (n = 355 colonoscopies) and then with their knowledge (n = 203 colonoscopies). RESULTS: The median withdrawal time when gastroenterologists were unaware of being monitored was 4.5 minutes (interquartile range [IQR] 4 ­â€Š5.5 minutes) without intervention and 6 minutes (IQR 4 ­â€Š9 minutes) with intervention, increasing significantly to 7.3 minutes (IQR 6.5 ­â€Š9 minutes) and 8 minutes (IQR 7 ­â€Š11 minutes), respectively, when they were aware of being monitored (P < 0.001 both for colonoscopies with and without intervention). The ADR increased from 21.4 % when the gastroenterologists were unaware of being monitored to 36.0 % when they were aware (P < 0.001). In the multivariate regression model, the endoscopists knowing they were being monitored was the strongest factor associated with ADR (odds ratio 4.417; 95 % confidence interval [CI] 2.241 ­â€Š8.705; P < 0.001). CONCLUSIONS: Colonoscopy withdrawal time in unmonitored gastroenterologists is shorter than recommended and increases with awareness of monitoring. ADR significantly increases when gastroenterologists are aware of being monitored. Implementation of systematic monitoring, and analysis of withdrawal time and ADR for each endoscopist may help to increase the ADR.

Management of von hippel-lindau disease: an interdisciplinary review.

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumour predisposition syndrome with an incidence of 1:36,000 newborns, the estimated prevalence in Europe is about 1-9/100,000. It is associated with an increased risk of developing various benign and malignant tumours, thus affecting multiple organs at different time points in the life of a patient. Disease severity and diversity as well as age at first symptoms vary considerably, and diagnostic delay due to failure of recognition is a relevant issue. The identification of a disease-causing VHL germline mutation subsequently allows family members at risk to undergo predictive genetic testing after genetic counselling. Clinical management of patients and families should optimally be offered as an interdisciplinary approach. Prophylactic screening programs are a cornerstone of care, and have markedly improved median overall survival of affected patients. The aim of this review is to give an overview of the heterogeneous manifestations of the VHL syndrome and to highlight the diagnostic and therapeutic challenges characteristic for this orphan disease. A comprehensive update of the underlying genetic and molecular principles is additionally provided. We also describe how the St. Gallen VHL multidisciplinary group is organised as an example of interdisciplinary cooperation in a tertiary hospital in Switzerland.

Routine use of Hemospray for gastrointestinal bleeding: prospective two-center experience in Switzerland.

Hemospray (Cook Medical, Winston-Salem, North Carolina, USA) is a hemostatic agent recently introduced for the management of upper gastrointestinal bleeding (GIB). To date, there is little experience with this fairly new hemostatic tool. The aim of this case series was to reflect the use and effectiveness of Hemospray as a treatment option in GIB in everyday clinical practice at two tertiary referral centers. Consecutive patients (n = 16) with active GIB of various origins were treated with Hemospray. The rate of successful initial hemostasis was 93.75 % (15 /16; salvage therapy 92.85 % [13/14]; monotherapy 100 % [2 /2]). The rebleeding rate within 7 days was 12.5 % (2/16). One patient, in whom interventional radiology also failed, had to undergo surgery as salvage therapy. The effectiveness of Hemospray in the management of GIB in various clinical situations is promising. Future multicenter randomized prospective trials for clearly defined bleeding situations are needed for greater generalizability of case series findings.

How is the increased risk of colorectal cancer in first-degree relatives of patients communicated?

OBJECTIVES: Compared with the general population, first-degree relatives (FDRs) of colorectal cancer (CRC) patients have a two-fold to four-fold higher risk of developing CRC. Little data is available regarding communication between doctors and CRC patients about risk to FDRs. We aimed to evaluate CRC patients' knowledge of FDRs' increased CRC risk, and FDRs' knowledge of this risk and adherence to CRC screening. MATERIALS AND METHODS: In this retrospective, single-center, population-based observational study, patients aged 18-80 years who underwent surgery for CRC between January 2005 and May 2010 were asked to complete a questionnaire. A questionnaire sent to the patients' FDRs (siblings and children) asked whether they had been advised to undergo any CRC screening examination, whether they had done so, and if so, when initiated and by whom. Main outcome measurements were: CRC patients' and their FDRs' information status regarding the FDRs' increased CRC risk and screening status. RESULTS: Of 343 index patients (390 contacted, 47 deceased/moved), 134 replied to the survey (39.1% response rate). Among index patients, 82.1% (110/134) were informed about FDRs' increased CRC risk. This information was provided mainly by gastroenterologists and general practitioners (65.7 and 28.4%, respectively). Among FDRs, 85.1% (143/168) were informed about their increased CRC risk, but 69% did not undergo a screening colonoscopy. Among the FDRs more than 50 years of age, 40.8% did not undergo a screening colonoscopy. CONCLUSION: In Switzerland, CRC patients and their FDRs are well informed about FDRs' increased CRC risk. However, the majority of FDRs do not undergo the recommended CRC screening.

Perception of preference and risk-taking in laparoscopy, transgastric, and rigid-hybrid transvaginal NOTES for cholecystectomy.

QUESTIONS UNDER STUDY: Few data are available regarding patients' perceptions of new cholecystectomy (CC) techniques, in the context of the patients' risk behaviours. We investigated patients' preferences for transgastric pure natural orifice translumenal endoscopic surgery (NOTES; transgastric NCC) and rigid-hybrid transvaginal NOTES CC (tvNCC) compared with the standard laparoscopic CC (SL-CC), and patients' risk behaviours. METHODS: A total of 140 inpatients scheduled for elective laparoscopic CC were enrolled in this prospective single-centre study, from January 2009 to January 2010. Patients judged the potential advantages and disadvantages of transgastric NCC and tvNCC compared with SL-CC. The individual's risk behaviour was analysed by means of the validated 40-item Domain-Specific Risk Attitude Scale (DOSPERT). RESULTS: Of the 140 recruited patients, 57 (65% females; mean age 51.5 years) were analysed. Twenty-five percent of males opted for transgastric NCC and 75% opted for SL-CC. Among females, 10.8%, 37.8% and 51.4% opted for transgastric NCC, tvNCC and SL-CC, respectively. Faster convalescence was graded as the primary potential advantage of transgastric NCC, whereas the potential risk of long-term stomach injuries was considered a primary disadvantage. Females graded the reduction of hospital-acquired morbidity as the primary advantage of tvNCC. The risk assessment showed significantly more risk-taking behaviour in the recreational domain of life among patients who opted for innovative surgical techniques than among those opting for conventional surgery. CONCLUSIONS: Transgastric NCC is rarely accepted by females but accepted by a quarter of males. Females consider rigid-hybrid tvNCC and SL-CC similarly attractive. Despite promising new techniques, three-quarters of male and one half of female patients still prefer the standard laparoscopic CC.

Predictors for hospitalization and outpatient visits in patients with inflammatory bowel disease: results from the Swiss Inflammatory Bowel Disease Cohort Study.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) have a high resource consumption, with considerable costs for the healthcare system. In a system with sparse resources, treatment is influenced not only by clinical judgement but also by resource consumption. We aimed to determine the resource consumption of IBD patients and to identify its significant predictors. MATERIALS AND METHODS: Data from the prospective Swiss Inflammatory Bowel Disease Cohort Study were analysed for the resource consumption endpoints hospitalization and outpatient consultations at enrolment [1187 patients; 41.1% ulcerative colitis (UC), 58.9% Crohn's disease (CD)] and at 1-year follow-up (794 patients). Predictors of interest were chosen through an expert panel and a review of the relevant literature. Logistic regressions were used for binary endpoints, and negative binomial regressions and zero-inflated Poisson regressions were used for count data. RESULTS: For CD, fistula, use of biologics and disease activity were significant predictors for hospitalization days (all P-values <0.001); age, sex, steroid therapy and biologics were significant predictors for the number of outpatient visits (P=0.0368, 0.023, 0.0002, 0.0003, respectively). For UC, biologics, C-reactive protein, smoke quitters, age and sex were significantly predictive for hospitalization days (P=0.0167, 0.0003, 0.0003, 0.0076 and 0.0175 respectively); disease activity and immunosuppressive therapy predicted the number of outpatient visits (P=0.0009 and 0.0017, respectively). The results of multivariate regressions are shown in detail. CONCLUSION: Several highly significant clinical predictors for resource consumption in IBD were identified that might be considered in medical decision-making. In terms of resource consumption and its predictors, CD and UC show a different behaviour.

Predictors of temporary and permanent work disability in patients with inflammatory bowel disease: results of the swiss inflammatory bowel disease cohort study.

BACKGROUND: Inflammatory bowel disease can decrease the quality of life and induce work disability. We sought to (1) identify and quantify the predictors of disease-specific work disability in patients with inflammatory bowel disease and (2) assess the suitability of using cross-sectional data to predict future outcomes, using the Swiss Inflammatory Bowel Disease Cohort Study data. METHODS: A total of 1187 patients were enrolled and followed up for an average of 13 months. Predictors included patient and disease characteristics and drug utilization. Potential predictors were identified through an expert panel and published literature. We estimated adjusted effect estimates with 95% confidence intervals using logistic and zero-inflated Poisson regression. RESULTS: Overall, 699 (58.9%) experienced Crohn's disease and 488 (41.1%) had ulcerative colitis. Most important predictors for temporary work disability in patients with Crohn's disease included gender, disease duration, disease activity, C-reactive protein level, smoking, depressive symptoms, fistulas, extraintestinal manifestations, and the use of immunosuppressants/steroids. Temporary work disability in patients with ulcerative colitis was associated with age, disease duration, disease activity, and the use of steroids/antibiotics. In all patients, disease activity emerged as the only predictor of permanent work disability. Comparing data at enrollment versus follow-up yielded substantial differences regarding disability and predictors, with follow-up data showing greater predictor effects. CONCLUSIONS: We identified predictors of work disability in patients with Crohn's disease and ulcerative colitis. Our findings can help in forecasting these disease courses and guide the choice of appropriate measures to prevent adverse outcomes. Comparing cross-sectional and longitudinal data showed that the conduction of cohort studies is inevitable for the examination of disability.

Serum immunoglobin G4 (IgG4): an important marker in autoimmune pancreatitis?

A unique form of chronic pancreatitis has recently become widely recognised as an important clinical entity in the spectrum of pancreatic diseases under the term autoimmune pancreatitis (AIP). This entity is characterised by irregular narrowing of the pancreatic duct, swelling of parenchyma, lymphoplasmacytic infiltration and fibrosis as well as favourable response to corticosteroid treatment. In addition, increased concentration of serum immunoglobulin G4 (IgG4) is a notable characteristic marker. Some patients undergoing pancreaticoduodenectomy for presumed pancreatic ductal adenocarcinoma have instead been found to have AIP. Early recognition of AIP can prevent pancreaticoduodenectomy in these patients and effective treatment with steroids can be introduced. Based on an interesting case, we discuss the entity of AIP with the rare combination of sclerosing cholangitis and we focus on the relevance of serum IgG4 as a factor in diagnosis and monitoring therapy of AIP.