Michael C. Sulz

Fatal Liver Failure in an Adult Patient with Acute Lymphoblastic Leukemia following Treatment with L-Asparaginase

L-Asparaginase is commonly used in combination chemotherapy of both pediatric and adult acute lymphoblastic leukemia. The majority of adverse effects are hypersensitivity reactions, but serious liver injury may also occur. It has been shown that treatment with L-asparaginase can be associated mainly with macrovesicular hepatic steatosis which may be accompanied by alterations in lipid metabolism. So far, the mechanism for liver injury associated with L-asparaginase is not known. We report here an adult patient who developed mixed liver injury and predominantly microvesicular hepatic steatosis while being treated with L-asparaginase for acute lymphoblastic leukemia. The patient developed liver failure and died due to multiorgan failure. Both impaired liver mitochondrial function and alterations in very-low-density lipoprotein metabolism and secretion are discussed as two possible mechanisms explaining the findings observed in this patient.

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.

Multipurpose use of the over-the-scope-clip system (“Bear claw”) in the gastrointestinal tract: Swiss experience in a tertiary center

AIM To evaluate the outcome of over-the-scope-clip system (OTSC) for endoscopic treatment of various indications in daily clinical practice in Switzerland. METHODS This prospective, consecutive case series was conducted at a tertiary care hospital from September 2010 to January 2014. Indications for OTSC application were fistulae, anastomotic leakage, perforation, unroofed submucosal lesion for biopsy, refractory bleeding, and stent fixation in the gastrointestinal (GI) tract. Primary technical success was defined as the adequate deployment of the OTSC on the target lesion. Clinical success was defined as resolution of the problem; for instance, no requirement for surgery or further endoscopic intervention. In cases of recurrence, retreatment of a lesion with a second intervention was possible. Complications were classified into those related to sedation, endoscopy, or deployment of the clip. RESULTS A total of 28 OTSC system applications were carried out in 21 patients [median age 64 years (range 42-85), 33% females]. The main indications were fistulae (52%), mostly after percutaneous endoscopic gastrostomy tube removal, and anastomotic leakage after GI surgery (29%). Further indications were unroofed submucosal lesions after biopsy, upper gastrointestinal bleeding, or esophageal stent fixation. The OTSC treatments were applied either in the upper (48%) or lower (52%) GI tract. The mean lesion size was 8 mm (range: 2-20 mm). Primary technical success and clinical success rates were 85% and 67%, respectively. In 53% of cases, the suction method was used without accessories (e.g., twin grasper or tissue anchor). No endoscopy-related or OTSC-related complications were observed. CONCLUSION OTSC is a useful tool for endoscopic closure of various GI lesions, including fistulae and leakages. Future randomized prospective multicenter trials are warranted.

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.

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 – 5.5 minutes) without intervention and 6 minutes (IQR 4 – 9 minutes) with intervention, increasing significantly to 7.3 minutes (IQR 6.5 – 9 minutes) and 8 minutes (IQR 7 – 11 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 – 8.705; 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.

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.

Quality assurance of sphincterotomy: A prospective single-centre survey

Quality assurance becomes an increasingly important part of clinical medicine and of the field of endoscopy. Endoscopic sphincterotomy is associated with a fairly high complication rate. We aimed to assess our quality of sphincterotomy for benchmarking by using a prospective electronic database registry, and to identify potential risk factors for post-interventional complications. Over 2 years, 471 sphincterotomies were performed in a single tertiary referral centre. Patient- and procedure-related variables were prospectively recorded with the support of a multi-centre international sphincterotomy registry. Multivariate analysis was performed. The overall post-interventional complication rate was 9.3%. Pancreatitis happened in 5.5%, bleeding in 2.1%, perforation in 1.3%, and cholangitis in 0.4%. In the multivariate analysis following variables remained highly significant and predictive for complications: ‘papilla only in lateral view’ (p=0.001), antiplatelet therapy (p=0.024), and opacification with contrast up to the pancreatic tail (p=0.001). The primary success rate of sphincterotomy was 95.1%. The rate of post-interventional pancreatitis did not differ significantly regardless of the presence of prophylactic pancreatic stent (p=0.56). The outcome of sphincterotomy in our centre matches with literature data. The extent of pancreatic duct opacification has an influence on the pancreatitis rate. Prevention of pancreatitis by inserting pancreatic stents is not confirmed.

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.

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 Crohns 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.