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Summary Background & Aims Little is known about cholestasis including its most severe variant secondary sclerosing cholangitis (SSC), in critically ill patients with coronavirus disease 19 (COVID‐19). In this study we analyzed the occurrence of cholestatic liver injury and SSC, including clinical, serological, radiological and histopathological findings. Methods We conducted a retrospective single‐center analysis of all consecutive patients admitted to the intensive care unit (ICU) due to severe COVID‐19 at the University Hospital Zurich to describe cholestatic injury in these patients. The findings were compared to a retrospective cohort of patients with severe influenza A Results 34 patients with severe COVID‐19 admitted to the ICU were included. 14 patients (41%) had no cholestasis (group 0), 11 patients (32%, group 1) developed mild and 9 patients (27%, group 2) severe cholestasis. Patients in group 2 had a more complicated disease course indicated by significantly longer ICU stay (median 51 days IQR 25‐86.5) than the other groups (group 0 median 9.5 days IQR 3.8‐18.3 p =0.001 and group 1 median 16 days IQR 8‐30 p < 0.05 respectively). Four patients in group 2 developed SSC compared to none in the influenza A cohort. The available histopathological findings suggest an ischemic damage to the perihilar bile ducts. Conclusions The development of SSC represents an important complication of critically ill COVID‐19 patients and needs to be considered in the diagnostic work up in prolonged cholestasis. The occurrence of SSC is of interest in the ongoing pandemic since it is associated with considerable morbidity and mortality.

Summary Background Standard high‐resolution manometry (HRM) protocols are based on 10 single water swallows acquired in the supine position. Aims To assess the impact of position, rapid drink challenge and solid test meal on the diagnosis of oesophageal motility disorders. Methods Seventy‐two healthy volunteers (20‐76 years) and 366 consecutive patients (18‐90 years) completed HRM with 10 single water swallows in the supine and upright positions. Rapid drink challenge was performed twice, before and after the solid test meal. Diagnosis based on single water swallows in the supine position (Chicago Classification v3.0) was compared with results in the upright position and with provocative tests. Results Overall, diagnostic agreement in the supine and upright positions was present in 296/438 (67.6%) subjects. This increased to 90.0% when ineffective oesophageal motility was considered with normal motility. Integrated relaxation pressure was 4 mm Hg higher in the supine position. There was a higher prevalence of inconsistent, likely false positive, diagnoses of outlet obstruction in the supine compared to the upright position (16/20 vs 1/4 patients, P = 0.0007). Similarly, the difference in concordance for the diagnosis of oesophago‐gastric junction obstruction or achalasia between single water swallows in the supine and upright positions with solid test meal was significant (12/29 (41.4%) vs 12/14 (85.7%), P = 0.0087). Conclusion Diagnostic agreement for oesophageal motility disorders based on single water swallows in the upright and supine positions was moderate, with frequent discordant findings for ineffective motility and outlet obstruction. HRM studies can be performed in either position, using appropriate reference values. Rapid drink challenge or solid test meal can resolve diagnostic discrepancies.

Purpose Radiochemotherapy is the standard treatment for anal carcinoma (ACa). Intensity-modulated radiotherapy (IMRT) has been introduced, allowing focused irradiation of the tumor area. Whether physical benefits of IMRT translate to clinical benefits has not been sufficiently demonstrated. Methods We retrospectively reviewed data from 82 patients with newly diagnosed ACa. Patients treated with IMRT were compared with previous patients treated with conventional three-dimensional computational radiotherapy (3D-CRT). The influence of IMRT on complete remission and acute and chronic side effects was analyzed in univariate and multivariate analyses. Results 39/40 patients treated with IMRT were in complete remission after 1 year compared to 31/39 patients treated with 3D-CRT (p = 0.014). Multivariate analysis confirmed tumor T stage as well as lack of IMRT treatment as risk factors for persistent tumor at 6 months. No significant benefits of IMRT were apparent at later timepoints (median follow up 52 months, IQR: 31.5-71.8 months). Patients treated with IMRT had a significantly lower degree of skin toxicity (median 2 vs. 3 in a scale ranging from 0 to 3, p = 0.00092). Rates of hematological toxicity/proctitis were not reduced and rates of acute diarrhea increased (p = 0.034). Median length of hospitalization tended to be shorter in patients treated with IMRT (n. s.). ConclusionWe present a real-world experience of shifting radiation technique from conventional 3D-CRT to IMRT. IMRT patients had better tumor control at 1 year and lower degrees of skin toxicity. Our data indicate that IMRT can enable therapies with lower side effects with equal or better oncological results for patients with ACa.

Background and Aim Functional dyspepsia (FD) is a common disorder of gut–brain interaction with incompletely understood pathophysiology. Consequently, heterogeneous expert opinions on diagnostic tests and assessment of treatment efficacies exist. So far, no consensus about the most relevant diagnostic and outcome tool has been reached. In this study, we aimed to analyze the significance of a combined lactulose hydrogen breath test (LHBT) and liquid meal, yet representing a standardized test in irritable bowel syndrome (IBS), in FD. Methods We analyzed data of 146 FD, 204 IBS patients, and 50 healthy volunteers (HV). All patients underwent LHBT with a meal‐drink consisting of 30‐g Lactulose and 400‐mL Ensure®. Effect of abdominal symptom generation in FD/IBS compared with HV was assessed on a patient‐reported Likert‐scale. Results There was a significant difference between FD/IBS patients and HV in LHBT‐induced abdominal pain (odds ratio [OR] 246.9, 95% confidence interval [CI] 26.6–2290.7; OR 161.2, 95% CI 16.9–1534.8), abdominal bloating (OR 384.8, 95% CI 92.9–2135.4; OR 524.1, 95% CI 114.7–3432.3), borborygmi (OR 9.9, 95% CI 2.2–46.9; OR 17.7, 95% CI 4.7–67.4), nausea only in FD (OR 174.4, 95% CI 15.5–5375.5), and diarrhea in IBS only (OR 25.8, 95% CI 2.0–7012.6). Hydrogen production was not significantly different in FD/IBS and HV. Conclusions In this study, we demonstrated significant differences in postprandial symptom generation in FD and IBS compared with HV after LHBT. This does not only allow us to discriminate FD/IBS from HV but may also represent a diagnostic and monitoring tool for FD/IBS in the future, including monitoring of treatment effects.

Objective This study assessed whether high‐resolution manometry (HRM) with a test meal can detect clinically relevant, abnormal motility already in very early systemic sclerosis (SSc) and whether this finding is associated with subsequent disease progression. Methods This prospective, longitudinal cohort study recruited 68 consecutive SSc patients (group #1: 32 established disease (ACR, American College of Rheumatology /EULAR, The European League against Rheumatism 2013 and ACR 1980 criteria fulfilled); group #2: 24 early disease (only ACR/EULAR 2013 fulfilled); group #3: 12 very early disease (clinical expert diagnosis of SSc) and 72 healthy controls. HRM evaluated esophageal motility for water swallows and a solid test meal. Results Systemic sclerosis patients had less frequent effective esophageal contractions during the test meal compared to healthy controls even in very early disease (0.15, 1.0, 2.1 per minute for groups #1, #2, and #3, vs 2.5 per minute in health; P < 0.001, P < 0.001, and P < 0.0085, respectively). Ineffective motility at HRM was associated with a higher modified Rodnan skin score at baseline. Moreover, at mean 18 (10‐31) months of follow‐up, the presence of ineffective motility at baseline was associated with progression of skin disease (P = 0.01). Cox proportional hazard regression analysis identified hypotensive peristalsis in the test meal (<15% effective solid swallows) and low distal contractile integral (DCI; <400 mm Hg·cm·s) as predictors for skin aggravation, but not for new organ involvement. Conclusion Ineffective motility during a test meal is present already in patients with very early SSc. Findings on HRM studies are associated with disease severity at baseline, and low percentage of effective swallows in test meal and low mean DCI are both predictors of skin progression during follow‐up.

The reported incidental prostate cancer prevalence rates at radical cystoprostatectomy cover a range from 4 to 60 %. We investigated the influence of the histopathological work-up on prostate cancer prevalence rates. We identified 114 patients who had undergone cystoprostatectomy for bladder cancer between 2000 and 2012. Complete histopathological assessment was defined as follows: (i) complete embedding of the prostate gland, (ii) sectioning of 15 or more prostate sections, and (iii) processing as whole mount slides. Prostate cancer prevalence rates derived from complete and incomplete histopathological assessments were compared. The overall prostate cancer prevalence rate was 59.6 %. A mean of 14.4 macroscopic tissue sections (thickness 3-5 mm) were sectioned. Sectioning ≥15 sections resulted in a prostate cancer detection rate of 75 %, compared to 42.6 % when sectioning <15 sections (p < 0.001). Complete embedding yielded a prostate cancer detection rate of 72.3 and of 23.1 % for partly embedded prostates (p < 0.0001). Prostate cancer was detected in 68.8 % of the whole mounted samples and in 38.2 % of the samples sectioned as standard slides (p < 0.01); according to the criteria described by Epstein and Ohori, 44.1 % of the detected prostate cancers were clinically significant. The quality of the histopathological work-up significantly influences prostate cancer detection rates and might at least partially explain the highly variable reported incidental prostate cancer prevalence rates at cystoprostatectomy (CP). The high proportion of significant prostate cancer found in our series calls for a careful surgical approach to the prostate during CP.

INTRODUCTION: Despite enormous efforts during the past decades, pancreatic adenocarcinoma (PAC) remains one of the most deleterious cancer entities. A useful biomarker for early detection or prognosis of PAC does not yet exist. The goal of our study was the characterization of β 6 -integrin (ITGB6) as a novel serum tumor marker for refined diagnosis and prognosis of PAC. Serum ITGB6 levels were analyzed in 3 independent PAC cohorts consisting of retrospectively and prospectively collected serum and/or (metastatic) PAC tissue specimens. METHODS: Using 2 independent cohorts, we measured serum ITGB6 concentrations in 10 chronic pancreatitis patients, 10 controls, as well as in 27 (cohort 1) and 24 (cohort 2) patients with PAC, respectively. In these patients, we investigated whether ITGB6 serum levels correlate with known clinical and prognostic markers for PAC and whether they might differ between patients with PAC or benign inflammatory diseases of the pancreas. RESULTS: We found that elevated serum ITGB6 levels (≥0.100 ng/mL) in patients suffering from metastasizing PAC presented an unfavorable prognostic outcome. By correlating the ITGB6 tissue expression in primary and metastatic PAC with clinical parameters, we found that positive ITGB6 expression in the tumor tissue is linked to increased serum ITGB6 levels in nonmetastatic PAC and correlates with carbohydrate antigen 19-9 and clinical outcome. DISCUSSION: Our findings suggest that ITGB6 might serve as a novel serum biomarker for early diagnosis and prognosis of PAC. Given the limited specificity and sensitivity of currently used carbohydrate antigen 19-9–based assays, ITGB6 may have the potential to improve the diagnostic accuracy for PAC.