Protocol of a randomised controlled phase II clinical trial investigating PREoperative endoscopic injection of BOTulinum toxin into the sphincter of Oddi to reduce bile leakage after hepatic resection: the PREBOT-II trial.

INTRODUCTION: Bile leakage represents a major cause of morbidity following hepatic resection. Although most patients can be managed non-operatively, this complication requires diagnostics and therapeutic interventions. Preoperative endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi represents an innovative approach to prevent bile leakage. The aim of the PREBOT-II trial is to generate the first randomised controlled trial data on the safety, feasibility and efficacy of preoperative endoscopic BTX injection into the sphincter of Oddi to prevent bile leakage following hepatic resection. METHODS AND ANALYSIS: The PREBOT-II trial is an investigator-initiated, exploratory, multicentre, randomised, controlled, open-label, phase II clinical trial with two parallel study groups. 70 patients scheduled for hepatic resection will be randomised to either the intervention or the control group. Patients of the intervention group will undergo preoperative endoscopic injection of BTX into the sphincter of Oddi 3-10 days before surgery, whereas in the control group only hepatic resection will be performed. The primary endpoint is the occurrence of a postoperative bile leakage within 30 days after hepatic resection according to the definition of the International Study Group of Liver Surgery. The secondary endpoints comprise further postoperative morbidity parameters such as severity of postoperative bile leakage, post-hepatectomy haemorrhage or liver failure, mortality and quality of life up to 3 months after hepatic resection. Safety and feasibility of the procedure will also be recorded. ETHICS, FUNDING AND DISSEMINATION: The PREBOT-II trial has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4044932) and the Ethics Committee of Heidelberg University (reference number AFmu-558/2021). This trial is supported by the German Federal Ministry of Education and Research. The results will be presented at national and international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: DRKS00024061, EudraCT: 2020-006001-35.

Scheduled endoscopic treatment of biliary anastomotic and nonanastomotic strictures after orthotopic liver transplantation.

BACKGROUND AND AIMS: Biliary strictures after liver transplantation are associated with significant morbidity and mortality. Although various endoscopic treatment strategies are available, consensus on a particular strategy is lacking. Moreover, the influence of endoscopic therapy on overall survival has not been studied. This retrospective study aimed to evaluate the impact of scheduled endoscopic dilatation of biliary strictures after orthotopic liver transplantation on therapeutic success, adverse events, and survival. METHODS: Between 2000 and 2016, patients with post-transplant anastomotic and nonanastomotic strictures were treated with balloon dilatation at defined intervals until morphologic resolution and clinical improvement. The primary clinical endpoint was overall survival, whereas secondary outcomes were technical and sustained clinical success, adverse events, treatment failure, and recurrence. RESULTS: Overall, 165 patients with a mean follow-up of 8 years were included; anastomotic and nonanastomotic strictures were diagnosed in 110 and 55 patients, respectively. Overall survival was significantly higher in patients with anastomotic strictures than in those with nonanastomotic strictures (median, 17.6 vs 13.9 years; log-rank: P < .05). Sustained clinical success could be achieved significantly more frequently in patients with anastomotic strictures (79.1% vs 54.5%, P < .001), and such patients showed significantly superior overall survival (19.7 vs 7.7 years; log-rank: P < .001). Sustained clinical success and the presence of nonanastomotic strictures were independently associated with better and worse outcomes (P < .05), respectively. CONCLUSIONS: Scheduled endoscopic treatment of biliary anastomotic and nonanastomotic strictures after liver transplantation is effective and safe, with high success rates. The implementation of this strategy controls symptoms and significantly improves survival.

Effect of endoscopic treatment in patients with secondary sclerosing cholangitis.

BACKGROUND AND AIM: Secondary sclerosing cholangitis (SSC) is a progressive disease with high mortality and characterized by chronic inflammation and biliary obstruction. Therapeutic options are limited. The aim of this retrospective study was to evaluate the effects of endoscopic treatment in patients with SSC, the outcome, and association with potential risk factors. METHODS: Data from all patients with SSC from 1996 to April 2021 were included. RESULTS: Eighty patients with SSC were included. Seventy-five patients (93.8%) underwent diagnostic endoscopic retrograde cholangiography; 46 patients (57.5%) could be treated endoscopically. Endoscopic treatment comprised removal of biliary casts (n = 36/75), dilatation of bile ducts (n = 17/75), and intermittent stenting (n = 11/75). Twenty patients underwent orthotopic liver transplantation (25%); 27 patients died (33.8%). Transplantation-free survival was affected neither by endoscopic treatment nor by presence of biliary strictures, but bacteria positive bile culture was associated with better and increased levels of serum alkaline phosphatase and bilirubin levels with poor outcome. CONCLUSIONS: Secondary sclerosing cholangitis is a progressive disease with poor long-term prognosis. Endoscopic treatment options seem to be limited regarding transplantation-free survival but might improve quality of life and prevent local complications such as cholangitis. The observed limited effect of endoscopic treatment might be attributed to the rapid progression of this disease.

Impact of endobiliary radiofrequency ablation on biliary drainage in patients with malignant biliary strictures treated with uncovered self-expandable metal stents: a randomized controlled multicenter trial.

BACKGROUND AND AIMS: Endobiliary radiofrequency ablation (RFA), usually combined with endoscopic stent insertion, is a simple procedure with the potential to improve stent patency and patient survival for malignant biliary obstruction. We conducted this randomized multicenter trial to evaluate the impact of RFA on stent patency. METHODS: Eighty-six patients with malignant biliary obstruction and nonresectable tumors (pancreatic carcinoma, cholangiocarcinoma, or metastases) were included and randomly assigned to receive a self-expandable metal stent (SEMS) only (n = 44) or RFA followed by SEMS insertion (RFA+SEMS, n = 42). The primary outcome measure was stent patency after 3 and 6 months; secondary outcome measures were patient survival and early adverse events within 30 days. RESULTS: Technical success rates for RFA and stent insertion were 100% and 98.8%, respectively. Stent patency after 3 and 6 months did not differ significantly between groups (RFA+SEMS group, 73.1% and 33.3%, respectively; SEMS-only group, 81.8% and 52.4%, respectively; P = .6). Similarly, the addition of RFA did not impact overall survival (hazard ratio, .72; P = .389 for RFA+SEMS). The adverse event rate in the RFA+SEMS group was 10.5% compared with 2.3% in the SEMS-only group, without a statistically significant difference (P = .18). CONCLUSIONS: RFA as an addition to SEMS implantation had no positive impact on patency rate or survival. (Clinical trial registration number: DRKS00018993.).

Simultaneous, High-Precision Measurements of δ2H and δ13C in Nanomole Quantities of Acetate Using Electrospray Ionization-Quadrupole-Orbitrap Mass Spectrometry.

Stable hydrogen isotope compositions (2H/1H ratios) have been an invaluable tool for studying biogeochemical processes in nature, but the diversity of molecular targets amenable to such analysis is limited. Here, we demonstrate a new technique for measuring δ2H of biomolecules via Orbitrap mass spectrometry (MS) using acetate as a model analyte. Acetate was chosen as a target molecule because its production and consumption are central to microbial carbon cycling, yet the mechanisms behind acetate turnover remain poorly understood. δ2H of acetate could provide a useful constraint on these processes; however, it remains uncharacterized in nature due to analytical challenges. Electrospray ionization (ESI)-Orbitrap MS circumvents these challenges and delivers methyl-specific H-isotope compositions of acetate with nanomole sensitivity, enough to enable analyses of environmental samples. This approach quantifies the methyl-specific δ2H and molecular-average δ13C of acetate simultaneously while achieving <3 and <0.5‰ uncertainty, respectively. Using optimized ionization and Orbitrap parameters, this level of precision is obtained within 15 min using only 15 nmol of acetate. As a demonstration of our analytical approach, we cultured three acetogenic bacteria and found a large 2H-fractionation between acetate and water (>310‰ depletion) associated with the Wood-Ljungdahl pathway, while fermentation expressed a muted (∼80‰) fractionation. With its high precision and sensitivity, Orbitrap MS is a promising tool for investigating these signals in nature after offline purification. Furthermore, the ESI-Orbitrap method presented here could be applied to other molecules amenable to ESI, including central metabolites and sugars, greatly expanding the molecular targets used in hydrogen isotope biogeochemistry.

Endoscopic Stent Placement Can Successfully Treat Gastric Leak Following Laparoscopic Sleeve Gastrectomy If and Only If an Esophagoduodenal Megastent Is Used.

PURPOSE: Gastric staple line leakage (GL) is a serious complication of laparoscopic sleeve gastrectomy (LSG), with a specific mortality ranging from 0.2 to 3.7%. The current treatment of choice is stent insertion. However, it is unclear whether the type of stent which is inserted affects treatment outcome. Therefore, we aimed not only to determine the effectiveness of stent treatment for GL but also to specifically clarify whether treatment outcome was dependent on the type of stent (small- (SS) or megastent (MS)) which was used. PATIENTS AND METHODS: A single-centre retrospective study of 23 consecutive patients was conducted to compare the outcomes of SS (n = 12) and MS (n = 11) for the treatment of GL following LSG. The primary outcome measure was the success rate of stenting, defined as complete healing of the GL without changing the treatment strategy. Treatment change or death were both coded as failure. RESULTS: The success rate of MS was 91% (10/11) compared to only 50% (6/12) for SS (p = 0.006). An average of 2.3 ± 0.5 and 6.8 ± 3.7 endoscopies were required to achieve healing in the MS and SS groups respectively (p < 0.001). The average time to resumption of oral nutrition was shorter in the MS group (1.4 ± 1.1 days vs. 23.1 ± 33.1 days, p = 0.003). CONCLUSIONS: Stent therapy is only effective and safe for the treatment of GL after LSG if a MS is used. Treatment with a MS may not only increase treatment success rates but may also facilitate earlier resumption of oral nutrition and shorten the duration of hospitalization.

Deep learning and session-specific rapid recalibration for dynamic hand gesture recognition from EMG.

We anticipate wide adoption of wrist and forearm electomyographic (EMG) interface devices worn daily by the same user. This presents unique challenges that are not yet well addressed in the EMG literature, such as adapting for session-specific differences while learning a longer-term model of the specific user. In this manuscript we present two contributions toward this goal. First, we present the MiSDIREKt (Multi-Session Dynamic Interaction Recordings of EMG and Kinematics) dataset acquired using a novel hardware design. A single participant performed four kinds of hand interaction tasks in virtual reality for 43 distinct sessions over 12 days, totaling 814 min. Second, we analyze this data using a non-linear encoder-decoder for dimensionality reduction in gesture classification. We find that an architecture which recalibrates with a small amount of single session data performs at an accuracy of 79.5% on that session, as opposed to architectures which learn solely from the single session (49.6%) or learn only from the training data (55.2%).

Open surgical ablation of ventricular tachycardia: Utility and feasibility of contemporary mapping and ablation tools.

BACKGROUND: Ventricular tachycardia (VT) catheter ablation success may be limited when transcutaneous epicardial access is contraindicated. Surgical ablation (SurgAbl) is an option, but ablation guidance is limited without simultaneously acquired electrophysiological data. OBJECTIVE: We describe our SurgAbl experience utilizing contemporary electroanatomic mapping (EAM) among patients with refractory VT storm. METHODS: Consecutive patients with recurrent VT despite antiarrhythmic drugs (AADs) and prior ablation, for whom percutaneous epicardial access was contraindicated, underwent open SurgAbl using intraoperative EAM guidance. RESULTS: Eight patients were included, among whom mean age was 63 ± 5 years, all were male, mean left ventricular ejection fraction was 39% ± 12%, and 2 (25%) had ischemic cardiomyopathy. Reasons for surgical epicardial access included dense adhesions owing to prior cardiac surgery, hemopericardium, or pericarditis (n = 6); or planned left ventricular assist device (LVAD) implantation at time of SurgAbl (n = 2). Cryoablation guided by real-time EAM was performed in all. Goals of clinical VT noninducibility or core isolation were achieved in 100%. VT burden was significantly reduced, from median 15 to 0 events in the month pre- and post-SurgAbl (P = .01). One patient underwent orthotopic heart transplantation for recurrent VT storm 2 weeks post-SurgAbl. Over mean follow-up of 3.4 ± 1.7 years, VT storm-free survival was achieved in 6 (75%); all continued AADs, although at lower dose. CONCLUSION: Surgical mapping and ablation of refractory VT with use of contemporary EAM is feasible and effective, particularly among patients with contraindication to percutaneous epicardial access or with another indication for cardiac surgery.

Self-Expanding Metal Stents for Anastomotic Leaks After Upper Gastrointestinal Cancer Surgery.

BACKGROUND: Anastomotic leakage (AL) is a common and severe complication after upper gastrointestinal (UGI) surgery. Although evidence is scarce, endoscopic deployed self-expanding metal stents (SEMS) are well-established for the management of AL in UGI surgery. The present study aimed to evaluate the feasibility, effectiveness, and safety of SEMS in terms of success, mortality, and morbidity in patients with AL after UGI cancer surgery. MATERIALS AND METHODS: Patients with AL after primary UGI cancer surgery were retrospectively analyzed with regard to demographics, disease, surgical and endoscopic procedures, and complications. Stent treatment success was divided into technical, primary (within 72 hours of stent deployment), sustained (after 72 hours of stent deployment), and sealing success. RESULTS: In a total of 63 patients, 74 stents were used and 11 were deployed in endoscopic reinterventions. Stent deployment was successful in all patients. Primary and sustained success rates were 68.3% (n = 43) and 65.1% (n = 41), respectively. Of the primarily successfully treated patients, 87.8% remained successfully treated. If primary treatment was unsuccessful, it remained unsuccessful in 66.6% of the patients (P = 0.002). Final sealing of the leakage was observed in 65.1% of patients (n = 41). Longer stent shafts and wider stent end widths were correlated with successful stent treatment (P < 0.05). CONCLUSION: SEMS are a safe and sufficient tool in the treatment of AL after UGI cancer surgery. Treatment success is improved with longer stent shafts and wider stent end widths. Switching to alternative treatments is strongly suggested if signs of persistent leakage are present beyond 72 hours after stent placement, as this is highly indicative of sustained stent failure.

Feasibility, effectiveness, and safety of endoscopic vacuum therapy for intrathoracic anastomotic leakage following transthoracic esophageal resection.

BACKGROUND: Anastomotic leakage (AL) in the upper gastrointestinal (GI) tract is associated with high morbidity and mortality rates. Especially intrathoracic anastomotic leakage leads to life-threatening complications. Endoscopic vacuum therapy (EVT) for anastomotic leakage after transthoracic esophageal resection represents a novel concept. However, sound clinical data are still scarce. This retrospective, single-center study aimed to evaluate the feasibility, effectiveness, and safety of EVT for intrathoracic anastomotic leakage following abdomino-thoracic esophageal resection. METHODS: From March 2014 to September 2019 259 consecutive patients underwent elective transthoracic esophageal resection. 72 patients (27.8%) suffered from AL. The overall collective in-hospital mortality rate was 3.9% (n = 10). Data from those who underwent treatment with EVT were included. RESULTS: Fifty-five patients were treated with EVT. Successful closure was achieved in 89.1% (n = 49) by EVT only. The EVT-associated complication rate was 5.4% (n = 3): bleeding occurred in one patient, while minor sedation-related complications were observed in two patients. The median number of EVT procedures per patient was 3. The procedures were performed at intervals of 3-5 days, with a 14-day median duration of therapy. The mortality rate of patients with AL was 7.2% (n = 4). Despite successfully terminated EVT, three patients died because of multiple organ failure, acute respiratory distress syndrome, and urosepsis (5.4%). One patient (1.8%) died during EVT due to cardiac arrest. CONCLUSIONS: EVT is a safe and effective approach for intrathoracic anastomotic leakages following abdomino-thoracic esophageal resections. It offers a high leakage-closure rate and the potential to lower leakage-related mortalities. TRIAL REGISTRATION: This trial was registered and approved by the Institutional Ethics Committee of the University of Heidelberg on 16.04.2014 (Registration Number: S-635/2013).

Prognostic value of inflammatory markers for detecting anastomotic leakage after esophageal resection.

BACKGROUND: Early diagnosis of anastomotic leakage (AL) after esophageal resection is crucial for the successful management of this complication. Inflammatory serological markers are indicators of complications during the postoperative course. The aim of the present study was to evaluate the prognostic value of routine inflammatory markers to predict anastomotic leakage after transthoracic esophageal resection. METHODS: Data from all consecutive patients undergoing transthoracic esophageal resection between January 2010 and December 2016 were analyzed from a prospective database. Besides clinicodemographic parameters, C-reactive protein, white blood cell count and albumin were analyzed and the Noble/Underwood (NUn) score was calculated to evaluate their predictive value for postoperative anastomotic leakage. Diagnostic accuracy was measured by sensitivity, specificity, and negative and positive predictive values using area under the receiver operator characteristics curve. RESULTS: Overall, 233 patients with transthoracic esophageal resection were analyzed, 30-day mortality in this group was 3.4%. 57 patients (24.5%) suffered from AL, 176 patients were in the AL negative group. We found significant differences in WBCC, CRP and NUn scores between patients with and without AL, but the analyzed markers did not show an independent relevant prognostic value. For CRP levels below 155 mg/dl from POD3 to POD 7 the negative predictive value for absence of AI was > 80%. Highest diagnostic accuracy was detected for CRP levels on 4th POD with a cut-off value of 145 mg/l reaching negative predictive value of 87%. CONCLUSIONS: In contrast to their prognostic value in other surgical procedures, CRP, WBCC and NUn score cannot be recommended as independent markers for the prediction of anastomotic leakage after transthoracic esophageal resection. CRP is an accurate negative predictive marker and discrimination of AL and no-AL may be helpful for postoperative clinical management. Trial registration The study was approved by the local ethical committee (S635-2013).

Protocol of a randomised controlled phase II clinical trial investigating PREoperative endoscopic injection of BOTulinum toxin into the sphincter of Oddi to reduce postoperative pancreatic fistula after distal pancreatectomy: the PREBOTPilot trial.

INTRODUCTION: Postoperative pancreatic fistula (POPF) is still the most frequently occurring and clinically relevant complication after distal pancreatectomy (DP). Preoperative endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi represents an innovative approach to prevent POPF. The aim of this project (PREBOTPilot) is to generate the first randomised controlled trial data on the safety, feasibility and efficacy of preoperative endoscopic BTX injection into the sphincter of Oddi to prevent clinically relevant POPF following DP. METHODS AND ANALYSIS: PREBOTPilot is an investigator-initiated, single-centre, randomised, controlled, open-label, phase II clinical trial with two parallel study groups and an exploratory study design. 60 patients scheduled for DP will be randomised to intervention and control group. In the intervention group, patients will undergo preoperative endoscopic injection of BTX into the sphincter of Oddi, whereas in the control group no preoperative endoscopy will be performed. The combined primary endpoint is the occurrence of clinically relevant POPF and/or death within 30 days after DP. The secondary endpoints comprise further postoperative outcome parameters and quality of life up to 3 months after DP as well as safety and feasibility of the procedure. Statistical analysis is based on the modified intention-to-treat population, excluding patients without status post DP. For safety analysis, rates of adverse events (AEs) and serious AEs will be calculated with 95% CIs for group comparisons. ETHICS, FUNDING AND DISSEMINATION: PREBOTPilot has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4043654) and the Ethics Committee of Heidelberg University (reference number AFmo-523/2019). This trial is supported by the German Federal Ministry of Education and Research (BMBF). The results of the trial will be presented at national and international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: DRKS00020401.

Effects of Alternative Offers of Screening Sigmoidoscopy and Colonoscopy on Utilization and Yield of Endoscopic Screening for Colorectal Neoplasms: Protocol of the DARIO Randomized Trial.

BACKGROUND: Flexible sigmoidoscopy and colonoscopy are recommended screening options for colorectal cancer (CRC). Despite colonoscopy being offered for CRC screening in Germany, the uptake of this offer has been very limited. OBJECTIVE: The objective of this study was to assess the potential for increasing use of endoscopic CRC screening and the detection of advanced colorectal neoplasms by offering the choice between use of flexible sigmoidoscopy and colonoscopy. METHODS: The DARIO study includes a cross-sectional study (part I), followed by a prospective 2-arm randomized controlled intervention trial (part II) with an associated biobank study (part III). Participation is possible in part I of the DARIO study only, parts I and II, or all 3 study parts. After obtaining informed consent from the municipalities, 12,000 people, aged 50-54 years, from the Rhine-Neckar region in Germany were randomly selected from residential lists of the responsible population registries and invited to complete a standardized questionnaire to investigate the nature, frequency, timing, and results of previous CRC screening and eventual diagnostic colonoscopies. In study part II participants from study part I with no colonoscopy in the preceding 5 years are randomized into 2 arms: arm A offering screening colonoscopy only, and arm B offering both options, either screening colonoscopy or screening sigmoidoscopy. The primary endpoint is the proportion of participants in whom colorectal neoplasms >0.5 cm are detected and removed at screening endoscopy. The secondary endpoints are the detection rate of any neoplasm and use of any endoscopic screening. Part III of the study will use samples from participants in study part II to construct a liquid and tissue biobank for the evaluation of less invasive methods of early detection of colon cancer and for the more detailed characterization of the detected neoplasms. Blood, urine, stool, and saliva samples are taken before the endoscopy. Tissue samples are obtained from the neoplasms removed during endoscopy. RESULTS: A total of 10,568 from 12,000 randomly selected women and men aged 50-54 years living in the Rhine-Neckar-Region of Germany have been invited for participation. The remaining 1432 (11.93%) could not be invited because they reached the age of 55 at the time of contact. Of those invited, 2785/10,568 (26.35%) participated in study part I; 53.60% (1493/2785) of these participants were female. Study parts II and III are ongoing. CONCLUSIONS: This study will answer the question if alternative offers of either screening sigmoidoscopy or screening colonoscopy will increase utilization and effectiveness of endoscopic CRC screening compared with an exclusive offer of screening colonoscopy. In addition, alternative noninvasive screening tests will be developed and validated. TRIAL REGISTRATION: German Clinical Trials Register DRKS00018932; https://www.drks.de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00018932. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17516.

Sedation-related complications during anesthesiologist-administered sedation for endoscopic retrograde cholangiopancreatography: a prospective study.

BACKGROUND: Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) require adequate sedation or general anesthesia. To date, there is lack of consensus regarding who should administer sedation in these patients. Several studies have investigated the safety and efficacy of non-anesthesiologist-administered sedation for ERCP; however, data regarding anesthesiologist-administered sedation remain limited. This prospective single-center study investigated the safety and efficacy of anesthesiologist-administered sedation and the rate of successful performed ERCP procedures. METHODS: The study included 200 patients who underwent ERCP following anesthesiologist-administered sedation with propofol and remifentanil. Procedural data, oxygen saturation, systolic blood pressure (SBP), heart rate, recovery score, patient and endoscopist satisfaction, as well as 30-day mortality and morbidity data were analyzed. RESULTS: Sedation-related complications occurred in 36 of 200 patients (18%) and included hypotension (SBP < 90 mmHg) and hypoxemia (O2 saturation < 90%) in 18 patients (9%) each. Most events were minor and did not necessitate discontinuation of the procedure. However, ERCP was terminated in 2 patients (1%) secondary to sedation-related complications. Successful cannulation was performed in all patients. The mean duration of the examination was 25 ± 16 min. Mean recovery time was 14 ± 10 min, and high post-procedural satisfaction was observed in both, patients (mean visual analogue scale [VAS] 9.6 ± 0.8) and endoscopists (mean VAS 9.3 ± 1.3). CONCLUSION: This study suggests that anesthesiologist-administered sedation is safe in patients undergoing ERCP and is associated with a high rate of successful ERCP, shorter procedure time, and more rapid post-anesthesia recovery, with high patient and endoscopist satisfaction.

Evaluation of two functional CD24 polymorphisms in primary sclerosing cholangitis.

Background: Primary sclerosing cholangitis (PSC) is a progressive liver disease and characterized by chronic inflammation, sclerosis and strictures of bile ducts. Several genetic risk factors might contribute to pathogenesis. Functional single nucleotide polymorphisms (SNPs) in the CD24 gene have been associated with the development of autoimmune and autoinflammatory diseases and might contribute to the susceptibility for inflammatory bowel disease (IBD).Aim: This retrospective study aimed to evaluate the impact of two functional CD24 SNPs on clinical features and disease progression in patients with PSC.Methods: A C to T coding polymorphism (rs8734) and a TG deletion in the 3´- untranslated region (rs3838646) were genotyped. The study cohort comprises of 359 PSC patients for rs3838646 genotype and 335 PSC patients for rs8734 genotype. Clinical and laboratory parameters were collected by chart review.Results: For the rs8734 genotype, 175 patients (52.2%) were found to be homozygous wildtype ('Ala/Ala'), 127 (37.9%) patients were heterozygous ('Ala/Val') and 33 patients (9.9%) were homozygous mutant ('Val/Val'). The rs8734genotype was associated with a decreased risk for dominant strictures at first diagnosis of PSC (p = .04). For the rs3838646 genotype, 322 patients (89.7%) were found to be homozygous wildtype ('TG/TG'); 37 showed the 'TG/del' genotype (10.3%). The 'TG/del'genotype was associated with alower risk of IBD (p = .01).There was no influence of both CD24 SNPs with clinical end points or transplantation-free survival in our PSC cohort.Conclusion: Our results suggest a mild association of the rs8734 CD24 genotype with dominant strictures at first diagnosis of PSC. The rs3838646 CD24 genotype is associated with a lower rate of IBD. Both SNPs seem to modulate the clinical phenotype without major pathogenetic importance for disease progression in PSC.

Intrahepatic biliary strictures after liver transplantation are morphologically similar to primary sclerosing cholangitis but immunologically distinct.

OBJECTIVE: Biliary strictures are an important cause of morbidity and mortality in primary hepatic disease and after liver transplantation (LT). We aimed to characterize inflammatory cytokines in biliary fluids in biliary strictures to investigate their immunological origin. METHODS: We conducted a retrospective study on 72 patients with strictures after LT, eight patients with primary sclerosing cholangitis (PSC) and 15 patients with secondary sclerosing cholangitis (SSC). We measured cytokines interleukin (IL)-2, -4, -6, -10, -17, monocyte chemoattractant protein (MCP)-1, fibroblast growth factor (FGF)-2 and interferon (IFN)-γ as well as biochemical components such as protein and phospholipids in biliary fluid obtained from endoscopic retrograde cholangiography (ERC). Cell viability assays were performed on human cholangiocytes (H69) after being treated with IL-6, IL-4 and IFN-γ. RESULTS: Bile of patients with diffuse strictures after LT or due to SSC showed low values of all measured cytokines except for IL-6 levels, which were largely elevated in patients with diffuse strictures after LT. Patients high in biliary IL-6 showed an increase in profibrotic markers FGF-2 and MCP-1. In contrast, PSC bile was dominated by a Th1/Th17 profile with elevated IL-2, IL-17 and IFN-γ. In LT patients with biliary strictures, biliary IL-6 negatively predicted retransplantation-free survival after ERC. CONCLUSION: PSC patients showed a biliary Th1/Th17 cytokine profile, while SSC and diffuse strictures showed low values of cytokines except IL-6. In diffuse intrahepatic strictures after LT, biliary IL-6 is strongly associated with retransplantation-free survival after ERC.

Biliary calprotectin, lactoferrin and dimeric pyruvate kinase after liver transplantation are associated with biliary damage and graft survival in a case-control study.

BACKGROUND: After liver transplantation (LT), biliary complications are associated with reduced graft survival. We tested inflammation markers for their association with biliary damage and graft loss in bile. MATERIAL AND METHODS: The study design was a retrospective case-control study. Calprotectin, lactoferrin and pyruvate kinase were measured in endoscopically retrieved bile with ELISA. RESULTS: Calprotectin and lactoferrin were significantly higher in bile of ischemic-type biliary lesions and donor duct non-anastomotic strictures than in control, bile leakage, Cytomegalovirus infection, anastomotic stricture or acute cellular rejection patients (p<0.001) independent of serum liver values at endoscopy. Calprotectin (p=0.02) was independently associated with retransplantation free survival in multivariate analysis, as was γGT (p=0.03) but not ERC radiographic classification of the bile duct or cold ischemia time. CONCLUSION: Calprotectin and lactoferrin are bile markers for biliary damage and are associated with re-transplantation free survival. They can differentiate progressive biliary damage from non-biliary liver value alterations after LT.

Food fear, quick satiety and vomiting in a 16 years old girl: It's bulimia, or maybe not ? A case report of Wilkie's syndrome (superior mesenteric artery syndrome).

INTRODUCTION: Wilkie's syndrome (WS), also known as superior mesenteric artery syndrome, is a rare clinical entity caused by compression of the horizontal (third) part of the duodenum between the superior mesenteric artery and the abdominal aorta leading to duodenal obstruction. PRESENTATION OF CASE: We report a case of a 16 years girl with long-term history of spontaneous vomiting and self-induced vomiting, also suffering from recurrent retrosternal pain, weight loss and thus reduced quality of life. Contrast intestinal series showed a large axial hernia which was laparoscopically reduced and treated by hiatoplasty and anterior hemifundoplication. After initial relief, recurrent postprandial nausea and vomiting reoccurred 4 weeks postoperatively. Abdominal MRI study revealed findings compatible with WS. After endoscopic exclusion of an anatomical duodenal lumen stenosis, she was successfully treated by duodeno-jejunostomy with a favorable outcome. DISCUSSION: WS might be hidden behind presumably more evident diagnoses such as bulimia, significant axial hernia and gastro-esophageal reflux disease in patients with recurred vomiting, abdominal pain and weight loss. CONCLUSION: The rare clinical entity of a WS necessitates a targeted diagnostic evaluation and therapy. Clinical details, diagnostic studies and treatment are discussed here.

Association between serum IgG level and clinical course in primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis is a chronic cholestatic liver disease. The pathomechanism is still not fully understood, but there is evidence that immune-mediated processes may contribute to disease progression. METHODS: We studied the prognostic relevance of serum immunoglobulin G (IgG) elevated above the upper limit of normal as a marker for immune activation at initial diagnosis and its influence on transplantation-free survival in a well-defined cohort of PSC patients. RESULTS: The final study cohort comprises of 148 PSC patients. Elevated IgG levels were found in 66 patients (44.6%). Apart from their younger age at first diagnosis, there was no significant difference between patients with or without elevated IgG levels. The presence of a concomitant inflammatory bowel disease, an autoimmune hepatitis or immunosuppressive medication was equally distributed between both groups. Patients with elevated IgG levels reached the combined endpoint (34 (59.6%) vs. 23 (40.4%); p = 0.004) significantly more often and had reduced transplantation-free survival (Log-rank: 24.0 (10.2-37.9) vs. 14.0 (8.5-19.5); p < 0.05). Cox regression analysis including age, gender, presence of IBD, presence of dominant stricture (DS), Mayo Risk Score (MRS), immunosuppression, biochemical response to UDCA and elevated IgG-levels confirmed MRS (p = 0.03), DS (p = 0.04), biochemical response (p = 0.04) and elevated IgG level (p = 0.04) as independent risk factors for reduced transplantation-free survival. CONCLUSION: We identified elevated serum IgG levels at first diagnosis as an independent risk factor for reduced transplant free-survival in patients with PSC.