Search

Global warming enhances atmospheric moisture loading and will likely affect monsoon strength in Vietnam. Without a long written history in Vietnam, we need to rely on geoarchives such as lake sediments to reconstruct past monsoon variability and regional paleoenvironmental fluctuations and evaluate current climatic trends. Natural lakes in the Central Highlands of Vietnam have the potential to have recorded shifts of the monsoon belt over glacial/interglacial cycles. Since 2016, the EOS Geoscience Research Group at Vietnam National University, Hanoi (EOS group) has collaborated with international partners to collect and analyze Vietnamese lake sediments to reconstruct the Pleistocene-Holocene climate history. Numerous sediment cores have been retrieved from Biển Hồ, Ia Bang, Ea Tyn, Ea Sno and Lak lakes between 2016 and 2022. Of special importance is a 25 m long sediment core from Biển Hồ Lake (Gia Lai province) covering the last 57 ka, which the team retrieved in April 2021. Sediment cores were analyzed for geochemistry, sedimentology, magnetic susceptibility, and radiocarbon dating. This paper reviews the status of our currently available sedimentary records to assess the paleoenvironmental potential of lacustrine sediments in the Central Highlands of Vietnam. Current data suggest that the lakes in the Central Highlands provide reliable sedimentological and geochemical records and bear the potential to reconstruct the paleoenvironmental and paleoclimatic conditions in Vietnam across several glacial periods, with a high-resolution record at least in the Holocene. The records contribute to quantifying the effects of monsoon variability and assessing the changes in hydrological conditions before and after the onset of human land use by comparing different lakes in the region. Future fieldwork will focus on retrieving longer lake sediment sequences from the Central Highlands, possibly covering the full interglacial-glacial cycle (i.e. the last 125 ka, back to MIS-5e), and on the assessment of comparable lake archives in other parts of Vietnam where the timing and character of monsoon-related climatic variations may have differed.

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. Graphical Abstract

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.Data from all patients with SSC from 1996 to April 2021 were included.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.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.

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.

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.The study design was a retrospective case-control study. Calprotectin, lactoferrin and pyruvate kinase were measured in endoscopically retrieved bile with ELISA.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 (p0.001) 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.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.

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.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.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).RFA as an addition to SEMS implantation had no positive impact on patency rate or survival. (Clinical trial registration number: DRKS00018993.).

ObjectiveScheduled endoscopic dilatation of dominant strictures (DS) in primary sclerosing cholangitis (PSC) might improve outcome relative to endoscopic treatment on demand, but evidence is limited. Since randomisation is difficult in clinical practice, we present a large retrospective study comparing scheduled versus on-demand endoscopic retrograde cholangiopancreatography (ERCP) based on patient preferences.DesignBetween 1987 and 2017, all new patients with PSC had been offered scheduled ERCP with dilatation of a DS if diagnosed; the latter was repeated at defined intervals until morphological resolution, independent of clinical symptoms (treatment group). Patients who refused participation were clinically evaluated annually and received endoscopic treatment only on demand (control group). The primary clinical endpoint was transplantation-free survival. Secondary outcomes were overall survival, bacterial cholangitis episodes, hepatic decompensation of liver cirrhosis and endoscopy-related adverse events.ResultsThe final study included 286 patients, 133 (46.5%) receiving scheduled ERCP and 153 (53.5%) receiving on-demand ERCP. After a mean follow-up of 9.9 years, the rate of transplantation-free survival was higher in patients receiving scheduled ERCP (51% vs 29.3%; pConclusionIn our large retrospective study, regular ERCP with endoscopic balloon dilatation significantly benefits patients with PSC with DS, diagnosed both at initial presentation and during surveillance, even if asymptomatic. Further studies have to find out how to best identify stricture patients non-invasively.

Billions of animals migrate annually in pursuit of food, safety, and reproduction. Long-distance migration can be energetically expensive, which can force tradeoffs with investment in other physiological systems (e.g., suppressing immunity). Understanding the physiological impacts of migration is important to predict when and where such animals may be vulnerable to parasites and how changes to migration might affect infectious disease risks. To isolate relationships between migration and physiology from energetic tradeoffs and hormonal shifts associated with spring reproduction, we assessed differences in leukocyte profiles between seasonally sympatric resident and recently arrived fall migrant dark-eyed juncos (Junco hyemalis) in the Appalachian Mountains. When examining heterophil:lymphocyte (HL) ratios, which can elevate for long durations after even mild stressors, we found weak associations with migratory strategy (resident or migrant subspecies). In contrast, feather δ2H values showed that HL ratios were highest for juncos breeding at more northern latitudes, and this relationship was strongest for birds that arrived at the overwintering site infected with haemosporidian parasites (Plasmodium and Haemoproteus spp.). These patterns were more pronounced and better indicated hematological responses to stressors when using multivariate analyses. Our findings suggest that short- and long-distance migration may be more energetically costly in the presence of infection and highlight how approximating breeding latitude and using multivariate analyses can help understand host physiology.

Highlights • Wilkie’s syndrome (WS) is a rare but impairing condition. • WS is defined by an aorto-mesenteric artery angle, 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.

The neutron time-of-flight spectrometer NEAT has a long history of successful applications and is best suited to probe dynamic phenomena directly in the large time domain 10−14 – 10−10 s and on the length scale ranging from 0.05 to up to about 5 nm. To address user community needs for more powerful instrumental capabilities, a concept of the full upgrade of NEAT has been proposed. The upgrade started in 2010 after a rigorous internal and external selection process and resulted in 300-fold neutron count rate increase compared to NEAT′1995. Combined with new instrumental and sample environmental capabilities the upgrade allows NEAT to maintain itself at the best world class level and provide an outstanding experimental tool for a broad range of scientific applications. The advanced features of the new instrument include an integrated guide-chopper system that delivers neutrons with flexible beam properties: either highly homogeneous beam with low divergence suitable for single crystals studies or “hot-spot” neutron distribution serving best small samples. Substantial increase of the detector angle coverage is achieved by using 416 3He position sensitive detectors. Placed at 3 m from the sample, the detectors cover 20 m2 area and are equipped with modern electronics and DAQ using event recording techniques. The installation of hardware has been completed in June 2016 and on January 23, 2017 NEAT has welcomed its first regular users who took advantage of the high counting rate, broad available range of incoming neutron wavelengths and high flexibility of NEAT. Here we present details of NEAT upgrade, measured instrument characteristics and show first experimental results.

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).

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 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.

BackgroundAnastomotic leakage (AL) in the upper gastrointestinal (GI) tract is associated with high morbidity and mortality rates. Especially intrathoracic anastomotic leakage leads to life-threatening adverse events. Endoscopic vacuum therapy (EVT) for anastomotic leakage after transthoracic esophageal resection represents a novel concept. However, sound clinical data are still scarce. This prospective, single-center study aimed to evaluate the feasibility, effectiveness, and safety of EVT for intrathoracic anastomotic leakage following abdomino-thoracic esophageal resection. MethodsFrom 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. ResultsFifty-five patients were treated with EVT. Successful closure was achieved in 89.1% (n=49) by EVT only. The EVT-associated adverse event rate was 5.4% (n=3): bleeding occurred in one patient, while minor sedation-related adverse events 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. ConclusionsEVT 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.

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

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 2 saturation 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.

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.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.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.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.

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.

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. CLINICALTRIAL German Clinical Trials Register DRKS00018932; https://www.drks.de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00018932 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/17516

// Bruno Christian Kohler 1, 2 , Benjamin Goeppert 2, 3 , Nina Waldburger 2, 3 , Kai Schlamp 4 , Peter Sauer 5 , Dirk Jager 1, 2 , Karl Heinz Weiss 2, 5 , Stephan Macher-Goppinger 6 , Henning Schulze-Bergkamen 7 , Peter Schirmacher 2, 3 and Christoph Springfeld 1, 2 1 Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany 2 Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany 3 Department of Pathology, University of Heidelberg, Heidelberg, Germany 4 Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany 5 Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany 6 Institute of Pathology, University Medical Center Mainz, Mainz, Germany 7 Department of Internal Medicine II, Marien-Hospital, Wesel, Germany Correspondence to: Bruno Christian Kohler, email: bruno.koehler@nct-heidelberg.de Keywords: cholangiocarcinoma; Klatskin tumor; undifferentiated carcinoma; chemotherapy; endoscopic retrograde cholangiography Received: February 09, 2018 Accepted: March 22, 2018 Published: April 24, 2018 ABSTRACT Background: Neoplasms anatomically adjacent to the bile duct usually derive from malignantly transformed cholangiocytes forming cholangiocarcinoma (CCA). CCAs are divided in extrahepatic (eCCA) and intrahepatic (iCCA) tumors. Patients with irresectable CCAs are treated with systemic chemotherapy and have an unfavorable prognosis with a median survival of about one year. Here, we report a case of an undifferentiated carcinoma in Klatskin-position with long-term remission after systemic chemotherapy. Case Presentation: A 65-year-old Caucasian male presented with painless jaundice caused by an undifferentiated carcinoma in Klatskin-position (Type IIIb). Alpha fetoprotein (AFP; 3675 IU/mL) and carbohydrate antigen 19-9 (CA 19-9; 183 U/ml) were elevated. An exploratory laparotomy was carried out, but the patient was found to be irresectable due to severe fibrosis caused by biliary obstruction. Histology showed an undifferentiated carcinoma with high proliferation rate, and the patient was therefore subjected to poly-chemotherapy treatment according to the FOLFOX6-protocol. During therapy, AFP decreased to normal. Subsequent CT scans and ERC revealed a complete remission. Four years past initial diagnosis, a new suspicious lesion in the liver is visible on MRT; however, AFP and CA 19-9 are still in the normal range. Conclusions: Our case demonstrates that histopathological defined diagnosis may significantly inform therapeutic decision-making in irresectable cholangiocarcinoma even in regard to conventional systemic therapy. In case of an undifferentiated carcinoma poly-chemotherapy may provide significant success.