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.

Mechanical stretching and chemical pyloroplasty to prevent delayed gastric emptying after esophageal cancer resection-a meta-analysis and review of the literature.

BACKGROUND: Delayed gastric emptying (DGE) occurs in up to 40% of patients after esophageal resection and prolongs recovery and hospital stay. Surgically pyloroplasty does not effectively prevent DGE. Recently published methods include injection of botulinum toxin (botox) in the pylorus and mechanical interventions as preoperative endoscopic dilatation of the pylorus. The aim of this study was to investigate the efficacy of those methods with respect to the newly published Consensus definition of DGE. METHODS: A systematic literature search using CENTRAL, Medline, and Web of Science was performed to identify studies that described pre- or intraoperative botox injection or mechanical stretching methods of the pylorus in patients undergoing esophageal resection. Frequency of DGE, anastomotic leakage rates, and length of hospital stay were analyzed. Outcome data were pooled as odd's ratio (OR) or mean difference using a random-effects model. Risk of bias was assessed using the Robins-I tool for non-randomized trials. RESULTS: Out of 391 articles seven retrospective studies described patients that underwent preventive botulinum toxin injection and four studies described preventive mechanical stretching of the pylorus. DGE was not affected by injection of botox (OR 0.87, 95% confidence interval [CI] 0.37-2.03, P = 0.75), whereas mechanical stretching resulted in significant reduction of DGE (OR 0.26, 95% CI 0.14-0.5, P < 0.0001). CONCLUSION: Mechanical stretching of the pylorus, but not injection of botox reduces DGE after esophageal cancer resection. A newly developed consensus definition should be used before the conduction of a large-scale randomized-controlled trial.

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.

Gastric venous reconstruction to reduce gastric venous congestion after total pancreatectomy: study protocol of a single-centre prospective non-randomised observational study (IDEAL Phase 2A) - GENDER study (Gastric vENous DrainagE Reconstruction).

INTRODUCTION: Total pancreatoduodenectomy (TP) is the standard surgical approach for treating extended pancreas tumours. If TP is performed with splenectomy, the left gastric vein (LGV) sometimes needs to be sacrificed for oncological or technical reasons, which can result in gastric venous congestion (GVC). GVC can lead to gastric venous infarction, which in turn causes gastric perforation with abdominal sepsis. To avoid gastric venous infarction, partial or total gastrectomy is usually performed if GVC occurs after TP. However, gastrectomy can be avoided by reconstructing the gastric venous outflow to overcome GVC and avoid gastric venous infarction. The current study aims to assess the role of gastric venous outflow reconstruction to prevent GVC after TP and avoid gastrectomy. METHODS AND ANALYSIS: In the current single-centre observational pilot study, 20 patients will be assigned to study after intraoperative evaluation of gastric venous drainage after LGV resection during TP. During surgery, on-site evaluation by the surgeon, endoscopic examination, indocyanine green, gastric venous drainage flowmetry and spectral analysis will be performed. Postoperatively, patients will receive standard post-TP care and treatment. During hospitalisation, endoscopic examination with indocyanine green will be performed on the 1st, 3rd and 7th postoperative day to evaluate gastric ischaemia. Ischaemia markers will be evaluated daily after surgery. After discharge, patients will be followed-up for 90 days, during which mortality and morbidities will be recorded. The main endpoints of the study will include, rate of GVC, rate of gastric ischaemia, rate of postpancreatectomy gastrectomy, rate of reoperation, morbidity and mortality. ETHICS AND DISSEMINATION: The study protocol has been reviewed and approved by the Ethics Committee of the University of Heidelberg. The results will be actively disseminated through peer-reviewed journals and conference presentations, and are expected in 2022. TRIAL REGISTRATION NUMBER: NCT04850430.

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).

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.

Prolyl Hydroxylase Inhibition Mitigates Pouchitis.

BACKGROUND: Pouchitis is the most common long-term complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) or familial adenomatous polyposis (FAP), which can eventually progress to pouch failure, necessitating permanent stoma construction. Hypoxia-inducible transcription factor prolyl hydroxylase-containing enzymes (PHD1, PHD2, and PHD3) are molecular oxygen sensors that control adaptive gene expression through hypoxia-inducible factor (HIF). Emerging evidence supports PHDs as being therapeutic targets in intestinal inflammation. However, pharmacological inhibition of PHDs has not been validated as a treatment strategy in pouchitis. METHODS: PHD1-3 mRNA and protein expression were analyzed in mucosal pouch and prepouch ileal patient biopsies. After establishment of a preclinical IPAA model in rats, the impact of the pan-PHD small-molecule inhibitor dimethyloxalylglycine (DMOG) on dextran sulfate sodium (DSS)-induced pouchitis was studied. Clinical and molecular parameters were investigated. RESULTS: PHD1, but not PHD2 or PHD3, was overexpressed in pouchitis in biopsies of patients with IPAA for UC but not FAP. In addition, PHD1 expression correlated with disease activity. DMOG treatment profoundly mitigated DSS-induced pouchitis in a rodent IPAA model. Mechanistically, DMOG restored intestinal epithelial barrier function by induction of tight junction proteins zona occludens-1 and claudin-1 and alleviation of intestinal epithelial cell apoptosis, thus attenuating pouch inflammation. CONCLUSIONS: Together, these results establish a strong therapeutic rationale for targeting PHD1 with small-molecule inhibitors in pouchitis after IPAA for UC.

Is panendoscopy a necessary staging procedure in patients with lacking risk factors and oral squamous cell carcinoma?

OBJECTIVES: Routine panendoscopy is used to detect synchronous malignancies of the upper aerodigestive tract in staging of oral squamous cell carcinoma. The goal of this study was to investigate the occurrence of synchronous malignancies at time of diagnosis using panendoscopy. To challenge the role of panendoscopy as inherent part of routine staging procedures, we were especially interested in low risk patients. MATERIALS AND METHODS: Retrospectively, a cohort of 484 patients with pathologically confirmed diagnosis of primary oral and oropharyngeal squamous cell carcinoma was investigated. Electronically recorded findings of in-house conducted panendoscopy were retrieved and evaluated for the occurrence of pathological changes of the mucosa. In case of synchronous malignancies, findings were correlated to preoperative radiographic imaging. Patients were classified as high or low risk. Patients with lacking risk factors (no smoking, no drinking in history) were defined as low risk patients. RESULTS: Overall, we detected three synchronous malignancies of the upper aerodigestive tract (3/484; 0.6%). Two non-small cell lung cancers were detected in patients with a smoking history of 60 pack years. One esophageal carcinoma in situ was detected in a patient with reported alcohol consumption. No synchronous malignancy was detected in patients without risk factors and no malignancy was previously detected by diagnostic imaging. CONCLUSION: Pre-treatment panendoscopy can reveal synchronous malignancies of the upper aerodigestive tract in patients with primary oral squamous cell carcinoma. Risk stratification of patients can avoid unnecessarily conducted panendoscopy in patients without risk factors. This may lead to a higher cost-efficacy in public health system, less treatment-related complications and earlier treatment initiation.

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.

Effect of scheduled endoscopic dilatation of dominant strictures on outcome in patients with primary sclerosing cholangitis.

OBJECTIVE: Scheduled 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. DESIGN: Between 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. RESULTS: The 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%; p<0.001), as was transplantation-free survival time (median: 17.9 vs 15.2 years; log-rank: p=0.008). However, the benefit of scheduled ERCP was significant only in patients with the initial (17.1%) or later (45.5%) diagnosis of a DS (17.8 vs 11.1 years; log-rank: p<0.001). IBD (p=0.03), DS (p=0.006), higher Mayo Risk Score (p=0.02) and non-adherence to scheduled endoscopy (p=0.005) were independently associated with transplantation-free survival. CONCLUSION: In 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.

Risk Factors Associated With Pouch Adenomas in Patients With Familial Adenomatous Polyposis.

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal reconstruction is the standard prophylactic surgical procedure for patients with familial adenomatous polyposis. However, several groups have reported the development of adenomas and even carcinomas within the ileal pouch. The predisposing factor was the time interval after pouch surgery in some studies, but it was the severity of the initial colonic disease and duodenal adenomatosis in others. OBJECTIVE: The aim of this study was to further clarify the prevalence of pouch adenomas, clinical risk factors, and a possible phenotype-genotype relation in a large population of patients with familial adenomatous polyposis, as well as to analyze pouch adenoma-free survival. DESIGN: This study was designed as a cohort study. SETTINGS: This study was conducted in a specialized outpatient clinic at the University of Heidelberg. PATIENTS: A total of 192 patients with familial adenomatous polyposis were included, and all of the available endoscopy reports after pouch surgery were screened for pouch adenomas. Additional clinical information was retrieved from the Heidelberg Polyposis Register. MAIN OUTCOME MEASURES: This present study revealed 3 main independent risk factors for the development of pouch adenomas: age <18 years at the time of IPAA, male sex, and the presence of gastric adenomas. Secondary outcome measures were adenoma progression and overall pouch adenoma-free survival. RESULTS: Pouch adenomas were detected in 46.9% of patients. Median follow-up was 12.8 years (interquartile range, 9.0-17.0 y) for patients with pouch adenomas and 7.3 years (interquartile range, 2.5-12.2 y) for those without them. Patients underwent pouch surgery at a median age of 27.5 years (range, 10.2-58.5 y), and pouch adenomas occurred a median of 8.5 years (range, 0.9-25.1 y) after surgery. Also detected were gastric adenomas in 37.2%, duodenal adenomas in 80.3%, and desmoid tumors in 24.5% of patients. Estimation of pouch adenoma-free survival revealed that, after 20 years, only ≈22% of patients would be free of pouch adenomas. Male sex, age ≦18 years at the time of pouch surgery, and gastric adenomas were found to be independent risk factors for the development of pouch adenomas in a multivariate Cox regression analysis (p = 0.0002, p = 0.0059, and p = 0.0020). No predisposing germline mutation for pouch adenoma development was detected. LIMITATIONS: Detailed information on the initial preoperative findings was not fully available, and the study was only carried out as a single-center study. CONCLUSIONS: A severe upper intestinal phenotype, male sex, and age <18 years at the time of IPAA all increase the risk for development of pouch adenomas. See Video Abstract at http://links.lww.com/DCR/A675.

Significant decrease of mortality due to anastomotic leaks following esophageal resection: management makes the difference.

PURPOSE: Anastomotic leakage is the most frequent cause of postoperative mortality following esophageal surgery. However, no gold standard for diagnosing and managing leakage has been established. Continuous clinical judgment is extremely important; therefore, to optimize the management of leakage, we established a special group for decision-making in cases of suspected leakage in the early postoperative period. METHODS: Between January 2010 and December 2016, 234 consecutive patients underwent elective esophageal resection with a thoracoabdominal incision. In 2014, we established a group consisting of a surgeon, surgical endoscopist, and anesthesiologist for decision-making in cases of suspected leakage. They discussed emerging problems and decided on further diagnostics or therapy. The data were documented prospectively and compared to the years prior to 2014. RESULTS: Two hundred and thirty-four consecutive patients were enrolled in the study, 110 in the years 2010-2013 (group A), and 124 in the years 2014-2016 (group B). Neither patients' characteristics nor the rate of anastomotic leakage differed significantly between the two study groups. The hospital mortality rate was 10% (11 patients) in group A and 4.8% (six patients) in group B. Most interestingly, mortality due to anastomotic leakage was 35% in group A (9/26), whereas it decreased significantly to 6.5% (2/31 patients) (P < 0.001) in group B. CONCLUSIONS: Our data clearly demonstrated that optimizing the management of anastomotic leakage by making team decisions can lead to a significant decrease in mortality.

Androgen-mediated sex bias impairs efficiency of leukotriene biosynthesis inhibitors in males.

Proinflammatory leukotrienes (LTs) are produced by 5-lipoxygenase (5-LO) aided by 5-LO-activating protein (FLAP). LT biosynthesis inhibitors are currently under clinical investigation as treatments for respiratory and cardiovascular diseases. Here, we have revealed a sex bias in the efficiency of clinically relevant LT biosynthesis inhibitors, showing that their effects are superior in females. We found that androgens cause these sex differences by impeding the LT-biosynthetic 5-LO/FLAP complex assembly. Lower doses of the FLAP inhibitor MK886 were required to reduce LTB4 levels in exudates of female versus male mice and rats. Following platelet-activating factor-induced shock, MK886 increased survival exclusively in female mice, and this effect was abolished by testosterone administration. FLAP inhibitors and the novel-type 5-LO inhibitors licofelone and sulindac sulfide exhibited higher potencies in human blood from females, and bioactive 5-LO/FLAP complexes were formed in female, but not male, human and murine leukocytes. Supplementation of female blood or leukocytes with 5α-dihydrotestosterone abolished the observed sex differences. Our data suggest that females may benefit from anti-LT therapy to a greater extent than males, prompting consideration of sex issues in LT modifier development.

Laparoscopic transgastric circumferential stapler-assisted vs. endoscopic esophageal mucosectomy in a porcine model.

Background and study aims Extensive endoscopic mucosal resection (EMR) for Barrett's esophagus (BE) may lead to stenosis. Laparoscopic, transgastric, stapler-assisted mucosectomy (SAM) with the retrieval of a circumferential specimen is proposed. Methods SAM was evaluated in two phases. The feasibility of SAM and the quality of specimens were assessed in eight animals. The mucosal healing was evaluated in a 6-week survival experiment comparing SAM (n = 6) with EMR (n = 6). The ratio of the esophageal lumen width (REL) at the resection level measured on fluoroscopy at 6 weeks divided by the width immediately after resection was compared. Results In all animals, a circular mucosectomy specimen was successfully obtained, with a median area of 492 mm2 (interquartile range [IQR] 426 - 573 mm2) and 941 mm2 (IQR 813 - 1209 mm2) using a 21 mm and 25 mm stapler, respectively. In the survival experiments, symptomatic stenosis developed in two animals after EMR and in none after SAM. The REL was 0.27 (0.18 - 0.39) and 0.96 (0.9 - 1.04; P < 0.0001) for EMR and SAM, respectively. Conclusions SAM provides a novel technique for en bloc mucosectomy in BE. In contrast to EMR, mucosal healing after SAM was not associated with stenosis up to 6 weeks after intervention.

Location of a biliary leak after liver resection determines success of endoscopic treatment.

BACKGROUND: Bile leaks after hepatic resection are serious complications associated with substantial morbidity and mortality. The aim of this prospective observational study was to determine the therapeutic success of endoscopic treatment of biliary leakage after liver resection. PATIENTS AND METHODS: Grade B biliary leaks were considered for endoscopic treatment in patients after liver resection between 1/09 and 4/12. Endoscopic treatment (sphincterotomy only, plastic stent distal to leak or bridging) was defined as successful when the patient remained without symptoms after drain removal and without extravasation follow-up ERC 8 weeks later. RESULTS: Overall rate of biliary leak was 7.4 % (61/826). 35 patients with a grade B bile leak were considered for endoscopic treatment. 22 (63 %) had bile leaks that were peripherally located, and 13 (37 %) had bile leaks at central location. In 3 patients, sphincterotomy only was performed; in 19 patients, a stent distal to the leak and in 13 patients, a bridging stent was inserted. The overall success rate was 74 % (26/35 patients). Endoscopic treatment failed in 26 % (9/35), and mortality rate was 11 % (4/35). In all patients with leaks located at the right or left hepatic duct, treatment with the bridging stent was successful. CONCLUSION: Endoscopic therapy for biliary leakage after liver resection is safe and effective and should be considered as a first-line therapy in patients who are suitable for an interventional, non-surgical approach. Patients with a centrally located leak who are treated with a bridging stent are more likely to benefit from endoscopic intervention.

Immediate tumor resection in patients with locally advanced gastroesophageal adenocarcinoma with nonresponse to chemotherapy after 4 weeks of treatment versus resection after completion of chemotherapy (OPTITREAT trial, DRKS00004668): study protocol for a randomized controlled pilot trial.

BACKGROUND: Neoadjuvant chemotherapy is a standard of care for patients with adenocarcinoma of the esophagus and stomach in Europe, but still only 20-40 % respond to therapy and the critical issue; how to treat nonresponding patients is still unclear. So far, there is no randomized trial evaluating the impact of early termination of neoadjuvant chemotherapy and immediate tumor resection in nonresponding patients with locally advanced gastroesophageal cancer on postoperative outcome. With this exploratory pilot trial, we want to get first estimates about the effect of discontinuation of chemotherapy with the aim to plan and conduct a further definitive trial. METHODS/DESIGN: OPTITREAT is designed as a single-center, randomized controlled pilot trial with two parallel study groups. Four weeks after starting neoadjuvant chemotherapy in all patients, clinical response will be assessed by endoscopy and endosonographic ultrasound. Then, nonresponding patients (n = 84) will be randomized in a 1:1 ratio to intervention group with stopping chemotherapy and immediate tumor resection or control group with completion of chemotherapy before surgery. Outcome measures are overall survival, R0 resection rate, perioperative morbidity and mortality, histopathological response, and quality of life. Statistical analysis will be based on the intention-to-treat population. Due to the study design as an explorative pilot trial, no formal sample size calculation was performed. The planned total sample size of 120 patients is considered ethical and large enough to show the feasibility and safety of the concept. First data on differences between the study groups in the defined endpoints will also be generated. DISCUSSION: Individualized therapy is of utmost interest in the treatment of locally advanced gastroesophageal adenocarcinoma as less than half of the patients show objective response to current chemotherapy regimens. The findings of the OPTITREAT trial will help to get first data about clinical response evaluation followed by immediate tumor resection in nonresponding patients after 4 weeks of neoadjuvant chemotherapy. Based on the results of this pilot study, a future confirmatory trial will be planned to prove efficacy and evaluate significance. TRIAL REGISTRATION: German Clinical Trial Register number: DRKS00004668.