Biliary Adverse Events During Neoadjuvant Therapy for Pancreatic Cancer.

OBJECTIVE: To describe a high-volume experience with biliary drainage before neoadjuvant therapy (NAT) for patients with operable pancreatic cancer (PC) and characterize the association between biliary adverse events (BAEs) and patient outcome. BACKGROUND: Patients with PC presenting with biliary obstruction require durable decompression before NAT. METHODS: Patients with operable PC and tumor-associated biliary obstruction were examined and grouped by the presence or absence of a BAE during NAT. The incidence, timing, and management of BAEs are described, and outcomes, including the completion of all treatment and overall survival (OS), were compared. RESULTS: Of 426 patients who received pretreatment biliary decompression, 92 (22%) experienced at least 1 BAE during NAT, and 56 (13%) required repeat intervention on their biliary stent. The median duration of NAT was 161 days for all patients and was not different in the group that experienced BAEs. The median time from initial stent placement to BAE was 64 days. An interruption in the delivery of NAT (median 7 days) occurred in 25 (6%) of 426 patients. Among 426 patients, 290 (68%) completed all NAT, including surgery: 60 (65%) of 92 patients with BAE and 230 (69%) of 334 patients without BAE ( P =0.51). Among 290 patients who completed NAT and surgery, the median OS was 39 months, 26 months for the 60 patients with BAE, and 43 months for the 230 patients without BAE ( P =0.02). CONCLUSIONS: During extended multimodal NAT for PC, 22% of patients experienced a BAE. Although BAEs were not associated with a significant interruption of treatment, patients who experienced a BAE had worse OS.

The incidence of new mental health disorders after acute pancreatitis: A large, propensity-matched, observational study.

INTRODUCTION: The prevalence of acute pancreatitis (AP) and mental health disorders (MHDs) are rising. While the association between chronic pancreatitis (CP) and MHDs is established, it is unknown whether there is a risk of MHDs after an index episode of AP. The aim of this study was to evaluate the incidence of MHDs and pharmacotherapy use after an episode of AP. METHODS: This was a large observational study using the TriNetX research network, an electronic health record dataset containing inpatient and outpatient data from more than 50 healthcare organizations. Patients with AP from 2015-2020 were identified. Four cohorts were created: acute necrotizing pancreatitis (ANP), acute pancreatitis without necrosis (AP-WON), acute appendicitis, and healthy controls without pancreatitis. The cohorts were matched by age, sex, race, ethnicity, and nicotine and alcohol use. The primary outcome was new composite MHDs at one-year. Secondary outcomes included stratified MHDs, psychiatric medication use, opioid analgesic use, and all-cause mortality. RESULTS: The ANP, AP-WON, appendicitis, and healthy control cohorts contained 11,806, 177,266, 27,187, and 561,833 patients, respectively. Patients with AP-WON had significantly higher rates of composite MHDs compared with those hospitalized for appendicitis (9.7% vs 4.7%, HR 1.9, 95% CI 1.7-1.9). This association was augmented when comparing ANP to appendicitis (12.8% vs 5.2%, HR 2.4, 95% CI 2.1-2.7). All secondary outcomes were observed at significantly higher rates in the AP-WON cohort when compared to appendicitis. Again, these associations were augmented comparing ANP to appendicitis. CONCLUSION: Compared with controls, patients with AP had significantly higher rates of new MHDs and their associated pharmacotherapies at one-year, suggesting that a single episode of AP may independently place patients at risk for developing MHDs irrespective of whether they go on to develop CP.

Systematic review of cholangiocarcinoma in Africa: epidemiology, management, and clinical outcomes.

BACKGROUND: The prevalence, management, and clinical outcomes of cholangiocarcinoma in Africa are unknown. The aim is to conduct a comprehensive systematic review on the epidemiology, management, and outcomes of cholangiocarcinoma in Africa. METHODS: We searched PubMed, EMBASE, Web of Science and CINHAL from inception up to November 2019 for studies on cholangiocarcinoma in Africa. The results reported follow PRISMA guidelines. Quality of studies and risk of bias were adapted from a standard quality assessment tool. Descriptive data were expressed as numbers with proportions and Chi-squared test was used to compare proportions. P values < 0.05 were considered significant. RESULTS: A total of 201 citations were identified from the four databases. After excluding duplicates, 133 full texts were reviewed for eligibility, and 11 studies were included. The 11 studies are reported from 4 countries only: 8 are from North Africa (Egypt 6 and Tunisia 2), and 3 in Sub-Saharan Africa (2 in South Africa, 1 in Nigeria). Ten studies reported management and outcomes, while one study reported epidemiology and risk factors. Median age for cholangiocarcinoma ranged between 52 and 61 years. Despite the proportion with cholangiocarcinoma being higher among males than females in Egypt, this gender disparity could not be demonstrated in other African countries. Chemotherapy is mainly used for palliative care. Surgical interventions are curative and prevent cancer progression. Statistical analyses were performed with Stata 15.1. CONCLUSION: The known global major risk factors such as primary sclerosing cholangitis, Clonorchis sinensis and Opisthorchis viverrini infestation are rare. Chemotherapy treatment was mainly used for palliative treatment and was reported in three studies. Surgical intervention was described in at least 6 studies as a curative modality of treatment. Diagnostic capabilities such as radiographic imaging and endoscopic are lacking across the continent which most likely plays a role in accurate diagnosis.

Impact of Trainee Involvement on Pediatric ERCP Procedures: Results From the Pediatric ERCP Initiative.

This study examines the role of trainee involvement with pediatric endoscopic retrograde cholangiopancreatography (ERCP) and whether it affects the procedure's success, post-procedural adverse outcomes, and duration. A secondary analysis of the Pediatric ERCP Database Initiative, an international database, was performed. Consecutive ERCPs on children <19 years of age from 18 centers were entered prospectively into the database. In total 1124 ERCPs were entered into the database, of which 320 (28%) were performed by trainees. The results showed that the presence of trainees did not impact technical success ( P = 0.65) or adverse events rates ( P = 0.43). Rates of post-ERCP pancreatitis, pain, and bleeding were similar between groups ( P > 0.05). Fewer cases involving trainees were in the top quartile (>58 minutes) of procedural time (19% vs 26%; P = 0.02). Overall, our findings indicate trainee involvement in pediatric ERCP is safe.

Pediatric ERCP in the Setting of Acute Pancreatitis: A Secondary Analysis of an International Multicenter Cohort Study.

Previous studies have demonstrated the safety of performing endoscopic retrograde cholangiopancreatography (ERCP) in the pediatric population; however, few have addressed the outcomes of children undergoing ERCP during acute pancreatitis (AP). We hypothesize that ERCP performed in the setting of AP can be executed with similar technical success and adverse event profiles to those in pediatric patients without pancreatitis. Using the Pediatric ERCP Database Initiative, a multi-national and multi-institutional prospectively collected dataset, we analyzed 1124 ERCPs. One hundred and ninety-four (17%) of these procedures were performed in the setting of AP. There were no difference in the procedure success rate, procedure time, cannulation time, fluoroscopy time, or American Society of Anesthesiology class despite patients with AP having higher American Society of Gastrointestinal Endoscopy grading difficulty scores. This study suggests that ERCP can be safely and efficiently performed in pediatric patients with AP when appropriately indicated.

Updates and new directions in the use of radiation therapy for the treatment of pancreatic adenocarcinoma: dose, sensitization, and novel technology.

Panc reatic ductal adenocarcinoma (PDAC) is a devastating malignancy. There have been few advances that have substantially improved overall survival in the past several years. On its current trajectory, the deaths from PDAC are expected to cross that from all gastrointestinal cancers combined by 2030. Radiation therapy is a technically very complex modality that bridges multiple different treatment strategies. It represents a hybrid among advanced diagnostic imaging, local (often ablative) intervention, and heterogeneous biological mechanisms contributing to normal and oncologic cell kill. In this article, we bring an overview of the several promising strategies that are currently being investigated to improve outcomes using radiation therapy for patients with PDAC.

Predictors of Prolonged Fluoroscopy Exposure in Pediatric Endoscopic Retrograde Cholangiopancreatography: Results From the Large Pediatric Endoscopic Retrograde Cholangiopancreatography Database Initiative Multicenter Cohort.

BACKGROUND AND AIMS: Ionizing radiation exposure during endoscopic retrograde cholangiopancreatography (ERCP) is an important quality issue especially in children. We aim to identify factors associated with extended fluoroscopy time (FT) in children undergoing ERCP. METHODS: ERCP on children <18 years from 15 centers were entered prospectively into a REDCap database from May 2014 until May 2018. Data were retrospectively evaluated for outcome and quality measures. A univariate and step-wise linear regression analysis was performed to identify factors associated with increased FT. RESULTS: 1073 ERCPs performed in 816 unique patients met inclusion criteria. Median age was 12.2 years (interquartile range [IQR] 9.3-15.8). 767 (71%) patients had native papillae. The median FT was 120 seconds (IQR 60-240). Factors associated with increased FT included procedures performed on patients with chronic pancreatitis, ERCPs with American Society of Gastrointestinal Endoscopy (ASGE) difficulty grade >3, ERCPs performed by pediatric gastroenterologist (GI) with adult GI supervision, and ERCPs performed at non-free standing children's hospitals. Hispanic ethnicity was the only factor associated with lower FT. CONCLUSION: Several factors were associated with prolonged FTs in pediatric ERCP that differed from adult studies. This underscores that adult quality indicators cannot always be translated to pediatric patients. This data can better identify children with higher risk for radiation exposure and improve quality outcomes during pediatric ERCP.

Technical Outcomes in Pediatric Endoscopic Retrograde Cholangiopancreatography: Data from an International Collaborative.

OBJECTIVES: Endoscopic retrograde cholangiopancreatography (ERCP) in adults has been extensively studied through multicenter prospective studies. Similar pediatric studies are lacking. The Pediatric ERCP Database Initiative (PEDI) is a multicenter collaborative aiming to evaluate the indications and technical outcomes in pediatric ERCPs. METHODS: In this prospective cohort study, data were recorded for pediatric ERCPs performed across 15 centers. A pre-procedure, procedure, 2-week post-procedure follow-up, and adverse event form were completed for each ERCP performed. Univariate and stepwise linear regression was performed to identify factors associated with technically successful procedures and adverse events. RESULTS: A total of 1124 ERCPs were performed on 857 patients from May 1, 2014 to May 1, 2018. The median age was 13.5 years [interquartile range (IQR) 9.0-15.7]. Procedures were technically successful in the majority of cases (90.5%) with success more commonly encountered for procedures with biliary indications [odds ratio (OR) 4.2] and less commonly encountered for native papilla anatomy (OR 0.4) and in children <3 years (OR 0.3). Cannulation was more often successful with biliary cannulation (95.9%) compared to pancreatic cannulation via the major papilla (89.6%, P < 0.0001) or minor papilla (71.2%, P < 0.0005). The most commonly identified adverse events included post-ERCP pancreatitis (5%), pain not related to post-ERCP pancreatitis (1.8%), and bleeding (1.2%). Risk factors for the development of each were identified. CONCLUSIONS: This large prospective study demonstrates that ERCP is reliable and safe in the pediatric population. It highlights the utility of PEDI in evaluating the technical outcomes of pediatric ERCPs and demonstrates the potential of PEDI for future studies in pediatric ERCPs.

Clinical outcomes on weekly endoscopic dilations as the initial approach to manage patients with complex benign esophageal strictures: report on 488 dilations.

BACKGROUND: Success rate of endoscopic dilation (ED) of complex benign esophageal strictures (CBES) can be as low as 65%. Since EDs are usually performed at 2-4-week intervals, the aim of this study was to evaluate the clinical outcomes of EDs done initially at weekly intervals. METHODS: A cohort of patients with CBES (luminal diameter < 10 mm) underwent ED at weekly intervals and subsequent dilation intervals adjusted based on response. Weekly EDs were also re-initiated in those requiring additional interventions (electro-cautery/stents). Group A patients: Failed prior EDs done at ≥ 2-week intervals. Group B: CBES with no prior dilations. Success was defined as achieving and maintaining a luminal diameter of ≥ 14 mm and patient remaining dysphagia-free with minimal re-interventions. RESULTS: 488 EDs were performed on a cohort of 57 consecutive patients with CBES. Median follow-up was 4 years. Group A: 21 patients (mean age 65 ± 13 years; mean interval between prior failed dilations 17 ± 9 days). 57% of these patients achieved long-term success with weekly dilations (mean 8 ± 4.7 dilations/patient). Group B: 36 patients (mean age 61 ± 13 years, mean 6.5 ± 5.5 dilations/patient). Long-term success was 83.3% (P = 0.033). Despite weekly dilations, unable to achieve a diameter of 14 mm in 5 patients. AE: perforation 1 (0.2%), bleeding 1 (0.2%). CONCLUSION: Significant proportion of patients with CBES who failed prior dilations done at ≥ 2-week intervals achieved dysphagia-free status by initiating weekly dilations. Hence, before considering other options (electro-cautery/stents), one can consider using this approach. This approach can also be used upfront in patients with newly diagnosed CBES.

An Unsuccessful Randomized Trial of Percutaneous vs Endoscopic Drainage of Suspected Malignant Hilar Obstruction.

Percutaneous transhepatic biliary drainage (PTBD) and endoscopic retrograde cholangiopancreatography (ERCP) are widely accepted but competing approaches for the management of malignant obstruction at the hilum of the liver. ERCP is favored in the United States on the basis of high success rates for non-hilar indications, the perceived safety and superior tissue sampling capability of ERCP relative to PTBD, and the avoidance of external drains that are undesirable to patients. A recent randomized controlled trial (RCT) comparing the 2 modalities in patients with resectable hilar cholangiocarcinoma was terminated prematurely because of higher mortality in the PTBD group.1 In contrast, most observational data suggest that PTBD is superior for achieving complete drainage.2-6 Because the preferred procedure remains uncertain, we aimed to compare PTBD and ERCP as the primary intervention in patients with cholestasis due to malignant hilar obstruction (MHO).

Importance of Normalization of CA19-9 Levels Following Neoadjuvant Therapy in Patients With Localized Pancreatic Cancer.

OBJECTIVE: Carbohydrate antigen 19-9 (CA19-9) is a prognostic marker for patients with pancreatic cancer (PC), but its value as a treatment biomarker is unclear. SUMMARY BACKGROUND DATA: Although CA19-9 is an established prognostic marker for patients with PC, it is unclear how CA19-9 monitoring should be used to guide multimodality treatment and what level of change in CA19-9 constitutes a meaningful treatment response. METHODS: CA19-9 measurements at diagnosis (pretx), after completion of all planned neoadjuvant therapy (preop), and after surgery (postop) were analyzed in patients with localized PC who had an elevated CA19-9 (≥35 U/dL) at diagnosis. Patients were classified by: 1) quartiles of pretx CA19-9 (Q1-4); 2) proportional changes in CA19-9 (ΔCA19-9) after the completion of neoadjuvant therapy; 3) normalization (CA19-9 <35 U/dL) of preop CA19-9; and 4) normalization of postop CA19-9. RESULTS: Among 131 patients, the median overall survival (OS) was 30 months; 68 months for the 33 patients in Q1 of pretx CA19-9 (<80 U/dL) compared with 25 months for the 98 patients in Q2-4 (P = 0.03). For the 98 patients in Q2-4, preop CA19-9 declined (from pretx) in 86 (88%), but there was no association between the magnitude of ΔCA19-9 and OS (P = 0.77). Median OS of the 98 patients who did (n = 29) or did not (n = 69) normalize their preop CA19-9 were 46 and 23 months, respectively (P = 0.02). Of the 69 patients with an elevated preop CA19-9, 32 (46%) normalized their postop CA19-9. Failure to normalize preop or postop CA19-9 was associated with a 2.77-fold and 4.03-fold increased risk of death, respectively (P < 0.003) as compared with patients with normal preop CA19-9. CONCLUSIONS: Following neoadjuvant therapy, normalization of CA19-9, rather than the magnitude of change, is the strongest prognostic marker for long-term survival.

Endoscopic management and clinical outcomes of obstructive jaundice.

BACKGROUND: This study aimed at evaluating the endoscopic management and clinical outcomes in patients with obstructive jaundice undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP) within a newly established apprenticeship teaching model at an academic centre in a resource-limited setting. MATERIALS AND METHODS: We employed an apprenticeship-style model of ERCP training with graded responsibility, multidisciplinary group feedback and short-interval repetition. We collected sociodemographic and clinicopathologic data on consecutive patients who underwent ERCP from March 2018 to February 2020. RESULTS: A total of 177 patients were referred, of which 146 patients had an ERCP performed for obstructive jaundice and 31 excluded during the study period. The median age was 55 years, age range from 8 to 83 years. The most common referral diagnosis was pancreatic head cancer 56/146 (38.1%), followed by choledocholithiasis 29/146 (19.7%), cholangiocarcinoma 22/146 (15.0%) and gall bladder cancer 11/146 (7.5%). In all, 102 patients had a malignant indication for ERCP. The cannulation rate was 92%. The most common site for malignant biliary obstruction was proximal bile stricture in 31/102 (30.4%), followed by distal bile strictures in 30/102 (28.4%), periampullary cancer 20/102 (19.6%) and mid bile duct stricture in 9/102 (8.8%). The common benign obstructive etiology includes choledocholithiasis in 33/44 (75%) and mid duct obstruction from post-cholecystectomy bile duct injury in 3/44 (2.9%) while 2/44 (2.0%) patients had choledochal cyst. Overall complications were post-ERCP pancreatitis (8/146 patients), cholangitis (3/146 patients), stent migration and post-sphincterotomy bleeding (one patient each). Peri-procedural mortality was 5/146 (3.4%). CONCLUSION: ERCP is an effective and safe method of treatment of patients with benign and malignant biliary obstruction. The low morbidity and mortality and its immediate therapeutic benefits, together with the short duration of hospitalization, indicate that this procedure is an important asset in the management of such patients.

Older Age Reduces Upper Esophageal Sphincter and Esophageal Body Responses to Simulated Slow and Ultraslow Reflux Events and Post-Reflux Residue.

BACKGROUND & AIMS: It is not clear how age affects airway protective mechanisms. We investigated the effects of aging on upper esophageal sphincter (UES) and esophageal body pressure responses to slow and ultraslow simulated reflux events and post-reflux residue. METHODS: We performed a prospective study of 11 elderly (74 ± 9 years old) and 11 young (28 ± 7 years old) healthy volunteers. Participants were placed in a supine position and evaluated by concurrent high-resolution impedance manometry and an esophageal infusion technique. Potential conditions of gastroesophageal reflux were simulated, via infusion of 0.1 N HCl and saline. UES and esophageal pressure responses were measured during the following: slow infusion (1 mL/s) for 60 seconds, 60 seconds of postinfusion dwell period, ultraslow infusion (0.05 mL/s) for 60 seconds, and 60 seconds of a postinfusion dwell period. All infusions were repeated 3 times. We used the UES high-pressure zone contractile integral (UES-CI) to determine responses of the UES. RESULTS: Young and elderly subjects each had a significant increase in the UES-CI during slow infusions and during entire passive dwell intervals compared with baseline (P < .01, both groups). Ultraslow infusions were associated with a significant increase in UES-CI in only the young group, in the late infusion period, and into the dwell interval (P < .01). During the slow infusions and their associated dwell periods, young subjects had a higher frequency of secondary peristalsis than elderly subjects (P < .05). There was more secondary peristalsis during active infusions than dwell intervals. Secondary peristalsis was scarce during ultraslow infusions in both groups. CONCLUSIONS: UES and esophageal body pressure responses to low-volume ultraslow reflux and associated post-reflux residue are reduced in elderly individuals. This deterioration could have negative effects on airway protection for people in this age group.

Management of Acute Cholecystitis during Neoadjuvant Therapy in Patients with Pancreatic Adenocarcinoma.

BACKGROUND: Patients with localized pancreatic cancer (PC) can develop acute cholecystitis during neoadjuvant therapy; optimal management remains undefined. METHODS: Consecutive patients with localized PC who had indwelling biliary stents and received neoadjuvant therapy were reviewed. Time from stent placement to the development of acute cholecystitis was calculated. Patients were categorized as having surgical versus nonoperative management of cholecystitis. Time to PC resection was defined as the time from the start of treatment to pancreatic resection. RESULTS: Of the 283 patients with indwelling biliary stents, acute cholecystitis occurred in 17 (6%) patients. The median time from the date of stent placement to the development of cholecystitis was 2.3 months [interquartile range (IQR) 4.6 months]. Acute cholecystitis was managed with cholecystostomy tube placement in 15 (88%) patients and cholecystectomy in 2 (12%). In total, 189 (67%) of the 283 patients completed all intended neoadjuvant therapy and surgery; 10 (59%) of the 17 patients with cholecystitis (10 of 15 managed with a cholecystostomy tube and 0 of 2 managed with cholecystectomy) and 179 (67%) of the 266 patients without cholecystitis (p = 0.47). The median time to PC resection was 3.2 months for the 179 patients without cholecystitis and 3.6 months for the 10 patients with cholecystitis (p = 1.00). CONCLUSIONS: Acute cholecystitis occurred in 6% of patients with indwelling biliary stents during neoadjuvant therapy. Management with a cholecystostomy tube did not delay the completion of neoadjuvant therapy and surgery and should be considered the optimal management of this complication.

Covered and uncovered biliary metal stents provide similar relief of biliary obstruction during neoadjuvant therapy in pancreatic cancer: a randomized trial.

BACKGROUND AND AIMS: Preoperative biliary drainage with self-expanding metal stents (SEMSs) brings liver function within an acceptable range in preparation for neoadjuvant therapy (NATx) and provides relief of obstructive symptoms in patients with pancreatic cancer. We compared fully-covered SEMSs (FCSEMSs) and uncovered SEMSs (UCSEMSs) for sustained biliary drainage before and during NATx. METHODS: Patients with pancreatic cancer and planned NATx who need treatment of jaundice and/or cholestasis before pancreaticoduodenectomy were randomized to FCSEMSs versus UCSEMSs. The primary endpoint was sustained biliary drainage, defined as the absence of reinterventions for biliary obstructive symptoms, and was assessed from SEMS placement until curative intent surgery or at 1 year. RESULTS: The intention-to-treat population included 119 patients (59 FCSEMSs, 60 UCSEMSs). Sustained biliary drainage was equally successful with FCSEMSs and UCSEMSs (72.2% vs 72.9%, noninferiority P = .01). Reasons for FCSEMS and UCSEMS failure differed significantly between the groups and included tumor ingrowth in 0% versus 16.7% (P < .01), and stent migration in 6.8% versus 0% (P = .03), respectively. Serious adverse event rates related to stent placement were not significantly different in both groups (23.7% [14/59] vs 20.0% [12/60], P = .66), as were acute cholecystitis rates when the gallbladder was in situ (9.3% [4/43] vs 4.8% [2/42], P = .68) for FCSEMSs and UCSEMSs, respectively. In our study, independent of stent type, predictors of reinterventions were 4-cm stent length and presence of the gallbladder. CONCLUSION: FCSEMSs and UCSEMSs provide similar preoperative management of biliary obstruction in patients with pancreatic cancer receiving NATx, but mechanisms of stent dysfunction depend on stent type, stent length, and presence of the gallbladder. (Clinical trial registration number: NCT02238847.).

A phase III, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve (with video).

BACKGROUND AND AIMS: Self-expanding metal stents (SEMSs) when deployed across the gastroesophageal junction (GEJ) can lead to reflux with risks of aspiration. A SEMS with a tricuspid antireflux valve (SEMS-V) was designed to address this issue. The aim of this study was to evaluate the efficacy and safety of this stent. METHODS: A phase III, multicenter, prospective, noninferiority, randomized controlled trial was conducted on patients with malignant dysphagia requiring SEMSs to be placed across the GEJ. Patients were randomized to receive SEMSs with no valve (SEMS-NV) or SEMS-V. Postdeployment dysphagia score at 2 weeks and Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) questionnaire score at 4 weeks were measured. Patients were followed for 24 weeks. RESULTS: Sixty patients were randomized (SEMS-NV: 30 patients, mean age 67 ± 13 years; SEMS-V: 30 patients, mean age 65 ± 12 years). Baseline dysphagia scores (SEMS-NV, 2.5 ± .8; SEMS-V, 2.5 ± .8) and GERD-HRQL scores (SEMS-NV, 11.1 ± 8.2; SEMS-V, 12.8 ± 8.3) were similar. All SEMSs were successfully deployed. A similar proportion of patients in both arms improved from advanced dysphagia to moderate to no dysphagia (SEMS-NV, 71%; SEMS-V, 74%; 95% confidence interval, 1.93 [-17.8 to 21.7]). The dysphagia scores were also similar across all follow-up time points. Mean GERD-HRQL scores improved by 7.4 ± 10.2 points in the SEMS-V arm and by 5.2 ± 8.3 in the SEMS-NV group (P = .96). The GERD-HRQL scores were similar across all follow-up time points. Aspiration pneumonia occurred in 3.3% in the SEMS-NV arm and 6.9% in the SEMS-V arm (P = .61). Migration rates were similar (SEMS-NV, 33%; SEMS-V, 48%; P = .29). Two SEMS-V spontaneously fractured. There was no perforation, food impaction, or stent-related death in either group. CONCLUSIONS: The SEMS-V was equally effective in relieving dysphagia as compared with the SEMS-NV. Presence of the valve did not increase the risks of adverse events. GERD symptom scores were similar between the 2 stents, implying either that the valve was not effective or that all patients on proton pump inhibitors could have masked the symptoms of GERD. Studies with objective evaluations such as fluoroscopy and/or pH/impedance are recommended. (Clinical trial registration number: NCT02159898.).

A Phase II Clinical Trial of Molecular Profiled Neoadjuvant Therapy for Localized Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: One facet of precision medicine is the use of tumor molecular profiling to guide chemotherapeutic selection. We conducted the first prospective clinical trial of molecular profiling to guide neoadjuvant therapy in patients with operable pancreatic ductal adenocarcinoma (PDAC). We hypothesized that more effective systemic therapy would prevent disease progression during neoadjuvant therapy and, therefore, allow more patients to undergo surgery. METHODS: In patients with resectable and borderline resectable (BLR) PDAC, molecular profiling consisted of immunocytochemical staining of pretreatment endoscopic ultrasound-guided fine needle aspiration tumor biopsies using 6 biomarkers. Neoadjuvant systemic therapy was selected based on the molecular profiling results. The primary endpoint was the completion of all intended neoadjuvant therapy and surgery. RESULTS: The trial enrolled 130 patients; 61 (47%) resectable and 69 (53%) BLR. Molecular profiling was reported within a median of 5 business days (IQR: 3). Of the 130 patient samples, 95 (73%) had adequate cellularity for molecular profiling and 92 (71%) patients received molecular profile-directed therapy. Of the 92 patients who had predictive profiling, 74 (80%) received fluoropyrimidine-based therapy and 18 (20%) received gemcitabine-based therapies. Of the 130 patients, 107 (82%) completed all intended neoadjuvant therapy and surgery; 56 (92%) of the 61 with resectable PDAC and 51 (74%) of 69 with BLR PDAC. CONCLUSIONS: We report the first prospective clinical trial that utilized molecular profiling to select neoadjuvant therapy in patients with operable PDAC. Such high resectability rates have not been observed in prior neoadjuvant trials, suggesting that molecular profiling may improve the efficacy of chemotherapy in these patients.

Safety and efficacy of lumen-apposing metal stents with and without simultaneous double-pigtail plastic stents for draining pancreatic pseudocyst.

BACKGROUND AND AIMS: Lumen-apposing metal stents (LAMSs) are used to perform necrosectomy in walled-off necrosis (WON). Although necrosectomy is not required for pancreatic pseudocyst (PP), an increasing number of PPs are also being drained with LAMSs in view of their ease of deployment. The aim of the present study was to evaluate the safety and efficacy of using LAMSs to drain PPs. METHODS: At 1 tertiary center from January 2014 to May 2016, all consecutive patients with PPs were drained by LAMSs, and the data were retrospectively reviewed. After observing cyst-cavity infection in patients enrolled initially (group I), 10F double-pigtail stents (DPSs) were placed across LAMSs in the subsequent patients (group II). Data on technical success, PP resolution, adverse events, and reintervention rates were collected. RESULTS: Forty-seven patients with PPs (mean size, 9.5 ± 4.0 cm) were enrolled (group I, 24; group II, 23). There was 1 perforation at deployment (technical success, 98%). In the remaining 46 patients, resolution of the PP was observed in 44 patients (96%). Four patients (17%) in group I presented with PP infection requiring reinterventions. Food material was observed in the cyst cavity. None of the patients in group II had PP infection (relative risk, .84; 95% confidence interval, .71-1.0; P = .054). CONCLUSIONS: Similar to WON, LAMSs are also effective in endoscopic drainage of PPs. However, there was a trend toward higher PP infection with LAMSs, and placing a DPS across the LAMS minimized this risk.

Endoscopic Management of Difficult Bile Duct Stones.

PURPOSE OF REVIEW: In 10-15% of the cases, conventional methods for removing bile duct stones by ERCP/balloon-basket extraction fail. The purpose of this review is to describe endoscopic techniques in managing these "difficult bile duct stones." RECENT FINDINGS: Endoscopic papillary large balloon dilation with balloon extraction ± mechanical lithotripsy is the initial approach used to retrieve large bile duct stones. With advent of digital cholangioscopy, electrohydraulic and laser lithotripsy are gaining popularity. Enteroscopy-assisted or laparoscopic-assisted approaches can be used for those with gastric bypass anatomy. Difficulties in removing bile duct stones can be related to stone-related factors such as the size and location of the stone or to altered anatomy such as stricture in the bile duct or Roux-en-Y anatomy. Several endoscopy approaches and techniques have described in the recent past that have greatly enhanced our ability to remove these "difficult" bile duct stones.

In-vivo oesophageal regeneration in a human being by use of a non-biological scaffold and extracellular matrix.

BACKGROUND: Tissue-engineered extracellular matrix populated with autologous pluripotent cells can result in de-novo organogenesis, but the technique is complex, not widely available, and has not yet been used to repair large oesophageal defects in human beings. We aimed to use readily available stents and extracellular matrix to regenerate the oesophagus in vivo in a human being to re-establish swallowing function. METHODS: In a patient aged 24 years, we endoscopically placed a readily available, fully covered, self-expanding, metal stent (diameter 18 mm, length 120 mm) to bridge a 5 cm full-thickness oesophageal segment destroyed by a mediastinal abscess and leading to direct communication between the hypopharynx and the mediastinum. A commercially available extracellular matrix was used to cover the stent and was sprayed with autologous platelet-rich plasma adhesive gel. The sternocleidomastoid muscle was placed over the matrix. After 4 weeks, stent removal was needed due to stent migration, and was replaced with three stents telescopically aligned to improve anchoring. The stents were removed after 3·5 years and the oesophagus was assessed by endoscopy, biopsy, endoscopic ultrasonography, and high-resolution impedance manometry. FINDINGS: After stent removal we saw full-thickness regeneration of the oesophagus with stratified squamous epithelium, a normal five-layer wall, and peristaltic motility with bolus transit. 4 years after stent removal, the patient was eating a normal diet and maintaining a steady weight. INTERPRETATION: Maintenance of the structural morphology of the oesophagus with off-the-shelf non-biological scaffold and stimulation of regeneration with commercially available extracellular matrix led to de-novo structural and functional regeneration of the oesophagus. FUNDING: None.