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Introduction/Background: Multimodal neoadjuvant therapy has resulted in increased rates of histologic response in pancreatic tumors and adjacent lymph nodes. The biologic significance of the collective response in the primary tumor and lymph nodes is not understood. Methods: Patients with localized PC who received neoadjuvant therapy and surgery with histologic assessment of the primary tumor and local-regional lymph nodes were included. Histopathologic response was classified using the modified Ryan score as follows: no viable cancer cells (CR), rare groups of cancer cells (nCR), residual cancer with evident tumor regression (PR), and extensive residual cancer with no evident tumor regression (NR). Nodal status was defined by number of lymph nodes (LN) with tumor metastases: N0 (0 LN), N1 (1-3), N2 (≥4). Results: Of 341 patients with localized PC who received neoadjuvant therapy and surgery, 107 (31%) received chemoradiation alone, 44 (13%) received chemotherapy alone, and 190 (56%) received chemotherapy and chemoradiation. Histopathologic response consisted of 15 (4%) CRs, 59 (17%) nCRs, 188 (55%) PRs, and 79 (23%) NRs. Patients who received chemotherapy alone had the worst responses (n = 21 for NR, 48%) as compared to patients who received chemoradiation alone (n = 25 for NR, 24%) or patients who received both therapies (n = 33 for NR, 17%) (Table 1; p = 0.001). Median overall survival for all 341 patients was 39 months; OS by histopathologic subtype was not reached (CR), 49 months (nCR), 38 months (PR), and 34 months (NR), respectively (p = 0.004). Of the 341 patients, 208 (61%) had N0 disease, 97 (28%) had N1 disease, and 36 (11%) had N2 disease. In an adjusted hazards model, modified Ryan score of PR or NR (HR: 1.71; 95% CI: 1.15-2.54; p = 0.008) and N1 (HR: 1.42; 95% CI: 1.1.02-2.01; p = 0.04), or N2 disease (HR: 2.54, 95% CI: 1.64-3.93; p < 0.001) were associated with increased risk of death. Conclusions: Neoadjuvant chemotherapy alone is associated with lower rates of pathologic response. Patients with CR or nCR have a significantly improved OS as compared to patients with PR or NR. Nodal status is the most important pathologic prognostic factor. Neoadjuvant chemoradiation may be an important driver of pathologic response.

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.

Background Current guidelines recommend genetic testing for all patients with pancreatic cancer (PC). Methods Patients with localized PC who received neoadjuvant therapy between 2009 and 2018 were identified. Genetic consultation (including personal and family history of cancer), genetic testing, and variant data were abstracted. Results Of 510 patients identified, 163 (32%) underwent genetic counseling and genetic testing was performed in 127 (25%). Patients who underwent genetic testing were younger (median age: 63 vs. 67, p = 0.01). Multi-gene testing was performed in 114 (90%) of 127 patients, targeted gene testing was performed in 8 (6%), and not specified in 5 (4%). Of 127 patients who underwent genetic testing, 20 (16%) had pathogenic (P)/likely pathogenic (LP) variants, observed in ATM (n = 7/105,7%), CHEK2 (n = 3/98, 3%), BRCA1 (n = 2/117, 2%), BRCA2 (n = 2/122, 2%), PALB2 (n = 1/115, 1%), MUTYH (n = 1/98, 1%), CDKN2A (n = 1/94, 1%), STK11 (n = 1/97, 1%), NBN (n = 1/98, 1%), and MSH6 (n = 1/97, 1%). Of 20 patients with either a P/LP variant, nine (45%) had a prior cancer, three (15%) had a first-degree relative with PC, and six (30%) had an any-degree relative with PC. Conclusion Pathogenic/likely pathogenic variants were identified in 16% of patients who underwent genetic testing, 60% of which occurred in the homologous recombination pathway.

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.)

Patients with non-metastatic esophageal cancer routinely undergo endoscopic ultrasound (EUS) for loco-regional staging. Neoadjuvant therapy is recommended for ≥T3 tumors while upfront surgery can be considered for ≤T2 lesions. The aim of this study was to determine if the degree of dysphagia can predict the EUS T-stage of esophageal cancer. One hundred eleven consecutive patients with non-metastatic esophageal cancer were retrospectively reviewed from a database. Prior to EUS, patients' dysphagia grade was recorded. Correlation between dysphagia grade and EUS T-stage, especially in reference to predicting ≥T3 stage, was determined. The correlation of dysphagia grade with EUS T-stage (Kendall's tau coefficient) was 0.49 (P < 0.001) for the lower and 0.59 (P = 0.008) for the middle esophagus. The sensitivity and specificity of dysphagia grade ≥2 (can only swallow semi-solids/liquids) for T3 cancer were 56% (95% confidence interval [CI] 43-67%) and 93% (95% CI 79-98%), respectively. The sensitivity, specificity, and positive predictive value of dysphagia grade ≥3 (can only swallow liquids or total dysphagia) for T3 lesions were 36% (95% CI 25-48%), 100% (95% CI 89-100%), and 100% (95% CI 83-100%), respectively. Overall, there was a significant positive correlation between dysphagia grade and the EUS T-stage of esophageal cancer. All patients with dysphagia grade ≥3 had T3 lesions. This may have clinical implications for patients who can only swallow liquids or have complete dysphagia by allowing for prompt initiation of neoadjuvant therapy, especially in countries/centers where EUS service is difficult to access in a timely manner or not available.

Prior to withdrawing the EUS-FNA needle from the lesion, the stopcock of the suction syringe is closed to reduce contamination. Residual negative pressure (RNP) may persist in the needle despite closing the stopcock. To determine whether neutralizing RNP before withdrawing the needle will improve the cytology yield. Bench-top testing was done to confirm the presence of RNP followed by a prospective, randomized, cross-over study on patients with pancreas mass. Ten milliliters of suction was applied to the FNA needle. Before withdrawing the needle from the lesion, the stopcock was closed. Based on randomization, the first pass was done with the stopcock either attached to the needle (S+) or disconnected (S−) to allow air to enter and neutralize RNP and accordingly the second pass was crossed over to S+ or S−. On-site cytopathologist was blinded to S+/S−. Bench tests confirmed the presence of RNP which was successfully neutralized by disconnecting the syringe (S−) from the needle. Sixty patients were enrolled, 120 samples analyzed. S+ samples showed significantly greater GI tract contamination compared to S− samples (16.7 vs. 6.7 %, p = 0.03). Of the 53 patients confirmed to have pancreas adenocarcinoma, FNA using S− approach was positive in 49 (93 %) compared to 40 using the S+ approach (76 %, p = 0.02). Despite closing the stopcock of the suction syringe, RNP is present in the FNA needle. Neutralizing RNP prior to withdrawing the needle from the target lesion significantly decreased GI tract contamination of the sample thereby improving the FNA cytology yield. NCT01995474.

Among patients with localized pancreatic cancer (PC), the benefit of adjuvant therapy after neoadjuvant therapy and surgery is unknown. Patients with localized PC who completed all intended neoadjuvant therapy and surgery were categorized based on the receipt of adjuvant therapy and by pathologic lymph node status (LN−/LN+). Data was available from 234 consecutive patients, 121 (52%) with resectable and 113 (48%) with borderline resectable PC. Of the 234 patients, 92 (39%) were LN+ and 142 (61%) were LN−. The median overall survival (OS) for the 234 patients was 39 months, 42.3 months for patients who received any adjuvant therapy and 34.1 months for those who did not (p = 0.29). Of the 92 LN+ patients, the median OS with and without adjuvant therapy was 29.5 and 23.2 months, respectively (p = 0.02). Of the142 LN− patients, the median OS was 45 months with or without adjuvant therapy (p = 0.86). In an adjusted hazard model, additional adjuvant therapy had a significant protective effect among LN+ patients (HR 0.39; 95% CI 0.21–0.70; p = 0.002) but not in LN− patients (HR 0.89; 95% CI 0.53–1.52; p = 0.68). Among patients with localized PC who received neoadjuvant therapy and surgery, the benefit of adjuvant therapy was limited to those with node-positive disease.

Numerous published outbreaks, including one from our institution, have described endoscope-associated transmission of multidrug-resistant organisms (MDROs). Individual centers have adopted their own protocols to address this issue, including endoscope culture and sequestration. Endoscope culturing has drawbacks and may allow residual bacteria, including MDROs, to go undetected after high-level disinfection. To report the outcome of our novel protocol, which does not utilize endoscope culturing, to address our outbreak. All patients undergoing procedures with elevator-containing endoscopes were asked to permit performance of a rectal swab. All endoscopes underwent high-level disinfection according to updated manufacturer’s guidance. Additionally, ethylene oxide (EtO) sterilization was done in the high-risk settings of (1) positive response to a pre-procedure risk stratification questionnaire, (2) positive or indeterminate CRE polymerase chain reaction (PCR) from rectal swab, (3) refusal to consent for PCR or questionnaire, (4) purulent cholangitis or infected pancreatic fluid collections. Two endoscopes per weekend were sterilized on a rotational basis. From September 1, 2015 to April 30, 2016, 556 endoscopy sessions were performed using elevator-containing endoscopes. Prompted EtO sterilization was done on 46 (8.3%) instances, 3 from positive/indeterminate PCR tests out of 530 samples (0.6%). No CRE transmission was observed during the study period. Damage or altered performance of endoscopes related to EtO was not observed. In this pilot study, prompted EtO sterilization in high-risk patients has thus far eliminated endoscope-associated MDRO transmission, although no CRE infections were noted throughout the institution during the study period. Further studies and a larger patient sample will be required to validate these findings.

Portal hypertension due to liver disease can result in several endoscopic findings in the GI tract, all of which are similar in that they do not cause symptoms except for GI bleeding, which can sometimes be acute and severe. Endoscopic screening for esophageal varices is recommended and primary prophylaxis is indicated with either nonselective beta-blocker (NSBB) or endoscopic banding for select cirrhotics depending on the severity of underlying liver disease and endoscopic features of the varices. Acute esophageal variceal bleeding can be life-threatening and requires inpatient management with resuscitation with judicious use of IV fluids and blood transfusions, vasoactive drugs such as somatostatin, antibiotics, and endoscopic evaluation and/or therapy within 12 h of presentation. Secondary prophylaxis after bleeding is controlled includes both NSBB and endoscopic therapy. Refractory bleeding may require temporizing measures such as a covered esophageal stent or balloon tamponade as a bridge to definitive therapy, usually transhepatic portosystemic shunt (TIPS). Gastric variceal bleeding is more difficult to control endoscopically but tissue adhesives such as cyanoacrylate have an emerging role; TIPS is still often required. Portal hypertensive gastropathy/colopathy may cause chronic GI blood loss and rarely requires treatment but NSBB and endoscopic ablation along with iron supplementation are usually effective.

Background Increasing numbers of patients with resectable pancreatic cancer are receiving neoadjuvant therapy. Biliary drainage with plastic stents during this period can be associated with recurrent episodes of stent occlusion resulting in unplanned ERCPs and interruptions in therapy. Objective To evaluate the efficacy and safety of self-expandable metal stents (SEMSs) during the neoadjuvant period for resectable pancreatic cancer. Design Patients with proven pancreatic adenocarcinoma with biliary obstruction underwent placement of SEMSs, and data on stent patency and complication rates were collected prospectively. Setting Tertiary-care referral center. Patients This study involved 55 patients with resectable and borderline resectable pancreatic duct adenocarcinoma who were recruited between March 2009 and December 2010. Intervention SEMSs were placed for biliary decompression. The shortest length of stent required to bridge the stricture was used so as to leave enough of the normal bile duct above the stent available for subsequent surgical anastomosis. Endoscopic reintervention was performed in those with stent malfunction. Stents were not removed before surgery. Main Outcome Measurements Stent patency rate during the neoadjuvant period, stent malfunction rate, and complication rates. Information on stent-related difficulties, if any, during surgery. Results Fifty-five patients were recruited (29 men, 26 women; age, mean [± SD] 65.9 ± 11 years; resectable 23, borderline resectable 32). Median time for neoadjuvant therapy and restaging before surgery was 104 days (range 70-260 days). At the median time of 104 days, 88% of SEMSs remained patent. By 260 days, stent malfunction occurred in 15% of patients. These included stent occlusion in 13% and stent migration in 2%. SEMS malfunction occurred in 3 of 27 patients (11%) who ultimately underwent pancreaticoduodenectomy and in 5 of 21 patients (24%) with disease progression ( P = not significant). The presence of SEMSs did not interfere with pancreaticoduodenectomy in any patients who underwent surgery. Limitations Nonrandomized study. Conclusion SEMSs are effective and safe in achieving durable biliary drainage in patients with pancreatic cancer receiving neoadjuvant therapy. It is not necessary to remove SEMSs before surgery if the shortest length of stent required to bridge the stricture is used.

Background Comparative data regarding complications associated with ERCP alone or when performed with cholangiopancreatoscopy (CP) are lacking. Objective To determine whether ERCP complications are more frequent when concomitant CP is performed. Design A retrospective query of a prospectively maintained database of ERCP, CP, and complications. Main Outcome Measurements Consensus criteria complications and additional adverse events (AEs), including unplanned medical evaluation, cardiopulmonary/sedation events, and others. Setting Academic, tertiary referral center. Results A total of 4214 ERCPs were performed (337 sphincter of Oddi manometry cases excluded) during the study period, of which 3475 ERCPs and 402 ERCPs with CP were analyzed. There were 28 of 402 AEs (7.0%) in the ERCP with CP group and 101 of 3475 (2.9%) in the ERCP-only group (odds ratio [OR], 2.50; 95% CI, 1.56-3.89). Subgroup analysis revealed a significantly higher rate of cholangitis in the CP group versus ERCP group (1.0% vs 0.2%; OR, 4.98; 95% CI, 1.06-19.67) and similar rates of pancreatitis (2.2% vs 1.3%; OR, 1.75; 95% CI, 0.74-3.65) and perforation (1.0% vs 0.3%; OR, 3.16; 95% CI, 0.73-10.75). Limitations Retrospective review of a complications database that relies on physician self-reporting. Conclusions AEs from CP may be more than double those of ERCP alone (when sphincter of Oddi manometry cases are excluded). CP appears to be associated with a significantly higher rate of cholangitis, possibly because of intermittent intraductal irrigation required during the procedure.

Fully covered esophageal self-expandable metal stents (SEMSs) are potentially removable but can be associated with high migration rates. For precise positioning, non-foreshortening SEMSs are preferred. Recently, a new fully covered non-foreshortening SEMS with anti-migration features was introduced.To evaluate the efficacy and safety of this new esophageal SEMS.Retrospective study.Single, tertiary-care center.Consecutive patients with malignant and benign strictures with dysphagia grade of ≥3 and patients with fistulas/leaks were studied.Stent placement and removal.Technical success in stent deployment/removal, efficacy in relieving dysphagia and sealing fistulas/leaks, and adverse events.Forty-three stents were placed in 35 patients (mean [± standard deviation] age 65 ± 11 years; 31 male), 24 for malignant and 11 for benign (5 strictures, 6 leaks) indications. Technical success in precise SEMS placement was 100%. The after-stent dysphagia grade improved significantly (at 1 week: 1.5 ± 0.7; at 4 weeks: 1.2 ± 0.4; baseline: 3.8 ± 0.4; P .0001). Twenty stents were removed for clinical indications, with technical success of 100%. All leaks sealed after SEMS placement and did not recur after stent removal. All benign strictures recurred after stent removal. Adverse events included migration (14%), chest pain (11%), and dysphagia from tissue hyperplasia (6%). There was no stent-related mortality.Nonrandomized, single-center study.The new esophageal SEMS was effective in relieving malignant dysphagia, allowed for precise placement, and was easily removable. It was effective in treating benign esophageal fistulas and leaks. Stent-related adverse events were acceptable.

Techniques to confirm suspected pancreaticobiliary (PB) malignancy when index sampling is non-diagnostic include cholangiopancreatoscopy (CP) and endoscopic ultrasound (EUS). However, comparative data are lacking. The purpose of this study was to compare the yield of EUS and CP for the diagnosis of PB pathology. Consecutive patients with indeterminate PB pathology who underwent both CP and EUS within 3 months of each other were retrospectively identified. For CP, tissue sampling included biopsy under direct inspection (cholangioscopy-directed biopsy), biopsy following CP with fluoroscopic guidance (cholangioscopy-assisted biopsy), or brush cytology. For EUS–FNA, lesions included ductal strictures or hypoechoic masses. A comparison of operating characteristics between CP and EUS utilizing tissue confirmation or 12-month clinical course consistent with either benign or malignant disease was performed. Between February 2000 and June 2007, 66 (33 males, 33 females, median age 64.5) patients with indeterminate PB pathology who had undergone both CP and EUS within 3 months of each other were included. Lesions amenable to sampling were noted in 59 CP and 50 EUS patients. On follow-up, 39 patients had neoplasia and 27 were benign. The sensitivity/specificity for the diagnosis of neoplasia for CP and EUS was 48.7/96.3 % and 33.3/96.3 %, respectively (comparison of sensitivities, P = 0.183). The combined (CP and EUS) sensitivity/specificity was 66.7/96.3 % (P = 0.0064 and P = 0.0001 comparing combined sensitivity vs. sensitivity of either CP alone or EUS alone, respectively). In patients who undergo both EUS and CP for indeterminate PB pathology, the combined yield of EUS and CP to detect neoplasia appears to be higher than either examination alone.

transesophageal prosthesis). No perforations occurred. Endoscopic injection of steroids did not accelerate remediation compared to patients who did not receive injected steroids [median 24 (IQR 8, 38.5) weeks, mean 7.5 (+/-2.6) dilations vs. median 11 (IQR 2, 14) weeks, mean 3.8 (+/-2.3) dilations, p=0.16 and p=0.007]. Conclusions: 1. Radiation-induced strictures appear to have a delayed onset from time of injury. 2. Endoscopic dilation can achieve medium-term luminal remediation but has a high long-term recurrence rate. 3. Endoscopically injected steroids do not promote remediation of radiation strictures.

Eliminating the Residual Negative Pressure in the EUS-FNA Needle Before Withdrawal Enhances the FNA Cytology Yield A. Aziz Aadam*, Young OH, Sahibzada U. Latif, Abdul H. Khan, Mukund Venu, ADAM Schiro, Bryan C. Hunt, R. Nagarjun Rao, Vinod B. Shidham, Kulwinder S. Dua Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL; Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI; Department of Pathology, Wayne State University, Detroit, M

were divided into 4 quartiles of 25 procedures each. There was a non-significant trend towards increase in the diagnostic yield of the final cytopathology over the 4 quartiles. The diagnostic yield of ROSE as well as the agreement between ROSE and final cytopathology was similar across the 4 quartiles. There was a non-significant trend towards a decrease in the duration of procedure over time. The median number of passes remained the same over the time period. (Table 1). Conclusion: While echoendosonographer and cytopathologist performance improves over time with case volume, these data suggest that a multi-disciplinary team can deliver a high diagnostic yield from inception, provided that the individual team members have sufficient training and experience in other settings. Institutions wishing to establish a multi-disciplinary EUS-FNA program may see high performance early-on provided that team members are individually experienced.

This study characterizes the transport of [1-14C]glycyl-L-proline into purified brush border membrane vesicles prepared from human small intestine. Time-course uptake curves of glycyl-L-proline were similar under sodium thiocyanate or potassium thiocyanate gradient conditions (extravesicular greater than intravesicular) and did not show any overshoot phenomena. The transport of glycine and proline, however, was stimulated by the presence of sodium gradient. Measurement of peptide uptake with increasing medium osmolarity showed that glycyl-L-proline was transported into an osmotically reactive intravesicular space with insignificant binding to the surface of the vesicles. Only 2% of the glycyl-L-proline in the incubation media was hydrolyzed after 10 min of incubation. Also, there was no hydrolysis of peptide transported into the intravesicular space. The effects of increasing concentrations of glycyl-L-proline on uptake showed that uptake of the peptide was saturable and conformed to Michaelis-Menten kinetics with a Km of 4.1 +/- 0.5 mM and a Vmax of 1.53 +/- 0.07 nmol/mg protein X 0.5 min. Free amino acids did not inhibit the transport of glycyl-L-proline while dipeptides and tripeptides exerted appreciable inhibition (up to 60%). Our results show that human small intestinal brush border membrane vesicles transport glycyl-L-proline as an intact peptide by a carrier-mediated, Na+-independent process.