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Background & Aims The tumor microbiome of patients with pancreas ductal adenocarcinoma (PDAC) includes bacteria normally present in the upper gastrointestinal tract. If the predominant source of intratumoral bacteria in patients with PDAC is retrograde migration from the duodenum, duodenal fluid could be a representative biospecimen for determining microbiome profiles of patients with PDAC or at risk of developing PDAC. Methods We performed a case-control study comparing bacterial and fungal (16S and 18S rRNA) profiles of secretin-stimulated duodenal fluid collections from 308 patients undergoing duodenal endoscopy including 134 normal pancreas control subjects, 98 patients with pancreatic cyst(s) and 74 patients with PDAC. Results Alterations in duodenal fluid microbiomes with diminished alpha diversity were significantly associated with age >70 and proton pump inhibitor use. Patients with PDAC had significantly decreased duodenal microbial alpha diversity compared with age-matched control subjects with normal pancreata and those with pancreatic cyst(s). There was evidence of enrichment of Bifidobacterium genera in the duodenal fluid of patients with PDAC compared with control subjects and those with pancreatic cyst(s). There were also enrichment of duodenal fluid Fusobacteria and Rothia bacteria among patients with PDAC with short-term survival. Duodenal fluid microbiome profiles were not significantly different between control subjects and patients with pancreatic cyst(s). Conclusion Patients with PDAC have alterations in their duodenal fluid microbiome profiles compared with patients with pancreatic cysts and those with normal pancreata. ClinicalTrials.gov , Number: NCT02000089

BACKGROUND AND AIMS Endoscopic ablation can eradicate neoplastic Barrett's esophagus (BE) without visible lesions. Cryoballoon ablation (CBA) is an established but relatively newer ablative technique that can eliminate BE but data on the durability of its treatment effects are lacking. We assessed the durability of CBA treatment for neoplastic BE. METHODS We performed a single-center cohort study of consecutive BE patients with confirmed low-grade dysplasia (LGD), high-grade dysplasia (HGD) or intramucosal cancer (ImCA) treated with CBA to eradicate all BE. We excluded patients with prior ablative therapy. Visible lesions were removed with endoscopic mucosal resection (EMR) prior to CBA. Outcomes included complete eradication of dysplasia (CE-D) and complete eradication of intestinal metaplasia (CE-IM) at 1 year, durability at 2 and 3 years after initial ablation, cumulative recurrence rate of dysplasia and IM, and rate of neoplastic progression. RESULTS 59 patients (55.9% with HGD; 20.3% with prior EMR) were tracked for a median of 54.3 months. CE-D and CE-IM at 1 year were 94.6% (53/56) and 75% (42/56), respectively. Allowing for retreatment, rates of maintained CE-D and CE-IM for those who have achieved CE-D or CE-IM were 100% (53/53) and 98% (47/48) at 2 years; 100% (45/45) and 98% (40/41), at 3 years, respectively. Cumulative recurrence rate was 1.9% (1/53) for dysplasia and 14.6% (7/48) for IM (not allowing for retreatment). There was no neoplastic progression. CONCLUSION In treatment-naive patients with dysplastic BE, CBA is a durable endoscopic eradication therapy but endoscopic surveillance after eradication is still warranted.

Gene variants that encode pancreatic enzymes with impaired secretion can induce pancreatic acinar endoplasmic reticulum (ER) stress, cellular injury and pancreatitis. The role of such variants in pancreatic cancer risk has received little attention. We compared the prevalence of ER stress-inducing variants in CPA1 and CPB1 in patients with pancreatic ductal adenocarcinoma (PDAC cases), enrolled in the National Familial Pancreas Tumor Registry, to their prevalence in non-cancer controls in the Genome Aggregation Database (gnomAD). Variants of unknown significance were expressed and variants with reduced secretion assessed for ER stress induction. In vitro assessments were compared with software predictions of variant function. Protein variant software was used to assess variants found in only one gnomAD control ("n-of-one" variants). A meta-analysis of prior PDAC case/control studies was also performed. Of the 1385 patients with PDAC, 0.65% were found to harbor an ER stress-inducing variant in CPA1 or CPB1, compared to 0.17% of the 64,026 controls (Odds Ratio (OR): 3.80 [1.92-7.51] P=0.0001). ER stress-inducing variants in the CPA1 gene were identified in 4 of 1385 PDAC cases versus 77 of 64,026 gnomAD controls (OR: 2.4 [0.88-6.58], p=0.087), and variants in CPB1 were detected in 5 of 1385 cases versus 33 of 64,026 controls (OR: 7.02 [2.74-18.01], p=0.0001). Meta-analysis demonstrated strong associations for pancreatic cancer and ER-stress inducing variants for both CPA1 (OR: 3.65 [1.58, 8.39], p

Background and study aims Transoral incisionless fundoplication (TIF) is a safe and effective minimally invasive endoscopic technique for treating gastroesophageal reflux disease (GERD). The learning curve for this technique has not been reported. We studied the learning curve for TIF when performed by a gastroenterologist by identifying the threshold number of procedures needed to achieve consistent technical success or proficiency (consistent creation of TIF valve ≥ 270 degrees in circumference, ≥ 2 cm long) and efficiency after didactic, hands-on and case observation experience. Patients and methods We analyzed prospectively collected data from patients who had TIF performed by a single therapeutic endoscopist within 17 months after basic training. We determined thresholds for procedural learning using cumulative sum of means (CUSUM) analysis to detect changes in achievement rates over time. We used breakpoint analysis to calculate procedure metrics related to proficiency and efficiency. Results A total of 69 patients had 72 TIFs. The most common indications were refractory GERD (44.7 %) and proton pump inhbitor intolerance (23.6 %). Proficiency was achieved at the 18th to 20th procedure. The maximum efficiency for performing a plication was achieved after the 26th procedure, when mean time per plication decreased to 2.7 from 5.1 minutes (P Conclusions TIF can be safely, successfully, and efficiently performed in the endoscopy suite by a therapeutic endoscopist. The TIF learning curve is steep but proficiency can be achieved after a basic training experience and 18 to 20 independently performed procedures.

BACKGROUND: COVID-19 pandemic-related disruptions to EUS-based pancreatic cancer surveillance in high-risk individuals remain uncertain. METHODS: Analysis of enrolled participants in the CAPS5 Study, a prospective multicenter study of pancreatic cancer surveillance in high-risk individuals. RESULTS: Amongst 693 enrolled high-risk individuals under active surveillance, 108 (16%) had an EUS scheduled during the COVID-19 pandemic-related shutdown (median length of 78 days) in the spring of 2020, with 97% of these procedures being canceled. Of these canceled surveillance EUSs, 83% were rescheduled in a median of 4.1 months, however 17% were not rescheduled after 6 months follow-up. Prior history of cancer was associated with increased likelihood of rescheduling. To date no pancreatic cancer has been diagnosed among those whose surveillance was delayed. CONCLUSIONS: COVID-19 delayed pancreatic cancer surveillance with no adverse outcomes in efficiently rescheduled individuals. However, 1 in 6 high-risk individuals had not rescheduled surveillance, indicating the need for vigilance to ensure timely surveillance rescheduling.

Background: The use of peroral endoscopic myotomy (POEM) for achalasia has a high incidence of post-procedural gastroesophageal reflux (GER). Transoral incisionless fundoplication (TIF) may be an ideal endoscopic treatment. We report our experience with the use of post-POEM TIF. Methods: In this multicenter retrospective study, post-POEM patients with GER who underwent TIF were included. The study end points were: (i) technical success; (ii) safety; (iii) effectiveness (changes in symptoms, scores, proton pump inhibitor [PPI] use, pH studies). Results: 12 patients underwent TIF after POEM, nine of whom had daily symptoms, with 91.7% requiring twice daily (BID) PPIs. Technical success was achieved in all patients. Two adverse events occurred. There were significant decreases in the percentage of patients on BID PPIs (P = 0.03), frequency of daily symptoms (P = 0.03), Reflux Severity Index questionnaire, and GERD Health-related Quality of Life scores (P = 0.03 and P = 0.003; n = 6). pH studies performed in seven of the patients showed a significant reduction in the mean DeMeester score (P = 0.05) and mean percentage acid exposure time (P = 0.04). Conclusion: Our experience suggests that TIF may be effective and safe in treating GER after POEM. Larger prospective trials are needed.

PURPOSE To report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies. METHODS Individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and 2021. The primary end point was the stage distribution of pancreatic ductal adenocarcinoma (PDAC) detected (stage I v higher-stage). Overall survival was determined using the Kaplan-Meier method. RESULTS Of 1,461 high-risk individuals enrolled into CAPS5, 48.5% had a pathogenic variant in a PDAC-susceptibility gene. Ten patients were diagnosed with PDAC, one of whom was diagnosed with metastatic PDAC 4 years after dropping out of surveillance. Of the remaining nine, seven (77.8%) had a stage I PDAC (by surgical pathology) detected during surveillance; one had stage II, and one had stage III disease. Seven of these nine patients with PDAC were alive after a median follow-up of 2.6 years. Eight additional patients underwent surgical resection for worrisome lesions; three had high-grade and five had low-grade dysplasia in their resected specimens. In the entire CAPS cohort (CAPS1-5 studies, 1,731 patients), 26 PDAC cases have been diagnosed, 19 within surveillance, 57.9% of whom had stage I and 5.2% had stage IV disease. By contrast, six of the seven PDACs (85.7%) detected outside surveillance were stage IV. Five-year survival to date of the patients with a screen-detected PDAC is 73.3%, and median overall survival is 9.8 years, compared with 1.5 years for patients diagnosed with PDAC outside surveillance (hazard ratio [95% CI]; 0.13 [0.03 to 0.50], P = .003). CONCLUSION Most pancreatic cancers diagnosed within the CAPS high-risk cohort in the recent years have had stage I disease with long-term survival.

The newest addition in the management of achalasia and esophagogastric junction outflow obstruction (EGJOO) is a 30-mm hydrostatic balloon dilator that uses impedance planimetry technology. It allows for the measurement of the diameter and cross-sectional area to determine effective dilation. We aimed to (1) determine the clinical success (defined as a decrease in Eckardt score to ≤3) in the treatment of esophageal motility disorders and (2) report the safety (rate/severity of adverse events).This retrospective multicenter study involved 4 centers. Patients with esophageal motility disorders who underwent hydrostatic balloon dilation between January 2015 and October 2018 were included.Fifty-one patients (mean age, 54.1 years; women, 49%) underwent hydrostatic dilation for achalasia (n = 37) or EGJOO (n = 14) during the study period. Forty-seven patients had a median baseline Eckardt score of 5 (range, 3-8; achalasia, n = 35, 6 [range, 3-8]; EGJOO, n = 12, 4 [range, 3.25-6.5]). Clinical success was achieved in 60% of cases (achalasia vs EGJOO: 68.4% vs 33.3%, P = .18). Dilation resulted in a significant decrease in the median Eckardt score from 5 (range, 3-8) to 1.5 (range, 1-4.75; P .001). Patients with achalasia had a decrease in Eckardt score from 6 (range, 3-8) to 1 (range, 1-4; P .001), whereas those with EGJOO experienced no significant change. One patient had mild postprocedure chest pain.The hydrostatic balloon dilator is a new tool in our armamentarium to treat esophageal motility disorders. This is the first multicenter study showing the device to be safe and moderately efficacious.

Endoplasmic reticulum (ER) stress-inducing variants in several pancreatic secretory enzymes have been associated with pancreatic disease. Multiple variants in CEL, encoding carboxyl ester lipase, are known to cause maturity-onset diabetes of the young (MODY8) but have not been implicated in pancreatic cancer risk.The prevalence of ER stress-inducing variants in the CEL gene was compared among pancreatic cancer cases vs. controls. Variants were identified by next-generation sequencing and confirmed by Sanger sequencing. Variants of uncertain significance (VUS) were assessed for their effect on the secretion of CEL protein and variants with reduced protein secretion were evaluated to determine if they induced endoplasmic reticulum stress.ER stress-inducing CEL variants were found in 34 of 986 cases with sporadic pancreatic ductal adenocarcinoma, and 21 of 1045 controls (P = 0.055). Most of the variants were either the CEL-HYB1 variant, the I488T variant, or the combined CEL-HYB1/I488T variant; one case had a MODY8 variant.This case/control analysis finds ER stress-inducing CEL variants are not associated with an increased likelihood of having pancreatic cancer.

Background Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP; EDGE) is an alternative to enteroscopy- and laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy. Although short-term results are promising, the long-term outcomes are not known. The aims of this study were: (1) to determine the rates of long-term adverse events after EDGE, with a focus on rates of persistent gastrogastric or jejunogastric fistula; (2) to identify predictors of persistent fistula; (3) to assess the outcomes of endoscopic closure when persistent fistula is encountered. Methods This was a multicenter retrospective study involving 13 centers between February 2015 and March 2019. Adverse events were defined according to the ASGE lexicon. Persistent fistula was defined as an upper gastrointestinal series or esophagogastroduodenoscopy showing evidence of fistula. Results 178 patients (mean age 58 years, 79 % women) underwent EDGE. Technical success was achieved in 98 % of cases (175/178), with a mean procedure time of 92 minutes. Periprocedural adverse events occurred in 28 patients (15.7 %; mild 10.1 %, moderate 3.4 %, severe 2.2 %). The four severe adverse events were managed laparoscopically. Persistent fistula was diagnosed in 10 % of those sent for objective testing (9/90). Following identification of a fistula, 5 /9 patients underwent endoscopic closure procedures, which were successful in all cases. Conclusions The EDGE procedure is associated with high clinical success rates and an acceptable risk profile. Persistent fistulas after lumen-apposing stent removal are uncommon, but objective testing is recommended to identify their presence. When persistent fistulas are identified, endoscopic treatment is warranted, and should be successful in closing the fistula.

Gene variants that encode pancreatic enzymes with impaired secretion can induce pancreatic acinar endoplasmic reticulum (ER) stress, cellular injury and pancreatitis. The role of such variants in pancreatic cancer risk has received little attention. We compared the prevalence of ER stress-inducing variants in CPA1 and CPB1 in patients with pancreatic ductal adenocarcinoma (PDAC cases), enrolled in the National Familial Pancreas Tumor Registry, to their prevalence in non-cancer controls in the Genome Aggregation Database (gnomAD). Variants of unknown significance were expressed and variants with reduced secretion assessed for ER stress induction. In vitro assessments were compared with software predictions of variant function. Protein variant software was used to assess variants found in only one gnomAD control (“n-of-one” variants). A meta-analysis of prior PDAC case/control studies was also performed. Of the 1385 patients with PDAC, 0.65% were found to harbor an ER stress-inducing variant in CPA1 or CPB1, compared to 0.17% of the 64,026 controls (Odds Ratio (OR): 3.80 [1.92–7.51] P=0.0001). ER stress-inducing variants in the CPA1 gene were identified in 4 of 1385 PDAC cases versus 77 of 64,026 gnomAD controls (OR: 2.4 [0.88–6.58], p=0.087), and variants in CPB1 were detected in 5 of 1385 cases versus 33 of 64,026 controls (OR: 7.02 [2.74–18.01], p=0.0001). Meta-analysis demonstrated strong associations for pancreatic cancer and ER-stress inducing variants for both CPA1 (OR: 3.65 [1.58, 8.39], p

Objective: Patients with laryngopharyngeal reflux (LPR) symptoms may not respond to proton pump inhibitors (PPI) if they have an alternative laryngeal diagnosis or high-volume reflux. Transoral incisionless fundoplication (TIF) or TIF with concomitant hiatal hernia repair (cTIF) are effective in decreasing symptoms of gastroesophageal reflux disease (GERD) but are not well studied in patients with LPR symptoms. This prospective multicenter study assessed the patient-reported and clinical outcomes after TIF/cTIF in patients with LPR symptoms and proven GERD. Methods: Patients with refractory LPR symptoms (reflux symptom index [RSI] > 13) and with erosive esophagitis, Barrett’s esophagus, and/or pathologic acid reflux by distal esophageal pH testing were evaluated before and after a minimum of 6 months after TIF/cTIF. The primary outcome was normalization of RSI. Secondary outcomes were >50% improvement in GERD-Health-Related Quality of Life (GERD-HRQL), normalization of esophageal acid exposure time, discontinuation of PPI, and patient satisfaction. Results: Forty-nine patients had TIF (n = 26) or cTIF (n = 23) with at least 6 months follow-up. Mean pre- and post TIF/cTIF RSI were 23.6 and 5.9 (mean difference: 17.7, P Conclusion: In patients with objective evidence of GERD, TIF, or cTIF are safe and effective in controlling LPR symptoms as measured by normalization of RSI and improvement in patient satisfaction after TIF/cTIF. Level of Evidence Level 4

Background and Aims Serum diagnostic markers of early-stage pancreatic ductal adenocarcinoma (PDAC) are needed, especially for stage I disease. As tumors grow and cause pancreatic atrophy, markers derived from pancreatic parenchyma such as serum carboxypeptidase A (CPA) activity lose diagnostic performance. We evaluated, with CA19-9, serum CPA as a marker of early pancreatic cancer. Methods Serum CPA activity levels were measured in 345 controls undergoing pancreatic surveillance, divided into 2 sets, set 1 being used to establish a reference range. Variants within the CPA1 locus were sought for their association with pancreatic CPA1 expression to determine if such variants associated with serum CPA levels. A total of 190 patients with resectable PDAC were evaluated. Results Among controls, those having 1 or more minor alleles of CPA1 variants rs6955723 or rs2284682 had significantly higher serum CPA levels than did those without (P = .001). None of the PDAC cases with pancreatic atrophy had an elevated CPA. Among 122 PDAC cases without atrophy, defining serum CPA diagnostic cutoffs by a subject’s CPA1 variants yielded a diagnostic sensitivity of 18% at 99% specificity (95% confidence interval [CI], 11.7–26) (vs 11.1% sensitivity using a uniform diagnostic cutoff); combining CPA with variant-stratified CA19-9 yielded a sensitivity of 68.0% (95% CI, 59.0–76.2) vs 63.1% (95% CI, 53.9– 71.7) for CA19-9 alone; and among stage I PDAC cases, diagnostic sensitivity was 51.9% (95% CI, 31.9–71.3) vs 37.0% (95% CI, 19.4–57.6) for CA19-9 alone. In the validation control set, the variant-stratified diagnostic cutoff yielded a specificity of 98.2%. Conclusion Serum CPA activity has diagnostic utility before the emergence of pancreatic atrophy as a marker of localized PDAC, including stage I disease.

Background and study aims The role of the digital single-operator pancreatoscopy (D-SOP) with electrohydraulic (EHL) or laser lithotripsy (LL) in treating pancreatic ductal stones is unclear. We investigated the safety and efficacy of D-SOP with EHL or LL in patients with obstructing pancreatic duct stones. Patients and methods Retrospective analysis of 109 patients who underwent D-SOP for pancreatic stones at 17 tertiary centers in the United States and Europe from February 2015 to September 2017. Logistic regression was performed to identify factors associated with the need for more than one D-SOP with EHL/LL. Results Most patients were males (70.6 %),mean age 54.7 years. Fifty-nine (54.1 %) underwent EHL and 50 (45.9 %) underwent LL. Mean procedure time was longer in the EHL group (74.4 min vs 53.8 min; P Conclusion D-SOP with EHL or LL is effective and safe in patients with pancreatic ductal stones.

Background Multiple studies have examined the use of lumen-apposing metal stents (LAMSs) for the drainage of peripancreatic fluid collections. Data on the use of LAMSs for postoperative fluid collections (POFCs) are scarce. POFCs may lead to severe complications without appropriate treatment. We aimed to study the outcomes (technical success, clinical success, rate/severity of adverse events, length of stay, recurrence) of the use of LAMSs for the drainage of POFCs. Methods This international, multicenter, retrospective study involved 19 centers between January 2012 and October 2017. The primary outcome was clinical success. Secondary outcomes included technical success and rate/severity of adverse events using the ASGE lexicon. Results A total of 62 patients were included during the study period. The most common etiology of the POFCs was distal pancreatectomy (46.8 %). The mean (standard deviation) diameter was 84.5 mm (30.7 mm). The most common indication for drainage was infection (48.4 %) and transgastric drainage was the most common approach (82.3 %). Technical success was achieved in 60/62 patients (96.8 %) and clinical success in 57/62 patients (91.9 %) during a median (interquartile range) follow-up of 231 days (90 – 300 days). Percutaneous drainage was needed in 8.1 % of patients. Adverse events occurred intraoperatively in 1/62 patients (1.6 %) and postoperatively in 7/62 (11.3 %). There was no procedure-related mortality. Conclusion This is the largest study on the use of LAMSs for POFCs. It suggests good clinical efficacy and safety of this approach. The use of LAMSs in the management of POFCs is a feasible alternative to percutaneous and surgical drainage.

Background and study aims EUS-guided gastroenterostomy (GE) is a novel, minimally invasive endoscopic procedure for the treatment of gastric outlet obstruction (GOO). The direct-EUS-GE (D-GE) approach has recently gained traction. We aimed to report on a large cohort of patients who underwent DGE with focus on long-term outcomes. Patients and methods This two-center, retrospective study involved consecutive patients who underwent D-GE between October 2014 and May 2018. The primary outcomes were technical and clinical success. Secondary outcomes were adverse events (AEs), rate of reintervention, procedure time, time to resume oral diet, and post-procedure length of stay (LOS). Results A total of 57 patients (50.9 % female; median age 65 years) underwent D-GE for GOO. The etiology was malignant in 84.2 % and benign in 15.8 %. Technical success and clinical success were achieved in 93 % and 89.5 % of patients, respectively, with a median follow-up of 196 days in malignant GOO and 319.5 days in benign GOO. There were 2 (3.5 %) AEs, one severe and one moderate. Median procedure time was 39 minutes (IQR, 26 – 51.5 minutes). Median time to resume oral diet after D-GE was 1 day (IQR 1 – 2 days). Median post D-GE LOS was 3 days (IQR 2 – 7 days). Rate of reintervention was 15.1 %. Conclusions D-GE is safe and effective in management of both malignant and benign causes of GOO. Clinical success with D-GE is durable with a low rate of reintervention based on a long-term cohort.

Background There is growing interest in developing impedance planimetry as a tool to enhance the clinical outcomes for endoscopic and surgical management of achalasia. The primary aim of this study was to determine whether impedance planimetry measurements can predict clinical response and reflux following peroral endoscopic myotomy (POEM). Methods A multicenter cohort study of patients with achalasia undergoing POEM was established from prospective databases and retrospective chart reviews. Patients who underwent impedance planimetry before and after POEM were included. Clinical response was defined as an Eckardt score of ≤ 3. Tenfold cross-validated area under curve (AUC) values were established for the different impedance planimetry measurements associated with clinical response and reflux development. Results Of the 290 patients included, 91.7 % (266/290) had a clinical response and 39.4 % (108/274) developed reflux following POEM. The most predictive impedance planimetry measurements for a clinical response were: percent change in cross-sectional area (%ΔCSA) and percent change in distensibility index (%ΔDI), with AUCs of 0.75 and 0.73, respectively. Optimal cutoff values for %ΔCSA and %ΔDI to determine a clinical response were a change of 360 % and 272 %, respectively. Impedance planimetry values were much poorer at predicting post-POEM reflux, with AUCs ranging from 0.40 to 0.62. Conclusion Percent change in CSA and distensibility index were the most predictive measures of a clinical response, with a moderate predictive ability. Impedance planimetry values for predicting reflux following POEM showed weak predictive capacity.

Nitrous oxide cryoballoon (CB) ablation can effectively and safely eradicate dysplasia and intestinal metaplasia (IM) in patients with dysplastic BE but the durability of treatment effect is unknown. We evaluated the safety, efficacy and durability of CB ablation for complete eradication of dysplasia and IM Methods We analyzed the outcomes of consecutive BE patients treated with CB at a single academic medical center for dysplastic BE. We excluded patients with adenocarcinoma and those treated primarily with radiofrequency ablation (RFA). CB ablation was applied to all visible BE using the CB focal ablation system and default cryogen dose of 10 seconds, after eradication of neoplastic-type lesions with endoscopic mucosal resection (EMR). Primary endpoints were complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1, 2, 3, 4 years. Kaplan-Meir analysis was performed to assess durability where any recurrence was considered a failure. Results 70 patients (HGD = 64%; 65.7% = treatment-naive) were followed up for median of 27.4 months. CE-D and CE-IM at 1 year were 96.7% and 73.8%, respectively. The median number of CB sessions to achieve CE-IM at 1 year was 3 (IQR 2-3.5). The rates of CE-D and CE-IM allowing for re-treatment with CB or “touch-up” APC were above 90% at 2, 3 and 4 years, with no difference between treatment-naïve and previously-ablated patients. The durability of CB response in patients who achieved CE-D or CE-IM at 1 year followed until last follow-up or recurrence of dysplasia or IM are presented in Figure 1. Conclusion Recurrence rate of IM after initial CB eradication is low patient with no patients progressing to cancer or beyond their baseline dysplasia grade. CB ablation has high efficacy, safety, and durability for eradicating dysplasia and intestinal metaplasia in dysplastic BE as a primary or rescue therapy.

Background and Aims EMR is the preferred endoscopic therapy for duodenal adenomas (DAs) but is associated with an overall adverse event rate of 26%. Cryotherapy using a Cryoballoon Focal Ablation System (CbFAS) can safely and effectively eradicate esophageal intestinal metaplasia. We report our first experience with cryoballoon ablation for treatment of flat DAs. Methods This was an American, multicenter, retrospective study involving 5 centers. DAs (Paris 0-IIa and 0-IIb) were treated with nitrous oxide for 5 to 12 seconds using CbFAS. Follow-up EGD was performed at 3 to 12 months. Results Seventeen DAs (mean size, 22.7 ± 14.3 mm; 12 tubular, 5 tubulovillous) from 13 patients (mean age, 66.5 ± 9.99 years; 61.5% males) were included in the study. Thirteen of 17 DAs (76.5%) had failed previous treatment, and 4 of 17 (23.5%) were treatment naIve. All procedures were technically successful and achieved a >50% decrease in size after cryoballoon ablation There was no increase in size or progression of disease for any lesions. Overall, treatment was completed in 15 of 17 patients, and recurrence-free survival was achieved in 12 of 17 (71%) after a median follow-up of 15.5 months (interquartile range [IQR], 6.8-19.4). The median cryoablation time per polyp was 4 minutes (IQR, 1-7.5 minutes), and the median total procedure time was 25 minutes (IQR, 22-30.5 minutes). There were no intra- or postprocedural adverse events. Conclusions Nitrous oxide cryoballoon ablation of nonpolypoid DAs is feasible, with promising safety and efficacy.

Background & Aims Levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA-125) in blood are used as markers to determine the response of patients with cancer to therapy, but are not used to identify patients with pancreatic cancer. Methods We obtained blood samples from 504 patients undergoing pancreatic surveillance from 2002 through 2018 who did not develop pancreatic cancer and measured levels of the tumor markers CA19-9, CEA, CA-125, and thrombospondin-2. Single-nucleotide polymorphisms (SNPs) in FUT3, FUT2, ABO, and GAL3ST2 that have been associated with levels of tumor markers were used to establish SNP-defined ranges for each tumor marker. We also tested the association between additional SNPs (in FUT6, MUC16, B3GNT3, FAM3B, and THBS2) with levels of tumor markers. To calculate the diagnostic specificity of each SNP-defined range, we assigned the patients under surveillance into training and validation sets. After determining the SNP-defined ranges, we determined the sensitivity of SNP-adjusted tests for the tumor markers, measuring levels in blood samples from 245 patients who underwent resection for pancreatic ductal adenocarcinoma (PDAC) from 2010 through 2017. Results A level of CA19-9 that identified patients with PDAC with 99% specificity had 52.7% sensitivity. When we set the cut-off levels of CA19-9 based on each SNP, the test for CA19-9 identified patients with PDAC with 60.8% sensitivity and 98.8% specificity. Among patients with FUT3 alleles that encode a functional protein, levels of CA19-9 greater than the SNP-determined cut-off values identified 66.4% of patients with PDAC, with 99.3% specificity. In the validation set, levels of CEA varied among patients with vs without SNP in FUT2, by blood group, and among smokers vs nonsmokers; levels of CA-125 varied among patients with vs without the SNP in GAL3ST2. The use of the SNPs to define the ranges of CEA and CA-125 did not significantly increase the diagnostic accuracy of the assays for these proteins. Combining data on levels of CA19-9 and CEA, CA19-9 and CA-125, or CA19-9 and thrombospondin-2 increased the sensitivity of detection of PDAC, but slightly reduced specificity. Conclusions Including information on SNPs associated with levels of CA19-9, CEA, and CA-125 can improve the diagnostic accuracy of assays for these tumor markers in the identification of patients with PDAC. Clinicaltrials.gov no: NCT02000089 .

Background and study aims Per-oral endoscopic myotomy (POEM) is associated with a short-term clinical response of 82 % to 100 % in treatment of patients with achalasia. Data are limited on the long-term durability of the clinical response in these patients. The aim of this study was to determine the long-term outcomes of patients undergoing POEM for management of achalasia. Methods This was a retrospective multicenter cohort study of consecutive patients who underwent POEM for management of achalasia. Patients had a minimum of 4 years follow-up. Clinical response was defined by an Eckardt score ≤ 3. Results A total of 146 patients were included from 11 academic medical centers. Mean (± SD) age was 49.8 (± 16) years and 79 (54 %) were female. The most common type of achalasia was type II, seen in 70 (47.9 %) patients, followed by type I seen in 41 (28.1 %) patients. Prior treatments included: pneumatic dilation in 29 (19.9 %), botulinum toxin injection in 13 (8.9 %) and Heller myotomy in seven patients (4.8 %). Eight adverse events occurred (6 mucosotomies, 2 pneumothorax) in eight patients (5.5 %). Median follow-up duration was 55 months (IQR 49.9–60.6). Clinical response was observed in 139 (95.2 %) patients at follow-up of ≥ 48 months. Symptomatic reflux after POEM was seen in 45 (32.1 %) patients, while 35.3 % of patients were using daily PPI at 48 months post POEM. Reflux esophagitis was noted in 16.8 % of patients who underwent endoscopy. Conclusion POEM is a durable and safe procedure with an acceptably low adverse event rate and an excellent long-term clinical response.

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is mainly due to late-stage diagnosis [1]. Similarities in the clinical behavior and imaging features of PDAC and chronic pancreatitis further complicate the detection of PDAC [2]. There is an urgent need for noninvasive clinically translatable biomarkers of PDAC. Plasma based tests provide an attractive option for routine screening. Here we have applied neural network analysis to 1H magnetic resonance (MR) spectra of human plasma samples to differentiate between healthy subjects (control), subjects with benign lesions, and subjects with pancreatic ductal adenocarcinoma (PDAC). Our data support developing a neural-network approach to identify PDAC from 1H MRS of plasma samples. Plasma samples from healthy subjects (control, n=28), from subjects with benign pancreatic lesions (benign, n=32), and from subjects with PDAC (PDAC/malignant, n=34) were analyzed with 1H MRS. 1H MR spectra were acquired on a Bruker Avance III 750 MHz (17.6 T) MR spectrometer equipped with a 5 mm probe. After processing the spectral data for normalization against a reference peak signal and plasma volume, spectral features were extracted to develop an artificial neural-network technique to discriminate between the three classes of spectra. Three spectral features showed high probability for successful discrimination: (a) signal intensity weighted-mean of the spectra, (b) standard deviation of the spectra about the weighted-mean from (a), and (c) weighted mean of the difference spectra. This led to the design of our three-layer artificial neural network model to solve the discrimination problem. The artificial neural-network, developed in MATLAB 2019b (MathWorks, Inc), was limited to a stack of two auto-encoder layers and a ‘softmax' layer. Due to the limited size of the data all of the data were used to train the network while keeping low L2-regularization to avoid over-training. Cross-validation results were captured as confusion matrices and receiver operating characteristic (ROC) curves. With a combination of spectral features extraction and neural network processing of MRS data of plasma samples we could discriminate between control, benign and PDAC. The sensitivity and specificity for detecting PDAC was 84% and 95%, respectively. Our data suggest that the approach can be extended to encompass a large sample size to improve accuracy and provide a rigorous and robust solution for plasma based detection of PDAC. Acknowledgement: This work was supported by NIH R35CA209960 and R01CA193365. References: 1. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011;378(9791):607-20; 2. Steer ML, Waxman I, Freedman S. Chronic pancreatitis. N Engl J Med. 1995;332(22):1482-90. Citation Format: Meiyappan Solaiyappan, Santosh Kumar Bharti, Paul T. Winnard, Mohamad Dbouk, Michael G. Goggins, Zaver M. Bhujwalla. Detecting pancreatic cancer through neural network analysis of human plasma MR spectra [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2103.

Knowledge Discovery in Databases (KDD) tools emerged as a solution to discover information and knowledge from rapidly growing data; they allow the execution of interactive and iterative processes in order to obtain new useful information from data. In this work, we present a KDD tool extension that allows the execution of interactive software architecture extraction processes. Actually, even though every system has an architecture, not every system has a reliable architecture description that represents the system parts and their relationships. To overcome this problem that puts the system maintenance and reuse in danger, the extraction of the system architecture is proposed. The extraction of a software architecture from an existing system consists at analyzing the source code in order to discover a software architecture description (the system parts and their relationships). While several extraction approaches proved to be efficient, there is no approach allowing an architect to integrate his knowledge and interact with the extraction process. To deal with this lack, we suggest the use of KDD tools to extract a software architecture. Unfortunately, the KDD tools allow the execution of processes with user interaction but they do not support the execution of software architecture extraction processes. Thus, we provide in this work a KDD tool extension that enables the execution of software architecture extraction processes. To achieve our goal, we have firstly elaborated a process model for software architecture extraction, then we have implemented an extension for a KDD tool (called KNIME) that supports the proposed model.

It's a big challenge to deal with security in a city. Technology advancements are influencing our life, cities are evolving, and modern cities are referring more and more to digital technologies. Currently, a huge amount of standalone independent-systems operate in the city, their goal is to satisfy some business activities, e.g. banking, customs, hospitals, etc. Data collected by these systems represents, if integrated, a key element in any decision making process. This paper presents a, working, smart collaborative platform to integrate multiple systems to serve the surveillance activities in a city or country. It consists of a collaborative surveillance system, called CityPro. The architecture that we propose is a future vision to protect people and monitor public infrastructures, such as bridges, roads, buildings, etc.; it is designed to deal with and/or prevent abnormal activities like terrorist attacks. CityPro is expected to operate in live-mode by using (intended to use) city adapted IT-infrastructures. At the end of this paper, a typical case study is given, and challenges and future works are also discussed.