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Gastroesophageal reflux disease (GERD) is one of the most common diseases in North America and globally. The aim of this guideline is to provide evidence-based recommendations regarding the most utilized and available endoscopic and surgical treatments for GERD.Systematic literature reviews were conducted for 4 key questions regarding the surgical and endoscopic treatments for GERD in adults: preoperative evaluation, endoscopic vs surgical or medical treatment, complete vs partial fundoplication, and treatment for obesity (body mass index [BMI] ≥ 35 kg/mThe consensus provided 13 recommendations. Through the development of these evidence-based recommendations, an algorithm was proposed for aid in the treatment of GERD. Patients with typical symptoms should undergo upper endoscopy, manometry, and pH-testing; additional testing may be required for patients with atypical or extra-esophageal symptoms. Patients with normal or abnormal findings on manometry should consider undergoing partial fundoplication. Magnetic sphincter augmentation or fundoplication are appropriate surgical procedures for adults with GERD. For patients who wish to avoid surgery, the Stretta procedure and transoral incisionless fundoplication (TIF 2.0) were found to have better outcomes than proton pump inhibitors alone. Patients with concomitant obesity were recommended to undergo either gastric bypass or fundoplication, although patients with severe comorbid disease or BMI 50 should undergo Roux-en-Y gastric bypass for the additional benefits that follow weight loss.Using the recommendations an algorithm was developed by this panel, so that physicians may better counsel their patients with GERD. There are certain patient factors that have been excluded from included studies/trials, and so these recommendations should not replace surgeon-patient decision making. Engaging in the identified research areas may improve future care for GERD patients.

Background and study aims Post-ERCP pancreatitis (PEP) is the most common complication attributed to the procedure, its incidence being approximately 9.7 %. Numerous studies have evaluated the predictive efficacy of post-procedure serum amylase and lipase levels but with varied procedure-to-test time intervals and cut-off values. The aim of this meta-analysis was to present pooled data from available studies to compare the predictive accuracies of serum amylase and lipase for PEP. Patients and methods A total of 18 studies were identified after a comprehensive search of various databases until June 2021 that reported the use of pancreatic enzymes for PEP. Results The sample size consisted of 11,790 ERCPs, of which PEP occurred in 764 (6.48 %). Subgroups for serum lipase and amylase were created based on the cut-off used for diagnosing PEP, and meta-analysis was done for each subgroup. Results showed that serum lipase more than three to four times the upper limit of normal (ULN) performed within 2 to 4 hours of ERCP had the highest pooled sensitivity (92 %) for PEP. Amylase level more than five to six times the ULN was the most specific serum marker with a pooled specificity of 93 %. Conclusions Our analysis indicates that a lipase level less than three times the ULN within 2 to 4 hours of ERCP can be used as a good predictor to rule out PEP when used as an adjunct to patient clinical presentation. Multicenter randomized controlled trials using lipase and amylase are warranted to further evaluate their PEP predictive accuracy, especially in high-risk patients.

Background and study aims Duodenoscopes that are contaminated due to inadequate reprocessing are well-documented. However, studies have demonstrated poor reprocessing of other kinds of endoscopes as well, including echoendoscopes, gastroscopes, and colonoscopes. We estimated the contamination rate beyond the elevator of gastrointestinal endoscopes based on available data.Methods We searched PubMed and Embase from January 1, 2010 to October 10, 2020, for studies investigating contamination rates of reprocessed gastrointestinal endoscopes. A random-effects model was used to calculate the contamination rate of patient-ready gastrointestinal endoscopes. Subgroup analyses were conducted to investigate differences among endoscope types, countries, and colony-forming unit (CFU) thresholds.Results Twenty studies fulfilled the inclusion criteria, including 1,059 positive cultures from 7,903 samples. The total contamination rate was 19.98 % ± 0.024 (95 % confidence interval [Cl]: 15.29 %–24.68 %; I2 = 98.6 %). The contamination rates of colonoscope and gastroscope channels were 31.95 % ± 0.084 and 28.22 % ± 0.076, respectively. Duodenoscope channels showed a contamination rate of 14.41 % ± 0.029. The contamination rates among studies conducted in North America and Europe were 6.01 % ± 0.011 and 18.16% ± 0.053 %, respectively. The contamination rate among studies using a CFU threshold > 20 showed contamination of 30.36 % ± 0.094, whereas studies using a CFU threshold Conclusions On average, 19.98 % of reprocessed gastrointestinal endoscopes may be contaminated when used in patients and varies between different geographies. These findings highlight that the elevator mechanism is not the only obstacle when reprocessing reusable endoscopes; therefore, guidelines should recommend more surveillance of the endoscope channels as well.

Over 17.7 million gastrointestinal (GI) endoscopic procedures are performed annually, contributing to 68% of all endoscopic procedures in the United States. Usually, endoscopic procedures are low risk, but adverse events may occur, including cardiopulmonary complications, bleeding, perforation, pancreatitis, cholangitis, and infection. Infections after the GI endoscopies most commonly result from the patient's endogenous gut flora. Although many studies have reported infection after GI endoscopic procedures, a true estimate of the incidence rate of post-endoscopy infection is lacking. In addition, the infection profile and causative organisms have evolved over time. In recent times, multi-drug-resistant microorganisms have emerged as a cause of outbreaks of endoscope-associated infections (EAI). In addition, lapses in endoscope reprocessing have been reported, with some but not all outbreaks in recent times. This systematic review summarizes the demographical, clinical, and management data of EAI events reported in the literature. A total of 117 articles were included in the systematic review, with the majority reported from North America and Western Europe. The composite infection rate was calculated to be 0.2% following GI endoscopic procedures, 0.8% following ERCP, 0.123% following non-ERCP upper GI endoscopic procedures, and 0.073% following lower GI endoscopic procedures. Pseudomonas aeruginosa was the most common culprit organism, followed by other Enterobacteriaceae groups of organisms and Gram-positive cocci. We have also elaborated different prevention methods such as antimicrobial prophylaxis, adequate sterilization methods for reprocessing endoscopes, periodic surveillance, and current evidence supporting their utilization. Finally, we discuss disposable endoscopes, which could be an alternative to reprocessing to minimize the chances of EAIs with their effects on the environmental and financial situation.

Background Over the last few decades, advances have been made regarding gender equality starting from medical students to trainees, to leadership in academics. The female representation in specialty academic conferences not only reflects the existing gender disparities in that specialty but also can influence young female trainees to join that field. Digestive Disease Week (DDW) is the premier digestive disease event. We aimed to calculate the proportion of female representation among speakers and moderators at the DDW meetings held from 2018 to 2020. Methods The data for DDW 2018–2020 were collected via the online web-based planner. The gender of speakers of presentations and moderators of sessions were identified by a google search. We further categorized the data by each participating society (AGA, ASGE, AASLD, and SSAT), by presentation track, by session track, and total overall representation in each year. Results Despite the subject of the gender gap being in focus, the proportion of female moderators and speakers was low in DDW in the last 3 years. The female speakers constituted 31.6% in 2018, 33.8% in 2019 and 34.6% in 2020. There was slightly improved female representation in sessions of Inflammatory Bowel Disease, Stomach, and Small Bowel Disorders, Microbiome in GI & Liver disease, and Basic Science over the last 3 years. Conclusion Based on our study and those referenced in this article, we believe that strategies to promote the inclusivity of female moderators and speakers at DDW provide a huge opportunity to influence gender equity within GI.

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.

Gastroesophageal Reflux Disease (GERD) is an extremely common condition with several medical and surgical treatment options. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians, patients, and others in decisions regarding the treatment of GERD with an emphasis on evaluating different surgical techniques. Literature reviews were conducted for 4 key questions regarding the surgical treatment of GERD in both adults and children: surgical vs. medical treatment, robotic vs. laparoscopic fundoplication, partial vs. complete fundoplication, and division vs. preservation of short gastric vessels in adults or maximal versus minimal dissection in pediatric patients. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Recommendations for future research were also proposed. The panel provided seven recommendations for adults and children with GERD. All recommendations were conditional due to very low, low, or moderate certainty of evidence. The panel conditionally recommended surgical treatment over medical management for adults with chronic or chronic refractory GERD. There was insufficient evidence for the panel to make a recommendation regarding surgical versus medical treatment in children. The panel suggested that once the decision to pursue surgical therapy is made, adults and children with GERD may be treated with either a robotic or a laparoscopic approach, and either partial or complete fundoplication based on surgeon–patient shared decision-making and patient values. In adults, the panel suggested either division or non-division of the short gastric vessels is appropriate, and that children should undergo minimal dissection during fundoplication. These recommendations should provide guidance with regard to surgical decision-making in the treatment of GERD and highlight the importance of shared decision-making and patient values to optimize patient outcomes. Pursuing the identified research needs may improve future versions of guidelines for the treatment of GERD.

Introduction Antithrombotic therapy is often interrupted before the placement of a percutaneous endoscopic gastrostomy (PEG) tube because of potentially increased risk of hemorrhagic events. The aim of our study was to evaluate the risk of bleeding events and overall complication rates after PEG in patients on uninterrupted antiplatelet and anticoagulation therapy in a high-volume center. Methods Data regarding demographics, diagnoses, comorbidities, and clinical outcomes pertinent to PEG were collected from 2010 to 2016. Furthermore, data regarding antithrombotic therapy along with the rate of minor or major complications including bleeding associated with this procedure were analyzed. Significant bleeding was defined as postprocedure bleeding from PEG site requiring a blood transfusion and/or surgical/endoscopic intervention. Results We included 1,613 consecutive PEG procedures in this study, of which 1,540 patients (95.5%) received some form of uninterrupted antithrombotic therapy. Of those patients, 535 (34.7%) were on aspirin, 256 (16.6%) on clopidogrel, and 119 (7.7%) on both aspirin and clopidogrel. Subcutaneous heparin was uninterrupted in 980 (63.6%), intravenous heparin in 34 (2.1%), warfarin in 168 (10.9%), and direct-acting oral anticoagulation in 82 (5.3%) patients who overlapped on multiple drugs. We observed 6 significant bleeding events in the entire cohort (0.39%), and all were in subcutaneous heparin groups either alone or in combination with aspirin. No clinically significant bleeding was noted in patients on uninterrupted aspirin, warfarin, clopidogrel, or direct-acting oral anticoagulation groups. Only 5 patients (0.31%) had PEG-related mortality. Discussion The risk of significant bleeding associated with the PEG placement was minimal in patients on uninterrupted periprocedural antithrombotic therapy.

Background and study aims Peroral endoscopic myotomy (POEM) is increasingly being used as the preferred treatment option for achalasia. The aim of this systematic review and meta-analysis was to compare the efficacy and safety of POEM versus pneumatic balloon dilation (PD). Methods We performed a comprehensive review of studies that reported clinical outcomes of POEM and PD for the treatment of achalasia. Measured outcomes included clinical success (improvement of symptoms based on a validated scale including an Eckardt score ≤ 3), adverse events, and post-treatment gastroesophageal reflux disease (GERD). Results Sixty-six studies (6268 patients) were included in the final analysis, of which 29 studies (2919 patients) reported on POEM and 33 studies (3050 patients) reported on PD and 4 studies (299 patients) compared POEM versus PD. Clinical success with POEM was superior to PD at 12, 24, and 36 months (92.9 %, vs 76.9 % P = 0.001; 90.6 % vs 74.8 %, P = 0.004; 88.4 % vs 72.2 %, P = 0.006, respectively). POEM was superior to PD in type I, II and III achalasia (92.7 % vs 61 %, P = 0.01; 92.3 % vs 80.3 %, P = 0.01; 92.3 %v 41.9 %, P = 0.01 respectively)Pooled OR of clinical success at 12 and 24 months were significantly higher with POEM (8.97; P = 0.001 & 5.64; P = 0.006). Pooled OR of GERD was significantly higher with POEM (by symptoms: 2.95, P = 0.02 and by endoscopic findings: 6.98, P = 0.001). Rates of esophageal perforation (0.3 % vs 0.6 %, P = 0.8) and significant bleeding (0.4 % vs 0.7 %, P = 0.56) were comparable between POEM and PD groups. Conclusions POEM is more efficacious than PD in the treatment of patients with achalasia during short-term and long-term follow-up, albeit with higher risk of abnormal esophageal acid exposure.

INTRODUCTIONEmerging data suggests neoadjuvant chemotherapy for resectable pancreatic ductal adenocarcinoma (PDAC) is associated with improved survival. However, less than 40% demonstrate a meaningful radiographic response to NAC. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as a new modality to treat PDAC. We hypothesize that NAC plus EUS-RFA can be used in the management of resectable PDAC.METHODSProspective review of PDAC patients meeting criteria of resectable tumor anatomy that underwent NAC chemotherapy plus EUS-RFA followed by pancreatic resection. Radiographic imaging, perioperative and short-term outcomes were recorded. Surgical pathology specimens were analyzed for treatment response.RESULTSThree eligible patients with resectable PDAC received 4 months of neoadjuvant chemotherapy plus EUS-RFA. One month after completion of neoadjuvant treatment, all 3 patients underwent standard pancreaticoduodenectomy without complications. After a 6 week recovery, all patients completed 2 months of post-op adjuvant chemotherapy.CONCLUSIONSIn our institutional experience, this treatment protocol appears safe. Patients tolerated the combination of chemotherapy and endoscopic radiofrequency ablation. Patients underwent pancreatic resection with uneventful recovery. This novel neoadjuvant approach may provide a more effective alternative to chemotherapy alone.

724 Background: Perioperative chemotherapy with single regimen either FOLFIRINOX (FFX) or gemcitabine/nab-paclitaxel (Gem/NabP) is the current standard of care for pancreatic and periampullary cancers (PC) with overall survival (OS) of 2-3 years without pre-selected CA19-9 level. Sequential chemotherapy with FFX plus Gem/NabP has recently been investigated in metastatic PC and shown to improve OS. We investigated the outcome of patients who received sequential perioperative chemotherapy FFX plus Gem/NabP. Methods: Patients treated with curative intent surgery for PC who received perioperative sequential chemotherapy FFX plus Gem/NabP (each regimen was given at least two months) were identified. OS and recurrence-free survival (RFS) were calculated from the date of initial treatment (neoadjuvant chemotherapy or resection) to the date of last follow-up/death or recurrence via Kaplan-Meier analysis. Results: A total of 29 patients were identified: 24 (83%) patients had pancreatic cancer, 5 (17%) patients had periampullary cancer; 16 (55%) patients received neoadjuvant chemotherapy FFX plus Gem/NabP; 13 (45%) patients underwent upfront surgery and received adjuvant FFX plus Gem/NabP chemotherapy; 22 (76%) patients had resectable disease, the rest 7 (24%) patients had borderline or unresectable disease were all in the neoadjuvant cohort; node positivity was higher in the adjuvant cohort (n=8, 62%) than in the neoadjuvant cohort (n=8, 50%); 5 (17%) patients were found to have homologous recombination deficiency (HRD: BRCA2, CHEK, BARD, ATM) and received PARP inhibitors as part of the perioperative therapy combination. 10 (34%) patients had CA19-9 ≥ 500. Median age was 65 years (range, 45-79 years), 20 (69%) were male. During the study period, 4 (14%) patients died, and 6 (21%) patients had disease recurrence. Median RFS and OS were not reached with a median follow-up of 28 months (range, 10.9–119 months). The longest RFS was 10 years. The 2-years RFS and OS for the entire cohort was 76.7% and 88.8%, respectively. There was no statistical difference in RFS (log rank HR 1.72, 95% CI 0.23-13.15) or OS (log rank HR 0.99, 95% CI 0.20-4.93) for patients in the neoadjuvant cohort versus adjuvant cohort. Conclusions: Sequential perioperative chemotherapy combined FFX plus Gem/NabP for resected PC is effective and potentially prolongs survival, compared to historical controls who received single regimen.[Table: see text]

BACKGROUND At our academic tertiary care medical center, we have noted patients referred for endoscopic retrograde cholangiopancreatography (ERCP) who increasingly require advanced cannulation techniques. This trend is noted despite increased endoscopist experience and annual ERCP volume over the same period. AIM To evaluate this phenomenon of perceived escalation in complexity of cannulation at ERCP and assessed potential underlying factors. METHODS Demographic/clinical variables and records of ERCP patients at the beginning (2008), middle (2013) and end (2018) of the last decade were reviewed retrospectively. Cannulation approaches were classified as “standard” or “advanced” and duodenoscope position was labeled as “standard” (short position) or “non-standard” (e.g., long, semi-long). RESULTS Patients undergoing ERCP were older in 2018 compared to 2008 (69.7 ± 15.2 years vs 55.1 ± 14.7, P < 0.05). Increased ampullary distortion and peri-ampullary diverticula were noted in 2018 (P < 0.001). ERCPs were increasingly performed with a non-standard duodenoscope position, from 2.2% (2008) to 5.6% (2013) and 16.1% (2018) (P < 0.001). Utilization of more than one advanced cannulation technique for a given ERCP increased from 0.7% (2008) to 0.9% (2013) to 6.6% (2018) (P < 0.001). Primary mass size > 4 cm, pancreatic uncinate mass, and bilirubin > 10 mg/dL predicted use of advanced cannulation techniques (P < 0.03 for each). CONCLUSION Complexity of cannulation at ERCP has sharply increased over the past 5 years, with an increased proportion of elderly patients and those with malignancy requiring advanced cannulation approaches. These data suggest that complexity of cannulation at ERCP may be predicted based on patient/ampulla characteristics. This may inform selection of experienced, high-volume endoscopists to perform these complex procedures.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States. Despite the high prevalence of Kras mutations in pancreatic cancer patients, murine models expressing the oncogenic mutant Kras (Krasmut) in mature pancreatic cells develop PDAC at a low frequency. Independent of cell of origin, a second genetic hit (loss of tumor suppressor TP53 or PTEN) is important for development of PDAC in mice. We hypothesized ectopic expression and elevated levels of oncogenic mutant Kras would promote PanIN arising in pancreatic ducts. To test our hypothesis, the significance of elevating levels of K-Ras and Ras activity has been explored by expression of a CAG driven LGSL-KrasG12V allele (cKras) in pancreatic ducts, which promotes ectopic Kras expression. We predicted expression of cKras in pancreatic ducts would generate neoplasia and PDAC. To test our hypothesis, we employed tamoxifen dependent CreERT2 mediated recombination. Hnf1b:CreERT2;KrasG12V (cKrasHnf1b/+) mice received 1 (Low), 5 (Mod) or 10 (High) mg per 20 g body weight to recombine cKras in low (cKrasLow), moderate (cKrasMod), and high (cKrasHigh) percentages of pancreatic ducts. Our histologic analysis revealed poorly differentiated aggressive tumors in cKrasHigh mice. cKrasMod mice had grades of Pancreatic Intraepithelial Neoplasia (PanIN), recapitulating early and advanced PanIN observed in human PDAC. Proteomics analysis revealed significant differences in PTEN/AKT and MAPK pathways between wild type, cKrasLow, cKrasMod, and cKrasHigh mice. In conclusion, in this study, we provide evidence that ectopic expression of oncogenic mutant K-Ras in pancreatic ducts generates early and late PanIN as well as PDAC. This Ras rheostat model provides evidence that AKT signaling is an important early driver of invasive ductal derived PDAC., Summary In this study, the authors provide evidence that ectopic expression of oncogenic mutant Kras in pancreatic ducts generates early and late (PanIN) and pancreatic ductal adenocarcinoma (PDAC) . They characterized this Ras rheostat model which reveals elevated Kras mutation frequency and loss of PTEN are important drivers of PanIN and invasive ductal derived PDAC.

Background Flexible endoscopic myotomy has been increasingly performed for Zenker’s diverticulum using various endoscopic techniques and devices. The main aims of this study were to assess practice patterns and compare outcomes of endoscopic myotomy for Zenker’s diverticulum. Methods Procedures performed at 12 tertiary endoscopy centers from 1/2012 to 12/2018 were reviewed. Patients (≥ 18 years) with Zenker’s diverticulum who had dysphagia and/or regurgitation and underwent endoscopic myotomy were included. Outcomes assessed included technical success, clinical success, and adverse events. Results 161 patients were included. Traditional endoscopic septotomy was performed most frequently (137/161, 85.1 %) followed by submucosal dissection of the septum and myotomy (24/161, 14.9 %). The hook knife (43/161, 26.7 %) and needle-knife (33/161, 20.5 %) were used most frequently. Overall, technical and clinical success rates were 98.1 % (158/161) and 78.1 % (96/123), respectively. Adverse events were noted in 13 patients (8.1 %). There was no significant difference in technical and clinical success between traditional septotomy and submucosal dissection groups (97.1 % vs. 95.8 %, P = 0.56 and 75.2 % vs. 90.9 %, P = 0.16, respectively). Clinical success was higher with the hook knife (96.7 %) compared with the needle-knife (76.6 %) and insulated tip knife (47.1 %). Outcomes were similar between centers performing > 20, 11 – 20, and ≤ 10 procedures. Conclusions Flexible endoscopic myotomy is an effective therapy for Zenker’s diverticulum, with a low rate of adverse events. There was no significant difference in outcomes between traditional septotomy and a submucosal dissection approach, or with centers with higher volume, though clinical success was higher with the hook knife.

BackgroundLong term prognosis for pancreatic adenocarcinoma (PDAC) remains especially poor with an overall 5-year survival rate less than 9%. Endoscopic ultrasound (EUS) guided RFA (EUS-RFA) is an emerging technology and limited data exist regarding long-term outcomes of EUS-RFA for PDAC. In addition to thermal-induced coagulative necrosis and tissue damage, radiofrequency ablation (RFA) has potential to stimulate the host’s antitumor immunity. The aim of this study is to report long-term outcomes of EUS-RFA for unresectable PDAC.MethodsRetrospective chart review of adult patients with an established diagnosis of locally-advanced or metastatic PDAC undergoing EUS-RFA between October 2016 to March 2018 with long term follow up (>30 months). Patients included in the review underwent a total of 1-4 RFA sessions using the Habib EUS-RFA radiofrequency catheter. All patients were concurrently undergoing standard of care chemotherapy.Results10 patients (median age 62 years, male 70%) underwent EUS-RFA (Table 1). Location of the primary PDAC was in the head (4), neck (2), body (2), and tail (2). A total of 22 RFA sessions were performed with a range of 1-4 RFA sessions per patient. RFA was technically successful in all RFA sessions (100%). There were no major adverse events (bleeding, perforation, infection, pancreatitis) in immediate (up to 72 hours) and short-term follow up (4 week). Mild worsening of existing abdominal pain was noted during post-procedure observation in 12/22 (55%) of RFA treatments. Follow-up imaging after RFA treatment was available in 8/10 patients. Tumor progression was noted in 2 patients, whereas tumor regression was noted in 6 patients (>50% reduction in size in 3 patients). Median survival for the cohort was 20.5 months (95% CI, 9.93 to 42.2 months). Currently, 2 patients remain alive at 53 and 73 months follow-up since initial diagnosis. One patient had 3 cm PDAC with encasement of the portal confluence, abutment of the celiac axis, common hepatic and superior mesenteric artery. This patient had significant reduction in tumor size and underwent standard pancreaticoduodenectomy.ConclusionIn our experience, EUS-RFA was safe, well-tolerated and could be concurrently performed with standard of care chemotherapy. In this select cohort, median survival (20.5 months) was improved when compared to published survival based upon SEER database and clinical trials. Future prospective trials are needed to understand the role of EUS-RFA in overall management of PDAC.

The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding initial triggers of immunosuppression during the process of pancreatic tumorigenesis would aid in establishing novel targets for effective prevention and therapy. Here, we interrogate the differential molecular mechanisms dependent on cell of origin and pathology subtype that determine immunosuppression during PDAC initiation and in established tumors. Transcriptomic analysis of cell of origin dependent-epithelial gene signatures revealed that Nt5e/CD73, a cell surface enzyme that is the pacemaker for extracellular adenosine generation, is one of the top 10% of genes over-expressed in murine tumors arising from ductal pancreatic epithelium as opposed to those rising from acinar cells. These findings were confirmed by Imaging Mass Cytometry and High-Performance Liquid Chromatography. Our data indicate that ductal activation of oncogenic mutant Kras results in loss of PTEN and elevated AKT signaling which ultimately releases CD73 suppression. Delivery of CD73 small molecule inhibitors through various delivery routes reduced tumor development and growth in genetically engineered and syngeneic mouse models. Analysis in human PDAC subtypes indicates that high Nt5e in murine ductal PDAC models overlaps with high NT5E in human PDAC Squamous and Basal Subtypes, considered to have the highest immunosuppression and worst prognosis. These findings highlight a molecular trigger of the immunosuppressive PDAC microenvironment which is dependent on ductal cell of origin, linking biology with pathological subtype classification, critical components to personalized approaches for PDAC prevention and immunotherapeutic intervention.Abstract Figure

Simple Summary Gastrointestinal cancers cause over 2.8 million deaths annually worldwide. Currently, the diagnosis of various gastrointestinal cancer mainly relies on manual interpretation of radiographic images by radiologists and various endoscopic images by endoscopists. Artificial intelligence (AI) may be useful in screening, diagnosing, and treating various cancers by accurately analyzing diagnostic clinical images, identifying therapeutic targets, and processing large datasets. The use of AI in endoscopic procedures is a significant breakthrough in modern medicine. Although the diagnostic accuracy of AI systems has markedly increased, it still needs collaboration with physicians. In the near future, AI-assisted systems will become a vital tool for the management of these cancer patients. Abstract Gastrointestinal cancers are among the leading causes of death worldwide, with over 2.8 million deaths annually. Over the last few decades, advancements in artificial intelligence technologies have led to their application in medicine. The use of artificial intelligence in endoscopic procedures is a significant breakthrough in modern medicine. Currently, the diagnosis of various gastrointestinal cancer relies on the manual interpretation of radiographic images by radiologists and various endoscopic images by endoscopists. This can lead to diagnostic variabilities as it requires concentration and clinical experience in the field. Artificial intelligence using machine or deep learning algorithms can provide automatic and accurate image analysis and thus assist in diagnosis. In the field of gastroenterology, the application of artificial intelligence can be vast from diagnosis, predicting tumor histology, polyp characterization, metastatic potential, prognosis, and treatment response. It can also provide accurate prediction models to determine the need for intervention with computer-aided diagnosis. The number of research studies on artificial intelligence in gastrointestinal cancer has been increasing rapidly over the last decade due to immense interest in the field. This review aims to review the impact, limitations, and future potentials of artificial intelligence in screening, diagnosis, tumor staging, treatment modalities, and prediction models for the prognosis of various gastrointestinal cancers.