Background The preoperative classification of pancreatic cysts and detection of advanced neoplasia (high-grade dysplasia/pancreatic ductal adenocarcinoma [PDAC]) represents a significant diagnostic challenge. A prospective, multi-institutional study found that DNA-based testing (PancreaSeq) of pancreatic cyst fluid (PCF) improved the assessment of pancreatic cysts. Notable imitations to PancreaSeq necessitated the development of a DNA/RNA-based panel called PancreaSeq Genomic Classifier (GC). We validated PancreaSeq GC on a prospective patient cohort. Patients and Methods PancreaSeq GC was blindly tested on a prospective cohort of 241 patients with diagnostic follow-up. The performance of PancreaSeq GC in this cohort, which included 186 mucinous cysts (97 with advanced neoplasia), was benchmarked against traditional diagnostics and its DNA-only predecessor, PancreaSeq. Results PancreaSeq GC achieved 94.6% sensitivity and 96.4% specificity (area under the curve [AUC] of 0.955) for mucinous cysts. In comparison, increased fluid viscosity, elevated carcinoembryonic antigen (CEA), and PancreaSeq testing had lower sensitivities (71.4-88.2%) and lower AUC (0.824-0.941); however, PancreaSeq specificity was 100%. McNemar's test demonstrated higher sensitivity of PancreaSeq GC versus PancreaSeq for mucinous cysts (p < 0.001). For advanced neoplasia, PancreaSeq GC had 86.6% sensitivity and 97.9% specificity (AUC of 0.923), with McNemar's test confirming improved sensitivity over PancreaSeq (p = 0.031). Worrisome features, malignant cytopathology, and high-risk stigmata had lower sensitivities (44.3-84.5%) and lower AUC (0.604-0.892), while PancreaSeq had identical specificity to PancreaSeq GC. PancreaSeq GC had high accuracy in classifying intraductal oncocytic papillary neoplasms (IOPNs), intraductal tubulopapillary neoplasms (ITPNs), and cystic pancreatic neuroendocrine tumors (cPanNETs), with 97.1-100% sensitivity and 100% specificity. Conclusions This validation study demonstrates statistically significant improvements in PancreaSeq GC for mucinous cysts and advanced neoplasia, establishing it as a clinically valuable tool for the preoperative evaluation of pancreatic cysts.

Introduction There are limited data on the safety of same-day discharge (SDD) following peroral endoscopic myotomy for Zenker's diverticulum (Z-POEM). Our aim is to assess the frequency and etiology of emergency department (ED) visits or hospital admissions after SDD after Z-POEM. Methods Patients at our institution between 02/2020 and 08/2023 who had SDD after Z-POEM were identified. Criteria for SDD were: 1)no procedure-related serious adverse event; 2)post-POEM esophagram without leak; 3)stable vital signs; 4)ability to take liquids; 5)pain controlled without IV analgesia; 6)social support for transit to ED; 7)ASA class I-III. Relevant post-procedure events, ED visits and hospitalizations within 30 days were reported. A causative relationship between Z-POEM and ED visits and hospitalizations was assigned by consensus. Results 39 Z-POEMs were performed, and 26 (67 %) patients (58 % male, median age 72 years) had SDD. Mean ZD diameter was 29±14 mm and mean baseline Dakkak and Bennett's score was 2.9 ± 0.9. Within 30 days of Z-POEM, two(7.7 %) ED visits occurred 13 days and 9 days post-procedure for a COPD exacerbation(n = 1) and pneumonia(n = 1), respectively. Both patients were discharged without admission and only the visit for pneumonia was considered related to Z-POEM. Conclusion Eligible patients who follow and fulfill a strict protocol after Z-POEM may be safely discharged the same day of the procedure.

Indiana University School of Medicine, USA; Stanford University School of Medicine, USA; The University of Texas Medical Branch at Galveston, USA; Vanderbilt University Medical Center, USA; The University of Kansas Medical Center, USA; NorthShore University HealthSystem, USA; The University of Mississippi Medical Center, USA; Thomas Jefferson University, USA; Institut klinicke a experimentalni mediciny, Czechia; University of Virginia School of Medicine, USA; Sharp Healthcare, USA.

Background Pancreatic cysts (PC) are increasingly detected through abdominal imaging, prompting exploration of alternatives such as endoscopic ultrasound-guided pancreatic cyst ablation (EUS-PCA) due to the risks and costs associated with surgery. This study conducts a systematic review and meta-analysis of EUS-PCA's short-term efficacy and complications for PC management. Methods A systematic review and meta-analysis were carried out on PubMed, Ovid, Cochrane, and TRIP electronic databases. The primary outcome was cyst resolution (partial and complete) and persistence on imaging 12 months after ablation. The secondary outcome was procedure-related adverse events. Results Eight studies were eligible for analysis. Complete cyst resolution on imaging 12 months after EUS ablation was 50% [95% CI 36, 63, I2 = 85.31%]. Partial cyst resolution was 27% [95% CI 15, 41, I2 = 87.07%], and cyst persistence was 17% [95% CI 11, 24, I2 = 62.11%]. The rate of complete resolution varied depending on the treatment agent (for ethanol 29% [95% CI 10, 53], lauromacrogol 51% [95% Cl 36, 67], ethanol and paclitaxel 63% [95% CI 48, 76], paclitaxel and gemcitabine 67% [95% CI 45, 83], ethanol, paclitaxel and gemcitabine 61% [95% CI 39, 80]). Post-procedure adverse events included abdominal pain in 4% [95% CI 0, 11], pancreatitis in 3% [95% CI 1, 5], and fever in 1% [95% CI 0, 3] of all patients. Conclusion The treatment of pancreatic cysts with EUS ablation results in acceptable levels of complete resolution, and low incidence of severe adverse events. The effectiveness of this treatment is further enhanced when chemoablative agents are employed.

AdventHealth Orlando, USA; Indiana University School of Medicine, USA.

AdventHealth Orlando, USA; University of Florida, USA; White River Junction VA Medical Center, USA; Brigham and Women's Hospital, USA; Johns Hopkins University, USA; University of Louisville, USA; University of Toronto, Canada; Baylor College of Medicine, USA; Indiana University, USA; Fox Chase Cancer Center, USA; UVA Health, USA; Queens University, Canada; Columbia University Irving Medical Center, USA; Mayo Clinic Minnesota, USA; Northwestern University, USA; Parkview Health, USA; Medical University of South Carolina, USA; Mount Sinai Health System, USA.

Objective: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. Background and Aims: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. Methods: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA (CEACAM5) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. Results: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41–59%) and lower specificities (56–96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. Conclusions: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.

Objective: We evaluated a protocolized endoscopic necrosectomy approach with a lumen-apposing metal stent (LAMS) in patients with large symptomatic walled-off pancreatic necrosis (WON) comprising significant necrotic content, with or without infection. Summary Background Data: Randomized trials have shown similar efficacy of endoscopic treatment compared with surgery for infected WON. Design: We conducted a regulatory, prospective, multicenter single-arm clinical trial examining the efficacy and safety of endoscopic ultrasound -guided LAMS with protocolized necrosectomy to treat symptomatic WON ≥6 cm in diameter with >30% solid necrosis. After LAMS placement, protocolized WON assessment was conducted and endoscopic necrosectomy was performed for insufficient WON size reduction and persistent symptoms. Patients with radiographic WON resolution to ≤ 3 cm and/or 60-day LAMS indwell had LAMS removal, then 6-month follow-up. Primary endpoints were probability of radiographic resolution by 60 days and procedure-related serious adverse events. Results: Forty consecutive patients were enrolled September 2018 to March 2020, of whom 27 (67.5%) were inpatients and 19 (47.5%) had clinical evidence of infection at their index procedure. Mean WON size was 15.0 ± 5.6 cm with mean 53.2% ± 16.7% solid necrosis. Radiographic WON resolution was seen in 97.5% (95% CI, 86.8%, 99.9%) by 60 days, without recurrence in 34 patients with 6-month follow-up data. Mean time to radiographic WON resolution was 34.1 ± 16.8 days. Serious adverse events occurred in 3 patients (7.5%), including sepsis, vancomycin-resistant enterococcal bacteremia and shock, and upper gastrointestinal bleeding. There were no procedure-related deaths. Conclusions: Endoscopic ultrasound-guided drainage with protocolized endoscopic necrosectomy to treat large symptomatic or infected walled-off necrotic pancreatic collections was highly effective and safe. Clinicaltrials.-gov no: NCT03525808.

BACKGROUND AND AIMS:We have endoscopically encountered a zone of transitional mucosa between the colonic and ileal mucosa located in a 3- to 10-mm-wide ring around the ileocecal valve (ICV) orifice. We aimed to describe the features of the ICV transitional zone mucosa.METHODS:We used videos and photographs from normal ICVs and biopsy samples from normal colonic mucosa, transitional zone mucosa, and normal ileal mucosa to characterize the endoscopic and histologic features of the ICV transitional zone mucosa.RESULTS:The ICV transitional zone is identifiable on every ICV without a circumferential adenoma or inflammation that obliterates the zone. The zone is characterized endoscopically by an absence of villi, which distinguishes it from the ileal mucosa, but the pits are more tubular and with more prominent blood vessels compared with normal colonic mucosa. Histologically, the villi of the transitional zone are blunted, and the amount of lymphoid tissue is intermediate between the colonic mucosa and ileal mucosa.CONCLUSIONS:This is the first description of the normal transitional zone of mucosa on the ICV. This zone has unique endoscopic features that should be recognized by colonoscopists and that can potentially create difficulty in identifying the margins of adenomas located on the ICV.

Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm, postulated to arise from follicular dendritic cells, with approximately 343 reported cases. Less than 100 cases of FDCS were in the gastrointestinal tract, with only four cases described in the stomach, none of them diagnosed on fine needle aspiration (FNA) cytology. We report here the first case of FDCS of the stomach diagnosed on FNA. Our patient is a 31-year-old male who presented with several years history of intermittent abdominal pain prompting occasional emergency-room visits. Imaging showed a 10.6 cm mass arising from the stomach, concerning for gastrointestinal stromal tumor. FNA cytology was performed using five passes with a 22-gauge needle. The smears were moderately cellular consisting of sheets and large, loosely cohesive clusters of ovoid to spindle cells with indistinct cytoplasmic borders and abundant cytoplasm, peppered with numerous small mature lymphocytes. The nuclei of the tumor cells were oval with finely granular chromatin with frequent nuclear grooves, pseudoinclusions, and easily recognizable mitotic figures. The tumor cells were positive for FDCS markers (CD21, CD23, and CD35).

Introduction: Acute necrotizing pancreatitis (ANP) complicates up to 15% of acute pancreatitis cases. ANP has historically been associated with a significant risk for readmission, but there are currently no studies exploring factors that associate with risk for unplanned, early (<30-day) readmissions in this patient population.Methods: We performed a retrospective review of all consecutive patients presenting to hospitals in the Indiana University (IU) Health system with pancreatic necrosis between December 2016 and June 2020. Patients younger than 18 years of age, without confirmed pancreatic necrosis and those that suffered in-hospital mortality were excluded. Logistic regression was performed to identify potential predictors of early readmission in this group of patients.Results: One hundred and sixty-two patients met study criteria. 27.7% of the cohort was readmitted within 30-days of index discharge. The median time to readmission was 10 days (IQR 5-17 days). The most frequent reason for readmission was abdominal pain (75.6%), followed by nausea and vomiting in (35.6%). Discharge to home was associated with 93% lower odds of readmission. We found no additional clinical factors that predicted early readmission.Conclusion: Patients with ANP have a significant risk for early (<30 days) readmission. Direct discharge to home, rather than short or long-term rehabilitation facilities, is associated with lower odds of early readmission. Analysis was otherwise negative for independent, clinical predictors of early unplanned readmissions in ANP.Published by Elsevier B.V. on behalf of IAP and EPC.

DESCRIPTION: The purpose of this AGA Institute Clinical Practice Update is to review the available evidence supporting and examine opportunities for future research in endoscopic ultrasound-guided vascular investigation and therapies.METHODS: This Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors who are advanced endoscopists with expertise in endoscopic ultrasound-guided vascular investigation and therapy.

Yara Sarkis: NO financial relationship with a commercial interest | Anthony Perkins: NO financial relationship with a commercial interest | Sarah Stainko: NO financial relationship with a commercial interest | Destenee Dickason: NO financial relationship with a commercial interest | Mohammad Al- Haddad: YES financial relationship with a commercial interest;Cook Endoscopy:Grant/Research Support;Creatics LLC:Grant/Research Support | John Dewitt: YES financial relationship with a commercial interest;Vyaire Medical:Grant/Research Support;Boston Scientific:Consulting

Traditionally, surgery has been advocated to remove premalignant cysts over 3 cm in size, those associated with high-risk imaging stigmata or the presence of related symptoms such as weight loss or jaundice. However, pancreatic resection is associated with frequent morbidity and rare mortality. Pancreatic cyst ablation (PCA) has been evaluated as a possible alternative to surgery or clinical observation for selected benign pancreatic cystic neoplasms (PCNs). Data from these studies show that ablation with ethanol and paclitaxel or alternatively an alcohol-free regimen of gemcitabine and paclitaxel produces imaged-defined cyst ablation in 50–65% of patients with rare complications including pancreatitis and abdominal pain.