e16484 Background: Pancreatic acinar cell carcinoma (PACC) is an ultra-rare (~1%) pancreatic malignancy. Management is often extrapolated from pancreatic ductal adenocarcinoma (PDAC) despite distinct molecular drivers. We characterize the clinicopathologic and genomic features of PACC at our center to identify precision oncology targets. Methods: A retrospective review of histologically confirmed PACC at a tertiary academic center was performed. Clinical, radiographic, pathologic, treatment, and outcome data were extracted. Standard of care next-generation sequencing (NGS) results were reviewed, with focus on potentially actionable alterations. Results: Seven patients were identified (median age 64, range 46–70; 57% male). Symptoms included abdominal pain and weight loss; notably, jaundice was absent. Pathologic evaluation demonstrated variable lymph node involvement, lymphovascular and perineural invasion, and occasional mixed acinar neuroendocrine differentiation. NGS was performed in a subset of patients and actionable alterations included 9p21.3 co-deletion (CDKN2A/B and MTAP loss), IZKF1 loss, SEC24D-BRAF fusion, and BAP1 mutation (Table 1). All were KRAS wild-type. Surgical resection was performed in three patients, and FOLFIRINOX chemotherapy was commonly used. Treatment responses varied. A swimmer plot analysis revealed that 2/7 patients had prolonged progression-free survival ( > 90months and > 200months), while the remaining patients had follow-up < 5 years. At the time of data reporting, four patients were alive without disease recurrence and under ongoing surveillance. Conclusions: Our cohort confirms PACC is molecularly distinct from PDAC, characterized by absence of KRAS mutation and high prevalence of targetable alterations. The identification of MTAP loss and BRAF alteration suggests that PACC patients should be prioritized for specific precision medicine trials (e.g., PRMT5 or MAPK inhibitors) rather than traditional PDAC regimens. Early NGS is mandatory to optimize precision treatment in this rare cancer. Patient Age Sex Presenting Symptoms Tumor Location Resection performed NGS Findings MSI Status TMB Potential Target 1 46 F Abdominal pain, nausea, bloating, fatigue Head Yes Not tested Not tested Not tested N/A 2 68 F Pruritis, abdominal pain, appetite loss, constipation/diarrhea Head Yes TP53 mutation; KRAS wild type; CDKN2A/B loss; MTAP loss; SEC24D-BRAF fusion MSS Intermediate BRAF/MEK/PRMT5 inhibitors 3 67 M Abdominal pain Head Attempted (aborted) Not tested Not tested Not tested N/A 4 70 M Flank pain and hematuria Head No Not tested Not tested Not tested N/A 5 86 F Asymptomatic (incidental lab finding) Head No BAP1 mutation MSS 6.6 EZH2 inhibitors 6 55 M Abdominal pain Tail No CDKN2 A/B loss; IKZF1 loss; MTAP loss; KRAS wild type MSS 6.8 PRMT5 inhibitors 7 57 M Asymptomatic (incidental imaging finding) Head Yes Not tested Not tested Not tested N/A

730 Background: Nectin-4, a type I transmembrane protein, is critical for adherens junction formation and maintenance. Aberrant overexpression of Nectin-4 has been observed in pancreatic ductal adenocarcinoma (PDAC) and is associated with tumor proliferation and metastasis/ Enfortumab vedotin (EV), an antibody–drug conjugate targeting Nectin-4, delivers the microtubule-disrupting agent monomethyl auristatin E to Nectin-4–expressing cells. EV is approved in urothelial carcinoma, supporting its evaluation in other tumors. Methods: This open-label, single-arm, phase II trial evaluated EV in previously treated locally advanced, recurrent, or metastatic PDAC. Pts received EV 1.25 mg/kg IV on days 1, 8, and 15 of each 28-day cycle until progression or unacceptable toxicity. Imaging was performed every 8 weeks. Mandatory biopsies were obtained pre-treatment and on-treatment (C1, D15–21). Eligible patients had ECOG PS 0–1 and ≥1 prior line of therapy. The primary endpoint was ORR. Secondary endpoints included safety, DOR, DCR, PFS and OS. Exploratory endpoints included correlation of Nectin-4 expression and tumor mutational profile with ORR. A Simon’s two-stage design required ≥3 responses among 28 evaluable patients to reject the null hypothesis. Results: As of January 2025, 43 patients were enrolled (16 female, 27 male; mean age 64.7 y), with 28 evaluable for efficacy. ORR was 10.7% (3/28; 95% CI, 2.3–28.2%), with 1 confirmed PR. Two PRs progressed at confirmatory scans (day 50–55). Prior therapies among PRs included FOLFIRINOX (n=1), FOLFIRINOX→gemcitabine based (n=1), and FOLFIRINOX→gemcitabine/nab-paclitaxel (n=1). DCR for best response was 53.6% (95% CI, 33.9–72.5%); 16-week, 24-week, and 32-week DCRs were 28.6%, 21.4%, and 17.9%. At baseline, 24/28 (85.7%) had elevated CA19-9; 13/24 achieved PR/SD. Mean CA19-9 change from baseline to week 8 was +11,701 (PD group) vs +1,400 (PR/SD group); 6/13 in PR/SD group had ≥50% decrease. Similarly, 24/28 (85.7%) had elevated CEA; 12/24 achieved PR/SD. Mean CEA change was +179 (PD) vs +13 (PR/SD); 4/12 PR/SD patients had ≥30% decrease. Among 38 pts evaluable for safety, TRAE occurred in 79.0% (30/38), and Grade 3/4 TRAE occurred in 47.4% (18/38). The most common TRAE were fatigue (40.0%, 12/30), peripheral neuropathy (26.7%, 8/30), rash maculo-papular (23.3%, 7/30), anorexia (20.0%, 6/30), and neutropenia (20.0%, 6/30). Serious TRAE were reported in 10.5%% (4/38). Only deaths were Grade 5 Pneumonitis possibly related to EV in a pt with diffuse lung mets and death due to disease progression not related to study drug. Conclusions: In this phase II study, EV showed modest antitumor activity with ORR >10% and durable disease control in a heavily pretreated PDAC. Safety was consistent with prior reports. Survival outcomes and nectin 4 biomarker analyses will be reported during the presentation. Clinical trial information: NCT05915351 .

Certepetide (aka CEND-1, LSTA1) is a tumor-penetrating peptide that binds integrin αvβ3 on tumor endothelium and neuropilin-1, triggering transcytosis to enhance intratumoral drug delivery and modulate the tumor microenvironment (TME). We report findings from resectable and borderline resectable PDAC of the CENDIFOX trial evaluating Certepetide plus mFOLFIRINOX as neoadjuvant therapy. Eligible patients with resectable and borderline resectable PDAC received neoadjuvant mFOLFIRINOX for 3 cycles followed by addition of Certepetide (3.2 mg/kg IV on Day 1) to mFOLFIRINOX every 2 weeks from cycles 4 onward for at least 6 cycles, followed by evaluation for resection. The primary objective was safety; secondary endpoints included resection rate, pathologic response, PFS, OS, and immune profiling. Correlative biopsies were obtained pre-treatment and at end of therapy. 35 patients were enrolled. No dose-limiting toxicities were observed. Common Grade ≥3 AEs included neutropenia, mucositis, fatigue, anorexia, and gastrointestinal events. Toxicities were manageable with dose reductions or delays. Most AEs were attributed to mFOLFIRINOX; no serious AEs were attributed to Certepetide. Of the 35 patients enrolled, 10 underwent pancreatic cancer resection following treatment regimen. Among these evaluable cases, the pathologic partial response rate (Tumor Regression Grade 2) was 70%, and the R0 resection rate was 50%. At limited follow-up, the 2-year OS rate was 60% (95% CI, 26%–100%), and median DFS was 12 months (95% CI, 10–NA). Immunofluorescence staining of PDAC tissue demonstrated increased post-treatment expression of CD68 (tumor-associated macrophages, TAMs) and immune checkpoints PD-1/PD-L1. Mean log-transformed CD68 intensity increased from 13.96 to 15.20; PD-1 from 12.94 to 13.57; and PD-L1 from 13.33 to 13.54, suggesting enhanced immune infiltration. Certepetide combined with mFOLFIRINOX is safe and feasible in resectable PDAC. Encouraging early OS and PFS data, high pathologic partial response rates, and correlative immune findings support further evaluation in randomized trials. Enhancement of TAMs and PD-1/PD-L1 in the tumor microenvironment supports the potential to convert PDAC from an immune-cold to an immune-hot tumor, possibly sensitizing it to immunotherapy. NCT05121038 Anup Kasi, Raed Al-Rajabi, Anwaar Saeed, Jianzheng Wu, Milind Phadnis, Shannon Bradbury, Stacey Krepel, Subhrajit Saha, Grace Li Haug, Prasad Dandawate, Rashna Madan, Mojtaba Olyaee, Amit Rastogi, Timothy Schmitt, Sean Kumer, Weijing Sun, Joaquina Baranda. CENDIFOX: Phase I/II Trial of CEND-1 (LSTA1, certepetide) with Neoadjuvant mFOLFIRINOX in Resectable and Borderline Resectable PDAC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr A070.

TPS4229 Background: Pancreatic cancer is a highly lethal disease. Despite research and drug development efforts focused on KRAS, no effective RAS inhibitors have been approved for the treatment of pancreatic cancer with KRAS mutation. PLK1 inhibition is a potential target in KRAS-mutated pancreatic cancer and may provide a new first-line treatment option. Onvansertib (also known as PCM-075 and NMS-1286937) is the first PLK1-specific adenosine triphosphate competitive inhibitor administered by oral route to enter clinical trials with proven antitumor activity in different preclinical models. Methods: This is a phase 1b/II, non-randomized, open label single arm study being conducted at the University of Kansas Cancer Center and its affiliated sites. The study is open for enrollment. Eligibility: Key inclusion includes pts with locally advanced, unresectable, or metastatic pancreatic adenocarcinoma who are treatment naïve, have adequate archival tissue for biomarker evaluation or are willing to undergo a biopsy, and have an ECOG of 0-1. Key Exclusion: Planned concomitant use of medications known to prolong the QT/QTc interval, use of strong CYP3A4 or CYP2C19 inhibitors or strong CYP3A4 inducers. Treatment Plan: The phase 1b (safety lead-in) will follow a dose de-escalation phase in which up to 2 different Onvansertib dose levels will be tested in combination with standard NALIRIFOX. Onvansertib starting dose level is 30mg orally once daily. The Phase II portion of the study will be a single-arm open-label enrollment with dosing based on the starting dose determination in the Phase Ib portion of the study (30mg or 20mg). NALIRIFOX (Nano-liposomal Irinotecan 50 mg/m2, Oxaliplatin 60 mg/m2, Leucovorin 400 mg/m2, 5-FU 2400 mg/m2) will be administered intravenously on D1 of the 14-day cycle. Onvansertib will be dosed orally on D1-5 of each 14-day cycle. Imaging will be performed at baseline and after every 4 cycles. Objectives: The primary objective of this study is to determine anti-tumor activity by measuring Overall Response Rate (ORR). The secondary objectives are to determine treatment safety based on toxicities in participants who have received at least one dose of onvansertib, to determine anti-tumor activity by Progression Free Survival (PFS), to determine anti-tumor activity by Disease Control Rate (DCR), to determine Overall Survival (OS). Statistical Plan: Simon's two-stage Optimum design will be used. The null hypothesis that the true response rate is 41% will be tested against a one-sided alternative that the true response rate is 65%. In the first stage, 10 evaluable pts will be enrolled. If there are 4 or fewer responses in these 10 pts, the study will be stopped. Otherwise, 11 additional evaluable pts will be accrued for a total of 21 evaluable pts. The null hypothesis will be rejected if 12 or more responses are observed in 21 evaluable pts. Clinical trial information: NCT06736717 .

329 Background: Surgical rection is the only potentially curative intervention for locally advanced adenocarcinoma of esophagus, GEJ and stomach. Results from various studies have demonstrated the benefits of perioperative treatment including neoadjuvant and adjuvant chemotherapy or chemoradiation, however, there is lack of universally accepted standard. Recent data demonstrated the benefit of immune checkpoint inhibitor in adjuvant setting in patients who had pre-operative chemoradiation. This single arm phase 2 trial is aimed to evaluate efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in combination with mFOLFOX in patients with potentially resectable adenocarcinoma of distal esophagus, GEJ and stomach with the primary objectives of pathological response rate (ypRR with tumor regression score, TRS ≤ 2). We are reporting the preliminary analyses while the study nears completion. Methods: Patients with newly diagnosed locally advanced (T1N1-3M0 or T2-3NanyM0), potentially resectable adenocarcinoma of distal esophagus, GEJ and stomach by PET, EUS, CT C/A/P and staging laparoscopy were treated with pre-operative mFOLFOX6 (oxaliplatin 85mg/m2, Leucovorin 400mg/m2, 5-FU bolus 400mg/m2, and 5-FU 2400mg/m2 infusion every 2 weeks) for 4 cycles and pembrolizumab (200 mg IV q3week) for 3 cycles. Patients with no evidence of metastatic disease by PET and CT C/A/P who are eligible for resection underwent surgery. Post-operative treatment consisted of 4 cycles of mFOLFOX and 13 cycles of pembrolizumab 4-8 weeks postoperatively. Results: Of 35 patients enrolled (age range 44-86, mean of 65 years; with male:female of 28:7), 33 finished preoperative treatment, 26 had curative intended operations with R0 resection for all, 1 is pending for surgery, and 2 are still on pre-operative treatment. 5 of 26 pts achieved ypCR (19% regression score of 0). All except 2 patients (24/26, 92%) had shown pathologic response to the treatment with TRS ≤ 2. 23/26 (88%) finished post-operative treatment. 20 patients completed all planned treatment with an average follow-up of 22.7 months. Amount them, 2 patients had recurrence/ metastatic disease (at 9 and 10 months, respectively) with 1 died 23.3 months from enrollment, and the rest are all free of disease. G3/4 toxicities were reported in 19 of all 35 treated patients. There were no unexpected toxicities. Conclusions: The combination of FOLFOX and pembrolizumab as peri-operative (pre- and post-operative) therapy in patients with locally advanced adenocarcinoma of distal esophagus, GEJ and stomach is safe and preliminary benefit data are very encouraging with ypRR of 92% and ypCR of 19% and supporting the combination of chemotherapy and Immune checkpoint inhibitor at perioperative setting. Clinical trial information: NCT03488667.

Bleeding from the gastrointestinal tract can contribute to the development of iron deficiency anemia (IDA) among individuals without another obvious source of bleeding. In order to identify patients most likely to benefit from examination of the small bowel, our aim was to create a risk score for positive video capsule endoscopy (VCE) in IDA utilizing a multicenter collection of studies. We performed a retrospective multicenter study utilizing VCE studies performed for an indication of IDA between 1/1/2005 and 7/31/2018. VCE findings were graded based on the P0–P2 grading system. The primary outcome of interest was a positive (P2) VCE. Data were analyzed with Student’s t test for continuous variables and the Fisher’s exact test for categorical variables. Logistic regression was used to identify independent associations with positive VCE. In total, 765 VCE procedures were included with 355 (46.5

Introduction: Bouveret syndrome is a rare variant of gallstone ileus caused by an acquired fistula via the gallbladder and either the stomach or duodenum. Fistulization occurs due to inflammation and pressure via gallstones following acute cholecystitis which may result in an ischemic tear. There are approximately 300 documented case reports over the past 50 years, as Bouveret syndrome accounts for 1%-3% of cases of gallstone ileus and affects < 0.5% of patients with gallstones. The nonspecific symptoms make diagnosis difficult, as the majority of patients present with nausea, emesis, and abdominal pain. Case Description/Methods: A 77-year-old woman with prior medical history of complicated diverticulitis with colovesical fistula status post surgical repair presented with 2-3 weeks of nausea, emesis, abdominal pain and distention, and constipation. CT abdomen and MRCP revealed a cholecystoduodenal fistula and obstructing gallstone in the duodenum. EGD findings included an obstructing stone occupying the entire lumen of the third part of the duodenum and circumferential ulcerations from presumed stone impaction sites. Conservative management with NPO, IV fluids, and NG tube decompression was started prior to transfer. ERCP revealed a 12-15 mm cholecystoduodenal fistula not amenable to endoscopic closure. A large occlusive stone measuring approximately 5-7 cm was present in the third portion of the duodenum. The stone was fragmented via snare, electrohydraulic and mechanical lithotripsy, and balloon dilation. Multiple stones measuring 8-15 mm were present in the second portion of the duodenum and were extracted with Roth net. Additional stones were moved to the stomach and broken down further with lithotripsy before removal with Roth net. The patient's symptoms resolved, and she was discharged in stable condition (Figure 1). Discussion: Bouveret syndrome typically presents as similar to a bowel obstruction in elderly femans with a history of cholelithiasis. Imaging may reveal Rigler’s triad (dilated stomach, pneumobilia, radio-opaque shadow), although, this triad is only present in 40%-50% of cases. Management includes endoscopic removal, lithotripsy, or surgical management such as gastrotomy. Mortality is increased with surgical intervention and clinicians should attempt to treat Bouveret syndrome endoscopically +/- lithotripsy if able, as mortality is already estimated at 12%-30%. Given such high mortality, this should be included on a differential in an elderly woman with a history of cholelithiasis presenting with gastrointestinal symptoms.Figure 1.: Endoscopic imaging of obstructing gallstones present in second and third portions of the duodenum.

University of California, Irvine, USA; Brigham and Women's Hospital Department of Medicine, USA; Weill Cornell Medicine, USA; The Chinese University of Hong Kong, Hong Kong; University of Virginia School of Medicine, USA; The University of Kansas Health System, USA; Royal Brisbane and Women's Hospital, Australia; Cook Research Incorporated, USA.

TPS4205 Background: MRD detected by presence of circulating tumor DNA (ctDNA) after intended curative treatment is associated with high risk of relapse in pancreatic cancer. Early treatment of patients with presence of ctDNA after completion of surgery +/- adjuvant therapy may offer an opportunity to clear ctDNA and improve outcomes. TG01 is a RAS-neoantigen peptide vaccine adjuvanted by QS-21 (Stimulon) targeting the seven most frequent codon 12-13 RAS mutations. TG01 has previously demonstrated ability to activate mutant RAS specific CD4+ and CD8+ T-cell responses in vaccinated patients and repeated TG01 dosing in resected pancreatic cancer was found to be well tolerated and associated with a median OS of 33.4 months (95% CI 24.0, 45.8) 1,2 . Checkpoint inhibitors as single agents have not shown anti-tumor activity in pancreatic cancer, suggesting that a priming agent inducing tumor-specific T-cells may be required to support efficacy. Balstilimab is a human monoclonal antibody targeting programmed cell death protein 1 (PD-1) which is intended to reverse the immunosuppressive effects of this signaling pathway in the context of tumor immuno-surveillance by T-cells. Methods: Design: A two-arm, open-label, phase II randomized trial of TG01/QS-21 vaccine or TG01/QS-21 vaccine plus balstilimab (n=12 per arm, N=24) with surgically resected Stage 1-3 RAS mutant PDAC who are MRD+ following completion of standard adjuvant chemotherapy. Assay: MRD is detected by a commercially available ctDNA assay (Signatera, Natera). Somatic variants are identified by whole–exome sequencing of the primary tumor and the matched normal (whole blood) sample and a bespoke assay of up to 16 clonal, somatic variants are generated for each patient. This “tumor signature” will be monitored in plasma throughout the study. Treatment schedule: A priming phase of six vaccine administrations once every two weeks followed by a maintenance phase of administrations once every 8 weeks for up to 51 weeks. Balstilimab will be administered every 2 weeks for up to 51 weeks beginning at week 3. Imaging assessment will be done every 12 weeks. Eligibility: Surgically resected pancreatic adenocarcinoma with pathogenic RAS mutation, and no evidence of recurrent disease on baseline imaging. Inclusion criteria also include ECOG PS 0-1, and positive Signatera ctDNA MRD. Objectives: The primary objective is to assess the 6-month molecular disease control rate as defined by ctDNA stable, decreased or cleared. Secondary objectives include safety of TG01/QS-21 with or without balstilimab, 6 and 12-month DFS rate in each cohort, as well as correlation between the depth of molecular response and DFS. Exploratory: changes in clonality of RAS mutations and assess immune response. Enrollment is ongoing. 1) Gjertsen MK et al. Int J Cancer 1997, 72(5) 784-90. 2) Palmer DH et al. Br J Cancer 2020 122:971-77. Clinical trial information: NCT05638698 .

Background & Aims: Acetaminophen (APAP) overdose remains a frequent cause of acute liver failure, which is generally accompanied by increased levels of serum bile acids (BAs). However, the pathophysiological role of BAs remains elusive. Herein, we investigated the role of BAs in APAP-induced hepatotoxicity. Methods: We performed intravital imaging to investigate BA transport in mice, quantified endogenous BA concentrations in the serum of mice and patients with APAP overdose, analyzed liver tissue and bile by mass spectrometry and MALDI-mass spectrometry imaging, assessed the integrity of the blood-bile barrier and the role of oxidative stress by immunostaining of tight junction proteins and intravital imaging of fluorescent markers, identified the intracellular cytotoxic concentrations of BAs, and performed interventions to block BA uptake from blood into hepatocytes. Results: Prior to the onset of cell death, APAP overdose causes massive oxidative stress in the pericentral lobular zone, which coincided with a breach of the blood-bile barrier. Consequently, BAs leak from the bile canaliculi into the sinusoidal blood, which is then followed by their uptake into hepatocytes via the basolateral membrane, their secretion into canaliculi and repeated cycling. This, what we termed 'futile cycling' of BAs, led to increased intracellular BA concentrations that were high enough to cause hepatocyte death. Importantly, however, the interruption of BA re-uptake by pharmacological NTCP blockage using Myrcludex B and Oatp knockout strongly reduced APAP-induced hepatotoxicity. Conclusions: APAP overdose induces a breach of the blood-bile barrier which leads to futile BA cycling that causes hepatocyte death. Prevention of BA cycling may represent a therapeutic option after APAP intoxication. Lay summary: Only one drug, N-acetylcysteine, is approved for the treatment of acetaminophen overdose and it is only effective when given within similar to 8 hours after ingestion. We identified a mechanism by which acetaminophen overdose causes an increase in bile acid concentrations (to above toxic thresholds) in hepatocytes. Blocking this mechanism prevented acetaminophen-induced hepatotoxicity in mice and evidence from patients suggests that this therapy may be effective for longer periods after ingestion compared to N-acetylcysteine. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

Introduction: Patients with severe pancreatitis routinely develop walled off necrotic collections that require a procedure known as a Cystogastrostomy. This procedure creates an opening between the necrotic collection and the stomach to help facilitate removal of necrotic tissue. Serial endoscopic necrosectomies are often required to remove all the necrotic debris. Endoscopic powered resection (EPR) is a procedure used to perform mechanical mucosectomies of polyps within the gastrointestinal tract. This method of mechanical resection has recently been applied to endoscopic pancreatic necrosectomy and debridement. The following case highlights a novel application of EPR in performing pancreatic necrosectomies following cystogastrostomy to help decrease the number of repeat procedures. Case Description/Methods: A 47-year-old patient with past medical history of asthma, hyperlipidemia, breast cancer, recent hypertriglyceridemia-induced acute pancreatitis initially presented with fevers, chills and abdominal pain. Initial labs remarkable for leukocytosis WBC 19.7 K/UL. CT scan showed concern for new infected peripancreatic necrotic fluid collection measuring 9.5 x 6.0 cm extending inferiorly along the left paracolic gutter (Figure). An EUS with cystogastrostomy and endoluminal stent placement was performed to facilitate drainage of the necrotic collection. Repeat EGD with both EPR and snare necrosectomy was performed the following week. CT scan completed 2 days later showed marked interval decrease in the multiloculated peripherally enhancing peripancreatic air and fluid collection now measuring 7.3 x 4.0 cm. The patient underwent second necrosectomy one week later with EPR and snare mechanical debridement which revealed an 18 cm cyst cavity. Significant amount of necrotic tissue removed at that time and patient scheduled for repeat EGD in 3 weeks with endoluminal stent retreatment. Discussion: Endoscopic pancreatic necrosectomy is often performed 4 weeks after the initial episode of pancreatitis to allow formation of a true, walled off necrotic collection. When performing endoscopic necrosectomy of large collections, at least 5 procedures are often required to completely removal all necrotic tissue. As shown in this case, implementation of EPR with traditional endoscopic snare necrosectomy can facilitate efficient removal of debris and help decrease the number of repeat necrosectomies. This could ultimately improve resource utilization and have major implications on overall patient morbidity and mortality.Figure 1.: A. Large (9.5 x 6.0 cm) peripancreatic necrotic fluid collection with inferior extension into left paracolic gutter. B. Marked interval decrease in multiloculated necrotic collection following second EPR necrosectomy with endoluminal stent visualized.

Introduction: Gastric neuroendocrine tumors (gNETs) are rare malignancies which arise from enterochromaffin-like cell (ECL) precursors within the gastric mucosa. There are 4 classifications of gNETs primarily based on size, number of lesions, serum gastrin level, tissue invasion, proliferation index and immunohistochemistry. Applying a combination of factors, gNETs are typically classified into one of these four categories with relative ease. The following case highlights an exceedingly rare hybrid presentation of gNET containing features of all four classification subtypes. Case Description/Methods: A 78-year-old female with a past medical history of hypertension, diabetes mellitus, chronic kidney disease and gastroesophageal reflux disease (GERD) initially presented with worsening symptoms of GERD. The patient denied any alarm symptoms but did endorse persistence of reflux symptoms despite proton pump inhibitor use. Screening EGD with EUS showed polyps which were removed with mucosal resection. Initial pathology illustrated well differentiated gNET. She underwent a DOTA-TATE PET/CT scan which showed heterogenous uptake involving the gastric body reflecting focal gNET without evidence of metastatic disease. The patient underwent total gastrectomy and esophagojejunostomy with upper GI series revealing no evidence of anastomotic leak. On subsequent pathology, at least 46 semi pedunculated gastric polyps were identified of which the greatest tumor dimension was 0.6 cm with a mitotic rate less than 2 mitoses/2mm2. Pathology and immunohistochemistry revealed well differentiated gNET, grade 1 and 2, staining positivity for Chromogranin A (CgA), synaptophysin, CD56, and CAM 5.2 with a Ki67 proliferation index > 6%. Patient’s serum gastrin was within normal limits at 51pg/ml and 24-hour urine 5-HIAA revealed a normal level of 5.7 mg/24hr. She was referred to a geneticist for massive parallel sequencing also known as next generation sequencing (NGS). (Figure) Discussion: This case displays a rare, hybrid presentation of gNET with features of all four classification subtypes. The positive synaptophysin, normal serum gastrin and increased Ki67 index are characteristic of gNET Type 3 and 4 which carry a poor prognosis. Type 3 and 4 however, are typically large ( >2cm), single tumors. This patient had many, smaller tumors with positive CgA staining commonly seen in Type 1 and 2. Hybrid gNETs are extremely uncommon neoplasms which create both a diagnostic and therapeutic challenge requiring a truly multidisciplinary effort.Figure 1.: Ga-68 Dotatate PET-CT showing diffuse heterogenous uptake in the gastric body.

TPS4195 Background: The efficacy of chemotherapy is often compromised due to poor penetration of drugs in solid tumors. The tumor microenvironment, which is characterized by dense extracellular matrix‐rich stroma that creates a physical barrier to penetration of anti‐cancer drugs, is especially pronounced in Pancreatic Ductal Adenocarcinoma (PDAC) and in peritoneal metastases from Colorectal/Appendiceal Adenocarcinoma. CEND‐1 is a tumor‐penetrating peptide (scientifically also known as iRGD) that has preclinically demonstrated to enhance the tumor penetration of chemotherapy agents through binding and activation of alphav-integrins and neuropilin‐1 (NRP-1). The 2-step mechanism leads to a higher delivery and concentration of chemotherapeutics selectively in the tumor, while sparing normal tissue. Hence CEND-1 therapy has the potential to improve the efficacy of anti‐cancer therapies and reduce side effects through increased tumor access, specificity, and sensitivity. We hypothesize that CEND‐1 may become a powerful adjuvant that safely enhances standard anti‐neoplastic therapy in the neoadjuvant setting for the above populations. Methods: A safety lead-in 6-9 patients (Phase Ib) will be followed by an open label, single arm, parallel (3 cohorts) Phase IIa study. A total of 50 patients (20 PDAC, 15 colorectal/appendiceal with peritoneal metastases, 15 oligometastatic colorectal) will be enrolled. A starting CEND-1 dose of 3.2 mg/kg in combination with the standard doses of FOLFIRINOX (+/- Panitumumab if RAS/RAF wild type) will be used for the safety lead-in. CEND-1 dose will be lowered for Phase IIa if > 1/6 patients experienced DLTs. Participants enrolled will receive standard doses of FOLFIRINOX q2w +/- Panitumumab q2w 6mg/kg IV q2w (14-day cycles) for Cycles 1-3. After a subsequent research biopsy, the CEND-1 + chemotherapy combo will be continued at RP2D q2w for cycles 4-6, followed by CEND-1 +/- Panitumumab ̃72h prior to resection. Assessment of tumor response using RECIST v1.1 will be done every 3 cycles. Up to 10 patients may receive Panitumumab. Eligible Pts are untreated, newly diagnosed, resectable/borderline resectable PDAC or colorectal/appendiceal adenocarcinoma with peritoneal metastases or oligometastases eligible for cytoreductive surgery, as determined by multidisciplinary evaluation. Inclusion criteria also include ECOG PS 0-1, adequate organ function, measurable or evaluable disease. Primary objectives are safety and biological activity of CEND‐1. Secondary objectives include ORR, R0 resection rate, DFS, OS. Exploratory objectives include pathologic response, tissue immune response, EGFR expression, tumor tissue-to-plasma concentration of Panitumumab pre and post CEND-1 treatment. Enrollment to the CENDIFOX trial is currently ongoing. Clinical trial information: NCT05121038.

Introduction: Schwannomas are tumors which originate from Schwann cells responsible for fabricating myelin. Although Schwannomas are the most common benign peripheral nerve tumor in adults, there are several variants which are remarkably less common. Pancreatic schwannomas are an exceedingly rare type of nerve sheath tumor which arise from either sympathetic or parasympathetic vagal nerve fibers within the pancreas. In 2017, only 68 cases of pancreatic schwannoma had been reported in the preceding forty years with most occurring in the pancreatic head and body. In this case, we discuss an extraordinarily uncommon presentation of a pancreatic tail schwannoma in an asymptomatic 58-year-old female. Case Description/Methods: A 58-year-old female with a past medical history of hypertension and hypothyroidism presented with findings of a 2 cm exophytic pancreatic tail lesion seen on prior CT imaging (Figure). The patient reportedly had a strong family history of aortic aneurysms and was found to have a right renal lesion on screening CT. She subsequently underwent CT abdomen and pelvis which revealed a lesion concerning for pancreatic tail malignancy. Endoscopic ultrasound (EUS) was performed which showed a 17 x 20 mm isoechoic peripheral pancreatic tail lesion. Fine needle aspiration (FNA) was performed which revealed spindle cells concerning for malignancy. Pathology and immunohistochemistry were inconclusive due to scant FNA aspirate obtained during EUS. Patient was taken to the operating room for exploratory laparotomy with distal pancreatectomy and splenectomy. Pathology of resected pancreatic mass showed typical histology with nuclear palisading and thick-walled vessels. Immunohistochemical staining supported the diagnosis of Schwannoma with diffuse, strong positivity for S-100 and SOX10 as well as negative staining for desmin, smooth muscle actin, CD34, pancytokeratin, CD117 and DOG1. Discussion: Pancreatic schwannoma most commonly presents with abdominal pain although 30% of cases are found in asymptomatic patients with lesions discovered incidentally on screening CT scans. Although these lesions rarely display malignant transformation, they pose a significant diagnostic dilemma despite advances in radiographic imaging modalities. Endoscopic ultrasound is often limited by insufficient specimen collection and the preoperative diagnosis often becomes quite difficult. Enucleation of tumor is typically a sufficient therapeutic modality however radical resection is often required to establish the definitive diagnosis.Figure 1.: CT scan showing 2 cm exophytic pancreatic tail lesion (red arrow).

Background and Aims Reports on fluorescent in situ hybridization (FISH) of pancreatobiliary strictures have shown a wide range of sensitivities for malignancy detection. Our aim was to determine the sensitivity and specificity at our institution of biliary brushings, forceps biopsies, fine needle aspirations, FISH, and their combinations. Methods The study entailed a retrospective review of all cases with pancreatobiliary stricture specimens at our institution over a 5-year period. The medical record for each case was reviewed to independently confirm the presence or absence of malignancy. Sensitivities and specificities were calculated for each method. Results The cohort consisted of 181 sampling procedures from 154 patients. Of the patients, 39 (25.3%) had primary sclerosing cholangitis (PSC) and 41 (26.6%) had malignancy. Brush cytology sensitivity ranged from 24 to 63%. Forceps biopsy sensitivity ranged from 24 to 49%. FNA sensitivity ranged from 32 to 60%. Brush FISH ranged from 58 to 95%. Specificity was 99% for brush FISH and 100% for all other methods. The one false positive was an isolated FISH result in a case of PSC. Conclusion FISH should be performed since it is more sensitive than all other methods and nearly perfect in specificity outside the context of PSC. In PSC, isolated positive FISH results should be interpreted with caution.

Pancreatobiliary strictures are a common source of false negatives for malignancy detection. UroVysion is more sensitive than any other method but remains underutilized because of conflicting sensitivities and specificities due to a lack of standardized cutoff criteria and confusion in interpreting results in the context of primary sclerosing cholangitis. We set out to determine the sensitivities and specificities of UroVysion, brushing cytology, forceps biopsies, and fine needle aspiration (FNAs) for pancreatobiliary stricture malignancy detection. A retrospective review was performed of all biopsied pancreatobiliary strictures at our institution over 5 years. UroVysion was unquestionably the most sensitive method and all methods were highly specific. Sensitivity was highest while maintaining specificity when a malignant interpretation was limited to cases with 5+ cells with the same polysomic signal pattern and/or loss of one or both 9p21 signals. Only UroVysion detected the metastases and a neuroendocrine tumor. In reviewing and analyzing the signal patterns, we noticed trends according to location and diagnosis. Herein we describe our method for analyzing signal patterns and propose cutoff criteria based upon observations gleaned from such analysis.