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Early detection of pancreatic cancer (PC) remains challenging largely due to the low population incidence and few known risk factors. However, screening in at-risk populations and detection of early cancer has the potential to significantly alter survival. In this study, we aim to develop a predictive model to identify patients at risk for developing new-onset PC at two and a half to three year time frame . We used the Electronic Health Records (EHR) of a large medical system from 2000 to 2021 (N = 537,410). The EHR data analyzed in this work consists of patients’ demographic information, diagnosis records, and lab values, which are used to identify patients who were diagnosed with pancreatic cancer and the risk factors used in the machine learning algorithm for prediction. We identified 73 risk factors of pancreatic cancer with the Phenome-wide Association Study (PheWAS) on a matched case–control cohort. Based on them, we built a large-scale machine learning algorithm based on EHR. A temporally stratified validation based on patients not included in any stage of the training of the model was performed. This model showed an AUROC at 0.742 [0.727, 0.757] which was similar in both the general population and in a subset of the population who has had prior cross-sectional imaging. The rate of diagnosis of pancreatic cancer in those in the top 1 percentile of the risk score was 6 folds higher than the general population. Our model leverages data extracted from a 6-month window of time in the electronic health record to identify patients at nearly sixfold higher than baseline risk of developing pancreatic cancer 2.5–3 years from evaluation. This approach offers an opportunity to define an enriched population entirely based on static data, where current screening may be recommended.

Since its emergence as a diagnostic modality in the 1980s, endoscopic ultrasound (EUS) has provided the clinician profound access to gastrointestinal organs to aid in the direct visualization, sampling, and subsequent identification of pancreatic pathology. In recent years, advancements in EUS as an interventional technique have promoted the use of local ablative therapies as a minimally invasive alternative to the surgical management of pancreatic neuroendocrine tumors (pNETs) and pancreatic cystic neoplasms (PCNs), especially for those deemed to be poor operative candidates. EUS-guided local therapies have demonstrated promising efficacy in addressing a spectrum of pancreatic neoplasms, while also balancing local adverse effects on healthy parenchyma. This article serves as a review of the current literature detailing the mechanisms, outcomes, complications, and limitations of EUS-guided local ablative therapies such as chemical ablation and radiofrequency ablation (RFA) for the treatment of pNETs and PCNs, as well as a discussion of future applications of EUS-guided techniques to address a broader scope of pancreatic pathology.

Pancreatic cysts are often found incidentally on imaging tests for other indications. Imaging, symptom assessment, and laboratory tests can help distinguish benign cysts from those associated with a risk of malignant transformation.

Background Radiofrequency ablation of malignant biliary strictures has been offered for the last 3 years, but only limited data have been published. Aim To assess the safety, efficacy, and survival outcomes of patients receiving endoscopic radiofrequency ablation. Methods Between April 2010 and December 2013, 69 patients with unresectable neoplastic lesions and malignant biliary obstruction underwent 98 radiofrequency ablation sessions with stenting. Results A total of 69 patients (22 male, aged 66.1 ± 13.3) were included in the registry. The etiology of malignant biliary stricture included unresectable cholangiocarcinoma ( n  = 45), pancreatic cancer ( n  = 19), gallbladder cancer ( n  = 2), gastric cancer ( n  = 1), and liver metastasis from colon cancer ( n  = 3). Seventy-eight percentage of patients had prior chemotherapy. All strictures were stented post-radiofrequency ablation with either plastic stents or metal stents. The mean stricture length treated was 14.3 mm. There was a statistically significant improvement in stricture diameter post-ablation ( p  < 0.0001). The likelihood of stricture improvement was significantly greater in pancreatic cancer-associated strictures [RR 1.8 (95 % 1.03–5.38)]. Seven patients (10 %) had adverse events, not linked directly to radiofrequency ablation. Median survival was 11.46 months (6.2–25 months). Conclusion Radiofrequency ablation is effective and safe in malignant biliary obstruction and seems to be associated with improved survival.

Background Genetic testing is recommended for all pancreatic ductal adenocarcinoma (PDAC) patients. Prior research demonstrates that multidisciplinary pancreatic cancer clinics (MDPCs) improve treatment‐ and survival‐related outcomes for PDAC patients. However, limited information exists regarding the utility of integrated genetics in the MDPC setting. We hypothesized that incorporating genetics in an MDPC serving both PDAC patients and high‐risk individuals (HRI) could: (1) improve compliance with guideline‐based genetic testing for PDAC patients, and (2) optimize HRI identification and PDAC surveillance participation to improve early detection and survival. Methods Demographics, genetic testing results, and pedigrees were reviewed for PDAC patients and HRI at one institution over 45 months. Genetic testing analyzed 16 PDAC‐associated genes at minimum. Results Overall, 969 MDPC subjects were evaluated during the study period; another 56 PDAC patients were seen outside the MDPC. Among 425 MDPC PDAC patients, 333 (78.4%) completed genetic testing; 29 (8.7%) carried a PDAC‐related pathogenic germline variant (PGV). Additionally, 32 (9.6%) met familial pancreatic cancer (FPC) criteria. These PDAC patients had 191 relatives eligible for surveillance or genetic testing. Only 2/56 (3.6%) non‐MDPC PDAC patients completed genetic testing (p < 0.01). Among 544 HRI, 253 (46.5%) had a known PGV or a designation of FPC, and were eligible for surveillance at baseline; of the remainder, 15/291 (5.2%) were eligible following genetic testing and PGV identification. Conclusion Integrating genetics into the multidisciplinary setting significantly improved genetic testing compliance by reducing logistical barriers for PDAC patients, and clarified cancer risks for their relatives while conserving clinical resources. Overall, we identified 206 individuals newly eligible for surveillance or genetic testing (191 relatives of MDPC PDAC patients, and 15 HRI from this cohort), enabling continuity of care for PDAC patients and at‐risk relatives in one clinic. Genetic testing is recommended for all pancreatic ductal adenocarcinoma (PDAC) patients. Limited information exists regarding the utility of integrated genetics in the multidisciplinary pancreatic cancer clinic setting. We found that integrating genetics into the multidisciplinary setting significantly improved genetic testing compliance by reducing logistical barriers for PDAC patients, and clarified cancer risks for their relatives while conserving clinical resources.

ObjectiveLong-standing chronic pancreatitis is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). Interleukin-1β (IL-1β) has been associated in PDAC with shorter survival. We employed murine models to investigate the mechanisms by which IL-1β and chronic pancreatitis might contribute to PDAC progression.DesignWe crossed LSL-Kras +/G12D;Pdx1-Cre (KC) mice with transgenic mice overexpressing IL-1β to generate KC-IL1β mice, and followed them longitudinally. We used pancreatic 3D in vitro culture to assess acinar-to-ductal metaplasia formation. Immune cells were analysed by flow cytometry and immunohistochemical staining. B lymphocytes were adoptively transferred or depleted in Kras-mutant mice. B-cell infiltration was analysed in human PDAC samples.ResultsKC-IL1β mice developed PDAC with liver metastases. IL-1β treatment increased Kras+/G12D pancreatic spheroid formation. CXCL13 expression and B lymphocyte infiltration were increased in KC-IL1β pancreata. Adoptive transfer of B lymphocytes from KC-IL1β mice promoted tumour formation, while depletion of B cells prevented tumour progression in KC-IL1β mice. B cells isolated from KC-IL1β mice had much higher expression of PD-L1, more regulatory B cells, impaired CD8+ T cell activity and promoted tumorigenesis. IL-35 was increased in the KC-IL1β pancreata, and depletion of IL-35 decreased the number of PD-L1+ B cells. Finally, in human PDAC samples, patients with PDAC with higher B-cell infiltration within tumours showed significantly shorter survival.ConclusionWe show here that IL-1β promotes tumorigenesis in part by inducing an expansion of immune-suppressive B cells. These findings point to the growing significance of B suppressor cells in pancreatic tumorigenesis.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) presents a redoubtable challenge due to late-stage diagnosis and limited treatment options, necessitating innovative therapeutic strategies. Methods Here, we report our results investigating the safety and efficacy of talimogene laherparepvec (T-VEC), an FDA-approved oncolytic herpes simplex virus type 1, in patients with advanced PDAC. Nine patients with treatment-refractory advanced PDAC received escalating doses of T-VEC via endoscopic injection. Results While no objective responses were observed, stable disease was achieved in 44% of patients, with a median overall survival of 7.8 months, including one patient who survived 28 months. Adverse events were manageable, with the maximum tolerated dose determined to be 108 PFU/mL. Conclusion Our findings underscore the feasibility of intratumoral T-VEC administration in advanced PDAC. Further investigation, particularly in combination with immunotherapies administered systemically is warranted to more optimally assess T-VEC in this challenging malignancy. ClinicalTrials.gov Identifier: NCT03086642. Results of a study investigating the safety and efficacy of talimogene laherparepvec in patients with advanced pancreatic ductal adenocarcinoma are reported.

Introduction Intussusception (IS) is rare in adults. However, the more frequent use of cross-sectional imaging has resulted in an increase in its detection. Because of the reported association with celiac disease, we determined the prevalence of IS among a cohort with celiac disease. Methods An anonymized prospectively maintained celiac disease database and radiological database were reviewed. Results Of a total of 880 patients, 14 (age 47 ± 17.5 years; 50% female) had IS that was detected by CT in 10, capsule endoscopy in three, and barium studies in two. The reason for evaluation was abdominal pain in 78% (11/14), whereas in the remainder (3/14) were incidental. IS was the initial manifestation of celiac disease in 57% (8/14). Two patients were found to have lead-point intussusceptions and both had small-bowel adenocarcinoma, and 10/14 had severe villous atrophy (subtotal or total). Among those with established celiac disease, IS was detected early, within 3 years of diagnosis. Follow-up was available for 11 patients, 9 of who adhered strictly to a gluten-free diet, and six had no recurrence. Among all the patients diagnosed with IS on radiologic studies at our institution, 45 were considered to have idiopathic IS. Only two of these patients had evaluation for celiac disease. Conclusion IS occurs in celiac disease. It may be the initial presentation and is associated with abdominal pain. Adenocarcinoma needs to be excluded. The majority of patients do not have recurrent symptoms after adherence to a gluten-free diet. Celiac disease should be considered more frequently when IS is encountered.