The polymeric fluoropyrimidine CF10 overcomes limitations of 5-FU in pancreatic ductal adenocarcinoma cells through increased replication stress.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease soon to become the second leading cause of cancer deaths in the US. Beside surgery, current therapies have narrow clinical benefits with systemic toxicities. FOLFIRINOX is the current standard of care, one component of which is 5- Fluorouracil (5-FU), which causes serious gastrointestinal and hematopoietic toxicities and is vulnerable to resistance mechanisms.

Assessing Influence of Mismatch Repair Mutations on Survival in Patients After Resection of Pancreatic Ductal and Periampullary Adenocarcinoma.

: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States. Previous studies have indicated that microsatellite instability and deficient mismatch repair (MMR) may be associated with improved survival in patients with pancreatic cancer. Here, we aim to investigate the impact of deficient MMR (dMMR) status on oncologic outcomes in patients after resection of PDAC and periampullary adenocarcinoma.

Clinical and Financial Validation of the International Study Group for Pancreatic Surgery (ISGPS) Definition of Post-Pancreatectomy Acute Pancreatitis (PPAP): International Multicenter Prospective Study.

Objective: To validate the ISGPS definition and grading system of PPAP after pancreatoduodenectomy (PD).

Summary Background Data: In 2022, the International Study Group for Pancreatic Surgery (ISGPS) defined post-pancreatectomy acute pancreatitis (PPAP) and recommended a prospective validation of its diagnostic criteria and grading system.

Methods: This was a prospective, international, multicenter study including patients undergoing PD at 17 referral pancreatic centers across Europe, Asia, Oceania, and the United States.

Pancreaticoduodenectomy after endoscopic ultrasound-guided lumen apposing metal stent (LAMS): A case series evaluating feasibility and short-term outcomes.

Introduction: Endoscopic ultrasound (EUS)-guided lumen-apposing metal stents (LAMS) represent a novel tool in therapeutic endoscopy. However, the presence of LAMS may dissuade surgeons from operations with curative-intent. We report three clinical scenarios with deployment of LAMS in patients that subsequently underwent pancreaticoduodenectomy (PD).

The Financial Implications of Pancreatic Surgery: The Hospital Is the Big Winner, Not the Surgeon!

Background: High-volume pancreatic surgery centers require a significant investment in expertise, time, and resources to achieve optimal patient outcomes. A detailed understanding of the economics of major pancreatic surgery is limited among many clinicians and hospital administrators. A greater consideration of these financial aspects may in fact have implications for enhancing clinical care and for a broader sustainability of high-volume pancreatic surgery programs.

Major Pancreatic Resection Increases Bone Mineral Density Loss, Osteoporosis, and Fractures.

Objective: To assess whether long-term survivors of pancreatic surgery show increased risk to develop impaired bone mineral density, osteoporosis, and vitamin D deficiency.

Background: Pancreatic resection poses a risk for malabsorption of fat-soluble vitamins and other micronutrients essential for bone mineralization. Here, we evaluated the long-term effects of pancreatic resection on bone mineral density (BMD) and its clinical sequelae.

The Clinical Implications of KRAS Mutations and Variant Allele Frequencies in Pancreatic Ductal Adenocarcinoma.

The KRAS proto-oncogene is a major driver of pancreatic tumorigenesis and is nearly ubiquitously mutated in pancreatic ductal adenocarcinoma (PDAC). KRAS point mutations are detected in over 90% of PDAC cases, and these mutations have been shown to be associated with worse therapy response and overall survival. Pathogenic KRAS mutations are mostly limited to codons 12, 13 and 61, with G12D, G12V, G12R, Q61H, and G13D accounting for approximately 95% of the mutant cases.

Peripancreatic fluid collections following distal pancreatectomy and splenectomy-when is intervention warranted?

Background: Peripancreatic fluid collections after distal pancreatectomy and splenectomy are commonly identified on postoperative cross-sectional imaging. This study aimed to determine the incidence, natural history, and indications for intervention.

Methods: We conducted a retrospective review of patients with peripancreatic fluid collections after distal pancreatectomy with or without splenectomy between 2013 and 2018, approved by our institutional review board.

Impact of antecolic vs transmesocolic reconstruction on delayed gastric emptying following pancreaticoduodenectomy.

Background: Delayed gastric emptying (DGE) is a common complication after pancreaticoduodenectomy. There remains an active debate over the effect of gastrointestinal (GI) reconstruction techniques, such as antecolic (AC) or transmesocolic (TMC) reconstruction, on DGE rates. This study compared the rates of DGE between AC reconstruction and TMC reconstruction after pylorus-preserving pancreaticoduodenectomy (PPPD) and classic pancreaticoduodenectomy (PD).

Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

Context.—: Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood.

Contemporary report of surgical outcomes after single-stage total pancreatectomy: A 10-year experience.

Background: Surgeons rarely perform elective total pancreatectomy (TP). Our study seeks to report surgical outcomes in a contemporary series of single-stage (SS) TP patients.

Methods: Between the years 2013 to 2023 we conducted a retrospective review of 60 consecutive patients who underwent SSTP.

International Expert Consensus on Defining Textbook Oncologic Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastasis.

Background: Textbook oncologic outcome (TOO) is a composite metric shown to correlate with improved survival after curative intent oncologic procedures. Despite increasing use among disciplines in surgical oncology, no consensus exists for its definition in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Study Design: An international consensus-based study employed a Delphi methodology to achieve agreement.

Repurposing the FDA-approved anthelmintic pyrvinium pamoate for pancreatic cancer treatment: study protocol for a phase I clinical trial in early-stage pancreatic ductal adenocarcinoma.

Background: Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, we report about an ongoing phase I open-label, single-arm, dose escalation clinical trial to determine the safety and tolerability of PP in PDAC surgical candidates.

Methods And Analysis: In a 3+3 dose design, PP is initiated 3 days prior to surgery.

Increased glucose availability sensitizes pancreatic cancer to chemotherapy.

Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes.

Chronic Obstructive Pulmonary Disease Is Associated with Worse Oncologic Outcomes in Early-Stage Resected Pancreatic and Periampullary Cancers.

Pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer mortality in the United States. Hypoxic and hypercapnic tumor microenvironments have been suggested to promote tumor aggressiveness. The objective of this study was to evaluate the association between chronic obstructive pulmonary disease (COPD) and oncologic survival outcomes in patients with early-stage PDAC and periampullary cancers.

Association of Smoking and Respiratory Disease History with Pancreatic Pathologies Requiring Surgical Resection.

Background: The purpose of this study was to examine the relationship between various respiratory conditions, including hypercapnic respiratory disease, and a multitude of resected pancreatic lesions.

Methods: This retrospective case-control study queried a prospectively maintained database of patients who underwent pancreaticoduodenectomy between January 2015 and October 2021. Patient data, including smoking history, medical history, and pathology reports, were recorded.

Deletion of the mRNA stability factor (HuR) in pancreatic cancer cells disrupts the tumor microenvironment integrity.

Stromal cells promote extensive fibrosis in pancreatic ductal adenocarcinoma (PDAC), which is associated with poor prognosis and therapeutic resistance. We report here for the first time that loss of the RNA-binding protein human antigen R (HuR, ) in PDAC cells leads to reprogramming of the tumor microenvironment. In multiple models, CRISPR deletion of in PDAC cells resulted in a decrease of collagen deposition, accompanied by a decrease of stromal markers (i.

A Novel 3DNA® Nanocarrier effectively delivers payloads to pancreatic tumors.

Introduction: Standard-of-care systemic chemotherapies for pancreatic ductal adenocarcinoma (PDAC) currently have limited clinical benefits, in addition to causing adverse side effects in many patients. One factor known to contribute to the poor chemotherapy response is the poor drug diffusion into PDAC tumors. Novel treatment methods are therefore drastically needed to improve targeted delivery of treatments.

Peptides That Block RAS-p21 Protein-Induced Cell Transformation.

This is a review of approaches to the design of peptides and small molecules that selectively block the oncogenic RAS-p21 protein in ras-induced cancers. Single amino acid substitutions in this protein, at critical positions such as at Gly 12 and Gln 61, cause the protein to become oncogenic. These mutant proteins cause over 90 percent of pancreatic cancers, 40-50 percent of colon cancers and about one third of non-small cell cancers of the lung (NSCCL).

Hypercapnic Tissue Gene Expression and Survival in Early-Stage Pancreatic Ductal Adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal cancer. Hypercapnic tumor microenvironments were previously shown to promote cancer chemoresistance. In this study, we aimed to investigate the impact of tissue hypercapnia on PDAC prognosis.

Distress, Depression, and the Effect of ZIP Code in Pancreaticobiliary Cancer Patients and Their Significant Others.

Background: Distress screening of cancer patients is mandated by the American College of Surgeons Commission on Cancer. Clinical implementation remains limited, particularly in surgical oncology settings in individuals with pancreaticobiliary cancers.

Study Design: This study evaluated differences in mean distress scores based on the National Comprehensive Cancer Network Distress Thermometer & Problem List for patients with pancreaticobiliary cancers, benign pancreatic conditions, and for their significant others (SOs).

Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug.

Pyrvinium, a lipophilic cation belonging to the cyanine dye family, has been used in the clinic as a safe and effective anthelminthic for over 70 years. Its structure, similar to some polyaminopyrimidines and mitochondrial-targeting peptoids, has been linked with mitochondrial localization and targeting. Over the past two decades, increasing evidence has emerged showing pyrvinium to be a strong anti-cancer molecule in various human cancers in vitro and in vivo.

Glutamine stabilizes myc via alpha-ketoglutarate and regulates paclitaxel sensitivity.

Metabolic reprogramming wherein the cancer cells exhibit altered energetics is a hallmark of cancer. Although recent discoveries have enhanced our understanding of tumor metabolism, the therapeutic utility of targeting tumor metabolism is not yet realized. Glutamine, a non-essential amino acid, plays a critical role in regulating tumor metabolism and provides an alternative tumor energy source.

Euglycemic diabetic ketoacidosis (EDKA) after pancreaticoduodenectomy: An under-recognized metabolic abnormality with outcome implications.

Background: Euglycemic diabetic ketoacidosis is a metabolic condition characterized by relative euglycemia, ketonemia, and metabolic acidosis that occurs through mechanisms resembling starvation. Pancreaticoduodenectomy is a complex abdominal operation that subjects patients to a prolonged fasting and an inflammatory state. This study examined the incidence of euglycemic diabetic ketoacidosis and potential opportunities for early diagnosis and management in patients undergoing pancreaticoduodenectomy.