Bulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells.
View Article and Find Full Text PDFBackground: Studies indicate that patients can be "seeded" with their own cancer cells during oncologic surgery and that the immune response to these circulating cancer cells might influence the risk of cancer recurrence. Preliminary data from animal studies and some retrospective analyses suggest that anesthetic technique might affect the immune response during surgery and hence the risk of cancer recurrence. In 2015, experts called for prospective scientific inquiry into whether anesthetic technique used in cancer resection surgeries affects cancer-related outcomes such as recurrence and mortality.
View Article and Find Full Text PDFSERS immunoassay biosensors hold immense potential for clinical diagnostics due to their high sensitivity and growing interest in multi-marker panels. However, their development has been hindered by difficulties in designing compatible extrinsic Raman labels. Prior studies have largely focused on spectroscopic characteristics in selecting Raman reporter molecules (RRMs) for multiplexing since the presence of well-differentiated spectra is essential for simultaneous detection.
View Article and Find Full Text PDFThe diagnosis and monitoring of cancer have been facilitated by discovering tumor "biomarkers" and methods to detect their presence. Yet, for certain cancers, we still lack sensitive and specific biomarkers or the means to quantify subtle concentration changes successfully. The identification of new biomarkers of disease and improving the sensitivity of detection will remain key to changing clinical outcomes.
View Article and Find Full Text PDFBackground: Perioperative chemotherapy has been shown to improve overall survival (OS) for operable gastric and gastroesophageal cancer. However, optimal sequence of surgery and chemotherapy has not been clearly identified. Markov models are useful for analyzing the outcomes of different treatment strategies in the absence of adequately powered randomized clinical trials.
View Article and Find Full Text PDFBackground: Although bariatric surgery has been associated with a reduction in risk of obesity-related cancer, data on the effect of bariatric interventions on other cancers are limited.
Objectives: This study aimed to examine the relationship between bariatric interventions and the incidence of various cancers after bariatric surgery.
Setting: Administrative statewide database.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFGenomic analysis of a patient's tumor is the cornerstone of precision oncology, but it does not address whether metastases should be treated differently. Here we tested whether comparative single-cell RNA sequencing (scRNA-seq) of a primary small intestinal neuroendocrine tumor to a matched liver metastasis could guide the treatment of a patient's metastatic disease. Following surgery, the patient was put on maintenance treatment with a somatostatin analog.
View Article and Find Full Text PDFIntroduction: The HIV protease inhibitor nelfinavir (NFV) displays notable radiosensitizing effects. There have been no studies evaluating combined stereotactic body radiotherapy (SBRT) and NFV for borderline/unresectable pancreatic cancer. The primary objective of this phase I trial (NCT01068327) was to determine the maximum tolerated SBRT/NFV dose, and secondarily evaluate outcomes.
View Article and Find Full Text PDFBackground: Pancreatic cancer (PC) hijacks innate cellular processes to promote cancer growth. We hypothesized that PC exploits PD-1/PD-L1 not only to avoid immune responses, but to directly enhance growth. We also hypothesized that immune checkpoint inhibitors (ICIs) have direct cytotoxicity in PC.
View Article and Find Full Text PDFObjective: Comparative analyses of survival and funding statistics in cancers with high mortality were performed to quantify discrepancies and identify areas for intervention.
Background: Discrepancies in research funding may contribute to stagnant survival rates in pancreatic ductal adenocarcinoma (PDAC).
Methods: The Surveillance, Epidemiology, and End Results database was queried for survival statistics.
Background: Organoids are three-dimensional in vitro models of human disease developed from benign and malignant gastrointestinal tissues with tremendous potential for personalized medicine applications. We sought to determine whether gastric cancer patient-derived organoids (PDOs) could be safely established from endoscopic biopsies for rapid drug screening.
Methods: Patients underwent esophagogastroduodenoscopy (EGD) for surveillance or staging and had additional forceps biopsies taken for PDO creation.
Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer.
View Article and Find Full Text PDFBackground: In contrast to other cancers, survival rates for pancreatic ductal adenocarcinoma (PDAC) patients have improved but minimally over the past thirty years. The aim of this study was to perform a meta-analysis of clinical trials published since 1986 to determine trends in median overall survival in primarily metastatic PDAC.
Materials And Methods: All Phase 2-4 clinical trials published during or after 1986 investigating first-line systemic chemotherapy in metastatic PDAC were included in the meta-analysis.
Background And Aims: Pancreatic cancer organoids are tumor models of individualized human pancreatic ductal adenocarcinoma (PDA), created from surgical specimens and used for personalized treatment strategies. Unfortunately, most patients with PDA are not operative candidates. Creation of human PDA organoids at the time of initial tumor diagnosis is therefore critical.
View Article and Find Full Text PDFRationale: Heterotaxy with polysplenia is an extremely rare congenital condition resulting from abnormal arrangement of organs in the abdominal and thoracic cavities during embryologic development. When a malignancy such as pancreatic cancer develops under these conditions, surgical resection becomes particularly complex. This case report demonstrates successful pancreatic cancer resection despite the patient's complicated anatomy.
View Article and Find Full Text PDFPancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single-agent therapy for pancreatic cancer. Although the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging The Cancer Genome Atlas dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients.
View Article and Find Full Text PDFPoor response to cancer therapy due to resistance remains a clinical challenge. The present study establishes a widely prevalent mechanism of resistance to gemcitabine in pancreatic cancer, whereby increased glycolytic flux leads to glucose addiction in cancer cells and a corresponding increase in pyrimidine biosynthesis to enhance the intrinsic levels of deoxycytidine triphosphate (dCTP). Increased levels of dCTP diminish the effective levels of gemcitabine through molecular competition.
View Article and Find Full Text PDFObjective: The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications.
Background: The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported.
Gangliocytic paraganglioma (GP) is a rare tumor of uncertain origin most often located in the second portion of the duodenum. It is composed of three cellular components: Epithelioid endocrine cells, spindle-like/sustentacular cells, and ganglion-like cells. While this tumor most often behaves in a benign manner, cases with metastasis are reported.
View Article and Find Full Text PDFPurpose: Prospectively assess relationships between dosimetric parameters and histopathologic/clinical duodenal toxicities in patients on a phase I trial for pancreatic cancer.
Methods: Forty-six borderline resectable/unresectable patients were enrolled on a prospective trial testing neoadjuvant gemcitabine/5-fluorouracil followed by SBRT (5 daily fractions of 5-8Gy) and concurrent nelfinavir. Post-SBRT surgery was performed in 13 resectable patients, which constituted the patient population herein.