Objective: To examine the optimal method of assessing response to neoadjuvant therapy (NAT) in operable pancreatic ductal adenocarcinoma (PDAC) patients.
Summary Of Background Data: PDAC response to NAT is measured with biochemical, radiographic and pathologic parameters, which can often be discordant with each other.
Methods: PDAC patients undergoing resection after NAT at a single institution were retrospectively analyzed.
Background: Distal pancreatectomy with celiac axis resection (DP-CAR) has been used for selected patients with pancreatic cancer infiltrating the celiac axis. We compared the short- and long-term outcomes between DP-CAR and distal pancreatectomy alone (DP) in patients receiving neoadjuvant therapy.
Methods: Patients undergoing DP-CAR from 2013 to 2022 were retrospectively reviewed.
Reduction in muscle contractile force associated with many clinical conditions incurs serious morbidity and increased mortality. Here, we report the first evidence that JAK inhibition impacts contractile force in normal human muscle. Muscle biopsies were taken from patients who were randomized to receive tofacitinib (n = 16) or placebo (n = 17) for 48 h.
View Article and Find Full Text PDFIntroduction: Pancreatic pathologies causing portomesenteric occlusion complicate extirpative pancreatic resection due to portomesenteric hypertension and collateral venous drainage.
Methods: Patients with portomesenteric occlusion undergoing pancreatectomy were identified between 2007 and 2020 at Stanford University Hospital. Demographic and clinical data, technique and perioperative factors, and post-operative outcomes were analyzed.
Pancreatic ductal adenocarcinoma (PDAC) represents one of the only cancers with an increasing incidence rate and is often associated with intra- and peri-tumoral scarring, referred to as desmoplasia. This scarring is highly heterogeneous in extracellular matrix (ECM) architecture and plays complex roles in both tumor biology and clinical outcomes that are not yet fully understood. Using hematoxylin and eosin (H&E), a routine histological stain utilized in existing clinical workflows, we quantified ECM architecture in 85 patient samples to assess relationships between desmoplastic architecture and clinical outcomes such as survival time and disease recurrence.
View Article and Find Full Text PDFBackground: Minimally invasive distal pancreatectomy (MIDP) has established advantages over the open approach. The costs associated with robotic DP (RDP) versus laparoscopic DP (LDP) make the robotic approach controversial. We sought to compare outcomes and cost of LDP and RDP using propensity matching analysis at our institution.
View Article and Find Full Text PDFMultiome sequencing, which provides same-cell/paired single-cell RNA- and the assay for transposase-accessible chromatin with sequencing (ATAC-sequencing) data, represents a breakthrough in our ability to discern tumor cell heterogeneity-a primary focus of translational cancer research at this time. However, the quality of sequencing data acquired using this advanced modality is highly dependent on the quality of the input material. Digestion conditions need to be optimized to maximize cell yield without sacrificing quality.
View Article and Find Full Text PDFPancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death. Hallmarks include desmoplasia with variable extracellular matrix (ECM) architecture and a complex microenvironment with spatially defined tumor, stromal, and immune populations. Nevertheless, the role of desmoplastic spatial organization in patient/tumor variability remains underexplored, which we elucidate using two technologies.
View Article and Find Full Text PDFBackground: Spleen-preservation during minimally invasive distal pancreatectomy (MIDP) can be technically challenging and remains controversial. Our primary aim was to compare MIDP and splenectomy with spleen-preserving MIDP. Secondarily, we compared two spleen-preserving techniques.
View Article and Find Full Text PDFPancreatic cancer is one of the deadliest forms of cancer with one of the lowest 5-year survival rates of all cancer types. A defining characteristic of pancreatic cancer is the existence of dense desmoplastic stroma that, when exposed to stimuli such as cytokines, growth factors, and chemokines, generate a tumor-promoting environment. Cancer-associated fibroblasts (CAFs) are activated during the progression of pancreatic cancer and are a crucial component of the tumor microenvironment (TME).
View Article and Find Full Text PDFBackground: Radiographic calcifications and cystic morphology are associated with higher and lower tumor grade, respectively, in pancreatic neuroendocrine tumors (PNETs). Whether calcifications and/or cystic morphology could be used preoperatively to predict post-resection survival in patients with PNETs remains elusive.
Methods: Patients undergoing curative-intent resection of well-differentiated PNETs from 2000 to 2017 at eight academic institutions participating in the US Neuroendocrine Tumor Study Group were identified.
Cancer-associated fibroblasts (CAFs) are integral to the solid tumor microenvironment. CAFs were once thought to be a relatively uniform population of matrix-producing cells, but single-cell RNA sequencing has revealed diverse CAF phenotypes. Here, we further probed CAF heterogeneity with a comprehensive multiomics approach.
View Article and Find Full Text PDFBackground: The optimal surgical management of pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 is controversial. This study sought to compare clinicopathologic characteristics and outcomes of multiple endocrine neoplasia type 1-associated and sporadic pancreatic neuroendocrine tumors from a large multi-national database.
Methods: A multi-institutional, international database of patients with surgically resected pancreatic neuroendocrine tumors was analyzed.
Introduction: Gastric cancer is inherited as an autosomal dominant condition in hereditary diffuse gastric cancer (HDGC). The gene associated with HDGC is an E-cadherin gene CDH1. At the time of initiation of this study, it was estimated that 70% of patients who inherited the CDH1 gene mutation would develop gastric cancer.
View Article and Find Full Text PDFHigh-level amplification of MDM2 and other genes in the 12q13-15 locus is a hallmark genetic feature of well-differentiated and dedifferentiated liposarcomas (WDLPS and DDLPS, respectively). Detection of this genomic aberration in plasma cell-free DNA may be a clinically useful assay for non-invasive distinction between these liposarcomas and other retroperitoneal tumors in differential diagnosis, and might be useful for the early detection of disease recurrence. In this study, we performed shallow whole genome sequencing of cell-free DNA extracted from 10 plasma samples from 3 patients with DDLPS and 1 patient with WDLPS.
View Article and Find Full Text PDFObjectives: We review our institution's experience in treating leiomyosarcomas involving the inferior vena cava, and we offer guidance on the management.
Methods: A text-based search was performed to identify all patients who underwent surgical resection between January 2002 and October 2020. Clinicopathologic data, intraoperative variables, and outcomes were extracted from chart review.
Background: Enhanced Recovery After Surgery (ERAS) protocols have been successfully instituted for pancreaticoduodenectomy (PD). This study evaluates reasons patients fail to meet length of stay (LOS) and areas for pathway improvement.
Materials And Methods: A multidisciplinary team developed and implemented an ERAS protocol for open PD in 2017.
Proc Natl Acad Sci U S A
October 2021
In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive, in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a multimodal -omics platform for the comprehensive study of cell populations in complex tissue, which has allowed us to characterize the cells involved in wound healing across both time and space.
View Article and Find Full Text PDFBackground: The importance of regional lymph node sampling (LNS) during resection of hepatocellular carcinoma (HCC) is poorly understood. This study sought to ameliorate this knowledge gap through a nationwide population-based analysis.
Methods: Patients who underwent liver resection (LR) for HCC were identified from Surveillance, Epidemiology and End Results (SEER-18) database (2003-2015).
Importance: Although outcome of surgical resection of liver metastases from pancreatic neuroendocrine tumors (PNETs) has been extensively studied, little is known about surgery for locally advanced PNETs; it was listed recently by the European neuroendocrine tumor society as a major unmet need.
Objective: To evaluate the outcome of patients who underwent surgery for locally aggressive PNETs.
Design, Setting, And Participants: This retrospective single-center case series reviewed consecutive patients who underwent resection of T3/T4 PNETs at a single academic institution.
Single cell transcriptomics is revolutionising our understanding of tissue and disease heterogeneity, yet cell type identification remains a partially manual task. Published algorithms for automatic cell annotation are limited to known cell types and fail to capture novel populations, especially cancer cells. We developed northstar, a computational approach to classify thousands of cells based on published data within seconds while simultaneously identifying and highlighting new cell states such as malignancies.
View Article and Find Full Text PDFAdhesions are fibrotic scars that form between abdominal organs following surgery or infection, and may cause bowel obstruction, chronic pain, or infertility. Our understanding of adhesion biology is limited, which explains the paucity of anti-adhesion treatments. Here we present a systematic analysis of mouse and human adhesion tissues.
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