Incidence of Pancreatic Intraepithelial Neoplasia in an Autopsy Series.

Objectives: Pancreatic intraepithelial neoplasia (PanIN) is the currently preferred designation for putative preneoplastic changes in the pancreas. There are few data for the incidence of PanIN in the general population. Our goal was to determine the incidence of PanIN in a large group of pancreases obtained at autopsy.

Applying Telehealth Technologies and Strategies to Provide Acute Care Consultation and Treatment of Patients With Confirmed or Possible COVID-19.

Background And Purpose: The COVID-19 pandemic continues to grow, with 19% of total confirmed patients classified as severe or critical experiencing complications such as dyspnea, hypoxia, acute respiratory distress syndrome, or multiorgan failure. These complications require rehabilitative care. Considering the contagious nature of COVID-19 and the necessity to decrease the volume of health care professionals entering confirmed COVID-19 patient rooms and becoming a potential disease vector, can audiovisual technologies employed by telehealth and telerehabilitation help?

Case Description: This case discusses the Baylor Scott and White Institute for Rehab (BSWIR) Physical Medicine and Rehabilitation (PMR) department COVID-19 acute care therapy team's creation of a telehealth strategy to provide early rehabilitative intervention without increasing the odds of disease transmission.

Pancreatic Ductal Adenocarcinoma: Recent Updates.

This Guest Editorial introduces this month's special Pancreatic Cancer Theme Issue, a series of reviews intended to highlight the pathologic to molecular profiles and diagnoses of benign and neoplastic pancreatic lesions.

Association of IgG4 response and autoimmune pancreatitis with intraductal papillary-mucinous neoplasms.

Objectives: Concurrent intraductal papillary-mucinous neoplasm (IPMN) and autoimmune pancreatitis (AIP) was observed in a patient (index case) at our institution. Cases of coincidental IPMN and type 1 AIP and concurrent ductal adenocarcinoma (PDAC) and AIP have been previously reported. In this study we evaluate the hypothesis that IPMN elicits an IgG4 response.

Variability in Implementation of Interventions Aimed at Reducing Readmissions Among Patients With Heart Failure: A Survey of Teaching Hospitals.

Purpose: To highlight teaching hospitals' efforts to reduce readmissions by describing interventions implemented to improve care transitions for heart failure (HF) patients and the variability in implemented HF-specific and care transition interventions.

Method: In 2012, the authors surveyed a network of 17 teaching hospitals to capture information about the number, type, stage of implementation, and structure of 4 HF-specific and 21 care transition (predischarge, bridging, and postdischarge) interventions implemented to reduce readmissions among patients with HF. The authors summarized data using descriptive statistics, including the mean number of interventions implemented and the frequency and stage of specific interventions, and descriptive plots of the structure of two common interventions (multidisciplinary rounds and follow-up telephone calls).

A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas.

International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following: (1) To improve concordance and to align with practical consequences, a 2-tiered system (low vs. high grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low grade.

American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines.

The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed, and evidence-based statements are provided about their utility and limitations.

The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition.

Fenestral and stomatal diaphragms are endothelial subcellular structures of unknown function that form on organelles implicated in vascular permeability: fenestrae, transendothelial channels, and caveolae. PV1 protein is required for diaphragm formation in vitro. Here, we report that deletion of the PV1-encoding Plvap gene in mice results in the absence of diaphragms and decreased survival.

AGR2 is a SMAD4-suppressible gene that modulates MUC1 levels and promotes the initiation and progression of pancreatic intraepithelial neoplasia.

The mechanisms controlling expression of the putative oncogene Anterior gradient 2 (AGR2) in pancreatic ductal adenocarcinoma (PDAC) are not well understood. We now show that AGR2 is a transforming growth factor-β (TGF-β)-responsive gene in human pancreatic cancer cells, whose downregulation is SMAD4 dependent. We also provide evidence supporting a role for AGR2 as an ER-chaperone for the cancer-associated mucin, MUC1.

Invasive mucinous cystic neoplasms of the pancreas.

Mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN) of the pancreas both appear to have been included and intermixed in some early reports of pancreatic cystic neoplasms. Recognition of their distinguishing features evolved during the last decade of the twentieth century. One legacy of the early period is the statement that mucinous cystic neoplasms sometimes progress to invasive colloid carcinoma.

PV1 down-regulation via shRNA inhibits the growth of pancreatic adenocarcinoma xenografts.

PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis.

Acute pancreatitis accelerates initiation and progression to pancreatic cancer in mice expressing oncogenic Kras in the nestin cell lineage.

Targeting of oncogenic Kras to the pancreatic Nestin-expressing embryonic progenitor cells and subsequently to the adult acinar compartment and Nestin-expressing cells is sufficient for the development of low grade pancreatic intraepithelial neoplasia (PanIN) between 2 and 4 months. The mice die around 6 month-old of unrelated causes, and it is therefore not possible to assess whether the lesions will progress to carcinoma. We now report that two brief episodes of caerulein-induced acute pancreatitis in 2 month-old mice causes rapid PanIN progression and pancreatic ductal adenocarcinoma (PDAC) development by 4 months of age.

Autoimmune pancreatitis (AIP) type 1 and type 2: an international consensus study on histopathologic diagnostic criteria.

Objectives: To develop and validate histologic diagnostic criteria for autoimmune pancreatitis (AIP) and its types.

Methods: Thirteen pathologists participated in this 2-phase study to develop diagnostic criteria for AIP types 1 and 2 (phase 1) and validate them (phase 2). A virtual library of 40 resected pancreata with AIP and other forms of chronic pancreatitis (CP) was constructed.

Deletion of Rb accelerates pancreatic carcinogenesis by oncogenic Kras and impairs senescence in premalignant lesions.

Background & Aims: Rb1 encodes a cell-cycle regulator that is functionally disrupted in most human cancers. Pancreatic ductal adenocarcinomas (PDACs) have a high frequency of mutations in KRAS and INK4A/CDKN2A that might allow cells to bypass the regulatory actions of retinoblastoma (RB). To determine the role of loss of RB function in PDAC progression, we investigated the effects of Rb disruption during pancreatic malignant transformation initiated by oncogenic Kras.

MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Diagnosis and management of PDAC are hampered by the absence of sensitive and specific disease biomarkers. MicroRNAs (miRNA) are noncoding regulatory RNAs involved in initiation and progression of human cancers.

Intracellular activation of trypsinogen in transgenic mice induces acute but not chronic pancreatitis.

Background And Aims: Premature intra-acinar activation of trypsinogen is widely considered key for both the initiation of acute pancreatitis and the development of chronic pancreatitis. However, the biological consequences of intracellular trypsinogen activation have not been directly examined. To do so, a new mouse model was developed.

Commentary: Putting evidence to work: an expanded research agenda for academic medicine in the era of health care reform.

The historic Patient Protection and Affordable Care Act (HR 3590) signed into law by President Obama has brought into sharp focus the need and opportunity for an expanded continuum of biomedical research. An updated research agenda must build on basic science and classical clinical investigation to place a more deliberate emphasis on patient- and population-outcome-oriented science and to apply science to help transform our current inefficient and expensive health care system into a more evidence-based system of effective, coordinated, safe, and patient-centered health care. If academic medicine is to play a leading role in this 21st-century transformation of health care through research, as it did in the 20th century, those in the community must think strategically about what needs to be done to be part of the solution for transforming the nation's health care delivery systems and prevention strategies, and the changes in institutional, organizational, and individual behaviors and values required to get there.

Autoimmune pancreatitis: the clinicopathological characteristics of the subtype with granulocytic epithelial lesions.

Autoimmune pancreatitis (AIP) has been established as a distinct form of chronic pancreatitis that is distinguishable from other types such as alcoholic, hereditary or obstructive chronic pancreatitis. AIP seems to be a global disease, since it has been reported in many different countries, especially from Japan, USA and Europe (Germany, Italy, United Kingdom). Typical histopathological findings in the pancreas in AIP include a periductal lymphoplasmacytic infiltration with fibrosis, causing narrowing of the involved ducts.

Ras activity levels control the development of pancreatic diseases.

Background & Aims: Differentiated pancreatic acinar cells expressing endogenous levels of mutant K-Ras do not spontaneously develop pancreatic ductal adenocarcinoma (PDAC). However, we hypothesized that acinar cells would develop PDAC in the presence of Ras activity levels mimicking those of human tumor cells.

Methods: We measured Ras activity in PDAC cells from mice and humans using a Raf pull-down assay.

Acute pancreatitis markedly accelerates pancreatic cancer progression in mice expressing oncogenic Kras.

Chronic pancreatitis increases by 16-fold the risk of developing pancreatic ductal adenocarcinoma (PDAC), one of the deadliest human cancers. It also appears to accelerate cancer progression in genetically engineered mouse models. We now report that in a mouse model where oncogenic Kras is activated in all pancreatic cell types, two brief episodes of acute pancreatitis caused rapid PanIN progression and accelerated pancreatic cancer development.

Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia.

Primary cilia have been proposed to participate in the modulation of growth factor signaling pathways. In this study, we determined that ciliogenesis is suppressed in both pancreatic cancer cells and pancreatic intraepithelial neoplasia (PanIN) lesions in human pancreatic ductal adenocarcinoma (PDAC). Primary cilia were absent in these cells even when not actively proliferating.

Growing colorectal tumors: minimizing microbial and stromal competition and assessing in vitro selection pressures.

Development of primary colorectal cancer cell lines ishampered by contamination from regional microbes, overgrowthof stromal cells, and purported genetic drift from selectionpressures in vitro. We initiated 32 primaryadenocarcinomas, 3 recurrences and 6 distant metastases incell culture. Twelve cell lines from eleven tumors weregenerated (26.