Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes.

Most patients diagnosed with resected pancreatic adenocarcinoma (PDAC) survive less than 5 years, but a minor subset survives longer. Here, we dissect the role of the tumor microbiota and the immune system in influencing long-term survival. Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition in PDAC patients with short-term survival (STS) and long-term survival (LTS).

Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas.

The management of intraductal papillary mucinous neoplasm (IPMN) continues to evolve. In particular, the indications for resection of branch duct IPMN have changed from early resection to more deliberate observation as proposed by the international consensus guidelines of 2006 and 2012. Another guideline proposed by the American Gastroenterological Association in 2015 restricted indications for surgery more stringently and recommended physicians to stop surveillance if no significant change had occurred in a pancreatic cyst after five years of surveillance, or if a patient underwent resection and a non-malignant IPMN was found.

Evolution of cellular morpho-phenotypes in cancer metastasis.

Intratumoral heterogeneity greatly complicates the study of molecular mechanisms driving cancer progression and our ability to predict patient outcomes. Here we have developed an automated high-throughput cell-imaging platform (htCIP) that allows us to extract high-content information about individual cells, including cell morphology, molecular content and local cell density at single-cell resolution. We further develop a comprehensive visually-aided morpho-phenotyping recognition (VAMPIRE) tool to analyze irregular cellular and nuclear shapes in both 2D and 3D microenvironments.

Quality assessment of the guidelines on cystic neoplasms of the pancreas.

Background: Though cystic pancreatic neoplasms (CPNs) are being increasingly detected, their evaluation and management are still debated and have lead to publication of multiple guidelines for diagnostic work-up, indications for resection, and non-operative management with follow-up strategies of CPNs.

Aims: To analyze available guidelines in order to evaluate their overall quality and clinical applicability, indications for surgical resection and its extent, modalities and timing of follow-up when non-operative management is indicated.

Methods: After a systematic search of the English literature, we selected eight guidelines for assessment according to the Appraisal of Guidelines, Research and Evaluation in Europe (AGREE) II instrument.

Institutional experience with solid pseudopapillary neoplasms: focus on computed tomography, magnetic resonance imaging, conventional ultrasound, endoscopic ultrasound, and predictors of aggressive histology.

Objective: Solid pseudopapillary neoplasms (SPNs) are low-grade malignancies with an excellent prognosis, albeit with the potential for metastatic disease. This study details our institution's experience with the diagnosis and treatment of SPN, including clinical presentation, multimodality imaging findings, and potential predictors of aggressive tumor behavior.

Materials And Methods: The institutional pathology database was searched through for all cases of SPN since 1988, yielding 51 patients.

Tumor engraftment in nude mice and enrichment in stroma- related gene pathways predict poor survival and resistance to gemcitabine in patients with pancreatic cancer.

Purpose: The goal of this study was to evaluate prospectively the engraftment rate, factors influencing engraftment, and predictability of clinical outcome of low-passage xenografts from patients with resectable pancreatic ductal adenocarcinoma (PDA) and to establish a bank of PDA xenografts.

Experimental Design: Patients with resectable PDA scheduled for resection at the Johns Hopkins Hospital were eligible. Representative pieces of tumor were implanted in nude mice.

Integrated preclinical and clinical development of mTOR inhibitors in pancreatic cancer.

Background: The purpose of this work was to determine the efficacy of inhibiting mammalian target of rapamycin (mTOR) in pancreatic cancer preclinical models and translate preclinical observations to the clinic.

Methods: Temsirolimus (20 mg Kg(-1) daily) was administered to freshly generated pancreatic cancer xenografts. Tumour growth inhibition was determined after 28 days.

Inhibiting the cyclin-dependent kinase CDK5 blocks pancreatic cancer formation and progression through the suppression of Ras-Ral signaling.

Cyclin-dependent kinase 5 (CDK5), a neuronal kinase that functions in migration, has been found to be activated in some human cancers in which it has been implicated in promoting metastasis. In this study, we investigated the role of CDK5 in pancreatic cancers in which metastatic disease is most common at diagnosis. CDK5 was widely active in pancreatic cancer cells.

The role of surgery in the management of isolated metastases to the pancreas.

Metastasectomy with curative intent has become standard practice for the management of some malignancies. Resection of isolated metastatic colorectal cancer, gastrointestinal stromal tumours, neuroendocrine cancers, renal-cell cancer and sarcoma is associated with longer survival or even cure. The strongest evidence in favour of metastasectomy exists for colorectal cancer, in which resection of limited metastatic disease in some patients is associated with 5-year survival rates of more than 50%.

An in vivo platform for translational drug development in pancreatic cancer.

Effective development of targeted anticancer agents includes the definition of the optimal biological dose and biomarkers of drug activity. Currently available preclinical models are not optimal to this end. We aimed at generating a model for translational drug development using pancreatic cancer as a prototype.