Gastroenterology Commons^™

Trem2 Depletion In Pancreatic Cancer Elicits Pathogenic Inflammation And Accelerates Tumor Progression Via Enriching Il-1Β+ Macrophages, Daowei Yang, Xinlei Sun, Hua Wang, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen

Faculty, Staff and Student Publications

Background & aims: Pancreatic ductal adenocarcinoma (PDAC) has a complex tumor microenvironment enriched with tumor-associated macrophages. Triggering receptor expressed on myeloid cells 2 (TREM2) is highly expressed by a subset of macrophages in PDAC. However, the functional role of TREM2 in PDAC progression remains elusive.

Methods: We generated a novel transgenic mouse model (KPPC;Trem2-/-) that enables the genetic depletion of TREM2 in the context of spontaneous PDAC development. Single-cell RNA-sequencing analysis was used to identify changes in the tumor immune microenvironment on TREM2 depletion. We evaluated the impacts of TREM2 depletion on the tumor immune microenvironment to elucidate the functions …

Enhanced Anticancer Activity Of Novel Pyrimidine Nucleoside Analog In Pancreatic Cancer, Raviteja Bulusu, Joy Okoro, Esther Frimpong, Sunil Krishnan, Saunjoo Yoon, Bo Han, Xue Zhu, Edward Agyare

The Brown Foundation: Institute of Molecular Medicine

This study explores the synthesis, characterization, and therapeutic efficacy of AGY1, AGY2, AGY3, AGY4, and AGY5, which are novel 5-FU analogs designed to improve metabolic stability, prolong half-life, and anti-tumor activity against pancreatic cancer. The 5-FU molecule was chemically modified to bypass dihydropyrimidine dehydrogenase (DPD)-mediated inactivation, enhancing drug retention and increasing lipophilicity for improved cellular uptake. The analog cytotoxic activity was evaluated in 2D monolayer cultures and 3D pancreatic cancer spheroids and organoid models derived from MiaPaCa-2 and PANC-1 cells to simulate a more complex tumor environment. In the 2D model, AGY1, AGY2, AGY3, AGY4, and AGY5 displayed significantly higher …

Pancreatic Cancer; From Effective Prevention And Early Diagnosis To Personalized Therapy, Adrian Silaghi, Dragos Serban, Bogdan Gaspar, Valentin Verlas, Dragos Epistatu, Cristian Paius, Roxana Sfetea, Liliana Andronache, Ioana Paunica, Irina Ruxandra Strambu, Daniela Gabriela Bălan, Alexandru Florin Motofei, Vlad Denis Constantin

Journal of Mind and Medical Sciences

Despite substantial improvements in survival rates for most cancers, pancreatic cancer still remains a leading cause of death from malignancy. The disease has no symptoms in the initial stages, it can early invade the surrounding organs, and treatment methods have poor long-term prognosis. In addition, this neoplasia is starting to be diagnosed more and more frequently in young people. High incidences have been found in developed regions such as Europe, North America, Australia, but recent data show that this condition is increasing in other regions as well. Pancreatic cancer involves multiple factors such as cigarette smoking, obesity, diabetes, alcohol consumption, …

Pancreaticoduodenectomy After Endoscopic Ultrasound-Guided Lumen Apposing Metal Stent (Lams): A Case Series Evaluating Feasibility And Short-Term Outcomes: Whipple After Lumen Apposing Metal Stent, Luke Meredith, David Baek, Alisha Agarwal, Faisal Kamal, Anand R. Kumar, Alexander Schlachterman, Thomas E. Kowalski, Charles J. Yeo, Harish Lavu, Avinoam Nevler, Wilbur B. Bowne

Department of Surgery Faculty Papers

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).

Methods

Six patients identified from our IRB-approved pancreas cancer database had EUS-LAMS placement prior to PD. Patient, tumor, treatment-related variables, and outcomes are herein reported.

Results

Two patients underwent a LAMS gastrojejunostomy (GJ) for duodenal obstruction. Another patient underwent LAMS choledochoduodenostomy (CDS) for malignant biliary obstruction. In three patients, a LAMS gastrogastrostomy or jejunogastrostomy was deployed post …

Global Burden Of Five Major Types Of Gastrointestinal Cancer, Arjun Singh

Division of Gastroenterology and Hepatology Faculty Papers

Gastrointestinal (GI) cancers cause major global morbidity and mortality, with over 5 million new cases and 3.5 million deaths in 2020. The most prevalent GI malignancies are colorectal, gastric, liver, oesophageal, and pancreatic cancers. Marked geographic variations exist, with high incidence in developed regions contrasting with high mortality in developing areas. These patterns reflect disparities in risk factors and cancer control capacities. However, GI cancer incidence is rising with economic growth and lifestyle changes. Poor prognosis and increasing burden underscore the critical need for expanded prevention and research. This review examines global epidemiology, risks, prevention, detection, treatment, and priorities for …

Genetic Deletion Of Galectin-3 Inhibits Pancreatic Cancer Progression And Enhances The Efficacy Of Immunotherapy, Daowei Yang, Xinlei Sun, Rohan Moniruzzaman, Hua Wang, Citu Citu, Zhongming Zhao, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen

Faculty, Staff and Student Publications

Background & aims: Pancreatic ductal adenocarcinoma (PDAC) has a desmoplastic tumor stroma and immunosuppressive microenvironment. Galectin-3 (GAL3) is enriched in PDAC, highly expressed by cancer cells and myeloid cells. However, the functional roles of GAL3 in the PDAC microenvironment remain elusive.

Methods: We generated a novel transgenic mouse model (LSL-KrasG12D/+;Trp53loxP/loxP;Pdx1-Cre;Lgals3-/- [KPPC;Lgals3-/-]) that allows the genetic depletion of GAL3 from both cancer cells and myeloid cells in spontaneous PDAC formation. Single-cell RNA-sequencing analysis was used to identify the alterations in the tumor microenvironment upon GAL3 depletion. We investigated both the cancer cell-intrinsic function and immunosuppressive function of GAL3. We also evaluated …

Medical And Psychological Management Of Patients With A History Of Surgical Treatment For Pancreatic Diseases, Magdalena Țone, Daniel Cochior, Oana Denisa Balalau, Tomescu Dana Rodica, Cristian Balalau, Teodora Mocan, Aurelian Udristoiu, Gabriel Petre Gorecki

Journal of Mind and Medical Sciences

Background. Pancreatic cancer, known for its high mortality rate and late diagnosis, remains a significant health concern. Surgery offers a potential therapeutic remedy, but it is only valid in the early stage of detection. Increasing risk factors and an aging population are expected to raise the incidence of pancreatic cancer, further challenging healthcare systems. Methods. The general objective of this study was to analyze doctors' experiences regarding the health status of patients with benign pancreatic pathology who underwent surgery and were admitted to CF2 Clinical Hospital in Bucharest. The research involved a specialized questionnaire addressing various aspects of patient health, …

Protein Biomarkers And Alternatively Methylated Cell-Free Dna Detect Early Stage Pancreatic Cancer, Roni Ben-Ami, Qiao-Li Wang, Jinming Zhang, Julianna G Supplee, Johannes F Fahrmann, Roni Lehmann-Werman, Lauren K Brais, Jonathan Nowak, Chen Yuan, Maureen Loftus, Ana Babic, Ehsan Irajizad, Tal Davidi, Aviad Zick, Ayala Hubert, Daniel Neiman, Sheina Piyanzin, Ofer Gal-Rosenberg, Amit Horn, Ruth Shemer, Benjamin Glaser, Natalia Boos, Kunal Jajoo, Linda Lee, Thomas E Clancy, Douglas A Rubinson, Kimmie Ng, John A Chabot, Fay Kastrinos, Michael Kluger, Andrew J Aguirre, Pasi A Jänne, Nabeel Bardeesy, Ben Stanger, Mark H O'Hara, Jacob Till, Anirban Maitra, Erica L Carpenter, Andrea J Bullock, Jeanine Genkinger, Samir M Hanash, Cloud P Paweletz, Yuval Dor, Brian M Wolpin

Faculty, Staff and Student Publications

Objective: Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage. Liquid biopsy approaches may facilitate detection of early stage PDAC when curative treatments can be employed.

Design: To assess circulating marker discrimination in training, testing and validation patient cohorts (total n=426 patients), plasma markers were measured among PDAC cases and patients with chronic pancreatitis, colorectal cancer (CRC), and healthy controls. Using CA19-9 as an anchor marker, measurements were made of two protein markers (TIMP1, LRG1) and cell-free DNA (cfDNA) pancreas-specific methylation at 9 loci encompassing 61 CpG sites.

Results: Comparative methylome analysis identified nine loci that were differentially …

Rational Prescribing Of Pancreatic Enzymes For Patients With Pancreatic Cancer, Mary Acelle G Garcia, Syed Imam, Ursula K Braun, Leanne K Jackson

Center for Medical Ethics and Health Policy Staff Publications

Most patients with pancreatic cancer at some point present with symptoms related to exocrine pancreatic insufficiency (EPI). These include diarrhea, abdominal bloating, indigestion, steatorrhea, weight loss, and anorexia. Even though up to 80% of pancreatic cancer patients eventually present with symptoms related to exocrine pancreatic insufficiency, only 21% are prescribed pancreatic enzyme replacement therapy (PERT). Its effectiveness is also highly dependent on its proper timing of administration, and patients must be thoroughly educated about this. The impact of symptoms of EPI can lead to poorer overall well-being. Pharmacists play a crucial role in properly educating patients on the correct use …

Characteristics Of Early Pancreatic Cancer: Comparison Between Stage 1a And Stage 1b Pancreatic Cancer In Multicenter Clinical Data Warehouse Study, Hyo Suk Kim, Young Hoon Choi, Jae Sin Lee, Ik Hyun Jo, Sung Woo Ko, Kyu Hyun Paik, Hyun Ho Choi, Han Hee Lee, Yeon Soo Lim, Chang Nyol Paik, In Seok Lee, Jae Hyuck Chang

Faculty, Staff and Student Publications

BACKGROUND: Little is known about the characteristics of early pancreatic cancer. We aimed to identify the characteristics, clues for early detection, and prognostic factors for early pancreatic cancer by analyzing a large number of patients with stage 1 pancreatic cancer.

METHODS: A clinical data warehouse that includes databases of all the medical records of eight academic institutions was used to select and analyze patients with pancreatic cancer that had been diagnosed from January 2010 to May 2023.

RESULTS: In total, 257 stage 1 pancreatic cancer patients were included. There were 134 men (52%), and the average age was 67.2 ± …

Impact Of Kras Mutations And Co-Mutations On Clinical Outcomes In Pancreatic Ductal Adenocarcinoma, Abdelrahman Yousef, Mahmoud Yousef, Saikat Chowdhury, Kawther Abdilleh, Mark Knafl, Paul Edelkamp, Kristin Alfaro-Munoz, Ray Chacko, Jennifer Peterson, Brandon G Smaglo, Robert A Wolff, Shubham Pant, Michael S Lee, Jason Willis, Michael Overman, Sudheer Doss, Lynn Matrisian, Mark W Hurd, Rebecca Snyder, Matthew H G Katz, Huamin Wang, Anirban Maitra, John Paul Shen, Dan Zhao

Faculty, Staff and Student Publications

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRASG12R had a similar OS (median 34 months), while patients with KRASQ61 and KRASG12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p < 0.001], respectively). There was enrichment of KRASG12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p = 0.001) and enrichment of KRASG12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor® dataset, n = 408).

Single-Cell Analysis Differentiates The Effects Of P53 Mutation And P53 Loss On Cell Compositions Of Oncogenic Kras-Driven Pancreatic Cancer, Xinlei Sun, Daowei Yang, Yang Chen

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignant disease with a dismal prognosis. In the past decades, a plethora of genetically engineered mouse models (GEMMs) with autochthonous pancreatic tumor development have greatly facilitated studies of pancreatic cancer. Commonly used GEMMs of PDAC often harbor the oncogenic KRAS driver mutation (KrasG12D), in combination with either p53 mutation by knock-in strategy (Trp53R172H) or p53 loss by conditional knockout (Trp53cKO) strategy, in pancreatic cell lineages. However, the systematic comparison of the tumor microenvironment between KrasG12D; Trp53R172H (KPmut) mouse models and KrasG12D; Trp53cKO (KPloss) mouse models …

Endoscopic Ultrasound-Guided Fiducial Placement For Stereotactic Body Radiation Therapy In Patients With Pancreatic Cancer, Irina M Cazacu, Ben S Singh, Rachael M Martin-Paulpeter, Sam Beddar, Stephen Chun, Emma B Holliday, Albert C Koong, Prajnan Das, Eugene J Koay, Cullen Taniguchi, Joseph M Herman, Manoop S Bhutani

Faculty, Staff and Student Publications

Accurate delivery of stereotactic body radiotherapy (SBRT) to pancreatic tumors relies on successful EUS-guided placement of fiducial markers. The aim of this study is to report the technical feasibility and safety of EUS-guided fiducial placement and to evaluate the characteristics and technical benefit of SBRT in a cohort of patients with pancreatic cancer (PC). A retrospective chart review was performed for all (n = 82) PC patients referred for EUS-guided fiducial placement by a single endosonographer at a tertiary cancer center. Data regarding EUS-related technical details, SBRT characteristics, adverse events, and continuous visibility of fiducials were recorded and analyzed. …

A Blood-Based Metabolomic Signature Predictive Of Risk For Pancreatic Cancer, Ehsan Irajizad, Ana Kenney, Tiffany Tang, Jody Vykoukal, Ranran Wu, Eunice Murage, Jennifer B Dennison, Marta Sans, James P Long, Maureen Loftus, John A Chabot, Michael D Kluger, Fay Kastrinos, Lauren Brais, Ana Babic, Kunal Jajoo, Linda S Lee, Thomas E Clancy, Kimmie Ng, Andrea Bullock, Jeanine M Genkinger, Anirban Maitra, Kim-Anh Do, Bin Yu, Brian M Wolpin, Sam Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Emerging evidence implicates microbiome involvement in the development of pancreatic cancer (PaCa). Here, we investigate whether increases in circulating microbial-related metabolites associate with PaCa risk by applying metabolomics profiling to 172 sera collected within 5 years prior to PaCa diagnosis and 863 matched non-subject sera from participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. We develop a three-marker microbial-related metabolite panel to assess 5-year risk of PaCa. The addition of five non-microbial metabolites further improves 5-year risk prediction of PaCa. The combined metabolite panel complements CA19-9, and individuals with a combined metabolite panel + CA19-9 score in the …

Comparative Analyses Of The Clinicopathologic Features Of Short-Term And Long-Term Survivors Of Patients With Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy And Pancreatoduodenectomy, Tom Z Liang, Matthew H G Katz, Laura R Prakash, Deyali Chatterjee, Hua Wang, Michael Kim, Ching-Wei D Tzeng, Naruhiko Ikoma, Robert A Wolff, Dan Zhao, Eugene J Koay, Anirban Maitra, Suprateek Kundu, Huamin Wang

Faculty, Staff and Student Publications

Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15-60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p = 0.03), tumor resectability prior to NAT (p = 0.04), poorly differentiated …

Ether Phospholipids Are Required For Mitochondrial Reactive Oxygen Species Homeostasis, Ziheng Chen, I-Lin Ho, Melinda Soeung, Er-Yen Yen, Jintan Liu, Liang Yan, Johnathon L Rose, Sanjana Srinivasan, Shan Jiang, Q Edward Chang, Ningping Feng, Jason P Gay, Qi Wang, Jing Wang, Philip L Lorenzi, Lucas J Veillon, Bo Wei, John N Weinstein, Angela K Deem, Sisi Gao, Giannicola Genovese, Andrea Viale, Wantong Yao, Costas A Lyssiotis, Joseph R Marszalek, Giulio F Draetta, Haoqiang Ying

Faculty, Staff and Student Publications

Mitochondria are hubs where bioenergetics, redox homeostasis, and anabolic metabolism pathways integrate through a tightly coordinated flux of metabolites. The contributions of mitochondrial metabolism to tumor growth and therapy resistance are evident, but drugs targeting mitochondrial metabolism have repeatedly failed in the clinic. Our study in pancreatic ductal adenocarcinoma (PDAC) finds that cellular and mitochondrial lipid composition influence cancer cell sensitivity to pharmacological inhibition of electron transport chain complex I. Profiling of patient-derived PDAC models revealed that monounsaturated fatty acids (MUFAs) and MUFA-linked ether phospholipids play a critical role in maintaining ROS homeostasis. We show that ether phospholipids support mitochondrial …

Multifaceted Role For P53 In Pancreatic Cancer Suppression, Stephano S Mello, Brittany M Flowers, Pawel K Mazur, James J Lee, Fabian Müller, Sarah K Denny, Sofia Ferreira, Kathryn Hanson, Seung K Kim, William J Greenleaf, Laura D Wood, Laura D Attardi

Faculty, Staff and Student Publications

The vast majority of human pancreatic ductal adenocarcinomas (PDACs) harbor TP53 mutations, underscoring p53's critical role in PDAC suppression. PDAC can arise when pancreatic acinar cells undergo acinar-to-ductal metaplasia (ADM), giving rise to premalignant pancreatic intraepithelial neoplasias (PanINs), which finally progress to PDAC. The occurrence of TP53 mutations in late-stage PanINs has led to the idea that p53 acts to suppress malignant transformation of PanINs to PDAC. However, the cellular basis for p53 action during PDAC development has not been explored in detail. Here, we leverage a hyperactive p53 variant-p5353,54-which we previously showed is a more robust PDAC suppressor than …

Neoadjuvant Chemotherapy Is Associated With Altered Immune Cell Infiltration And An Anti-Tumorigenic Microenvironment In Resected Pancreatic Cancer, Andressa Dias Costa, Sara A Väyrynen, Akhil Chawla, Jinming Zhang, Juha P Väyrynen, Mai Chan Lau, Hannah L Williams, Chen Yuan, Vicente Morales-Oyarvide, Dalia Elganainy, Harshabad Singh, James M Cleary, Kimberly Perez, Kimmie Ng, William Freed-Pastor, Joseph D Mancias, Stephanie K Dougan, Jiping Wang, Douglas A Rubinson, Richard F Dunne, Margaret M Kozak, Lauren Brais, Emma Reilly, Thomas Clancy, David C Linehan, Daniel T Chang, Aram F Hezel, Albert C Koong, Andrew J Aguirre, Brian M Wolpin, Jonathan A Nowak

Faculty, Staff and Student Publications

PURPOSE: Neoadjuvant chemotherapy is increasingly administered to patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC), yet its impact on the tumor immune microenvironment is incompletely understood.

DESIGN: We employed quantitative, spatially resolved multiplex immunofluorescence and digital image analysis to identify T-cell subpopulations, macrophage polarization states, and myeloid cell subpopulations in a multi-institution cohort of up-front resected primary tumors (n = 299) and in a comparative set of resected tumors after FOLFIRINOX-based neoadjuvant therapy (n = 36) or up-front surgery (n = 30). Multivariable-adjusted Cox proportional hazards models were used to evaluate associations between the immune microenvironment and patient …

Leveraging Single Cell Technologies For The Characterization And Treatment Of Refractory Pancreatic Cancer, Maria Monberg

Dissertations and Theses (Open Access)

Heterogeneity is a hallmark of cancer, and the advent of multimodal single-cell technologies has helped uncover heterogeneity in a high-throughput manner in different cancers across varied contexts at an unprecedented resolution. In an effort to improve precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy with a mere 11% 5-year survival rate, this dissertation focuses on first questioning the assumptions of the most basic models used to study PDAC via multimodal single-cell characterization methods at multiple levels of biological organization (scCNVseq and snATACseq for DNA assays, scRNAseq for transcriptomics, and paired protein assays such as multiplexed immunofluorescence …

Differential Effects Of Dietary Macronutrients On The Development Of Oncogenic Kras-Mediated Pancreatic Ductal Adenocarcinoma, Liang Zhu, Juntao Ji, Jianjia Ma, Dan Wang, Muyun Liu, James Xianxing Du, Rong Chen, Wei Hou, James L Abbruzzese, Craig D Logsdon, Vincent W Yang, Yongde Luo, Weiqin Lu

Faculty, Staff and Student Publications

KRAS mutations are prevalent in patients with pancreatic ductal adenocarcinoma (PDAC) and are critical to fostering tumor growth in part by aberrantly rewiring glucose, amino acid, and lipid metabolism. Obesity is a modifiable risk factor for pancreatic cancer. Corroborating this epidemiological observation, mice harboring mutant KRAS are highly vulnerable to obesogenic high-fat diet (HFD) challenges leading to the development of PDAC with high penetrance. However, the contributions of other macronutrient diets, such as diets rich in carbohydrates that are regarded as a more direct source to fuel glycolysis for cancer cell survival and proliferation than HFD, to pancreatic tumorigenesis remain …

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Interventional Treatment With The Transjugular Intrahepatic Portosystemic Shunt (Tips) Procedure May Offer A Preferable Alternative To Systemic Anticoagulation In Patients With Cirrhosis And Portal Vein Thrombosis, Molly N. Pantelic

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Wang Z, Jiang MS, Zhang HL, et al. Is post-tips anticoagulation therapy necessary in patients with cirrhosis and portal vein thrombosis? A randomized controlled trial. Radiology. 2016;279(3):943-951. https://doi.org/10.1148/radiol.2015150369

for a patient with cryptogenic cirrhosis, gastroesophageal varices, pancreatic cancer, and portal vein thrombosis.

Emerging Role Of Fascin-1 In The Pathogenesis, Diagnosis, And Treatment Of The Gastrointestinal Cancers., Bojana Ristic, Jonathan Kopel, Syed A A Sherazi, Shweta Gupta, Sonali Sachdeva, Pardeep Bansal, Aman Ali, Abhilash Perisetti Md, Hemant Goyal

PCI Publications and Projects

Gastrointestinal (GI) cancers, including esophageal, gastric, colorectal, liver, and pancreatic cancers, remain as one of the leading causes of death worldwide, with a large proportion accounting for fatalities related to metastatic disease. Invasion of primary cancer occurs by the actin cytoskeleton remodeling, including the formation of the filopodia, stereocilia, and other finger-like membrane protrusions. The crucial step of actin remodeling in the malignant cells is mediated by the fascin protein family, with fascin-1 being the most active. Fascin-1 is an actin-binding protein that cross-links filamentous actin into tightly packed parallel bundles, giving rise to finger-like cell protrusions, thus equipping the …

Comparisons Of Oral, Intestinal, And Pancreatic Bacterial Microbiomes In Patients With Pancreatic Cancer And Other Gastrointestinal Diseases, Mei Chung, Naisi Zhao, Richard Meier, Devin C. Koestler, Guojun Wu, Erika De Castillo, Bruce J. Paster, Kevin Charpentier, Jacques Izard, Karl T. Kelsey, Dominique S. Michaud

Department of Food Science and Technology: Faculty Publications

Background: Oral microbiota is believed to play important roles in systemic diseases, including cancer. Methods: We collected oral samples (tongue, buccal, supragingival, and saliva) and pancreatic tissue or intestinal samples from 52 subjects, and characterized 16S rRNA genes using high-throughput DNA sequencing.

Results: Bray–Curtis plot showed clear separations between bacterial communities in the oral cavity and those in intestinal and pancreatic tissue samples. PERMANOVA tests indicated that bacterial communities from buccal samples were similar to supragingival and saliva samples, and pancreatic duct samples were similar to pancreatic tumor samples, but all other samples were significantly different from each …

Pancreatic Cancer: Leading To Failure Of Rivaroxaban As An Anticoagulant, Pratikkumar Vekaria Md, Chandrika Raiyani, Daniel Robitshek Md, Tejas Raiyani Md

Internal Medicine

Vascular Thromboembolism (VTE) is seen with hypercoagulable state and it can be a reason of significant morbidity and mortality. Cancer is considered as one of the most common causes of hypercoagulability and developing VTE. Since novel oral anticoagulants (NOAC) have been introduced in market for VTE prophylaxis and treatment, their use have been increased significantly as they are easy to use without episodic monitoring. Rivaroxaban is one of the commonly used NOACs and some of studies have shown its good efficacy for VTE.

Genetic Evolution And Prognostic Determinants Of Pancreatic Cancer On Longitudinal Liquid Biopsies, Vincent Bernard

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates amongst solid tumors. As early detection of PDAC is unusual and typically incidental, most patients present with locally advanced and metastatic disease where effective therapeutic strategies remain a significant unmet need. Specifically, surrogate biomarkers for tumor monitoring of PDAC may lead to improved elucidation of clinical actionability and prognostic potential. On the other hand, tumor tissue is rarely sampled in patients presenting with de novo or recurrent metastatic PDAC, apart from a fine needle aspiration or a core needle biopsy performed for diagnosis. This precludes the opportunity for …

Effect Of The Time Of Day And Queue Position In The Endoscopic Schedule On The Performance Characteristics Of Endoscopic Ultrasound-Guided Fine-Needle Aspiration For Diagnosing Pancreatic Malignancies., Jason Korenblit, Danielle M Tholey, Joanna Tolin, David Loren, Thomas Kowalski, Douglas G. Adler, Julie Davolos, Ali A. Siddiqui

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND AND OBJECTIVES: Recent reports have indicated that the time of day may impact the detection rate of abnormal cytology on gynecologic cytology samples. The aim of this study was to determine if procedure time or queue position affected the performance characteristics of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosing solid pancreatic malignancies.

PATIENTS AND METHODS: We conducted a retrospective study evaluating patients with solid pancreatic lesions in whom EUS-FNA was performed. Three timing variables were evaluated as surrogate markers for endoscopist fatigue: Procedure start times, morning versus afternoon procedures, and endoscopy queue position. Statistical analyses were performed to determine …

Modified Appleby Procedure With Arterial Reconstruction For Locally Advanced Pancreatic Adenocarcinoma: A Literature Review And Report Of Three Unusual Cases., Jessica A. Latona, Kathleen M. Lamb, Michael J. Pucci, Warren R. Maley, Charles J. Yeo

Department of Surgery Faculty Papers

BACKGROUND: Pancreatic body and tail ductal adenocarcinomas are often diagnosed with local vascular invasion of the celiac axis (CA) and its various branches. With such involvement, these tumors have traditionally been considered unresectable. The modified Appleby procedure allows for margin negative resection of some such locally advanced tumors. This procedure involves distal pancreatectomy with en bloc splenectomy and CA resection and relies on the presence of collateral arterial circulation via an intact pancreaticoduodenal arcade and the gastroduodenal artery to maintain prograde hepatic arterial perfusion. When the resultant collateral circulation is inadequate to provide sufficient hepatic and gastric arterial inflow, arterial …

Role Of Prostaglandin E2 In The Regulation Of Pancreatic Stellate Cells Hyper Activity Associated With Pancreatic Cancer, Chantale Charo

Dissertations and Theses (Open Access)

Pancreatic cancer is one of the most lethal type of cancer due to its high metastasis rate and resistance to chemotherapy. Pancreatic fibrosis is a constant pathological feature of chronic pancreatitis and the hyperactive stroma associated with pancreatic cancer. Strong evidence supports an important role of cyclooxygenase-2 (COX-2) and COX-2 generated prostaglandin E2 (PGE2) during pancreatic fibrosis. Pancreatic stellate cells (PSC) are the predominant source of extracellular matrix production (ECM), thus being the key players in both diseases. Given this background, the primary objective is to delineate the role of PGE2 on human pancreatic stellate cells (PSC) hyper activation associated …