Gastroenterology Commons^™

Therapeutic Resistance In Pancreatic Ductal Adenocarcinoma: Current Challenges And Future Opportunities, Aditi Jain, Phd, Vikas Bhardwaj

Kimmel Cancer Center Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancerrelated deaths in the United States. Although chemotherapeutic regimens such as gemcitabine+ nab-paclitaxel and FOLFIRINOX (FOLinic acid, 5-Fluroruracil, IRINotecan, and Oxaliplatin) significantly improve patient survival, the prevalence of therapy resistance remains a major roadblock in the success of these agents. This review discusses the molecular mechanisms that play a crucial role in PDAC therapy resistance and how a better understanding of these mechanisms has shaped clinical trials for pancreatic cancer chemotherapy. Specifically, we have discussed the metabolic alterations and DNA repair mechanisms observed in PDAC and current approaches in targeting …

Intrahepatic Cholangiocarcinoma Presenting As Li-Rads 5 "Hcc", Raja K. Dhanekula, Md, Donald Mitchell, Md, John Farber, Md, Ashwin R. Sama, Md, Jesse M. Civan, Md

Division of Gastroenterology and Hepatology Posters

Background

• Hepatocellular Carcinoma (HCC), if within Milan Criteria, is an indication for liver transplantation.

• In contrast, intrahepatic cholangiocarcinoma (IHCC) is a contra-indication to liver transplantation due to high rates of recurrence.

• LI-RADS 5 classification (synonymous with OPTN-5) carries a near 100% positive predictive value for HCC, allowing prioritization of patients for liver transplantation without histological confirmation.

• The “LI-RADS M” classification indicates the presence of malignancy not meeting diagnostic criteria for HCC. In theory, IHCC lesions should be identified as LI-RADS M and not LI-RADS 5.

Efficacy And Safety Of Infliximab In Older Inflammatory Bowel Disease Patients, Christina Cress Lindenmeyer, Md, Stephanie M. Moleski, Md, Maureen P. Whitsett, Med., Patricia L. Kozuch, Md

Division of Gastroenterology and Hepatology Faculty Papers

Background:

The limited data regarding treatment of inflammatory bowel disease (IBD) with anti-tumor necrosis factor antibodies in older patients suggest equal efficacy but higher morbidity and mortality compared to younger patients. This retrospective case control study aims to clarify the efficacy and safety of infliximab (IFX) in older IBD patients.

Limited Sampling Estimates Of Epigallocatechin Gallate Exposures In Cirrhotic And Noncirrhotic Patients With Hepatitis C After Single Oral Doses Of Green Tea Extract., Dina Halegoua-De Marzio, Walter K. Kraft, Constantine Daskalakis, Xie Ying, Roy L Hawke, Victor J. Navarro

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Epigallocatechin-3-gallate (EGCG) has antiangiogenic, antioxidant, and antifibrotic properties that may have therapeutic potential for the treatment of cirrhosis induced by hepatitis C virus (HCV). However, cirrhosis might affect EGCG disposition and augment its reported dose-dependent hepatotoxic potential.

OBJECTIVE: The safety, tolerability, and disposition of a single oral dose of EGCG in cirrhotic patients with HCV were examined in an exploratory fashion.

METHODS: Eleven patients with hepatitis C and detectable viremia were enrolled. Four had Child-Pugh (CP) class A cirrhosis, 4 had Child-Pugh class B cirrhosis, and 3 were noncirrhotic. After a single oral dose of green tea extract 400 …

Melena With Fever, Monica Patel, Jennifer Wilhelm

The Medicine Forum

The patient is a 62 year old Indian male with a past medical history significant for myasthenia gravis, hypertension, and diabetes mellitus, who presented to an outside hospital with fever, fecal incontinence, and melena. Work up at that hospital was remarkable for elevated liver function tests, heme-positive brown stool and a CT of the abdomen showing a thick ascending colon suggesting possible mass. The patient had an episode of desaturation and fever to 105 degrees Fahrenheit prior to transfer to Thomas Jefferson University Hospital for further evaluation. Upon arrival, the patient was in respiratory distress with oxygen saturation of 70% …

Nevirapine Hepatotoxicity: Case Report And Discussion, Matt Baichi

The Medicine Forum

Nevirapine (viramune) is a nonnucleoside reverse transcriptase inhibitor commonly used in combination with other antiretroviral medicines in the treatment of HIV/AIDS. The safety profile of nevirapine, as determined by review of prospective clinical trials, reports rash with an incidence of 16% as the most common side effect. Clinical hepatitis is reported to occur with an incidence of 1%. A review of the literature shows many case reports of nevirapine-induced hepatotoxicity in patients receiving both treatment and prophylaxis for HIV. The purpose of this case report is to stress the importance of early recognition and withdrawal of the offending drug.

A Case Of Chronic Intestinal Pseudo-Obstruction, Matt Baichi

The Medicine Forum

Scleroderma is a systemic disease characterized by the deposition of excessive collagen and other matrix elements in the skin as well as in multiple internal organs. Scleroderma can be classified into diffuse cutaneous disease and limited cutaneous disease. Limited cutaneous disease is characterized by skin involvement limited to the hands, face, feet, and forearms; it includes the CREST variant (calcinosis, raynauds, esophageal dysmotility, sclerodactyly, and telangiectasia). Diffuse cutaneous disease is characterized by skin involvement as well as early and diffuse visceral involvement. Clinically significant gastrointestinal involvement occurs in approximately 50% of all patients with scleroderma. The esophagus is the most …

Sleep Disturbances And Hypnotic Medication Use In Relation To Risk Of Barrett’S Esophagus And Esophageal Adenocarcinoma, Anastasia Shnitser, Md, Abhik Roy, Md, Sidney Cohen, Md, Anthony J. Dimarino, Md

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND

The incidence of esophageal adenocarcinoma (EA) has increased more rapidly than any other cancer (with the exception of malignant melanoma) in the United States over the past 30 years. Gastroesophageal reflux disease (GERD) is the strongest risk factor for the development of Barrett’s esophagus, which in turn leads to the rise of most EA’s. In a large portion of persons with sleep disorders, perhaps as high as 30%, GERD is a major causal or contributing factor. It has been proposed that the use of hypnotics for the treatment of sleep disorders may exacerbate the damaging effects of refluxate on …

Rhoa/Rock Pathway Is The Major Molecular Determinant Of Basal Tone In Intact Human Internal Anal Sphincter, Satish Rattan, Jagmohan Singh

Division of Gastroenterology and Hepatology Faculty Papers

Poster presented at: Digestive Disease Week (DDW) International meeting in San Diego, California.

Background and Aims

Knowledge of molecular control mechanisms underlying the basal tone in the intact human IAS is critical for the pathophysiology and rational therapy for debilitating rectoanal motility disorders.

Effect Of Pooled Human Intravenous Globulin (Ivig) On The Reversal Of Cholinergic Inhibition Of Smooth Muscle By Immunoglobulins (Iggs) From Patients With Scleroderma (Ssc), Jagmohan Singh, Vaibhav Mehendiratta, Sergio A. Jimenez, Sidney Cohen, Anthony J. Dimarino, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

Poster presented at: Digestive Disease Week (DDW) International meeting in San Diego, California.

Backgrounds and Aims:

The gastrointestinal (GI) tract is the most common internal organ system affected in SSc. We and others have shown before that the SSc immunoglobulins (IgGs) cause selective blockade of muscarinic type-3 cholinergic (M3-R) in the GI tract. Presently, there is no effective treatment for SSc although numerous cytotoxic and immunomodulatory agents have been employed with limited success and are marred with serious side effects. Present studies investigated the reversibility of SScIgGs-caused M3-R blockade by the pooled Intravenous immunoglobulins (IVIG).

Development Of Myogenic Ias Reconstructs From Human Internal Anal Sphincter (Ias) Smooth Muscle Cells (Smcs) With Functional And Molecular Properties Similar To Intact Human Ias, Jagmohan Singh, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

Poster presented at: Digestive Disease Week (DDW) International meeting in San Diego, California.

Background and Aims:

Rectoanal incontinence is associated with defective Internal Anal Sphincter (IAS). Current therapies are not satisfactory, raising a potential for the replacement of the dysfunctional IAS with the reconstructs. Present studies were performed to develop human IAS smooth muscle reconstructs with functional and molecular attributes similar to the intact human IAS Smooth muscle (SM).

The Use Of Infliximab In Older Inflammatory Bowel Disease Patients, Stephanie M. Moleski, Christina C. Lindenmeyer, Patricia L. Kozuch

Department of Medicine Faculty Papers

Limited data suggest anti-tumor necrosis factor (TNF) antibodies have equal efficacy but higher morbidity and mortality in older compared to younger inflammatory bowel disease (IBD) patients(1).

Boerhaave's Syndrome As A First Presentation Of Eosinophilic Esophagitis, Whitney E. Jackson, Vaibhav Mehendiratta, Juan P. Palazzo, Anthony J. Dimarino, Sidney Cohen

Division of Internal Medicine Faculty Papers & Presentations

Purpose: Prior studies have reported esophageal rupture following endoscopy or bolus impaction in eosinophilic esophagitis. The purpose of this study is to examine the frequency and characteristics of spontaneous rupture (Boerhaave's Syndrome) associated with vomiting S-435 AGA Abstracts in eosinophilic esophagitis.

Methods: A retrospective search of inpatient and outpatient records was conducted for the diagnoses "Boerhaave's", "eosinophilic esophagitis", and "esophageal rupture" from January 2001 to January 2011 within the gastroenterology division at an urban tertiary care hospital. For each subject identified, medical records, endoscopy reports, biopsy reports and radiographic studies were reviewed. A faculty member of the Department of Pathology …

Self Expanding Metal Stents (Sems) For Management Of Peri-Pancreatic Fluid Collections (Pfc): A Single Center Experience, Whitney E. Jackson, Jason Korenblit, Vaibhav Mehendiratta, Jason Lewis, Ali A. Siddiqui, Thomas E. Kowalski, David E. Loren

Division of Internal Medicine Faculty Papers & Presentations

Background

Endoscopic management of peri-pancreatic fluid collections (PFC) with or without organizing necrosis has been shown to decrease morbidity and mortality compared to early surgical management. Plastic stents are often used for transmural drainage, although the use of self-expanding metal stents (SEMS) has been reported. Theoretical benefits of SEMS include a large diameter for drainage and facilitation of endoscopic necrosectomy. We report a single-center experience to evaluate the efficacy and safety of SEMS for management of PFC.

Methods

A single-center retrospective review was performed of patients undergoing endoscopic management of PFC using SEMS from January through November 2011. Electronic database …

Patterns Of Acetaminophen Use At A Tertiary Care Center: Exposures Exceeding 4 Grams Daily, Jesse Civan, Victor Navarro, Jeffrey Riggio, Paul Adams, Steven Herrine, Simona Rossi

Jefferson Hospital Staff Papers and Presentations

Unintentional hepatotoxicity due to acetaminophen use at the recommended daily dose of up to four grams daily has increasingly been recognized as a significant problem. The phrase "therapeutic misadventure" has been coined in the literature, in reference to biochemical evidence of hepatocellular injury associated with acetaminophen use at recommended doses. Previous studies have documented a 25% to 40% incidence of two- to three-fold alanie aminotransferase (ALT) elevation, in healty volunteers administered one gram of acetaminophen every six hours.

The recognition of this problem is reflected in part by recent changes in FDA recommendations, including more stringent controls on the amount …

A Conserved Tissue-Specific Homeodomain-Less Isoform Of Meis1 Is Downregulated In Colorectal Cancer., Richard C Crist, Jacquelyn J Roth, Scott A Waldman, Arthur M Buchberg

Department of Microbiology and Immunology Faculty Papers

Colorectal cancer is one of the most common cancers in developed nations and is the result of both environmental and genetic factors. Many of the genetic lesions observed in colorectal cancer alter expression of homeobox genes, which encode homeodomain transcription factors. The MEIS1 homeobox gene is known to be involved in several hematological malignancies and solid tumors and recent evidence suggests that expression of the MEIS1 transcript is altered in colorectal cancer. Despite this potential connection, little is known about the role of the gene in the intestines. We probed murine gastrointestinal tissue samples with an N-terminal Meis1 antibody, revealing …

Assessment Of Adherence To Guidelines For Hepatocellular Carcinoma Screening In Hiv/Hcv Coinfected Patients, Jonathan M. Fenkel, Md, Victor J. Navarro, Md

Division of Gastroenterology and Hepatology Faculty Papers

Conclusions:

1. Self-reported adherence with published guidelines for HCC screening is poor among primary providers for HIV/HCV coinfected patients, including HIV specialists and University-based providers.

2. Unnecessary imaging is also frequently ordered on non-cirrhotics, particularly by University-based providers.

3. Improved adherence to guidelines is needed among primary providers as over 50% of HCC's may be missed, and many patients many not be referred for subspecialty GI or Liver care, where screening practices may differ.

Pegylated Interferon 2a And 2b In Combination With Ribavirin For The Treatment Of Chronic Hepatitis C In Hiv Infected Patients., Ravinder Dhillon, Simona Rossi, Steven K Herrine

Department of Medicine Faculty Papers

Coinfection with hepatitis C virus (HCV) and HIV is an increasingly recognized clinical dilemma, particularly since the advent of highly active antiretroviral therapy. Several studies of this population have demonstrated both more rapid progression of liver disease and poorer overall prognosis compared to HCV monoinfected patients. Consensus guidelines, based primarily on the results of 4 major randomized trials, recommend treatment with peginterferon and ribavirin for 48 weeks in coinfected patients. However, this current standard of care is associated with lower response rates to therapy than those seen in monoinfected patients. Important predictors of response include HCV genotype, pretreatment HCV RNA …