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UPMC Liver and Pancreas Institute (LPI) Molecular Mechanisms of Fatty Liver Disease by David A

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UPMC Liver and Pancreas Institute (LPI) Molecular Mechanisms of Fatty Liver Disease by David A Fall 2007 Pitt Digest Inside This Issue Page Two UPMC Liver and Pancreas Institute (LPI) Molecular Mechanisms of Fatty Liver Disease by David A. Geller, MD The UPMC Liver Cancer Center (LCC) was launched five years ago as a division of the Page 3 he UPMC Liver and Pancreas Institute Starzl Transplant Institute, and evaluates over Pancreaticobiliary (LPI) was established in 2006 to coordi- 500 new liver cancer patients per year. The Cancer Diagnosis T nate efforts among the clinical physicians and physicians and staff at the LCC specialize in Pages Four and Five scientists managing patients with liver and the management of HCC, cholangiocarcinoma, GI Grand Rounds pancreatic diseases. Flagship LPI programs gallbladder cancer, neuroendocrine cancer, include the Liver Cancer Center (LCC) and the and metastatic colorectal cancer to the liver. Page Seven Pancreatic Cancer Center (PCC). The LCC Treatment options for liver cancer include Expanded Hepatology Services and PCC function as multidisciplinary health surgical resection, liver transplantation, care teams at the forefront of providing regional chemotherapy, Yttrium-90 internal clinical services, innovative radiation, radiofrequency treatment strategies, and ablation (RFA), systemic cutting-edge research for PATIENT REFERRALS chemotherapy and novel patients with liver and For Liver Cancer: gene therapy approaches. Page Eight pancreatic cancer. 412-692-2001 LCC surgeons, pioneers in What Is This? The LPI, directed by livercancercenter.upmc.com laparoscopic liver resection Dr. Adam Slivka (see surgery for cancer, have CENTERS OF EXCELLENCE: related article on page 3 of For Pancreatic Cancer: performed more than 200 this issue) and Dr. David of these minimally invasive • PANCREAS &BILIARY DISEASES 888-623-PANC (7262) Geller, has the following hepatic resections. • INFLAMMATORY BOWEL DISEASE pancreaticcancercenter.upmc.com specific goals: The UPMC Pancreatic • LIVER DISEASES Cancer Center (PCC) was • NEUROGASTROENTEROLOGY AND ✔ Establishment of an organizational structure MOTILITY DISEASES established in 2006 and is co-directed by implementing efficient delivery of healthcare • INTESTINAL HEALTH & Drs. Herbert Zeh and James Moser. The PCC services for patients with liver and pancre- NUTRITION SUPPORT provides state-of-the-art treatment for patients atic cancer within the UPMC Health System; • GASTROINTESTINAL CANCER with pancreatic cancer, pancreatic cysts, and PREVENTION & TREATMENT chronic pancreatitis. The PCC evaluates more ✔ Coordination and cross-fertilization of the • WOMEN’S DIGESTIVE HEALTH than 300 patients with pancreatic cancer or established liver and pancreas centers of pancreatic lesions each year. excellence at UPMC Presbyterian, Monte- Pitt Digest fiore, Shadyside, and Passavant hospitals; is a publication of the ✔ A system-wide increase in overall clinic visits, Dr. Geller is Director of the UPMC University of Pittsburgh admissions, operative procedures, regional Liver & Pancreas Institute and is Division of Gastroenterology, therapies and transplant referrals; and the Co-Director of the Liver Cancer Hepatology and Nutrition Center. He is the Richard L. ✔ Promotion of clinical and basic research Simmons Professor of Surgery Editors: activities for liver and pancreatic diseases. at the University of Pittsburgh. Toby O. Graham, MD Janet R. Harrison, MD Brian Ng, MD Joy Jenko Merusi, MA Division Highlights Understanding the Molecular Mechanisms of Fatty Liver Disease ittsburgh, in the minds of many physicians, is by Jaideep Behari, MD, PhD P synonymous with liver transplantation. The pioneering efforts of Thomas Starzl MD, recent recipient of the presti- gious National Medial of Science, made organ transplantation onalcoholic fatty liver disease, characterized by the a modern-day miracle. New developments in the care of N accumulation of fat in the liver in the absence of patients with liver disease are featured in this Pitt Digest. significant alcohol intake, is an increasingly common reason Dr. David Geller’s cover page feature on the new multi- for referral to hepatology clinics. NASH (for nonalcoholic disciplinary UPMC Liver Pancreas Institute (LPI) is comple- steatohepatitis) is a progressive form of fatty liver disease mented by articles by Drs. Adam Slivka and Kapil Chopra, that can lead to cirrhosis and liver cancer. Molecular who share leadership roles in the LPI. signaling pathways in the liver cell play an important role UPMC liver and pancreas teams have been highly effec- in the development of this disease. tive in providing innovative patient care and in advancing medical and surgical knowledge. Recently, LPI’s multidisci- plinary pancreas team authored the June, 2007 issue of Gastroenterology Clinics of North America, entitled Advances in the Diagnosis and Treatment of Pancreatic Diseases. Thirty-three faculty and advanced fellows from the University of Pittsburgh contributed to this state-of-the-art update, covering both malignant and non-malignant diseases. In this Digest, Dr. Jaideep Behari focuses on complex liver disease research, highlighting the clinical problems of fatty Compared with normal mice (panel A), knockout mice lacking β-catenin liver diseases. Having completed our group’s NIDDK T-32 protein in the liver (panel B) show increased steatohepatitis when exposed to a steatogenic diet. training program under the mentorship of Dr. Satdarshan Paul Monga, Dr. Behari joined our faculty in June, 2006 and Research in my laboratory is focused on understanding is a promising physician scientist in our Division. the role of one such molecular signaling pathway, called the Two of our clinical fellows, Drs. Carmen Meier and Wnt/β-catenin pathway, in the development of fatty liver Scott Cooper (who also contributed to the production of disease. We use genetically engineered mice lacking the another GI Rounds Online physician education program on β-catenin protein in the liver (called “knockout” mice) and chronic pancreatitis http://girounds.pitt.edu), provide the teaching cases in this issue. Our annual live physician experimentally induce hepatic steatosis to study alterations education program, What’s New in GI and Hepatology will in molecular processes within liver cells. Recently, we feature the Management of Female-Predominant GI Diseases found that our knockout mice, when exposed to a steato- and will be held on November 15 and 16, 2007. genic diet, have a striking increase in hepatic steatosis, in We look forward to future opportunities to address your some cases approaching 100 percent. Knockout mice also questions about UPMC’s digestive disease programs, patient have disturbances in several important metabolic pathways collaborations and research breakthroughs. Join us for Pitt in the liver and show more hepatic fibrosis. We are currently GI’s educational offerings –- either in person or online! dissecting the molecular interactions that underlie these results, and future research plans include developing In good health, strategies which utilize these observations to design therapeutic interventions for this disease. Dr. Behari is an assistant professor of medicine with the University of David C. Whitcomb, MD, PhD Pittsburgh Division of Gastroenterology, Giant Eagle Foundation Professor Hepatology and Nutrition. He practices of Cancer Genetics in the Division’s Center for Liver Diseases. Professor of Medicine, Cell Biology & Physiology and Human Genetics Chief, Division of Gastroenterology, Hepatology and Nutrition 2 R ESEARCH U PDATE The State of Pancreaticobiliary Cancer Diagnosis by Adam Slivka, MD, PhD 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) may be elevated. Diagnostic imaging studies include CT scans and ith the unique dedication and expertise existing endoscopic ultrasound (EUS). CT scans using helical recon- W among faculty members of the Division of struction and IV contrast equipment can detect tumors up Gastroenterology, Hepatology and Nutrition and to 1cm in size, provide information about spread UPMC’s Oncologic Surgery and Transplant to distant organs, most commonly the liver Surgery groups, along with the creation and regional lymph nodes, and confirm of the Liver and Pancreas Institute invasion of blood vessels making the (LPI), UPMC is making major tumor inoperable. EUS can detect even advances to improve the early smaller tumors and has the added diagnosis and care of patients advantage of allowing safe fine needle afflicted with diseases of the aspiration with high diagnostic accuracy. pancreas and biliary system. The Although more than 90 percent of article which follows highlights our pancreatic cancers are adenocarcinomas, current knowledge and practice in the there is an increasing recognition of early diagnosis and management of two precancerous conditions in both solid and potentially devastating diseases, cancer of the cystic pancreas tumors. Pioneering work at UPMC and pancreas and cholangiocarcinoma. other institutes has examined the role of molecular derangements in early diagnosis in susceptible individuals Pancreas Cancer and the recognition of precancerous lesions. DNA from individual cells can be examined for oncogenic mutations. Of the 32,180 people in the United States diagnosed The only treatment offering a potential pancreatic cancer with pancreatic cancer every year, 31,800 will die from their cure is surgical resection with the operative approach disease. Pancreas cancer is the most lethal of all cancers depending on the location of the tumor. Although the and is the fourth highest cancer
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