Shadyside Gastroenterology Group at UPMC Pancreatic Problems After Gastric Bypass by Randall E

Spring 2009 Pitt Dige st

Inside This Issue Page Two Shadyside Gastroenterology Group at UPMC Pancreatic Problems after Gastric Bypass by Randall E. Brand, MD Page Three Division Highlights he Division of Gastro- Pages Four and Five T enterology, Hepatology GI Grand Rounds and Nutrition’s new group

Page Six located at UPMC Shadyside Faculty Update illustrates a triumphant union between private practice and Page Seven academic medicine. Building Advances in Research and Endoscopic Therapy upon the successful private gastroenterology practice of Page Eight Drs . Howard Dubner and Lee • What Is This? Weinberg, our group has • PancreasFest 2009 expanded to five gastroen - terologists with the additions of Drs. Andres Gelrud , Scott CENTERS OF EXCELLENCE : Cooper and myself. Amid this • PANCREAS & B ILIARY DISEASES expansion, the team has • INFLAMMATORY BOWEL DISEASE maintained a commitment to • LIVER DISEASES the general gastroenterology • NEUROGASTROENTEROLOGY AND service at UPMC Shadyside , MOTILITY DISEASES Hillman Cancer Center and • INTESTINAL HEALTH & N UTRITION SUPPORT the surrounding community ,

• GASTROINTESTINAL CANCER while simultaneously offering P REVENTION & T REATMENT the clinical expertise and

• WOMEN ’S DIGESTIVE HEALTH resources of a major, academic institution. The Division of Gastro- Division of Gastroenterology, Hepatology and Nutrition at UPMC enterology, Hepatology and Shadyside (L to R, starting with back row): Lee Weinberg, MD; Heather Hathy, PA-C; Andres Gelrud, MD; Randall Brand, MD; Scott Cooper, MD; Nutrition recruited Dr. Gelrud Howard Dubner, MD. Pitt Digest from the University of Cincin - is a publication of the nati to serve as the director University of Pittsburgh of Therapeutic Endoscopy at Dr. Gelrud’s research may instructor of medicine, he is Division of Gastroenterology, UPMC Shadyside. Dr. Gelrud be found on page 7 of this an advanced EUS and ERCP Hepatology and Nutrition provides tertiary therapeutic issue. Dr. Cooper graduated trainee and will join the prac - endoscopic support including from the University of Pitts - tice on a full-time basis in Editors: ERCP, single balloon enter- burgh GI Fellowship Program June 2009. As you may know, Toby O. Graham, MD oscopy and stent placement. in July 2008. Currently an Janet R. Harrison, MD More information about continued on page 6 Brian Ng, MD Joy Jenko Merusi, MA D IVISION C LINICAL R ESEARCH

Malnutrition and Pancreatic Problems After Gastric Bypass Surgery for Morbid Obesity

fter gastric bypass surgery for morbid Division of Gastroenterology, Hepatology and A obesity (BMI > 40kg/m2), stomach Nutrition, Clinical & Translational Science Institute volume is reduced and the duodenum and (CTSI ) and Magee Bariatric Surgery with support from proximal jejunum is bypassed, resulting in Solvay Pharmaceuticals. Patients with excessive, malabsorption and weight loss. While most continued weight loss after bariatric surgery will be patients tolerate surgery well with weight loss screened for fat absorption and loss of pancreatic plateauing near ideal body weight, some secretion. Those with > 20% fat malabsorption will be patients continue to lose weight, becoming so treated with pancreatic enzyme supplements for a malnourished that a reversal of the surgery is three-month period to assess weight stabilization or considered. Until now, no studies have investigated gain. After three months, fat absorption and a pancreatic pancreatic function in obese patients following bypass stimulation test will be repeated to determine if fat digestion surgery. It is likely that the pancreas atrophies due to and absorption are improved after enzyme supplementation. bypass of pancreatic stimulation paired with perpetual stimulation of the inhibitory ileal break. More subjects are needed for this study. Gastric bypass This current research examines pancreatic secretion and patients with uncontrolled weight loss may be referred to food absorption in patients who have lost >100 lbs. in the Dr. Tina Rakitt – pager: (412) 571-4038 – or Dr. Stephen first year following bypass surgery. Collaborators include the O’Keefe (412) 648-7217 for study information .

Division’s Expansion to Serve Patients Better

by Chad J. Scott, MA, MPM at UPMC Shadyside, as Dr. Brand enhance services in Monroeville to discussed in this issue’s cover story. complement UPMC’s new Monroeville espite the outstanding services Also, both male and female patients hospital, scheduled to open in 2011. Davailable to GI and liver patients are cared for at the Magee-Womens Referrals for interested patients in the Division of Gastroenterology, Hospital of UPMC. are easy. Simply call the main UPMC Hepatology and Nutrition’s main UPMC More recently, our faculty physicians Presbyterian Digestive Disorders Presbyterian location, Oakland is have started seeing more patients in Center number at (412) 647-8666 not an easy destination for some – the east, north and south suburbs. or, toll-free, 1-866-4GASTRO especially for those already nervous Procedure clinics now operate at the (1-866-442-7876) , and the reception - about a colonoscopy! Monroeville Surgery Center, South ist can refer you to the preferred Over the past few years, our Division Side Surgical Center, McKeesport service location for your patient. expanded clinical and procedure ser - Hospital and the Bethel Surgical vice locations to optimize patient con - Center. Additionally, the Monroeville Mr. Scott is the chief venience . Highly specialized patient Image Center hosts a gastroenter- administrator for the services are still performed in the ology outpatient clinic, and UPMC University of Pittsburgh Division’s primary Oakland location. Passavant has a liver consult clinic. Division of Gastroenterology, Hepatology and Nutrition. Consults and most procedures are We plan to offer even more services now done “off campus ” as well. in the South Hills of Pittsburgh within Extensive outpatient clinics and the coming year, as well as in a new procedure services have been added North Hills location . Of course, we will

2 D IVISION H IGHLIGHTS

he University of Pittsburgh Medical Center (UPMC) is a network of over 20 health care facilities in Western T Pennsylvania with two flagship hospitals: UPMC Presbyterian, linked to a world famous transplant center, and UPMC Shadyside, linked to the Hillman Cancer Center. The clinical, research and education mission of the Division of Gastroenterology, Hepatology and Nutrition is thriving at both facilities and in other specialty and outreach locations. Expansion to UPMC Shadyside began several years ago with the recruitment of Drs. Howard Dubner and Lee Weinberg , representing one of our region’s top consultative groups and members of our Division ’s training faculty. The UPMC Shadyside group has rapidly expanded with the recruitment of Drs. Randall Brand, Andres Gelrud, Scott Copper and Marc Schwartz (starting July 2009 ). This extraordinary team is featured in this issue of Digest .

Amidst this expansion, our Division continues to attend to the discovery of new knowledge about complex inflammatory diseases of the digestive systems and to treat related complications of these diseases . Complex disorders, by definition, are syndromes which occur through the interaction of multiple variables (genetic, metabolic, and environmental) that may not be independently pathologic but can combine in various permutations to alter disease severity and progression in the same underlying disease. Being able to characterize and quantify the individual and synergistic contributions of these factors could result in accurate, predictive tools to provide the right treatment to the right patient at the right dose at the right time – i.e. personalized medicine.

The Division’s 2009 GI Division Research Retreat focused on personalized medicine, particularly for diseases of the liver and pancreas as well as IBD and functional pain syndromes. Clinical faculty met with scientists from the University of Pittsburgh, Carnegie Mellon University and other institutions, on March 7 –8, 2009. Physicians discussed unpredictable outcomes and features of inflammatory disorders with scientists specializing in immunology, tissue repair & regeneration, neuroscience, DNA repair and oncogenesis, psychology, epidemiology, genetics and biomarkers. Bonding started during the Pitt –UConn basketball game, while research collaborations developed during the poster sessions and subsequent meetings .

Anticipated retreat outcomes include the development of more than a dozen NIH Challenge Grant applications, plans for collaborative RO1s and related discussions. Stay tuned for details. I hope that you continue to enjoy reading about Division happenings and discoveries in this publication. We look forward to close interactions in the future.

In good health,

David C. Whitcomb, MD, PhD Giant Eagle Foundation Professor of Cancer Genetics Professor of Medicine, Cell Biology & Physiology and Human Genetics Chief, Division of Gastroenterology, Hepatology and Nutrition

3 GRAND ROUNDS

A Perplexing Patient with Refractory Ascites

AST 58). HCV RNA was 2200 copies/ml, Genotype 4; ANA was by Behar Madani, MD 1:80; and serum complements, C3 41, C4<10 . There was Hepatology Fellow hematuria (RBC 15/hpf) and proteinuria (6.5gm/24hr). The ascites was chylous with elevated triglycerides (261 mg/dl), a SAAG < 1.1 g/dl; gram stain and cultures for bacteria and acid fast organisms were negative. A CT scan of the Case Presentation abdomen revealed splenomegaly, large ascites, patent hepatic vessels and no evidence of cirrhosis or portal hyper - 39-year-old Saudi woman returned to Pittsburgh after tension. Liver biopsy showed mild fibrosis and peritoneal A a 17-year absence due to worsening ascites. She biopsy was nega - underwent a liver transplant at UPMC in 1991 secondary to tive for TB and autoimmune hepatitis. In 2003, she developed HCV and lymphoma. A was treated with standard interferon (IFN) for one year with kidney biopsy no response. In 2006 , she developed ascites secondary was performed to tuberculous peritonitis and was treated with isoniazid, showing changes ethambutol and rifampin. Initially yellow, the ascitic fluid consistent with became milky six months prior to current presentation. membranoprolifer - Though initially responsive to diuretics, the ascites became ative glomerulo- refractory requiring large volume paracenteses every two nephritis (MPGN) weeks. Concurrent with the refractory ascites, she devel - associated with Figure 2: Glomerulus with “tram track” which oped acute renal injury cryoglobulinemia results from basement membrane splitting and and was told she may (CG) , and blood reduplication (white arrows). require hemodialysis. An work was positive August 2007 liver biopsy for cryoprecipitate, type III, polyclonal (IgG, IgM,IgA) revealed grade I hepatitis confirming the diagnosis. C activity index and Cryoglobulinemia (CG) is defined by the presence of CG stage II/IV fibrosis. in serum and immune complex deposits in small to medium Past medical history is vessels and presents typically with a classical triad of pur - significant for diabetes pura, weakness and arthralgia. Type II and III are mixed and hypertension , and polyclonal (IgM and IgG) and can be seen with viral infec - medications include tions such as hepatitis C. MPGN associated with type II CG tacrolimus, spironolac - is the predominant type of HCV-related glomerulonephritis

Figure 1: Kidney biopsy with membrano- tone, furosemide, (GN) and presents with nephritic syndrome or acute nephritis proliferative form of glomerulonephritis. amlodipine and insulin. with rapid deterioration in renal function. MPGN and CG are The glomerulus (arrow) has accentuated Married and living with late presentations in the natural course of HCV infection lobularity and a more solid appearance. her husband, she had no and are often clinically unsuspected. Adjacent to the glomerulus is an area of interstitial fibrosis and tubular atrophy. children and denied any The treatment of HCV-CG includes symptomatic therapy, tobacco, alcohol or illicit anti-HCV therapy and immunosuppressives. Recommended drug use. She worked as an office manager prior to her screening for HCV patients should include assessment of return to Pittsburgh. renal function and serum cryoglobulin, complements and Examination was notable for cachexia . Her abdomen rheumatoid factor. was severely distended, diffusely tender with a peritoneal Our patient was started on antiviral therapy with pegylated catheter in situ draining milky fluid. IFN and ribavarin , and her HCV-RNA became undetectable Labs were notable for mild hyponatremia; creatinine 1.3 at four weeks. mg/dl; normal platelets; hemoglobin 10.7 mg/dl; hypoal- buminemia 1.8 mg/dl; and mild transaminases (ALT 30;

4 GRAND ROUNDS

Epistaxis and a Bloody Liver

of hepatic veins with mild ascites in a non-cirrhotic liver. Abdominal ultrasound showed a combination of fatty infiltra - by Joseph Rodemann, MD tion and hereditary hemorrhagic telangiectasia and patent Gastroenterology Fellow major hepatic vessels. After undergoing an uneventful cholecystectomy, the patient was discharged home . One month later, she was admitted with recurrent abdom - inal pain, acute renal failure, leukocytosis, and abnormal Case Presentation LFTs including a total bilirubin of 4.1 and an INR of 2.4. During this hospital course, the patient became acutely ill 32-year-old female with recurrent epistaxis was with mental status changes and was transferred to the ICU A admitted to Magee Women’s Hospital of UPMC at for blood pressure support and mechanical ventilation. 29 weeks gestation with a three-week She was diagnosed with Enterocccal history of sharp, intermittent RUQ bacteremia of unknown etiology pain and nausea . She had no other without signs of endocarditis on past medical or surgical history. TEE. The patient was listed status Her family history was only signifi - 1 for liver transplant and received a cant for epistaxis in her father. liver , but she died intraoperatively. The patient’s labs were consis - Pathology of the native liver tent with gallstone pancreatitis. revealed multiple abnormal venous Ultrasound displayed cholelithiasis channels, shunts and arteriovenous with findings of acute cholecystitis. malformations consistent with Labor was induced one week later hereditary hemorrhagic telangiecta - due to the patient’s deteriorating sia (HHT). Notable were central Figure 1: CT scan showing numerous telangiectasia seen clinical status, and normal vaginal vein sclerosis and focal hepatic within the liver parenchyma. Numerous arteriovenous fistulas delivery occurred. Following ERCP with early filling and enlargement of the hepatic veins. venous obliteration with marked with sphincterotomy and stone congestion and hemorrhage , severe extraction, her symptoms and labs ischemic cholangiopathy with wide - improved , and she was sent home. spread bile duct necrosis and tissue Four weeks later, the patient necrosis containing gram positive was admitted to UPMC for interval coccoid bacteria, and moderately cholecystectomy. At that time, she severe steatohepatitis. represented with abnormal LFTs and HHT, also known as Osler-Weber- abdominal pain. Hepatology was Rendu syndrome, was first recog - consulted prior to surgery. nized in the 19th century as a examination revealed an obese familial disorder with abnormal female in no overt distress with normal Figure 2: Pathology demonstrates tortuous thin-to-thick- vascular structures causing bleeding vital signs. Sclera were anicteric. walled abnormal vessels. from the nose and gastrointestinal Abdomen was distended with moder - tract. Common symptoms are epis - ate RUQ tenderness and hepatomegaly. There were no stig - taxis, gastrointestinal bleeding and iron deficiency anemia, mata of chronic liver disease, and neurologic exam was normal. and incidence is 1:20,000 in retrospective U.S. studies. Notable labs including albumin of 2.2, total bilirubin 2.2, The Curaçao Criteria, used to diagnose HHT, includes epis - direct bilirubin of 1.4, AST 87, ALT 53, AP 652, lipase 245, taxis, telangiectasias, visceral lesions and family history . and INR of 2.2 indicated a mixed hepatocellular and Hepatic involvement occurs in 30 to 80 percent of cases cholestatic liver injury pattern with synthetic dysfunction. of HHT with common complications including portal hyper - Testing for viral, autoimmune, and metabolic causes of liver tension, high-output cardiac failure and biliary disease. disease was unremarkable. Abdominal CT scan displayed Treatment options include hepatic artery embolization, liver numerous telangiectasia in liver parenchyma, numerous transplant and antibodies targeting vascular endothelial arteriovenous fistuli with early filling and enlargement growth factor receptor.

5 F ACULTY U PDATE

Robert E. Schoen, MD, MPH, professor of Dr. Slivka is a professor of medicine with the University of medicine and epidemiology with the Univer - Pittsburgh Division of Gastroenterology, Hepatology and sity of Pittsburgh Division of Gastroenterol - Nutrition, where he serves as the Division’s associate chief ogy, Hepatology and Nutrition, has initiated for clinical services. Dr. Slivka’s research interests include testing on a vaccine that could prevent clinical applications of gastrointestinal endoscopy for colon cancer in people at high risk. In a diagnosis and therapy, including the development and novel approach to cancer prevention, his study will explore testing of new instrumentation and therapy to improve an abnormal variant of a self-made cell protein called endoscopic outcomes in pancreaticobiliary disease. MUC1, which is altered and produced in excess in advanced For more information on NPF’s gala, visit adenomas and cancer. If shown to be effective, Dr. Schoen’s www.pancreasfoundation.org or call, toll free, 1-866-726-2737. research may spare patients the risk and inconvenience of repeated invasive surveillance tests. Miguel Regueiro, MD and colleagues have Pitt’s colon cancer vaccine research is sponsored by the found that infliximab prevents Crohn’s dis - National Cancer Institute and The Nathan S. Arenson Fund. ease recurrence after surgery. (Regueiro M., Dr. Schoen’s co-investigator is Olivera Finn, PhD , professor et. al. Gastroenterology 2009; 136:441-50). and chair in the Department of Immunology. One year after resective intestinal surgery only nine percent of patients receiving Adam Slivka, MD, PhD will be honored infliximab had endoscopic recurrence compared to with the National Pancreas Foundation’s 85 percent of patients on placebo (p=0.0006). 2009 Courage Award recognizing his distin - Dr. Regueiro is an associate professor of medicine with the guished achievements and dedication to Division of Gastroenterology, Hepatology and Nutrition. He patients with pancreas diseases. Dr. Slivka serves as the associate chief for education and as the pro- will receive this award at NPF’s annual gala gram director for the University of Pittsburgh’s Gastroenterology on Friday evening, June 26, 2009 at the Circuit Center on Fellowship Program. Dr. Regueiro co-directs the UPMC Inflam - Pittsburgh’s South Side. matory Bowel Disease Center and heads IBD clinical services.

Gastroenterology Group at UPMC Shadyside continued from page 1

I hail from Evanston Northwestern procedural environment with a dedi - Information about Division of University and am an established EUS cated emphasis on patient comfort . Gastroenterology, Hepatology specialist and also perform stent The primary intention of the GI and Nutrition services at UPMC placements in the gastrointestinal Division at UPMC Shadyside is to Shadyside campus may be found tract . Drs. Dubner and Weinberg are provide continuity of care for the gen - at http: //www.dom.pitt.edu/gi. outstanding gastroenterologists with eral GI needs of UPMC Shadyside Physician referrals may be made by interests in IBD, and their leadership complemented by solid expertise in calling 1-800-544-2500 . and collegiality have made our Division advanced GI procedures and special - expansion possible. Finally, we are ized care for GI oncology patients Dr. Brand is a visiting welcoming Marc Schwartz, MD from served by the Shadyside and Hillman professor of medicine with the University of Chicago to further facilities . For example, my research on the Division of Gastroen - terology, Hepatology and strengthen the Division’s IBD program. the early detection of pancreatic cancer Nutrition and serves as the State-of-the-art renovation of the and high risk pancreatic cancer fami - academic director of the GI UPMC Shadyside GI Laboratory reflects lies, will hopefully translate to better Division, UPMC Shadyside. He also directs the administration’s commitment to care for these at-risk individuals. In the GI Malignancy Early Detection, Diagnosis program success. Construction will collaboration with genetics counselor and Prevention Program for the University be complete this summer and will Sally Hollister, MS, we are also available of Pittsburgh Department of Medicine. provide a technologically advanced to assist in the management of hered- itary GI diseases including cancer syndromes and pancreatic disorders .

6 7

Answer to What Is This? photos on page eight: Diagnosis: Colo-colonic intussusception secondary to a giant lipoma The CT scan of the abdomen and pelvis two years ago showed a lobulated, fat-attenuated mass in the ascending colon consistent with lipoma. The CT scan of the abdomen and pelvis during the current admission showed a colo-colonic intus - susception with the ascending colon lipoma (5.8 x 4.6 cm) as the lead point . The patient underwent a laparoscopic-assisted right hemicolectomy with ileocolic anastomosis. Surgical pathology revealed a large submucosal lipoma with overlying mucosal ischemic changes.

What Is This? provided by Vinay Sundaram, MD, Gastroenterology Fellow References upon request.

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c i p o c s o d n E d n a h c r a e s e R n i s e c n a v d A y p a r e h T e d i s y d a h S C M P U t a

U R E T A D P H C R A E S E Nonprofit Org. U.S. Postage Digestive Health Network PAID Division of Gastroenterology, Hepatology and Nutrition Pittsburgh, PA 200 Lothrop Street Permit No. 425 Pittsburgh, PA 15213

Information concerning Pitt Digest or requests for additional newsletter copies may be directed to Joy Jenko Merusi at [email protected] or 1-866-4-GASTRO (1-866-442-7876). Visit our website at www.dom.pitt.edu/gi

What Is This? PancreasFest 2009: Personalizing the Pancreas Presentation: A 32-year-old woman presented with abdominal pain, bilious vomiting and watery diarrhea. Advancements in Pancreatic Cancer and CT scan of the abdomen and pelvis was performed Pancreatitis for Physicians and Researchers (Figure 1). The patient had an abdominal CT scan two years earlier for workup of non-specific abdominal he University of Pittsburgh Division of Gastroenterology, pain (Figure 2). What is your diagnosis? T Hepatology and Nutrition will again host one of the nation’s most innovative pancreas education and research Compare your answer to Dr. Sundaram’s on page 6. meetings, PancreasFest 2009 . Education programs are interspersed with investigative research meetings (sponsored in part by NIDDK and Figure 1 NAPCG) to further the multi-disciplinary under - standing and treatment of pancreas diseases. This program will be held July 23 –25, 2009 at The University Club in Pittsburgh, PA. Overnight accommoda -

Figure 2 tions will be available. For registration and overall program informa - tion, contact Joy Merusi at [email protected] or (412) 578-9518 or visit www.dom.pitt.edu/gi/education.html .

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