Deborah Bethards, M.D.

Most gastroenterologists have encountered patients who complain of chronic constipation. Colonoscopy shows no anatomical abnormalities. Nonetheless, conservative treatment with laxatives and bulking agents brings only temporary, minor relief. After several failed treatment attempts, the patient is distressed, uncomfortable and anxious; the gastroenterologist is frustrated. Deborah Bethards, M.D., a gastroenterologist at Penn State Hershey Medical Center’s Neurogastroenterology and Motility Clinic explains, “Failure of conservative treatment to resolve constipation should be a red flag. With no other detectable abnormality, the possibility of a chronic pelvic floor disorder that primarily affects women—known as dyssynergic defecation—should be considered.”

With this disorder, the rectosigmoid area does not function properly so that during attempted defecation, paradoxical anal contraction occurs, and pelvic floor muscles fail to relax. The result is that stool is retained in the rectum. If left untreated, complications such as fecal impaction, rectocele, megacolon, and fecal incontinence may occur.

Diagnosis of dyssynergic defecation is based on an in-depth patient interview, along with digital rectal exam (DRE) and anorectal manometry. Bethards notes, “It’s important to ask the patient pointed questions about their bowel habits as they often do not volunteer sometimes embarrassing details. Patients may report that when trying to defecate, they sit for long periods of time, strain, and use different positions, as well as digital maneuvers. Even with defecation, the patient senses incomplete evacuation. DRE may show diminished sphincter tone and inability to relax the sphincter when asked to strain.”

While traditional anorectal manometry is useful, new higher resolution technology yields more precise, readily interpretable measures. Penn State Hershey’s Neurogastroenterology and Motility Clinic is one of only eleven state-of-the-art facilities in the United States that serves as a motility disorder teaching center for GI fellows. Bethards explains, “By using high-resolution anorectal manometry available in our center, we can detect different causes of dyssynergic defecation such as absence of reflexive anal sphincter relaxation in response to increased pressure in the rectum [via balloon inflation] that may represent a congenital problem, or failure to relax the anal sphincter and pelvic floor when simulating defecation that represents an acquired behavioral problem. Patients with pelvic floor dysfunction are unable to expel the balloon and less likely to sense its inflation.”

Additional investigations may be needed to detect motility problems involving other areas of the gut, such as slow transit constipation. “Patients may also have complications like rectocele, severe hemorrhoids, or urinary incontinence. In our motility clinic, we interact with colorectal surgeons, urologists, radiologists, and gynecologists,” says Bethards.

Dyssynergic defecation often significantly improves with biofeedback training. Bethards notes, “Patients receive between six and eight biofeedback sessions that retrain the involved pelvic floor and sphincter muscles. Patients should be instructed to continue the technique at home but still need bi-annual ‘refresher sessions’ to maintain healthy bowel movement patterns.”

To watch a video about the motility clinic at Penn State Hershey Medical Center, visit PennStateHershey.org/motility.

Deborah Bethards, M.D.
Associate Professor of Medicine
Penn State Hershey Gastroenterology
PHONE: 717-531-1441
FELLOWSHIP: Gastroenterology & Hepatology, Penn State Milton S. Hershey Medical Center
RESIDENCY AND INTERNSHIP: Internal Medicine, Penn State Milton S. Hershey Medical Center
MEDICAL SCHOOL: George Washington University, School of Medicine

Over the past fourteen years, nearly 300 patients have been identified to carry a genetic predisposition to cancer. Hereditary gastrointestinal cancer syndromes identified include not only the more common ones such as Lynch syndrome, FAP, and MYH-Associated Polyposis (MAP), but also the more rare conditions such as Cowden syndrome (or PTEN Hamartoma Tumor syndrome), Peutz-Jeghers syndrome, and Hereditary Diffuse Gastric Cancer syndrome.

Referrals to the Cancer Genetics Program continue to increase with more than 450 referrals last year alone. Fortunately, to address this increasing demand, the Cancer Genetics Program has expanded to include an additional genetic counselor, Rio C. Stenner, M.G.C., C.G.C., who graduated with her Master’s degree in genetic counseling from the University of Maryland, School of Medicine.

One of the program’s research interests involves identifying barriers that prevent high risk patients from receiving cancer genetic counseling services and the option of genetic testing. According to Maria Baker, Ph.D., “Our paper by Mukherjee et al., entitled The revised Bethesda guidelines: extent of utilization in a university hospital medical center with a cancer genetics program, identified a number of barriers that prevent patients from being diagnosed with Lynch syndrome, the most common hereditary cause of colorectal cancer (CRC).” As a result of these findings, Penn State Hershey Medical Center along with a growing number of institutions across the country, are considering the pros and cons of implementing universal screening of all CRC specimens for Lynch syndrome. Studies show that one in 35 patients (or 2.9 percent) with CRC has Lynch syndrome, and that only 72 percent of CRC patients with Lynch syndrome meet revised Bethesda guidelines. The Penn State Hershey study showed that of those patients whose family histories did meet revised Bethesda guidelines, only 4.9 percent over the course of one year met with a genetic counselor to discuss concerns regarding family history and consider the option of genetic screening.

Given the underutilization of cancer genetic counseling services by this high-risk population, it is imperative that we take a public health approach to identifying patients and their family members with Lynch syndrome. Studies have shown that the cost-effectiveness ratio of universal screening of all CRC for Lynch syndrome is <$25,000 per life year saved, which is comparable to other preventative services such as colonoscopy every ten years. Based on our research findings and that of others, it should come as no surprise that one of the Healthy People 2020 objectives is to increase the proportion of individuals with newly diagnosed CRC who receive genetic testing to identify Lynch syndrome.

For more information about the program or to refer a patient, please call 717-531-1631. Visit us online at PennStateHershey.org/geneticcounseling.

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Maria Baker, Ph.D., F.A.C.M.G., M.S., C.G.C. Associate Professor of Medicine Department of Medicine Penn State Hershey Cancer Genetics Program Penn State Hershey Cancer Institute PHONE: 717-531-1631 EDUCATION: Penn State University (Ph.D.)	Maria Baker, Ph.D., F.A.C.M.G., M.S., C.G.C.
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Rio Stenner, M.G.C., C.G.C. Penn State Hershey Cancer Genetics Program Penn State Hershey Cancer Institute PHONE: 717-531-1631 EDUCATION: University of Maryland School of Medicine (MA)	Rio Stenner, M.G.C., C.G.C.

The multidisciplinary and coordinated nature of the program is unique to the central Pennsylvania region. Patients admitted into the program receive coordinated care from a team of surgeons, gastroenterologists, hepatologists, medical oncologists, radiation oncologists, radiologists, geneticists, and psychiatrists. Diagnostic questions are optimally clarified by modalities such as endoscopic ultrasound and computed tomography, with expert gastrointestinal pathologists providing immediate interpretation when biopsy procedures are necessary, resulting in high diagnostic accuracy with less repeat procedures. Such facets of the program allow surgeons to optimally address the challenges of tumor removal in these cases.

Kimchi explains, “All of the surgeons have completed specialized fellowships in addition to their general surgical residency. Our level of clinical focus on this set of cancers allows us to gain skill with cutting-edge techniques for particularly challenging cases.”

Laparoscopic tumor removal or ablative techniques in particular are gaining ground, as they offer an equivalent level of effectiveness while leading to less post-operative pain and shorter recovery times.

Most patients who successfully complete acute surgical treatment enter into a GI Cancer Survivorship Clinic. Gusani explains, “The Survivorship Clinic began in 2009 to offer coordinated follow-up care for patients who have undergone any GI or abdominal surgery; 95 percent of the approximately 100 patients we see every month are cancer survivors. This clinic is unusual in that it is led by a group of GI surgeons who recognized that long-term care of GI cancer survivors tends to fall through the cracks and needs to be centrally coordinated.”

As highlighted in a recent issue of the Journal of Clinical Oncology, there is growing awareness in the medical community of a need for survivorship care that includes nutritionists, social workers, psychologists, and nurse practitioners, in addition to routine GI cancer monitoring. The combination of the Liver, Pancreas, and Foregut Tumor Program with the GI Cancer Survivorship Clinic means that patients with some of the most challenging and complex malignancies receive coordinated care beginning upon initial diagnosis and continuing through to long-term survival follow-up.

Read two of the team’s publications:

• Cancer Survivorship: A New Challenge for Surgical and Medical Oncologists – J Gen Intern Med 24(Suppl 2): 456-8
• Quality of Life Assessment in Postoperative Patients with Upper GI Malignancies – J Surgical Research 163, 40-46 (2010)

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Kevin Staveley O’Carroll, M.D., Ph.D. Professor of Surgery Penn State Hershey Surgical Oncology PHONE: 717-531-8887 FELLOWSHIP: Surgical Oncology, Johns Hopkins Hospital RESIDENCY: General Surgery, Johns Hopkins Hospital MEDICAL SCHOOL: University of Oklahoma College of Medicine	Kevin Staveley O’Carroll, M.D., Ph.D.
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Eric T. Kimchi, M.D., F.A.C.S. Associate Professor of Surgery Penn State Hershey Surgical Oncology Penn State Hershey Cancer Institute PHONE: 717-531-8887 FELLOWSHIP: Surgical Oncology, University of Chicago Hospitals RESIDENCY: General Surgery, Wayne State University Hospital MEDICAL SCHOOL: Penn State College of Medicine	Eric T. Kimchi, M.D., F.A.C.S.
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Niraj J. Gusani, M.D., M.S., F.A.C.S. Assistant Professor of Surgery and Public Health Sciences Penn State Hershey Surgical Oncology PHONE: 717-531-8887 FELLOWSHIP: Surgical Oncology, University of Pittsburgh Medical Center RESIDENCY AND INTERNSHIP: General Surgery, University of Chicago Medical Center MEDICAL SCHOOL: University of Pennsylvania School of Medicine	Niraj J. Gusani, M.D., M.S., F.A.C.S.
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Jussuf T. Kaifi, M.D., Ph.D. Assistant Professor of Surgery and Medicine Penn State Hershey Surgical Oncology Penn State Hershey Cancer Institute PHONE: 717-531-8887 FELLOWSHIP: Surgical Oncology, University of Hamburg Medical School RESIDENCY: General Surgery, University of Hamburg Medical School MEDICAL SCHOOL: University of Hamburg Medical School	Jussuf T. Kaifi, M.D., Ph.D.

Douglas G. Field, M.D.

Proper daily nutrition is a necessary part of growth and development and usually a source of comfort and pleasure. But for many pediatric patients with congenital or acquired medical issues or behaviorally-based impairments, “Feeding problems can be a source of stress for patients, parents, family members, and may endanger the child’s overall health and development,” according to Douglas Field, M.D., a pediatric gastroenterologist and medical director of the Penn State Hershey Pediatric Feeding Program.

Field, along with Keith Williams, Ph.D., B.C.B.A., director of the pediatric feeding program and practicing behavioral psychologist, have tailored the program to provide diagnostic, treatment planning, and interventions for children with problems ranging from food refusal to motor impairments that hinder proper swallowing. Prior to their appointments at Penn State Hershey, both Field and Williams worked in the Pediatric Feeding Disorders Program at the Kennedy Krieger Institute in Baltimore, Maryland.

Penn State Hershey’s Pediatric Feeding Program is one of few in the United States and tackles some of the most difficult pediatric feeding problems. Field says, “Services are extended from infants to adolescents. Many are pre-term infants, have autism spectrum disorder, or have cerebral palsy. These types of feeding problems cross therapeutic boundaries. To address the needs of the patient as a whole, a treatment team typically consists of some combination of a pediatric gastroenterologist, behavioral psychologist, nutritionist, and a speech pathologist.” In addition to usual outpatient interventions, an intensive day treatment program is offered that attracts patients from across the country and around the world who need serious feeding issues resolved.

By partnering with The Ronald McDonald House in Hershey, intensive program patients may live in the community on an outpatient basis and come to the clinic to undergo feeding therapy for seven to eight hours per day over approximately one month. Field notes, “With the interdisciplinary, intensive approaches we use, patients tend to make tremendous progress. Some enter the program with a G-tube, never having swallowed food before. By the time they leave, they’re able to get at least part of their daily nutrition from normal oral feeding.”

For more information about the pediatric feeding program or to refer a patient, please call 717-531-7117. Visit us online at PennStateHershey.org/feedingprogram.

Douglas G. Field, M.D.
Chief, Pediatric Gastroenterology and NutritionProfessor of Pediatrics
Medical Director, Pediatric Feeding Program
Penn State Hershey Pediatric Gastroenterology
PHONE: 717-531-6955
FELLOWSHIP: Pediatric Gastroenterology, Johns Hopkins University
RESIDENCY: Pediatrics, Thomas Jefferson University Hospital
MEDICAL SCHOOL: Jefferson Medical College

A colon mass lesion in the process of being resected by ESD.

Moyer notes that the benefits of EMR and ESD outweigh the risks when performed in a high volume center with an appropriate team who have the correct equipment and procedure volume; however, complications can occur and should be explained to the patient. “Complications include bleeding, which occurs in five to ten percent of cases, and a lower risk of perforation (1 percent EMR, 2 to 5 percent ESD). Incomplete removal of abnormal tissue is a longer-term complication with EMR (between 1 and 11 percent) and ESD (1 percent).”

Risks are potentially greater in patients with lesions unsuccessfully removed during a screening procedure. This team strongly advises referring physicians to avoid attempting to remove any lesion that is not felt to be appropriate for complete removal during the screening procedure. Dye explains, “With failed attempts at lesion removal, the resulting inflammatory reaction can adhere remaining abnormal tissue to the muscularis propria, making subsequent endoscopic removal difficult and raising the potential for major surgery.” Referring physicians are advised to mark the target lesion, obtain a biopsy from the periphery if necessary, and refer the patient to tertiary care so that removal is complete and risks are minimized.

Patients typically undergo routine surveillance endoscopy at three or six months and one year after. Mathew notes, “Minimally invasive procedures like EMR and ESD can make a real difference in the life of a patient. They can return to normal activities usually the next day with a very low risk of any complication or lesion recurrence.”

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Indications for EMR or ESD

• Mucosal lesions of the esophagus (cancerous or potentially cancerous) including lesions within Barrett’s esophagus and short-segment Barrett’s esophagus with dysplasia
• Gastric mucosal lesions
• Duodenal lesions, including ampullary lesions requiring ERCP-assisted ampullectomy
• Adenomatous colon and rectal lesions not amendable to safe or complete removal during screening colonoscopy
• Limited gastric and rectal carcinoid tumors
• Select submucosal lesions

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	Charles Dye, M.D. Associate Professor of Medicine, Medical Director, Endoscopy Center Penn State Hershey Gastroenterology PHONE: 717-531-1441 FELLOWSHIP: Therapeutic Endoscopy, University of Chicago Medical Center; Gastroenterology, University of Chicago Medical Center RESIDENCY: Internal Medicine, University of Chicago Medical Center MEDICAL SCHOOL: Penn State College of Medicine
	Abraham Mathew, M.D. Professor of Medicine, Penn State Hershey Gastroenterology PHONE: 717-531-1441 FELLOWSHIP: Gastroenterology, Penn State Milton S. Hershey Medical Center RESIDENCY: Internal Medicine, Abington Memorial Hospital MEDICAL SCHOOL: Mahatma Gandhi University
	Matthew Moyer, M.D. Assistant Professor of Medicine, Penn State Hershey Gastroenterology PHONE: 717-531-1441 FELLOWSHIP: Gastroenterology, Penn State Milton S. Hershey Medical Center RESIDENCY: Internal Medicine, Penn State Milton S. Hershey Medical Center MEDICAL SCHOOL: Penn State College of Medicine

David Soybel, M.D.

Physicians at Penn State Hershey Medical Center and Penn State College of Medicine are investigating how to better detect and address nutritional needs before and after major complex GI surgery. According to David Soybel, M.D., “A significant proportion of patients with complex medical histories have pre-existing deficiencies in specific micronutrients such as zinc, copper, selenium, and magnesium. Major procedures place high demands on already compromised micronutrient stores, and often put these patients into a state of ‘micronutrient distress’ that may be associated with longer and more complicated recovery.”

Soybel’s research aims to establish methods to routinely detect and treat these deficiencies in high-risk patients, both before and after surgery. “Pre-surgical recognition of micronutrient deficiencies would provide the opportunity for micronutrient repletion and other interventions, and better prepare patients to get well post-surgery,” says Soybel. “Likewise, in acute situations, recognition of such deficiencies and rapid intervention could help patients better recover after emergency procedures.”

Gordon Lee Jensen, M.D., Ph.D.

Based in State College and one of few physicians in the country who specializes in management of intestinal failure, Gordon Lee Jensen, M.D., Ph.D., explains, “In the past, many of these intestinal failure patients would have died or become indefinitely dependent on intravenous, total parenteral nutrition (TPN). But now, because of new medications and advances in medical nutrition therapy, some can eventually come off of TPN and lead more normal lives. Today, TPN is more often a temporary supportive measure. Successful transition off of TPN depends on a number of factors. If a patient has at least 100 cm of small bowel length and a portion of intact colon (or at least 150 cm of small bowel and no functional or intact colon), and residual disease is controlled, then the odds are favorable for them to eventually adapt to enteral or oral nutrition.”

Jensen adds, “All such patients should receive consultation with an expert in the medical nutrition field who will develop a comprehensive, individualized nutritional therapy, and pharmacologic management plan.” Because such plans can be implemented by the patient’s regular community physician, consultations need not be limited by geography; consulting medical nutrition experts routinely serve large referral regions and work closely with referring medical care teams.

Soybel and Jensen are beginning to establish the foundations of comprehensive research and clinical programs to manage the nutritional status of patients with complex abdominal and GI problems. “It’s important to make a long-term commitment to these patients, often over several years,” notes Jensen.

“By addressing nutritional and absorption issues throughout the full continuum of the treatment process, patients have improved chances of a smooth recovery and long-term treatment success,” explains Soybel.

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Post-surgical medical nutrition plans are also key to helping patients lead more normal lives long-term. For many patients who undergo complex abdominal surgery or have chronic GI disease, large portions of the intestine are removed or become dysfunctional. In these cases, intestinal failure may result, marked by functioning gut mass below the minimal amount necessary for adequate nutrient and fluid absorption.

Factors Associated with Micronutrient Deficiency

• Obesity
• Tobacco use
• Chronic pulmonary disease
• Advanced age
• Diabetes
• Depression
• Immunosuppression from illness or medication

Common Causes of Intestinal Failure

• Massive entrectomies secondary to:
  • Necrotizing enterocilitis
  • Crohn’s disease
  • Mesenteric infarction
  • Volulus
  • Trauma
  • Tumor
• Intestinal dysfunction
  • Inflammatory bowel disease
  • Pseudo-obstruction
  • Radiation enteritis
  • Congenital villus atrophy

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David Soybel, M.D.
Professor of Surgery
Chief, Division of General Surgery
Penn State Hershey Surgery
PHONE: 717-531-8887
RESIDENCY: Surgery (General), Washington University-St. Louis
MEDICAL SCHOOL: University of Chicago-Pritzker School of Medicine

Gordon Lee Jensen, M.D., Ph.D.
Professor of Medicine
Department of Nutritional Sciences
Penn State University
PHONE: 814-865-0108
FELLOWSHIP: Hyperalimentation/Nutrition, New England Deaconess Hospital
RESIDENCY: Internal Medicine, New England Deaconess Hospital/ Harvard Medical School
MEDICAL SCHOOL: Cornell University Medical College

Douglas B. Stairs, Ph.D.

The rising incidence of Barrett’s esophagus (BE) over the past two decades, coincident with increases in obesity, chronic heartburn, and gastroesophageal reflux disease, has focused attention on questions about how to monitor and treat these patients. About four in 1,000 BE patients annually develop esophageal adenocarcinoma (EAC), a 30- to 40-fold greater risk than in the general public. EAC, in turn, is linked to five-year survival rates of only about 20 percent. While early identification of high-risk BE patients is critical to improve EAC survival, factors predictive of cancer progression have not been identified.

“We really don’t understand yet why some patients with BE progress to develop esophageal dysplasia and EAC, while most others don’t. The research we’re beginning to conduct at Penn State Hershey Medical Center aims to identify molecular red flags in BE patients that predict EAC,” says Douglas Stairs, Ph.D. Stairs, along with colleagues at Penn State Hershey Gastroenterology and Hepatology, including Thomas J. McGarrity, M.D., and Atul Bhardwaj, M.D. recently launched efforts to build a BE tissue bank, using blood and tissue samples obtained from routine endoscopic monitoring in Medical Center BE patients. “We expect to enroll about 150 patients in the tissue bank project in this first year; each time a participant undergoes endoscopy, additional samples will be obtained. The tissue bank will allow us to conduct prospective, longitudinal, population analyses of gene expression patterns in patients with BE,” explains Stairs.

An over-arching goal of the BE tissue bank research program is to identify biomarkers that predict short- and long-term clinical outcomes. Stairs adds, “In the short-term, we plan to look for biomarkers associated with esophageal dysplasia and presence of EAC. After several years, different research questions will be examined. With years of follow-up data for individual patients, we plan to identify gene expression patterns that predict a positive response to treatment.”

A longer-term goal is to develop a blood test that will allow stratification of BE patients upon diagnosis into low versus high EAC risk groups. Theoretically, high-EAC risk patients may undergo closer monitoring and more aggressive treatment, and low-EAC risk patients relatively less frequent monitoring and more conservative treatment. Looking to the future, BE biomarker data may help to make early EAC identification and improved survival a routine event.

Douglas B. Stairs, Ph.D.
Assistant Professor of Pathology and Pharmacology
Department of Pathology, Department of Pharmacology
Penn State Hershey Cancer Institute
PHONE: 717-531-6725
MEDICAL SCHOOL: University of Pennsylvania (Ph.D.)

Surgeons at Penn State Hershey Medical Center, the only Medicare-approved center for liver transplantation in central Pennsylvania, performed the region’s first adult living donor liver transplant on Jestine Reider and John Kreider, brother and sister from Elizabethtown, Pa. in July 2008.

One of the greatest challenges facing patients who require a liver transplant is surviving the wait for a donor organ. Each year, nearly 16,000 patients in the United States are on the liver transplant waiting list, according to UNOS; yet only between 5,000 and 6,000 receive a transplant from a deceased donor.¹ Zakiyah Kadry, M.D., said “Although liver transplant patients are stratified based on MELD scores, some die while waiting. To decrease wait times and associated mortality, some patients can receive grafts from live donors.”

In 2011, only 247 live donor liver transplants were performed in the United States, according to HRSA/ OPTN statistics.² “Live donor programs must be UNOS-certified and require at least two surgeons trained in hepato-biliary surgery, as well as transplantation,” notes Kadry.

In 2008, she began the adult live donor liver transplantation program at Penn State Hershey Medical Center, and implemented a highly rigorous, selective process for screening donors and recipients, and for conducting transplant surgeries. “Only about 30 percent of live liver donor applicants in our program are accepted. First, an independent donor advocate team examines the applicant’s overall medical and psychosocial health. Applicants are excluded if donation presents risks to their health, psychosocial situation, employment, or if there is evidence of coercion to donate.” Applicants who remain eligible then undergo anatomic liver studies. Kadry explains, “Donors must be able to provide sufficient graft volume and still have approximately 40 percent remaining functional liver volume. Only those with a positive anatomical evaluation undergo liver biopsy. Based on the biopsy, we rule out individuals with 15 percent or more hepatic fat content, and we sometimes find unexpected congenital, metabolic, and infectious problems that may also exclude donation. The goal is to select healthy individuals for whom liver donation presents minimal risk. The recipients on our waiting list qualify for live donor liver transplantation but are required to have a MELD score ≤ 25. Patients with higher MELD scores are often too compromised to fully benefit from a live donor transplant and tend to develop ‘small-for-size’ syndrome, with prolonged jaundice and increased risk of infection and death,” says Kadry.

Zakiyah Kadry, M.D., F.A.C.S.

The program is unique in its adult focus; the majority of live donor programs focus on pediatric recipients. Adult live donor liver transplants are particularly challenging given the liver volume requirements and the technical complexity associated with this. The program, however, addresses a relatively larger need.

“We have been fortunate to have excellent results in our live donor liver transplant program,” explains Kadry. “Donors have fared well post-donation with a very low incidence of minor complications that have resolved without sequelae. The high level of success we’ve accomplished is not only related to our donor and recipient selection process, but also our sophisticated team. Everyone from the transplant coordinators, donor advocate group, nursing and OR staff, anesthesiologists, critical care team, histocompatibility group, hepatologists and surgeons, as well as well-defined protocols focus on identifying and following recipients most likely to benefit from live liver transplantation while minimizing donor risk.”

For more information, visit PennStateHershey.org/transplant

References
1. United States, transplant waiting list candidates, by organ; http://optn. transplant.hrsa.gov/data/default.asp, accessed June 26, 2012
2. United States, Liver Transplants Performed; Summary January 1, 1988 March 31, 2012. at: http://optn. transplant.hrsa.gov/latestData/rptData.asp, accessed June 26, 2012.

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Zakiyah Kadry, M.D., F.A.C.S.

Professor of Surgery
Chief, Division of Transplantation
Penn State Hershey Transplant Surgery
PHONE: 717-531-6092
FELLOWSHIP: Surgery, University Health Center of Pittsburgh
RESIDENCY: Surgery (General), Penn State Milton S. Hershey Medical Center
MEDICAL SCHOOL: Royal College of Surgeons in Ireland

Walter Koltun, M.D.

Walter A. Koltun, M.D., explains, “Because about 25 percent of patients with IBD have a family history of the disease, a crucial starting point for the IBD BioBank was to establish a patient registry to gather medical and demographic data not only from IBD patients but also their family members. Since beginning this work in 1998, we now have nearly 1,400 patients, some with three generations of family members entered into the registry. This is a powerful tool for investigating not only the genetic basis of the disease but also environmental, microbiological and epigenetic IBD risk factors.”

Blood samples obtained from IBD registry participants have been used to create the BioBank’s DNA specimen bank. DNA is derived from registry participant’s immortalized leukocytes and is used in research aimed at identifying IBD-associated genes, with the goal of identifying genetic factors that can predict or affect clinical care and outcome of therapies. Koltun notes, “The addition of the IBD tissue library in 2006 marked the beginning of an important expansion of the IBD BioBank. Originally serum specimens obtained from IBD patients allowed for DNA analysis of patients recruited, but now patients who are undergoing surgery also have the harvesting of tissue samples. This extends our research into how such DNA alterations express themselves in the actual gastrointestinal tissue.”

Zen Wu Lin, Ph.D., Walter A. Koltun, M.D., and Lisa S. Poritz, M.D., director of colorectal research, review a patient’s research data.

The IBD BioBank has become a rich and valuable resource for investigators at the Medical Center and College of Medicine who are focused on the study of IBD-associated pathology. As an example, a recent publication from Rishahb Sehgal, M.B., M.R.C.S., and colleagues from the Medical Center (DISEASES OF THE COLON & RECTUM,2012; 55:115-21), demonstrated a link between an alteration in the IRGM immunity-related GTPase family gene and the risk for recurrent ileocolonic Crohn’s disease. Other researchers at the Medical Center and College of Medicine, including Zhenwu Lin, Ph.D., and Lisa Poritz, M.D., have launched long-term research programs that involve studying genetic factors which affect and predict IBD-related disease phenomena, including pouchitis, altered intestinal permeability, and even more common pathology such as diverticulitis. Their projects aim to identify the genes and cellular pathways that control the inflammatory cascade in the human intestine and their relation to the emergence and progression of IBD. Koltun notes, “The [Penn State Hershey Medical Center’s] IBD BioBank fosters strong academic and clinical collaboration. We have partnered with the basic science groups at our institution to truly bring the translational concept of bedside clinical problems to the scientific bench and then back again to bedside as a physical and scientific reality.” The sharing of clinical perspectives and biologic material, uniquely available at institutions such as the Medical Center, will continue to inspire new directions in IBD clinical research.

Contact:
Walter A. Koltun, M.D., F.A.C.S., F.A.S.C.R.S.
Professor of Surgery
Chief, Division of Colon and Rectal Surgery
Peter and Marshia Carlino Chair in Inflammatory Bowel Disease
Penn State Hershey Colon and Rectal Surgery
Penn State Hershey Cancer Institute
Phone: 717-531-5164
Fellowship: Surgery (Colon/Rectal), Lahey Clinic
Fellowship: Surgery (General), Harvard Medical School
Residency: Brigham and Women’s Hospital
Medical School: Harvard Medical School

Click to enlarge image

By contrast, surgery can be curative in patients with ulcerative colitis. Koltun says, “In ulcerative colitis, inflammation and disease are limited to the colon, and so complete removal of the colon eliminates the disease and represents a full cure. For ulcerative colitis patients who undergo a proctocolectomy, a subsequent reconstruction with ileal pouch anal anastomosis (IPAA) is the surgical procedure of choice.” Although technically demanding and typically only performed at specialty surgical centers, this operation presents several important advantages over the more conventional total proctocolectomy with ileostomy—the most obvious being that IPAA patients maintain bowel continence and defecate normally through the anus. During the IPAA procedure, the colon is removed and a new fecal reservoir is created using a portion of the healthy small intestine, which is anastomosed directly to the anus. Typically, a temporary ileostomy is also created, and after a two-month healing period, the ileostomy is taken down and flow of feces through the anus is re-established.

Koltun notes, “As minimally invasive surgical techniques and devices have become available, we have incorporated these into our colorectal surgery practice for IBD patients.” Currently, Penn State Hershey Medical Center is among the leaders in terms of the number of laparoscopic surgeries performed on IBD patients. Unlike open surgeries, laparoscopic procedures result in a smaller incision and shorter recovery time, and are linked to fewer surgery-related infections and complications. The smaller incisions are especially important to IBD patients who are usually younger and may require repetitive surgery in the future. “We perform 200-250 major operations on IBD patients per year, and depending on degree of disease severity, about 30-40 percent of these are managed at least in part laparoscopically. Crohn’s disease is commonly treated with laparoscopic surgery that gets the patient out of the hospital usually in two to four days. For ulcerative colitis patients, we have completed more than 400 IPAA procedures, increasingly via the laparoscopic technique, and more than forty without even a temporary ileostomy. These numbers continue to increase over time as the number of patients we treat rises.”

Although approximately 5 percent of patients experience complications from IPAA surgery that result in placement of a permanent ileostomy, Medical Center IPAA patients surveyed had an average satisfaction of 9.2 (on a scale of one to 10). Koltun says, “Most of these patients resume their pre-illness level of activity and commonly state that they should have had the surgery sooner.”