GASTROENTEROLOGY CLINICSOF NORTH AMERICA

Advances in the Diagnosisand Treatment of Pancreatic Diseases

CONTENTS VOLUME 36 � NUMBER 2 � JUNE 2007

Preface xiiiDavid C. Whitcomb, Adam Slivka, and Kenneth K. Lee

Alcohol-Associated Pancreatitis 219Dhiraj Yadav, Georgios I. Papachristou, and David C. Whitcomb

Only a small proportion of heavy drinking individuals developpancreatitis. The environmental and host cofactors shown to have anassociation with alcoholic pancreatitis are smoking and race. Theknown genetic variations and polymorphisms do not seem to play animportant role in alcoholic pancreatitis. Newer developments in theunderstanding of complex disorders allow clinicians to understandbetter the role of cofactors and interactions between known and yetunknown environmental and genetic factors in causing alcoholicpancreatitis.

Autoimmune Pancreatitis 239Alyssa M. Krasinskas, Amit Raina, Asif Khalid,Mitchell Tublin, and Dhiraj Yadav

Autoimmune pancreatitis (AIP) is a benign, IgG4-related, fibroinflam-matory form of chronic pancreatitis that can mimic pancreatic ductaladenocarcinoma both clinically and radiographically. Laboratorystudies typically demonstrate elevated serum IgG4 levels and imagingstudies reveal a diffusely or focally enlarged pancreas with associateddiffuse or focal narrowing of the pancreatic duct. The pathologicfeatures include periductal lymphoplasmacytic inflammation, oblitera-tive phlebitis, and abundant IgG4-positive plasma cells. The treatmentof choice for AIP is steroid therapy. Diagnostic criteria for AIP havebeen proposed that incorporate histologic, radiographic, serologic, andclinical information.

Incidence, Risk Factors, and Prevention of Post-ERCPPancreatitis 259Scott T. Cooper and Adam Slivka

Pancreatitis is the most common complication of endoscopic retrogradecholangiopancreatography (ERCP). Because of the potential risks andconsequences of post-ERCP pancreatitis, considerable efforts have been

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made to define patient- and procedure-related factors that may beassociated with an increased risk of this complication, along withdetermining interventions that can be done to reduce post-ERCPpancreatitis.

Risk and Markers of Severe Acute Pancreatitis 277Georgios I. Papachristou, Gilles Clermont, Arun Sharma,Dhiraj Yadav, and David C. Whitcomb

Acute pancreatitis begins with pancreatic injury, elicits an acuteinflammatory response, and encompasses a variety of potentialcomplications in a subset of patients. Early determination of severityand risk of complications is crucial for instituting immediateinterventions to improve outcome. The severity of acute pancreatitisis a function of the amount of pancreas that is injured and the intensityof the inflammatory response. Early death is mainly linked to anoverwhelming inflammatory response leading to cardiovascular col-lapse or acute respiratory distress syndrome, whereas late death isassociated with infected pancreatic necrosis and sepsis. This articlereviews recent advancements in understanding the pathogenesis,immunology, and genetics of severe acute pancreatitis, and theliterature on laboratory-based markers, which predict a severe clinicalcourse and pancreatic necrosis.

Nutrition Support in Severe Acute Pancreatitis 297Stephen J.D. O’Keefe and Sumit Sharma

Nutritional support can improve the outcome from severe acutepancreatitis in two ways: first by providing the building blocks for tissuerepair and recovery, and second, by modulating the inflammatoryresponse and preventing organ failure, both of which are responsible formost of the morbidity and mortality associated with the disease. Thisreview discusses the evidence on which these statements are based.

Necrotizing Pancreatitis 313Steven J. Hughes, Georgios I. Papachristou, Michael P. Federle,and Kenneth K. Lee

Necrotizing pancreatitis continues to challenge clinicians, and few othermedical subjects currently elicit as much debate. Host characteristics orunderlying differences in pathophysiology that lead to pancreaticnecrosis remain poorly understood. Severe pancreatitis follows a two-phase clinical course. The early first phase manifests the features of thesystemic inflammatory response syndrome, and the second late phase ischaracterized by infectious complications. This article presents a multi-disciplinary literature-based approach to the treatment of patients withnecrotizing pancreatitis.

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Genetic Counseling for Nonsyndromic Pancreatitis 325Erin N. Fink, Jeffrey A. Kant, and David C. Whitcomb

An appreciation for the background of disease, not to mention themedical management of individuals, may be significantly affected bytesting for mutations and genetic variants associated with pancreatitis.Pretest and posttest counseling are essential for patients and families tobenefit fully from genetic testing for a susceptibility to developpancreatitis. The clinician, often working directly with a qualifiedgenetic counselor, must ensure that patients and families appreciate thebenefits and limitations of genetic tests, that results are interpretedaccurately, and that patients understand implications of information forboth their medical care and personal decisions. This article focuses onthe approach to genetic counseling for pancreatitis and implications ofrecent advances.

Pain in Chronic Pancreatitis and Pancreatic Cancer 335Kenneth E. Fasanella, Brian Davis, John Lyons, Zongfu Chen,Kenneth K. Lee, Adam Slivka, and David C. Whitcomb

Chronic, debilitating abdominal pain is arguably the most importantcomponent of chronic pancreatitis, leading to significant morbidity anddisability. Attempting to treat this pain, which is too often unsuccessful,is a frustrating experience for physician and patient. Multiple studies toimprove understanding of the pathophysiology that causes pain in somepatients but not in others have been performed since the most recentreviews on this topic. In addition, new treatment modalities have beendeveloped and evaluated in this population. This review discusses newadvances in neuroscience and the study of visceral pain mechanisms, aswell as genetic factors that may play a role. Updates of establishedtherapies, as well as new techniques used in addressing pain fromchronic pancreatitis, are reviewed. Lastly, outcome measures, whichhave been highly variable in this field over the years, are addressed.

Cystic Neoplasms of the Pancreas 365Michael P. Federle and Kevin M. McGrath

This article presents the approach to the most commonly encounteredpancreatic cystic masses that the authors employ at the University ofPittsburgh Medical Center. Variations on this approach are to beexpected, based on several factors, including the availability ofsophisticated imaging equipment and personnel.

Intraductal Papillary Mucinous Neoplasia 377Kevin M. McGrath, Alyssa M. Krasinskas, and Michael P. Federle

Intraductal papillary mucinous neoplasia is a neoplastic disorder ofvarying degree and extent that affects the pancreatic ductal epithelium.Clinical presentations may vary from an asymptomatic incidentalfinding to obstructive jaundice. Harbingers of malignancy include

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symptoms of jaundice, weight loss, or new-onset diabetes. In theabsence of findings that correlate with malignancy, natural history isunknown. Management of these patients is controversial, and should beindividualized based on surgical risk.

Multimodality Therapy for Pancreatic Cancer 391Jan Franko, Julia B. Greer, Coleen M. Moran, Asif Khalid,and A. James Moser

Neoadjuvant chemoradiotherapy can be administered safely to patientswith pancreatic cancer. Complete pathologic responses are rare,however, and the benefits of this approach compared with standardadjuvant therapy are uncertain. The only way to evaluate the efficacy ofneoadjuvant chemoradiotherapy is a prospective trial involvinga uniform patient population comparing the results of neoadjuvantand adjuvant therapy and a cohort receiving surgery alone. Sucha study can be designed in an ethically sound manner but requires thecollaboration of numerous institutions and careful coordination toachieve statistically conclusive results. The future of pancreatic cancerresearch rests on the availability and rapid transfer of new therapiesfrom the laboratory to clinical research.

Early Detection and Staging of Adenocarcinomaof the Pancreas 413Sam Pappas, Michael P. Federle, Anna E. Lokshin,and Herbert J. Zeh, III

Early diagnosis is likely to improve the outcome and survival in patientswho have pancreatic cancer. The sensitivity and specificity of currentscreening methods, however, limit their applicability to individuals athigh risk for developing pancreatic cancer. Further development ofserum markers may lead to improved diagnostic accuracy and allowscreening to be implemented more broadly. Proteomic profiling andevaluation of panels of markers hold particular promise for the future.This article provides a review of current methods and results for theearly detection and staging of pancreatic cancer, and discusses somepotential areas for future development.

Pancreatic Endocrine Tumors 431Niraj Jani, A. James Moser, and Asif Khalid

Incidental, nonfunctional pancreatic endocrine tumors (PET) areobserved with increasing frequency. Most are insulinomas. Endoscopicultrasound with fine-needle aspiration plays a significant role in thelocalization and tissue diagnosis of PET. Establishing PET behavior asaggressive or indolent remains challenging especially preoperatively.Newer techniques including DNA and micro-RNA analysis may playa role in this arena. Small benign PET may be enucleated or removedlaparascopically. Surgery is the mainstay of treating advanced diseaseincluding those with metastases and Zollinger-Ellison syndrome. The

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management of multiple endocrine neoplasia type 1 continues to bea challenge, including treating symptoms, targeted resections, and closeobservation. Diagnosis, management, and prognostication of PET areunder evolution and a number of changes in these fronts areanticipated.

Minimally Invasive Treatment of Pancreatic Disease 441Kenneth K. Lee, Dawei Chen, and Steven J. Hughes

Although open surgical procedures remain the standard for both benignand malignant diseases of the pancreas, in recent years a wide variety ofsurgical procedures performed on the pancreas have been completedlaparoscopically. This article reviews the application of minimallyinvasive surgery to the management of both benign and malignantdiseases of the pancreas.

Endoscopic Palliation of Pancreatic Cancer 455Michael Sanders, Georgios I. Papachristou, Kevin M. McGrath,and Adam Slivka

Endoscopic approaches have revolutionized the palliation of advancedpancreatic cancer. The ideal management consists of a multidisciplinaryapproach involving surgeons, endoscopists, radiologists, and oncolo-gists. Concurrent advances in the fields of interventional radiology andlaparoscopic surgical oncology should be readdressed and directlycompared with endoscopic approaches in randomized controlled trials.Exciting novel endoscopic techniques are being developed andevaluated; however, these approaches require further validation withrandomized clinical trials to determine the safety and efficacy whencompared with more traditional approaches.

Index 477

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