Evidence-Based Management of Pancreatic Malignancy

Contents

Foreword: Evidence-Based Management of Pancreatic Malignancy xiii

Ronald F. Martin

Preface xv

Richard K. Orr

Outcomes in Pancreatic Cancer Surgery 219

Richard K. Orr

The increase in surgery for pancreatic cancer during the last 3 decadescan be correlated with a gradual decline in operative mortality and postop-erative complications. Although not all surgeons (nor all hospitals) canhave equal outcomes, the definition and tabulation of these outcomeshave been difficult. This article asks several pertinent questions: (1) whatis the scientific rationale for pancreatic resection? (2) what are the bestavailable results at this time? (3) who should be performing pancreatic re-sections? The article analyzes results of resection for adenocarcinoma ofthe exocrine pancreas, and excludes duodenal and ampullary cancers,pancreatic endocrine tumors, and tumors of less malignant potential.

Evidence-Based Imaging of Pancreatic Malignancies 235

Timothy Kinney

A high-quality pancreatic protocol computed tomography (CT) is the pri-mary imaging modality for diagnosing and staging pancreatic malignancy.The main limitation of CT is the lack of sensitivity for early pancreatic le-sions. Endoscopic ultrasound (EUS) provides an excellent complementto CT for both diagnosis and staging of pancreatic cancer, and allowseasy access for needle aspiration and tissue diagnosis. Magnetic reso-nance (MR) can be helpful for evaluating small hepatic nodules or cysticlesions of the pancreas, but in general, the role of MR and positron emis-sion tomography remains limited to special situations when the results ofCT and EUS are equivocal.

The Role of Endoscopic Ultrasonography in the Evaluationof Pancreatico-Biliary Cancer 251

Shyam Varadarajulu and Mohamad A. Eloubeidi

Accurate staging of pancreatico-biliary cancer is essential for surgicalplanning and for identification of locally advanced and metastatic diseasethat is incurable by surgery. The complex regional anatomy of the pancrea-tico-biliary system makes histologic diagnosis of malignancy at this regiondifficult. The ability to position the endoscopic ultrasound transducer atendoscopy in direct proximity to the pancreas and the bile duct, combinedwith the use of fine-needle aspiration, enables accurate preoperative stag-ing of cancer, especially cancer too small to be characterized by CT or

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MRI. Endoscopic ultrasonography (EUS) identifies patients unlikely to becured by surgery due to vascular invasion or regional nodal metastasis,thereby limiting procedure-related morbidity and mortality. This articlefocuses on the utility and recent advances of EUS in the evaluation ofpancreatico-biliary cancer.

The Evidence for Technical Considerations in Pancreatic Resections for Malignancy 265

Ronald F. Martin and Kashif A. Zuberi

The surgeon who wishes to perform successful resections for malignantprocesses involving the pancreas has to be conversant with a broad rangeof topics. There are extensive collections of data that usually give excellentguidance, but sometimes also provide conflicting advice. No matter whatthe data suggest might work best, the surgeon and local collaboratorsmust be able to deliver the quality care cited in some of these reports; usu-ally it is the best results that are published. There is a difference betweenresults that are statistically significant, clinically significant, and importantto the patient, and these concepts should never be confused.

Solid Tumors of the Body andTail of the Pancreas 287

Katherine A. Morgan and David B. Adams

Solid lesions of the body and tail of the pancreas challenge all the diagnos-tic and technical skills of the modern gastrointestinal surgeon. The infor-mation available from modern computed tomography (CT), magneticresonance (MR), and endoscopic ultrasound (EUS) imaging provide diag-nostic and anatomic data that give the surgeon precise information withwhich to plan an operation and to discuss with the patient during the pre-operative visit. A preoperative evaluation includes a thorough history anda pancreas protocol CT scan, supplemented by MR imaging and EUSwhen needed, to differentiate between the various potential diagnoses.These same modalities can be essential in proper staging in the case ofmalignant lesions, thus aiding in management decisions. Most lesionsultimately require operative resection, barring metastatic disease, withthe notable exception of autoimmune pancreatitis.

PortalVein Resection 309

Kathleen K. Christians, Alysandra Lal, Sam Pappas, Edward Quebbeman,and Douglas B. Evans

The American Hepato-Pancreatico-Biliary Association and Society of Sur-gical Oncology published a consensus statement in 2009 on the subject ofvein resection and reconstruction during pancreaticoduodenectomy (PD),and concluded that PD with vein resection and reconstruction is a viableoption for treatment of some pancreatic adenocarcinomas. This article de-scribes the current approaches and recent advances in the management,staging, and surgical techniques regarding portal vein resection. Withproper patient selection, a detailed understanding of the anatomy of theroot of mesentery, and adequate surgeon experience, vascular resectionand reconstruction can be performed safely and does not impact survivalduration. Isolated venous involvement is not a contraindication to PD when

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performed by experienced surgeons at high-volume centers as part ofa multidisciplinary and multimodal approach to localized pancreaticcancer.

Adjuvant and NeoadjuvantTherapy in Curable Pancreatic Cancer 323

F.W. Nugent and Keith Stuart

Pancreatic cancer is the tenth most common cancer in the United Statesand the fourth leading cause of cancer death. Afflicting approximately37,000 Americans yearly, more than 80% of patients are unresectableand, therefore, incurable at the time of their diagnosis. Although surgical re-section offers the only opportunity for cure, it remains largely unsuccessful;most patients who are candidates for surgical resection relapse and die infewer than 5 years. This mortality leaves a 5-year overall survival of about4% for patients diagnosed with pancreatic cancer. Perhaps the mostdaunting realization for physicians involved in the management of this dis-ease is the understanding that these numbers have not changed in morethan 30 years. As surgery remains the foundation of curative therapy forpancreatic cancer, this article reviews the data on adjuvant chemotherapyand adjuvant chemotherapy with radiotherapy as efforts to boost curerates.

Curative RadiationTherapy for Pancreatic Malignancies 341

Ellen W. Cooke and Lisa Hazard

Surgery is generally considered as the only curative therapy for pancreaticcancer; however, even with optimal surgery, long-term cure is achieved invery few patients, thus highlighting the need for adjuvant therapies. Radi-ation therapy, usually in combination with chemotherapy, plays a role inthe setting of unresectable, nonmetastatic pancreatic cancer. Its role inthe adjuvant setting remains controversial and as yet undefined. This arti-cle reviews the role of radiation therapy in the adjuvant and definitive set-tings, and describes recent improvements in the delivery of radiotherapythat allow for improved dose delivery with decreased toxicity.

Palliation in Pancreatic Cancer 355

E. James Kruse

Pancreatic cancer is rarely curable, and because of its location causes sig-nificant symptoms for patients in need of palliation. The common problemsof incurable pancreatic cancer are biliary obstruction, duodenal obstruc-tion, and pain. Approaches include surgical, endoscopic and radiologicinterventions. This article discusses the palliative options and controver-sies related to these symptoms.

Palliative Chemotherapy for Pancreatic Malignancies 365

Sharmila P. Mehta

Metastatic pancreatic cancer is often one of the most challenging malig-nancies a medical oncologist faces. Although the primary endpoint ofmany studies remains overall survival, palliation and quality of life are

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now more commonly being addressed. The author discusses the mostcommon chemotherapeutic modalities for the treatment of metastaticpancreatic cancer, such as single agent chemotherapy, combination ther-apy, targeted therapy, and second line treatment.

Intraductal Papillary Mucinous Neoplasm: A Clinicopathologic Review 377

Toms Augustin and Thomas J. VanderMeer

Intraductal papillary mucinous neoplasm (IPMN) is an intraductal mucin-producing epithelial neoplasm that arises from the main pancreatic duct(MD-IPMN), secondary branch ducts (BD-IPMN), or both (mixed type;Mix-IPMN). Neoplastic progression from benign adenoma to invasive ade-nocarcinoma has not been proven but is generally thought to occur. Withincreasing recognition of IPMN, our understanding of the diagnosis andmanagement of the tumors is evolving. At present, treatment options forpatients with IPMN range from observation to pancreatic resection de-pending on the natural history of the lesion. This review focuses on currentlyavailable data that guide management decisions for patients with IPMN.

Diagnostic Evaluation of Pancreatic Cystic Malignancies 399

Grant Hutchins and Peter V. Draganov

Cystic neoplasms of the pancreas are increasingly recognized because ofexpanding use and improved sensitivity of cross-sectional imaging studies.Major advances in the last decade have led to an improved understandingof the various types of cystic lesions and their biologic behavior. Despitesignificant improvement in imaging technology and the advent of endo-scopic ultrasound-guided fine-needle aspiration (EUS-FNA) the diagnosisand management of pancreatic cystic lesions remains a significant clinicalchallenge. Previous ‘‘operate in all cases of pancreatic cyst’’ strategieshave been refined and largely replaced using EUS and cyst fluid analysisas the crux for a more practical management approach. The first diagnosticstep remains the differentiation between pancreatic pseudocyst and cysticneoplasm. If a pseudocyst has been effectively excluded, the cornerstoneissue becomes to determine the malignant potential of the pancreatic cysticneoplasm. In most cases the correct diagnosis and successful manage-ment is based not on a single test but on incorporating data from varioussources including patient history, radiologic studies, endoscopic evalua-tion, in particular EUS, and cyst fluid analysis obtained during fine-needleaspirate. This review focuses on describing the various types of cystic neo-plasms of the pancreas and their malignant potential, and provide the clini-cian with a comprehensive diagnostic approach.

Pancreatic Cystic Neoplasms 411

Jennifer E. Verbesey and J. Lawrence Munson

Cystic neoplasms of the pancreas have been recognized for almost 2 cen-turies, but the principles of management continue to evolve. Clinicianshave a better understanding now of the diverse pathologies and behaviorsof cystic neoplasms, and can characterize them more precisely into be-nign, malignant, and of uncertain potential in their manifestations. Treat-ment is dependent on accurate diagnosis and tailored to the potential

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aggressiveness of the lesion, the surgical fitness of the patient, and theprobability of effecting long-term palliation or survival of the patient. Inthis article the authors review the classification based on the World HealthOrganization classification and the latest evidence-based literature of cys-tic neoplasms, and present their considerations for surgical managementof the various lesions. A better understanding of the biologic potential ofcystic neoplasms such as intraductal papillary mucinous neoplasms al-lows for a more patient-specific evidence-based management plan.

Laparoscopic Management of Pancreatic Malignancies 427

David A. Kooby and Carrie K. Chu

Laparoscopic pancreatic resection is performed with increasing frequencyfor malignant tumors. Data are emerging demonstrating the safety of thelaparoscopic approach for distal (left) pancreatectomy, with potential ben-efits over the standard open approach; however, less information exists asto the effects of laparoscopic resection of cancers of the pancreas. Thisarticle reviews and analyzes the existing literature on laparoscopic pancre-atectomy for pancreatic malignancies.

Index 447