PANCREATIC CANCER – CLINICAL MANAGEMENT Edited by Sanjay K. Srivastava Pancreatic Cancer – Clinical Management Edited by Sanjay K. Srivastava Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Martina Blecic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published March, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Pancreatic Cancer – Clinical Management, Edited by Sanjay K. Srivastava p. cm. ISBN 978-953-51-0394-3 Contents Preface IX Chapter 1 The Genetics of Pancreatic Cancer 1 Dagan Efrat and Gershoni-Baruch Ruth Chapter 2 Systems and Network-Centric Understanding of Pancreatic Ductal Adenocarcinoma Signalling 15 Irfana Muqbil, Ramzi M. Mohammad, Fazlul H. Sarkar and Asfar S. Azmi Chapter 3 Novel Biomarkers in Pancreatic Cancer 31 Simona O. Dima, Cristiana Tanase, Radu Albulescu, Anca Botezatu and Irinel Popescu Chapter 4 Medical Therapy of Pancreatic Cancer: Current Status and Future Targets 55 Edward Livshin and Michael Michael Chapter 5 Temporal Trends in Pancreatic Cancer 77 Tadeusz Popiela and Marek Sierzega Chapter 6 Current Perspectives and Future Trends of Systemic Therapy in Advanced Pancreatic Carcinoma 89 Purificacion Estevez-Garcia and Rocio Garcia-Carbonero Chapter 7 Immunotherapy of the Pancreatic Cancer 109 Yang Bo Chapter 8 An Overview on Immunotherapy of Pancreatic Cancer 137 Fabrizio Romano, Luca Degrate, Mattia Garancini, Fabio Uggeri, Gianmaria Mauri and Franco Uggeri Chapter 9 Bacterial Immunotherapy-Antitumoral Potential of the Streptococcal Toxin Streptolysin S- 163 Claudia Maletzki, Bernd Kreikemeyer, Peggy Bodammer, Joerg Emmrich and Michael Linnebacher VI Contents Chapter 10 Anesthesia and Pain Management: Techniques and Practice 177 Maurizio Marandola and Alida Albante Chapter 11 Multi-Disciplinary Management of Metastatic Pancreatic Cancer 197 Marwan Ghosn, Colette Hanna and Fadi El. Karak Chapter 12 Pancreatic Cancer – Clinical Course and Survival 205 Birgir Gudjonsson Chapter 13 Endoscopic Management of Pancreatic Cancer: From Diagnosis to Palliative Therapy 213 Erika Madrigal and Jennifer Chennat Chapter 14 Role of Guided – Fine Needle Biopsy of the Pancreatic Lesion 237 Luigi Cavanna, Roberto Di Cicilia, Elisabetta Nobili, Elisa Stroppa, Adriano Zangrandi and Carlo Paties Chapter 15 Coagulation Disorders in Pancreatic Cancer 255 A. Albu, D. Gheban, C. Grad and D.L. Dumitrascu Chapter 16 Clinical Implications of an Expandable Metallic Mesh Stent for Malignant Portal Vein Stenosis in Management of Unresectable or Recurrent Pancreatic Cancer 271 Yoshinori Nio Chapter 17 Pancreatic Neuroendocrine Tumors: Emerging Management Paradigm 271 Syed F. Zafar and Bassel El-Rayes Chapter 18 Generation and Impact of Neural Invasion in Pancreatic Cancer 295 Ihsan Ekin Demir, Helmut Friess and Güralp O. Ceyhan Dedicated to my mother Vidya Srivastava and father Dr. Balramji Srivastava, who provided me constant love and support. Preface Pancreatic cancer is one of the most fatal human malignancies with extremely poor prognosis making it the fourth leading cause of cancer-related deaths in the United States. The molecular mechanisms of pancreatic carcinogenesis are not well understood. The major focus of these two books is towards the understanding of the basic biology of pancreatic carcinogenesis, identification of newer molecular targets and the development of adjuvant and neoadjuvant therapies. Book 1 on pancreatic cancer provides the reader with an overall understanding of the biology of pancreatic cancer, hereditary, complex signaling pathways and alternative therapies. The book explains nutrigenomics and epigenetics mechanisms such as DNA methylation, which may explain the etiology or progression of pancreatic cancer. Apart from epigenetics, book summarizes the molecular control of oncogenic pathways such as K-Ras and KLF4. Since pancreatic cancer metastasizes to vital organs resulting in poor prognosis, special emphasis is given to the mechanism of tumor cell invasion and metastasis. Role of nitric oxide and Syk kinase in tumor metastasis is discussed in detail. Prevention strategies for pancreatic cancer are also described. The molecular mechanisms of the anti-cancer effects of curcumin, benzyl isothiocyante and vitamin D are discussed in detail. Furthermore, this book covers the basic mechanisms of resistance of pancreatic cancer to chemotherapy drugs such as gemcitabine and 5- flourouracil. The involvement of various survival pathways in chemo-drug resistance is discussed in depth. Major emphasis is given to the identification of newer therapeutic targets such as mesothalin, glycosylphosphatidylinositol, cell cycle regulatory proteins, glycans, galectins, p53, toll-like receptors, Grb7 and telomerase in pancreatic cancer for drug development. Book 2 covers pancreatic cancer risk factors, treatment and clinical procedures. It provides an outline of pancreatic cancer genetic risk factors, signaling mechanisms, biomarkers and disorders and systems biology for the better understanding of disease. As pancreatic cancer suffers from lack of early diagnosis or prognosis markers, this book encompasses stem cell and genetic makers to identify the disease in early stages. The book uncovers the rationale and effectiveness of monotherapy and combination therapy in combating the devastating disease. As immunotherapy is emerging as an attractive approach to cease pancreatic cancer progression, the present book covers various aspects of immunotherapy including innate, adaptive, active, passive and X Preface bacterial approaches. The book also focuses on the disease management and clinical procedures. Book explains the role of pre-existing conditions such as diabetes and smoking in pancreatic cancer. Management of anesthesia during surgery and pain after surgery has been discussed. Book also takes the reader through the role of endoscopy and fine needle guided biopsies in diagnosing and observing the disease progression. As pancreatic cancer is recognized as a major risk factor for vein thromboembolism, this book reviews the basics of coagulation disorders and implication of expandable metallic stents in the management of portal vein stenosis of recurrent and resected pancreatic cancer. Emphasis is given to neuronal invasion of pancreatic tumors along with management of pancreatic neuroendocrine tumors. We hope that this book will be helpful to the researchers, scientists and patients providing invaluable information of the basic, translational and clinical aspects of pancreatic cancer. Sanjay K. Srivastava, Ph.D. Department of Biomedical Sciences Texas Tech University Health Sciences Center Amarillo, Texas USA [...]... cancer syndrome ascribed to mutations in BRCA1/2 genes, especially BRCA2; familial pancreatic and breast cancer syndrome due to mutations in PALB2 gene; familial isolated pancreatic cancer caused by mutations in PALLD encoding palladin; and familial multiple mole melanoma with pancreatic cancer (FAMMM-PC) attributed to 2 Pancreatic Cancer – Clinical Management mutations in CDKN2A Other hereditary cancer. .. inhibits cyclin D1 by binding to the cyclin-dependent kinases Cdk4 and Cdk6 thereby causing G1-S cell-cycle arrest (Schutte et al., 1997) Loss of p16 function, 4 Pancreatic Cancer – Clinical Management consequent to several different mechanisms, including homozygous deletion, intragenic mutation and epigenetic silencing by gene promoter methylation, is seen in approximately 90% of pancreatic cancers (Caldas... Melanoma – Pancreatic Cancer (FAMMM-PC) syndrome (MIM 606719) The association between mutations in p16 (CDKN2A) and familial pancreatic cancer was previously noted by Caldas et al (1994) and others (Liu et al., 1995; Whelan et al., 1995; Schutte et al., 1997) Further evidence for a plausible role of CDKN2A in pancreatic cancer was provided by Whelan et al (1995) who described a kindred at risk for pancreatic. .. depicted by the KRAS detection technology, it seems that most pancreatic neoplasms in the general population will remain undetectable before invasive cancer develops However, the recognition of early genetic somatic changes can advocate for presymptomatic chemo or 8 Pancreatic Cancer – Clinical Management surgical prevention schemes that may alleviate those with pre cancerous neoplasms before an invasive cancer. .. dominant pancreatic cancer maps to chromosome 4q32-34 Am J Hum Genet 70:1044-1048 10 Pancreatic Cancer – Clinical Management Feldmann G, Beaty R, Hruban RH, Maitra A (2007) Molecular genetics of pancreatic intraepithelial neoplasia J Hepatobiliary Pancreat Surg 14:224-32 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC CancerBase... KL, Tung N (2011) PALB2 mutations in familial breast and pancreatic cancer Fam Cancer 10:225-231 Hruban RH, Petersen GM, Ha PK, Kern SE (1998) Genetics of pancreatic cancer From genes to families Surg Oncol Clin N Am 7:1-23 Hruban RH, Canto MI, Yeo CJ (2001) Prevention of pancreatic cancer and strategies for management of familial pancreatic cancer Dig Dis 19:76-84 Hustinx SR, Leoni LM, Yeo CJ, Brown... Marzo A, Cameron JL, Yeo CJ, Hruban RH (2003) Multicomponent analysis of the pancreatic adenocarcinoma progression model using a pancreatic intraepithelial neoplasia tissue microarray Mod Pathol 16:90 2–9 12 12 Pancreatic Cancer – Clinical Management Maitra A, Kern SE, Hruban RH (2006) Molecular pathogenesis of pancreatic cancer Best Pract Res Clin Gastroenterol 20:211-226 McWilliams RR, Rabe KG, Olswold... the molecular mechanism that underlines pancreatic cancers, and may serve as therapeutic targets in the early stages of pancreatic cancer 4 Genome-maintenance genes Several gene ensembles, that play a role in caring for genome stability, were found to be mutated in pancreatic cancer, more so, in familial rather than sporadic cancer, including familial pancreatic cancer BRCA2 is with no doubt the prominent... colleagues provided pancreatic expression database that was a generic model for organization, integration and mining of 22 Pancreatic Cancer – Clinical Management complex pancreatic cancer datasets (Chelala et al 2007) The database holds 32 datasets comprising 7636 gene expression measurements extracted from 20 different published gene or protein expression studies from various PDAC types, pancreatic precursor... instability observed in pancreatic cancers (Hingorani et al., 2005); and that TP53 gene mutations constitute late events in pancreatic cancer progression (Maitra et al., 2003) 3.2.1 Li- Fraumeni syndrome (MIM 151623) Li-Fraumeni syndrome is a rare, clinically and genetically heterogeneous, inherited cancer syndrome caused by germline mutations in TP53 Li-Fraumeni syndrome is characterized by autosomal dominant . PANCREATIC CANCER – CLINICAL MANAGEMENT Edited by Sanjay K. Srivastava Pancreatic Cancer – Clinical Management Edited by Sanjay. Multi-Disciplinary Management of Metastatic Pancreatic Cancer 197 Marwan Ghosn, Colette Hanna and Fadi El. Karak Chapter 12 Pancreatic Cancer – Clinical Course