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Pancreatic Cancer, An Issue of Hematology/Oncology Clinics of North America, E-Book

Pancreatic Cancer, An Issue of Hematology/Oncology Clinics of North America, E-Book

Brian M. Wolpin

(2015)

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Book Details

Abstract

This issue of Hematology/Oncology Clinics of North America is devoted to Pancreatic Cancer. Guest Editor Brian Wolpin, MD has assembled a group of expert authors to review the following topics: Biology and genetics of pancreatic adenocarcinoma; Mouse models of pancreatic adenocarcinoma; Epidemiology and inherited predisposition for sporadic pancreatic adenocarcinoma; Familial pancreatic adenocarcinoma; Imaging and endoscopic approaches to pancreatic cancer; Diagnosis and management of pancreatic cystic neoplasms; Surgical management of pancreatic cancer; Peri-operative therapy for surgically resectable pancreatic adenocarcinoma; Diagnosis and management of borderline resectable pancreatic adenocarcinoma; Treatment approaches to locally advanced pancreatic adenocarcinoma; Therapeutic approaches for metastatic pancreatic adenocarcinoma; Supportive and end-of-life care for patients with pancreatic adenocarcinoma; and Novel therapeutics for pancreatic adenocarcinoma.

Table of Contents

Section Title Page Action Price
Front Cover Cover
Pancreatic Cancer i
Copyright\r ii
Contributors iii
Contents vii
Hematology/Oncology Clinics Of North America\r xi
Preface\r xiii
Genetics and Biology of Pancreatic Ductal Adenocarcinoma 595
Key points 595
Genetics 595
KRAS 596
INK4a/CDKN2A/P16 597
TP53 Tumor Suppressor Pathway 597
DPC4/SMAD4/Transforming Growth Factor Beta 598
Advanced Genetic Sequencing Reveals Novel Mutations 598
Genetic Pathogenesis 599
Microenvironment 600
Immune response 602
Metabolic requirements 602
Summary 604
References 604
Mouse Models of Pancreatic Ductal Adenocarcinoma 609
Key points 609
Introduction 609
Mouse xenograft models 610
The Immunocompromised Mouse 610
Cell Line Derived Xenografts 611
Patient Derived Xenografts 611
Genetically engineered mouse models 612
LSL-KrasG12D Model 612
LSL-Trp53R172H/- Model 612
Translational uses of the LSL-Trp53R172H/- model 613
Future directions 614
References 615
Epidemiology and Inherited Predisposition for Sporadic Pancreatic Adenocarcinoma 619
Key points 619
Epidemiology for pancreatic adenocarcinoma 619
Descriptive Epidemiology 619
Risk Factors 620
Diabetes 620
Biomarkers for diabetes and insulin resistance 620
Pancreatitis and type 3c diabetes 623
Maturity-onset diabetes of the young 623
Antidiabetic drugs 624
Modifiable risk factors 624
Tobacco use 624
Overweight and obesity 624
Dietary exposures 625
Inherited predisposition for sporadic pancreatic adenocarcinoma 626
Common Low-Risk Pancreatic Cancer Susceptibility Loci 626
Common Pancreatic Cancer Risk Loci in Non-European Populations 629
Pathway Analyses of pancreatic Cancer Genome-Wide Association Studies Data Sets 630
Functional Understanding of Common Pancreatic Cancer Risk Loci 630
Future Gene Mapping Approaches 630
Summary 631
Acknowledgments 631
References 631
Familial Pancreatic Adenocarcinoma 641
Key points 641
Introduction 641
Evidence for genetic basis of pancreatic cancer 642
Familial Clustering 642
Familial Aggregation Studies and Analysis of Families 642
Familial Pancreatic Cancer Defined to Advance Research 644
Characteristics of familial pancreatic cancer: sex, incident risk, age at onset, smoking, other cancers 644
Genetic studies of familial pancreatic cancer 645
Hereditary Syndromes with Increased Risk of Pancreatic Cancer 645
Gene Discovery Studies in Familial Pancreatic Cancer 645
Novel gene discovery in patients with familial pancreatic cancer using next-generation sequencing 647
Genetic analysis of cancer syndrome genes 647
Clinical translation of familial pancreatic cancer research 649
Personalized Therapy 649
Genetic Testing and Cancer Risk Assessment 649
Screening Options for High-Risk Individuals 649
Summary 650
References 650
Diagnosis and Management of Pancreatic Cystic Neoplasms 655
Key points 655
Introduction 656
Disease entities 656
Intraductal Papillary Mucinous Neoplasm 656
Prevalence 658
Demographics 658
Radiologic features 658
Management 658
Outcomes 660
Current controversies and future directions 660
Mucinous Cystic Neoplasm 661
Prevalence 662
Demographics 662
Radiologic features 662
Management 662
Outcomes 663
Current controversies and future directions 663
Serous Cystadenoma 663
Prevalence 663
Demographics 663
Radiologic features 664
Management 664
Outcomes 665
Current controversies and future directions 665
Cystic Pancreatic Endocrine Neoplasm 665
Prevalence 665
Demographics 665
Radiologic features 665
Management 666
Outcomes 666
Current controversies and future directions 666
Solid Pseudopapillary Neoplasm 667
Prevalence 667
Demographics 667
Radiologic features 667
Management 667
Outcomes 667
Current controversies and future directions 668
General approach to diagnosis and management 668
Initial Evaluation 669
Further Investigation 669
Management: Resection versus Surveillance 670
Outcomes 670
Summary and discussion 670
References 670
Imaging and Endoscopic Approaches to Pancreatic Cancer 675
Key points 675
Introduction 675
Noninvasive imaging in pancreatic cancer 676
Image-Based Anatomy of the Pancreas 676
Ductal anatomy 676
Vascular anatomy 677
Adjacent structures 678
Imaging Techniques 679
Imaging Across the Spectrum of Care 681
Initial diagnosis 681
Initial staging 684
Primary tumor T stage 684
Regional nodes 686
Metastatic disease 686
Resectability 686
Treatment monitoring 687
After neoadjuvant therapy 687
After surgery 687
During adjuvant and palliative chemotherapy 687
Surveillance 687
Future Considerations 687
Dual-energy computed tomography imaging 687
Stromal transport characterization 688
Endoscopy in pancreatic cancer 688
Introduction 688
Diagnosis 688
Endoscopic retrograde cholangiopancreatography 688
Biliary aspirate 689
Brushing 689
Biopsy 689
Ductoscopy 689
Endoscopic ultrasonography 689
Fine-needle aspiration 691
Staging 691
Novel techniques 691
Endoscopic retrograde cholangiopancreatography with intraductal ultrasonography 691
Endoscopic ultrasonography with trucut biopsy 692
Endoscopic ultrasonography with elastography 692
Contrast-enhanced endoscopic ultrasonography 692
Upper endoscopy with optical spectroscopy 692
Treatment 693
Therapy for biliary obstruction 693
Endoscopic retrograde cholangiopancreatography with stenting 693
Endoscopic ultrasonography-assisted biliary drainage 693
Therapy for other complications 693
Gastroduodenal obstruction: enteral stenting 693
Adjunctive therapy: endoscopic ultrasonography-guided fiducial placement 694
Direct therapy: endoscopic ultrasonography-guided fine-needle injection 694
Endoscopy: Conclusion 696
Summary 696
References 696
Surgery for Pancreatic Cancer 701
Key points 701
Introduction 701
Indications/Contraindications 702
Imaging 702
Endoscopic Evaluation 702
Indications and Contraindications to Resection 703
Diagnostic Laparoscopy 704
Technique/Procedure 705
Pancreaticoduodenectomy: Technical Considerations 706
Exposure of anterior and posterior pancreatic head 706
Exposure of superior mesenteric vein 706
Dissection of porta hepatis 706
Inframesocolic dissection 706
Dissection of pancreatic head from mesenteric vessels 706
Reconstruction 706
Pancreaticoduodenectomy: Additional Considerations 706
Pylorus preservation 706
Vascular reconstruction 707
Distal Pancreatectomy: Technical Considerations 707
Complications and management 708
Perioperative Mortality 708
Perioperative Morbidity 709
Pancreatic fistula 709
Delayed gastric emptying 709
Postoperative hemorrhage 709
Outcomes 709
Controversies/Future considerations 710
Minimally Invasive Surgery 710
Neoadjuvant Therapy for Resectable Tumors 710
Summary 711
References 711
Perioperative Therapy for Surgically Resectable Pancreatic Adenocarcinoma 717
Key points 717
Introduction 718
Definition of resectable pancreatic adenocarcinoma 718
Adjuvant therapy 718
Major Phase III Trials of Adjuvant Therapy 718
Controversy over Adjuvant Radiation Therapy 721
Neoadjuvant therapy 722
Biomarkers predictive of outcome 722
What is on the horizon 723
Summary 724
References 724
Diagnosis and Management of Borderline Resectable Pancreatic Adenocarcinoma 727
Key points 727
Introduction 727
Definitions 728
Anatomic Staging (Borderline Resectable Pancreatic Ductal Adenocarcinoma Type A) 728
Anatomic, Biologic and Physiologic Criteria for Borderline Resectable Pancreatic Ductal Adenocarcinoma 729
Borderline Resectable Pancreatic Ductal Adenocarcinoma (Type B) 730
Borderline Resectable Pancreatic Ductal Adenocarcinoma (Type C) 730
Diagnosis and staging 731
Computed Tomography and MRI 731
Endoscopic Ultrasonography 731
Radiologic Reporting 732
Management 732
Rationale for Preoperative Therapy 733
Metrics of Response to Neoadjuvant Therapy 734
Surgical issues 736
Staging Laparoscopy 736
Laparotomy After Neoadjuvant Therapy 736
Surgical Standards 736
Summary 736
References 736
Treatment Approaches to Locally Advanced Pancreatic Adenocarcinoma 741
Key points 741
Introduction 742
Definition of locally advanced pancreatic cancer: accurate diagnosis and staging 742
Treatment of locally advanced pancreatic cancer 742
Chemoradiation: Is There a Role? 742
The Question of Timing: Induction Chemoradiation 743
Delayed Chemoradiation Following Induction Chemotherapy 743
Systemic therapy in locally advanced pancreatic cancer 747
Selection of Chemotherapy Administered Independently of Radiation 747
Selection of Radiosensitizing Agents 747
Advances in pancreatic radiation techniques 748
Treatment Volumes 748
Respiratory-Motion Management 748
Stereotactic body radiotherapy 749
Technical Considerations of Stereotactic Body Radiotherapy 749
Efficacy and Toxicity 753
Summary/discussion 753
References 753
Therapeutic Approaches for Metastatic Pancreatic Adenocarcinoma 761
Key points 761
Introduction 761
Patient evaluation and prognostic markers 762
Gemcitabine 763
Strategies to Improve Gemcitabine Effectiveness 763
Gemcitabine Treatment Doublets 763
Gemcitabine and Erlotinib 765
Folinic acid, 5-fluorouracil, irinotecan, oxaliplatin 767
Gemcitabine plus nab-paclitaxel 767
Folinic acid, 5-fluorouracil, irinotecan, oxaliplatin versus gemcitabine plus nab-paclitaxel 769
Second-line therapy 770
New approaches 771
Summary 771
References 772
Novel Therapeutics for Pancreatic Adenocarcinoma 777
Key points 777
Immunotherapy 777
GVAX, CRS207 vaccines 778
Hyperacute vaccination 778
Checkpoint blockade 779
Immune microenvironment 779
T-cell manipulation 779
BRCA-related therapies and poly-ADP ribose polymerase inhibitors 779
Molecularly targeted therapies 781
Targeting KRAS 781
JAK-STAT pathway and inflammation 782
Autophagy 782
Notch and stem cell targeting 782
Stromal targeting therapies 783
PEGPH20 783
TH302 783
Necuparanib 784
Novel cytotoxic formulations 784
Summary 785
References 785
Index 789
HOC_BLANK (2) 800
HOC_BLANK (3) 801
HOC_BLANK (4) 802
HOC_BLANK (5) 803
HOC_BLANK 804