Methods of Cancer Diagnosis, Therapy, and Prognosis. Vol. 4: Colorectal Cancer

About this book

This fourth volume in the series Methods of Cancer Diagnosis, Therapy and Prognosis discusses various methodologies for the diagnosis, therapy and prognosis of Colorectal Cancer. Both standard and emerging therapies for this cancer, written by expert oncologists/pathologists in this field, are included.

This fully illustrated volume

• Presents surgical, radiological, and molecular therapies and prognostic markers for colorectal cancer.
• Highlights a large number of methods for diagnosing colorectal cancer at various stages of development, including immunohistochemistry,in situ hybridization immunoscintigraphy, RT- PCR, free circulating DNA levels in blood and stool, ultrasonography, CT, PET, and MRI.
• Includes imaging technologies for assessing the treatment results, as are details related to colonoscopy and sigmoidoscopy.
• Explains the use of anticancer agents and monoclonal antibodies, including 5-fluorouracil, fluoropyrimidines, leucovorin, irinotecan, oxaliplatin, raltitrexed, capecitabine, cetuximab, and bevacizumab.
• Compares preoperative chemoradiotherapy with postoperative chemoradiotherpy.

The technological advances presented in this volume are expected to expedite new discoveries and their translation to clinical practice. Oncology will benefit the most from these advanced methods, as a combination of therapies and personalized medicine will improve early detection of colorectal cancer and other cancer types.

Professor Hayat has summarized the problems associated with the complexities of research publications and has been successful in editinga must-read volume for oncologists, cancer researchers, medical teachers and students of cancer biology.

Written for:

Oncologists, Clinicians, Surgeons, Medical Teachers, Hospital Laboratories, Medical Students, Drug Industries and Libraries

Keywords:

Colorectal

Table of contents

Authors and Co-Authors of Volume 4

Preface

Contents of Volume 1, 2, and 3

PART I. COLORECTAL CANCER

1. INTRODUCTION: COLORECTAL CANCER
M.A. Hayat

INTRODUCTION
Screening for Colorectal Cancer
Treatment
Rectal Cancer
REFERENCES

A. Diagnosis

2. POORLY DIFFERENTIATED COLORECTAL ADENOCARCINOMA: (METHODOLOGY)
Seiichi Shinji, Zenya Naito, Toshiyuki Ishiwata, Yoko Matsuda, Tomoko Seya, and Takashi Tajiri

INTRODUCTION
HISTOPATHOLOGY
IMMUNOHISTOCHEMISTRY FOR DIFFERENTIAL DIAGNOSIS
IMMUNOHISTOCHEMISTRY FOR MALIGNANT CHARACATERISTICS OF POORLY DIFFERENTIATED ADENOCARCINOMA
IN SITU HYBRIDIZATION FOR MALIGNANT CHARACTERISTICS OF POORLY DIFFERENTIATED ADENOCARCINOMA
THERAPY
REFERENCES

3. COLORECTAL CANCER: IMMUNOHISTOCHEMICAL; DIAGNOSIS WITH HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN K
Ayham Alnabulsi, Brian Carpenter, Colin Telfer, and Graeme I. Murray

INTRODUCTION
BIOMARKERS
Approved Biomarkers – Problems
Biomarkers of Colorectal Cancer
Demand for Colorectal Biomarkers
COLORECTAL BIOMARKER HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN K
Methodology
2D Gel Electrophoresis (2DGE)
Semiquantitative Reverse Transcription-Polymerase Chain Reaction
Monoclonal Antibody to Heterogeneous Nuclear Ribonucleoprotein K
Immunohistochemistry (IHC)
RESULTS
DISCUSSION
FUTURE DIRECTION
REFERENCES

4. METASTASES AND RECURRENCE OF COLORECTAL CANCER: DIAGNOSTIC ROLE OF IMMUNOSCINTIGRAPHY
Vladimir Obradovic and Vera Artiko

INTRODUCTION
GENERAL CONSIDERATIONS
Radiopharmaceuticals
Imaging Systems and Techniques
IMMUNOSCINTIGRAPHIC METHODS USED FOR DIAGNOSTICS OF
COLORECTAL CANCER
Immunoscintigraphy Based on Radiopharmaceuticals Labeled with Radioiodines
Immunoscintigraphy Based on Radiopharmaceuticals Labeled with 111In
Immunoscintigraphy Based on Radiopharmaceuticals Labeled with 99mTc
Comparison of Diagnostic Values of Different Radiopharmaceuticals
Immunoscintigraphy and Positron Emission Tomography
Radioimmunoguided Surgery
CONCLUSION
REFERENCES

5. COLORECTAL CANCER DIAGNOSIS USING DNA LEVELS IN BLOOD AND STOOL
Emanuela Flamini, Daniele Calistri, Laura Mercatali, Claudia Rengucci and Dino Amadori

INTRODUCTION
AVAILABLE TESTS AND THEIR COST BENEFITS
Fecal Occult Blood Test
Flexible Sigmoidoscopy
Colonoscopy
Barium Enema with Air Contrast
Virtual Colonoscopy
MOLECULAR MARKERS AND THEIR COST BENEFITS
FREE CIRCULATING DNA IN BLOOD
Biological Mechanisms of Free Circulating DNA Release
Methodological Aspects of Free Circulating DNA
Sources and Influence of Pre-Analytical Factors
Isolation and Quantification
Free Circulating DNA Levels in Colorectal Cancer Diagnosis
INTEGRITY OF GENOMIC EXTRACTED DNA FROM STOOL
Analysis of Long Fragment DNA in Stool
Advantages and Technical Problems
CONCLUSIONS
REFERENCES

6. COLORECTAL CARCINOMA: IDENTIFICATION OF microRNAs USING REAL-TIME POLYMERASE CHAIN REACTION
Eva Bandres, Nerea Bitarte, Natalia Ramirez, Ruth Zarate, and Jesus Garcia-Foncillas

INTRODUCTION
GENOMICS OF microRNA
microRNA BIOGENESIS AND FUNCTION
EVIDENCE FOR THE INVOLVEMENT OF microRNA IN CANCER
REGULATION OF microRNA EXPRESSION
IDENTIFICATION OF microRNA TARGETS: BIOINFORMATIC AND FUNCTIONAL TOOLS
TECHNOLOGY TO QUANTIFY microRNAs
EXPERIMENTAL WORKFLOW FOR microRNA EXPRESSION BY REAL- TIME POLYMERASE CHAIN REACTION
IDENTIFICATION OF DIFFERENTIALLY EXPRESSED microRNA IN COLORECTAL CANCER USING REAL-TIME POLYMERASE CHAIN REACTION
QUANTIFICATION OF microRNA IN CLINICAL SAMPLES
FUTURE APPLICATION AND POTENTIAL LIMITATIONS
REFERENCES

B. Treatment

7. COLORECTAL CANCER: OPTIMIZATION OF THE COMBINATION OF 5-FLUOROURACIL AND IRINOTECAN
Carlo Barone, Matteo Landriscina, and Alessandra Cassano

INTRODUCTION
COMBINATION OF 5-FLUOROURACIL AND IRINOTECAN IN HUMAN COLORECTAL CANCER
CLINICAL PHARMACOLOGY OF THE INTERACTION BETWEEN 5- FLUOROURACIL AND IRINOTECAN
CLINICAL OPTIMIZATION OF 5-FLUOROURACIL AND IRINOTECAN COMBINATION
INTEGRATION OF IRINOTECAN/5-FLUOROURACIL REGIMENS WITH MOLECULAR-TARGETED AGENTS
PHARMACOGENOMICS OF 5-FLUOROURACIL AND IRINOTECAN COMBINATION
FUTURE PERSPECTIVES
REFERENCES

8. DETECTION OF ABDOMINAL ABSCESSES AFTER COLORECTAL SURGERY: ULTRASONOGRAPHY, COMPUTED TOMOGRAPHY, AND GALLIUM SCAN
Wan-Yu Lin, Jyh-Wen Chai, and Te-Hsin Chao

INTRODUCTION
RISK FACTORS
CLINICAL DIAGNOSIS
CLINICAL MANAGEMENT
ABDOMINAL RADIOGRAPHY
ULTRASONOGRAPHY
COMPUTED TOMOGRAPHY
GALLIUM-67 CITRATE SCAN
OTHER RADIONUCLIDE METHODS
REFERENCES

9. ANTIMETASTATIC THERAPY IN COLORECTAL CANCER: ROLE OF TUMOR CELL MATRIX METALLOPROTEINASE 9 (METHODOLOGY)
Wilhelm J. Lubbe and Giovanni M. Pitari

INTRODUCTION
COLORECTAL
CANCER METASTASIS
Mechanisms of Pathogenesis
MATRIX METALLOPROTEINASE-9 (MMP-9)
Function and Regulation of MMP-9
Signaling of MMP-9 in Metastasis
Tumor Cell MMP-9
TARGETING MMP-9 IN COLORECTAL CANCER METASTASIS
Detection of MMP-9 in Tumor Cell Compartments
Reducing MMP-9 Expression in Cancer Cells
Suppressing MMP-9 Signaling in Cancer Cells
CONCLUDING REMARKS
REFERENCES

10. ENDOSCOPIC RESECTION OF EARLY COLORECTAL TUMOURS: NOVEL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES
P. Hurlstone, S. Brown, and W. Baraza

EARLY COLORECTAL CANCER: A PARADIGM SHIFT
ENDOSCOPIC OPTICAL BIOPSY TECHNIQUES
ENDOLUMINAL STAGING OF COLORECTAL LESIONS
ENDOSCOPIC MUCOSAL RESECTION: RATIONALE AND METHODOLOGY
ENDOSCOPIC SUBMUCOSAL DISSECTION: RATIONALE AND METHODOLOGY
RETROFLEXION ENDOSCOPIC DISSECTION
ENDOSCOPIC RESECTION IN CHRONIC ULCERATIVE COLITIS
POST RESECTION PROTOCOLS
SAFETY AND APPLICABILITY OF ENDOSCOPIC RESECTION TECHNIQUES
REFERENCES

11. ROLE OF STROMAL VARIABLES IN DEVELOPMENT AND PROGRESSION OF COLORECTAL CANCER
Xiao-Feng Sun and Hong Zhang

INTRODUCTION
ANGIOGENESIS AND LYMPHANGIOGENESIS IN COLORECTAL CANCER
MICROVESSELS IN TUMOR DEVELOPMENT AND PROGRESSION
VASCULAR ENDOTHELIAL GROWTH FACTOR IN DEVELOPMENT AND PROGRESSION OF COLORECTAL CANCER
LYMPHATIC DENSITY IN STROMA OF COLORECTAL CANCER
INFLAMMATORY INFILTRATION
LYMPHOCYTIC INFILTRATION AND PROGNOSIS IN COLORECTAL CANCER
EXTRACELLULAR MATRIX AND MICROENVIRONMENT
FUNCTIONS OF PINCH
Expression of PINCH in Different Organs
PINCH in Development and Progression of Colorectal Cancer
FUNCTIONS OF MATRIX METALLOPROTEINASES
STROMELYSIN-3 IN DEVELOPMENT AND PROGRESSION OF COLORECTAL CANCER
REFERENCES

12. QUANTITATIVE ASSESSMENT OF COLORECTAL CANCER PERFUSION - PERFUSION COMPUTED TOMOGRAPHY AND DYNAMIC CONTRAST-ENHANCED MAGNETIC RESONANCE IMAGING
Vicky Goh

INTRODUCTION
TECHNICAL CONSIDERATIONS
Contrast Agents
Contrast Kinetics
Contrast Administration
Contrast Concentration and Tissue Enhancement
Macromolecular Contrast Agents
Data Acquisition and Mathematical Modeling
Perfusion Computed Tomography
Dynamic Contrast-Enhanced Magnetic Resonance Imaging
VALIDATION AND MEASUREMENT REPRODUCIBILITY
CLINICAL UTILITY
Distinction between Benign and Malignant Disease
Assessment of Chemoradiotherapy
Assessment of Anti-Angiogenic Drugs
Assessment of Hepatic Metastatic Disease
Primary Tumor Perfusion and Development of Metastatic Disease
WHICH IMAGING TECHNIQUE SHOULD BE USED?
CHALLENGES FOR PERFUSION IMAGING
REFERENCES

C. Prognosis

13. COLORECTAL CANCER: POSITRON EMISSION TOMOGRAPHY
Ur Metser

INTRODUCTION
PROGNOSIS AND PRINCIPLES IN THERAPY
IDENTIFICATION OF PRIMARY COLONIC LESION WITH 18F- FLUORODEOXYGLUCOSE – POSITRON EMISSION TOMOGRAPHY
STAGING: LOCAL TUMOR, LYMPH NODE, AND DISTANT METASTASES
ASSESSMENT OF RESPONSE TO THERAPY
Neoadjuvant Chemoradiation Therapy
Chemotherapy for Metastatic Colorectal Cancer
Other Radiopharmaceuticals for Metastatic Colorectal Cancer
Local Therapy for Metastases
IDENTIFICATION OF TUMOR RECURRENCE
POSITRON EMISSION TOMOGRAPHY AND COLORECTAL CANCER:
FUTURE DIRECTIONS
REFERENCES

14. PROGNOSTIC SIGNIFICANCE OF PROTEIN MARKERS IN COLORECTAL CANCER STRATIFIED BY MISMATCH REPAIR STATUS
Inti Zlobec and Alessandro Lugli

INTRODUCTION
TISSUE MICROARRAY TECHNOLOGY
MANAGEMENT OF TISSUE MICROARRAY DATASET
SCORING SYSTEMS AND STATISTICAL ANALYSIS
PROGNOSTIC FACTORS IN COLORECTAL CANCER STRATIFIED WITH MISMATCH REPAIR STATUS
USE OF MULTIMARKER PHENOTYPES
DISCUSSION
REFERENCES

15. COLORECTAL CANCER: LACTATE DEHYDROGENASE (LDH) ACTIVITY AS A PROGNOSTIC MARKER
Michael I. Koukourakis, Alexandra Giatromanolaki, and Efthimios Sivridis

LACTATE DEHYDROGENASE
CANCER CELLS AND THE WARBURG EFFECT
ACTIVITY OF LACTATE DEHYDROGENASE IN COLORECTAL CANCER TISSUES
EXPRESSION OF LACTATE ISOENZYMES IN COLORECTAL CANCER
SUBCELLULAR PATTERNS OF LACTATE DEHYDROGENASE-5 EXPRESSION AND SCORING OF TUMORS
LACTATE DEHYDROGENASE AND TUMOR AGGRESSIVENESS
LACTATE-5 EXPRESSION AND PROGNOSIS OF PATIENTS WITH COLORECTAL CANCER
SERUM LACTATE DEHYDROGENASE VS. CANCER CELL LACTATE
DEHYDROGENASE-5 EXPRESSION
SERUM LACTATE DEHYDROGENASE-5 LEVELS AND PROGNOSIS IN PATIENTS WITH COLORECTAL CANCER
LACTATE DEHYDROGENASE AND THE PTK/ZK TRIAL
TARGETING LACTATE DEHYDROGENASE FOR THERAPY
REFERENCES

PART II. COLON CANCER

16. DETECTION OF TUMOR CELLS IN LYMPH NODES OF COLON CANCER PATIENTS USING REAL-TIME QUANTITATIVE REVERSE TRANSCRIPTION-POLYMERASE CHAIN REACTION
Lina Ohlsson, Anne Israelsson, Åke Öberg, Marie-Louise Hammarström, Gudrun Lindmark, and Sten Hammarström

INTRODUCTION
MATERIALS
METHODS
Preparation of Lymph Nodes
RNA Extraction
Preparation of Copy Standard
Real-Time Quantitative RT-PCR for 18S rRNA
Real-Time Quantitative RT-PCR for Determination of CEA mRNA,
CK20 mRNA, and MUC2 mRNA
RESULTS AND DISCUSSION
REFERENCES
A. Treatment

17. COLON CANCER: LAPAROSCOPIC SURGERY
David W. Larson and Heidi Nelson

INTRODUCTION
PRESENTATION
COMPLICATIONS
OUTCOMES IN CANCER
TREATMENT TECHNIQUE OF OPERATION
Exploration
Right Colectomy
The Anastomosis
Left or Sigmoid Colectomy
REFERENCES

18. SENTINEL NODE-BASED IMMUNOTHERAPY OF COLON CANCER
Per Marits, Mona Karlsson, Magnus Thörn, and Ola Winqvist

INTRODUCTION
TUMOR IMMUNE SURVEILLANCE
Immune Surveillance in Colon Cancer
Tumor Antigens in Colon Cancer
Tumor Escape Mechanisms
Central Tolerance
IMMUNOTHERAPY OF CANCER
Active Immunotherapy-Vaccination
Passive, Specific Immunotherapy
Adoptive Immunotherapy in Colon Cancer
THE IMMUNE RESPONSE IN THE LYMPH NODE
Lymph Node Anatomy
Antigen Recognition in the Lymph Node
Outcome of T Cell Activation
Immunological Memory
SENTINEL-NODE BASED IMMUNOTHERAPY OF COLON CANCER
Sentinel Node Detection in Colon Cancer
Immune Responses in Sentinel Lymph Nodes
Lymph Node-Based Treatments
REFERENCES

PART III. RECTAL CANCER

A. Diagnosis

19. RECTAL CANCER: PREOPERATIVE STAGING USING ENDORECTAL ULTRASONOGRAPHY (METHODOLOGY)
Ho-Kyung Chun, Yong Beom Cho, and Soon Jin Lee

INTRODUCTION
INSTRUMENTS AND TECHNIQUE
IMAGE INTERPRETATION
Tumor Staging with Endorectal Ultrasonography
Lymph Node Staging with Endorectal Ultrasonography
ACCURACY FOR STAGING RECTAL CANCER
ACCURACY OF ENDORECTAL ULTRASONOGRAPHY COMPARED WITH COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING
THREE-DIMENTIONAL ENDORECTAL ULTRASONOGRAPHY
REFERENCES

20. RECTAL CANCER: SPECTRAL IMAGING AND IMMUNOHISTOCHEMISTRY OF THYMIDYLATE SYNTHASE
Gary K. Atkin and George D. Wilson

INTRODUCTION
Thymidylate Synthase
Immunohistochemical Quantification of Tissue Sections
Spectral Imaging
METHODOLOGY
Immunohistochemistry of Thymidylate Synthase in Rectal Cancer
Quantification of Thymidylate Synthase Expression Using Spectral Imaging
DISCUSSION
REFERENCES

B. Treatment

21. CANCER OF THE RECTUM: ABDOMINOPERINEAL AND SPHINCTER-SAVING RESECTIONS
Federico Bozzetti

INTRODUCTION
OUTCOME AFTER ABDOMINOPERINEAL RESECTION AND SPHINCTER-SAVING RESECTION
POTENTIAL PROGNOSTIC FACTORS DIFFERENTIATING ABDOMINOPERINEAL AND SPHINCTER-SAVING RESECTIONS
TECHNICAL ASPECTS OF THE ABDOMINOPERINEAL RESECTION
Incision
Posterior Dissection
Lateral Dissection
Anterior Dissection
REFERENCES

22. CHEMORADIATION FOR RECTAL CANCER
Max Mano and Jean-Pascal Machiels

INTRODUCTION
APPLICATIONS OF PRE- OR POSTOPERATIVE CHEMORADIATION
PREOPERATIVE RADIATION ONLY VERSUS CHEMORADIATION
INTEGRATION OF NEW CYTOTOXIC AND BIOLOGICAL AGENTS IN THE PREOPERATIVE SETTING
Patients and Methods
Capecitabine
Oxaliplatin
Targeted Therapy
REFERENCES

23. RESECTABLE RECTAL CANCER: PREOPERATIVE SHORT-COURSE RADIATION
Krzysztof Bujko

INTRODUCTION
SHORT-COURSE SCHEDULE
TESTING THE SHORT-COURSE PREOPERATIVE RADIOTHERAPY
Randomized Trials
LOCAL EFFICACY AND SURVIVAL
EARLY ADVERSE EFFECTS AND COMPLIANCE
POSTOPERATIVE COMPLICATIONS
LATE ADVERSE EFFECTS
TESTING THE SHORT-COURSE PREOPERATIVE RADIOTHERAPY
Non-randomized Trials
ADVANTAGES AND LIMITATIONS OF SHORT-COURSE SCHEDULE
REFERENCES

24. PREOPERATIVE CHEMORADIOTHERAPY ALLOWS FOR LOCAL CONTROL IN RECTAL CANCER, BUT DISTANT METASTASES REMAIN AN UNSOLVED PROBLEM
Verena Voelter

INTRODUCTION
SURGERY
PREOPERATIVE VERSUS POSTOPERATIVE RADIOTHERAPY
RATIONALE FOR COMBINED CHEMORADIOTHERAPY
CHEMOTHERAPY-RADIOTHERAPY IN THE CLINIC
PREOPERATIVE VERSUS POSTOPERATIVE CHEMORADIOTHERAPY
DETERMINATION OF PROGNOSIS
Histopathological Prognostic Factors
Pathological Complete Remission
CLINICAL STAGING
NEW DRUGS TO CONTROL DISTANT METASTASES
5-fluorouracil and Leucovorin
Irinotecan
Cetuximab
Oxaliplatin and Bevacizumab
NEW PREDICTIVE MARKERS
EGFR Signaling Pathway
Cell Cycle Associated Proteins and Circulating Tumor Cells
UNSOLVED QUESTIONS IN THE TREATMENT OF RECTAL CANCER
REFERENCES

25. LOCALLY ADVANCED RECTAL CANCER: COMBINED CHEMOTHERAPY DURING PREOPERATIVE RADIATION THERAPY
Antonio Avallone, Paolo Delrio, Luigi Aloj, Elena Di Gennaro, Cesare Guida, Fabiana Tatangelo, Antonella Petrillo, Giuseppe Lucio Cascini, Valerio Parisi, Alfredo Budillon, Secondo Lastoria, and Pasquale Comella

INTRODUCTION
CHEMOTHERAPY OF LOCALLY ADVANCED RECTAL CANCER
SELECTION OF CHEMOTHERAPY
5-Fluorouracil
Oral Fluoropyrimidines
Raltitrexed
Irinotecan
Oxaliplatin
Cetuximab
Bevacizumab
PATIENT SELECTION
REFERENCES

PART IV. COLORECTAL LIVER METASTASES

26. COLORECTAL CANCER LIVER METASTASES: NEOADJUVANT THERAPY WITH BEVACIZUMAB
Thomas Gruenberger and Birgit Gruenberger

INTRODUCTION
BEVACIZUMAB IN THE NEOADJUVANT SETTING
SURGERY AFTER BEVACIZUMAB IN THE NEOADJUVANT SETTING
FUTURE PROSPECTIVE
CONCLUSION
REFERENCES

27. COLORECTAL LIVER METASTASES: RADIOFREQUENCY ABLATION
Andrew Mckay, Elijah Dixon, and Oliver Bathe

INTRODUCTION
TECHNICAL ASPECTS OF RADIOFREQUENCY ABLATION
PATIENT SELECTION
OPERATIVE TECHNIQUE
FOLLOW-UP AFTER SURGERY
SAFETY
OUTCOMES
RATES OF TUMOR NECROSIS
RECURRENCE RATES
SURVIVAL
CURRENT STATUS OF RADIOFREQUENCY ABLATION FOR COLORECTAL LIVER METASTASES
REFERENCES

PART V. ANAL CANCER

28. ANAL SQUAMOUS CELL CARCINOMAS: DIAGNOSIS USING p63 IMMUNOHISTOCHEMISTRY
Scott R. Owens

INTRODUCTION
Anal Carcinoma
p63
p63 IMMUNOSTAINING IN ANAL CARCINOMA
Utility
Advantages
PROCEDURE AND INTERPRETATION
SPECIAL CONSIDERATIONS
REFERENCES