The enormity of the global healthcare costs vical. One-fifth of all cancers worldwide as a result of cancer infliction cannot be are caused by a chronic infection, for overemphasized. There are more than 100 example, human papilloma virus (HPV) types of cancers; any part of the body can causes cervical cancer and hepatitis B be affected. More than 11 million people virus (HBV) causes liver cancer. Tobacco are diagnosed with cancer every year, and use is the most common preventable cause it is estimated that there will be 16 mil- of cancer in the world. Approximately, lion new cases per year by the year 2020. 168,000 cancer deaths are expected to be In 2005, 7. 6 million people died of can- caused by tobacco use. Approximately, cer, that is, 13% of the 58 million deaths 40% of cancer could be prevented, mainly worldwide. It is estimated that 9 million by not using tobacco, having a healthy people will die from cancer worldwide in diet, being physically active, preventing 2015 and 11. 4 million will die in 2030. infections that may cause cancer, reduc- More than 70% of all cancer deaths occur ing exposure to sunlight, and avoidance of in low and middle income countries. excessive alcohol consumption and stress Five major cancer causing overall mor- (anger). A third of cancers could be cured talities per year worldwide are (WHO): if detected early and treated adequately. It is well established that scientific 1. Lung: 1.

Cancer is the leading cause of death, in the number of older cancer patients is after cardiovascular diseases, in the expected. Approximately, 77% of all types United States. A total of ? 1,399,790 new of cancers are diagnosed in persons of 55 cancer cases and ? 564,830 deaths were years and older. It was estimated that o- reported in the year 2006 in the country. third of the 559,650 cancer deaths in 2007 Approximately, one in every two men and in the United States were related to ov- one in every three women in the country weight or obesity, physical inactivity, and will have some type of cancer during nutrition, and thus could also be prevented their lifetime. Healthcare costs exceed (Am. Cancer Society, 2007). However, 1. 7 trillion dollars per year in the United in developed countries, including United States, which is ? 15% of the country’s States, the average person of 65 years can gross domestic product. expect to live another 15 years in a fairly Tobacco use is the most serious prevent- good health. Persons of 75 or 85 years old able cause of cancer. Tobacco use causes have an average expectancy of 10 and 6 cancer of the lung, throat, mouth, pancreas, years, respectively. urinary bladder, stomach, liver, kidney, and During the last three decades, intensive other types. Passive smoking causes lung clinical research has resulted in reduced cancer.

Each year, tens of millions of people are respectively. The following data indicate diagnosed worldwide with cancer, and the burden (seriousness) of gastrointestinal more than half of these patients eventu- cancer, liver cancer, and colorectal cancers ally die from this disease. The severity of globally and in the United States. (Table 1) the burden of cancer becomes really clear Surgical and molecular therapies and pr- by knowing that there were ? 10, 862, 496 nostic markers for gastrointestinal stromal new cancer cases (excluding skin cancer) tumors are discussed in this volume. Role in the world in 2002, and the number of of anticancer drugs and monoclonal an- deaths caused by this disease in the same bodies specific for these tumors are also year was ? 6,723,887 (GLOBOCAN). discussed. Imaging modality assessing the The number of deaths due to cancer in the effect of anticancer imatinib on these tumors United States was estimated to be 559, 650 is included. Diagnostic and prognostic (Am. Cancer Soc. ). Cancer is caused by markers of clinical outcomes using che- both external factors (tobacco, chemicals, therapy and hormone replacement therapy radiation, and infectious organisms) and for gastric adenocarcinoma are detailed. internal factors (inherited mutations, hor- Also, are discussed immunohistochem- mones, immune conditions, and mutations try of esophageal cancer progression, and that occur from metabolism). diagnostic and therapeutic methodologies All cancer types caused by cigarette for biliary tumors.

This volume discusses various methodolo- discoveries and their translation to clinical gies for the diagnosis, therapy, and prog- practice. Oncology will benefit the most nosis of colorectal cancer (CRC). Volumes from these various advanced methodologies, 1, 2, 3, and 4 of this series present similar as a combination of the rapies and person- methods for breast cancer, lung and pros- ized medicine will improve early detection tate cancers, and gastrointestinal cancer, of CRC and other cancer types. respectively. The current volume presents The use of anticancer agents, including surgical, radiological, and molecular thera- 5-fluorouracil, fluoropyrimidines, leuc- pies and prognostic biomarkers for CRC. orin, irinotecan, oxaliplatin, raltitrexed, A large number of methods, including capecitabine, cetuximab, and bevacizumab, immunohistochemistry, in situ hybridiza- is also presented. Preoperative chemora- tion, immunoscintigraphy, RT-PCR, free otherapy is compared with postoperative circulating DNA levels in blood and stool, chemoradiotherapy.In addition, treatments ultrasonography, CT, PET, and MRI are such as immunotherapy, laparoscopic detailed for diagnosing CRC at various surgery, radiofrequency ablation, pho- stages of development. Imaging technolo- dynamic therapy, and preoperative che- gies for assessing the treatment results are radiotherapy, are presented. Preoperative also included as are details related to colon- short-course radiation for resectable r- oscopy and sigmoidoscopy. In addition, the tal cancer is also detailed. role of mircoRNA as a biomarker for this This volume included the efforts of 89 type of cancer is elaborated.

This volume presents a detailed survey of imaging, multidetector-row computed t- various methodologies related to diagno- ography, helical computed tomography, sis, therapy, and prognosis of liver cancer, ultrasonography, and power Doppler ult- including colorectal liver metastases and sound, for the prognosis and assessment of biliary tract carcinomas, while the already liver cancer treatment (including HCC) and published Volumes 1, 2, 3, and 4 detail liver metastases from colorectal cancer are similar aspects of breast, lung, prostate, discussed in detail, as is the use of radiof- gastrointestinal, and colorectal cancer, quency ablation in hepatic tumors. respectively. Approximately 50% of colorectal cancer Surgical resection is the standard therapy (CRC) patients develop liver metastases for resectable liver disease, resulting in during the course of their disease, and 5-year overall survival rates of 20–40%. more than 50% of patients who die of CRC One the other hand, the median overall have liver metastases at autopsy. Regional survival of patients with unresectable liver lymph node (RLN) involvement in patients metastases does not exceed 18–20 months, with colorectal liver metastases is one with a 5-year survival rate approaching of the worst prognostic factors. Recent zero. In other words, there is virtually no studies indicate that for these patients, long-term survival. Both resectable and combined liver resection and pedicular unresectable liver cancers are discussed lymphadenectomy can be recommended, in this volume. The method of selecting when RLN metastases respond to p- patients for resection of hepatic colorectal operative chemotherapy.

This volume presents a detailed survey of cancers. This volume was written by of various methodologies related to diag- 94 oncologists representing 13 countries. nosis, therapy, and prognosis of ovar- Their practical experience highlights their ian cancer, renal cancer, urinary bladder writings, which should build and further cancer, and cervical uterine cancer, while the endeavors of the readers in this imp- the already published Volumes 1–5 detail tant area of disease. The text of each c- similar aspects of breast, lung, prostate, cer type is divided into subheadings for liver, gastrointestinal, colorectal, and bil- the convenience of the readers. It is my iary tract carcinomas. hope that the current volume will join the It is well established that cancer is the preceding volumes of this series for assi- deadliest of human diseases. The follow- ing in the more complete understanding ing estimated global incidence of seven of globally relevant cancer syndromes. types of cancers discussed in this volume There exists a tremendous, urgent demand indicated the seriousness of this malig- by the public on the scientific community nancy. to address cancer prevention, diagnosis, treatment, and hopefully cures. Cervical uterine cancer 493,342 I am grateful to the contributors for their Urinary bladder cancer 357,000 promptness accepting my suggestions. I respect their dedication and diligent work Leukemia 300,522 in sharing their invaluable knowledge with Renal cancer 208,480 the public through this series.

There are more than 100 types of cancers In Part II, head and neck cancer is d- affecting all parts of the human body. cussed. The global number of annual new More than 11 million people are diagnosed cases of this malignancy is ~500,000. These with cancer every year, and it is estimated malignancies include oral squamous cell that there will be 16 million new cases by carcinoma, salivary gland tumors, tons- the year 2020. In 2005, 7. 6 million peo- lar cancer, tongue cancer, nasopharyngeal ple died of cancer, that is, 13% of the 58 carcinoma, and retinoblastoma, which are million deaths worldwide. It is estimated detailed. In Part III, diagnosis, therapy, and that 9 million people will die from can- prognosis of thyroid carcinoma are d- cer worldwide in 2015 and 11. 4 million cussed. The global number of new cases of will die in 2030. More than 70% of all thyroid cancer is ~141,000, and the number cancer deaths occur in low and middle of worldwide thyroid mortalities is ~35,375. income countries. These statistics underlie The number of new cases of this cancer in the fact that cancer is the deadliest of all the United States is ~33,550. Molecular human diseases. The enormity of the glo- genetics of thyroid cancer, gene expr- bal healthcare costs as a result of cancer sion markers for diagnosis, papillary t- cannot be overemphasized.

The enormity of the global healthcare costs vical. One-fifth of all cancers worldwide as a result of cancer infliction cannot be are caused by a chronic infection, for overemphasized. There are more than 100 example, human papilloma virus (HPV) types of cancers; any part of the body can causes cervical cancer and hepatitis B be affected. More than 11 million people virus (HBV) causes liver cancer. Tobacco are diagnosed with cancer every year, and use is the most common preventable cause it is estimated that there will be 16 mil- of cancer in the world. Approximately, lion new cases per year by the year 2020. 168,000 cancer deaths are expected to be In 2005, 7. 6 million people died of can- caused by tobacco use. Approximately, cer, that is, 13% of the 58 million deaths 40% of cancer could be prevented, mainly worldwide. It is estimated that 9 million by not using tobacco, having a healthy people will die from cancer worldwide in diet, being physically active, preventing 2015 and 11. 4 million will die in 2030. infections that may cause cancer, reduc- More than 70% of all cancer deaths occur ing exposure to sunlight, and avoidance of in low and middle income countries. excessive alcohol consumption and stress Five major cancer causing overall mor- (anger). A third of cancers could be cured talities per year worldwide are (WHO): if detected early and treated adequately. It is well established that scientific 1. Lung: 1.

Cancer is the leading cause of death, in the number of older cancer patients is after cardiovascular diseases, in the expected. Approximately, 77% of all types United States. A total of ? 1,399,790 new of cancers are diagnosed in persons of 55 cancer cases and ? 564,830 deaths were years and older. It was estimated that o- reported in the year 2006 in the country. third of the 559,650 cancer deaths in 2007 Approximately, one in every two men and in the United States were related to ov- one in every three women in the country weight or obesity, physical inactivity, and will have some type of cancer during nutrition, and thus could also be prevented their lifetime. Healthcare costs exceed (Am. Cancer Society, 2007). However, 1. 7 trillion dollars per year in the United in developed countries, including United States, which is ? 15% of the country’s States, the average person of 65 years can gross domestic product. expect to live another 15 years in a fairly Tobacco use is the most serious prevent- good health. Persons of 75 or 85 years old able cause of cancer. Tobacco use causes have an average expectancy of 10 and 6 cancer of the lung, throat, mouth, pancreas, years, respectively. urinary bladder, stomach, liver, kidney, and During the last three decades, intensive other types. Passive smoking causes lung clinical research has resulted in reduced cancer.

Each year, tens of millions of people are respectively. The following data indicate diagnosed worldwide with cancer, and the burden (seriousness) of gastrointestinal more than half of these patients eventu- cancer, liver cancer, and colorectal cancers ally die from this disease. The severity of globally and in the United States. (Table 1) the burden of cancer becomes really clear Surgical and molecular therapies and pr- by knowing that there were ? 10, 862, 496 nostic markers for gastrointestinal stromal new cancer cases (excluding skin cancer) tumors are discussed in this volume. Role in the world in 2002, and the number of of anticancer drugs and monoclonal an- deaths caused by this disease in the same bodies specific for these tumors are also year was ? 6,723,887 (GLOBOCAN). discussed. Imaging modality assessing the The number of deaths due to cancer in the effect of anticancer imatinib on these tumors United States was estimated to be 559, 650 is included. Diagnostic and prognostic (Am. Cancer Soc. ). Cancer is caused by markers of clinical outcomes using che- both external factors (tobacco, chemicals, therapy and hormone replacement therapy radiation, and infectious organisms) and for gastric adenocarcinoma are detailed. internal factors (inherited mutations, hor- Also, are discussed immunohistochem- mones, immune conditions, and mutations try of esophageal cancer progression, and that occur from metabolism). diagnostic and therapeutic methodologies All cancer types caused by cigarette for biliary tumors.

This volume presents a detailed survey of imaging, multidetector-row computed t- various methodologies related to diagno- ography, helical computed tomography, sis, therapy, and prognosis of liver cancer, ultrasonography, and power Doppler ult- including colorectal liver metastases and sound, for the prognosis and assessment of biliary tract carcinomas, while the already liver cancer treatment (including HCC) and published Volumes 1, 2, 3, and 4 detail liver metastases from colorectal cancer are similar aspects of breast, lung, prostate, discussed in detail, as is the use of radiof- gastrointestinal, and colorectal cancer, quency ablation in hepatic tumors. respectively. Approximately 50% of colorectal cancer Surgical resection is the standard therapy (CRC) patients develop liver metastases for resectable liver disease, resulting in during the course of their disease, and 5-year overall survival rates of 20–40%. more than 50% of patients who die of CRC One the other hand, the median overall have liver metastases at autopsy. Regional survival of patients with unresectable liver lymph node (RLN) involvement in patients metastases does not exceed 18–20 months, with colorectal liver metastases is one with a 5-year survival rate approaching of the worst prognostic factors. Recent zero. In other words, there is virtually no studies indicate that for these patients, long-term survival. Both resectable and combined liver resection and pedicular unresectable liver cancers are discussed lymphadenectomy can be recommended, in this volume. The method of selecting when RLN metastases respond to p- patients for resection of hepatic colorectal operative chemotherapy.

This eighth volume in the series Methods of Cancer Diagnosis, Therapy, and Prognosis discusses in detail the classification of the CNS tumors as well as brain tumor imaging. Scientists and Clinicians have contributed state of the art chapters on their respective areas of expertise, providing the reader a whole field view of the CNS tumors and brain tumor imaging in Europe.This fully illustrated volume:Explains the genetics of malignant brain tumors and gene amplification using quantitative-PCR;Presents a large number of standard and new imaging modalities, including magnetic resonance imaging, functional magnetic resonance imaging, diffusion tensor imaging, amide proton transfer imaging, positron emission tomography, single photon emission computed tomography, magnetic resonance single voxel spectroscopy and intraoperative ultrasound imaging, for staging and diagnosing various primary and secondary brain cancers;Explains the usefulness of imaging methods for planning and monitoring (assessment) therapy for cancers;Discusses diagnosis and treatment of primary CNS lymphomas, CNS atypical teratoid/rhabdoid and CNS Rosai-Dorfman disease;Includes the subject of translational medicine. Professor Hayat has summarized the problems associated with the complexities of research publications and has been successful in editing a must-read volume for oncologists, cancer researchers, medical teachers and students of cancer biology.

There are more than 100 types of cancers In Part II, head and neck cancer is d- affecting all parts of the human body. cussed. The global number of annual new More than 11 million people are diagnosed cases of this malignancy is ~500,000. These with cancer every year, and it is estimated malignancies include oral squamous cell that there will be 16 million new cases by carcinoma, salivary gland tumors, tons- the year 2020. In 2005, 7. 6 million peo- lar cancer, tongue cancer, nasopharyngeal ple died of cancer, that is, 13% of the 58 carcinoma, and retinoblastoma, which are million deaths worldwide. It is estimated detailed. In Part III, diagnosis, therapy, and that 9 million people will die from can- prognosis of thyroid carcinoma are d- cer worldwide in 2015 and 11. 4 million cussed. The global number of new cases of will die in 2030. More than 70% of all thyroid cancer is ~141,000, and the number cancer deaths occur in low and middle of worldwide thyroid mortalities is ~35,375. income countries. These statistics underlie The number of new cases of this cancer in the fact that cancer is the deadliest of all the United States is ~33,550. Molecular human diseases. The enormity of the glo- genetics of thyroid cancer, gene expr- bal healthcare costs as a result of cancer sion markers for diagnosis, papillary t- cannot be overemphasized.

This eighth volume in the series Methods of Cancer Diagnosis, Therapy, and Prognosis discusses in detail the classification of the CNS tumors as well as brain tumor imaging. Scientists and Clinicians have contributed state of the art chapters on their respective areas of expertise, providing the reader a whole field view of the CNS tumors and brain tumor imaging in Europe.This fully illustrated volume:Explains the genetics of malignant brain tumors and gene amplification using quantitative-PCR;Presents a large number of standard and new imaging modalities, including magnetic resonance imaging, functional magnetic resonance imaging, diffusion tensor imaging, amide proton transfer imaging, positron emission tomography, single photon emission computed tomography, magnetic resonance single voxel spectroscopy and intraoperative ultrasound imaging, for staging and diagnosing various primary and secondary brain cancers;Explains the usefulness of imaging methods for planning and monitoring (assessment) therapy for cancers;Discusses diagnosis and treatment of primary CNS lymphomas, CNS atypical teratoid/rhabdoid and CNS Rosai-Dorfman disease;Includes the subject of translational medicine. Professor Hayat has summarized the problems associated with the complexities of research publications and has been successful in editing a must-read volume for oncologists, cancer researchers, medical teachers and students of cancer biology.

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 INTRODUCTIONScreening for Colorectal CancerTreatmentRectal CancerREFERENCESA. Diagnosis 2. POORLY DIFFERENTIATED COLORECTAL ADENOCARCINOMA: (METHODOLOGY) Seiichi Shinji, Zenya Naito, Toshiyuki Ishiwata, Yoko Matsuda, Tomoko Seya, and Takashi Tajiri INTRODUCTIONHISTOPATHOLOGYIMMUNOHISTOCHEMISTRY FOR DIFFERENTIAL DIAGNOSISIMMUNOHISTOCHEMISTRY FOR MALIGNANT CHARACATERISTICS OF POORLY DIFFERENTIATED ADENOCARCINOMAIN SITU HYBRIDIZATION FOR MALIGNANT CHARACTERISTICS OF POORLY DIFFERENTIATED ADENOCARCINOMATHERAPYREFERENCES 3. COLORECTAL CANCER: IMMUNOHISTOCHEMICAL; DIAGNOSIS WITH HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN K Ayham Alnabulsi, Brian Carpenter, Colin Telfer, and Graeme I. Murray INTRODUCTIONBIOMARKERSApproved Biomarkers - ProblemsBiomarkers of Colorectal CancerDemand for Colorectal BiomarkersCOLORECTAL BIOMARKER HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN KMethodology2D Gel Electrophoresis (2DGE)Semiquantitative Reverse Transcription-Polymerase Chain ReactionMonoclonal Antibody to Heterogeneous Nuclear Ribonucleoprotein KImmunohistochemistry (IHC)RESULTSDISCUSSIONFUTURE DIRECTIONREFERENCES 4. METASTASES AND RECURRENCE OF COLORECTAL CANCER: DIAGNOSTIC ROLE OF IMMUNOSCINTIGRAPHY Vladimir Obradovic and Vera Artiko INTRODUCTION GENERAL CONSIDERATIONSRadiopharmaceuticalsImaging Systems and TechniquesIMMUNOSCINTIGRAPHIC METHODS USED FOR DIAGNOSTICS OF COLORECTAL CANCERImmunoscintigraphy Based onRadiopharmaceuticals Labeled with RadioiodinesImmunoscintigraphy Based on Radiopharmaceuticals Labeled with 111InImmunoscintigraphy Based on Radiopharmaceuticals Labeled with 99mTcComparison of Diagnostic Values of Different RadiopharmaceuticalsImmunoscintigraphy and Positron Emission TomographyRadioimmunoguided SurgeryCONCLUSIONREFERENCES 5. COLORECTAL CANCER DIAGNOSIS USING DNA LEVELS IN BLOOD AND STOOL Emanuela Flamini, Daniele Calistri, Laura Mercatali, Claudia Rengucci and Dino Amadori INTRODUCTIONAVAILABLE TESTS AND THEIR COST BENEFITSFecal Occult Blood TestFlexible SigmoidoscopyColonoscopyBarium Enema with Air ContrastVirtual ColonoscopyMOLECULAR MARKERS AND THEIR COST BENEFITSFREE CIRCULATING DNA IN BLOODBiological Mechanisms of Free Circulating DNA ReleaseMethodological Aspects of Free Circulating DNASources and Influence of Pre-Analytical FactorsIsolation and QuantificationFree Circulating DNA Levels in Colorectal Cancer DiagnosisINTEGRITY OF GENOMIC EXTRACTED DNA FROM STOOLAnalysis of Long Fragment DNA in StoolAdvantages and Technical ProblemsCONCLUSIONSREFERENCES 6. COLORECTAL CARCINOMA: IDENTIFICATION OF microRNAs USING REAL-TIME POLYMERASE CHAIN REACTION Eva Bandres, Nerea Bitarte, Natalia Ramirez, Ruth Zarate, and Jesus Garcia-Foncillas INTRODUCTIONGENOMICS OF microRNAmicroRNA BIOGENESIS AND FUNCTIONEVIDENCE FOR THE INVOLVEMENT OF microRNA IN CANCERREGULATION OF microRNA EXPRESSIONIDENTIFICATION OF microRNA TARGETS: BIOINFORMATIC AND FUNCTIONAL TOOLSTECHNOLOGY TO QUANTIFY microRNAsEXPERIMENTAL WORKFLOW FOR microRNA EXPRESSION BY REAL- TIME POLYMERASE CHAIN REACTIONIDENTIFICATION OF DIFFERENTIALLY EXPRESSED microRNA IN COLORECTAL CANCER USING REAL-TIME POLYMERASE CHAIN REACTIONQ

The enormity of the global healthcare costs vical. One-fifth of all cancers worldwide as a result of cancer infliction cannot be are caused by a chronic infection, for overemphasized. There are more than 100 example, human papilloma virus (HPV) types of cancers; any part of the body can causes cervical cancer and hepatitis B be affected. More than 11 million people virus (HBV) causes liver cancer. Tobacco are diagnosed with cancer every year, and use is the most common preventable cause it is estimated that there will be 16 mil- of cancer in the world. Approximately, lion new cases per year by the year 2020. 168,000 cancer deaths are expected to be In 2005, 7. 6 million people died of can- caused by tobacco use. Approximately, cer, that is, 13% of the 58 million deaths 40% of cancer could be prevented, mainly worldwide. It is estimated that 9 million by not using tobacco, having a healthy people will die from cancer worldwide in diet, being physically active, preventing 2015 and 11. 4 million will die in 2030. infections that may cause cancer, reduc- More than 70% of all cancer deaths occur ing exposure to sunlight, and avoidance of in low and middle income countries. excessive alcohol consumption and stress Five major cancer causing overall mor- (anger). A third of cancers could be cured talities per year worldwide are (WHO): if detected early and treated adequately. It is well established that scientific 1. Lung: 1.

Cancer is the leading cause of death, in the number of older cancer patients is after cardiovascular diseases, in the expected. Approximately, 77% of all types United States. A total of ? 1,399,790 new of cancers are diagnosed in persons of 55 cancer cases and ? 564,830 deaths were years and older. It was estimated that o- reported in the year 2006 in the country. third of the 559,650 cancer deaths in 2007 Approximately, one in every two men and in the United States were related to ov- one in every three women in the country weight or obesity, physical inactivity, and will have some type of cancer during nutrition, and thus could also be prevented their lifetime. Healthcare costs exceed (Am. Cancer Society, 2007). However, 1. 7 trillion dollars per year in the United in developed countries, including United States, which is ? 15% of the country’s States, the average person of 65 years can gross domestic product. expect to live another 15 years in a fairly Tobacco use is the most serious prevent- good health. Persons of 75 or 85 years old able cause of cancer. Tobacco use causes have an average expectancy of 10 and 6 cancer of the lung, throat, mouth, pancreas, years, respectively. urinary bladder, stomach, liver, kidney, and During the last three decades, intensive other types. Passive smoking causes lung clinical research has resulted in reduced cancer.

Each year, tens of millions of people are respectively. The following data indicate diagnosed worldwide with cancer, and the burden (seriousness) of gastrointestinal more than half of these patients eventu- cancer, liver cancer, and colorectal cancers ally die from this disease. The severity of globally and in the United States. (Table 1) the burden of cancer becomes really clear Surgical and molecular therapies and pr- by knowing that there were ? 10, 862, 496 nostic markers for gastrointestinal stromal new cancer cases (excluding skin cancer) tumors are discussed in this volume. Role in the world in 2002, and the number of of anticancer drugs and monoclonal an- deaths caused by this disease in the same bodies specific for these tumors are also year was ? 6,723,887 (GLOBOCAN). discussed. Imaging modality assessing the The number of deaths due to cancer in the effect of anticancer imatinib on these tumors United States was estimated to be 559, 650 is included. Diagnostic and prognostic (Am. Cancer Soc. ). Cancer is caused by markers of clinical outcomes using che- both external factors (tobacco, chemicals, therapy and hormone replacement therapy radiation, and infectious organisms) and for gastric adenocarcinoma are detailed. internal factors (inherited mutations, hor- Also, are discussed immunohistochem- mones, immune conditions, and mutations try of esophageal cancer progression, and that occur from metabolism). diagnostic and therapeutic methodologies All cancer types caused by cigarette for biliary tumors.

This volume discusses various methodolo- discoveries and their translation to clinical gies for the diagnosis, therapy, and prog- practice. Oncology will benefit the most nosis of colorectal cancer (CRC). Volumes from these various advanced methodologies, 1, 2, 3, and 4 of this series present similar as a combination of the rapies and person- methods for breast cancer, lung and pros- ized medicine will improve early detection tate cancers, and gastrointestinal cancer, of CRC and other cancer types. respectively. The current volume presents The use of anticancer agents, including surgical, radiological, and molecular thera- 5-fluorouracil, fluoropyrimidines, leuc- pies and prognostic biomarkers for CRC. orin, irinotecan, oxaliplatin, raltitrexed, A large number of methods, including capecitabine, cetuximab, and bevacizumab, immunohistochemistry, in situ hybridiza- is also presented. Preoperative chemora- tion, immunoscintigraphy, RT-PCR, free otherapy is compared with postoperative circulating DNA levels in blood and stool, chemoradiotherapy.In addition, treatments ultrasonography, CT, PET, and MRI are such as immunotherapy, laparoscopic detailed for diagnosing CRC at various surgery, radiofrequency ablation, pho- stages of development. Imaging technolo- dynamic therapy, and preoperative che- gies for assessing the treatment results are radiotherapy, are presented. Preoperative also included as are details related to colon- short-course radiation for resectable r- oscopy and sigmoidoscopy. In addition, the tal cancer is also detailed. role of mircoRNA as a biomarker for this This volume included the efforts of 89 type of cancer is elaborated.

This volume presents a detailed survey of imaging, multidetector-row computed t- various methodologies related to diagno- ography, helical computed tomography, sis, therapy, and prognosis of liver cancer, ultrasonography, and power Doppler ult- including colorectal liver metastases and sound, for the prognosis and assessment of biliary tract carcinomas, while the already liver cancer treatment (including HCC) and published Volumes 1, 2, 3, and 4 detail liver metastases from colorectal cancer are similar aspects of breast, lung, prostate, discussed in detail, as is the use of radiof- gastrointestinal, and colorectal cancer, quency ablation in hepatic tumors. respectively. Approximately 50% of colorectal cancer Surgical resection is the standard therapy (CRC) patients develop liver metastases for resectable liver disease, resulting in during the course of their disease, and 5-year overall survival rates of 20–40%. more than 50% of patients who die of CRC One the other hand, the median overall have liver metastases at autopsy. Regional survival of patients with unresectable liver lymph node (RLN) involvement in patients metastases does not exceed 18–20 months, with colorectal liver metastases is one with a 5-year survival rate approaching of the worst prognostic factors. Recent zero. In other words, there is virtually no studies indicate that for these patients, long-term survival. Both resectable and combined liver resection and pedicular unresectable liver cancers are discussed lymphadenectomy can be recommended, in this volume. The method of selecting when RLN metastases respond to p- patients for resection of hepatic colorectal operative chemotherapy.

This volume presents a detailed survey of cancers. This volume was written by of various methodologies related to diag- 94 oncologists representing 13 countries. nosis, therapy, and prognosis of ovar- Their practical experience highlights their ian cancer, renal cancer, urinary bladder writings, which should build and further cancer, and cervical uterine cancer, while the endeavors of the readers in this imp- the already published Volumes 1–5 detail tant area of disease. The text of each c- similar aspects of breast, lung, prostate, cer type is divided into subheadings for liver, gastrointestinal, colorectal, and bil- the convenience of the readers. It is my iary tract carcinomas. hope that the current volume will join the It is well established that cancer is the preceding volumes of this series for assi- deadliest of human diseases. The follow- ing in the more complete understanding ing estimated global incidence of seven of globally relevant cancer syndromes. types of cancers discussed in this volume There exists a tremendous, urgent demand indicated the seriousness of this malig- by the public on the scientific community nancy. to address cancer prevention, diagnosis, treatment, and hopefully cures. Cervical uterine cancer 493,342 I am grateful to the contributors for their Urinary bladder cancer 357,000 promptness accepting my suggestions. I respect their dedication and diligent work Leukemia 300,522 in sharing their invaluable knowledge with Renal cancer 208,480 the public through this series.

There are more than 100 types of cancers In Part II, head and neck cancer is d- affecting all parts of the human body. cussed. The global number of annual new More than 11 million people are diagnosed cases of this malignancy is ~500,000. These with cancer every year, and it is estimated malignancies include oral squamous cell that there will be 16 million new cases by carcinoma, salivary gland tumors, tons- the year 2020. In 2005, 7. 6 million peo- lar cancer, tongue cancer, nasopharyngeal ple died of cancer, that is, 13% of the 58 carcinoma, and retinoblastoma, which are million deaths worldwide. It is estimated detailed. In Part III, diagnosis, therapy, and that 9 million people will die from can- prognosis of thyroid carcinoma are d- cer worldwide in 2015 and 11. 4 million cussed. The global number of new cases of will die in 2030. More than 70% of all thyroid cancer is ~141,000, and the number cancer deaths occur in low and middle of worldwide thyroid mortalities is ~35,375. income countries. These statistics underlie The number of new cases of this cancer in the fact that cancer is the deadliest of all the United States is ~33,550. Molecular human diseases. The enormity of the glo- genetics of thyroid cancer, gene expr- bal healthcare costs as a result of cancer sion markers for diagnosis, papillary t- cannot be overemphasized.

The enormity of the global healthcare costs vical. One-fifth of all cancers worldwide as a result of cancer infliction cannot be are caused by a chronic infection, for overemphasized. There are more than 100 example, human papilloma virus (HPV) types of cancers; any part of the body can causes cervical cancer and hepatitis B be affected. More than 11 million people virus (HBV) causes liver cancer. Tobacco are diagnosed with cancer every year, and use is the most common preventable cause it is estimated that there will be 16 mil- of cancer in the world. Approximately, lion new cases per year by the year 2020. 168,000 cancer deaths are expected to be In 2005, 7. 6 million people died of can- caused by tobacco use. Approximately, cer, that is, 13% of the 58 million deaths 40% of cancer could be prevented, mainly worldwide. It is estimated that 9 million by not using tobacco, having a healthy people will die from cancer worldwide in diet, being physically active, preventing 2015 and 11. 4 million will die in 2030. infections that may cause cancer, reduc- More than 70% of all cancer deaths occur ing exposure to sunlight, and avoidance of in low and middle income countries. excessive alcohol consumption and stress Five major cancer causing overall mor- (anger). A third of cancers could be cured talities per year worldwide are (WHO): if detected early and treated adequately. It is well established that scientific 1. Lung: 1.

Cancer is the leading cause of death, in the number of older cancer patients is after cardiovascular diseases, in the expected. Approximately, 77% of all types United States. A total of ? 1,399,790 new of cancers are diagnosed in persons of 55 cancer cases and ? 564,830 deaths were years and older. It was estimated that o- reported in the year 2006 in the country. third of the 559,650 cancer deaths in 2007 Approximately, one in every two men and in the United States were related to ov- one in every three women in the country weight or obesity, physical inactivity, and will have some type of cancer during nutrition, and thus could also be prevented their lifetime. Healthcare costs exceed (Am. Cancer Society, 2007). However, 1. 7 trillion dollars per year in the United in developed countries, including United States, which is ? 15% of the country’s States, the average person of 65 years can gross domestic product. expect to live another 15 years in a fairly Tobacco use is the most serious prevent- good health. Persons of 75 or 85 years old able cause of cancer. Tobacco use causes have an average expectancy of 10 and 6 cancer of the lung, throat, mouth, pancreas, years, respectively. urinary bladder, stomach, liver, kidney, and During the last three decades, intensive other types. Passive smoking causes lung clinical research has resulted in reduced cancer.

Each year, tens of millions of people are respectively. The following data indicate diagnosed worldwide with cancer, and the burden (seriousness) of gastrointestinal more than half of these patients eventu- cancer, liver cancer, and colorectal cancers ally die from this disease. The severity of globally and in the United States. (Table 1) the burden of cancer becomes really clear Surgical and molecular therapies and pr- by knowing that there were ? 10, 862, 496 nostic markers for gastrointestinal stromal new cancer cases (excluding skin cancer) tumors are discussed in this volume. Role in the world in 2002, and the number of of anticancer drugs and monoclonal an- deaths caused by this disease in the same bodies specific for these tumors are also year was ? 6,723,887 (GLOBOCAN). discussed. Imaging modality assessing the The number of deaths due to cancer in the effect of anticancer imatinib on these tumors United States was estimated to be 559, 650 is included. Diagnostic and prognostic (Am. Cancer Soc. ). Cancer is caused by markers of clinical outcomes using che- both external factors (tobacco, chemicals, therapy and hormone replacement therapy radiation, and infectious organisms) and for gastric adenocarcinoma are detailed. internal factors (inherited mutations, hor- Also, are discussed immunohistochem- mones, immune conditions, and mutations try of esophageal cancer progression, and that occur from metabolism). diagnostic and therapeutic methodologies All cancer types caused by cigarette for biliary tumors.

This volume presents a detailed survey of imaging, multidetector-row computed t- various methodologies related to diagno- ography, helical computed tomography, sis, therapy, and prognosis of liver cancer, ultrasonography, and power Doppler ult- including colorectal liver metastases and sound, for the prognosis and assessment of biliary tract carcinomas, while the already liver cancer treatment (including HCC) and published Volumes 1, 2, 3, and 4 detail liver metastases from colorectal cancer are similar aspects of breast, lung, prostate, discussed in detail, as is the use of radiof- gastrointestinal, and colorectal cancer, quency ablation in hepatic tumors. respectively. Approximately 50% of colorectal cancer Surgical resection is the standard therapy (CRC) patients develop liver metastases for resectable liver disease, resulting in during the course of their disease, and 5-year overall survival rates of 20–40%. more than 50% of patients who die of CRC One the other hand, the median overall have liver metastases at autopsy. Regional survival of patients with unresectable liver lymph node (RLN) involvement in patients metastases does not exceed 18–20 months, with colorectal liver metastases is one with a 5-year survival rate approaching of the worst prognostic factors. Recent zero. In other words, there is virtually no studies indicate that for these patients, long-term survival. Both resectable and combined liver resection and pedicular unresectable liver cancers are discussed lymphadenectomy can be recommended, in this volume. The method of selecting when RLN metastases respond to p- patients for resection of hepatic colorectal operative chemotherapy.

This eighth volume in the series Methods of Cancer Diagnosis, Therapy, and Prognosis discusses in detail the classification of the CNS tumors as well as brain tumor imaging. Scientists and Clinicians have contributed state of the art chapters on their respective areas of expertise, providing the reader a whole field view of the CNS tumors and brain tumor imaging in Europe.This fully illustrated volume:Explains the genetics of malignant brain tumors and gene amplification using quantitative-PCR;Presents a large number of standard and new imaging modalities, including magnetic resonance imaging, functional magnetic resonance imaging, diffusion tensor imaging, amide proton transfer imaging, positron emission tomography, single photon emission computed tomography, magnetic resonance single voxel spectroscopy and intraoperative ultrasound imaging, for staging and diagnosing various primary and secondary brain cancers;Explains the usefulness of imaging methods for planning and monitoring (assessment) therapy for cancers;Discusses diagnosis and treatment of primary CNS lymphomas, CNS atypical teratoid/rhabdoid and CNS Rosai-Dorfman disease;Includes the subject of translational medicine. Professor Hayat has summarized the problems associated with the complexities of research publications and has been successful in editing a must-read volume for oncologists, cancer researchers, medical teachers and students of cancer biology.

There are more than 100 types of cancers In Part II, head and neck cancer is d- affecting all parts of the human body. cussed. The global number of annual new More than 11 million people are diagnosed cases of this malignancy is ~500,000. These with cancer every year, and it is estimated malignancies include oral squamous cell that there will be 16 million new cases by carcinoma, salivary gland tumors, tons- the year 2020. In 2005, 7. 6 million peo- lar cancer, tongue cancer, nasopharyngeal ple died of cancer, that is, 13% of the 58 carcinoma, and retinoblastoma, which are million deaths worldwide. It is estimated detailed. In Part III, diagnosis, therapy, and that 9 million people will die from can- prognosis of thyroid carcinoma are d- cer worldwide in 2015 and 11. 4 million cussed. The global number of new cases of will die in 2030. More than 70% of all thyroid cancer is ~141,000, and the number cancer deaths occur in low and middle of worldwide thyroid mortalities is ~35,375. income countries. These statistics underlie The number of new cases of this cancer in the fact that cancer is the deadliest of all the United States is ~33,550. Molecular human diseases. The enormity of the glo- genetics of thyroid cancer, gene expr- bal healthcare costs as a result of cancer sion markers for diagnosis, papillary t- cannot be overemphasized.

This eighth volume in the series Methods of Cancer Diagnosis, Therapy, and Prognosis discusses in detail the classification of the CNS tumors as well as brain tumor imaging. Scientists and Clinicians have contributed state of the art chapters on their respective areas of expertise, providing the reader a whole field view of the CNS tumors and brain tumor imaging in Europe.This fully illustrated volume:Explains the genetics of malignant brain tumors and gene amplification using quantitative-PCR;Presents a large number of standard and new imaging modalities, including magnetic resonance imaging, functional magnetic resonance imaging, diffusion tensor imaging, amide proton transfer imaging, positron emission tomography, single photon emission computed tomography, magnetic resonance single voxel spectroscopy and intraoperative ultrasound imaging, for staging and diagnosing various primary and secondary brain cancers;Explains the usefulness of imaging methods for planning and monitoring (assessment) therapy for cancers;Discusses diagnosis and treatment of primary CNS lymphomas, CNS atypical teratoid/rhabdoid and CNS Rosai-Dorfman disease;Includes the subject of translational medicine. Professor Hayat has summarized the problems associated with the complexities of research publications and has been successful in editing a must-read volume for oncologists, cancer researchers, medical teachers and students of cancer biology.

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 INTRODUCTIONScreening for Colorectal CancerTreatmentRectal CancerREFERENCESA. Diagnosis 2. POORLY DIFFERENTIATED COLORECTAL ADENOCARCINOMA: (METHODOLOGY) Seiichi Shinji, Zenya Naito, Toshiyuki Ishiwata, Yoko Matsuda, Tomoko Seya, and Takashi Tajiri INTRODUCTIONHISTOPATHOLOGYIMMUNOHISTOCHEMISTRY FOR DIFFERENTIAL DIAGNOSISIMMUNOHISTOCHEMISTRY FOR MALIGNANT CHARACATERISTICS OF POORLY DIFFERENTIATED ADENOCARCINOMAIN SITU HYBRIDIZATION FOR MALIGNANT CHARACTERISTICS OF POORLY DIFFERENTIATED ADENOCARCINOMATHERAPYREFERENCES 3. COLORECTAL CANCER: IMMUNOHISTOCHEMICAL; DIAGNOSIS WITH HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN K Ayham Alnabulsi, Brian Carpenter, Colin Telfer, and Graeme I. Murray INTRODUCTIONBIOMARKERSApproved Biomarkers - ProblemsBiomarkers of Colorectal CancerDemand for Colorectal BiomarkersCOLORECTAL BIOMARKER HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN KMethodology2D Gel Electrophoresis (2DGE)Semiquantitative Reverse Transcription-Polymerase Chain ReactionMonoclonal Antibody to Heterogeneous Nuclear Ribonucleoprotein KImmunohistochemistry (IHC)RESULTSDISCUSSIONFUTURE DIRECTIONREFERENCES 4. METASTASES AND RECURRENCE OF COLORECTAL CANCER: DIAGNOSTIC ROLE OF IMMUNOSCINTIGRAPHY Vladimir Obradovic and Vera Artiko INTRODUCTION GENERAL CONSIDERATIONSRadiopharmaceuticalsImaging Systems and TechniquesIMMUNOSCINTIGRAPHIC METHODS USED FOR DIAGNOSTICS OF COLORECTAL CANCERImmunoscintigraphy Based onRadiopharmaceuticals Labeled with RadioiodinesImmunoscintigraphy Based on Radiopharmaceuticals Labeled with 111InImmunoscintigraphy Based on Radiopharmaceuticals Labeled with 99mTcComparison of Diagnostic Values of Different RadiopharmaceuticalsImmunoscintigraphy and Positron Emission TomographyRadioimmunoguided SurgeryCONCLUSIONREFERENCES 5. COLORECTAL CANCER DIAGNOSIS USING DNA LEVELS IN BLOOD AND STOOL Emanuela Flamini, Daniele Calistri, Laura Mercatali, Claudia Rengucci and Dino Amadori INTRODUCTIONAVAILABLE TESTS AND THEIR COST BENEFITSFecal Occult Blood TestFlexible SigmoidoscopyColonoscopyBarium Enema with Air ContrastVirtual ColonoscopyMOLECULAR MARKERS AND THEIR COST BENEFITSFREE CIRCULATING DNA IN BLOODBiological Mechanisms of Free Circulating DNA ReleaseMethodological Aspects of Free Circulating DNASources and Influence of Pre-Analytical FactorsIsolation and QuantificationFree Circulating DNA Levels in Colorectal Cancer DiagnosisINTEGRITY OF GENOMIC EXTRACTED DNA FROM STOOLAnalysis of Long Fragment DNA in StoolAdvantages and Technical ProblemsCONCLUSIONSREFERENCES 6. COLORECTAL CARCINOMA: IDENTIFICATION OF microRNAs USING REAL-TIME POLYMERASE CHAIN REACTION Eva Bandres, Nerea Bitarte, Natalia Ramirez, Ruth Zarate, and Jesus Garcia-Foncillas INTRODUCTIONGENOMICS OF microRNAmicroRNA BIOGENESIS AND FUNCTIONEVIDENCE FOR THE INVOLVEMENT OF microRNA IN CANCERREGULATION OF microRNA EXPRESSIONIDENTIFICATION OF microRNA TARGETS: BIOINFORMATIC AND FUNCTIONAL TOOLSTECHNOLOGY TO QUANTIFY microRNAsEXPERIMENTAL WORKFLOW FOR microRNA EXPRESSION BY REAL- TIME POLYMERASE CHAIN REACTIONIDENTIFICATION OF DIFFERENTIALLY EXPRESSED microRNA IN COLORECTAL CANCER USING REAL-TIME POLYMERASE CHAIN REACTIONQ