**Meet the editor**

Jim Khan is a specialist colorectal surgeon with a comprehensive training in general, colorectal, laparoscopic and robotic surgery. After graduation in 1996, he specialised in general surgery and became a fellow of the Royal College of Physicians & Surgeons Glasgow. He completed his specialist registrar training in colorectal surgery in Wessex. He learned complex pelvic and

rectal cancer surgery while working with Professor Heald at Basingstoke. His specialist colorectal training included the UK National Laparoscopic Fellowship at Colchester, where he received training from Prof Roger Motson in advanced laparoscopic pelvic surgery. Later on he was awarded a travelling clinical fellowship at Mayo Clinic Rochester (US). He has vast experience of laparoscopic surgery and his main practice is application of laparoscopic and robotic surgery for treating colorectal cancer and inflammatory bowel disease. He, in collaboration with Prof Amjad Parvaiz, has published and presented widely on this subject. At Portsmouth he is actively involved in medical education and clinical training. He trains on a variety of courses both nationally and internationally including basic surgical skills, laparoscopic skills, ATLS, TEMS, Laparoscopic colorectal surgery and coloproctology courses. He has been a national trainer for consultants' training in laparoscopic colorectal surgery (LapCo)—a programme run by the Department of Health for promotion of training in key-hole bowel cancer surgery.

Contents

**Preface IX**

Chapter 1 **Screening for Colorectal Cancer 3**

**Rectal Cancer 53**

Robert Partyka

**Section 3 Surgery for colorectal cancer 99**

Kirilova and Krassimir Ivanov

Syed Naqvi and Syeda Farah Nazir

Chapter 2 **Diagnostic Modalities in Colorectal Cancer –Endoscopy, Ct and**

**Ultrasound and Intraoperative Ultrasound 29**

Chapter 3 **Role of Magnetic Resonance Imaging in Locally Advanced**

Chapter 4 **Role of Tumour Markers in Diagnosis and Follow up of**

Chapter 5 **Laparoscopy in the Management of Colorectal Cancer 101**

Chapter 6 **Single-Incision Laparoscopic Colectomy: A New Era in the**

Fabio Cianchi, Fabio Staderini and Benedetta Badii

**Treatment of Colorectal Cancer? 125**

Paolo Delrio, Fabiana Tatangelo and Antonella Petrillo

**Colorectal Cancer — Potential for Future Research 75**

**Pet Scanning, Magnetic Resonance Imaging (Mri), Endoluminal**

Valentin Ignatov, Nikola Kolev, Anton Tonev, Shteryu Shterev, Elitsa Encheva, Tanya Kirilova, Tsvetelina Teneva and Krassimir Ivanov

Roberta Fusco, Mario Sansone, Mario Petrillo, Antonio Avallone,

Anton Tonev, Nikola Kolev, Valentin Ignatov, Vasil Bojkov, Tanya

**Section 1 Screening 1**

**Section 2 Diagnostics 27**

## Contents

#### **Preface XIII**


Paolo Delrio, Fabiana Tatangelo and Antonella Petrillo


Chapter 15 **Prospects of 'Omics Based Molecular Approaches in Colorectal**

Chapter 16 **COL11A1 — Genetic Biomarker Targeted in Stool Samples for**

Chapter 17 **The Complexity of Colorectal Cancer Biology — Putting Bricks on the Path to Personalized Medicine 433** Emilia Balboa, Angel Carracedo and Francisco Barros

Chapter 18 **The Role, Significance and Applicability of Aberrant Crypt Foci**

Raúl Sánchez-Jiménez, Alberto Blanco Álvarez, Jacobo Trebol López, Antonio Sánchez Jiménez, Fernando Gutiérrez Conde and

Chapter 20 **Psychosocial Care for Patients with Colorectal Cancer 505**

**in Clinical Practice 467** Martina Perše and Anton Cerar

Chapter 19 **ERAS (Enhanced Recovery after Surgery) in Colorectal Surgery 487**

José Antonio Carmona Sáez

**Section 6 Post operative care 485**

Hitoshi Okamura

**Case Study in Cape Town, South Africa 363**

Blackburn

**Cancer Diagnosis and Treatment in the Developing World: A**

Contents **VII**

Henry Adeola, Ryan William Goosen, Paul Goldberg and Jonathan

**Early Diagnosis of Colorectal Cancer in Patients at Risk 403** Andra Iulia Suceveanu, Laura Mazilu and Adrian-Paul Suceveanu


Chapter 7 **Robotic Colorectal Cancer Surgery 141**

**VI** Contents

**Colorectal Cancer 165**

**Colorectal Cancer 191**

García and C. Cano

Vicente Portugal

**Section 4 Adjuvant Therapy 281**

**Section 5 Genomics 329**

Chapter 8 **Surgical Strategies for Liver Metastases from**

Ray Swayamjyoti, Jim Khan and Amjad Parvaiz

Ivanov, Alexander Zlatarov and Krassimir Ivanov

Chapter 10 **New Strategies to Enhance the Efficacy of Surgical Treatment**

Chapter 12 **Current State-of-the-Science Adjuvant and Neoadjuvant**

**Therapy in Surgically Resected Colorectal Cancer 283**

Krassimir Ivanov, Nikola Kolev, Ivan Shterev, Anton Tonev, Valentin

Chapter 9 **Management of Non-Hepatic Metastatic Disease in**

**for Colorectal Liver Metastasis 219**

Chapter 11 **Rare Tumors of the Colon and Rectum 253** Goran Stanojević and Zoran Krivokapić

I.H. Sahin and C.R. Garrett

Chapter 13 **Adjuvant Treatment in Colorectal Cancer 305**

**Population Based Study 331**

Hussain and Khurshid I. Andrabi

Ignatov, Vasil Bojkov and Tanya Kirilova

Chapter 14 **Possible Role of Proto-Oncogenes in Colorectal Cancer — A**

Syed Mudassar, Mosin S Khan, Nighat P. Khan, Mahboob ul-

Nikola Kolev, Valentin Ignatov, Anton Tonev, Tanya Kirilova, Georgi

C. Alberto Blanco, R. Sánchez, F. Piniella, D. Pescador, G. Borobio, A.

Teodoro Palomares, Ana Alonso-Varona, Ignacio García-Alonso and


Preface

into the topic.

Colorectal cancer is one of the commonest cancers affecting both men and women in the western world. Surgery has been the mainstay of treatment with 5 years survival rates be‐ tween 80-90% for stage I and II and dropping to 40% for advanced disease. The last decade has seen significant developments in the diagnosis and management of colorectal cancer. Better survival and improved patient outcomes have been reported across the globe due to

It's extremely important for any clinician dealing with colorectal cancer patients to stay up to date with their knowledge of the disease, its behavior, management options and response to therapy. This book provides state of the art papers on some very important topics in the field of management of colorectal cancer. The chapter on screening critically analyses the different screening tests and also gives a comprehensive review of different screening mo‐ dalities used in different countries. An update on MRI, PET and Ultrasound imaging for col‐ orectal cancer is provided. Advances in surgical technology including laparoscopic surgery, single port surgery and robotic surgery are discussed in detail and the data from published literature & authors experiences are presented in a simple and comprehensible way for the readers. Section on adjuvant therapy covers the role of chemotherapy and radiotherapy very well, with particular emphasis on newer biological agents and targeted therapy. Genomics in colorectal cancer have been the focus of some significant research and this area has been covered very well by expert authors sharing their experience and providing useful insights

This book will be an interesting read for any clinician dealing with colorectal cancer in their practice. This will also prove a useful update manual for any trainees in colorectal surgery, gastroenterology and radiology. I am grateful to all the authors for sharing their experience and valuable work and also would like to thank Sandra Bakic for her unreserved support in editing this work. Last but not least I am very grateful to my wife, Sadaf for providing me

**Jim Khan**

Portsmouth, UK

Consultant Colorectal & Minimal Access Surgeon

Portsmouth Hospitals NHS Trust

with the inspiration and help all the way along, enabling me to complete this task.

advances in technology, better diagnostics and improvements in adjuvant therapy.

## Preface

Colorectal cancer is one of the commonest cancers affecting both men and women in the western world. Surgery has been the mainstay of treatment with 5 years survival rates be‐ tween 80-90% for stage I and II and dropping to 40% for advanced disease. The last decade has seen significant developments in the diagnosis and management of colorectal cancer. Better survival and improved patient outcomes have been reported across the globe due to advances in technology, better diagnostics and improvements in adjuvant therapy.

It's extremely important for any clinician dealing with colorectal cancer patients to stay up to date with their knowledge of the disease, its behavior, management options and response to therapy. This book provides state of the art papers on some very important topics in the field of management of colorectal cancer. The chapter on screening critically analyses the different screening tests and also gives a comprehensive review of different screening mo‐ dalities used in different countries. An update on MRI, PET and Ultrasound imaging for col‐ orectal cancer is provided. Advances in surgical technology including laparoscopic surgery, single port surgery and robotic surgery are discussed in detail and the data from published literature & authors experiences are presented in a simple and comprehensible way for the readers. Section on adjuvant therapy covers the role of chemotherapy and radiotherapy very well, with particular emphasis on newer biological agents and targeted therapy. Genomics in colorectal cancer have been the focus of some significant research and this area has been covered very well by expert authors sharing their experience and providing useful insights into the topic.

This book will be an interesting read for any clinician dealing with colorectal cancer in their practice. This will also prove a useful update manual for any trainees in colorectal surgery, gastroenterology and radiology. I am grateful to all the authors for sharing their experience and valuable work and also would like to thank Sandra Bakic for her unreserved support in editing this work. Last but not least I am very grateful to my wife, Sadaf for providing me with the inspiration and help all the way along, enabling me to complete this task.

> **Jim Khan** Consultant Colorectal & Minimal Access Surgeon Portsmouth Hospitals NHS Trust Portsmouth, UK

**Section 1**

**Screening**

**Section 1**

## **Screening**

**Chapter 1**

**Screening for Colorectal Cancer**

Additional information is available at the end of the chapter

to the patients with identified and treated cancer.

It has become an acknowledged fact that Colorectal Cancer (CRC) is a worldwide problem, with an annual incidence of approximately 1 million cases and an annual mortality of more than 500,000. Furthermore, the absolute number of cases will increase over the next two decades as a result of the aging and expansion of populations in both the developed and

Apparently, CRC is the second most common cause of cancer related mortality among men and women in the world; so, most CRCs arise from sporadic adenomas, and a few from genetic polyposis syndromes or inflammatory bowel disease (IBD). The term "polyp" refers to a discrete mass that protrudes into the intestinal lumen. Therefore, the reported prevalence of adenomatous polyps, on the basis of screening colonoscopy data, is in the range of 18–36%.

The fact is that the risk for CRC varies from country to country and even within countries; the risk also varies among individual people based on diet, lifestyle, and hereditary factors. The most common neoplastic outcome of colorectal cancer screening is the adenoma. After having removed, patients need to be placed in a follow-up surveillance programme, very much similar

In the western world, we are very much aware that colorectal cancer has become an important health problem as each year, over 380,000 persons are diagnosed with colorectal cancer; bout half of these, patients die of the disease making colorectal cancer the second leading cause of cancer deaths in Europe. An estimated figure reveals that almost one million people suffering from colorectal cancer are going through cost – intensive treatments putting a huge burden on

Screening is defined as population based testing in an asymptomatic individual to identify particular disease. The aim of screening is to lower the burden of cancer in the population by

> © 2014 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Syed Naqvi and Syeda Farah Nazir

http://dx.doi.org/10.5772/57506

**1. Introduction**

developing countries.

the healthcare system.

## **Chapter 1**

## **Screening for Colorectal Cancer**

Syed Naqvi and Syeda Farah Nazir

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/57506

## **1. Introduction**

It has become an acknowledged fact that Colorectal Cancer (CRC) is a worldwide problem, with an annual incidence of approximately 1 million cases and an annual mortality of more than 500,000. Furthermore, the absolute number of cases will increase over the next two decades as a result of the aging and expansion of populations in both the developed and developing countries.

Apparently, CRC is the second most common cause of cancer related mortality among men and women in the world; so, most CRCs arise from sporadic adenomas, and a few from genetic polyposis syndromes or inflammatory bowel disease (IBD). The term "polyp" refers to a discrete mass that protrudes into the intestinal lumen. Therefore, the reported prevalence of adenomatous polyps, on the basis of screening colonoscopy data, is in the range of 18–36%.

The fact is that the risk for CRC varies from country to country and even within countries; the risk also varies among individual people based on diet, lifestyle, and hereditary factors. The most common neoplastic outcome of colorectal cancer screening is the adenoma. After having removed, patients need to be placed in a follow-up surveillance programme, very much similar to the patients with identified and treated cancer.

In the western world, we are very much aware that colorectal cancer has become an important health problem as each year, over 380,000 persons are diagnosed with colorectal cancer; bout half of these, patients die of the disease making colorectal cancer the second leading cause of cancer deaths in Europe. An estimated figure reveals that almost one million people suffering from colorectal cancer are going through cost – intensive treatments putting a huge burden on the healthcare system.

Screening is defined as population based testing in an asymptomatic individual to identify particular disease. The aim of screening is to lower the burden of cancer in the population by

© 2014 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

discovering latent disease in its early stages and treating it more effectively than diagnosed later when symptoms have appeared. As such, screening is a commendable method to reduce the burden of the disease. However, population screening targets a predominantly healthy population, and should therefore only be conducted after a careful consideration of both harms and benefits.

**•** Support by influential professional and patient advocacy groups and from the media is

Screening for Colorectal Cancer http://dx.doi.org/10.5772/57506 5

**•** Evaluate the feasibility of the proposed programme. Address the development and

**•** Identify the target unit for implementation, and ensure communication (training and education) with providers (general practitioners and others) and the target population. **•** Develop and disseminate guidelines on screening, diagnosis, treatment, and surveillance in

**•** Careful, timely monitoring of following rates: screening uptake, re-screening, and follow-

**•** Outcomes, including detection rates, cancer stage distribution, adenoma detection, compli‐

**2. Colorectal cancer risk assessment tools and referral system in different**

It is believed that colorectal cancer risk varies regionally according to geographical distribution of the population. As we will see in following sections, colorectal screening is yet to be implemented fully in general population of developed countries of the world. So in different regions, colorectal cancer risk assessment tools has been introduced to identify the high risk patients needs to be screened in general population of the society. Usually these risk assess‐ ment tools are for GPs and primary care units to identify the high risk patients to be screened.

The risk assessment tool was based on work done by Professor Willie Hamilton in the CAPER studies (Cancer Prediction in Exeter), a series of case control studies which identified symp‐ toms of common cancers that were presented to primary care and quantified the risk of cancer associated with them. The tool acts as reminder to GPs to consider the likelihood of an individual patient aged 40 or over having lung or bowel cancer given the symptom or combination of symptoms they present with. It is presented as three tables (colorectal cancer,

**•** Measurement of the programme quality should be in place, and evaluated regularly.

cations, and finally, the effect on the population incidence and mortality.

allocation of the resources (financial, personnel, facilities).

**•** Develop methods for initial patient enrollment and follow-up.

Implementation of screening programme:

Monitoring the Screening program:

up of the positive test.

**countries in the world**

a patient friendly and culture sensitive manner.

**•** Compliance with surveillance recommendations.

**2.1. Hamilton risk assessment tool for colorectal cancer**

**•** Evaluate the specific cultural and language needs of the population.

essential.

In 1968 the World Health Organization [1] (WHO) defined the first set of principles of population screening (Wilson &Junger 1968). These principles are still valid today.

The desirable features for community screening program for any disease are:


Recommendation for action- general:


Recommendation for action –Programme design:

Planning the screening programme:


Implementation of screening programme:

discovering latent disease in its early stages and treating it more effectively than diagnosed later when symptoms have appeared. As such, screening is a commendable method to reduce the burden of the disease. However, population screening targets a predominantly healthy population, and should therefore only be conducted after a careful consideration of both harms

In 1968 the World Health Organization [1] (WHO) defined the first set of principles of

**6.** The test should have high sensitivity and specificity and should be safe, effective,

**•** Develop and disseminate structured educational programme for members of the public, providers, health-care systems, and policy-makers/political leaders. Effective educational programmes should be directed to each of the important participants in an acceptable

**•** Develop evidence-based standards for quality throughout the screening process. **•** Develop and disseminate inexpensive, easy-to-use clinical management systems.

**•** Promote colorectal cancer screening as a part of comprehensive clinical preventive care.

**•** A target population should identify-asymptomatic men and women, age, risk factors (e.g.,

**•** The decision to implement colorectal cancer screening should be based on the relative

**•** The screening strategy (test, interval, age range) should be based on medical evidence (guidelines), availability of resources, level of risk, and cultural acceptance by population.

population screening (Wilson &Junger 1968). These principles are still valid today.

The desirable features for community screening program for any disease are:

**1.** The disease should be an important health problem

**3.** The disease should be detectable at an early stage

**7.** Services should be in place to treat the early disease

**•** Advocate screening through national and local venues.

burden of the colorectal cancer in the population to be screened.

Recommendation for action –Programme design:

Planning the screening programme:

acceptable, inexpensive, and repeatable after an interval

**8.** Benefits of decrease mortality and morbidity should be there

**2.** Natural history of the disease must be known

**4.** Benefits of early detection should be there **5.** Simple test should be available at early stage

4 Colorectal Cancer - Surgery, Diagnostics and Treatment

Recommendation for action- general:

and benefits.

manner.

familial)


Monitoring the Screening program:


## **2. Colorectal cancer risk assessment tools and referral system in different countries in the world**

It is believed that colorectal cancer risk varies regionally according to geographical distribution of the population. As we will see in following sections, colorectal screening is yet to be implemented fully in general population of developed countries of the world. So in different regions, colorectal cancer risk assessment tools has been introduced to identify the high risk patients needs to be screened in general population of the society. Usually these risk assess‐ ment tools are for GPs and primary care units to identify the high risk patients to be screened.

#### **2.1. Hamilton risk assessment tool for colorectal cancer**

The risk assessment tool was based on work done by Professor Willie Hamilton in the CAPER studies (Cancer Prediction in Exeter), a series of case control studies which identified symp‐ toms of common cancers that were presented to primary care and quantified the risk of cancer associated with them. The tool acts as reminder to GPs to consider the likelihood of an individual patient aged 40 or over having lung or bowel cancer given the symptom or combination of symptoms they present with. It is presented as three tables (colorectal cancer, lung cancer for non smokers and lung cancer for smokers) containing the risk values for each symptom in isolation or combination and is available as mouse mat or a desk easel so as to be easy to hand.

colitis or Crohn`s disease), certain inherited genetic conditions, such as familial adenoma‐ tous polyposis or hereditary nonpolyposis colorectal cancers) or a personal history of colorectal cancer. These conditions are known to carry a high risk of colorectal cancer.

Screening for Colorectal Cancer http://dx.doi.org/10.5772/57506 7

From a development set of 860 asymptomatic subjects undergoing screening colonoscopy, multiple logistic regression was applied to identify significant risk factors advanced colorectal neoplasia defined as invasive carcinoma or advance adenoma. Odd Ratios for significant risk factors were utilised to develop risk score ranging from 0 to 7 (Asia- pacific Colorectal Screening (APCS score). Three tiers of risk were arbitrarily defined:0-1 `average risk` (AR); 2-3 `moderate risk` (MR); 4-7 `high risk` (HR). In this study performance of the APCS score in

**3. Current tests for colorectal screening and emerging screening tools**

Guaiac-Based faecal occult bleeding test (gFOBT) is at present the most frequently used method in screening programme throughout the world. It detects the peroxidase reaction of Hemo‐ globin, which causes the detection paper impregnated with guaiac resin to turn blue. As it can react with animal haemoglobin, dietetic restrictions are necessary to exclude the false- positive results. A number of studies showed limited sensitivity of this test for both, advanced adenomas (11%) and carcinomas (13%). With gFOBT, a decrease in mortality for colorectal

Immunological faecal occult bleeding test (iFOBT) reacts exclusively to human haemoglo‐ bin, so no dietetic restrictions are seen as necessary.Taking and assessing the stool samples are easier than the case with gFOBTs, which may explain a higher participation in the target population. A wide range of qualitative and quantitative tests are available, with varying levels of sensitivity and specificity. The advantage of quantitative tests is the possibility to set cut-off limits; the most frequently used values are 75 or 10 ng/ml. The disadvantage of iFOBT is its cost. It is, no doubt, an expensive test as compared to gFOBT. But, presently, the price is approaching that of gFOBT for qualitative tests. As this test has higher sensitivity and specificity as compared to gFOBT, iFOBT is being increasingly used

New screening methods include tests which examine the stool for the presence of abnormal DNA. Generally, these tests have higher sensitivity but lower specificity than gFOBT. They

Flexible sigmoidoscopy is an endoscopic examination with maximum reach to splenic flexure. On the basis of emerging evidence---this is a promising screening test. A number of studies are under progress to accumulate enough evidence for usage of flexible

are expensive tests and a major obstacle in their implementation is their price. [3]

**2.3. Asia-Pacific Colorectal Screening (APCS) score**

predicting risk of advanced neoplasia was evaluated

cancer by 15 to 33% has been proved.

in screening programmes.

The following screening methods are currently used globally:

The parameter used in Hamilton risk assessment tool are: constipation, diarrhoea, rectal bleeding, loss of weight, abdominal pain, abdominal tenderness, abnormal rectal examination and haemoglobin <10g/dl.

#### **2.2. USA National Cancer Institute (NCI USA TOOL)**

A recent online tool for calculating colorectal cancer risk in men and women age 50 or older was launched, based on a new risk assessment model developed by researchers at the National Cancer Institute (NCI), part of the National Institute of Health. This new tool may help health care providers and their patients in making informed choices about when and how to screen for colorectal cancers and can be used in designing colorectal cancer screening and prevention trials.

So, by using easily obtainable information (e.g., personal and family medical history, lifestyle behaviours, and age), the tool provides an estimate of an individual`s risk of developing colorectal cancer over certain time periods (within five years, ten years, and over the course of lifetime). This risk-assessment model is first to provide an absolute risk estimate for colorectal cancer (i.e., the probability of developing colorectal cancer over a given period of time) for general non –Hispanic white population age 50 or older in United States.

In order to develop the risk assessment model, the researcher used data from two large- based case control studies. Several factors that have been previously associated with colorectal risk were shown to be predicted of a colorectal cancer diagnosis in those two studies including age; family history of colorectal cancer; consumption of vegetables; body mass index; cigarette smoking; use of aspirin or other non-steroidal anti inflammatory drugs; physical activity; use of hormone replacement therapy; previous history of sigmoidoscopy and/or colonoscopy; and history of polyps. Estimates of relative risk (comparisons of risk in one group to another) from the case-control studies were combined with population based data on colorectal cancer incidence from NCI`sSEER (Surveillance, Epidemiology and End Results) cancer registries to make the model broadly applicable in United States. [2]

"This colorectal cancer risk model should provide physicians and their patients a new tool to help in making informed decisions about cancer screening and other cancer prevention strategies. It may also assist policy makers in evaluating the usefulness of current and future population colorectal cancer screening approaches" said Andrew Freedman,Ph.D., lead author of the paper that describes the development of the risk-assessment model.

It has been observed that the majority of participants in the two case-control studies used to develop the model were non-Hispanic whites aged 50 or older, the researchers were unable to estimate relative risks for other age and racial/ethnic groups. However, there are plans to expand the tool to include these populations in the future. In addition, the tool is not applicable to individuals with certain gastrointestinal disorders (such as ulcerative colitis or Crohn`s disease), certain inherited genetic conditions, such as familial adenoma‐ tous polyposis or hereditary nonpolyposis colorectal cancers) or a personal history of colorectal cancer. These conditions are known to carry a high risk of colorectal cancer.

#### **2.3. Asia-Pacific Colorectal Screening (APCS) score**

lung cancer for non smokers and lung cancer for smokers) containing the risk values for each symptom in isolation or combination and is available as mouse mat or a desk easel so as to be

The parameter used in Hamilton risk assessment tool are: constipation, diarrhoea, rectal bleeding, loss of weight, abdominal pain, abdominal tenderness, abnormal rectal examination

A recent online tool for calculating colorectal cancer risk in men and women age 50 or older was launched, based on a new risk assessment model developed by researchers at the National Cancer Institute (NCI), part of the National Institute of Health. This new tool may help health care providers and their patients in making informed choices about when and how to screen for colorectal cancers and can be used in designing colorectal cancer screening and prevention

So, by using easily obtainable information (e.g., personal and family medical history, lifestyle behaviours, and age), the tool provides an estimate of an individual`s risk of developing colorectal cancer over certain time periods (within five years, ten years, and over the course of lifetime). This risk-assessment model is first to provide an absolute risk estimate for colorectal cancer (i.e., the probability of developing colorectal cancer over a given period of

In order to develop the risk assessment model, the researcher used data from two large- based case control studies. Several factors that have been previously associated with colorectal risk were shown to be predicted of a colorectal cancer diagnosis in those two studies including age; family history of colorectal cancer; consumption of vegetables; body mass index; cigarette smoking; use of aspirin or other non-steroidal anti inflammatory drugs; physical activity; use of hormone replacement therapy; previous history of sigmoidoscopy and/or colonoscopy; and history of polyps. Estimates of relative risk (comparisons of risk in one group to another) from the case-control studies were combined with population based data on colorectal cancer incidence from NCI`sSEER (Surveillance, Epidemiology and End Results) cancer registries to

"This colorectal cancer risk model should provide physicians and their patients a new tool to help in making informed decisions about cancer screening and other cancer prevention strategies. It may also assist policy makers in evaluating the usefulness of current and future population colorectal cancer screening approaches" said Andrew Freedman,Ph.D., lead author

It has been observed that the majority of participants in the two case-control studies used to develop the model were non-Hispanic whites aged 50 or older, the researchers were unable to estimate relative risks for other age and racial/ethnic groups. However, there are plans to expand the tool to include these populations in the future. In addition, the tool is not applicable to individuals with certain gastrointestinal disorders (such as ulcerative

of the paper that describes the development of the risk-assessment model.

time) for general non –Hispanic white population age 50 or older in United States.

easy to hand.

trials.

and haemoglobin <10g/dl.

6 Colorectal Cancer - Surgery, Diagnostics and Treatment

**2.2. USA National Cancer Institute (NCI USA TOOL)**

make the model broadly applicable in United States. [2]

From a development set of 860 asymptomatic subjects undergoing screening colonoscopy, multiple logistic regression was applied to identify significant risk factors advanced colorectal neoplasia defined as invasive carcinoma or advance adenoma. Odd Ratios for significant risk factors were utilised to develop risk score ranging from 0 to 7 (Asia- pacific Colorectal Screening (APCS score). Three tiers of risk were arbitrarily defined:0-1 `average risk` (AR); 2-3 `moderate risk` (MR); 4-7 `high risk` (HR). In this study performance of the APCS score in predicting risk of advanced neoplasia was evaluated

## **3. Current tests for colorectal screening and emerging screening tools**

The following screening methods are currently used globally:

Guaiac-Based faecal occult bleeding test (gFOBT) is at present the most frequently used method in screening programme throughout the world. It detects the peroxidase reaction of Hemo‐ globin, which causes the detection paper impregnated with guaiac resin to turn blue. As it can react with animal haemoglobin, dietetic restrictions are necessary to exclude the false- positive results. A number of studies showed limited sensitivity of this test for both, advanced adenomas (11%) and carcinomas (13%). With gFOBT, a decrease in mortality for colorectal cancer by 15 to 33% has been proved.

Immunological faecal occult bleeding test (iFOBT) reacts exclusively to human haemoglo‐ bin, so no dietetic restrictions are seen as necessary.Taking and assessing the stool samples are easier than the case with gFOBTs, which may explain a higher participation in the target population. A wide range of qualitative and quantitative tests are available, with varying levels of sensitivity and specificity. The advantage of quantitative tests is the possibility to set cut-off limits; the most frequently used values are 75 or 10 ng/ml. The disadvantage of iFOBT is its cost. It is, no doubt, an expensive test as compared to gFOBT. But, presently, the price is approaching that of gFOBT for qualitative tests. As this test has higher sensitivity and specificity as compared to gFOBT, iFOBT is being increasingly used in screening programmes.

New screening methods include tests which examine the stool for the presence of abnormal DNA. Generally, these tests have higher sensitivity but lower specificity than gFOBT. They are expensive tests and a major obstacle in their implementation is their price. [3]

Flexible sigmoidoscopy is an endoscopic examination with maximum reach to splenic flexure. On the basis of emerging evidence---this is a promising screening test. A number of studies are under progress to accumulate enough evidence for usage of flexible

sigmoidoscopy as a screening test based on WHO guidelines. Recommended interval varies from 3 to 5 years. A recent pilot study carried out in Darby UK\* [36]. In the UK flexible sigmoidoscopy trial, 90% of all CRC detected at screening was found in the distal colon. According to one report by Sophie White et al from university of Sheffield, more than 60% adenomas are detected in left side of colon at screening age of the population and more than 70% CRC detected by flexible sigmoidoscopy at the screening age of the population.

**4. Current global colorectal cancer screening pathways**

Until 2007 Colorectal Cancer Screening was running or being established in 19 of 27 European countries [4] The target group contains approximately 136 million individuals suitable for colorectal screening ( aged 50 to 74 years). Of this number, 43% individual come from 12 countries where colorectal population screening is performed or being prepared on either national or regional level; 34% come from the five countries where national population screening has been implemented (Finland, France, Italy, Poland and United Kingdom).

Screening for Colorectal Cancer http://dx.doi.org/10.5772/57506 9

In 2007,gFOBT (which in 2003 was the only test recommended by the council of the European union) was used as the only screening method in twelve countries (Bulgaria, Czech republic, Finland, France, Hungary, Latvia, Portgal, Romania, Slovena, Spain, Sweedon, and United Kingdom). Colonoscopy was the only screening method used in Poland. In six countries, two types of the tests were used: i FOBT and flexible sigmoidoscopy in Italy, and g FOBT and colonoscopy in Austria, Cyprus, Germany, Greece, and Slovak republic. In the remaining 8 states, (Belgium, Denmark, Estonia, Ireland, Lithuania, Luxembourg, Malta, and the Nether‐ lands), colorectal cancer screening has not been implemented yet. The age limit for target

After 2007 Report, EU countries progressed toward the implementation of population screening programme. Recently, new EU guidelines for screening of colorectal cancers have

In United Kingdom, a screening programme was announced in 2004 and initiated in 2006, with prospects of national coverage in 2009. It has been designed in two stages: with gFOBT tests at two yearly intervals with colonoscopy for positive tests. In 2007, the compliance was 52%. The program is carried out through regional centres falling under one of the five national hubs.

The NHS Bowel Cancer Screening has achieved nation-wide coverage by 2010. The programme hubs operate a national call and recall system to send out FOBT kits, analyse samples and dispatch results. Consequently, each hub is responsible for coordinating the programme in their area and works up-to 20 local screening centres. The screening centres provide endoscopy services and specialist screening nurse clinics for people receiving abnormal results. Screening centres are also responsible for referring those requiring treatment to local hospital multidis‐

In Ireland, colorectal screening programme was launched in 2009 after National Screening Board Report which was published in December 2008 [6] A summary of the screening

**•** An immunochemical faecal occult blood test (iFOBT) is the primary screening tool for

**•** A target population for screening of all men and women aged 55 and 74 years with a

**4.1. Europe**

population varies across EU countries.

The role of general practitioners is less significant here. [5]

population-based colorectal screening programme.

been introduced.

ciplinary team (MDT).

programme highlights:

screening interval of two years.

Colonoscopy is another screening tool used in diagnostic and therapeutic endoscopic proce‐ dure which also detects lesion in proximal colon. It is more sensitive in detecting both adenomas and carcinomas. This is an established screening procedure for synchronous and metachronous tumours and surveillance of polyposis and non polyposis hereditary colorectal cancers. This is also a primary surveillance tool for multiple polyps according to guidelines. The risk of serious adverse events is higher than any other screening test with one in five hundred colonic perforation rate in expert hands. In spite of being gold standard, colonoscopy will not establish itself as an ideal population screening test due to its cost and adverse events and a lack of wide spread skills available.

Computed tomographic colonography (virtual colonoscopy) can detect lesions in the colon and rectum by reconstructing two-and three-dimentional images. To date, there is no evidence of reduction in incidence and mortality of colorectal cancer by this method in comparison with other screening tools. In cases, where caecum is not reached during colonoscopy due to patient related factors, CT colonography is the preferable screening tool to complete the examination. According to current NICE guidelines, the evidence of meta-analysis of data of 14 studies with a total of 1324 patients concluded that for CT colonography, the pooled per-patient sensitivity for polyps 10mm or larger was 88%, for polyps 6-9mm it was 84% and for polyps 5mm or smaller it was 65%. The pooled per-polyp sensitivity for polyps 10mm or larger was 81%, for polyps 6-9mm it was 62% and for polyp 5mm or smaller it was 43%. The overall specificity for the detection of polyps 10mm or larger was 95%. No significant complications were reported in the studies

Double contrast barium enema shows entire colon and rectum, although with significantly lower sensitivity and specificity than colonoscopy. The percentage of undetected carcinomas is upto 22%. This test is no longer widespread and in clinical practice due to its low sensitivity and specificity and availability of other better screening tools. Despite the fact, it still has a role in the areas in the world where colonoscopy and flexible sigmoidoscopy resources are severely limited.

It is quite obvious that Colorectal Screening is a complex process which in order to function requires the coexistence of number of factors such as a functioning invitation-reminder system, media campaigns targeted at the general public, the development of recommendations for general practitioners, patients compliance, sufficient funding, stratification of risks, and last but not least the election of the most suitable screening test. Among all available screening tests, only Fecal Occult Blood Test meets the WHO criteria.

## **4. Current global colorectal cancer screening pathways**

#### **4.1. Europe**

sigmoidoscopy as a screening test based on WHO guidelines. Recommended interval varies from 3 to 5 years. A recent pilot study carried out in Darby UK\* [36]. In the UK flexible sigmoidoscopy trial, 90% of all CRC detected at screening was found in the distal colon. According to one report by Sophie White et al from university of Sheffield, more than 60% adenomas are detected in left side of colon at screening age of the population and more than 70% CRC detected by flexible sigmoidoscopy at the screening age of the population.

Colonoscopy is another screening tool used in diagnostic and therapeutic endoscopic proce‐ dure which also detects lesion in proximal colon. It is more sensitive in detecting both adenomas and carcinomas. This is an established screening procedure for synchronous and metachronous tumours and surveillance of polyposis and non polyposis hereditary colorectal cancers. This is also a primary surveillance tool for multiple polyps according to guidelines. The risk of serious adverse events is higher than any other screening test with one in five hundred colonic perforation rate in expert hands. In spite of being gold standard, colonoscopy will not establish itself as an ideal population screening test due to its cost and adverse events

Computed tomographic colonography (virtual colonoscopy) can detect lesions in the colon and rectum by reconstructing two-and three-dimentional images. To date, there is no evidence of reduction in incidence and mortality of colorectal cancer by this method in comparison with other screening tools. In cases, where caecum is not reached during colonoscopy due to patient related factors, CT colonography is the preferable screening tool to complete the examination. According to current NICE guidelines, the evidence of meta-analysis of data of 14 studies with a total of 1324 patients concluded that for CT colonography, the pooled per-patient sensitivity for polyps 10mm or larger was 88%, for polyps 6-9mm it was 84% and for polyps 5mm or smaller it was 65%. The pooled per-polyp sensitivity for polyps 10mm or larger was 81%, for polyps 6-9mm it was 62% and for polyp 5mm or smaller it was 43%. The overall specificity for the detection of polyps 10mm or larger was 95%. No significant complications were reported

Double contrast barium enema shows entire colon and rectum, although with significantly lower sensitivity and specificity than colonoscopy. The percentage of undetected carcinomas is upto 22%. This test is no longer widespread and in clinical practice due to its low sensitivity and specificity and availability of other better screening tools. Despite the fact, it still has a role in the areas in the world where colonoscopy and flexible sigmoidoscopy resources are severely

It is quite obvious that Colorectal Screening is a complex process which in order to function requires the coexistence of number of factors such as a functioning invitation-reminder system, media campaigns targeted at the general public, the development of recommendations for general practitioners, patients compliance, sufficient funding, stratification of risks, and last but not least the election of the most suitable screening test. Among all available screening

tests, only Fecal Occult Blood Test meets the WHO criteria.

and a lack of wide spread skills available.

8 Colorectal Cancer - Surgery, Diagnostics and Treatment

in the studies

limited.

Until 2007 Colorectal Cancer Screening was running or being established in 19 of 27 European countries [4] The target group contains approximately 136 million individuals suitable for colorectal screening ( aged 50 to 74 years). Of this number, 43% individual come from 12 countries where colorectal population screening is performed or being prepared on either national or regional level; 34% come from the five countries where national population screening has been implemented (Finland, France, Italy, Poland and United Kingdom).

In 2007,gFOBT (which in 2003 was the only test recommended by the council of the European union) was used as the only screening method in twelve countries (Bulgaria, Czech republic, Finland, France, Hungary, Latvia, Portgal, Romania, Slovena, Spain, Sweedon, and United Kingdom). Colonoscopy was the only screening method used in Poland. In six countries, two types of the tests were used: i FOBT and flexible sigmoidoscopy in Italy, and g FOBT and colonoscopy in Austria, Cyprus, Germany, Greece, and Slovak republic. In the remaining 8 states, (Belgium, Denmark, Estonia, Ireland, Lithuania, Luxembourg, Malta, and the Nether‐ lands), colorectal cancer screening has not been implemented yet. The age limit for target population varies across EU countries.

After 2007 Report, EU countries progressed toward the implementation of population screening programme. Recently, new EU guidelines for screening of colorectal cancers have been introduced.

In United Kingdom, a screening programme was announced in 2004 and initiated in 2006, with prospects of national coverage in 2009. It has been designed in two stages: with gFOBT tests at two yearly intervals with colonoscopy for positive tests. In 2007, the compliance was 52%. The program is carried out through regional centres falling under one of the five national hubs. The role of general practitioners is less significant here. [5]

The NHS Bowel Cancer Screening has achieved nation-wide coverage by 2010. The programme hubs operate a national call and recall system to send out FOBT kits, analyse samples and dispatch results. Consequently, each hub is responsible for coordinating the programme in their area and works up-to 20 local screening centres. The screening centres provide endoscopy services and specialist screening nurse clinics for people receiving abnormal results. Screening centres are also responsible for referring those requiring treatment to local hospital multidis‐ ciplinary team (MDT).

In Ireland, colorectal screening programme was launched in 2009 after National Screening Board Report which was published in December 2008 [6] A summary of the screening programme highlights:


**•** Colonoscopy to be offered to those individuals who test positive with iFOBT

In France, Screening program was initiated in 2003, based on gFOBT tests at 2 years intervals with colonoscopy for positive result [7]. The role of general practitioners as coordinators is of crucial importance. The major advantage of French program is its good organization, with a call-recall system comprising central management at national level and individual steps taken by centres in individual departments. Asymptomatic individuals aged from 50-70yrs are mailed gFOBT tests, with the reminder at three monthly intervals for nonparticipants. Compliance in referred districts achieved 42%, and overall positive test rate was 2.7%. The screening programme has been generalised to the whole French territory since 2008.

asymptomatic individuals more than 50 years of age by their general practitioners at preven‐ tative medical checks, followed by colonoscopies if tests were positive. Now both gFOBT and iFOBT are being offered. The implementation of the newly designed programme is supported

Screening for Colorectal Cancer http://dx.doi.org/10.5772/57506 11

According to a recent survey, one in 12 Australians are likely to develop the colorectal cancers in their lifetime. [14] In Australia, CRC is second most common cause of cancer-related mortality. [15] survival from colorectal cancer is stage-dependent, yet fewer than 40% of

In Australia, clinical practice guidelines for the prevention, early detection and management of colorectal cancer (the national guidelines) recommend that asymptomatic people classified as "at or slightly above risk" receive FOBT screening biennially, commencing at 50 years of age, with sigmoidoscopy (preferable flexible) consider every 5 yrs. [17]. Colonoscopy screening is endorsed only for asymptomatic people who are considered to be at "moderately increased risk" or "potentially high risk"due to risk features including personal or family history of CRC, adenoma and chronic ulcerative colitis. The recently re-funded National Bowel Cancer Screening Programme (NBCSP) offers one-off Immunochemical FOBT screening to people

Implementation of biennial CRC screening in Australia for all those aged 50-74 years could prevent up to 500 deaths per year, [18] with cost effectiveness comparable to breast and cervical

In USA, men and women who are 50 to 75 year old should be screened for colorectal cancer

Colorectal screening rates rose for both men and women. The rate for women increased slightly faster, so that the rates for men and women were about the same in 2010 [58.5% for men and 50.8%for women.The colorectal cancer screening was 58.6%, below the target of 70.5%.

In Asia colorectal screening percentage is at its lowest level and research revealed that colorectal cancer burden rapidly increasing in Asian countries [21]. A study to evaluate the cost-effectiveness of FOBT, flexible sigmoidoscopy and colonoscopy in Asian countries

**•** Sigmoidoscopy every five years and a high-sensitivity FOBT every three years.

Recently, the following EU guidelines for Colorectal Screening are published:

by intense media campaign. [12,13]

turning 50, 55 or 65 years of age.

cancer screening Programs. [19]

**•** A colonoscopy every10 year.

in one of the following three ways; [20]

**•** A high-sensitivity faecal occult blood test (FOBT) every year.

**4.3. United States**

**4.4. Asia**

individuals are diagnosed at a localised stage. [16]

**4.2. Australia**

In Italy, a nation-wide campaign was initiated in 2005; the implementation was entrusted entirely to 21 regional centres, including choice of the testing method. In Piedmont region, flexible sigmoidoscopy is the method of choice, in other regions iFOBT, with colonoscopy for positive tests. [8]

In Spain, the main obstacle to its implementation was the highly heterogeneous healthcare system, in terms of organization and insurance coverage in individual self governing units. That is why they are behind in implementation of screening program as compared to the UK, Germany, France, Italy and Finland.

In Finland, a structured screening programme was initiated in 2004. The target population, aged from 60 to 69 years (106000 individuals), was randomised into two groups. Individuals in the screening group were mailed a gFOBT test at intervals of 2 years. The finish program shows a high level compliance of the target population (70.8%), particularly for females [9]

Poland is the only state at the moment using colonoscopy as the only screening method, without the alternative of of FOBTs. An opportunistic screening programme was initiated in 2000, and by 2005, this had grown to 57 centres across Poland. The program is financed by ministry of health, independent of the overall healthcare system. The target population (Asymptomatic individuals aged 55-66 years) is recruited through general practitioners. High emphasis is placed on the quality control of the colonoscopies, with complications reported for 0.1% of the procedures, and no patient mortality. The advantage of the programme is through monitoring and evaluation, including monitoring of interval cancers. [10]

Germany was the first country to introduce a population screening program (in 1976) based on annual gFOBT for individuals more than 44 year of age. Since 2002, it has been offering participants a choice between colonoscopy at 55 year of age and FOBT at annual intervals between 50 and 55 year of age. After 55 year of age, examinations are carried out at 2 year, if the test results are positive colonoscopy is indicated. Those who undergo a screening colono‐ scopy with no neoplasia detected at initial examination are recommended re-examination at 10 years time if the first colonoscopy was carried out before they were 65. The positive feature of screening and data gathering is the emphasis on staging the disease at the time of its diagnosis. [11]

In the Czech Republic, CRC screening has many years of tradition. The country was the second in the world to start screening nation-wide, in 2000. In the initial years, gFOBT was offered to asymptomatic individuals more than 50 years of age by their general practitioners at preven‐ tative medical checks, followed by colonoscopies if tests were positive. Now both gFOBT and iFOBT are being offered. The implementation of the newly designed programme is supported by intense media campaign. [12,13]

Recently, the following EU guidelines for Colorectal Screening are published:

#### **4.2. Australia**

**•** Colonoscopy to be offered to those individuals who test positive with iFOBT

screening programme has been generalised to the whole French territory since 2008.

positive tests. [8]

diagnosis. [11]

Germany, France, Italy and Finland.

10 Colorectal Cancer - Surgery, Diagnostics and Treatment

In France, Screening program was initiated in 2003, based on gFOBT tests at 2 years intervals with colonoscopy for positive result [7]. The role of general practitioners as coordinators is of crucial importance. The major advantage of French program is its good organization, with a call-recall system comprising central management at national level and individual steps taken by centres in individual departments. Asymptomatic individuals aged from 50-70yrs are mailed gFOBT tests, with the reminder at three monthly intervals for nonparticipants. Compliance in referred districts achieved 42%, and overall positive test rate was 2.7%. The

In Italy, a nation-wide campaign was initiated in 2005; the implementation was entrusted entirely to 21 regional centres, including choice of the testing method. In Piedmont region, flexible sigmoidoscopy is the method of choice, in other regions iFOBT, with colonoscopy for

In Spain, the main obstacle to its implementation was the highly heterogeneous healthcare system, in terms of organization and insurance coverage in individual self governing units. That is why they are behind in implementation of screening program as compared to the UK,

In Finland, a structured screening programme was initiated in 2004. The target population, aged from 60 to 69 years (106000 individuals), was randomised into two groups. Individuals in the screening group were mailed a gFOBT test at intervals of 2 years. The finish program shows a high level compliance of the target population (70.8%), particularly for females [9]

Poland is the only state at the moment using colonoscopy as the only screening method, without the alternative of of FOBTs. An opportunistic screening programme was initiated in 2000, and by 2005, this had grown to 57 centres across Poland. The program is financed by ministry of health, independent of the overall healthcare system. The target population (Asymptomatic individuals aged 55-66 years) is recruited through general practitioners. High emphasis is placed on the quality control of the colonoscopies, with complications reported for 0.1% of the procedures, and no patient mortality. The advantage of the programme is

Germany was the first country to introduce a population screening program (in 1976) based on annual gFOBT for individuals more than 44 year of age. Since 2002, it has been offering participants a choice between colonoscopy at 55 year of age and FOBT at annual intervals between 50 and 55 year of age. After 55 year of age, examinations are carried out at 2 year, if the test results are positive colonoscopy is indicated. Those who undergo a screening colono‐ scopy with no neoplasia detected at initial examination are recommended re-examination at 10 years time if the first colonoscopy was carried out before they were 65. The positive feature of screening and data gathering is the emphasis on staging the disease at the time of its

In the Czech Republic, CRC screening has many years of tradition. The country was the second in the world to start screening nation-wide, in 2000. In the initial years, gFOBT was offered to

through monitoring and evaluation, including monitoring of interval cancers. [10]

According to a recent survey, one in 12 Australians are likely to develop the colorectal cancers in their lifetime. [14] In Australia, CRC is second most common cause of cancer-related mortality. [15] survival from colorectal cancer is stage-dependent, yet fewer than 40% of individuals are diagnosed at a localised stage. [16]

In Australia, clinical practice guidelines for the prevention, early detection and management of colorectal cancer (the national guidelines) recommend that asymptomatic people classified as "at or slightly above risk" receive FOBT screening biennially, commencing at 50 years of age, with sigmoidoscopy (preferable flexible) consider every 5 yrs. [17]. Colonoscopy screening is endorsed only for asymptomatic people who are considered to be at "moderately increased risk" or "potentially high risk"due to risk features including personal or family history of CRC, adenoma and chronic ulcerative colitis. The recently re-funded National Bowel Cancer Screening Programme (NBCSP) offers one-off Immunochemical FOBT screening to people turning 50, 55 or 65 years of age.

Implementation of biennial CRC screening in Australia for all those aged 50-74 years could prevent up to 500 deaths per year, [18] with cost effectiveness comparable to breast and cervical cancer screening Programs. [19]

#### **4.3. United States**

In USA, men and women who are 50 to 75 year old should be screened for colorectal cancer in one of the following three ways; [20]


Colorectal screening rates rose for both men and women. The rate for women increased slightly faster, so that the rates for men and women were about the same in 2010 [58.5% for men and 50.8%for women.The colorectal cancer screening was 58.6%, below the target of 70.5%.

#### **4.4. Asia**

In Asia colorectal screening percentage is at its lowest level and research revealed that colorectal cancer burden rapidly increasing in Asian countries [21]. A study to evaluate the cost-effectiveness of FOBT, flexible sigmoidoscopy and colonoscopy in Asian countries indicated that FOBT is cost-effective compared to flexible sigmoidoscopy or colonoscopy for colorectal screening in average risk population. [22]

**•** Intermediate risk; Patients with 3-4 small adenomas or at least one >1cm.Three yearly

Screening for Colorectal Cancer http://dx.doi.org/10.5772/57506 13

**•** High risk; Patients with >5 adenomas or > 3 adenomas at least one of which >1cm. An extra examination should be undertaken at 12 months before returning to three yearly surveil‐

The cut off age for stopping surveillance is usually 75 years but should also depends upon

Patients with incomplete examinations due to failed colonoscopies, for whatever reasons, should undergo repeat colonoscopy or alternative complete colonic examination (ct colonog‐ raphy). These guidelines are based on accurate detection of adenomas; otherwise risk status

Large sessile adenomas removed piecemeal should be re-examined every three months. Small areas of residual polyp can be retreated endoscopically, for further check for complete eradications in three months. If extensive residual polyp is seen, open surgical resection needs to be considered. If there is complete healing of polypectomy site, then there should be sigmoidoscopy or colonoscopy at one year before returning to three yearly Surveillance. India

The cut-off age for stopping surveillance is usually quoted as 75 years as the remaining life expectancy is likely to be less than the average time required for new adenomas to become malignant. After this age, it is unlikely that the benefits of surveillance will outweigh the potential risk of the procedure. However, this should not preclude further surveillance in a fit and motivated person who has a tendency to produce multiple or advanced adenomas at

The risk and benefit of adenoma surveillance needs to be balanced at all ages, particularly in

The decision to undertake each colonoscopy examination at follow up should depend not only on the number and type of adenomas, but also on the patient's age and wishes, and the presence of significant co morbidity. The Patient status should be established prior to attendance for

**6. Importance of audit in screening and screening relating colonoscopies**

In any screening programme, as with any other medical service programme, adequate steps must be taken to ensure that the original objectives are being met and that methodology meets appropriate standard. The importance of maintaining the quality of screening programmes should never be under estimated. Evaluation, audit and quality control should be an integral

part of any screening programme to ensure that it is achieving what it meant to be.

colonoscopy until two consecutive negative examinations.

ink tattooing aids recognition of the polypectomy site at follow up.

lance.

patients wishes and comorbidity.

will be under estimated.

Stopping Surveillance.

patients who have significant co morbidity.

each examination possibly by questionnaires.

follow up.

The Increasing rate of colorectal cancer in Asia means that we need to take action immediately to prevent colorectal cancer and to diagnose the disease at early stages. The cost-effectiveness of screening programmes must be assessed in each individual country and research should be done to elucidate the epidemiology, genetic and environmental factors in development of colorectal cancer. [21]

## **5. Management of screening detected polyps**

It is now widely accepted that the majority of colonic cancers arise from pre-existing adenom‐ atous polyps (adenoma-carcinoma sequence).The supporting evidence being as follows: [23]


The patients who have undergone colonoscopy and had adenomas removed are at increased risk of developing colorectal cancer (CRC) in future, and therefore might benefit from colonoscopic surveillance. [24]

Surveillance Guidelines about colorectal adenomas are established by British Society of Gastroentrology. According to these guidelines surveillance of the colorectal adenomas depends upon ; number of polys, size of polyps and grade of dysplasia present in histology. Risk of colorectal cancer and adenomas with advanced pathology (>1cm or severely dysplastic) is greater. Risk can be stratified according to the findings at baseline and refined at each subsequent surveillance examination.

A Summary of surveillance guidelines [25] is:

**•** Low risk Patients with only 1-2 small <1cm) adenomas. No follow up or five yearly until one negative examination.


The cut off age for stopping surveillance is usually 75 years but should also depends upon patients wishes and comorbidity.

Patients with incomplete examinations due to failed colonoscopies, for whatever reasons, should undergo repeat colonoscopy or alternative complete colonic examination (ct colonog‐ raphy). These guidelines are based on accurate detection of adenomas; otherwise risk status will be under estimated.

Large sessile adenomas removed piecemeal should be re-examined every three months. Small areas of residual polyp can be retreated endoscopically, for further check for complete eradications in three months. If extensive residual polyp is seen, open surgical resection needs to be considered. If there is complete healing of polypectomy site, then there should be sigmoidoscopy or colonoscopy at one year before returning to three yearly Surveillance. India ink tattooing aids recognition of the polypectomy site at follow up.

Stopping Surveillance.

indicated that FOBT is cost-effective compared to flexible sigmoidoscopy or colonoscopy for

The Increasing rate of colorectal cancer in Asia means that we need to take action immediately to prevent colorectal cancer and to diagnose the disease at early stages. The cost-effectiveness of screening programmes must be assessed in each individual country and research should be done to elucidate the epidemiology, genetic and environmental factors in development of

It is now widely accepted that the majority of colonic cancers arise from pre-existing adenom‐ atous polyps (adenoma-carcinoma sequence).The supporting evidence being as follows: [23] **1.** The prevalence of adenomas correlates well with that of carcinomas, average age of adenoma patients being around 5 years younger than patients with carcinomas.

**2.** Adenomatous tissue often accompanies cancer, and it is unusual to find small cancers

**3.** Sporadic adenomas are identical histologically to the adenomas of familial adenomatous

**4.** Large adenomas are more likely to display cellular atypia and genetic abnormalities than

**6.** Adenomas are found up to one-third of all surgical specimens resected for colorectal

**7.** The incidence of colorectal cancer has been shown to fall with long-term screening

The patients who have undergone colonoscopy and had adenomas removed are at increased risk of developing colorectal cancer (CRC) in future, and therefore might benefit from

Surveillance Guidelines about colorectal adenomas are established by British Society of Gastroentrology. According to these guidelines surveillance of the colorectal adenomas depends upon ; number of polys, size of polyps and grade of dysplasia present in histology. Risk of colorectal cancer and adenomas with advanced pathology (>1cm or severely dysplastic) is greater. Risk can be stratified according to the findings at baseline and refined at each

**•** Low risk Patients with only 1-2 small <1cm) adenomas. No follow up or five yearly until

**5.** Distribution of adenomas throughout the colon is similar to that of carcinomas.

polyposis (FAP), and this condition is unequivocal premalignant.

programme involving colonoscopy and polypectomy.

colorectal screening in average risk population. [22]

12 Colorectal Cancer - Surgery, Diagnostics and Treatment

**5. Management of screening detected polyps**

with no contagious adenomatous tissue.

colorectal cancer. [21]

small lesions.

colonoscopic surveillance. [24]

subsequent surveillance examination.

one negative examination.

A Summary of surveillance guidelines [25] is:

cancers

The cut-off age for stopping surveillance is usually quoted as 75 years as the remaining life expectancy is likely to be less than the average time required for new adenomas to become malignant. After this age, it is unlikely that the benefits of surveillance will outweigh the potential risk of the procedure. However, this should not preclude further surveillance in a fit and motivated person who has a tendency to produce multiple or advanced adenomas at follow up.

The risk and benefit of adenoma surveillance needs to be balanced at all ages, particularly in patients who have significant co morbidity.

The decision to undertake each colonoscopy examination at follow up should depend not only on the number and type of adenomas, but also on the patient's age and wishes, and the presence of significant co morbidity. The Patient status should be established prior to attendance for each examination possibly by questionnaires.

## **6. Importance of audit in screening and screening relating colonoscopies**

In any screening programme, as with any other medical service programme, adequate steps must be taken to ensure that the original objectives are being met and that methodology meets appropriate standard. The importance of maintaining the quality of screening programmes should never be under estimated. Evaluation, audit and quality control should be an integral part of any screening programme to ensure that it is achieving what it meant to be.

Colonoscopy is gold standard in important ultimate diagnostic tool in population screening programmes. Skilful colonoscopy with more then 95% caecal intubation rate is requirement for effective colorectal screening.

not be less than 20%. Inadequate skills in colonoscopy can also lead to higher percentage of

Screening for Colorectal Cancer http://dx.doi.org/10.5772/57506 15

In 2004, the largest prospective study of colonoscopic practice in UK revealed poor outcome in terms of completion and perforation rate, as well as deficiencies in all aspect of training. The

Colonoscopy training and its accreditation is a challenging task. Structured colonoscopy training is lacking in most of the countries. The NHS Bowel Cancer Screening Programme (NHS BCSP) commenced in July 2006 and recruited expert colonoscopists to carry out colonoscopies in the programme. Owing to the known variability in colonoscopy skills, strict criteria have been developed for the accreditation of screening endoscopists to minimize the

The Joint Advisory Group of GI Endoscopy (JAG) was established under the Academy of Medical Royal Colleges and now has a number of colleges and societies with an interest in endoscopy as members who are responsible for agreeing and setting policy and strategy and advising its constituent bodies and organizations (such as GMC and NHS )on standard and in endoscopy. The Jag office manages the administrative functions of the screening Assessor Accreditation System process on behalf of the NHS BCSP which is a web-based application

There are several advantages of this accreditation process, to both the unit and the individual endoscopists involved. Accreditation is an essential part of preparation for the implementation of local screening programme in UK. It also provides opportunities to demonstrate high level colonoscopic skills and improve the local endoscopy service. In addition it helps clinicians who wish to teach colonoscopy locally or on courses. The accreditation process leads to the Joint Advisory Group on GI Endoscopy (JAG) certificate of competency to perform screening

**8. Hereditary risk cancer and colorectal cancer screening protocol**

Inherited bowel cancer comprises of 5% of the total colorectal cancers. Based on risk of Inherited bowel cancer population can be divided into three groups: Low risk group, Moderate risk group and High risk group based on family history. Approach for screening surveillance

**1.** No personal history of bowel cancer: no confirmed family history of bowel cancer; or

**2.** No first degree relative (i.e. parent sibling or child ) with bowel cancer; or

**3.** One first degree relative with bowel cancer at or above the age of 40 years.

guidelines on training have been published both in UK and the USA. [30-31]

risk of the complications and inaccurate and incomplete examinations.

the procedure related complications.

process.

derived colonoscopy.

is different in three groups:

It includes the individuals with:

**8.1. Low risk group**

In the UK, before rolling out of the National Bowel Cancer Screening Programme, a large-scale study of colonoscopy practice was carried out. [26] The study demonstrated disappointing results with poor caecal intubation rates (76.95) and higher than expected complication rates. Since then there has been significant investment in endoscopic training, a quality assurance framework for endoscopic units has been implemented and National Bowel Screening Programme (NBSP) has been rolled out.

A nationwide audit of colonoscopy practice was conducted over a 2-weeks periods from 28 February 2011 until 11 March 2011. [27]. The study was performed prospectively, with the data entry occurring electronically through the purpose built website. All units performing >100 colonoscopies annually on NHS patients were included. Data on 20085 colonoscopies and 2681 colonoscopists were collected from 301units. Results showed 95.8% adjusted caecal intubation, 32.1% polyp detection rate, 92.3% resected polyps were retrieved and 90.2% o procedures achieved acceptable level of comfort. A total of 8 perforations and 52 significant haemorrhages were reported. Eight patients underwent surgery as a consequence of a complication.

The audit confirms that there has been significant improvement in performance of colonoscopy in UK since the last study reported 7 Years ago (caecal intubation rate 76.9%) and the per‐ formance is above the required national standard. But there is continuous need for assessment and audit of screening tools to keep the required national standard.

## **7. Colonoscopy capacity, training and accreditation**

Most colon cancers are assumed to have adenomatous polyp phase. Therefore, colonoscopic detection and polypectomy provides the opportunity for cancer prevention [25]. So, colono‐ scopy is gold standard in high risk patients and patients with FOBT positive in population screening program. As we have discussed in previous sections, effective colorectal screening depends on available colonoscopy expertise in different part of the world

The aim of colonoscopy is to visualize whole of the colonic mucosa in order to identify pathology. A systemic review [28] of back-to-back studies has shown polyp miss rate at colonoscopy of 22% even in expert hands, especially polyps less than 1cm. Available data about polyp miss rates have shown a variation in performance between endoscopists, but this can be wider in very expert endoscopists. This shows that there is link between individual technical skill and polyps detection rate [29]. The single most important factor in the technique is withdrawal time after caecal intubation. The current recommendation is that colonoscopists should spend 6-10 minutes during withdrawal inspecting the colonic mucosa [30].

Skills in colonoscopy technique and coecal intubation rates are directly proportional to adenoma detection rate. In a standard endoscopy unit, single adenoma detection rate should not be less than 20%. Inadequate skills in colonoscopy can also lead to higher percentage of the procedure related complications.

In 2004, the largest prospective study of colonoscopic practice in UK revealed poor outcome in terms of completion and perforation rate, as well as deficiencies in all aspect of training. The guidelines on training have been published both in UK and the USA. [30-31]

Colonoscopy training and its accreditation is a challenging task. Structured colonoscopy training is lacking in most of the countries. The NHS Bowel Cancer Screening Programme (NHS BCSP) commenced in July 2006 and recruited expert colonoscopists to carry out colonoscopies in the programme. Owing to the known variability in colonoscopy skills, strict criteria have been developed for the accreditation of screening endoscopists to minimize the risk of the complications and inaccurate and incomplete examinations.

The Joint Advisory Group of GI Endoscopy (JAG) was established under the Academy of Medical Royal Colleges and now has a number of colleges and societies with an interest in endoscopy as members who are responsible for agreeing and setting policy and strategy and advising its constituent bodies and organizations (such as GMC and NHS )on standard and in endoscopy. The Jag office manages the administrative functions of the screening Assessor Accreditation System process on behalf of the NHS BCSP which is a web-based application process.

There are several advantages of this accreditation process, to both the unit and the individual endoscopists involved. Accreditation is an essential part of preparation for the implementation of local screening programme in UK. It also provides opportunities to demonstrate high level colonoscopic skills and improve the local endoscopy service. In addition it helps clinicians who wish to teach colonoscopy locally or on courses. The accreditation process leads to the Joint Advisory Group on GI Endoscopy (JAG) certificate of competency to perform screening derived colonoscopy.

## **8. Hereditary risk cancer and colorectal cancer screening protocol**

Inherited bowel cancer comprises of 5% of the total colorectal cancers. Based on risk of Inherited bowel cancer population can be divided into three groups: Low risk group, Moderate risk group and High risk group based on family history. Approach for screening surveillance is different in three groups:

#### **8.1. Low risk group**

Colonoscopy is gold standard in important ultimate diagnostic tool in population screening programmes. Skilful colonoscopy with more then 95% caecal intubation rate is requirement

In the UK, before rolling out of the National Bowel Cancer Screening Programme, a large-scale study of colonoscopy practice was carried out. [26] The study demonstrated disappointing results with poor caecal intubation rates (76.95) and higher than expected complication rates. Since then there has been significant investment in endoscopic training, a quality assurance framework for endoscopic units has been implemented and National Bowel Screening

A nationwide audit of colonoscopy practice was conducted over a 2-weeks periods from 28 February 2011 until 11 March 2011. [27]. The study was performed prospectively, with the data entry occurring electronically through the purpose built website. All units performing >100 colonoscopies annually on NHS patients were included. Data on 20085 colonoscopies and 2681 colonoscopists were collected from 301units. Results showed 95.8% adjusted caecal intubation, 32.1% polyp detection rate, 92.3% resected polyps were retrieved and 90.2% o procedures achieved acceptable level of comfort. A total of 8 perforations and 52 significant haemorrhages

were reported. Eight patients underwent surgery as a consequence of a complication.

and audit of screening tools to keep the required national standard.

**7. Colonoscopy capacity, training and accreditation**

depends on available colonoscopy expertise in different part of the world

The audit confirms that there has been significant improvement in performance of colonoscopy in UK since the last study reported 7 Years ago (caecal intubation rate 76.9%) and the per‐ formance is above the required national standard. But there is continuous need for assessment

Most colon cancers are assumed to have adenomatous polyp phase. Therefore, colonoscopic detection and polypectomy provides the opportunity for cancer prevention [25]. So, colono‐ scopy is gold standard in high risk patients and patients with FOBT positive in population screening program. As we have discussed in previous sections, effective colorectal screening

The aim of colonoscopy is to visualize whole of the colonic mucosa in order to identify pathology. A systemic review [28] of back-to-back studies has shown polyp miss rate at colonoscopy of 22% even in expert hands, especially polyps less than 1cm. Available data about polyp miss rates have shown a variation in performance between endoscopists, but this can be wider in very expert endoscopists. This shows that there is link between individual technical skill and polyps detection rate [29]. The single most important factor in the technique is withdrawal time after caecal intubation. The current recommendation is that colonoscopists

Skills in colonoscopy technique and coecal intubation rates are directly proportional to adenoma detection rate. In a standard endoscopy unit, single adenoma detection rate should

should spend 6-10 minutes during withdrawal inspecting the colonic mucosa [30].

for effective colorectal screening.

14 Colorectal Cancer - Surgery, Diagnostics and Treatment

Programme (NBSP) has been rolled out.

It includes the individuals with:


In this group, the risk of bowel cancer may be twice the average risk [31] and there is no evidence to support invasive surveillance in his group [24]. These individuals should be explained that they are atonly marginally increased risk of developing colorectal cancer, and that this risk is not sufficient to outweigh the disadvantages of colonoscopy. They should be educated regarding symptoms of colorectal cancer, and importance of reporting if further members of the family develop cancers. And they should be encouraged to take part in the population screening for colorectal cancer.

**8.4. Lynch syndrome or Hereditary Non Polyposis Colorectal Cancers (HNPCC)**

urothelial carcinoma (5%) and others (small bowel pancreas and brain)< %5

**•** Annual CA125 level and clinical examination (pelvic and abdominal).

**•** Annual abdominal ultrasound of renal tracts, pelvis, and pancreas.

It is less common than Lynch syndrome. In FAP risk of colorectal cancer is 100%.

**•** Hundred of colorectal adenomatous polyps at a young age (second or third decade of life);

If family mutation is known, at risk family member should be offered predictive genetic testing in their early teens. If this is not possible, then clinical surveillance is required. Usually, polys develop in teenage. Colonoscopy should only be performed in symptomatic children before teenage years. Otherwise annual flexible sigmoidoscopy starting at 13-15 years of age is recommended. If no polyps are detected, 5 yearly colonoscopy at the age of 20 years with annual flexible sigmoidoscopy in the intervening years. [24]. Flexible sigmoidoscopy should be performed carefully to avoid false negative results. Chromo-endoscopy is an option in

**•** Upper gastrointestinal endoscopy every two years.

gastroscopy should be done two yearly.

**•** Annual urinalysis /cytology.

FAP is characterised by:

doubtful cases.

**•** Annual liver function tests,CA19-9,CEA

Familial adenomatous polyposis (FAP)

**•** Duodenal adenomatous polyps;

**•** Mutation in the APC gene at chromosome5q

**•** extra-intestinal manifestation;

are;

Lynch syndrome is inherited as an autosomal dominant fashion. It comprises of 2% of the colorectal cancers and is commonest of inherited bowel cancers. It is associated with endome‐ trial carcinoma (30-70%), gastric carcinoma (5-10%), ovarian carcinoma in females (5-10%),

Screening for Colorectal Cancer http://dx.doi.org/10.5772/57506 17

Predictive genetic testing should be offered. These individuals should have first colonoscopy at the age of 25 years or five years before earliest colonoscopy in the family and gastroscopy at the age of 50 or five years before earliest gastric cancer in family. [24]. Colonoscopy and

Screening for extracoloic cancers in Lynch syndrome is available. There is little evidence of benefit. Recommendation varies from centre to centre, but surveillance is advised if there is family history of particular cancer. Recommended options for extracolonic surveillance [32]

**•** Annual transvaginal ultrasound, colour flow Doppler imaging and endometrial sampling.

#### **8.2. Moderate risk group**

Individuals are included in this category if there is:


In this group there is three to six fold relative risk of colorectal cancer. [31]. There is only marginal benefit from invasive surveillance (colonoscopy). Current recommendations are that individuals should be offered colonoscopy at 35-40 year of age (or at presentation if they are older), and again at the age of 55 years. [24]. Coecal intubation is mandatory, as neoplasms in individuals with a strong family history are often proximal; if the caecum is not reached, virtual colonoscopy should be performed.

#### **8.3. High risk group**

In this group, hereditary non-polyposis colorectal cancer (HNPCC) and various polyposis syndromes are included. Criteria for inclusion in this group includes:


In this group the individuals have one upto a 1 in 2 chance of inheriting a lifetime risk and more than 50 % chances of developing colorectal cancers. They must be referred to a clinical genetics service.

According to World Gastroenterology Organisation, the low risk group and population without obvious inherited colorectal cancer history are labelled as average risk population, while moderate rick and high risk groups are considered as one group with increased risk of colorectal cancer. Global screening guidelines cascades are established in 2007 based on these risk groups.

#### **8.4. Lynch syndrome or Hereditary Non Polyposis Colorectal Cancers (HNPCC)**

Lynch syndrome is inherited as an autosomal dominant fashion. It comprises of 2% of the colorectal cancers and is commonest of inherited bowel cancers. It is associated with endome‐ trial carcinoma (30-70%), gastric carcinoma (5-10%), ovarian carcinoma in females (5-10%), urothelial carcinoma (5%) and others (small bowel pancreas and brain)< %5

Predictive genetic testing should be offered. These individuals should have first colonoscopy at the age of 25 years or five years before earliest colonoscopy in the family and gastroscopy at the age of 50 or five years before earliest gastric cancer in family. [24]. Colonoscopy and gastroscopy should be done two yearly.

Screening for extracoloic cancers in Lynch syndrome is available. There is little evidence of benefit. Recommendation varies from centre to centre, but surveillance is advised if there is family history of particular cancer. Recommended options for extracolonic surveillance [32] are;


In this group, the risk of bowel cancer may be twice the average risk [31] and there is no evidence to support invasive surveillance in his group [24]. These individuals should be explained that they are atonly marginally increased risk of developing colorectal cancer, and that this risk is not sufficient to outweigh the disadvantages of colonoscopy. They should be educated regarding symptoms of colorectal cancer, and importance of reporting if further members of the family develop cancers. And they should be encouraged to take part in the

**1.** One first-degree relative with colorectal cancer below the age of 45 without any feature

**2.** Two first-degree relatives with bowel cancer diagnosed at any age without any of the

In this group there is three to six fold relative risk of colorectal cancer. [31]. There is only marginal benefit from invasive surveillance (colonoscopy). Current recommendations are that individuals should be offered colonoscopy at 35-40 year of age (or at presentation if they are older), and again at the age of 55 years. [24]. Coecal intubation is mandatory, as neoplasms in individuals with a strong family history are often proximal; if the caecum is not reached, virtual

In this group, hereditary non-polyposis colorectal cancer (HNPCC) and various polyposis

**1.** Family member of familial adenomatous polyposis (FAP) or other polyposis syndrome;

**3.** Pedigree suggestive of autosomal dominantly inherited colorectal (or other lynch

In this group the individuals have one upto a 1 in 2 chance of inheriting a lifetime risk and more than 50 % chances of developing colorectal cancers. They must be referred to a clinical

According to World Gastroenterology Organisation, the low risk group and population without obvious inherited colorectal cancer history are labelled as average risk population, while moderate rick and high risk groups are considered as one group with increased risk of colorectal cancer. Global screening guidelines cascades are established in 2007 based on these

syndromes are included. Criteria for inclusion in this group includes:

**2.** Member of family with known lynch syndrome; or

population screening for colorectal cancer.

16 Colorectal Cancer - Surgery, Diagnostics and Treatment

Individuals are included in this category if there is:

**8.2. Moderate risk group**

of high risk group.

feature of high risk group.

colonoscopy should be performed.

syndrome associated) cancers.

**8.3. High risk group**

or

genetics service.

risk groups.


Familial adenomatous polyposis (FAP)

It is less common than Lynch syndrome. In FAP risk of colorectal cancer is 100%.

FAP is characterised by:


If family mutation is known, at risk family member should be offered predictive genetic testing in their early teens. If this is not possible, then clinical surveillance is required. Usually, polys develop in teenage. Colonoscopy should only be performed in symptomatic children before teenage years. Otherwise annual flexible sigmoidoscopy starting at 13-15 years of age is recommended. If no polyps are detected, 5 yearly colonoscopy at the age of 20 years with annual flexible sigmoidoscopy in the intervening years. [24]. Flexible sigmoidoscopy should be performed carefully to avoid false negative results. Chromo-endoscopy is an option in doubtful cases.

## **9. Future research for improvement of screening programme**

Although most of the screening programme based on research has shown improved survival in patients whose tumours are detected by screening, all population screening studies are prone to biases.

collaboration between university of Oxford and newly formed NHS cancer screening pro‐

Screening for Colorectal Cancer http://dx.doi.org/10.5772/57506 19

The pilot studies started early in 2008 and the study will eventually involve over 200,000 screening programme participants, including about 2,500people with a positive FOB test result

This trial looked at bowel cancer incidence and mortality reduction 11 years after a single

170,000 people were entered into the trial. Cumulative incidence, including prevalent cancers detected at screening, was reduced by 50% for the cancers in the rectum and sigmoid colon, and 33 percent for bowel cancer overall. Bowel cancer mortality was reduced by 43 percent. The trial concluded that flexible sigmoidoscopy screening-with removal of small polyps at the examination is safe and, when offered only once between the ages 55 and 64, confers a

**9.4. HTA: Frequency of follow-up for patients with intermediate grade colorectal adenomas** Beginning in September 2006, this study examined the effort of extending intervals between follow-up colonoscopies in people found to have intermediate adenomas, as defined by the British Society of Gastroentrology guidelines. It is using data from hospitals ad from bowel cancer screening initiatives to identify groups of patients with intermediate adenomas. The risk of cancer and severe adenomas will be assessed according to the interval between

Firstly, the study will identify whether all patients with intermediate adenomas require surveillance; secondly, whether the intervals are of the appropriate length; thirdly, it should also demonstrate how many follow-up examinations are needed. Finally, it will determine whether informing patients they need to have colonoscopy distresses them or whether they feel reassured as a result. A health economist will analyze the cost to individual patients and

The NHS Bowel Cancer Screening Programme Evaluation Group reviews and develops criteria used for evaluation and monitoring the progress of the Bowel Cancer Screening

**•** A once only flexible sigmoidoscopy screen between ages 55 and 64 years.

examinations and the number, size and features of adenomas detected.

to the NHS and compare these with any potential benefit.

**9.5. NHS bowel cancer screening programme evaluation group**

grammes` Research unit, which is based in the university` cancer epidemiology unit.

who are categorized as normal following a colonoscopy.

screening examination with flexible sigmoidoscopy [36]

**9.3. UK flexible sigmoidoscopy screening trial**

It examined the efficacy and duration of effect of ;

**•** Removal of small polyps (<10m) during screening

**•** Colonoscopy only for high risk adenomas.

substantial and long lasting benefit.

Programme.

**Selection bias** arises from the tendency of people who accept screening to be particularly health conscious and therefore atypical of population as a whole.

**Length bias** indicates the tendency for screening to detect a disproportionate number of cancers which are slow growing, which thereby has good prognosis.

**Lead-time bias** results from the time between the date detection of cancer by screening and date when it would have been diagnosed had the subject not been screened. As survival is measured from time of diagnosis, screening advances the date at which diagnosis is made, thus lengthening the survival time without necessarily altering the date of death.

Because of these biases effectiveness of any screening can be assessed only by well designed randomized trials comparing disease –specific mortality in a population offered screening with that in an identical population not offered screening.

Initially three large randomized trials, using FOBT (Minnesota, Nottingham, in Funen Denmark) [33,34,35] showed reduction in mortality. These trials provided solid ground to initiate colorectal screening programme in western countries and US.

Randomized controlled trials are expensive and difficult to manage and may be ethically questionable in situations where control group is denied treatment for the condition in question. Despite this, UK National Screening Committee will only recommend the introduc‐ tion of any new programme after assessing the findings of a properly conducted randomized controlled trial. The committee also keeps all screening programmes under regular review to ensure that they continue to perform in the way intended and continue to be effective.

#### **9.1. Bowel cancer screening programme research committee**

The research committee considers the feasibility and scientific value of research projects that arises from the screening programme in UK. It encourages collaboration between researchers and tries to prevent duplication.

The committee, chaired by Professor John Scholefield, meets quarterly and has considered over 60 research applications. The area of research considered by the committee included uptake/ acceptability of screening test, epidemiology/histopathology and screening technologies. Here we will mention some important research project in relation with screening.

#### **9.2. False positive research study**

A research project to investigate the causes of false positive results on Foecal Occult Blood (FOB) testing is now under way. The five year project, funded by cancer research UK is a collaboration between university of Oxford and newly formed NHS cancer screening pro‐ grammes` Research unit, which is based in the university` cancer epidemiology unit.

The pilot studies started early in 2008 and the study will eventually involve over 200,000 screening programme participants, including about 2,500people with a positive FOB test result who are categorized as normal following a colonoscopy.

### **9.3. UK flexible sigmoidoscopy screening trial**

**9. Future research for improvement of screening programme**

health conscious and therefore atypical of population as a whole.

that in an identical population not offered screening.

cancers which are slow growing, which thereby has good prognosis.

initiate colorectal screening programme in western countries and US.

**9.1. Bowel cancer screening programme research committee**

and tries to prevent duplication.

**9.2. False positive research study**

prone to biases.

18 Colorectal Cancer - Surgery, Diagnostics and Treatment

Although most of the screening programme based on research has shown improved survival in patients whose tumours are detected by screening, all population screening studies are

**Selection bias** arises from the tendency of people who accept screening to be particularly

**Length bias** indicates the tendency for screening to detect a disproportionate number of

**Lead-time bias** results from the time between the date detection of cancer by screening and date when it would have been diagnosed had the subject not been screened. As survival is measured from time of diagnosis, screening advances the date at which diagnosis is made,

Because of these biases effectiveness of any screening can be assessed only by well designed randomized trials comparing disease –specific mortality in a population offered screening with

Initially three large randomized trials, using FOBT (Minnesota, Nottingham, in Funen Denmark) [33,34,35] showed reduction in mortality. These trials provided solid ground to

Randomized controlled trials are expensive and difficult to manage and may be ethically questionable in situations where control group is denied treatment for the condition in question. Despite this, UK National Screening Committee will only recommend the introduc‐ tion of any new programme after assessing the findings of a properly conducted randomized controlled trial. The committee also keeps all screening programmes under regular review to ensure that they continue to perform in the way intended and continue to be effective.

The research committee considers the feasibility and scientific value of research projects that arises from the screening programme in UK. It encourages collaboration between researchers

The committee, chaired by Professor John Scholefield, meets quarterly and has considered over 60 research applications. The area of research considered by the committee included uptake/ acceptability of screening test, epidemiology/histopathology and screening technologies. Here

A research project to investigate the causes of false positive results on Foecal Occult Blood (FOB) testing is now under way. The five year project, funded by cancer research UK is a

we will mention some important research project in relation with screening.

thus lengthening the survival time without necessarily altering the date of death.

This trial looked at bowel cancer incidence and mortality reduction 11 years after a single screening examination with flexible sigmoidoscopy [36]

It examined the efficacy and duration of effect of ;


170,000 people were entered into the trial. Cumulative incidence, including prevalent cancers detected at screening, was reduced by 50% for the cancers in the rectum and sigmoid colon, and 33 percent for bowel cancer overall. Bowel cancer mortality was reduced by 43 percent.

The trial concluded that flexible sigmoidoscopy screening-with removal of small polyps at the examination is safe and, when offered only once between the ages 55 and 64, confers a substantial and long lasting benefit.

#### **9.4. HTA: Frequency of follow-up for patients with intermediate grade colorectal adenomas**

Beginning in September 2006, this study examined the effort of extending intervals between follow-up colonoscopies in people found to have intermediate adenomas, as defined by the British Society of Gastroentrology guidelines. It is using data from hospitals ad from bowel cancer screening initiatives to identify groups of patients with intermediate adenomas. The risk of cancer and severe adenomas will be assessed according to the interval between examinations and the number, size and features of adenomas detected.

Firstly, the study will identify whether all patients with intermediate adenomas require surveillance; secondly, whether the intervals are of the appropriate length; thirdly, it should also demonstrate how many follow-up examinations are needed. Finally, it will determine whether informing patients they need to have colonoscopy distresses them or whether they feel reassured as a result. A health economist will analyze the cost to individual patients and to the NHS and compare these with any potential benefit.

#### **9.5. NHS bowel cancer screening programme evaluation group**

The NHS Bowel Cancer Screening Programme Evaluation Group reviews and develops criteria used for evaluation and monitoring the progress of the Bowel Cancer Screening Programme.

It Includes representatives from all the professional groups in the programme as from the Cancer Screening Evaluation Unit, the Health and Social Care Information Centre and Bowel Screening Wales.

For average- risk 10 yearly colonoscopies starting at 50 years.

For average- risk once in life time colonoscopy at the age of 50.

For increased risk recommendations are same as cascade1.

limited but flexible sigmoidoscopy resources are available.

workup with full colonoscopy in case of positive flexible sigmoidoscopy.

Recommendations for increased- risk are same as level 1 cascade.

Recommendations for increased risk are same as level 1 cascade.

at 40 yrs of age.

more limited.

*10.1.2. Cascade Level 2*

*10.1.3. Cascade Level 3*

*10.1.4. Cascade Level 4*

on availability of resources.

*10.1.5. Cascade level 5*

is severely limited.

*10.1.6. Cascade Level 6*

colonoscopy resources are severely limited.

available.

colonoscopy resources are more limited.

For increased- risk patients more frequently two yearly or five yearly colonoscopies starting

Screening for Colorectal Cancer http://dx.doi.org/10.5772/57506 21

Recommendations are same as cascade level 1 but they apply when colonoscopy resources are

Recommendation are same as cascade level 1 but apply when colonoscopy resources are more

For average- risk flexible colonoscopy 5 yearly starting from 50 years of age with diagnostic

Recommendations are same as level 3 but they apply when flexible sigmoidoscopy and

For average-risk screening flexible sigmoidoscopy once in life time at the age of 50 years. Diagnostic colonoscopy workup for positive flexible sigmoidoscopy or neoplasia depending

Recommendations are same as resource level 4 but they apply when diagnostic colonoscopy

For average- risk population flexible sigmoidoscopy is recommended once in a life time at the

Recommendations for screening increased-risk patients depend on colonoscopy resources

Recommendations are same as for level 1 but they apply when flexible sigmoidoscopy and

age of 50 years. Diagnostic colonoscopy only when advanced neoplasia is detected.

## **10. Current screening percentage of at risk world population and future of colorectal screening**

World Gastroenterology Organization (WGO), in affiliation with International Digetive Cancer Alliance (IDCA), launched guidelines for international colorectal screening pro‐ grammes after indicating the low percentage of screening programme in place in different coutries of the world. In these guidelines, they emphasise the need of some kind of screening programme in place based on locally available screening facilities

As mentioned earlier, the risk for colorectal cancers varies from country to country and even within countries. The risk also varies among individual people based on diet, lifestyle, and hereditary factors. Colorectal cancer screening is particularly challenging, as reflected in current low screening rates in most countries where there is high risk for colorectal cancer. Colorectal cancer screening is complex as there are multiple options, it requires considerable patient effort (Fecal Occult Blood Slides, Colonoscopy Preparation etc.), and it requires sedation and health-care partner for some tests (colonoscopy). [37]

It is an acknowledged fact that the lowest screening percentage of on risk population for colorectal cancer is in Asia and Africa. In most Asian and African countries, National Health Care systems and Health Insurance cover only a minority of people. So, access to healthcare facilities is limited in many rural areas and communities of low socio-economic status. In Asian countries, there is little health authority support for colorectal cancer screening and very low public awareness for this emerging epidemic in Asia. [38]

For the screening programme to be successful, multiple steps need to be taken correctly, beginning from awareness and recommendation from the primary-care physician, patient acceptance, financial coverage, risk stratification, screening test, timely diagnosis, timely treatment and appropriate follow-up. If any one of these steps is left faulty or not of high quality, the screening programme will certainly fail. (WGO)

#### **10.1. International colorectal screening cascade**

According to WGO guidelines, colorectal screening cascade consist of set of recommendations based on availability of resources in different countries of the world beginning with 1 (highest resources available) and ending with 6 (minimal resources available. [37]

#### *10.1.1. Cascade Level 1*

This is a set of recommendations for countries where high level of resources (Financial, professional, facilities) available.

For average- risk 10 yearly colonoscopies starting at 50 years.

For increased- risk patients more frequently two yearly or five yearly colonoscopies starting at 40 yrs of age.

#### *10.1.2. Cascade Level 2*

It Includes representatives from all the professional groups in the programme as from the Cancer Screening Evaluation Unit, the Health and Social Care Information Centre and Bowel

**10. Current screening percentage of at risk world population and future of**

World Gastroenterology Organization (WGO), in affiliation with International Digetive Cancer Alliance (IDCA), launched guidelines for international colorectal screening pro‐ grammes after indicating the low percentage of screening programme in place in different coutries of the world. In these guidelines, they emphasise the need of some kind of screening

As mentioned earlier, the risk for colorectal cancers varies from country to country and even within countries. The risk also varies among individual people based on diet, lifestyle, and hereditary factors. Colorectal cancer screening is particularly challenging, as reflected in current low screening rates in most countries where there is high risk for colorectal cancer. Colorectal cancer screening is complex as there are multiple options, it requires considerable patient effort (Fecal Occult Blood Slides, Colonoscopy Preparation etc.), and it requires

It is an acknowledged fact that the lowest screening percentage of on risk population for colorectal cancer is in Asia and Africa. In most Asian and African countries, National Health Care systems and Health Insurance cover only a minority of people. So, access to healthcare facilities is limited in many rural areas and communities of low socio-economic status. In Asian countries, there is little health authority support for colorectal cancer screening and very low

For the screening programme to be successful, multiple steps need to be taken correctly, beginning from awareness and recommendation from the primary-care physician, patient acceptance, financial coverage, risk stratification, screening test, timely diagnosis, timely treatment and appropriate follow-up. If any one of these steps is left faulty or not of high

According to WGO guidelines, colorectal screening cascade consist of set of recommendations based on availability of resources in different countries of the world beginning with 1 (highest

This is a set of recommendations for countries where high level of resources (Financial,

programme in place based on locally available screening facilities

sedation and health-care partner for some tests (colonoscopy). [37]

public awareness for this emerging epidemic in Asia. [38]

quality, the screening programme will certainly fail. (WGO)

resources available) and ending with 6 (minimal resources available. [37]

**10.1. International colorectal screening cascade**

*10.1.1. Cascade Level 1*

professional, facilities) available.

Screening Wales.

**colorectal screening**

20 Colorectal Cancer - Surgery, Diagnostics and Treatment

Recommendations are same as cascade level 1 but they apply when colonoscopy resources are more limited.

For average- risk once in life time colonoscopy at the age of 50.

For increased risk recommendations are same as cascade1.

#### *10.1.3. Cascade Level 3*

Recommendation are same as cascade level 1 but apply when colonoscopy resources are more limited but flexible sigmoidoscopy resources are available.

For average- risk flexible colonoscopy 5 yearly starting from 50 years of age with diagnostic workup with full colonoscopy in case of positive flexible sigmoidoscopy.

Recommendations for increased- risk are same as level 1 cascade.

#### *10.1.4. Cascade Level 4*

Recommendations are same as level 3 but they apply when flexible sigmoidoscopy and colonoscopy resources are more limited.

For average-risk screening flexible sigmoidoscopy once in life time at the age of 50 years. Diagnostic colonoscopy workup for positive flexible sigmoidoscopy or neoplasia depending on availability of resources.

Recommendations for increased risk are same as level 1 cascade.

#### *10.1.5. Cascade level 5*

Recommendations are same as resource level 4 but they apply when diagnostic colonoscopy is severely limited.

For average- risk population flexible sigmoidoscopy is recommended once in a life time at the age of 50 years. Diagnostic colonoscopy only when advanced neoplasia is detected.

Recommendations for screening increased-risk patients depend on colonoscopy resources available.

#### *10.1.6. Cascade Level 6*

Recommendations are same as for level 1 but they apply when flexible sigmoidoscopy and colonoscopy resources are severely limited.

For average -risk population, Faecal Occult Blood Testing (FOBT) should be done every year starting at the age of 50 years. The type of test used depends upon colonoscopy resources available and dietary habits of the population. The diagnostic work-up can be done either with colonoscopy, if available or barium enema, if colonoscopy is not readily available.

[7] Goulard H, BoussacZarebska M,AncellePark R, Bloch J. French colorectal cancer screening pilot programme. : results of first rounds.J MED Screen. 2008;15:143148. [8] Zorzi M, Falcini F, Fedato C, Grazini G et al. Screening for colorectal cancer in Italy.:

Screening for Colorectal Cancer http://dx.doi.org/10.5772/57506 23

[9] Malila N, Oivanen T, Malminiemi O, Hakama M. Test, episode, and programme sen‐ sitivities of screening for colorectal cancers as a public health policies in Finland. Ex‐

[10] Regula J, Rupinski M, Kraszewska E, Polkowski M, et al colonoscopy in colorectal‐ cancer screening for detection of advanced neoplasia. N Eng J Med.

[11] Pox C, Schmiegel W, Classen M. Current status of screening colonoscopy in Europe

[12] Fric P, Zavoral M, Dvorakova H, Zoubek, et al. An adapted programme of colorectal cancer screening – 7 years experianceand cost benefit analysis. Hepatogastroentrolo‐

[13] Zavoral M, Zavada Filip, Salek C, Czech society of gastroenterology: colorectal can‐

[14] Australian institute of health and welfare. Australian cancer incidence and mortality (ACIM) books. Bowel Cancer for Australia Canberra:AIHW, 2011. http://

[15] Australian institute of health and welfare. Cancer in Australia 2010:An Over‐ view.Canberra :AIHW,2010 (AIHWCat No.CAN 56. Cancer Series No. 60. http://

[16] National Cancer Institute.Surveilance epidemiology and end results. SEER Stat Fact Sheets: colon and rectum. (http://seer.cancer.gov/statfacts/html/colorec.html.

[17] Australian Cancer Network Colorectal Guidelines revision Comittee. Guidelines for prevention, early detection and management of colorectal cancer. Sydney: The cancer council Australia and Australian Cancer Network.,2005. http://www.nhmrc.gov.au/

[18] Pignone MP, Flitcroft KL, Howard K et al. Costs and cost effectiveness of full imple‐ mentation of biennial foecal occult blood test screening program for bowel cancer in

[19] Anderson R, Haas M, Shanahan M. Cost –effectiveness of cervical screening in Aus‐ tralia:what is the inpact of screening in different intervels or over a different age

[20] .Centre for Disease Control and Prevention (CDC). Cancer screening –United states.

2006 survey.Epidemiol prev.2008;32:5568.

perimental design.BMJ. 2008;337:a2261

and in united states. Endoscopy.2007;39:168173

cer screening in Czech republic. Endoscopy. 2006;38:7480

www.aihw.gov.au/publicationdetail/?id=6442472459

filesnhmrc/publications/attachments/cp106 0 pdf

Australia. Med J Aust 2011;194:180185.

2010 MMWR2012;61 (3):4145

range.Aust N ZJ Public Health 2008:32: 4352.

2006;355:18631872.

gy. 1994:41:413416

www.aihw.gov.au/acimbooks

Therefore, recommendations for increased risk individuals are to identify them separately for special screening (level 1) and the decision depends on available colonoscopy resources. If not available, these people can be screened with average-risk individuals.

These guidelines are established considering a lack of resources in poor socioeconomically countries and can provide a base for the structured global screening programme. We hope the world will take measures to implement population screening programmes to save mankind from the cruel hands of colorectal cancer.

## **Author details**

Syed Naqvi\* and Syeda Farah Nazir

FRCS Colorectal surgery, RCSI, Dublin, Ireland

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For average -risk population, Faecal Occult Blood Testing (FOBT) should be done every year starting at the age of 50 years. The type of test used depends upon colonoscopy resources available and dietary habits of the population. The diagnostic work-up can be done either with

Therefore, recommendations for increased risk individuals are to identify them separately for special screening (level 1) and the decision depends on available colonoscopy resources. If not

These guidelines are established considering a lack of resources in poor socioeconomically countries and can provide a base for the structured global screening programme. We hope the world will take measures to implement population screening programmes to save mankind

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and Syeda Farah Nazir

FRCS Colorectal surgery, RCSI, Dublin, Ireland

World Health Organization.

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Syed Naqvi\*

**References**


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**Section 2**

**Diagnostics**

**Section 2**

## **Diagnostics**

**Chapter 2**

**Diagnostic Modalities in Colorectal Cancer –Endoscopy,**

**Ct and Pet Scanning, Magnetic Resonance Imaging (Mri),**

**Endoluminal Ultrasound and Intraoperative Ultrasound**

Colorectal cancer (CRC) is the third most diagnosed cancer in men, next to prostate and lung cancer. In women it is the second most diagnosed cancer, next to breast cancer. In a time of limited resources in health care, there has been considerable debate which imaging modality offers the best non-invasive examination of colorectal cancer, offering both detection and characterization. The use of multiple diagnostic modalities is both costly and time-consuming. Clinical evidence amassed over the last several decades indicates that routine colorectal cancer (CRC) screening, compared to no screening, detects CRC at an earlier stage, reduces the incidence of CRC or the progression early CRC through polypectomy, and reduces CRC

The first complete examination of the colon using a flexible fiber optic endoscope is reported by Wolff and Shinya in 1971 [42]. Nowadays colonoscopy is the gold standard for evaluation of the entire colonic mucosa with therapeutic capability of resecting detected malignancies.

In the last years the colonoscopy is the modality of choice to detect and correct the adenomatous polyps and colorectal cancer. The diagnosis CRC can be confirmed after biopsy in a known

> © 2014 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Valentin Ignatov, Nikola Kolev, Anton Tonev, Shteryu Shterev, Elitsa Encheva, Tanya Kirilova,

Tsvetelina Teneva and Krassimir Ivanov

http://dx.doi.org/10.5772/57508

**1. Introduction**

mortality.

**2. Endoscopy**

Additional information is available at the end of the chapter
