Colorectal Surgery

Clinical Care and Management

Bruce George, Richard Guy, Oliver Jones, Jon Vogel, Bruce George, Richard Guy, Oliver Jones, Jon Vogel

• Publisher: Wiley-Blackwell
• Year: 2016
• Print ISBN: 9781118674789
• eBook ISBN: 9781118674772
• Edition: 1
• Topic: Medicine
• Subtopic: Gastroenterology & Hepatology

Using a case-based approach, Colorectal Surgery: Clinical Care and Management provides practical, clinical and expert guidance to illustrate the best care and clinical management of patients requiring colorectal surgery for colorectal disease.

Real-life cases illustrate the entire syllabus of GI/colorectal surgery, being specially selected to highlight topical or controversial aspects of colorectal care.  Cases have a consistent approach throughout and as well as outlining the actual management of each individual case, also offer an honest appraisal of the chosen management route, its successes and areas that could have been managed differently.   Pedagogic features such as learning and decision points boxes aid rapid understanding/learning, enabling the reader to improve their patient management.

In full colour and containing over 100 outstanding clinical photos and slides to support the cases, each section also covers recent developments/ landmark papers/ scoring systems and a thorough discussion of clinical management based on the major society guidelines from NICE, ASCRS and ECCO. 

Reliable, well-written and perfect for consultation in the clinical setting,  Colorectal Surgery: Modern Clinical Care and Management is the perfect tool for all members of the multi-disciplinary team managing patients suffering from colorectal disease, specifically GI surgeons, gastroenterologists, oncologists and general surgeons.

Section A
Colorectal cancer

Bruce George

Oxford University Hospitals NHS Foundation Trust, Oxford, UK

Incidence

Colorectal cancer (CRC) is the second most common cause of cancer-related mortality in the Western world. Approximately 6% of the population will develop CRC during their lifetime.

Pathogenesis

Colorectal cancer develops through a stepwise accumulation of genetic and epigenetic alterations. There are three major molecular mechanisms involved in colorectal carcinogenesis:

• chromosomal instability
• microsatellite instability
• CpG island methylation.

Chromosomal instability

In the late 1980s, Vogelstein et al. described a series of genetic alterations resulting in change from normal colonocytes through adenoma to carcinoma. Key genes in this process include adenomatous polyposis coli (APC), k-ras and p53, all of which code for proteins critically involved in regulation of cell turnover. APC is a tumor suppressor gene on chromosome 5q21 (long arm of chromosome 5). The APC protein controls degradation of beta-catenin which is involved in the control of epithelial cell turnover. Mutation of the APC gene results in accumulation of beta-catenin which, in turn, alters expression of several genes affecting cell proliferation, differentiation, and apoptosis. Germline mutation in the APC gene results in familial adenomatous polyposis (FAP).

Microsatellite instability

Microsatellites are short repeat nucleotide sequences found throughout the genome and are prone to errors during replication. Mutations in mismatch repair genes result in an increased risk of CRC. Tumors associated with defects in DNA mismatch repair are characterized by increased microsatellite instability. Germline mutations in mismatch repair genes result in hereditary nonpolyposis colorectal cancer (HNPCC).

CpG island methylation

More recently, epigenetic influences such as DNA methylation have been found to be involved in tumorigenesis. Normally, only about 3–4% of all cytosines in DNA are methylated and methylation only occurs at cytosines at the 5' end of guanine (CpGs). Clusters of CpGs tend to occur in the promoter region of many genes. Increased methylation of CpGs at the promoter end of tumor suppressor genes may result in reduced activation of the genes, resulting in increased tumor risk. Environmental factors may exert their influence on carcinogenesis through epigenetic mechanisms.

Awareness of the molecular changes in individual tumors is likely to become increasingly important in individualizing treatment. Sporadic tumors, for example, with features of high microsatellite instability, tend to respond poorly to 5-fluorouracil (5FU) chemotherapy.

Risk factors for colorectal cancer

Increasing age, a family history of CRC and long-term ulcerative colitis (UC) or Crohn's colitis are major risk factors for the development of CRC. Rare situations in which the risk is slightly increased include acromegaly, renal transplantation, and a history of abdominal irradiation.

Family history

Twin studies suggest that about 20% of CRC have an inherited predisposition. The mechanism of inherited risk is well characterized in patients with FAP (about 1% of all CRC) and HNPCC (about 3–5% of all CRC), but not in the remainder of those with a positive family history.

Familial adenomatous polyposis is an autosomal dominant condition resulting from mutation in the APC gene. The disease is characterized by the development of multiple polyps, usually over 100, in adolescence and, unless treated, inevitable progression to colon cancer. Extracolonic features include gastroduodenal polyps – with a lifetime risk of duodenal cancer of 12% – and desmoid tumors. The precise site of the mutation in the APC gene correlates with the clinical phenotype, for example the risk of developing desmoid tumors.

Hereditary nonpolyposis colorectal cancer is an autosomal dominant condition caused by a germline mutation in DNA mismatch repair genes. Loss of mismatch repair genes results in replication errors, increased mutations, and an increased risk of malignancy. The hallmark of HNPCC is microsatellite instability. Individuals with HNPCC tend to develop tumors at a younger age than those with sporadic tumors and are also at increased risk of other tumors, especially endometrial, gastric, ovarian, and urinary tract.

It is impractical to genetically test all family members of patients with CRC for HNPCC, and various criteria have been developed to identify patients and families likely to have HNPCC, the most common being the Amsterdam Criteria (Box A.1).

Box A.1 Amsterdam criteria for the diagnosis of HNPCC

Amsterdam I

• At least three relatives with CRC, one of which should be a first-degree relative of the other two
• At least two successive generations affected
• At least one CRC diagnosed before the age of 50 years
• FAP excluded
• Tumors verified histologically

Amsterdam II

• At least three relatives with an HNPCC-associated cancer, one of which should be a first-degree relative of the other two
• At least two successive generations affected
• At least one CRC diagnosed before age 50 years
• FAP excluded
• Tumors verified histologically

Diet and lifestyle

A high-fiber diet has been postulated for many years to be associated with a reduced risk of CRC, although results from several meta-analyses show conflicting results. The EPIC study suggests that a high-fiber diet is associated with a 40% risk reduction. On the other hand, red meat, smoking, alcohol, and obesity have been associated with an increased risk. Increased physical exercise has been shown to be independently associated with a reduced risk.

Long-term aspirin therapy has been shown in several studies with over 20-year follow-up to be associated with a reduced risk, although a recent consensus group felt that further research was needed before aspirin could b...

Table of contents

• Cover
• Title Page
• Copyright
• Table of Contents
• List of contributors
• Foreword
• Section A: Colorectal cancer
• Section B: Inflammatory bowel disease
• Section C: Pelvic floor disorders
• Section D: Proctology
• Section E: Emergency colorectal surgery
• Section F: Surprise cases
• Section G: New technologies and techniques
• Index
• End User License Agreement