Tap icon
to view sections

Objectives

The following module was designed to supplement medical students’ learning in the clinic. Please take the time to read through each module by clicking the headings below. Information on epidemiology, screening & testing, classification, signs & symptoms, diagnosis, radiology, pathology, staging, management, and treatment of colorectal cancer is provided.

‍By the end of the tutorial, the following objectives should be addressed:

  1. Discuss dietary factors that may play a role in colon cancer.
  2. Discuss what dietary advice is considered prudent in preventing colon cancer.
  3. Identify the importance of family history as a risk factor for colon cancer.
  4. Discuss the relative roles of genetics (including specific syndromes), inflammatory bowel disease and diet in the etiology of colorectal cancer.
  5. Understand the current recommendations for colorectal cancer screening in British Columbia.
  6. List the histopathological types of colorectal cancer.
  7. Understand the relative frequencies and prognostic significance of each histological type of colorectal cancer.
  8. Understand histologic grading of colorectal cancer.
  9. Describe the common signs and symptoms of colorectal cancer.
  10. Understand the common areas of metastasis.
  11. Understand the general approach to colorectal cancer diagnosis.
  12. Understand the laboratory tests and imaging techniques used in the investigation of colorectal cancer.
  13. Understand the general TNM staging for colorectal cancer.
  14. Be aware of the Dukes and Modified Astler Coller classification systems for staging of colorectal cancer, for historical purposes.
  15. Understand that colorectal cancer treatment is different depending on whether the tumour is primarily located in the colon or rectum.
  16. Describe the modalities used in colon and rectal cancer treatment.
  17. Describe some indications, advantages, and disadvantages of the varying treatment modalities.
  18. Understand the purpose of follow-up after treatment of colorectal cancer.
  19. Describe the frequency of follow-up after treatment of colorectal cancer.
  20. Describe the tasks that should be performed at each follow-up visit.

Anatomy Review

Layers of the Bowel Wall

Moving from the internal lumen outwards, the layers of the bowel wall are:

  • Mucosa
  • Surface epithelium
  • Lamina propria
  • Muscularis mucosae
  • Submucosa
  • Muscularis propria
  • Subserosa, which is also sometimes called retroperitoneal fat, or pericolic fat
  • Serosa
Illustration of bowel wall layers

The Boundary Between Colon & Rectum

The rectum is approximately 12 cm in length. The upper 1/3 is covered by peritoneum on the anterior and lateral aspects. The middle 1/3 is covered by peritoneum on the anterior aspect only. The peritoneum is reflected laterally to form the perirectal fossa, and anteriorly to form the rectovesicular fold (in men) or rectouterine fold (in women). The lower 1/3 is not covered by peritoneum at all, and is referred to as the rectal ampulla.

‍Illustration of the rectum

The colon is the peritonealized large colon, and spans from the cecum to the start of the rectum.

The true anatomical boundary between the colon and rectum is the point at which the taenia coli fuse to the circumferential longitudinal muscle of the rectum. For the purpose of determining treatment options, however, the colon ends and rectum begins at the point of peritoneal reflection.

Epidemiology

Colorectal cancer is the third most common cancer in men and women, with lung and prostate or breast being the first and second most common. It is the second leading cause of cancer deaths, exceeded only by lung cancer. The risk of being diagnosed with colorectal cancer is equal in men and women. In the US, the lifetime risk developing colorectal cancer is 6%, with an average age at time of diagnosis of 66.

Risk Factors

Age

The risk of colorectal cancer significantly increases in the population of age 45 and older.

Lifestyle/Diet

Sedentary lifestyle, diet, and smoking appear to play a role.

Studies have shown that having an obese body mass index may increase the risk of colorectal cancer up to 1.5 times the amount of the non-obese population. Colorectal cancer has a substantially higher rate of incidence and mortality in the developed Western world as compared to other geographic regions such as Asia and Africa. This is thought to be explained by the increased consumption of meats and sedentary lifestyle of economically privileged nations. Supporting evidence includes a study that showed that Chinese immigrants to the US subsequently acquired the higher risk of colorectal cancer that exists in the US.

Foods that are generally accepted to increase the risk of colorectal cancer:

  • Red meat
  • Fried, barbequed, and processed meat
  • High fat content
  • Alcohol has demonstrated a minimal increase in risk for men more than women

Foods/food components that are generally accepted to decrease the risk of colorectal cancer:

  • Fruits and vegetables
  • Calcium
  • Magnesium

Foods that have an undetermined effect on colorectal cancer risk:

  • Fibre – varying results from studies, with some claiming a significant decrease in colorectal cancer in populations that consumed high amounts of fibre, where other studies failed to find the same inverse relationship between amount of dietary fibre and risk of colorectal cancer.
  • Coffee and tea – no association with colorectal cancer found.
  • Folic acid – some studies have shown an actual increased incidence of colon cancer, whereas others have shown a decrease in incidence.

Prolonged cigarette smoking (> 35 pack years) is known to be associated with a significant increase in colorectal cancer risk.

Ethnicity

There is a higher risk of colorectal cancer in certain Ashkenazi Jewish families, and African Americans, due to an increased incidence of genetic mutations that predispose to colorectal cancer.

Genetic Factors

In most cases, patients with colorectal cancer do not have a hereditary component. In fact, only 15-30% of patients with colorectal cancer appear to have a major hereditary component. It is therefore said that most cases of colorectal cancer are sporadic.

The most prevalent predisposing genetic syndromes for colorectal cancer are familial adenomatous polyposis (FAP), and hereditary non-polyposis colorectal cancer (HNPCC). These are highly penetrant genetic conditions, with definite links to colorectal cancer. However, they only comprise about 5% of the incidence of colorectal cancer. There are numerous other rarer forms of genetic syndromes that may cause colorectal cancer, such as Peutz-Jeghers syndrome.

An individual that has a first-degree relative with colorectal cancer, not attributed to FAP or HNPCC, has double the risk of developing colorectal cancer within his or her lifetime.

Familial Adenomatous Polyposis (FAP)

FAP accounts for 1% of all colorectal cancers. Although FAP is inherited in an autosomal dominant pattern, the development of disease requires both alleles of the adenomatous polyposis coli (APC) gene to be mutated (two hit model). Individuals with FAP will inevitably have up to thousands of adenomatous polyps in their colon by their twenties. Nearly 100% of individuals with FAP will develop colorectal carcinoma between age 20-50 if colectomy is not performed.

There are some variant forms of FAP. Gardner syndrome is one such variant where the polyposis is accompanied by epidermoid cysts, desmoids tumours, and osteomas. Another variant, known as Turcot syndrome, is characterized by colonic polyposis and brain tumours.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

HNPCC, also known as Lynch syndrome, accounts for 3% of all colorectal cancers. It is inherited in an autosomal dominant pattern, with an 80% penetrance. The disease, like FAP, follows the two hit model, requiring both alleles of a DNA mismatch repair gene to be mutated (3). This subsequently causes contraction or expansion of areas with repetitive nucleotide sequences, known as microsatellites. It is therefore said that the loss of both alleles of a DNA mismatch repair gene causes microsatellite instability.

HNPCC type I is a subtype that is characterized by colorectal cancer only, whereas HNPCC type II is distinguished by colorectal cancer accompanied by extra colonic tumors, including endometrial, ovarian, gastric, small bowel, bile duct, renal pelvis, ureter, bladder, and skin cancers.

The mean age at diagnosis of colorectal caner for individuals with Lynch syndrome is 43 years old. There is a predilection for involvement of the right side of the colon.

Unlike FAP, which is characterized by the growth of thousands of polyps, patients with HNPCC may have only up to 100 colonic polyps. The lack of distinctive clinical features makes it much more difficult to diagnose than FAP.

Peutz-Jeghers Syndrome

Peutz-Jeghers syndrome is the cause of less than 1% of colorectal cancers. It is a rare autosomal dominant disease with high penetrance, characterized by hamartomatous polyposis and skin pigmentation. It confers a 9-13 fold increase in the risk of both GI and non GI cancers. Hamartomatous polyps are typically large, but few in number. They may be present in the colon as well as in the small bowel. Hallmark features of Peutz-Jeghers syndrome include freckles on hands, around the lips, in buccal mucosa, and periorbitally.

Inflammatory Bowel Disease

Chronic, severe colitis increases the lifetime risk of developing colorectal cancer. Pancolitis caused by ulcerative colitis confers up to a 15-fold increase in risk of developing colorectal cancer1. A similar magnitude of increased risk is thought to exist with pancolitis due to Crohn disease.

Protective Factors

The protective effect of non-steroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer has been demonstrated by numerous studies. Although some ideas including enhanced apoptosis and COX-2 inhibition have been proposed, no concrete mechanism of action has been proven.

Statins have also been shown by a few studies to be protective against colorectal cancer, but results have not been as conclusive as for NSAIDs.

Anatomical Site

In the past, colon cancer was believed to almost exclusively affect only the left side of the colon. However, the incidence of right-sided colon cancer appears to be increasing in both North America and Europe. This trend in anatomical localization of disease affects both screening and treatment considerations.

Screening

Most colorectal cancers evolve from pathologically benign adenomatous precursor lesions, known as polyps, although sometimes the benign lesions are sessile (flat). Most colorectal cancer cases can be prevented through regular screening and removal of these precancerous lesions.

Screening guidelines vary according to regional protocols. In BC, the screening protocol is developed by the Guidelines and Protocols Advisory Committee (GPAC), sponsored by the BCMA, Medical Services Commission, and the Government of BC.

According to the GPAC guidelines, patients are stratified into three different groups based on their risk of developing colorectal cancer, and then screened according to which risk group they fall under. These groups include high risk, moderate risk, and average risk patients. In addition to the guidelines for their particular risk group, all patients aged 50 and over should have an annual digital rectal examination.

TABLE 1: RISK GROUPS USED FOR PURPOSE OF SCREENING

High Risk Asymptomatic Patients

FAP & FAP Variants

All 1st degree relatives of individuals with FAP or an FAP variant should be offered genetic counseling and testing. This should be carried out through a referral to the Hereditary Cancer Program at the BC Cancer Agency.

If the result of the genetic test for FAP is negative, the individual should continue to be screened under the guidelines for the average-risk population.

If the result of the genetic test for FAP is positive, or indeterminate, the individual should be referred to a specialist for further testing and monitoring. These patients will require flexible sigmoidoscopy:

  • Every year starting at age 12
  • Every 2 years from age 25
  • Every 3 years from age 35
  • As per guidelines for average-risk individuals at age 50

If polyposis is detected, colectomy should be performed, as the risk of developing colon cancer is 100% if the colon is not removed.

Upper endoscopy has also been recommended by some sources, due to the increased risk of gastric and duodenal polyps. However, this recommendation has not shown a proven benefit in clinical trials.

HNPCC

There are two separate sets of criteria for determining individuals who are at high risk of having Lynch syndrome. These are known as the Amsterdam II criteria, and the revised Bethesda guidelines. The Amsterdam criteria have low sensitivity, but high specificity, whereas the Bethesda guidelines have high sensitivity, but low specificity. As a physician, it is prudent to be aware of both systems.

The Amsterdam II criteria are as follows:

  1. Three (or more) relatives with histologically verified Lynch syndrome associated cancers (colorectal, endometrial, small bowel, or transitional cell carcinoma of the ureter or renal pelvis), one of whom is a first degree relative of the other two, AND
  2. At least two successive generations affected, AND
  3. In at least one of the affected relatives, diagnosis of the cancer occurred prior to age 50, AND
  4. FAP is excluded

The revised Bethesda criteria are as follows:

  1. Colorectal cancer diagnosed in a patient who is less than 50 years of age.
  2. Presence of synchronous, metachronous colorectal or other HNPCC-associated tumors, regardless of age.
  3. Colorectal cancer with “microsatellite instability – high” histology diagnosed in a patient who is less than 60 years of age.
  4. Colorectal cancer diagnosed in a patient with one or more first degree relatives with an HNPCC-related tumor, with one of the cancers being diagnosed under age 50 years.
  5. Colorectal cancer diagnosed in a patient with two or more first or second-degree relatives with HNPCC-related tumors, regardless of age.

Individuals that meet the Amsterdam II or revised Bethesda criteria are at high risk of having HNPCC. These at-risk individuals should be offered genetic counseling and testing, through a referral to the Hereditary Cancer Program at the BC Cancer Agency. The revised Bethesda guidelines recommend microsatellite instability testing for any individuals meeting the criteria, and subsequent genetic mutation testing for DNA mismatch repair genes if the individual is found to have a microsatellite unstable cancer.

Individuals with a family history of HNPCC should be screened via colonoscopy starting at age 25, or 10 years less than the age of the earliest case in the family member who had colorectal cancer, whichever comes first. Colonoscopy should be performed:

  • Every 2 years until age 40
  • Every year thereafter

Moderate Risk Asymptomatic Patients

Colorectal cancer in 1st degree relative, age 55 or younger; or two or more 1st degree relatives of any age

  • Colonoscopy – every 5 years beginning at age 40 or 10 years before the age of presentation of the youngest case in the family, whichever is lower

Colorectal cancer in 1st degree relative over age 55

  • Colonoscopy – every 10 years beginning at age 40

Personal history of polyp >1cm, or multiple colorectal adenomas of any size

  • Colonoscopy – 3 years after polypectomy and every 5 years thereafter if recurrent adenomas are present; if no further adenomas then every 10 years thereafter

Personal history of 1 or 2 colorectal adenomas <1cm

  • Colonoscopy – 5 years after polypectomy and every 5 years thereafter if recurrent adenomas are present; if no further adenomas then every 10 years thereafter

Inflammatory Bowel Disease involving entire colon (pancolitis) for over eight years or the left colon for over 15 years

  • Colonoscopy every 1-2 years in patients without dysplasia
  • If high-grade dysplasia found, or low-grade dysplasia is persistent in several pathological examinations, colectomy is recommended.

Patients with primary sclerosing cholangitis represent a population with an even higher risk of developing colorectal cancer than patients with inflammatory bowel disease. Although the GPAC guidelines for colorectal cancer have no mention of this fact, the Canadian Association of Gastroenterology recommends screening these patients with colonoscopy on an annual basis.

Average Risk Asymptomatic Patients

No known risk factors

  • Fecal occult blood test (FOBT) – yearly, between age 50 and 75 (recommended)
  • Flexible Sigmoidoscopy – every 5 years, between age 50 and 75 (optional, in addition to FOBT)

Colorectal cancer in 2nd degree relatives of any age

  • Colonoscopy – every 10 years between age 50 and 75, or
  • Double contrast barium enema (DCBE) and flexible sigmoidoscopy – every 5-10 years, between age 50 and 75. See “Diagnosis” section for description on double contrast barium enema

Adenomatous polyp in a 1st degree relative younger than age 60

  • Colonoscopy – every 10 years between age 50 and 75, or
  • DCBE and flexible sigmoidoscopy – every 5-10 years, between age 50 and 75

Summary

All patients aged 50 and over should have an annual digital rectal examination.

Flexible sigmoidoscopy
  • Every year starting at age 12
  • Every 2 years from age 25
  • Every 3 years from age 35
  • As per guidelines for average-risk individuals at age 50

HNPCC

Colonoscopy
  • Starting at age 25, or 10 years before the age of the youngest case of CRC in the family
  • Every 2 years until age 40
  • Every year thereafter

Moderate risk patients, CRC in 1st degree relative, age 55 or younger; or two or more 1st degree relatives of any age

Colonoscopy
  • Start at age 40 or 10 years before the age of youngest case in the family, whichever is lower
  • Every 5 years

CRC in 1st degree relative over age 55

Colonoscopy:
  • Start at age 40
  • Every 10 years

Personal history of polyp >1cm, or multiple colorectal adenomas of any size

Colonoscopy:
  • Start 3 years after polypectomy
  • Every 5 years if recurrent adenomas are present
  • Every 10 years thereafter if no further adenomas

Personal history of 1 or 2 colorectal adenomas <1cm

Colonoscopy:
  • Start 5 years after polypectomy
  • Every 5 years if recurrent adenomas are present; Every 10 years if no further adenomas

IBD involving entire colon for over 8 years, or the left colon for over 15 years

Colonoscopy:
  • Start when over 8 years of pancolitis, or 15 years of left-sided colitis
  • Every 1-2 years in patients without dysplasia

Primary sclerosing cholangitis

Colonoscopy:
  • Annually

Average risk patients; No known risk factors

FOBT (recommended)
  • Between age 50 and 75
  • Annually
Flexible sigmoidoscopy (optional, in addition to FOBT)
  • Between age 50 and 75
  • Every 5 years

Colorectal cancer in 2nd degree relatives of any age

Colonoscopy
  • Between age 50 and 75
  • Every 10 years

OR

DCBE and flexible sigmoidoscopy
  • Between age 50 and 75
  • Every 5-10 years

Adenomatous polyp in a 1st degree relative younger than age 60

Colonoscopy
  • Between age 50 and 75
  • Every 10 years

OR

DCBE and flexible sigmoidoscopy
  • Between age 50 and 75
  • Every 5-10 years

Classification

While pathological staging offers the best postoperative outlook for colorectal cancer, histopathological typing and grading of the tumour can offer additional valuable prognostic information.

Histopathological Type

TABLE 1: WHO HISTOPATHOLOGICAL CLASSIFICATIONS OF COLORECTAL CANCER

Many tumours produce mucin. The mucin can be intracellular or extracellular. When a tumour produces a large amount of extracellular mucin that comprises ≥ 50% of the tumour mass, it is called a mucinous adenocarcinoma. Mucinous adenocarcinomas of the colon and rectum are associated with poor response to chemotherapy and they tend to present at a more advanced stage. However, the overall prognostic significance of colorectal mucinous adenocarcinoma remains controversial.

Signet-ring cell carcinoma counts for 1-2% of all colorectal cancers.When ≥ 50% of the tumour is made up of cells with large amounts of intracellular mucin, it is classified as a signet-ring cell carcinoma. It is called this name, because the intracellular mucin displaces the nucleus and cytoplasm to the sides of the cell, and the cell subsequently looks like a signet ring on histopathological examination. Colorectal signet-ring cell carcinomas are aggressive, with a high potential for extensive intramural spread and peritoneal carcinomatosis. Patients usually present at an advanced stage at the time of diagnosis.Squamous cell (epidermoid) carcinomaExtremely rare. Only 18 cases have been described in the medical literature between 1943 and 2002.They present at an advanced stage at diagnosis, behave aggressively, and are associated with a poor prognosis.

Adenosquamous carcinoma is 0.06% of all colorectal cancers. These are adenocarcinomas with areas of squamous differentiation. They present at an advanced stage at diagnosis, behave aggressively, and are associated with a poor prognosis.

Small-cell carcinoma, aka oat-cell carcinoma count for less than 1% of all colorectal cancers.These tumous have neuroendocrine differentiation. Colorectal small-cell carcinomas have a poor prognosis.

Medullary carcinoma3.6% of all colorectal cancers. This colorectal cancer type is associated with high microsatellite instability and HNPCC. It has a more favourable prognosis than other colorectal cancer types. Undifferentiated carcinomaLess favourable outcome.7

Histologic Grade

GX – grade cannot be assessed

G1 – Well differentiatedG2 – Moderately differentiated

G3 – Poorly differentiated

G4 – Undifferentiated (corresponds to the histological type “undifferentiated carcinoma”)

The terms “low-grade” and “high-grade” refer to the grades G1-G2 and G3-G4 respectively.

Histologic grading of the tumour is based primarily on the presence or absence of well-formed glands. Tumours that are graded as “low-grade” have glands that are present. Conversely, tumours that are “high-grade” have do not have evidence of well-formed glandular tissue.

Signs & Symptoms

Patients with colorectal cancer may present with any number of the symptoms listed in table 1 below, with the most common symptoms being1:

  1. Abdominal pain
  2. Change in bowel habit
  3. Hematochezia or melena

20% of patients with colorectal cancer have metastatic disease at the time of presentation. In order to effectively ask the appropriate questions and perform an adequate physical exam, the physician must understand the nature of colorectal cancer, including how the tumour cells tend to spread. There are three main ways that colorectal cancer spreads. These include spreading via local extension, lymphatics, and hematogenously. Rarely, colorectal cancer spreads transperitoneally. The most common sites of spread are regional lymph nodes, the liver, lungs, and peritoneum. Since lymphatics and blood vessels are found in the submucosa, tumours confined to the mucosa have a lower risk of metastasizing.

The liver is usually the first site of hematogenous dissemination, because the intestines are drained by the portal vein. The exception to this is cancer in the distal rectum, which is an area that drains into the inferior vena cava via the inferior rectal veins. As such, tumour cells of the distal rectum may spread initially to the lungs.

One effective approach to thinking about signs and symptoms of colorectal cancer, is to categorize the clinical manifestations according to route of spread (i.e., local invasion, lymphatic invasion, or hematogenous invasion). The table below summarizes this approach.

TABLE 1: SIGNS AND SYMPTOMS OF COLORECTAL CANCER

There also exist some additional constitutional symptoms of cancer that should be assessed during the patient interview, including weight loss, anorexia, muscle weakness, and malaise. While these symptoms can be a direct effect of the cancer, they can also be explained as a manifestation of a paraneoplastic syndrome, where the tumour is releasing substances that interact with receptors and result in increased metabolism.

Impact on Prognosis

Patients who are symptomatic due to obstruction or perforation at the time of diagnosis carry a worse prognosis than patients who are asymptomatic. In addition, the presence of signs and symptoms of obstruction or perforation may influence the choice of therapeutic modalities.

Diagnosis

History

A complete history should be taken. Symptoms associated with colorectal cancer should be elicited during the patient interview. In addition, taking a detailed family history of disease is essential, due to the possibility of a familial cancer syndrome.

Physical Exam

Possible findings during the physical exam include a palpable abdominal mass, bright red blood per rectum, or melena. Metastatic disease may manifest as adenopathy, hepatomegaly, jaundice, or pulmonary signs.

If a lesion is palpable on digital rectal exam, the size of the tumour, mobility, and distance from the anal verge should be documented. For female patients, a pelvic and rectovaginal examination should be performed to look for local invasion of the tumour into pelvic structures (e.g., vagina, rectovaginal septum).

Lab Investigations

There are no blood tests that are effective at detecting colorectal cancer.2 However, laboratory investigations that raise suspicion of colorectal cancer include a CBC that shows an iron-deficiency anemia, and a positive fecal occult blood test.

Other tests that are ordered for the workup of colorectal cancer include kidney and liver function tests, ALP, CEA, and genetic testing.

TABLE 1: LABORATORY INVESTIGATIONS FOR COLORECTAL CANCER WORKUP

Imaging

‍Sigmoidoscopy

Individuals who are symptomatic or have abnormal test results that warrant suspicion of colorectal cancer will require either a colonoscopy or a double contrast barium enema. Colonoscopy is the most useful test, as the physician can view the lumen of the rectum and colon, and at the same time take biopsies of lesions, remove polyps, and detect synchronous lesions. However, approximately 5% of patients will have colon cancers that can not be viewed using colonoscopy, due to an obstruction, tortuous colon, or poor bowel prep. In these patients, the best diagnostic imaging is the double contrast barium enema. A double contrast barium enema involves receiving a barium enema followed by injection of air to expand the colon for a better view, followed by multiple X-ray images. In addition, patients with a pre-operative obstruction that prevents full examination of the colon should have a study of the entire colon after the obstruction is removed.

For rectal cancers, endorectal ultrasound (EUS) and pelvic MRI are important for staging purposes. EUS is cheaper, less time-consuming, and more accurate than MRI at predicting T stage and N stage. Furthermore, EUS allows simultaneous ultrasound guided biopsies to be taken. It should be noted that although EUS is specific for nodal disease, it has low sensitivity. In other words, negative nodal findings on EUS do not effectively rule out the possibility of nodal disease.

TABLE 2: IMAGING FOR COLORECTAL CANCER WORKUP

Pathology

No diagnosis is complete without a biopsy to confirm malignancy. The biopsy is obtained during colonoscopy. The pathologist will also determine the histopathological type of the cancer (see section on classification of colorectal cancer).

Staging

There are many factors that influence the prognosis of a case of colorectal cancer, including histological typing of the tumour, and the magnitude of symptoms owing to obstruction and perforation, among other things. However, staging provides the most valuable prognostic information. There are multiple staging classification systems that should be known for colorectal cancer, including the Dukes classification, the modified Astler-Coller (MAC) classification and the TNM classification. The TNM classification system has superior value in terms of determining prognosis, and therefore is now the standard staging system in clinical practice. The Dukes and MAC classifications are of historical importance, and are no longer recommended for use.

Staging helps in deciding a patient’s treatment plan, understanding prognosis and allowing research comparison. Staging also allows different health care professionals to communicate and provides international standardization.

Staging of colorectal cancer is based on medical history, physical examination, imaging, and pathology.

Dukes and MAC Classification

The Dukes classification system was developed in 1930. The modified Astler-Coller (MAC) system is an enhanced version of the Dukes classification system. The major limitations of the Dukes and MAC classification systems are lack of information regarding adequacy of node sampling, extent of node involvement, and tumour grade. As the number of positive nodes is the most significant prognostic factor,3 the Dukes and MAC classification systems have been deemed inadequate, and are no longer recommended. However, it is important to be aware of these older classification systems, as historical records may be staged using them. The appropriate mapping from a Dukes/MAC stage to TNM stage is provided in Table 9 below.

TABLE 1: DUKES CLASSIFICATION
TABLE 2: MAC CLASSIFICATION

TNM Staging

Note: the BC Cancer Agency supplies its own staging diagrams, based on the TNM staging system. However, as of the writing of this training module (July 16, 2010), the BCCA staging diagrams are outdated, as they are based on the 2002 AJCC staging guidelines, while the AJCC released new staging guidelines in 2010. Nevertheless, you can download the outdated BCCA staging diagrams for colon cancer and rectal cancer.

Primary Tumor (T)

TX – primary tumour cannot be assessed

T0 – No evidence of primary tumour

Tis – Carcinoma in situ: intraepithelial or invasion of lamina propria. The terms “high grade dysplasia”, and “severe dysplasia” are synonymous with in situ carcinoma and in situ adenocarcinoma.

T1 – Tumour invades submucosa

T2 – Tumour invades muscularis propria

T3 – Tumour invades through the muscularis propria into pericolorectal tissues

T4a – Tumour penetrates to the surface of the visceral peritoneum

T4b – Tumour directly invades or is adherent to other organs or structures

Regional Lymph Nodes

Regional lymph nodes are the nodes along the colon, and the nodes along the blood vessels that supply the colon. The regional lymph nodes are further divided into groups depending on which portion of the colon or rectum is affected. During surgical resection of the colon or rectum, the surgeon must try to attain at least 12 lymph nodes for staging purposes. However, this number is quite controversial, and some institutions advocate resecting at least 17 nodes. In general, the more nodes attained, the better the prognostic accuracy. For similar reasons, the pathologist must make a note of how many nodes were actually analyzed in the determination of the pathological N-stage of the tumour.

TABLE 3: REGIONAL LYMPH NODES

Distant Metastasis (M)

M0 – no distant metastasis

M1 – distant metastasis

M1a – metastasis confined to one organ or site (e.g., liver, lung, ovary, nonregional node)

M1b – metastasis in more than one organ/site or the peritoneum

Table 9: TNM stage grouping for colorectal cancer

Other Prognostic Factors That Are Recommended for Collection

  • Pre-treatment serum CEA
  • Tumour deposits – the number of satellite tumour deposits that are discontinuous from the leading edge of the tumour, and that lack evidence of a residual lymph node.
  • Circumferential resection margin
  • Perineural invasion – histological evidence of invasion of regional nerves
  • Microsatellite instability
  • Tumour regression grade (with neoadjuvant therapy) – the pathological response to preoperative neoadjuvant therapy. A significant decrease in disease after neoadjuvant therapy is associated with a good prognosis.
  • KRAS gene analysis – presence of mutation in KRAS is associated with a poor response to anti-EGFR antibody therapy.

Management

For the purpose of managing colorectal cancer, the division between the colon and rectum is located at the point of the peritoneal reflection. The approach to management of colorectal cancer is different depending on whether the tumour is located in the colon, or in the rectum. For instance, adjuvant therapy for colon cancer is mainly achieved through chemotherapy, while for rectal cancer it is achieved through both radiation and chemotherapy. The reasoning behind this is that colon cancer tends to recur as distal metastases, whereas rectal cancer has an equal propensity to recur locally (pelvis) and distally (liver, lung). This is attributed to the difficulty in obtaining clear resection margins in the surgical removal of rectal cancers.

As with all other types of cancer, application of general cancer management principles involves consideration of patient, tumour and treatment factors when deciding the best course of treatment for each individual case. Based on these factors, the treatment goal may be either curative or palliative.

Treatment: Colon Cancer

Curative Intent

Surgery

Surgery is the primary treatment modality when the patient is amenable to curative therapy. The surgeon attempts to achieve wide clearance, with resection margins of 5-10 cm from the cancer, and concurrent removal of a large area of the mesentery that is supplied/drained by common vasculature. The surgeon also obtains at least 12 nodes for pathological evaluation – any less than this number is inadequate, and can result in increased mortality due to inaccurate staging.

Laparoscopic surgery decreases hospitalization time, without compromising outcome. However, the ability to offer laparoscopic surgery is dependent on availability of resources and trained personnel.

Solitary metastatic lesions to the liver and lungs are potentially curable by surgical excision. There are reports of 25-30% disease free survival rates after excision of isolated liver metastases. If such a surgery is to be undertaken, the patient requires a preoperative evaluation to exclude extrahepatic metastases, and a CT or PET scan to assess involvement of intrahepatic vasculature. Similar data are not available for cases of isolated lung metastases, but the potential for curative surgery exists.

Adjuvant Therapy

Chemotherapy is the choice of therapy for adjuvant treatment of colon cancer. Radiation therapy has a small role in palliative treatment of colon cancer, and a larger role in treatment of rectal cancer.

The decision to give adjuvant chemotherapy is based on the stage of disease. Higher stages of disease are associated with higher risk of recurrence, which can be reduced through the administration of adjuvant chemotherapy. Adjuvant chemotherapy is not indicated in stage I and low-risk stage II disease. It is recommended for stage II disease with high-risk factors, and stage III disease. Factors that are considered high-risk include:

  • Perforation
  • T4 status
  • Poorly differentiated histologic grade, without microsatellite instability
  • Inadequate nodal evaluation

Studies have shown that adjuvant chemotherapy increases the cure rate by 10-15% for stage III disease. The effect of adjuvant therapy is optimal if commenced within 8 weeks post-op. It is administered on an outpatient basis, lasting a duration of approximately 6 months. Note that there are multiple chemotherapy regimens available, and that the frequency of administration varies according to treatment regimen. Treatment route may be oral or intravenous.

Palliative Therapy

Initiation of palliative treatment may be delayed in patients who are asymptomatic, and are not at risk of rapid deterioration, if they have predictors of poor tolerance of chemotherapy such as old age and multiple comorbidities. On the other hand, asymptomatic patients that have good performance status are preferentially treated early, before the development of symptoms.

Chemotherapy

Chemotherapy is the mainstay treatment modality in palliative treatment of colon cancer. There are multiple agents available for use. These include traditional cytotoxic drugs, as well as more novel biologic agents that target vascular endothelial growth factor (anti-angiogenisis), and epidermal growth factor receptor.

A patient with poor performance status will most likely have overall better quality of life on a single-agent regimen, whereas patients with good performance status will likely benefit from combination therapy.

In patients whose disease progresses after initial treatment, retreatment with different agents may be considered if their condition permits.

Surgery

Surgical resection, bypass or colostomy may be indicated for palliative treatment in select individuals.

Radiation Therapy

Radiation therapy has a limited role in palliative treatment of colon cancer. Radiation therapy is useful for controlling localized pain and bleeding. External beam radiation therapy can also be used to treat non-resectable liver metastatic lesions.

Other Local Palliative Therapies
  • Transanal laser therapy – control of bleeding or obstruction from tumours in lower rectal/anal area
  • Transanal stenting – relieve obstruction
  • Radiofrequency ablation – for non-resectable liver metastatic lesions

Treatment: Rectal Cancer

There is a role for surgery, radiation therapy, as well as chemotherapy in the treatment of rectal cancer, whether the intent is curative or palliative. The final decision on treatment regimen will rest on patient, tumour and treatment factors.

Curative Intent

Surgery

Surgery is the main treatment modality when the intent is curative. There are different techniques when it comes to surgery for rectal cancer, with advantages and disadvantages to each:

Surgery: segmental resection
Low anterior resection(LAR)
  • Dissection and anastomosis below the peritoneal reflection, with anastomosis of superior and middle hemorrhoidal arteriesPreserves anal sphincterUsed for upper, mid, and some lower rectal cancers
Abdomino-perineal resection (APR)
  • Involves removal of the anus and sphincter muscles, and requires a permanent colostomyUsed for lower rectal cancersResults in high incidence of sexual and urinary dysfunction.
Hartmann resection
  • Removal of tumour, closure of distal portion, and creation of a stoma with the proximal segment
Total mesorectal excision (TME)
  • The removal of the entire mesorectumTME is a technique that is combined with other techniques (e.g. LAR with TME, or APR with TME)Shown to result in better control of local recurrence compared to non-TME surgeries.
Surgery: Local excision – only used for certain favourable lesions:
  • Well or moderately differentiated histology
  • Size < 3 cm
  • Absence of lymphatic or vascular invasion

It is not important at this stage to know the all specific criteria used to decide the surgical approach, but rather to understand the main factors. These include distance of the distal edge of the tumour from the anal verge, body habitus, tumour size, and patient comorbidity.

The ideal surgery will spare the anal sphincter preserving bowel continence, and spare the nervi erigentes preserving rectal, urinary, and erectile function. The nervi erigentes are the pelvic splanchnic nerves, which arise from S2-4 and provide parasympathetic innervation to structures arising from the hindgut.

Neoadjuvant Therapy

Neoadjuvant therapy refers to therapy given before the main treatment modality. Neoadjuvant therapy for rectal cancer may involve radiation ± chemotherapy.

Why give chemoradiation preoperatively, as opposed to postoperatively?

  • There is a lower side effect profile and lower rate of local recurrence when chemoradiation is employed preoperatively.
  • For distal rectal tumours, preoperative chemoradiation may shrink the tumour and allow the use of sphincter-preserving techniques, such as LAR, as opposed to APR which requires permanent colostomy.

There are different regimens of preoperative radiation therapy:

Short-course preoperative radiation (also called short-course, Swedish style RT)
  • Short-course (5 days), high dose per fraction
  • Used for stage II/III cancers that have lower risk factors (i.e. not adhered to nearby structures such as the sacrum, pelvic sidewalls, prostate, or bladder).
  • Does not immediately shrink tumour, but has other benefits:
  • Minimizes delay to surgery, as compared to preoperative radical radiotherapy which has a longer courseIncreases local control and survival rate, compared to surgery alone.
Radical preoperative radiotherapy
  • Long-course (5 weeks), lower dose per fraction
  • This is used for cases of stage II/III cancers that have high risk factors, such as fixation (i.e. adherence to nearby structures such as the sacrum, pelvic sidewalls, prostate, or bladder).
  • Benefit is reduction of tumour size, which facilitates resection.

Adding chemotherapy to the radiation results in higher rate of pathologic complete response, as well as lower local recurrence as compared to radiation alone. However, this benefit must be balanced with the increase in toxicity.

Adjuvant Therapy

Adjuvant chemotherapy and radiation therapy may be used, and has been shown to improve local control and survival in Stage II and III rectal cancer.7 Studies have shown that adjuvant chemoradiation results in a significant improvement in local control and survival rate as compared to surgery or surgery + radiation alone.

  • Started 4-8 weeks after operation.
  • 6 months of outpatient therapy
Treatment By Clinical Stage

The decision whether to give preoperative or postoperative chemoradiation therapy is dependent on the clinical stage of disease.

TABLE 1: TREATMENT OF RECTAL CANCER BY CLINICAL STAGE

Palliative Therapy

Clinical Stage IV Disease

Most clinical stage IV disease is considered incurable, and is therefore treated palliatively.

Surgery
  • Isolated liver and lung metastases may benefit from resection, and a modest proportion of these patients are cured.
  • Surgical resection may still provide the best form of local palliation. Preoperative chemotherapy and radiation therapy may be helpful in some circumstances.
  • Other surgical palliative techniques:
  • Diverting colostomy to relieve obstructionHartmann resection
Radiation
  • Control of pain and bleeding, especially from local recurrence of rectal cancer.
  • Does not help obstruction, and is contraindicated in the intact, obstructed bowel.
Chemotherapy
  • Controls symptoms, delays progression, prolongs survival.
Other palliative techniques
  • Laser fulguration
  • Endoluminal radiation
  • Internal stent placement
  • Radiofrequency ablation for non-resectable liver lesions

Follow-Up

Purpose of Follow-up

  1. To ensure that problems due to primary therapy are found and resolved
  2. To detect and offer therapy for recurrence
  3. To detect new polyps, or second primary neoplasms, which have a higher propensity to occur in individuals that have had prior colorectal cancer
  4. To assess the results of therapy

Frequency and Duration

The schedule for follow-up is every 3 months for 3 years, and then every 6 months for 2 more years. During the course of therapy and recovery, follow-up is coordinated by the care team, which consists of the patient’s family physician, gastroenterologist, surgeon, medical oncologist and radiation oncologist.

Follow-up Tasks

Tasks that may be completed at each follow-up visit include:

History
  • Every visit
  • Ask about GI and constitutional symptoms
Physical examination
  • Every visit
  • Abdominal exam
  • DRE
  • Lymphadenopathy
  • With particular attention to left supraclavicular fossa (the location of Virchow’s node, a common location for metastases from gastrointestinal cancers).
Lab investigations
  • Every visit
  • Serum CEA: If elevated, do additional imaging of thorax and abdomen to rule out recurrenceDiscontinue if normal for 5 years.
Colonoscopy
  • Every 3 years, until no new adenomas found. Thereafter, repeat colonoscopy every 5 years until detection of new cancers is unlikely to affect patient’s lifespan.
  • Remove and biopsy suspicious lesions
  • May use double-contrast barium enema with flexible sigmoidoscopy as an alternative if colonoscopy is not available.
Liver imaging
  • Every 6 months for 3 years, and then annually for 2 years
  • Indicated in patients who are candidates for resection of isolated liver metastases

In addition to the above tests, the following recommendations apply to patients with rectal cancer:

DRE and proctoscopy or sigmoidoscopy
  • If underwent low anterior resection of rectal cancer, to assess for recurrence at the site of anastomosis.
  • At 3 months, 6 months, 1 year, and 2 years.
Chest x-ray
  • Every 6-12 months for 5 years.

Virtual Patient Case

This case study was designed to supplement your knowledge on the workup of colorectal cancer and test what you have learned after going through module. Use your mouse to click through the slides and answer each question in the text box provided.

Note: This case can be completed on an iPad. To do this download the (free) Articulate Mobile Player for the iPad by clicking here.

References

Anatomy Review

  1. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual. 7th ed. New York: Springer-Verlag; 2010.
  2. Health professionals info: cancer management guidelines: gastrointestinal: colon [Internet]. BC Cancer Agency; [updated 2008 May 6; cited 2010 Jul 16]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/05.Colon/default.html

Epidemiology

  1. Ahnen DJ, Macrae FA. UpToDate: Colorectal cancer: epidemiology, risk factors and protective factors. 2010. Available at: http://www.uptodate.com Accessed June 2010.
  2. DeVita VT, Lawrence TS, Rosenberg SA. Cancer: Principles & Practice of Oncology 8th Edition Vol 1. Lippincott Williams & Wilkins, Philadelphia; 2008.

Screening

  1. Detection of colorectal neoplasms in asymptomatic patients. Victoria: Guidelines and Protocols Advisory Committee; 2004 Mar. 11 p. Available from: http://www.bcguidelines.ca/gpac/pdf/colorectal_det.pdf
  2. Health professionals info: cancer management guidelines: gastrointestinal: colon: screening/early detection [Internet]. BC Cancer Agency; [updated 2005 Nov 16; cited 2010 Jul 14]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/05.Colon/5Screening.htm
  3. Bonis PA, Ahnen DJ, Axell L. UpToDate: Screening and management strategies for patients and families with familial colon cancer syndromes. 2010. Available at: http://www.uptodate.com Accessed July 2010.
  4. Ahnen DJ, Axell L. UpToDate: Clinical features and diagnosis of Lynch syndrome (hereditary nonpolyposis colorectal cancer). 2010. Available at: http://www.uptodate.com Accessed July 2010.
  5. Leddin D, Hunt R, Champion M, Cockeram A, et al. Canadian Association of Gastroenterology and the Canadian Digestive Health Foundation: Guidelines on colon cancer screening. Can J Gastroenterol 2004 Feb;18(2):93-9.

Classification

  1. Cagir B, Nagy MW, Topham A, Rakinic J, Fry RD. Adenosquamous carcinoma of the colon, rectum, and anus: epidemiology, distribution, and survival characteristics. Dis Colon Rectum 1999 Feb;42(2):258-63.
  2. Compton CC. UpToDate: Pathology and prognostic determinants of colorectal cancer. 2010. Available at: http://www.uptodate.com Accessed July 2010.
  3. DeVita VT, Lawrence TS, Rosenberg SA. Cancer: Principles & Practice of Oncology 8th Edition Vol 1. Lippincott Williams & Wilkins, Philadelphia; 2008.
  4. El Demellawy D, Khalifa MA, Ismiil N, Wong S, Ghorab Z. Primary colorectal small cell carcinoma: a clinicopathological and immunohistochemical study of 10 cases. Diagn Pathol 2007 Sep 5;2:35.
  5. Gelas T, Peyrat P, Francois Y, Gerard JP, et al. Primary squamous-cell carcinoma of the rectum: report of six cases and review of the literature. Dis Colon Rectum 2002 Nov;45(11)1535-40.
  6. Verma S, Balachandra B, Butts C, Koski S, et al. Squamous and adenosquamous carcinoma of the colon and rectum: Institutional and literature review. Proc Am Soc Clin Concol 22:2003 (abstr 1339).
  7. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual. 7th ed. New York: Springer-Verlag; 2010.
  8. Lanza G, Gafà R, Matteuzzi M, Santini A. Medullary-type poorly differentiated adenocarcinoma of the large bowel: a distinct clinicopathologic entity characterized by microsatellite instability and improved survival. J Clin Oncol 1999 Aug;17(8):2429-38.

Signs and Symptoms

  1. Ahnen DJ, Macrae FA. UpToDate: Clinical manifestations, diagnosis, and staging of colorectal cancer. 2010. Available from: http://www.uptodate.com Accessed July 2010.
  2. Just the facts: symptoms [Internet]. Colorectal Cancer Association of Canada; [cited 2010 Jul 16]. Available from: http://www.colorectal-cancer.ca/en/just-the-facts/symptoms/
  3. Coll DM, Meyer JM, Mader M, Smith RC. Imaging appearances of Sister Mary Joseph nodule. Br J Radiol 1999 Dec;72(864):1230-3.
  4. Theologides A. Cancer cachexia. Cancer 1979 May;43(5 Suppl):2004-12.
  5. DeVita VT, Lawrence TS, Rosenberg SA. Cancer: Principles & Practice of Oncology 8th Edition Vol 1. Lippincott Williams & Wilkins, Philadelphia; 2008.

Diagnosis

  1. DeVita VT, Lawrence TS, Rosenberg SA. Cancer: Principles & Practice of Oncology 8th Edition Vol 1. Lippincott Williams & Wilkins, Philadelphia; 2008.
  2. Holleb AI, Fink DJ, Murphy GP. Clinical Oncology 1st Edition. American Cancer Society, Atlanta; 1991.
  3. Ahnen DJ, Macrae FA. UpToDate: Clinical manifestations, diagnosis, and staging of colorectal cancer. 2010. Available at: http://www.uptodate.com Accessed July 2010.

Staging

  1. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual. 7th ed. New York: Springer-Verlag; 2010.
  2. Health professionals info: cancer management guidelines: gastrointestinal: colon [Internet]. BC Cancer Agency; [updated 2008 May 6; cited 2010 Jul 16]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/05.Colon/default.htm
  3. DeVita VT, Lawrence TS, Rosenberg SA. Cancer: Principles & Practice of Oncology. 8th ed. Vol 1. Philadelphia: Lippincott Williams & Wilkins; 2008.
  4. Lester SG. Radiation therapy in colorectal carcinoma. J Natl Med Assoc. 1988 October; 80(10): 1090–1093.
  5. Health professionals info: cancer management guidelines: gastrointestinal: colon: management: curative treatment [Internet]. BC Cancer Agency; [updated 2008 May 6; cited 2010 Jul 16]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/05.Colon/Management/Curative.htm
  6. Blackbourne LH. Surgical recall. 5th ed. Baltimore: Lippincott Williams and Wilkins; 2009.
  7. Silva AC, Vens EA, Hara AK, Fletcher JG, Fidler JL, Johnson CD. Evaluation of Benign and Malignant Rectal Lesions with CT Colonography and Endoscopic Correlation. RadioGraphics 2006;26: 1085-1099.

Treatment: Colon Cancer

  1. Health professionals info: cancer management guidelines: gastrointestinal: colon: management: curative treatment [Internet]. BC Cancer Agency; [updated 2008 May 6; cited 2010 Jul 16]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/05.Colon/Management/Curative.htm
  2. Health professionals info: cancer management guidelines: gastrointestinal: colon: management: isolated liver or lung metastases [Internet]. BC Cancer Agency; [updated 2008 May 6; cited 2010 Jul 16]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/05.Colon/Management/IsolatedLiverorLungMets.htm
  3. Health professionals info: cancer management guidelines: gastrointestinal: colon: management: palliative treatment [Internet]. BC Cancer Agency; [updated 2008 May 6; cited 2010 Jul 16]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/05.Colon/Management/Palliative.htm
  4. Health professionals info: cancer management guidelines: gastrointestinal: colon: management [Internet]. BC Cancer Agency; [updated 2005 Sep 2005; cited 2010 Jul 19]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/05.Colon/Management/default.htm

Treatment: Rectal Cancer

  1. Willett CG, Ryan DP. UpToDate: Neoadjuvant chemoradiotherapy for rectal cancer. 2010. Available at: http://www.uptodate.com Accessed July 2010.
  2. Health professionals info: cancer management guidelines: gastrointestinal: rectum: management: curative treatment [Internet]. BC Cancer Agency; [cited 2010 Jul 20]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/06.Rectum/Management/Curative.htm
  3. Meeks GR, Trenhaile T. UpToDate: Neuropathies associated with pelvic surgery. 2009. Available at: http://www.uptodate.com Accessed July 2010.
  4. Health professionals info: cancer management guidelines: gastrointestinal: rectum: management [Internet]. BC Cancer Agency; [cited 2010 Jul 20]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/06.Rectum/Management/default.htm
  5. Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997 Apr; 336(14):980-7.
  6. Willett CG, Rodriguez-Bigas MA, Ryan DP. UpToDate: Treatment of locally advanced unresectable or recurrent rectal cancer. 2009. Available at: http://www.uptodate.com Accessed July 2010.
  7. Health professionals info: cancer management guidelines: gastrointestinal: rectum: management: adjuvant treatment [Internet]. BC Cancer Agency; [cited 2010 Jul 20]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/06.Rectum/Management/Adjuvant.htm
  8. Krook JE; Moertel CG; Gunderson LL; Wieand HS; Collins RT; Beart RW; et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 1991 Mar 14;324(11):709-15.
  9. Health professionals info: cancer management guidelines: gastrointestinal: rectum: management: palliative treatment [Internet]. BC Cancer Agency; [cited 2010 Jul 20]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/06.Rectum/Management/Palliative.htm

Follow-up

  1. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual. 7th ed. New York: Springer-Verlag; 2010.
  2. Health professionals info: cancer management guidelines: gastrointestinal: colon [Internet]. BC Cancer Agency; [updated 2008 May 6; cited 2010 Jul 16]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/05.Colon/default.htm
  3. DeVita VT, Lawrence TS, Rosenberg SA. Cancer: Principles & Practice of Oncology. 8th ed. Vol 1. Philadelphia: Lippincott Williams & Wilkins; 2008.
  4. Lester SG. Radiation therapy in colorectal carcinoma. J Natl Med Assoc. 1988 October; 80(10): 1090–1093.
  5. Health professionals info: cancer management guidelines: gastrointestinal: colon: management: curative treatment [Internet]. BC Cancer Agency; [updated 2008 May 6; cited 2010 Jul 16]. Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Gastrointestinal/05.Colon/Management/Curative.htm
  6. Blackbourne LH. Surgical recall. 5th ed. Baltimore: Lippincott Williams and Wilkins; 2009.
  7. Silva AC, Vens EA, Hara AK, Fletcher JG, Fidler JL, Johnson CD. Evaluation of Benign and Malignant Rectal Lesions with CT Colonography and Endoscopic Correlation. RadioGraphics 2006;26: 1085-1099.

Whiteboard Videos