Colorectal cancer and adenoma

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Contents

Introduction

Cancer of the colon and rectum is the most common internal cancer in the Western world. It is the second most common cause of death from cancer after lung cancer. The prognosis for colorectal cancer is relatively good compared with that for other solid tumours such as lung cancer and stomach cancer. Improvement in outcome has come from meticulous surgical techniques and more sophisticated medical management. Endorectal ultrasound has enabled a more precise staging of low rectal cancer and has allowed stratification of surgical treatment. Excision of the rectum and anus and a permanent colostomy is now rarely performed. Early trials of adjuvant therapy offer possibilities for further reduction in deaths from cancer recurrence. Strategies for mass screening for polyps and cancers are yet to be finalised but may further reduce mortality from colorectal cancers.

Epidemiology

Rectal cancers are twice as common in men, and rightsided cancers are more common in women. For the rest of the large bowel, the incidence is almost equal between the sexes. Colorectal cancers are common in the urban Western world but rare in Asia, Africa and most of South America. The lifetime risk for colorectal cancer is 1 in 18 for men and 1 in 28 for women, but its occurrence under 50 years of age is very low. After that age, the incidence increases rapidly. The peak incidence is in the seventh decade, some 5–10 years later than the peak for adenoma.

Aetiology

Epidemiological studies suggest that environmental factors predominate in the causation of most large bowel cancers. A diet rich in fat and meat, and low in fibre, is commonly associated with colorectal cancers. Dietary fibre increases the bulk of stool by retaining water and decreases the colonic transit time in most people. Fibre alters the colonic bacterial flora and absorbs luminal toxins. The net result is to reduce the carcinogenic capacity of the luminal contents. A number of minor dietary constituents may also inhibit carcinogenesis. These include beta-carotene, selenium and vitamins C and E.

Other risk factors for colorectal cancer are listed in Risk factors for colorectal cancer.

Pathology

The outcome of colorectal cancer depends on its biological behaviour. More aggressive cancers may present with a shorter history and are advanced at the time of presentation. The clinicopathological stage (thus the amount of spread) of the disease is a ‘snapshot’ in the life of a cancer; together with the histopathological features, it provides the most accurate prognostic index at the moment. Other phenotypic features, as yet unidentified, may provide further prognostic information.

Staging

The most common staging methods are Dukes' classification (Table 27, “Staging methods for colorectal cancer”) and its various derivatives, including the Australian clinicopathological staging (ACPS), or the Union Internationale Centre Cancer (UICC) TNM classification.

Table 27. Staging methods for colorectal cancer
Modified Dukes' Staging
A Tumour confined to bowel wall
B Tumour invading through serosa
B1 Through muscularis propria
B2 Through serosa or perirectal fat
C Lymph node involvement
C1 Apical node clear
C2 Apical node involved
UICC TNM Staging Tumour depth (T)
T1 Submucosa
T2 Muscularis propria
T3 Subserosa or pericolic tissues
T4 Invade adjacent organs or visceral peritoneum
Nodes (N)
N0 Nodes not involved
N1 1–3 pericolic nodes involved
N2 ≥4 pericolic nodes involved
Metastasis (M)
M0 No distant metastases
M1 Distant metastases
Stage I T1,2 N0
Stage II T3,4 N0
Stage III T1–4 N1,2
Stage IV M1

Dukes' staging has the attraction of its simplicity but it is relatively imprecise because several important prognostic factors are not included. These include the depth of cancer penetration, the extent of spread outside the bowel, the number of lymph nodes involved and the presence of distant metastases. Patients with Dukes' C cancers are more likely to have occult liver metastases than B or A cancers.

Histopathology

Poorly differentiated cancers have a worse outlook than those that are well to moderately differentiated. Other adverse features include lymphovascular or perineural invasion and a histology of signet ring, mucinous and small cell cancers.

Other characteristics

The anatomic site of the cancer has an influence on the outcome. Rectal cancers tend to have a better outcome than colonic cancers because of earlier detection. However, there is a higher incidence of local recurrence in rectal cancer from technical failure in radical removal of the tissues at risk. Stage for stage, right-sided colonic cancers tend to have a better prognosis than left-sided cancers.

Prognosis

Tumour stage is the main determinant (Table 28, “Prognosis in colorectal cancer”) of prognosis. The survival of patients with Dukes' A cancers after adequate resection is similar to that of the general population of similar age. Patients with superficial cancers confined to the submucosa will be cured by adequate surgery. The adverse prognostic effects of lymph node metastases are dependent on their number and extent. While metastatic disease may develop somewhat later than for other solid tumours, such as breast or lung cancer, few develop metastases beyond 5–10 years after surgical resection of the primary disease. The majority (85%) of patients with liver metastases die within 1 year of diagnosis.

Table 28. Prognosis in colorectal cancer
5-Year survival (%)
Stage Colon cancer Rectal cancer
Dukes' A 99 90
Dukes' B 80 60
Dukes' C 50 40
Distant metastases 10 10

Clinical presentation

The clinical presentations vary with the primary site and extent of disease. About 50% of cancers occur at the rectosigmoid junction or in the rectum.

Caecal and right-sided carcinoma

Caecal and right-sided carcinoma account for 20% of all large bowel cancers. Clinical presentations include:

  • Insidious onset of iron deficiency anaemia from occult faecal blood loss. This is the most common finding.
  • Distal ileal obstruction. As the faecal content entering the caecum is liquid, this is a relatively late presentation.
  • Palpable right iliac fossa mass.
  • Lethargy or fever of unknown origin. These symptoms are due to a small occult, localised perforation or from tumour burden. Metastases tend to be more aggressive and grow more rapidly than the primary tumour. Ischaemic infarction and necrosis may occur in the metastases, producing pain, fever and malaise.
  • Acute appendicitis. This occasionally develops following occlusion of the appendiceal orifice by caecal cancer.

Left-sided and sigmoid carcinoma

By the time the stool reaches the left colon, it becomes harder because most of the fluid is absorbed. The diagnosis is sometimes confused with irritable bowel syndrome or diverticular disease. Common clinical presentations include:

  • Alteration of bowel habit: constipation alternating with diarrhoea.
  • Lower abdominal colic, distension and a desire to defecate.
  • Passage of altered blood and sometimes mucus. Rectal bleeding is usually intermittent, with a small amount of dark blood mixed with the stool.
  • A palpable mass in the left side of the abdomen.

Complications of colon cancer

Large bowel obstruction with abdominal distension is more common with right-sided cancers. The caecum becomes very distended and tender. If the ileocaecal valve is incompetent, the obstructed large bowel decompresses into the small bowel, producing a mixed clinical picture of large and small bowel obstruction.

Local invasion into the lateral abdominal wall or a loop of small bowel may occur, producing either a small bowel obstruction or an ileocolic fistula with severe diarrhoea. Sigmoid cancers may invade the bladder to form a colovesical fistula. Patients present with recurrent urinary tract infection, haematuria and later with pneumaturia and faecaluria. Other organs that may be invaded include the uterus and ovaries.

Rectal cancer

Rectal cancers generally cause symptoms early in their course and the tumours are accessible to digital examination or rigid sigmoidoscopy. However, the diagnosis is often delayed because the symptoms are attributed to haemorrhoids or anal fissure. There is a general reluctance of both the patients and primary care physicians to undertake anorectal examination. Clinical presentations include:

  • Rectal bleeding. The blood may be dark and mixed with stool or bright and quite separate from the faeces.
  • Changes in bowel habit, such as frequent bowel movement or mucous diarrhoea. Passage of potassium-rich mucus and resultant hypokalaemia is particularly associated with a large villous adenoma, often with malignant foci.
  • Tenesmus or a continuous urge to defecate is indicative of a large rectal neoplasm, causing a fullness in the rectum.
  • Anal and perineal pain, initially on defecation and later continuous, occurs with low rectal cancer invading the anal sphincters. Sacral pain, sometimes radiating down the legs, results from tumour invasion of the sacrum and sacral nerve plexus.

Metastatic disease

Local transcoelomic spread within the peritoneal cavity may produce an ascites rich in protein. Sometimes a chylous ascites results from obstruction of the lymphatics by widespread peritoneal seeding. A Sister Marie Joseph nodule may develop at the umbilicus from tumour infiltration.

Liver metastases are quite asymptomatic in the early stages. Initially, hepatomegaly, vague hepatic pain and later jaundice may ensue. Lung metastases may produce a persistent cough. Bone marrow infiltration may produce leucoerythroblastic anaemia.

Clinical assessment

A careful history and physical examination remain the most important assessment with regard to the diagnosis, the extent of spread and the patient's fitness for surgery. An estimation of the nutritional state preoperatively is also important. Digital rectal examination is important in order to feel for a rectal mass, its location and relationship to the anal sphincters, its fixity to adjacent structures and to feel for any enlarged extrarectal nodule.

A proctosigmoidoscopic examination of the rectum and anus should follow. Rigid sigmoidoscopy allows examination of the rectum without any bowel preparation. The mucosa, faeces, blood and mucus are examined in their natural state. A flexible sigmoidoscopy allows examination of the rectum, the sigmoid colon and a variable portion of the left colon with comfort.

Investigations

Faecal occult blood

Two main types of tests are available.

  • Guaiac tests (Hemoccult, Hemoccult SENSA), based on the pseudoperoxidase activity of haematin, a degradation product of haemoglobin, to produce a blue colour on the test strip.
  • Immunochemical tests (HemeSelect, Hemolex) use antibodies to human haemoglobin.

The traditional guaiac tests will detect 40–80% of asymptomatic colorectal cancer, especially left-sided cancer. Dietary restrictions are necessary (not with immunochemical tests) to prevent a false positive result. Red meat, melons, horse-radish, vitamin C and non-steroidal inflammatory drugs must be avoided for 3 days before testing. Ninety-eight per cent of healthy subjects (specificity) will test negative for faecal occult blood. In general, the greater the sensitivity, the lower the specificity of the test.

The newer guaiac tests and immunochemical tests are more sensitive. They may detect 80% of cancers at an earlier stage than those diagnosed at the time when symptoms occur. They will be positive in 70% of patients with adenomas larger than 1 cm. The specificity is lower than that of guaiac tests.

In general, faecal occult blood testing is used for screening asymptomatic individuals and not for investigating symptoms. A positive faecal occult blood test must be followed by further investigation of the entire colon and rectum.

Colonoscopy or barium enema

Colonoscopy enables a detailed study of the entire colon, visualising lesions of less than 0.5 cm. Any lesion visualised may be biopsied and small polyps may be removed by cautery. Colonoscopy is more involved than a barium enema as sedation is needed and there is a small risk of perforation.

Double-contrast barium enema provides good anatomical information of the colon and any lesion seen (Double contrast barium enema showing a cancer in the ascending colon.). However, detection of small lesions and mucosal abnormalities such as inflammation is much more limited than colonoscopy. Any abnormality identified by barium enema often needs confirmation by colonoscopy and biopsy. A sigmoidoscopy is a mandatory adjunct to barium enema as the rectum is not well visualised in barium enema.

Double contrast barium enema showing a cancer in the ascending colon.

In most specialist colorectal centres, the first-line test is a colonoscopy. Barium enema is performed if the colonoscopy is incomplete owing to anatomical or pathological factors.

Endorectal ultrasound

A rigid endorectal ultrasound probe is a new but established method of assessing the depth of penetration of a rectal tumour through the bowel wall (Endorectal ultrasound showing (A) tumour invasion through the muscular wall to the perirectal fat, T3 and (B) an enlarged lymph node in the mesorectum.). Enlarged mesorectal lymph nodes can be identified, although confirmation of nodal metastases is less reliable. The test is performed as an outpatient procedure without any sedation or bowel preparation. While the test is simple, it is best performed by a colorectal specialist with a detailed knowledge of the rectum and anal canal.

Endorectal ultrasound showing (A) tumour invasion through the muscular wall to the perirectal fat, T3 and (B) an enlarged lymph node in the mesorectum.

This improved diagnostic information is helpful in planning a transanal local excision of an early-stage rectal tumour and sometimes when choosing between an abdominoperineal excision of the rectum and an ultra-low anterior resection. A locally advanced rectal cancer may benefit from pre-operative adjuvant chemoradiotherapy.

Computed tomography, ultrasound or magnetic resonance imaging

Either computed tomography (CT) or ultrasound may be used to screen for intra-abdominal metastases, although CT scan (Computed tomography scan of the abdomen showing multiple metastases in both the right and left lobes of the liver.) tends to provide more information than an ultrasound. Routine screening for distant metastases by CT scan or ultrasound incurs significant costs and has not been shown to alter the outcome significantly. Pre-operative CT scan or ultrasound should be reserved for patients in whom distant metastases are suspected, or in the elderly and frail when a less radical surgical treatment may be justified. Magnetic resonance imaging (MRI) is helpful in defining the extent of loco-regional invasion of rectal cancer.

Computed tomography scan of the abdomen showing multiple metastases in both the right and left lobes of the liver.

Intra-operative hepatic ultrasound

This is useful in detecting secondary liver deposits and locating their site in the anatomic segments of the liver. It helps in assessment of the resectability of liver metastases and in planning the extent of liver resection. Intra-operative hepatic ultrasound is more sensitive than transabdominal ultrasonography and complements pre-operative CT scan.

Carcinoembryonic antigen

Carcinoembryonic antigen (CEA) is a non-specific, circulating, tumour-associated antigen in colorectal cancer. It has little diagnostic value but has a limited use in the follow-up after resection for cancer. While a rise in CEA may antedate clinical recurrence, the practice of routine CEA monitoring has not affected the cancerrelated mortality significantly, because of limitations by its sensitivity and specificity.

Treatment

The principle of potential surgical cure demands that the cancer be excised with an adequate margin of surrounding tissue and lymphovascular clearance. It is rare for a cancer to spread up or down the bowel as much as 2 cm from the primary unless it is a mucinous or undifferentiated tumour. Distal spread exceeds 2 cm in less than 3% of patients. Most of these patients are Dukes' C cases with high-grade malignancy. A large segment of the colon (up to 10–15 cm) is usually resected because of the extent of lymphovascular clearance.

For rectal tumours, less of the bowel is removed to allow restoration of bowel continuity. A 5 cmmargin of clearance is usually preferred, although as little as 2 cm may be taken for a small mid-rectal tumour. Spread is equally likely into surrounding tissues such as the mesorectum. Thus, a wide lateral resection including all of the mesorectum is important for a rectal cancer.

Meticulous handling of tissues and the techniques used are more important than the material with which the anastomosis is made. The anastomosis may be stapled or hand-sewn using an inverting, interrupted technique.

A laparoscopically assisted technique is being developed. Most of the large bowel is mobilised using laparoscopic techniques. The large bowel is delivered through a small abdominal incision where the mobilisation, resection and anastomosis or stoma are completed extracorporeally by hand. Alternatively, the entire operation may be performed laparoscopically. Certain tumours, such as those in the transverse colon or distal rectum or locally advanced tumours are less amenable to laparoscopic resection. Laparoscopic colorectal surgery is technically more difficult to perform, and there is a steep learning curve. When performed expertly, patients undergoing laparoscopic resection have significant benefits with smaller and more cosmetic scars, a shorter hospital stay and much earlier return to normal activity. The oncologic outcome is similar to conventional open surgery. However the success of laparoscopic colorectal surgery is very dependent on surgical experience; otherwise protracted long operations or conversion to open surgery after prolonged attempts at laparoscopic surgery are detrimental to patient outcome.

Peri-operative preparation

Bowel preparation

Mechanical preparation with Golytely, Fleet phosphosoda or picolax on the pre-operative day are currently the most widely used methods. Reduction of faecal load reduces both the wound and anastomotic sepsis (see Thyroid).

In patients with partial bowel obstruction, a more gentle and prolonged bowel preparation over 2-3 days is necessary. In the more acute situation with a complete obstruction, intra-operative antegrade lavage of the colon using a small Foley catheter through the appendix stump or the distal ileum may be performed if a primary anastomosis is intended.

Antibiotic prophylaxis

Prophylactic broad-spectrum antibiotics against aerobic and anaerobic bowel pathogens have greatly reduced incidence of wound infection and intraabdominal sepsis (see Thyroid). While one good dose may be adequate, most clinicians would continue the prophylactic antibiotics for 24 hours postoperatively. An unnecessarily prolonged course of antibiotics is expensive, predisposes to pseudomembranous colitis and may encourage growth of antibioticresistant organisms.

Thromboembolism prophylaxis

Patients undergoing surgery for colorectal carcinoma have many risk factors for deep vein thrombosis. Increasing age, malignancy, immobilisation and operations of the abdomen and pelvis are all well recognised risk factors (see Pre-operative management).

Colon cancer

Carcinoma of caecum or ascending colon

Right hemicolectomy is the standard operation (Right hemicolectomy for ascending colon cancer. (---) Resected material; RCA, right colic artery; MCA, middle colic artery; LCA, left colic artery.). The ileocolic vessels are divided at their origins while maintaining the blood supply to the residual terminal ileum. The right colic vessels and the right branch of the middle colic vessels are also removed. The amount of bowel removed is influenced by the extent of lymphovascular clearance, which, in turn, is dependent on the site of the primary colon cancer. More terminal ileum and less transverse colon may need to be removed for tumours in the caecum. Less terminal ileum and more transverse colon may be removed for cancers near the hepatic flexure.

Right hemicolectomy for ascending colon cancer. (---) Resected material; RCA, right colic artery; MCA, middle colic artery; LCA, left colic artery.

Carcinoma of transverse colon

The blood supply to this area is derived from the middle colic vessels as well as from the right and the left colic vessels. If the cancer is at the hepatic flexure end of the transverse colon, a right hemicolectomy is performed. Lesions of the mid-transverse colon are treated by extended right hemicolectomy, which entails an anastomosis between the terminal ileum and the descending colon. The omentum is removed en bloc with the tumour.

A carcinoma at the splenic flexure can spread to regional lymphatics along the middle colic and left colic arteries. Thus, a more radical operation of subtotal colectomy, which allows an easy anastomosis between the terminal ileum and the sigmoid colon, is undertaken.

Carcinoma of descending colon

Left hemicolectomy is the operation of choice (Fig. 24.5 Left hemicolectomy for descending colon cancer. (---) Resected material; IMA, inferior mesenteric artery; LCA, left colic artery.). The inferior mesenteric artery is divided at its origin and the left colic vessels, and the sigmoid vessels are included in the resection. The anastomosis is performed between the mid-transverse colon and the upper rectum.

Fig. 24.5 Left hemicolectomy for descending colon cancer. (---) Resected material; IMA, inferior mesenteric artery; LCA, left colic artery.

Carcinoma of sigmoid colon

A high anterior resection is favoured, anastomosing the mid-descending colon to the upper rectum. The inferior mesenteric artery and the left colic vessels together with the sigmoid branches are resected. If the sigmoid colon is redundant, or in a frail patient, a more limited sigmoid colectomy is performed.

Obstructing colon carcinoma

Obstructing carcinoma of the right and transverse colon usually can be treated by resection and primary anastomosis. The treatment of a left-sided obstruction is more controversial. A resection with or without a primary anastomosis is favoured. The surgical options include:

  • Hartmann's operation: The obstructing lesion is resected. The proximal colon is brought out as a left iliac fossa colostomy and the distal bowel is oversewn or stapled closed. Re-anastomosis is established 4–6 months later.
  • Subtotal colectomy and ileosigmoid or ileorectal anastomosis: This removes all the obstructed and often ischaemic colon and allows a primary anastomosis without bowel preparation. However, increased stool frequency is likely because of the more extensive resection.
  • Single-stage resection with intra-operative on-table colonic lavage and a primary colorectal anastomosis: This has good results with a clinical anastomotic leak rate of 5% but is not always possible because of oedematous bowel wall.
  • Proximal diverting stoma alone without resection. This is considered if the proximal colon is very dilated, if resection is hazardous and the patient is very unwell. Elective resection can be undertaken 2 weeks later.
  • Colonic stent can be placed endoscopically under guidance with fluoroscopy to relieve obstruction. There is a risk of colonic perforation and stent migration. A colonic stent is generally deployed in a palliative setting.

Perforated carcinoma of the colon

Perforation is less common than obstruction and is usually via the tumour as a result of tumour necrosis. The prognosis is poor and the risk of local recurrence is high. Hartmann's operation is generally performed with en bloc excision of the contained perforation. The proximal end is brought out as an end colostomy and the distal end either oversewn or brought out as a mucous fistula. A primary anastomosis is generally not performed because it is more likely to leak in the presence of sepsis. The peritoneal cavity should be lavaged with saline to reduce faecal contamination.

Rectal cancer

Management of rectal cancer is challenging because of the technical expertise and clinical judgement required. About 25% of large bowel cancers develop in the rectum. Skill and judgement comes in selecting patients for restorative anterior resection, transanal local excision, abdominoperineal resection (APR) or a palliative procedure. About 30 years ago, nearly all patients with a rectal cancer were treated by an APR of the rectum and anus with a permanent left iliac fossa end colostomy. In more recent times, APR is used in less than 10% of rectal cancers.

Factors influencing choice of operation

Level of lesion

The distance of the lower edge of the tumour from the dentate line is the most important factor in the choice of operation. As a rule, a tumour that is less than 5 cm from the dentate line requires APR. A 2 cmdistal margin is acceptable and may permit restorative resection in most cases without damaging the anal sphincter complex.

Nature of carcinoma

A high-grade, poorly differentiated tumour tends to be more widely infiltrative. This is best treated by rectal resection with a greater margin. Evidence of tumour invasion into the anal sphincters or fixation in the pelvis will contraindicate sphincter preservation procedures.

Patient factors

The age and medical fitness of the patient and the presence of metastases are important factors in deciding the magnitude of the operation. Pre-operative sphincter impairment usually precludes a restorative procedure.

Mesorectal lymph node status

Endorectal ultrasound examination will give some guidance as to the presence of lymph node metastases. Resection should be performed in the presence of lymph node metastases.

Anterior resection

Anterior resection (Anterior resection for rectal cancer. (---) Resected material; IMA, inferior mesenteric artery.) is the standard radical operation for cancers of the upper and mid-rectum. It is also used for the smaller tumours of the distal rectumwhen a 2 cmdistal margin of resection is possible without damaging the anal sphincters. The level of colorectal anastomosis may be as low as the dentate line (coloanal anastomosis).

Anterior resection for rectal cancer. (---) Resected material; IMA, inferior mesenteric artery.

The sigmoid colon and the rectum are resected. The inferior mesenteric artery and left colic artery are divided at the highest possible level to enable a tensionfree anastomosis between a well-vascularised left colon and the rectum, while ensuring an adequate resection of the lymphovascular pedicle. The mesorectum is removed as completely as possible beyond the distal line of rectal transection.

Anterior resection has a similar incidence of pelvic recurrence to APR provided a wide lateral margin and adequate distal margins are achieved. Both operative approaches deal with the proximal lymphovascular pedicle in an equivalent manner.

Anterior resection is high or low depending on whether the colorectal anastomosis is intraperitoneal or extraperitoneal. Colorectal anastomosis may be constructed by hand-sewn or stapled anastomosis ((A) Hand-sewn anastomosis. (B) Double-stapled anastomosis where the rectal stump has been occluded with a linear stapler followed by construction of a colorectal anastomosis with a circular stapler. (C) Single-stapled anastomosis using a circular stapler.).

(A) Hand-sewn anastomosis. (B) Double-stapled anastomosis where the rectal stump has been occluded with a linear stapler followed by construction of a colorectal anastomosis with a circular stapler. (C) Single-stapled anastomosis using a circular stapler.

The functional results after anterior resection are usually good but vary with the level of anastomosis. Bowel function continues to improve spontaneously for 12 to 18 months post-operatively. With a very distal anastomosis, there is a loss of rectal reservoir and impairment of the internal anal sphincter function. There may be stool frequency of 3–6 times in 24 hours, urgency and impaired continence.

With improved techniques, anastomotic leakage has become less common. Clinically significant anastomotic leaks for high anterior resection and low anterior resection are 1% and 4%, respectively. Although neither a protective defunctioning colostomy nor a pelvic drain prevents anastomotic leaks, it may abrogate generalised sepsis should anastomotic leakage occur.

Abdominoperineal resection of the rectum

Abdominoperineal resection of the rectum is now largely reserved for larger T2, T3 or poorly differentiated tumours of the distal rectum (Abdominoperineal resection of the rectum. (---) Resected material; IMA, inferior mesenteric artery.). The rectum is mobilised down to the pelvic floor through an abdominal incision. The large bowel is divided and the sigmoid colon brought out as a left iliac fossa end colostomy. A separate perianal elliptical incision is made to mobilise and deliver the anus and distal rectum. The surgery may be expedited by having the abdominal and perineal surgeons operating simultaneously.

Abdominoperineal resection of the rectum. (---) Resected material; IMA, inferior mesenteric artery.

Hartmann's operation

Hartmann's operation is an anterior resection of the rectum without an anastomosis (Hartmann's procedure for cancer of the sigmoid colon or upper rectum and sigmoid end colostomy.). The operation is usually reserved for palliation or as a preliminary procedure for acute malignant obstruction or perforation.

Hartmann's procedure for cancer of the sigmoid colon or upper rectum and sigmoid end colostomy.

Transanal local excision

Transanal local excision is considered in early-stage rectal cancers that are too distal to allow restorative resection, or when age or infirmity of the patient or presence of metastases precludes major resection. Appropriate guidelines for a curative local excision are:

  • mobile tumour located in the lower third of the rectum
  • tumour size <3 cm
  • T1 (submucosal invasion) or T2 (muscularis propria) tumour on endorectal ultrasound
  • well or moderately differentiated histology on biopsy
  • no detectable mesorectal lymph nodes clinically or by endorectal ultrasound.

Long-term surveillance is essential.

Palliative procedures

Palliative procedures include a diverting stoma, radiotherapy and chemotherapy. Local therapy includes laser therapy, electrocoagulation and cryosurgery. Severe pelvic and perineal pain may be improved by a variety of nerve block procedures.

Locally advanced colorectal carcinoma

En bloc resection of the cancer with adherent viscera and portions of the abdominal wall is performed. This reduces the risk of seeding viable tumour cells. Sometimes the adherence is inflammatory rather than neoplastic. The increased morbidity of such radical en bloc resection should be weighed against the likelihood of cure and the effect on the patient.

If vital structures such as the inferior vena cava or pancreas are involved, a palliative operation (e.g. bypass with ileocolic anastomosis) is preferred. A diverting stoma is considered if an internal bypass is not possible.

Adjuvant therapy

Patients with more bulky disease (T3, N1, N2) are at greatest risk of having microscopic residual disease. Chemotherapy, radiotherapy and immunotherapy have all been tried alone and in various combinations as adjuvant treatments after and, less often, before surgery with variable success. However, the regimens of adjuvant therapy in various trials are not uniform, further compounding the confusion.Various new protocols are in trial, but currently most centres would recommend post-operative adjuvant therapy for Dukes' C colon cancer with 6 months of 5-fluorouracil and folinic acid, and 6 months of 5-fluorouracil and pelvic radiotherapy for Dukes' C and some B2 rectal cancer. Pelvic radiotherapy may, however, adversely affect fertility, sexual and bowel function.

Combined chemotherapy and radiotherapy may be administered pre-operatively to ‘downstage’ or shrink a large T3 or T4 rectal cancer fixed to the pelvis. This is followed by a resection 6 to 8 weeks later.

Treatment of metastases

The magnitude of treatment should be weighed against any potential gain, in the relief of symptoms and the quality of remaining life. The prospect of cure to some extent justifies radical therapy of isolated metastases. The treatment options include surgery, radiotherapy, chemotherapy and drug management of symptoms (Treatment of metastases).

Liver metastases

The presence of liver metastases usually indicates incurability. Occasionally, a liver metastasis is isolated and allows liver resection, to be followed by prolonged survival. Hepatic lobectomy may be necessary if several metastases are confined to one lobe. Intra-operative ultrasonography is a useful adjunct to exclude other occult liver metastases and to define the liver anatomy.

Generally, hepatic resection is delayed until after resection of the primary colorectal cancer. Patients are carefully monitored with CT scan after 2–3 months to assess the growth of the metastasis and the development of other metastases by a positron emission tomography (PET). In a fit patient with a truly isolated liver metastasis, hepatic resection remains the mainstay of therapy. Other treatments such as radiofrequency ablation, cryosurgery and chemotherapy given systemically or via hepatic artery infusion are useful in a palliative role but are unlikely to lead to any long-term survival.

Follow-up

The need for and the intensity of follow-up is controversial. Most would agree that routine follow-up should cease after the patient reaches 75 years of age. Followup review provides reassurance for patients and allows a surgical audit of outcome. Occasionally, a structured and directed review protocol (CT scan, chest X-ray, CEA, liver function test) may detect minimal recurrent disease, which enables earlier treatment. This may improve survival and give better palliation. However, detection of minimal disease requires more than clinical examination and a proctosigmoidoscopy. As there is an increased risk of metachronous colorectal neoplasm, routine colonoscopy surveillance every 3 to 5 years is recommended.

Adenoma

Adenoma is a benign neoplasm of the large bowel that is associated with colorectal cancers. The most common variety is a tubular adenoma that is usually well differentiated and more often pedunculated (Sessile (A) and pedunculated (B) polyp.). By contrast, a villous adenoma is less differentiated and is sessile, often extending as a carpeting lesion over several centimetres. Tubulovillous adenoma lies between the two both in frequency and morphology and is polypoid with a fairly broad base or a short stalk.

Sessile (A) and pedunculated (B) polyp.

Adenoma-carcinoma sequence

Most colorectal carcinomas arise from, or within, preexisting benign adenomas. The risk of carcinoma is significant in adenomas greater than 1 cm and polypectomy should be performed. The risk of malignancy increases with the size and the histology of the adenoma. Large villous adenomas have the greatest risk (Table 29, “Relationship of adenoma to invasive carcinoma”). Carcinoma in polyps smaller than 1 cm in diameter is uncommon.

Table 29. Relationship of adenoma to invasive carcinoma
Incidence of malignancy (%)
Size Tubular Tubulovillous Villous
<1 cm 0.3 1.5 2.5
1–2 cm 4 6 6
2–3 cm 7 12 17
>3 cm 11 15 20

Clinical features

Most adenomas are silent and only diagnosed during the investigation of bowel symptoms. They may cause episodic bleeding. The bleeding is usually occult and is detected by faecal occult blood testing. Less commonly, the bleeding is copious and mixed in the faeces, especially when a large polyp partially sloughs from its pedicle. Large villous adenomas may cause urgency at stool, mucous diarrhoea and hypokalaemia from excessive loss of potassium-rich mucus.

Management

Double-contrast barium enema may reliably detect polyps 0.5 cm or more in diameter. Colonoscopy can detect smaller lesions and has the added benefit of being therapeutic as well as diagnostic. Very small adenomas are treated with biopsy cautery. Bigger polyps are snared (Endoscopic snare polypectomy during colonoscopy.). Very large, flatter polyps are snared in a piecemeal fashion.

Endoscopic snare polypectomy during colonoscopy.

Low rectal villous adenomas are treated by transanal disc excision. Larger and more proximal rectal villous adenomas may be treated with anterior resection of the rectum, especially if the patient is young.

Follow-up

The incidence of further polyps is 25% when one polyp is found initially and 50% when more than one polyp is detected. Most of these probably represent polyps that were overlooked at the initial colonoscopy. Most centres would recommend, after colonoscopic clearance of two or more polyps and of any polyp greater than 1 cm, repeat colonoscopy annually until the colon is clear of polyps, after which the intervals are increased to 3–5 years. For smaller single polyps, the first follow-up colonoscopy may be performed after 3 years.

Screening

Population screening for cancer or adenoma requires the use of a simple, non-invasive, cheap and accurate method of testing. The protocol for screening for colorectal cancer or adenoma is controversial. The following is modified from the guidelines published by the National Health and Medical Research Council.

Average risk

Average risk refers to people aged between 50 and 75 years, who have no bowel symptoms and no special risk factors. The need for screening is not clear. Options are either faecal occult blood testing and sigmoidoscopy or a full colonoscopy. The interval between screenings is uncertain but current evidence suggests that, in a well-structured screening program, 2-yearly faecal occult blood testing will reduce mortality due to colorectal cancer.

Colonoscopy is clearly the best method of diagnosing and treating the cancer precursors, adenomas. There is considerable interest in once-in-a-lifetime colonoscopy surveillance between 50 and 55 years. However, it is too invasive and expensive to be an acceptable means of screening the entire population. Its use is still limited to screening subjects at higher risk of developing colorectal cancer.

Above-average risk

Previous colorectal cancer or adenoma

A colonoscopy surveillance program that entails colonoscopy every 3 years is recommended. More frequent examinations should be made if there are large or multiple adenomas.

Chronic inflammatory bowel disease

For total or extensive ulcerative colitis, surveillance colonoscopy is started 8 years after onset of symptoms, and is carried out at 2–3-year intervals. Multiple biopsies are taken randomly throughout the colon to detect dysplasia, and from plaque-like or mass lesions. Cancer risk is not increased with distal proctosigmoiditis, and surveillance colonoscopy is not necessary.

The need for surveillance colonoscopy in Crohn's colitis is unclear but is generally similar to ulcerative colitis.

Family history of colorectal cancer: uncertain genetic basis

Colonoscopy surveillance is offered every 5 years from the age of 50 or at an age 5 years younger than the age of the earliest diagnosis of cancer in the family (whichever comes first). Faecal occult blood testing is offered annually in the intervening years.

Familial adenomatous polyposis and hereditary non-polyposis colorectal cancer (HNPCC-Lynch syndrome)

These are discussed below.

Hereditary colorectal cancer syndromes

Introduction

Polyp is a descriptive term that refers to a lump arising from an epithelial or endothelial surface. Histological types of intestinal polyps are neoplastic, hyperplastic, inflammatory, hamartomatous or lymphoid. The neoplastic polyp or adenoma is the type most commonly associated with colorectal cancer. Multiple polyps of the colon and rectum (polyposis) are usually related to an inherited predisposition of the colorectal mucosa towards abnormal growth; however, hereditary polyposis is uncommon. Of all forms of colonic polyposis, familial adenomatous polyposis (FAP) is the most common. Its association with colorectal cancer is strongest and much is known about its molecular and genetic background. Other conditions to be considered are hereditary non-polyposis colorectal cancer syndrome, juvenile polyposis and Peutz-Jeghers syndrome.

Familial adenomatous polyposis

Familial adenomatous polyposis is an autosomal dominant disorder characterised by the formation of multiple colorectal adenomas. However, spontaneous new mutations account for about 25% of new cases, so patients may present without a family history. It is a generalised growth disorder affecting 1:10 000 individuals per year. Offspring of FAP patients have a 50% chance of developing the disease. If left untreated, all FAP patients will develop colorectal carcinomas with time; FAP is responsible for 0.5% of all colorectal cancers.

Familial adenomatous polyposis registries have been instrumental in developing a knowledge of FAP and in tracing affected family members. With the help of the registries, the risk of FAP patients dying of colorectal cancer (previously the main cause of death) has been halved by appropriate prophylactic colorectal surgery.

Progressive development of hundreds of colorectal adenomas begins during the teenage years. A number of extra-colonic manifestations of FAP have been recognised: intra-abdominal desmoid tumours, osteomas, sebaceous cysts (Gardner's syndrome), pigmented ocular lesions and brain tumours (Turcot syndrome).

Diagnosis

Most affected individuals develop polyps by the age of 10 years, although there is wide variation in age of expression. Rarely, patients may present at as late as 70 years of age. There is also variation in the numbers and location of polyps. Most individuals have more than 100 colorectal adenomas with rectal involvement (Colonoscopic views of familial adenomatous polyposis.). An attenuated form of FAP with a few polyps and a frequently spared rectum has been recognised. This has a specific genotypic correlation to mutations in exons 3 and 4 and at the distal (3′) end of the gene.

Colonoscopic views of familial adenomatous polyposis.

Molecular genetics

The adenomatous polyposis coli (APC) gene is associated with FAP. The APC gene is one of the tumour suppressor genes responsible for regulation of cell growth in normal cells. Inactivation of tumour suppressor genes can result in a loss of control over cell proliferation, thus promoting neoplasia.

The APC gene is a large gene located on the long arm of chromosome 5 (5q21). Individuals affected with FAP have a germline mutation in one of the two alleles of the APC gene. It is likely that both APC alleles have to be inactivated for the development of colorectal tumorigenesis. Because FAP patients already have one inactivated allele in their cells, loss of both alleles can occur much more frequently in the colonocytes. Hence, these patients are predisposed to the development of hundreds to thousands of colonic neoplasms.

Polyposis registry

A careful genetic history and construction of family pedigrees are vital. The aim is to screen parents and children at the same time. This facilitates education and helps to allay anxieties. A FAP registry is available to facilitate this.

Surveillance strategies

Patient education relating to FAP is very important. Symptoms associated with FAP usually indicate the development of cancer. Therefore, it is crucial to diagnose the condition at a presymptomatic stage. The conventional strategy of endoscopic surveillance is giving way to the rapidly developing molecular genetic tests.

Molecular diagnosis

Presymptomatic carrier risk assessment of the offspring of FAP patients can be performed by either linkage analysis or direct mutational analysis of the APC gene.

Linkage analysis used to be the mainstay of most early diagnosis programs that assign individuals into high-risk and low-risk groups. The method depends on the presence of the microsatellite sequences that are closely associated with the APC gene and does not involve the direct characterisation of the APC mutations. The performance of linkage analysis is dependent on the availability of DNA (from blood or formalinembedded tissues) from parents and other members of the family. Linkage analysis is now rarely required because of progress in direct mutational analysis of the APC gene.

Direct mutational analysis of the APC gene is now performed as a diagnostic test for families with clinical FAP. About 85% of such families will have a mutation identified, either by the detection of a truncated APC protein in vitro (PTT) or tests seeking deletions of the APC gene that are not dependent on DNA amplification. Inactivation of APC function results in a premature signal for the end point of translation, resulting in the generation of a truncated protein product. Functional assays for APC mutation detection have been developed based on detection of the truncated protein on electrophoresis. This protein truncation test is a rapid and efficient means of obtaining de facto evidence of the presence of a causative mutation.

If a mutation is characterised in a family, other clinically unaffected members in the family can be offered predictive DNA testing for FAP. If a mutation is identified, the risk of the individual developing FAP is 100%. Those family members who tested negative on molecular genetic testing are not at risk for FAP but are still at risk for common colorectal cancers as they get older. Application of molecular technology has revolutionised the management of FAP. Presymptomatic diagnosis using molecular technology will reduce anxiety in low-risk individuals and increase compliance with regards to surveillance in high-risk patients. Considerable savings are made by avoiding multiple screening endoscopies if an individual is recognised as not carrying a mutated allele. An important application is the correlation between different mutations and the clinical severity and spectrum of disease.

Flexible sigmoidoscopy

The rectum is invariably involved with polyps in FAP, although the number of polyps in various sites in the colon and rectum varies between individuals. Flexible sigmoidoscopic examination of family members is commenced around puberty and continues to the age of 40 years at 1–2-year intervals. The presence of a rectal adenoma dictates the need for a colonoscopy to assess the numbers of polyps in the large bowel and to exclude cancer. With development of molecular genetics, a more selective endoscopic screening policy is evolving. Family members at no risk on the basis of negative molecular genetic testing for the family-specific mutation do not need special surveillance other than that appropriate for average-risk individuals from 50 years of age onwards.

Extracolonic manifestations

Osteomas

Gardner's syndrome is characterised by the presence of sebaceous cysts and osteomas, particularly of the skull and mandible. These extracolonic manifestations may precede the expression of colorectal polyps. Almost all individuals with FAP will have these manifestations if sufficiently sensitive clinical and radiological examinations are undertaken.

Desmoid tumours

Desmoid tumours can be found in about 10% of FAP patients (Computed tomography scan of an abdomen showing a large desmoid tumour occupying almost the entire peritoneal cavity.). These are fibroblastic tumours commonly affecting the abdominal wall or small bowel mesentery. They are benign because they do not metastasise but can be lethal because of aggressive local growth with pressure on the neighbouring viscera.

Computed tomography scan of an abdomen showing a large desmoid tumour occupying almost the entire peritoneal cavity.

Desmoid tumours may present as a discrete lump or more commonly as an area of thickening. Trauma of any abdominal surgery precipitates the rapid growth of desmoid tumour, which may preclude subsequent ileo- anal pouch procedures. These patients tend to have unusually dense post-operative adhesions.With reduction in mortality from colorectal cancer, desmoid tumours are now a common cause of death, usually from mesenteric strangulation.

No treatment has proven consistently efficacious for intra-abdominal desmoid tumours. Response to medical management with sulindac, a non-steroidal antiinflammatory drug, or tamoxifen is variable. Surgery is performed to deal with the complications. The recurrence rate is very high but aggressive desmoid tumours are fortunately uncommon. As a last resort, chemotherapy may be attempted (see Soft tissue tumours).

Gastroduodenal polyps

Almost all FAP patients have gastroduodenal polyps, although only 5% will develop fatal duodenal cancer. Gastric polyps are usually hamartomas (fundic gland polyps) and cause no symptoms. Duodenal polyps are usually adenomatous. Patients with FAP do not generally suffer an excess risk of gastric cancer. The risk of duodenal cancer in FAP is, however, increased to more than 100 times that of the normal population. Adenomas around the ampulla of Vater are particularly prone to development of cancer. Duodenal cancer now accounts for most cancer deaths after successful colorectal surgery for FAP.

The screening strategy for gastroduodenal polyps is not well defined. Diagnosis of periampullary adenoma requires side-viewing upper gastrointestinal endoscopy. Asymptomatic patients should have their first upper gastrointestinal endoscopy between the ages of 20 and 25 years or at the time of colorectal surgery. The presence of a large number of duodenal polyps more than 5–10 mm in size is an indication for annual surveillance. Otherwise, surveillance can be every 5 years, and more frequent after 45 years of age.

As there is no genetic marker that predicts the likelihood of progression of adenoma to cancer, the degree of dysplasia is currently the best index for potential surgical intervention. Large polyps may be treated endoscopically using laser or argon plasma coagulation, although the consequences of complications such as perforation are severe at this site. Surgery is indicated if polyps show villous change, severe dysplasia, rapid growth or induration at endoscopic probing. Radical surgery with pancreaticoduodenectomy is done in younger patients with severe duodenal polyposis. Local excision is associated with a higher recurrence rate. Sulindac is not effective for gastroduodenal polyps.

Retinal pigmentation

The overall incidence of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in patients with FAP is 80%. There appears to be an inverse relationship between the presence of CHRPE lesions and desmoid tumours. The presence of CHRPE is associated with mutations at specific locations in the APC gene. While CHRPE lesions are themselves harmless, their presence or absence will guide the search for the causative mutations in FAP families.

Surgical management

In affected individuals, the principal treatment is surgery. There are essentially two groups presenting for prophylactic colorectal surgery: screen-detected members of a known FAP family (usually in teenage years) and symptomatic individuals (mostly in their 30s). Colectomy before the age of 20 years is desirable to prevent cancer (the risk of cancer by the age of 20 years is 5%).

Total abdominal colectomy and ileorectal anastomosis

Total abdominal colectomy and ileorectal anastomosis eliminates the colonic polyps, and rectal polyps may regress after surgery. Careful surveillance of the rectal remnant by flexible sigmoidoscopy is performed every 6 months. Small polyps can safely be left but larger ones need to be removed.

Colectomy with ileorectal anastomosis has a low complication rate, good post-operative bowel function and is ideally suited to young patients. In most cases, the surgery can be performed laparoscopically. The risk of cancer in the rectum is about 15% at 15 years. Advanced-stage rectal cancer may develop insidiously despite careful surveillance by sigmoidoscopy. The risk of cancer in the retained rectum increases with age and with the number and size of polyps in the rectum. Removal of the retained rectum and conversion to ileal pouch-anal anastomosis is generally recommended in patients older than 40.

Restorative proctocolectomy and ileal pouch-anal anastomosis

Restorative proctocolectomy and ileal pouch-anal anastomosis removes the entire colon and rectum and thus eliminates the risk of colorectal cancer. Faecal continence is preserved by construction of an ileal reservoir anastomosed to the upper anal canal. The morbidity is higher than for an ileorectal anastomosis and the function is marginally worse. With improvement in surgical techniques and surgical results, pouch surgery is becoming increasingly popular as the primary prophylactic surgery for FAP, especially for individuals with mutations associated with dense rectal and colonic polyposis.

Total proctocolectomy and permanent end ileostomy

Total proctocolectomy and permanent end ileostomy is now rarely performed except in FAP patients presenting with a very low-risk rectal cancer.

Hereditary non-polyposis colorectal cancer syndrome

Hereditary non-polyposis colorectal cancer (HNPCC) is inherited in an autosomal dominant pattern. Gene carriers have a very high risk of colon cancer, with an estimated lifetime penetrance of 85%. The cardinal features are early age of colorectal cancer onset (approximately 44 years), proximal colonic cancer predilection (approximately 70%), an excess of synchronous and metachronous colorectal cancers (approximately 45% at 10 years after primary resection), and often an excess of certain extracolonic cancers (endometrial carcinoma, transitional cell carcinoma of the ureter and kidney, adenocarcinomas of the stomach, small bowel, ovary, pancreas and biliary tract). Polyposis is not a feature of HNPCC and the incidence of adenomas in HNPCC approximates that observed in the general population. The colon cancers ofHNPCChave histological features highly suggestive of the syndrome; they are more likely to be poorly differentiated and mucinous.

The clinical diagnosis of HNPCC once depended entirely on family history and was imprecise because it lacks definitive clinical features. The genes linked to HNPCC have now been defined by the genes MSH2 at chromosome 2p, MLH1 at chromosome 3p, and PMS2 at chromosome 7q, hMSH6 and TGFBRII. The critical genes on 2p, 3p and 7q are concerned with DNA mismatch repair, a proofreading function that helps ensure replication fidelity. Defective DNA mismatch repair results in a steady accumulation of mutations. The mutation load can be detected as errors in long tandem repeat sequences; that is, errors that produce microsatellite instability (MSI). Microsatellite instability is much more frequent in colorectal cancers in young HNPCC patients than in sporadic cases but the reverse is true for older patients. Microsatellite instability testing in tissue sections is frequently used as an adjunct to select families for mutational analysis, where there is doubt about HNPCC on pedigree studies. However, MSI is not specific for colon cancer and may be present in other cancers associated with HNPCC.

Management

Genetic counselling, with discussions about surveillance and management, should be extended to all available first-degree relatives of HNPCC-affected patients, starting in the late teenage years. Because of the proximal predominance of colon cancer, a colonoscopy should be given at the age of 25 years and repeated at 2-year intervals through to the age of 35 years, then annually thereafter.

In subjects who have undergone DNA testing and were found to have one of the HNPCC germline mutations, a more intensive surveillance program is initiated. Colonoscopy is started at age 20 and is repeated annually. If a patient develops colorectal cancer, abdominal colectomy and ileorectal anastomosis is recommended because of the risk for synchronous and metachronous colonic cancers. Prophylactic colectomy may be offered in patients with proven evidence of the HNPCC germline mutations.

The role of screening for endometrial and ovarian cancers in female kindreds of an HNPCC family is less certain. It entails endometrial aspiration biopsy and transvaginal ovarian ultrasound, respectively, and CA125 blood testing. Screening for ovarian cancer is particularly limited. Women presenting with colonic cancer in HNPCC (Lynch syndrome II) families and who have completed their families, should be considered for prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy at the same time as their abdominal colectomy.

Hamartomatous polyposis

A hamartoma is the result of disordered differentiation during embryonic development and is a disorganised caricature of normal tissue components. Common variants include juvenile polyposis and Peutz-Jeghers syndrome.

Juvenile polyposis

The juvenile polyp is the most common large bowel polyp observed in children. It is usually pedunculated and has a smooth surface with a distinctive cherry-red appearance. The long-term risk of developing colorectal cancer is probably similar to that in the general population, although adenomatous and carcinomatous change may develop.

In juvenile polyposis, multiple (more than five) juvenile polyps occur in the colon, rectum and even in the small bowel and stomach. The disease is inherited in an autosomal dominant pattern, although in some individuals the pattern of inheritance is not obvious. Juvenile polyps, particularly those located in the rectum, are prone to prolapse and trauma and often present with rectal bleeding. Auto-amputation of the pedunculated juvenile polyps may occur.

Endoscopic polypectomy will remove isolated and smaller juvenile polyps. Continued colonoscopic surveillance at 3-year intervals is performed. When the polyps are too many or too large for endoscopic therapy, abdominal colectomy with ileorectal anastomosis is performed. The rectal polyps can be treated through an operating sigmoidoscope. Firstdegree relatives of patients with juvenile polyposis are screened with colonoscopy, starting in the early teenage years.

Peutz-Jeghers syndrome

This is an autosomal dominant, inherited condition in which dozens of polyps (usually less than 100) occur throughout the stomach, small bowel, colon and rectum. They arise from glandular epithelium on a branching muscular framework. These polyps may be quite large, up to 4 cm in diameter, and may be sessile or pedunculated. Symptoms usually occur in the third decade of life. Clinical presentations include:

  • small bowel intussusception from small bowel polyp, causing colicky abdominal pain and bowel obstruction
  • rectal bleeding from colorectal polyps
  • prolapsing rectal polyps
  • melanin deposition in the mouth, around the lips, on the eyelids and fingers.

There are associations with gastric, small bowel and colorectal cancer. The estimated frequency of gastrointestinal cancer is 2%. Neoplastic transformation may occur in the hamartomatous polyps or from adenomas occurring synchronously. There are also lesser associations with cancers of the cervix, endometrium, ovary, breast and pancreas.

Management of Peutz-Jehgers syndrome is symptomatic. If endoscopic polypectomy is not possible, removal via laparotomy is required. Small bowel polyps need to be removed at laparotomy. Intra-operative endoscopy is an important part of the surgery. Because the hamartomatous polyps are present diffusely throughout the gastrointestinal tract, prophylactic colectomy is not recommended.

Surveillance colonoscopy and gastroduodenoscopy should be performed at intervals determined by the rate of formation of polyps. Regular abdominal and pelvic examination, breast examination and Papanicolaou (PAP) smear should also be performed.

Further reading

Ooi BS, Tjandra JJ, Green M. Morbidity of adjuvant chemotherapy and radiotherapy for resectable rectal cancer. Dis Colon Rectum. 1999;42:403–418.

Gibbs P, Chao MW, Tjandra JJ. Optimizing the outcome for patients with rectal cancer. Dis Colon Rectum. 2003;46:389–402.

Sengupta S, Tjandra JJ. Transanal excision of rectal cancer: what is the evidence ? Dis Colon Rectum. 2001;44:1345–1361.

Prichard PJ, Tjandra JJ. Colorectal cancer. Med J Aust. 1998;169:493–498.

Tjandra JJ. Surgical management of the locally advanced pelvic malignancy - the colorectal surgeon's view. Ann Acad Med Singapore 1995;24:271–276.

NHMRC. NHMRC Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer (CRC). Commonwealth of Australia; 1999.

Tjandra JJ, Fazio VW, Church JM, et al. Functional results after restorative proctocolectomy are similar in patients with familial adenomatous polyposis and mucosal ulcerative colitis. Am J Surg. 1993;165:322–325.

Morpurgo E, Vitale GC, Galandiuk S, Kimberling J, Ziegler C, Polk HC Jr. Clinical characteristics of familial adenomatous polyposis and management of duodenal adenomas. J Gastrointest Surg. 2004 Jul-Aug;8(5):559–564.

Jass JR. Diagnosis of hereditary non-polyposis colorectal cancer (HNPCC). Gut. 2004 Jul;53(7):1055.

Church J, Kiringoda R, LaGuardia L. Inherited colorectal cancer registries in the United States. DisColon Rectum. 2004 May;47(5):674–678. E-pub 2004 Mar 25.
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