Colon Cancer


1.

At least three relatives with histopathologically verified colorectal cancer; one must be a first-degree relative of the other

2.

At least two successive generations affected

3.

At least one of the relatives with colorectal cancer diagnosed at less than 50 years of age

4.

Familial adenomatous polyposis has been excluded




Table 25.2
Revised Bethesda guidelines
























Tumors from individuals should be tested for MSI in the following situations

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 the MSI-H histology diagnosed in a patient who is less than 60 years of age

4.

Colorectal cancer diagnosed in one or more first-degree relatives with an HNPCC-related tumor, with one of the cancers being diagnosed under the age of 50 years

5.

Colorectal cancer diagnosed in two or more first- or second-degree relatives with HNPCC-related tumors, regardless of age


General tumor risk in patients with HNPCC is considered to be 80–90 %, with colorectal cancer being the most common (at a median age of 44 years; uncommon before 25 years). The second most common cancer in patients with HNPCC is endometrial carcinoma; lifetime risk is 40–60 % at a median age between 46 and 48 years. Ovarian cancer occurs in 10–15 %; gastric cancer, mostly the intestinal tumor type, in 2–13 %; and small-bowel cancer in 1–4 % (around one-third occur in the duodenum). The relative risk for urothelial cancer in men with a mutation in the MMR germ line is 4.2; for women it is 2.2-fold higher.

Performing additional molecular (pathologic) diagnostics regarding HNPCC is recommended in every person fulfilling one Bethesda criterion. Diagnostic evaluation should include immunohistochemical staining of MMR protein expression and analysis of MSI.



25.4.2.5 Hamartomous Polyposis Syndrome


Peutz-Jeghers syndrome and juvenile polyposis coli (familial juvenile polyposis) are rare hamartomatous polyposis syndromes. Peutz-Jeghers syndrome is an autosomal-dominant germ-line mutation of the STK11/LKB1 gene. The cumulative lifetime risk for malignant tumors reaches 90 %; the risk for colorectal cancer is 39 % and is mostly commonly diagnosed at an age of 30–50 years.


25.4.2.6 Chronic Inflammatory Bowel Disease


Colorectal cancer risk is increased in patients with ulcerative colitis and is dependent on the manifestations, extent, and duration of the disease. The cumulative lifetime risk of developing cancer in patients with pancolitis is 2 % after 10 years, 9 % after 20 years, and 18 % after 30 years.

Crohn’s disease is also associated with an increased risk for colorectal and small-bowel cancers, although it is less well defined. A 3.5- to 7-fold increase is suggested, specifically when the colon is involved in Crohn’s disease.




25.5 Diagnosis


Colorectal cancer is diagnosed either as a result of a screening program or when a patient becomes symptomatic. Early colorectal cancer is often asymptomatic (especially if located in the right hemicolon) or presents with nonspecific symptoms; thus screening programs for early detection are of major importance. Since the late 1950s, a gradual shift toward right-sided or proximal colon cancers has been observed.


25.5.1 Screening in the Healthy Population


Screening for colorectal cancer aims for early detection and the removal of precancerous lesions in sporadic colorectal cancer developing in patients older than 50 years. Complete flexible colonoscopy is the gold standard in early detection of colorectal neoplasias. It shows the highest sensitivity and specificity. Two case-control studies demonstrated a 66–90 % reduction in colorectal cancer incidence by flexible colonoscopy. Negative colonoscopy should be repeated after a period of 10 years.

The protective effect of flexible sigmoidoscopy for distal neoplasms seems to last 6–10 years. However, a study of nearly 10,000 patients showed a 0.8 % detection rate for distal adenomas or carcinomas 3 years after negative sigmoidoscopy. The recommend control interval for sigmoidoscopy without pathological findings is 5 years.

The second recommended screening method is fecal occult blood testing (FOBT). The sensitivity of FOBT for confirmed colorectal cancer is 50 % and for polyps is around 10 %. The predictive value of a positive test averages 10 % for cancer. Any (single) positive test result must be followed by complete flexible colonoscopy. The efficacy of FOBT was demonstrated in four large, randomized trials in which colorectal cancer mortality was reduced by 25 % in individuals participating in an annual screening program. Biennial testing is less effective. FOBT is unnecessary in individuals participating in an regular colonoscopy screening program.

Randomized trials have demonstrated that some immunologic FOBTs are superior regarding the detection rate of advanced neoplasias compared with guaiac FOBT. The studies show some immunologic FOBTs (e.g., OC-Sensor) afford the same specificity (>90 %) but higher sensitivity.

The Advisory Committee on Cancer Prevention in the European Union suggested in 1999 that screening programs for colorectal cancer should use FOBT. Colonoscopy should be used to follow-up on positive findings. Screening should be offered to men and women aged 50 to approximately 74 years, with an interval of 1–2 years.


25.5.2 Screening in Populations at Increased Risk


Persons with increased risk for colorectal cancer due to certain predispositions comprise the following three groups:



  • Increased family risk (genetic background unknown)


  • Proven or potential risk of hereditary colorectal cancer


  • Presence of chronic inflammatory bowel disease

First-degree relatives of patients with colorectal cancer are at increased risk of developing colorectal cancer. If an index patient older than 60 years develops cancer, the risk of developing cancer is only minimally increased for his or her relatives.

In patients with a family history of colorectal cancer or adenomatous polyps, advise screening colonoscopy beginning at age 40 years or 10 years younger than the youngest age at the diagnosis in the family. Screening should be repeated at 5-year intervals. This protocol should followed in two groups of patients:



  • Persons with a first-degree relative (parent, sibling, or child) with colon cancer or adenomatous polyps diagnosed at an age ≤60 years


  • Persons with two first-degree relatives diagnosed with colorectal cancer at any age

These screening recommendations must be considered provisional, as mortality-reduction studies are not yet available.

Colorectal cancer mortality is lower in patients with FAP who have been screened than in those who present with symptoms. Genetic testing should be performed at age 10 years; if a genetic mutation can be excluded, no further special screening is required. Annual colonoscopy from age 10–12 years should be advised in:



  • Persons with a genetic diagnosis of FAP


  • Persons with a risk of FAP in whom genetic testing has not been performed and/or a mutation cannot be excluded

In patients with attenuated FAP, treatment should be based on age, the number of polyps, and the histopathological findings. Colonoscopy should be performed annually throughout the patient’s life if colectomy is not indicated. In persons from a family with attenuated FAP, the first colonoscopy should be at age 15 years; if there are no findings, the next colonoscopy should be performed in 5 years. From age 20 years, colonoscopy is recommend annually.

Colonoscopy can reduce risk and mortality from colorectal cancer in families fulfilling the Amsterdam criteria for HNPCC. Genetic testing for HNPCC should be offered to first-degree relatives of persons with a known inherited MMR gene mutation. Among persons with a genetic or clinical diagnosis of HNPCC, yearly or biennial colonoscopy should start at age 20–25 years or 10 years earlier than the youngest age at diagnosis of colorectal cancer in the family.

In asymptomatic biallelic MUTYH mutation carriers, colonoscopy is recommended at age 18–20 years. If there are no polyps these patients should undergo lifetime surveillance. In patients with MAP, colonoscopy should be performed annually.

History of Adenomatous Polyps (see Chap. 8.1)

In patients with a history of colorectal cancer, if synchronous neoplasm is excluded at the time of resection with curative intent, subsequent colonoscopy should be performed 2 and 5 years after surgery and every 5 years thereafter.

Colonoscopy with systematic four-quadrant biopsies at 10-cm intervals should be performed in patients with inflammatory bowel disease/ulcerative colitis presenting as long-standing pancolitis (>8 years) or left-sided inflammatory colitis (>15 years). If intraepithelial neoplasia is detected and confirmed, colectomy is indicated. No general recommendation can be given for patients with Crohn’s disease.

No randomized controlled trials have studied surveillance colonoscopy in patients with ulcerative colitis or Crohn’s colitis. A meta-analysis of case-control studies showed a reduction in the risk of colorectal cancer mortality in patients with ulcerative colitis following a surveillance program.


25.5.3 Symptoms


The majority of patients present with alteration in bowel habit, frank rectal bleeding, or anemia as a result of occult bleeding. Symptoms such as intermittent abdominal pain, nausea, and vomiting are often secondary to partial obstruction or peritoneal dissemination. Patients may occasionally notice a palpable mass, which is more common in right-sided colon cancer.

Intestinal obstruction is most commonly associated with cancer of the sigmoid colon. This may lead to acute colonic perforation if the ileocecal valve is competent. If the valve is incompetent, presentation is less dramatic, with increasing constipation and abdominal distension noticed over many days, ending in a typical symptomatic ileus.

Perforation of colon cancer may be acute or chronic. It may occur at the site of the tumor or more proximal in the distended part of the colon. Perforation may extend into the retroperitoneum, bladder, or genital tract, with fistula formation.


25.5.4 Diagnostic Strategies


Diagnosis is established by colonoscopy and biopsy. The precise location of the neoplasm must be documented and the base of any suspicious polyp tattooed at the time of snare excision. Careful clinical examination for regional lymphatic and distant metastatic disease should be performed.

To exclude liver metastasis, ultrasonography or multislice computed tomography (CT) are the imaging techniques with highest sensitivity (63–86 % and 75–83 %, respectively) and best specificity (98 % and 98 %, respectively). CT has advantages in assigning metastases to anatomic structures such as liver veins, hilar vessels, and the caval vein, which is necessary to estimate resectability. However, magnetic resonance imaging is the optimal tool to evaluate the extent of liver metastasis. To exclude synchronous malignancies, the entire large bowel should be examined if the lumen is not obstructed. If colonoscopy is not possible or complementary information is required, virtual colonography (based on CT or magnetic resonance tomography) or radiography with water-soluble contrast (if there is a risk of perforation) is mandatory.


25.6 Differential Diagnosis


The most common differential diagnoses are:



  • Diverticular disease with stenosis or phlegmon


  • Inflammatory bowel disease


  • Colonic ischemia


  • Infection


  • Other malignancies


25.7 Staging


Clinical staging aims to determine the local and distant extent of the disease according to the clinical TNM system (see Chap. 23). Staging requires local assessment of the tumor and screening for metastatic disease. The clinical classification, cTNM, is the basis for clinical decision making and determines the therapeutic algorithm.


25.7.1 Clinical Staging


History, including family history (Amsterdam and Bethesda criteria)

Physical examination


25.7.2 Investigations






  • Colonoscopy


  • Chest radiography


  • CT of the abdomen and pelvis


  • Positron emission tomography, which is indicated in the following scenarios:



    • Candidates for resection of isolated colorectal cancer metastases to prevent unnecessary laparotomy


    • Restaging of possible local recurrence or metastatic disease


25.7.3 Laboratory Testing


Elevated levels of serum carcinoembryonic antigen (CEA) that do not normalize after surgical resection imply persistent disease and the need for further evaluation. A postoperative increase in CEA during follow-up indicates a potential recurrence. A liver chemistry panel should also be performed.


25.8 Treatment


Primary treatment for colon cancer is surgical resection of the primary tumor and lymph nodes. Open and laparoscopic approaches are equally safe in experienced hands. The term curative resection (R0) should be used when there is histological confirmation of complete excision without residual tumor.


25.8.1 Curative Intent



25.8.1.1 Operative Intervention


Any operative intervention should start with intraoperative staging by inspection and palpation of the liver. As long as a sufficient preoperative diagnostic test (magnetic resonance imaging, CT) is performed, intraoperatively only subserosal metastases (>2 mm) may additionally be detected (by palpation and inspection). In addition, intraoperative liver sonography provides high sensitivity and has a very high positive predictive value (−100 %).

Operative intervention aims to achieve a curative resection. If adjacent organs are involved, en bloc resection is indicated. In colon cancer (unlike rectal cancer), the need for a radical approach has not been proved in prospective randomized trials. However, based on histopathological results, prospective observational studies, and theoretical concepts, surgeons performing colon cancer resections should adhere to the following principles of radicality:

Oct 30, 2017 | Posted by in ABDOMINAL MEDICINE | Comments Off on Colon Cancer
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