Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

COLON AND RECTUM

of a colon carcinoma. Other rarer associations include pericarditis caused by Bacteroides fragilis, an anaerobic colon organism, and Clostridium septicum gas gangrene. Liver metastases may become infected. A rare primary colon carcinoma, however, manifests as a primary liver abscess without liver metastases.

A migratory thrombophlebitis precedes some gastrointestinal malignancies, including colon cancer. An occasional necrotizing vasculitis serves the same purpose. The Leser-Trelat sign consists of an association of multiple seborrheic keratoses with an internal malignancy; several colorectal cancers have been reported as a component of the Leser-Trelat sign. A rare association was increasing body hair growth (hypertrichosis lanuginosa) before a rectal cancer was discovered (109).

Genetics

One definition of hereditary nonpolyposis colorectal cancer is that at least three relatives should be affected, one is a first-degree relative of the other two, and that at least two successive generations be involved. An autosomaldominant inheritance is evident for these hereditary cancers, and they are characterized by early age of onset, the predominance of rightsided lesions, and an increased prevalence of synchronous and metachronous neoplasms. Two subtypes of this syndrome are described:

Lynch syndrome I: cancers limited to the colon and rectum

Lynch syndrome II: similar, but extracolonic cancers also involve the endometrium, ovaries, and stomach

The true prevalence of hereditary nonpolyposis colorectal cancer is debated. About 1% to 2% of patients with colorectal cancer fit a definition of hereditary nonpolyposis colorectal cancer syndrome, although considerable geographic variation in the prevalence of this syndrome exists. Because of the high worldwide prevalence of colorectal cancer, this is one of the more common if not the most common inherited neoplasm currently known. The cumulative risk of colorectal cancer for relatives of patients with a colorectal cancer at or under 45 years begins rising at age 40 years, reaching 5% at age 50 and 10% at age 70 years. The lifetime risk of colorectal cancer among

members of families with pathogenic mutations at some of these gene carriers is up to 80%; the risk of nongastrointestinal cancers is also increased for some of these gene carriers. Thus, is an upper urinary tract tumor in a patient with a hereditary nonpolyposis colorectal cancer due to a genetic abnormality or due to chance (110)?

At least five genes have been identified as sites of germline mutations associated with hereditary nonpolyposis colorectal cancer syndrome. Considerable data point to the p53 gene playing a role in colorectal carcinoma development. Among adenomas, 8% of those containing low-grade dysplasia were p53 positive compared to 73% of those containing highgrade dysplasia, suggesting a role for the p53 gene in the transition between adenoma and carcinoma (111), and the observed increase of p53 expression supports an adenoma– carcinoma sequence. Expression of p53 in nonpolypoid carcinomas argues for another carcinogenesis pathway.

A large Dutch cancer registry found the relative risk of brain tumors in hereditary colorectal cancer patients and their firstdegree relatives to be six times greater than that in the general population (112). The relative lifetime risk for these patients is low, and the authors do not recommend screening for brain tumors.

Associated Conditions

Does a colon polypectomy predict future colorectal cancer occurrence? A Milan colonoscopic polypectomy study of over 1000 patients with adenomatous polyps identified the presence of multiple adenomas and high-grade dysplasia as significant predictors of future cancer (113); presumably this subgroup of patients benefits from increased surveillance.

Prior studies have suggested an association between gallstones (or cholecystectomy) and risk of colon cancer; but more recent prospective studies fail to support this association. The same conclusions have been reached for previous gastric surgery for peptic ulcer disease.

A threeto eightfold increased risk for colon adenomas and carcinomas exists in patients with acromegaly. Patient with acromegaly also develop gastric cancer, pancreatic mucinous cystic tumors and other tumors; the known

tumorigenesis of elevated growth hormone and insulin-like growth factor levels appear to be responsible for these neoplasms.

An increased risk of colon cancer probably exists in patients with a Barrett’s esophagus. An association is also suggested with ZollingerEllison syndrome with its hypergastrinemia; a significant number of patients with colon carcinoma have increased serum gastrin levels.

Synchronous Cancers

An increased prevalence of synchronous colorectal cancers has long been known. A multiinstitutional database of 4878 colon cancer patients recorded 3.3% having synchronous tumors (114); of these, 8% had more than two tumors at the time of diagnosis. An occasional patient with multiple synchronous colonic adenocarcinomas is reported (115). Considering the highest stage synchronous tumor, survival appears to be the same as for patients with a single colonic tumor (114).

Once one colorectal cancer is diagnosed, the need to study the remaining colon is known to most clinicians (Fig. 5.20). Yet, in spite of this, some patients still undergo cancer resection without preoperative study for synchronous lesions.

A rare patient develops a synchronous colorectal carcinoma and lymphoma, including Hodgkin’s disease; this association appears to be fortuitous.

Metachronous Cancers

The definition of metachronous cancer varies. Most authors use this term to describe a second separate cancer, while some also include intraluminal recurrences, arguing that a pathologist cannot readily differentiate recurrences from a new focus of adenocarcinoma.

Metachronous colorectal neoplasms consist of adenomas and carcinomas, related through the adenoma-carcinoma cycle (Fig. 5.21). Patient who have one colorectal cancer resected are at increased risk of developing a second cancer (metachronous cancer). Overall, the prevalence of metachronous cancers ranges from 1% to 5%, but the prevalence of metachronous adenomas is considerably higher. Adenoma surveillance reduces the risk of

ADVANCED IMAGING OF THE ABDOMEN

metachronous colon cancers. Patients with a synchronous adenoma or carcinoma discovered at initial presentation are at significantly higher risk for metachronous adenomas and carcinomas, compared to those without a synchronous tumor.

The interval between first and second cancers ranges from months up to a decade or more. Carcinoembryonic antigen (CEA) levels do not aid in detecting a second cancer.

Screening

Why screen? To a large extent, colorectal cancer screening consists of detecting adenomas, with a reduction of colon cancer mortality achieved by resecting these precancerous adenomas. Among colorectal cancers detected by screening asymptomatic individuals at one Japanese institution, 61% were either stage 0 or stage I; among comparable symptomatic patients only 16% had tumors of these early stages (116).

Controversy exists about the size of adenomas that require resection. Should severalmillimeter adenomas found at colonoscopy be resected? Also, what is the chance of a malignancy being present in a small colonic polyp (Fig. 5.22)? Histology of polyps not detected by a CT colonography study revealed that 58% of those 5 mm or smaller were not adenomas and 43% of those 6–9mm were not adenomas (117). An analysis of over 11,000 adenomas detected during colonoscopy at the Erlangen Registry of Colorectal Polyps detected no invasive carcinoma in adenomas <5mm (118); the malignancy rate for larger adenomas not only showed a right-sided shift but also the rate was significantly modified by histology, the presence of synchronous lesions, and other factors.

A Japanese study of sessile colonic adenomas <5mm followed these polyps for an average of 24 months (119); none developed carcinomatous transformation. The authors concluded that polypectomy of these small lesions is not necessary, and they can be followed either radiologically or endoscopically.

Colorectal cancer screening has become prevalent in the Western world. A survey for occult blood, flexible sigmoidoscopy, colonoscopy, and barium enema are the screening modalities used. The role of CT colonography as a routine screening examination is still evolving. Still, only a minority of colorectal

Figure 5.21. Metachronous colon carcinoma. A barium enema performed through a descending colostomy identifies a right colon cancer (arrow). The patient had had a previous rectal carcinoma resected.

four years does not appear to affect over-all risk of developing a new adenoma. Even if a more protracted study leads to a slight increased risk of new neoplasms, this risk should be counterbalanced by the fewer examinations necessary and thus presumably decreased over-all colonoscopic complication rate. In general, in averagerisk individuals the interval between screening examinations can be expanded beyond 5 years, provided the initial examination does not detect a neoplasm.

Assuming a compliance of 60% with initial screening, a hypothetical study of 50-year-old white individuals at average risk for colorectal cancer found the most effective strategy to be annual fecal occult blood testing plus sigmoidoscopy every 5 years starting at age 50 years, followed by colonoscopy if a polyp is detected (121); such a scenario achieved an 80% reduction in colorectal cancer mortality compared with no screening. If, on the other hand, screening compliance is assumed to be 100%, the study concluded that screening more often than every 10 years was prohibitively expensive. Similar to other modeling studies, the optimal recommen-

ADVANCED IMAGING OF THE ABDOMEN

dations suggested depend on the initial assumptions used.

First degree relatives of colorectal cancer patients are at increased risk for adenomas and cancers. A French case-control colonoscopic screening study of first-degree relatives of colorectal cancer patients (i.e., those of moderate risk) found an odds ratio of 1.5 for adenomas, including an odds ratio of 2.6 for high-risk adenomas (≥1cm in size or containing a villous component) (122); the prevalence of high-risk adenomas in relatives was higher when the index patient was younger than 65 years, was male, and had a distal rather than proximal cancer.

The above discussion involves mostly conventional colonoscopy; a double-contrast barium enema was not considered as an alternative. Barium enema sensitivity for detecting a carcinoma or larger adenoma is 85% to 95%. Several studies have concluded that a doublecontrast barium enema is cost-effective for colorectal cancer screening. Using published estimates of cost and effectiveness of colorectal cancer screening of a double-contrast barium

Figure 5.22. A 15-mm sigmoid adenocarcinoma (arrow) detected on a screening barium enema. Initial colonoscopy could not detect this tumor, probably because of extensive colon redundancy. The patient eventually underwent sigmoid resection.

COLON AND RECTUM

enema performed every 3 years (or every 5 years with annual fecal occult blood testing), an incremental cost-effectiveness ratio of <$55,600 per life-year saved was achieved, compared to colonoscopic screening with a costeffectiveness ratio of >$100,000 per life-year saved (123).

Women with previous breast, endometrial, or ovarian cancer are at increased risk of developing a colorectal cancer. Should women with these cancers undergo preoperative barium enema or colonoscopic screening? Reccomendations vary, because risk of colon adenomas and carcinomas is low. A typical one is that in otherwise asymptomatic women under 50 years of age no colon screening is necessary, but in those over age 70 years such screening is recommended.

A double-contrast barium enema is associated with a perforation rate of about 1/25,000, which is less than one tenth that of colonoscopy.

Pathology

Normally proliferating cells are located in colonic crypt bases, on the other hand, transforming growth factor-b (TGF-b) immunoreactive and apoptotic cells are close to the surface, corresponding to normal migration of colonocytes. Distribution of proliferating and TGF-b immunoreactive cells is reversed in adenomatous polyps, suggesting that cell migration in adenomas is not toward the lumen but inward.

Traditionally, development of colorectal carcinomas was ascribed to an adenoma-to- carcinoma transformation sequence. This concept was modified when it was realized that some small adenomas also have a malignant potential, albeit small, and was modified further when flat carcinomas were detected developing de novo from polyp-free mucosa. These flat (also called depressed) carcinomas appear to arise from a different precursor and suggest a different pathway for their carcinogenesis than the adenoma-to-carcinoma cycle. Finally, molecular biology enters the picture by showing a lack of K-ras mutations in carcinogenesis of flat colonic carcinomas.A multipotential stem cell is probably located within the mucosa. The presence of neuroendocrine or squamous differentiation in some colorectal carcinomas argues that such differentiation evolves in several directions; such differentiation is more common in

the midgut portion of the colon as compared to the hindgut. In general, the presence of neuroendocrine differentiation is associated with a poor prognosis.

Superficial spreading intramucosal tumors (defined as epithelial tumors >30mm in diameter), consist of both adenomas and carcinomas and tend to be located in the cecum and rectum; most superficial spreading carcinomas have an adenomatous component and consist of a low-grade carcinoma. Thus most superficial spreading tumors develop initially as an adenoma.

One uncommon histologic subtype is a signet ring cell carcinoma. These tumors tend to infiltrate readily, and some even have a scirrhous or linitis plastica appearance. They occur in younger patients; patient survival is shorter than with more typical adenocarcinomas.

A clear cell adenocarcinoma, similar to renal clear cell adenocarcinomas, also develops on rare occasions in the colon.

A rare colon adenocarcinoma <10mm in size infiltrates the submucosa or invades the submucosal lymphatics or blood vessels. These lesions typically have a polypoid appearance, although an occasional one is flat. An rare early colonic cancer will metastasize to the liver (124).

Proximal and distal colon cancers have different clinical presentations, differ in prognosis, and have different epidemiologic aspects. A study of DNA ploidy and overexpression of nuclear p53 found proximal tumors to be more often diploid than distal ones and distal tumors to have more p53 overexpression than proximal ones, suggesting a different carcinogenesis for these tumors (125). Some investigators believe these cancers should be considered different tumors.

Some colorectal adenocarcinomas are associated with considerable mucin production. Different properties between mucinous and nonmucinous colorectal carcinomas suggest different carcinogenic pathways.

A colorectal carcinoma occasionally calcifies. Most of these are mucinous adenocarcinomas. Distinctly unusual, however, is heterotopic bone formation.

Although imaging and colonoscopy can suggest that a particular lesion is a carcinoma, the final diagnosis is established by a pathologist from either a biopsy or a surgically resected bowel. Whether a pre-resection biopsy should