Colorectal Cancer _ ___________________________________________________________________________
Prophylactic surgery is an alternative to annual colorectal cancer and endometrial cancer screening. The high risk of developing metachronous lesions is the basis for prophylactic surgery [103]. The incidence of metachronous colorectal cancers has been reported to be 16% at 10 years, 41% at 20 years, and 63% at 30 years following segmental colectomy [104]. With the increased incidence of synchronous and metachronous neoplasms, the treatment of choice for a patient with Lynch syndrome with neoplastic lesions in the colon is generally an extended colectomy. The results of a follow-up study help in the selection of surgical approach. In this trial, 382 MMR mutation carriers were followed over time after surgery. During follow-up, metachronous colorectal cancer developed in no patient receiving total or subtotal colectomy compared with 22% of patients receiving segmental colectomy [105; 106]. An important factor in the decision to offer prophylactic surgery is the ability of the patient to comply with surveillance examinations. Consideration of total or subtotal colectomy should be balanced with patient comorbidities, clinical stage of the disease, patient wishes, and surgical expertise. One retrospective study examined data collected on 242 patients with Lynch syndrome who underwent surgery for a first colon cancer between 1984 and 2009 [107]. Patients underwent either standard segmental colectomy or extended colectomy. Primary outcomes measured were risk of subsequent colorectal cancer, overall and disease-specific survival, and operative mortality. One patient died of postoperative septicemia within 30 days after segmental colectomy. Subtotal colectomy decreased the risk of subsequent colorectal cancer compared with segmental resection. The cumulative risk of subsequent colorectal cancer was 20% in 10 years and 47% within 25 years after standard resection, and 4% and 9% after extended surgery, respectively. However, disease-specific and overall survival within 25 years did not differ significantly between the standard and extended surgery groups (82.7% vs. 87.2%) [107]. Although no data have been published showing a survival advantage in extended versus segmental resection for patients with Lynch syndrome, clinicians might consider extensive colectomy to prevent subsequent colorectal cancer in patients with Lynch syndrome [108]. Also, subtotal or total colectomy does not eliminate rectal cancer risk, and the risk of developing rectal cancer following abdominal colectomy is estimated at 12% at 12 years post-surgery [104; 109]. Familial Adenomatous Polyposis FAP accounts for 1% of all colorectal cancers and involves germline mutations in the tumor suppressor gene APC [90; 96]. Ashkenazi Jews have elevated risk of colorectal cancer due to APC gene mutation, which occurs in 6% to 7% of this population [110]. Other FAP disorder variants include [90; 96]: • Attenuated FAP: APC gene • Turcot syndrome: APC gene, MMR genes • Hyperplastic polyposis syndrome: BRAF and KRAS2 genes • MYH -associated polyposis: MYH gene
Genetic diagnosis of FAP in pre-symptomatic patients is performed with linkage or direct detection of APC mutations by analyzing lymphocyte DNA in a blood sample. Linkage analysis tests blood samples from multiple persons to identify gene carriers in close and ancillary family members [90; 96; 103]. Clinical Features . FAP is caused by parental transmission of mutation in the APC gene, a tumor suppressor or gatekeeper gene that controls cell proliferation. The most common FAP phenotype is development of hundreds to thousands of colorectal polyps, with usual onset during adolescence or early adulthood. Malignancy develops in one or more polyps as early as 20 years of age, and colorectal cancer develops in almost 100% of patients by 40 years of age if the colon is not removed for primary prevention. Other characteristics of FAP can include polyps in the upper gastrointestinal tract; extracolonic manifestations, such as congenital hypertrophy of retinal pigment epithelium, osteomas and epidermoid cysts, supernumerary teeth, and desmoid formation; and other malignancies, such as thyroid tumors, small bowel cancer, hepatoblastoma, and brain tumors (particularly medulloblastoma) [90; 96; 103]. The lifetime risk of extracolonic tumor development in FAP is [89]: • Desmoid: 15% • Duodenum: 5% to 12% • Thyroid: 2% • Brain: 2% • Ampullary: 1.7% • Pancreas: 1.7% • Hepatoblastoma: 1.6% • Gastric: 0.6% Diagnosis . The clinical diagnostic criteria of FAP is a patient with 10 to 99 adenomatous colon polyps diagnosed by 40 years of age, or more than 100 polyps diagnosed at an older age than expected [89]. Surveillance . The recommended age at which surveillance for polyposis should begin involves a trade-off. On one hand, a patient who waits until the late teens to begin surveillance faces a remote possibility that a cancer will have developed at an earlier age. Although it is rare, colorectal cancer can develop in a teenager who carries an APC mutation. On the other hand, it is preferable to allow people at risk to develop emotionally before they are faced with a major surgical decision regarding the timing of colectomy. Therefore, surveillance is usually begun in the early teenage years (10 to 15 years of age) [111]. Surveillance has consisted of either flexible sigmoidoscopy or colonoscopy (preferred) every year. If flexible sigmoidoscopy is utilized and polyps are found, colonoscopy should be performed. Historically, sigmoidoscopy may have been a reasonable approach at the time in identifying early adenomas in a majority of the patients [112]. However, colonoscopy should be considered the tool of choice in light of improved instrumentation for full colonoscopy, safer and deeper sedation
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