Radical surgery with curative intent is the treatment of choice in the majority of colorectal cancers. The basic surgical principles are removal of the major vascular pedicle feeding the tumor along with its lymphatics, obtaining a tumor-free margin, and en bloc resection of any organs or structures attached to the tumor. True colonic mucosal recurrences are rare. More common are para-anastomotic recurrences reflecting possibly an inadequate lymphadenectomy. In colon cancer, it is recommended that at least a 5 cm margin of normal bowel be obtained on either side of the tumor in order to minimize the possibility of a local recurrence. For right-sided tumors, the length of ileum apparently does not influence the local recurrence rate. In rectal cancer surgery, retrospective studies have demonstrated that inadvertent perforation at the time of surgery occurs in approximately 7 to 25% of the cases and statistically reduces survival and increases local recurrence.
Curative resections in rectal cancer may require a permanent colostomy. As technology has advanced, so have the efforts to preserve sphincter function without compromising cure. A distal surgical margin of at least 2 cm in the fresh specimen is desired in rectal cancer resections. Rarely, rectal adenocarcinomas will have distal submucosal spread.
In patients with distal rectal adenocarcinomas at least a 1 cm margin of resection is desirable. Some authors have reported margins less than 1 cm in patients who received neoadjuvant chemoradiation and underwent sphincter saving procedures without compromising either recurrence or disease-free survival.
Performance of an adequate lymphadenectomy cannot be overemphasized. Adequate lymph node resection is imperative for staging and selection of patients for adjuvant treatment. In colon cancer, a minimum of 12 negative lymph nodes should be examined to confirm node-negative disease. In rectal cancer, there is no evidence that high ligation of the inferior mesenteric artery offers any benefit over ligation at the level of the origin of the superior rectal artery. Even though it has been recommended that a minimum of 4 lymph nodes be examined for entry into adjuvant rectal trials, Tepper and colleagues reported that 14 lymph nodes need to be sampled to accurately define nodal status in rectal cancer accurately. Four cm of attached distal mesorectum should be obtained with the resected specimen. Routine extended lateral pelvic node dissection is not recommended in rectal cancer surgery. Metastases to these lymph nodes occur in about 10% of patients and imply a dire prognosis. If clinically indicated, an attempt to remove these lymph nodes at the time of surgery is warranted.
Sentinel lymph node mapping has changed the management of melanoma and breast cancer. At this time it appears not to have a major effect in altering therapy in colorectal cancer. By identifying the sentinel lymph node(s), immunohistochemical and molecular techniques can be utilized to evaluate for the presence of micrometastases otherwise not diagnosed by conventional pathology. In both single- and multi-institutional studies, it has been shown that lymphatic mapping is feasible in colon cancer patients and indeed may upstage 14 to 18% lymph node negative tumors to node positive status. Not all studies have been encouraging. In a multi-institutional trial, Bertagnolli and colleagues reported that the sentinel node evaluated with multilevel sectioning failed to predict nodal status in 54% of patients. The authors concluded that sentinel node examination with multilevel sectioning is unlikely to improve risk stratification for resectable colon cancer. Sentinel lymph node for rectal cancer is more tedious and has not been as extensively evaluated as in colon cancer.
The significance of lymph node micrometastases in colorectal carcinoma is not known. Similar to reports of micrometastases in the bone marrow of patients with colorectal carcinoma undergoing curative resection, a report from the Netherlands suggested that lymphatic micrometastases adversely affected prognosis. Prospective studies are needed to clarify the significance of molecular detection of lymphatic micrometastases.
Laparoscopic-assisted colectomy is a minimally invasive technique that has been gaining popularity in the management of colon and rectal cancer. The procedure consists of mobilization of the colon laparoscopically and performing an extracorporal anastomosis. In some situations, especially in the low sigmoid colon, an intracorporal anastomosis can be performed. In rectal cancer the technique is utilized to mobilize the mesorectum. The main potential benefits from laparoscopic colectomy have been earlier postoperative recovery and less narcotic use. The Clinical Outcomes of Surgical Therapy Study Group (COST) conducted a multi-institutional prospective randomized trial comparing laparoscopic-assisted colectomy with open colectomy for colorectal cancer in the United States. After 3 years of follow-up, there were no differences in recurrence rates, wound recurrence rates, survival, or complication rates. In that trial, patients undergoing laparoscopically assisted colectomy had a shorter median hospital stay and briefer use of parenteral narcotics and oral analgesics than those undergoing open colectomy. Therefore, the equivalency of laparoscopic-assisted colectomy in experienced surgeons (performing > 20 procedures) to open colectomy has been established by the COST trial. Laparoscopic rectal cancer surgery is being performed, but it has not been evaluated and reported in randomized controlled trials.
MANAGEMENT OF CARCINOMA IN POLYP
It is not uncommon for the clinician to be faced with a patient who had an invasive carcinoma in an adenoma. The treatment in these patients has to be individualized. Favorable histopathological characteristics are free margins of resection, well- or moderately well-differentiated adenocarcinoma, and no lymphatic or vascular invasion. In addition, the endoscopist has to be confident that the lesion was completely removed. If these characteristics are met, and the polyp is limited to the submucosa, the incidence of lymph node metastases is less than 5%, but not zero. There are patients who will not tolerate the risk of having lymph node metastases, and therefore will choose surgical resection. Since the majority of the surgical resections will not reveal residual cancer and/or lymph node metastases, it is important to balance the surgical risks with the benefits of the procedure and discuss them clearly with the patient. In patients who choose endoscopic follow-up, colonoscopy should be performed 3 months after endoscopic polypectomy to evaluate the area of excision. If the colonoscopy is normal, then colonoscopy follow-up is repeated in 1 year and, if normal, in 3 years time. Polyps where the cancer has invaded into the muscularis propria should not be treated by endoscopic excision unless surgery resection is contraindicated. The incidence of lymph node metastases in T2 lesions is as high as 20%.
LOCAL THERAPY FOR RECTAL ADENOCARCINOMA
Local therapy has been evaluated in selected patients with rectal adenocarcinoma. These therapies include electrofulguration, endocavitary radiation with or without brachytherapy, and local excision with or without external beam radiation or chemoradiation. Of these techniques, local excision has the advantage of providing a specimen for pathological evaluation. Surgical approaches to local excision include transanal, transsacral, or transsphincteric approaches. The latter two procedures are less commonly performed than transanal procedure.
Full thickness transanal local excision has been used for selected small (4cm) rectal tumors. Patients are staged clinically with history and physical exam, CAT scan of the abdomen and pelvis, and transrectal ultrasound. Patients with clinically enlarged lymph nodes or fixed tumors are not considered good candidates for local excision. Ideally the tumor should be easily palpated during rectal exam, be mobile, and should not involve greater than 40% of the bowel circumference. After full thickness excision, the histopathology is examined. Patients without disease extension to the muscularis propria (T1 tumors) and with favorable histology (moderate or well differentiated) have a local failure risk of
< 10%. Because of the low overall risk of recurrence, postoperative chemoradiation is not usually recommended. Patients who have poorly differentiated T1 tumors or T2 tumors with any differentiation have routinely been treated with postoperative chemoradiation in order to reduce the risk of pelvic recurrence. Initial reports with short follow-up were very encouraging and stimulated a significant amount of enthusiasm. Postoperative radiation is recommended among T1 tumors with unfavorable characteristics or T2 tumors because the local disease recurrence risk is about 20%.
In the Cancer and Leukemia Group B (CALGB) multi-institutional trial of local excision for T1 tumors and local excision and chemoradiation for T2 tumors, at a median 48 months follow-up, the 6-year actuarial survival and failure-free rates for the eligible T1 and T2 patients were 85% and 78%, respectively. There were 4 failures (2 local only, 1 distant only, and 1 local and distant) in 59 T1 patients. In 51 T2 patients there were 10 recurrences (5 local only, 2 local and distant, and 3 distant only). The salvage rate for local recurrences only was over 50%, but with a short follow-up reported. A retrospective analysis from the University of Minnesota revealed a recurrence rate of 18% and 37% in patients undergoing local excision alone for T1 and T2 tumors, respectively. These investigators subsequently published their results of salvage radical surgery in 29 patients after failed local excision. Twenty-three of 29 patients had surgery with curative intent. At a mean follow-up of 39 months, the disease-free survival was 59%.
Local excision has been used after preoperative (chemo) radiation in medically inoperable patients and patients who refuse abdominal perineal resection and in those patients whose tumors have had a complete or near complete clinical response after neoadjuvant chemoradiation has been reported. However, the follow-up in the latter studies is short, and there have been reports of lymph node metastases in specimens of pathologically T0 tumors after neoadjuvant chemoradiation. Another approach has been observation in patients who achieve clinical complete response to chemoradiation. There has been a single report of high local control and survival in such patients without surgery. These results require further validation. Local excision or observation after clinical complete response after neoadjuvant therapy is investigational and should be performed only in the context of a clinical trial.
Endocavitary radiation (contact therapy) is a technique that administers very high doses of radiation that is concentrated in the tumor with minimal radiation dose to surrounding tissues. This treatment is appropriate for medically inoperable patients, or patients who refuse surgery, or early small rectal tumors.
Miguel A. Rodriguez-Bigas, MD, Paulo Hoff, MD, Christopher H. Crane, MD
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