anatomy of the bony pelvis makes complete tumor resection and dissection of mesenteric nodes at risk for metastasis within the mesorectum technically difficult (6). In addition, the close proximity of soft-tissue organs such as the bladder, vagina, and ureters, along with the absence of a serosal barrier allowing for early tumor extension into the perirectal tissue, further impacting the complexity level. Early randomized trials of patients with stage II/III Z-VAD-FMK ic50 disease found local recurrence (LR) rates of approximately 25-30% for patients treated with surgery alone (7)-(10). Surgery in these studies often relied Inhibitors,research,lifescience,medical on blunt dissection of the rectal fascia, a technique that many times failed in removing all tumor-bearing tissue, particularly at the circumferential margin (11),(12).
These relatively high recurrence rates led to a focus on a more anatomically precise surgery; the total mesorectal excision (TME). With TME, Inhibitors,research,lifescience,medical sharp dissection of the entire mesentery of the hindgut is performed. In several reports, results of TME were shown to be quite impressive both in terms of LR and overall recurrence (11)-(14). While TME is a more extensive surgery, data suggest no significant differences in operative mortality or complications between TME and conventional surgery (15). Inhibitors,research,lifescience,medical Maximal radial margin should be attained during surgery, as positive and close margins have been shown to increase rates of both local and distant Inhibitors,research,lifescience,medical recurrence (16)-(18). In the United States, it is recommended that patients with stage II/III rectal cancers undergo transabdominal resection, and sphincter preservation is preferable if technically feasible. For those patients with tumors in the upper rectum, a low anterior resection (LAR) can be performed, extended several centimeters past the tumor distally with subsequent creation of a Inhibitors,research,lifescience,medical colorectal anastomosis. For those
tumors in the low rectum, it is recommended that patients undergo TME with colorectal or coloanal anastomosis or alternatively, an abdominoperineal resection (APR) with the only creation of a colostomy (4),(19). Rationale for radiation therapy In patients with stage II/III disease treated with conventional surgery, radiation therapy has often been employed, with and without systemic therapy, in order to reduce the risk of local recurrence. The timing (preoperative versus [vs.] postoperative), treatment dose and duration, and its sequence with adjuvant systemic therapy have all been investigated in this patient population. In Europe, 25 Gray (Gy) in 5 daily treatment fractions delivered preoperatively followed immediately by surgery has been extensively studied.
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- Estimates regarding the completeness of endoscopic resection were