However, the interval did not have an effect on morbidity, local relapse, short-term survival and sphincter preservation. That study did not include a preoperative chemotherapy regimen. In 2002 and 2003, two studies with no long-term recurrence and survival data

were published (6,10). These two studies, a prospective study #JAK inhibitor keyword# by Stein et al. (10) and a retrospective study by Moore et al. (6), failed to demonstrate any benefit of long-term delay before surgery in terms of tumor downstaging, pathological response or sphincter preservation. A recent retrospective study by Tulchinsky et al. (8) examined both short and long-term results and found better pathological complete response, metastasis and disease free survival rates but similar overall survival and local recurrence. In line with most but not all of the Inhibitors,research,lifescience,medical findings of previous studies, the present prospective randomized study did not find any difference between surgery performed 4 weeks after neoadjuvant therapy and surgery performed after 8 weeks of delay, in terms of both early benefits of neoadjuvant therapy and long-term success of combined treatment. Two groups had similar pathological

complete response, T and N downgrading, lateral surgical margin positivity, sphincter preservation rates as well as similar local recurrence, Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical distant metastasis and 5-year survival rates. Lateral or circumferential resection margin (CRM) has been shown to be the most important factor for the risk of local recurrence after rectal cancer surgery (13). The relevance of a positive CRM has been confirmed in many subsequent

studies not only for local recurrence, but also for systemic failure (14-16). All studies that included the development of distant metastases as a separate outcome variable show a significant difference in prognosis between the CRM-positive and the CRM-negative patients (HR, 2.8; 95% CI, 1.9 Inhibitors,research,lifescience,medical to 4.3) regardless of the use of neoadjuvant therapy (11). In combination with lymph node status, CRM status seems to provide a better prognostic model than current TNM system (13). In the study by Bujka et al., the addition of fluorouracil/folinic Olopatadine acid to long-term radiotherapy did not decrease the number of positive margins although there was more downstaging in the radiochemotherapy arm (16). Similarly, more downstaging was present in the radiochemotherapy arm compared with the radiotherapy arm in the European Organization for Research and Treatment of Cancer trial but CRM positivity rate was similar. Thus, downstaging does not necessarily translate into CRM negativity, probably not into better long-term results in term of local recurrence and survival.