Pancreatic cancer has an extremely poor prognosis and prolonged survival is achieved only by resection with macroscopic tumor clearance. There is a strong rationale for a neoadjuvant approach, since a relevant percentage of pancreatic cancer patients present with non-metastatic but locally advanced disease and microscopic incomplete resections are common. The objective of the present analysis was to systematically review studies concerning the effects of neoadjuvant therapy on tumor response, toxicity, resection, and survival percentages in pancreatic cancer. Trials were identified by searching MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 1966 to December 2009 as well as through reference lists of articles and proceedings of major meetings. Retrospective and prospective studies analyzing neoadjuvant radiochemotherapy, radiotherapy, or chemotherapy of pancreatic cancer patients, followed by re-staging, and surgical exploration/resection were included. Two reviewers independently extracted data and assessed study quality. Pooled relative risks and 95% confidence intervals were calculated using random-effects models. Primary outcome measures were proportions of tumor response categories and percentages of exploration and resection. A total of 111 studies (n = 4,394) including 56 phase I–II trials were analyzed. A median of 31 (interquartile range [IQR] 19–46) patients per study were included. Studies were subdivided into surveys considering initially resectable tumors (group 1) and initially non-resectable (borderline resectable/unresectable) tumors (group 2). Neoadjuvant chemotherapy was given in 96.4% of the studies with the main agents gemcitabine, 5-FU (and oral analogues), mitomycin C, and platinum compounds. Neoadjuvant radiotherapy was applied in 93.7% of the studies with doses ranging from 24 to 63 Gy. Averaged complete/partial response probabilities were 3.6% (95% CI 2%–5.5%)/30.6% (95% CI 20.7%–41.4%) and 4.8% (95% CI 3.5%–6.4%)/30.2% (95% CI 24.5%–36.3%) for groups 1 and 2, respectively; whereas progressive disease fraction was estimated to 20.9% (95% CI 16.9%–25.3%) and 20.8% (95% CI 14.5%–27.8%). In group 1, resectability was estimated to 73.6% (95% CI 65.9%–80.6%) compared to 33.2% (95% CI 25.8%–41.1%) in group 2. Higher resection-associated morbidity and mortality rates were observed in group 2 versus group 1 (26.7%, 95% CI 20.7%–33.3% versus 39.1%, 95% CI 29.5%–49.1%; and 3.9%, 95% CI 2.2%–6% versus 7.1%, 95% CI 5.1%–9.5%). Combination chemotherapies resulted in higher estimated response and resection probabilities for patients with initially non-resectable tumors (“non-resectable tumor patients”) compared to monotherapy. Estimated median survival following resection was 23.3 (range 12–54) mo for group 1 and 20.5 (range 9–62) mo for group 2 patients. In patients with initially resectable tumors (“resectable tumor patients”), resection frequencies and survival after neoadjuvant therapy are similar to those of patients with primarily resected tumors and adjuvant therapy. Approximately one-third of initially staged non-resectable tumor patients would be expected to have resectable tumors following neoadjuvant therapy, with comparable survival as initially resectable tumor patients. Thus, patients with locally non-resectable tumors should be included in neoadjuvant protocols and subsequently re-evaluated for resection. Please see later in the article for the Editors' Summary

The role of a defunctioning stoma in patients undergoing low anterior resection for rectal cancer is still the subject of controversy. Recent studies suggest reduced morbidity after low anterior rectal resection with a defunctioning stoma. Retrospective and prospective studies published between 1966 and 2007 were systematically reviewed. Randomized controlled trials (RCTs) comparing anterior resections with or without defunctioning stoma were included in a meta-analysis. The pooled estimates of clinically relevant anastomotic leakages and of reoperations were analyzed using a random effects model (odds ratio and 95% confidence interval, CI). Relevant retrospective single (n = 18) and multicenter (n = 9) studies were identified and included in the systematic review. Analysis of incoherent data of the leakage rates in these nonrandomized studies demonstrated that a defunctioning stoma did not influence the occurrence of anastomotic failure but seemed to ameliorate the consequences of the leak. Four RCTs were included in the meta-analysis. The odds ratio for clinically relevant anastomotic leakage was 0.32 (95% CI 0.17–0.59), revealing a statistically significant benefit conferred through a defunctioning stoma (Z = 3.65, P = 0.0003). The odds ratio for reoperation because of leakage-caused complications was 0.27 (95% CI 0.14–0.51), with significantly fewer reoperations in patients with a defunctioning stoma (Z = 3.95, P < 0.0001). Overall mortality rates were comparable regardless of the presence of a defunctioning stoma. A defunctioning stoma reduces the rate of clinically relevant anastomotic leakages and is thus recommended in surgery for low rectal cancers.