Increased Local Recurrence and Reduced Survival From Colorectal Cancer Following Anastomotic Leak Systematic Review and Meta-Analysis

Somers Cancer Research Building, University of Southampton Cancer Sciences Division, Southampton University Hospital NHS Trust, Tremona road, Southampton, United Kingdom.
Annals of surgery (Impact Factor: 8.33). 03/2011; 253(5):890-9. DOI: 10.1097/SLA.0b013e3182128929
Source: PubMed


To examine the long-term oncological impact of anastomotic leakage (AL) after restorative surgery for colorectal cancer using meta-analytical methods. Outcomes evaluated were local recurrence, distant recurrence, and survival.
Recurrence after potentially curative surgery for colorectal cancer remains a significant clinical problem and has a poor prognosis. AL may be a risk factor for disease recurrence, however available studies have been conflicting. A meta-analysis was conducted to investigate the impact of AL on disease recurrence and long-term survival.
Studies published between 1965 and 2009 evaluating the long-term oncological impact of AL were identified by an electronic literature search. Outcomes evaluated included local recurrence, distant recurrence, and cancer specific survival. Meta-analysis was performed using the DerSimonian-Laird random-effects model to compute odds ratio and 95% confidence intervals. Study heterogeneity was evaluated using Q statistics and I and publication bias assessed with funnel plots and Egger's test.
Twenty-one studies comprising 13 prospective nonrandomized studies, 1 prospective randomized, and 7 retrospective studies met the inclusion criteria, yielding a total of 21,902 patients. For rectal anastomoses, the odd ratios (OR) of developing a local recurrence when there was AL was 2.05 (95% CI = 1.51-2.8; P = 0.0001). For studies describing both colon and rectal anastomoses, the OR of local recurrence when there was an AL was 2.9 (95% CI = 1.78-4.71; P < 0.001). The OR of developing a distant recurrence after AL was 1.38 (95% CI = 0.96-1.99; P = 0.083). Long term cancer specific mortality was significantly higher after AL with an OR of 1.75 (95% CI = 1.47-2.1; P = 0.0001).
AL has a negative prognostic impact on local recurrence after restorative resection of rectal cancer. A significant association between colorectal AL and reduced long-term cancer specific survival was also noted. No association between AL and distant recurrence was found.

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    • "Clinical studies support the relationship between events that increase perioperative inflammatory response and adverse oncological outcomes in CRC patients. Postoperative infections and anastomotic leaks that modulate the immune system are associated with an increased risk of disease recurrence and decreased disease-free survival [2] [3] [4]. Furthermore , studies in animal models have shown that intraabdominal surgical trauma may increase cancer aggressiveness and the degree of trauma is correlated with the risk of tumor growth and spread [5] [6] [7]. "
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    ABSTRACT: Clinical data and animal models support an association between postoperative inflammatory response and the risk of colorectal cancer recurrence. Our aim was to evaluate postoperative peritoneal inflammation and its impact on cultured colon cancer cells’ migration capacity. Methods. 23 patients undergoing elective colorectal resection with uneventful recovery were prospectively enrolled. Patients were operated on for both malignant and benign etiologies. Peritoneal fluids collected at surgery initiation and after surgery were evaluated for their effect on migration potential of human colon cancer cells using an in vitro scratch assay and on TNF- α , IL-1 β , IL-6, and IL-10 levels using bead-based fluorokine-linked multianalyte profiling. Results. Postoperative peritoneal fluid from all patients increased the migration capacity of colon cancer cells compared to preoperative levels. This effect was significant during the first two postoperative days and decreased thereafter. The increase in colon cancer cell migration capacity correlated with increased levels of peritoneal TNF- α and IL-10. Conclusion. In this pilot study, we have demonstrated that the intraperitoneal environment following colorectal resection significantly enhances colon cancer cells migration capacity. This effect is associated with postoperative intra-abdominal cytokines level. A larger scale study in colorectal cancer patients is needed in order to correlate these findings with perioperative parameters and clinical outcome.
    Full-text · Article · Jan 2016 · Gastroenterology Research and Practice
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    • "A unique international accepted definition of anastomotic leakage (AL) is paramount to gather knowledge about the true incidence of AL and to perform valid comparison between different departments, regions, or countries. Furthermore it is important for the study of risk factors and the consequences of AL on local cancer recurrence and longterm cancer specific survival [1] [2]. "
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    ABSTRACT: Purpose . Anastomotic leakage accounts for up to 1/3 of all fatalities after rectal cancer surgery. Evidence suggests that anastomotic leakage has a negative prognostic impact on local cancer recurrence and long-term cancer specific survival. The reported leakage rate in 2011 in Denmark varied from 7 to 45 percent. The objective was to clarify if the reporting of anastomotic leakage to the Danish Colorectal Cancer Group was rigorous and unequivocal. Methods . An Internet-based questionnaire was e-mailed to all Danish surgical departments, who reported to Danish Colorectal Cancer Group (DCCG) in 2011. There were 23 questions. Four core questions were whether pelvic collection, fecal appearance in a pelvic drain, rectovaginal fistula, and “watchfull” waiting patients were reported as anastomotic leakage. Results . Fourteen out of 17 departments, who in 2011 according to DDCG performed rectal cancer surgery, answered the questionnaire. This gave a response rate of 82%. In three of four core questions there was disagreement in what should be reported as anastomotic leakage. Conclusion . The reporting of anastomotic leakage to the Danish Colorectal Cancer Group was not rigorous and unequivocal. The reported anastomotic leakage rate in Danish Colorectal Cancer Group should be interpreted with caution.
    Full-text · Article · Nov 2015
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    • "Giaccaglia). impact on patient's outcome, involving higher morbidity and mortality, longer hospital stay and, over all, worse oncological and functional outcomes (Mirnezami et al., 2011). More than two decades have passed since surgeons have begun to use staplers in GI surgery; they help shortening operating room time, standardizing surgical technique, and are an essential tool for minimally invasive approaches (laparoscopic and robotic intracorporeal anastomosis) but they are more expensive than hand sewn technique and might have misfiring and malfunctioning during surgery (Picardi, 2002; Guivarc&apos;h, 2004; Korolija, 2008). "
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    ABSTRACT: Anastomotic leak after gastrointestinal surgery is a severe complication associated with relevant short and long-term sequelae. Most of the anastomoses are currently performed with a surgical stapler that is required to have appropriate characteristics in order to guarantee good performances. The aim of our study was to evaluate, ex vivo, pressure resistance and tensile strength of anastomosis performed with different circular staplers available in the market. We studied 7 circular staplers of 3 different companies, 3 of them used for gastrointestinal anastomosis and 4 staplers for hemorrhoidal prolapse excision. A total of 350 anastomoses, 50 for each of the 7 staplers, were performed using healthy pig fresh intestine, then injected saline solution and recorded the leaking pressure. There were no statistically significant differences between the mean pressure necessary to induce an anastomotic leak in the various instruments (p>0.05). For studying tensile strength, we performed a total of 350 anastomoses with 7 different circular staplers on a special strong paper (Tyvek), and then recorded the maximal tensile force that could open the anastomosis. There were statistically significant differences between one brand stapler vs other 2 companies staplers about the strength necessary to open the staple line (p<0.05). In conclusion, we demonstrated that different circular staplers of three companies available in the market give comparable anastomotic pressure resistance but different tensile strengths. This is probably due to different technical characteristics.
    Full-text · Article · Sep 2015
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