Worldwide, colorectal cancer (CRC) is the third-most common cancer in men, the second-most common cancer in women, and the fourth-most common cause of cancer mortality.1 In 2015, it was reported that there were about 1.478 million CRC patients worldwide, which accounted for 9.7% of total cancer cases, and estimated CRC-caused deaths were 753,000.2 Kinds of risk factors and potential factors were found to be relevant to CRC, and subsequently various preventive interventions were investigated.3,4 For patients diagnosed with CRC, surgery is still a curative option. However, colorectal surgery was reported to be related to a very high incidence of complication, especially postoperative infections. López et al reported the overall rate of complication was 39.5%, and nearly half of them were infections.5 The prevention and treatment of severe postoperative infections of the abdominal and pelvic cavity in CRC patients have always been an important issue for colorectal surgeons.
Omega-3 polyunsaturated fatty acids (PUFAs) are one of the two kinds of essential FAs in humans and must be supplied from outside the body. Two common forms of omega-3 PUFAs are eicosapentaenoic acid and docosahexaenoic acid, both found in fish oil and both with nutritional and pharmacological effects.6 Currently, omega-3 PUFA enriched enteral nutrition (EN) and parenteral nutrition (PN) are regarded as one kind of immunonutrition therapy in both intensive care unit and surgical patients.7 Although no significant association between omega-3 PUFA supplements and cancer-incidence reduction has been found,8 its positive roles on host immune function seem to be promising in the postoperative management of cancer patients. Also, previous meta-analyses including all kinds of surgical patients indicated that omega-3 PUFAs improved clinical outcomes, such as reduced infection incidence and hospital stay.9,10
However, due to the influence of different diseases and surgeries, the findings would be difficult to be applied to clinical practice in specific CRC patients. Other studies have investigated the efficacy of omega-3 PUFA-enriched nutrition for CRC patients undergoing surgery,11–21 and the primary results indicated that the immunological function of omega-3 PUFAs would be helpful in preventing postoperative infectious complications. Considering the results and conclusions in these studies were not completely consistent because of limited sample size, different study designs, and potential bias, we performed a meta-analysis of all relevant randomized control trials (RCTs) to focus mainly on the efficacy of omega-3 PUFAs in the prevention of postoperative complications for CRC patients undergoing surgery.
MATERIALS AND METHODS
We searched the online databases of PubMed (January 1966 to March 2016), the Cochrane Library (2016, issue 3), and Embase (January 1974 to March 2016) by using free terms as follows: (“omega-3” OR “n-3” OR “polyunsaturated”) AND (“fatty acid” OR “fish oil”) AND (“cancer” OR “carcinoma” OR “tumor” OR “surgery” OR “operation”) AND (“colorectal” OR “colon” OR “rectum”). Related articles on PubMed and Google Scholar and references of related reviews were also used and screened to find potential literature.
Clinical studies investigating the efficacy of short-term omega-3 PUFA-enriched nutrition in CRC patients undergoing surgery were eligible. After duplicates had been removed, the searched citations were firstly screened on the basis of titles and abstracts, and then potential studies were evaluated by reading the full texts to ensure their suitability of inclusion. The study had to be an RCT, and omega-3 PUFAs ideally needed to be administered additionally in the study group (omega-3 group). The daily dose of omega-3 PUFAs was not limited; the route of administration needed to be oral or though enteral tube in EN or intravenous infusion in PN; the timing of administration had to be short-term duration before or after surgery, or both before and after surgery. The inclusion process was completed by two independent reviewers, and only articles published in English were considered.
Primary outcome measures needed to include at least the incidence of infectious complications, surgical site infection (SSI), or total complications. Secondary outcome measures would include serum inflammatory cytokines (tumor necrosis factor [TNFα] and interleukin-6 [IL-6]), CD4+:CD8+ cell ratio, hospital stay, and medical cost. As reported, all outcome measures were collected during both hospital stay and follow-up period.
Data extraction and quality assessment
We extracted both information and outcome data from the included studies. Cases, age, sex, interventions (daily dose, timing, and duration of omega-3 PUFA administration), operation time, and blood loss are presented to show the baseline characteristics. Data of outcomes were extracted as mentioned earlier, including primary and secondary outcome measures. Quality assessment was performed by using the Cochrane bias-risk tool,22 which includes six domains: selection bias, performance bias, detection bias, attrition bias, reporting, bias and other bias.
Data synthesis was performed by Reviewer Manager (RevMan 5.3; Cochrane Collaboration, London, UK). Because the timing of preoperative or postoperative administration was obviously of shorter duration than perioperative administration, a subgroup separating administration timing was firstly established to reduce clinical heterogeneity. Then, statistical heterogeneity was calculated by χ2 and I2 statistical tests, and a random-effect model or a fixed-effect model was chosen accordingly. Risk ratios (RRs), mean difference (MD), or standard MD (SMD) with 95% confidence intervals (CIs) were used to show the combined effect size. Sensitivity analyses were performed though changing the synthesis model to test its stability, and inverted funnel plots were visually judged to explore the risk of publication bias.