l‐Alanine‐l‐glutamine supplementation improves the outcome after colorectal surgery for cancer

Dear Sir, We read this article with considerable interest. The authors conclude that parenteral glutamine supplementation decreases postoperative complications as well as duration of hospital stay in patients undergoing colorectal surgery for cancer. This really is the pot of gold under the rainbow: a single nutrient intervention having a significant impact on morbidity in elective surgical patients. Clinicians with an interest in nutrition and metabolism have been searching for this panacea for many years. Sadly, however, we think the authors’ conclusions simply amount to a type 1 statistical error which has occurred as a consequence of inappropriate use of statistical methods. The study has a number of flaws: 1 It is arguably unethical to administer enteral nutrition to patients who are unable to eat. This is particularly the case in the preoperative period when there is no evidence for the benefits of preoperative enteral nutrition. 2 The aim of the study was to assess the benefits or otherwise of parenteral glutamine. Both groups in this study received enteral nutrition and were allowed to eat ‘ad libitum’, although the amounts ingested are not recorded. As such, differences between the groups cannot be attributed solely to the use of glutamine. 3 There is an absence of clarity as to how randomization was carried out. 4 The study was not blinded. 5 There is a lack of clarity as to the primary outcome measure and to the definition of some of the end points, which seem too numerous to mention. 6 There is no statistical calculation indicating the numbers required to power this study. 7 Wound infection was defined by redness and tenderness. This is entirely subjective. This is subject to bias particularly as the study was not blinded. This would also affect assessments of length to stay. 8 No mention is made as to who reviewed the patients and assessed morbidity. No information is provided as to ‘fitness for discharge’ criteria and who made this decision. 9 It is not appropriate to use T tests for data which is not normally distributed. 10 Most damning of all, it is wrong on the authors’ part to quote chi-squared results for wound infection (P = 0.038), abdominal abscess (P = 0.044) and wound dehiscence (P = 0.044) when these are clearly small cohorts for which their methodology correctly states Fisher’s exact test was meant to be used. When one recalculates the statistics, it becomes evident that, should the correct test have been used, the respective P-values would have been P = 0.087, P = 0.097 and P = 0.097, all incidentally not significant. One of their results is most curious, however, they state that five of their control patients could not tolerate enteral nutrition. We would suggest to them that this was indicative of the fact that they had gut failure. There is increasing evidence to suggest that gut failure, or at least inadequate gut function, does modify outcome. We suggest the authors reappraise their data from this point of view.