To the Editor:
We read with interest the study by Sugawara et al,1 which concluded that preoperative oral administration of synbiotics is likely to reduce postoperative infectious complications after hepatobiliary resection of biliary tract cancer.
The trial design is adequate for drawing conclusions regarding the timing of synbiotic dosing for patients undergoing surgery; however, the absence of a placebo significantly limits its ability to describe the efficacy of nutritional supplements in the reduction of postoperative complication rates. This is compounded by the fact that the study is not blinded. Furthermore, the method of randomization is not explained, and no evidence is presented to suggest sample sizes were considered. This makes many of the conclusions drawn by the authors difficult to justify.
Patients in past trials of functional foods have complained of side effects, such as diarrhea or altered bowel habit,2 but sadly no mention is made of synbiotic tolerance or withdrawals from the study due to side effect profiles. This is important if we are expecting our patients to take a 2-week course of this treatment preoperatively. A more major concern has been the potential for sepsis caused by the treatment organisms,3,4 especially in immunocompromised patients and those undergoing surgery. In this study, blood cultures were taken if patients had a temperature greater that 38.5°C, yet the authors do not report the species that were grown in the 6 patients that were found to be bacteremic. If synbiotics are to be accepted by the surgical community, it is important that these data are reported in all future trials.
The number of viable bacteria reaching or colonizing the intestine depends on many factors other than dose, particularly the probiotic formulation, coadministration of food, gastric pH, intestinal motility, and prior composition of intestinal microbiota.5 Patients were fed enterally via jejunal feeding tubes, and the authors state that parenteral nutrition was also supplied by a central venous catheter. But it is unclear which parenteral feed was used and what proportion of patients were fed in this manner. This has the potential to dramatically alter the efficacy of any synbiotic, and these data should be presented in future trials.
It is interesting to note that the study did not demonstrate a statistically significant increase in the fecal population of the Lactobacillus strain. The importance of this has been contested because Lactobacilli may persist within colonic mucosa even after its disappearance from fecal samples.6 However, it has also been shown that Lactobacilli probiotics are largely digested in the stomach, thus reducing their efficacy.7,8 This study adds weight to this belief, as it only demonstrated a significant increase in the Bifidobacterium population, suggesting that the efficacious component of the synbiotic is provided by the galacto-oligosaccharide.
The authors claim that jaundice-related physical damage to the intestinal mucosa may be reversed with bile replacement rather than preoperative use of symbiotics; 75% of group A and 80.4% of group B underwent percutaneous transhepatic biliary drainage preoperatively and had this replaced orally or via a nasoduodenal tube. However, no subgroup data analysis is offered for those that did not undergo this procedure, all patients had a synbiotic at some point in the study, and no control group is used. Therefore, it is not possible to state whether the reduction in intestinal permeability and improved mucosal integrity is caused by biliary replacement alone or whether a synbiotic is in fact responsible for the protection of the intestinal mucosa.
Functional foods are a potentially significant development in the reduction of sepsis and the inflammatory response in patients undergoing major surgery. The study by Sugawara et al1 represents progress in this area. However, it is vital that future trials of synbiotics adhere to the high standards required of randomized control studies to allow clear elucidation of their role.
James Kinross, MRCS
Oliver Warren, MRCS
David Silk, MD, FRCP
Ara Darzi, MD, FACS, FMedSci
Department of BioSurgery and Surgical
Technology
Division of Surgery, Oncology,
Reproductive Biology and Anaesthetics
Imperial College
St. Mary’s Hospital
London, UK
j.kinross@imperial.ac.uk
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