Impact of perioperative administration of synbiotics in patients with esophageal cancer undergoing esophagectomy: A prospective randomized controlled trial

doi:10.1016/j.surg.2012.02.021

Surgery

Volume 152, Issue 5, November 2012, Pages 832-842

https://doi.org/10.1016/j.surg.2012.02.021 Get rights and content

Background

The clinical value of synbiotics in patients undergoing esophagectomy remains unclear. This study investigated the effects of synbiotics on intestinal microflora and surgical outcomes in a clinical setting.

Methods

We studied 70 patients with esophageal cancer who were scheduled to undergo esophagectomy. They were randomly allocated to 2 groups: 1 group received synbiotics before and after surgery, and the other did not. Fecal microflora and organic acid concentrations were determined. Postoperative infections, abdominal symptoms, and duration of systemic inflammatory response syndrome (SIRS) were recorded.

Results

Of the patients, 64 completed the trial (synbiotics, 30; control, 34). The counts of beneficial bacteria and harmful bacteria in the group given synbiotics were significantly larger and smaller, respectively, than those in the control group on postoperative day (POD) 7. The concentrations of total organic acid and acetic acid were higher in the synbiotics group than in the control group (P < .01), and the intestinal pH in the synbiotics group was lower than that in the control (P < .05) on POD 7. The rate of infections was 10% in the synbiotics group and 29.4% in the control group (P = .0676). The duration of SIRS in the synbiotics group was shorter than in the control group (P = .0057). The incidence of interruption or reduction of enteral nutrition by abdominal symptoms was 6.7% in the synbiotics group and 29.4% in the control group (P = .0259).

Conclusion

Perioperative administration of synbiotics in patients with esophagectomy is useful because they suppress excessive inflammatory response and relieve uncomfortable abdominal symptoms through the adjustment of the intestinal microfloral environment.

Section snippets

Patients

This open study involved 70 patients with esophageal cancer who were scheduled to undergo esophagectomy at the Osaka Medical Center for Cancer and Cardiovascular Diseases. Briefly, eligible patients had histologically proven and potentially curable esophageal cancer, could take orally and receive enteral nutrition, and were younger than 80 years of age. Exclusion criteria were as follows: previous or concomitant other cancer; renal, hepatic, or metabolic disorders (eg, severe diabetes); or

Demographic characteristics of study patients

Of the 70 patients initially enrolled in this study between February 2007 and March 2010, 6 were excluded from the study after surgery (4 patients had severe pleural adhesion and thus underwent resection alone, and reconstruction was postponed; the other 2 patients had T4 tumors and underwent noncurative or palliative surgery). The remaining 64 patients who underwent curative resection completed the trial; 34 were assigned to the control group (postoperative enteral feeding without synbiotics),

Discussion

Based on the results in the control group, the intestinal microflora underwent drastic changes after esophagectomy, as had been anticipated, with decreases in the beneficial bacteria, such as Lactobacillus and Bifidobacterium species, and increases in the harmful bacteria, such as Pseudomonas, Enterobacteriacae, and Enterococcus species. In contrast, the synbiotics group showed a quite different pattern of intestinal microflora after surgery, with the beneficial bacteria being rather increased

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Citation Excerpt :
The numbers of almost all representative obligate anaerobes, such as C. coccoides group, C. leptum subgroup, Bifidobacterium, and B. fragilis group, were significantly lower after chemotherapy than before chemotherapy in both groups. This indicates that chemotherapy disrupted the intestinal microbiota, which is consistent with previous reports [14,36,37]. The numbers of Bifidobacterium (P < 0.05) and BbrY (P < 0.001) were significantly higher in the Syn + EN group on day 8 than before treatment.
Established supportive care to reduce the toxicity of neoadjuvant chemotherapy (NAC) is lacking. This multicenter randomized study compared the administration of synbiotics combined with enteral nutrition (EN) versus that of prophylactic antibiotics as supportive care treatment for patients with esophageal cancer undergoing NAC.
Patients with advanced esophageal cancer scheduled to receive NAC were randomly administered either prophylactic antibiotics (antibiotic group) or synbiotics combined with EN (Syn + EN group). The primary endpoint was the febrile neutropenia (FN) incidence during the first course, and the secondary endpoints were other adverse events, changes in intestinal environment, including fecal microbiota, organic acid concentrations, pH, and chemotherapy tolerability.
Eighty-one patients were enrolled. The FN incidence was nonsignificantly lower (P = 0.088) in the Syn + EN group. The incidences of grade 4 neutropenia and grades 2–4 diarrhea were significantly lower in the Syn + EN group (P = 0.014 and 0.033, respectively). Relative dose intensity was significantly higher in the Syn + EN group (92.0 ± 10.9%) than in the antibiotic group (83.2 ± 18.2%) (P = 0.01). Alpfa diversity was significantly higher in the Syn + EN group than in the antibiotic after chemotherapy (P = 0.002). The numbers of Bifidobacterium (P < 0.05), Lacticaseibacillus (P < 0.001), and Enterobacteriaceae (P < 0.001) and the concentration of acetic acid (P < 0.001) were significantly higher in the Syn + EN group than in the antibiotic group after chemotherapy. The severity of diarrhea and occurrence of FN were significantly correlated with Clostridioides difficile abundance and were significantly inversely correlated with acetic acid concentration after chemotherapy.
Synbiotics combined with EN may be an alternative supportive care treatment to prophylactic antibiotics in patients with cancer undergoing toxic chemotherapy (https://jrct.niph.go.jp; jRCTs051180153).
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: Supported by a grant from Osaka Foundation for the Prevention of Cancer and Cardiovascular Diseases.

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Original CommunicationImpact of perioperative administration of synbiotics in patients with esophageal cancer undergoing esophagectomy: A prospective randomized controlled trial

Background

Methods

Results

Conclusion

Section snippets

Patients

Demographic characteristics of study patients

Discussion

Cytokine

Surgery

Gastroenterology

Int J Food Microbiol

J Microbiol Methods

J Biosci Bioeng

Am J Transplant

J Gastrointest Surg

Ann Thorac Surg

Nutrition

Gastroenterology

Prediction of pulmonary complications after transthoracic oesophagectomy

Br J Surg

Postoperative hyperbilirubinemia after resection of thoracic esophageal cancer

Am J Gastroenterol

Systemic cytokine response after major surgery

Br J Surg

Serum concentrations of interleukin-6, tumour necrosis factor-alpha, and C-reactive protein in patients undergoing major operations

Eur J Surg

Prebiotic effects: metabolic and health benefits

Br J Nutr

Insights into the roles of gut microbes in obesity

Interdiscip Perspect Infect Dis

Effects of the enteral administration of Bifidobacterium breveon patients undergoing chemotherapy for pediatric malignancies

Support Care Cancer

The role of interdigestive small bowel motility in the regulation of gut microflora, bacterial overgrowth, and bacterial translocation in rats

Ann Surg

Elemental diet and IV-TPN-induced bacterial translocation is associated with loss of intestinal mucosal barrier function against bacteria

Ann Surg

Gut microenvironment and immune function

Curr Opin Clin Nutr Metab Care

A criterion for completeness of vagotomy based on basal and vagally stimulated gastric acid secretion after esophagectomy or proximal gastric vagotomy

Scand J Gastroenterol

Role of the vagus nerve on the development of postoperative ileus

Langenbecks Arch Surg

Bacterial translocation in acute liver failure induced by 90 per cent hepatectomy in the rat

Br J Surg

Bacterial translocation and gram-negative bacteremia in patients with hematological malignancies

J Infect Dis

Perioperative synbiotic treatment to prevent postoperative infectious complications in biliary cancer surgery: a randomized controlled trial

Ann Surg

Original Communication
Impact of perioperative administration of synbiotics in patients with esophageal cancer undergoing esophagectomy: A prospective randomized controlled trial