Impact of synbiotics treatment on bacteremia induced during neoadjuvant chemotherapy for esophageal cancer: A randomised controlled trial

Masahide Fukaya; Yukihiro Yokoyama; Hiroaki Usui; Hironori Fujieda; Yayoi Sakatoku; Takamasa Takahashi; Kazushi Miyata; Mai Niikura; Takuya Sugimoto; Takashi Asahara; Masato Nagino; Tomoki Ebata

doi:10.1016/j.clnu.2021.10.004

Impact of synbiotics treatment on bacteremia induced during neoadjuvant chemotherapy for esophageal cancer: A randomised controlled trial

Clin Nutr. 2021 Dec;40(12):5781-5791. doi: 10.1016/j.clnu.2021.10.004. Epub 2021 Oct 13.

Affiliations

¹ Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
² Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan; Division of Perioperative Medicine, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: yyoko@med.nagoya-u.ac.jp.
³ Yakult Central Institute, Tokyo, Japan.
⁴ Aichi Cancer Center, Department of Gastrointestinal Surgery, Nagoya, Japan.

PMID: 34775221
DOI: 10.1016/j.clnu.2021.10.004

Abstract

Background & aims: To elucidate the impact of synbiotics on bacterial translocation and subsequent bacteremia during neoadjuvant chemotherapy for esophageal cancer.

Methods: Patients requiring neoadjuvant chemotherapy for esophageal cancer were randomized to receive synbiotics (synbiotics group) or no synbiotics (control group) during chemotherapy. Blood and fecal samples were taken before and after every chemotherapy cycle, and 1 day before surgery. Mesenteric lymph nodes (MLNs) were harvested at laparotomy (MLN-1) and after resection of the tumor (MLN-2). Bacteria in each sample were detected. Fecal microbiota and organic acid concentrations were also determined. The primary endpoint was the detection of bacteria in the blood samples, as well as the incidence of side effects during chemotherapy. The secondary endpoint was the detection rate of bacteria in the MLN samples collected during surgery.

Results: The study recruited a total of 42 patients (22 in the control group, 20 in the synbiotics group). Bacteria were detected in 16 of 101 blood samples in the control group, whereas those were detected only 2 of 100 blood samples in the synbiotics group (p < 0.001) during neoadjuvant chemotherapy. Additionally, bacteria were detected in 12 of 34 MLN samples in the control group, whereas no bacteria were detected in 38 MLN samples in the synbiotics group (p < 0.001). Suppression of bacterial translocation was at least partly associated with an increased fecal acetic acid concentration as well as a lowered fecal pH by synbiotics. The incidence rate of grade 3 gastrointestinal toxicity during chemotherapy was lower in the synbiotics group compared to the control group (8/22 vs. 1/20, p = 0.022).

Conclusions: Neoadjuvant chemotherapy for esophageal cancer may induce bacterial translocation and subsequent bacteremia, which can be prevented by synbiotics administration.

Trial registration: The University Hospital Medical Information Network (http://www.umin.ac.jp; registration number ID 000007651).

Keywords: Bacterial translocation; Esophageal cancer; Neoadjuvant chemotherapy; Synbiotics.

Publication types

Randomized Controlled Trial

MeSH terms

Adult
Aged
Bacteremia / chemically induced*
Bacteremia / prevention & control*
Bacteria / isolation & purification*
Bacterial Translocation / drug effects*
Esophageal Neoplasms / drug therapy*
Feces / microbiology
Female
Humans
Lymph Nodes / microbiology
Male
Middle Aged
Neoadjuvant Therapy / adverse effects*
Reverse Transcriptase Polymerase Chain Reaction
Synbiotics / administration & dosage*