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Antimicrobial prophylaxis for 1 day versus 3 days in liver cancer surgery: a randomized controlled non-inferiority trial

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Abstract

Purposes

This study compared the effectiveness of 1-day vs 3-days antibiotic regimen to prevent surgical site infection (SSI) in open liver resection.

Method

We performed a randomized controlled non-inferiority trial in 480 patients at 39 hospitals across Japan (registered as UMIN000002852). Patients with hepatocellular carcinoma scheduled to undergo resection were randomly assigned to receive either a 1-day regimen for antimicrobial prophylaxis, or a 3-day regimen. The primary endpoint was the incidence of SSI.

Results

Among 480 randomized patients, 232 assigned to the 1-day regimen and 235 to the 3-day regimen were included in the full analysis set. Baseline characteristics of the two groups were well balanced. SSI was diagnosed in 22 patients (9.5%) in the 1-day group vs 23 patients (9.8%) in the 3-day group (difference, – 0.30; 90% CI – 4.80 to 4.19% [95% CI – 5.66% to 5.05%]; one-sided P = 0.001 for non-inferiority), meeting the non-inferiority hypothesis. In both groups, remote site infection (16 [6.9%] vs 22 [9.4%], P ˂ 0.001 for non-inferiority) and drain-related infection (5 [2.2%] vs 4 [1.7%], P ˂ 0.001 for non-inferiority) were comparable.

Conclusion

To prevent SSI in liver cancer surgery, a 1-day regimen of flomoxef sodium is recommended for antimicrobial prophylaxis because of confirming the non-inferiority to longer usage.

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Abbreviations

CDC:

The Centers for Disease Control and Prevention

CI:

Confidence interval

CT:

Computed tomography

HCC:

Hepatocellular carcinoma

MRI:

Magnetic resonance imaging

SSI:

Surgical site infection

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Acknowledgements

Investigators who participated in this study: T. Itamoto (Hiroshima University Hospital, Hiroshima); O. Masaaki (Yamaguchi University Hospital, Yamaguchi); M. Shimada (Tokushima University Hospital, Tokushima); S. Isaji (Mie University Hospital, Mie); T. Kanematsu (Nagasaki University Hospital, Nagasaki); S. Kubo (Osaka City University Hospital, Osaka); K. Chijiiwa (Miyazaki University Hospital, Miyazaki); K. Dono (Toyonaka Municipal Hospital, Osaka); K. Yanaga (Jikei Medical University Hospital, Tokyo); Y. Doki (Osaka University Hospital, Osaka); I. Koyama (Saitama Medical University Hospital, Saitama); K. Hirata (Sapporo Medical University Hospital, Hokkaido); J. Iseki (Shizuoka General Hospital, Shizuoka); K. Miyazaki (Saga University Hospital, Saga); Yamaue (Wakayama Medical University Hospital, Wakayama); M. Miyazaki (Chiba University Hospital, Chiba); S. Uemoto (Kyoto University Hospital, Kyoto); Y. Nakajima (Nara Medical University Hospital, Nara); M. Unno (Tohoku University Hospital, Miyagi); H. Saitsu (National Kyushu Medical Center, Fukuoka); M. Yamamoto (Tokyo Women's Medical University Hospital, Tokyo); S. Kudo (Showa University Hospital, Yokohama); M. Watanabe (Kitasato University Hospital, Kanagawa); J. Nagao (Toho University Hospital Ohashi Medical Center, Tokyo); T. Nonami (Aichi Medical University Hospital, Aichi); S. Ono (National Defense Medical College Hospital, Saitama); M. Shibazaki (Tokyo Yamate Medical Center, Tokyo); K. Yamaguchi (University of Occupational and Environmental Health, Fukuoka); H. Baba (Kumamoto University Hospital, Kumamoto); I. Endo (Yokohama City University Hospital, Kanagawa); Y. Kitagawa (Keio University Hospital, Tokyo); S. Natsugoe (Kagoshima University Hospital, Kagoshima); K. Shirouzu (Kurume University Hospital, Fukuoka); G. Wakabayashi (Iwate Medical University Hospital, Iwate); H. Fujii (University of Yamanashi Hospital, Yamanashi); K. Hanazaki (Kochi Medical University Hospital, Kochi); Y. Sasaki (Yao Municipal Hospital, Osaka); K. Yoshida (Gifu University Hospital, Gifu).

We thank all patients and their relatives for participating in this study, and all medical staff at the 39 participating sites for their cooperation. We also thank Prof Yasuhiko Mohri, Department of Gastrointestinal and Pediatric Surgery, Mie University for his assistance with data management, Prof Yukinori Kurokawa, Department of Gastroenterological Surgery, Osaka University for providing a study protocol on antimicrobial prophylaxis in gastric cancer surgery, Prof Mitsuru Yanai, Department of General Medicine, Nihon University for his assistance with data interpretation, Prof Masashi Fujii, Department of Digestive Surgery, Nihon University for his statistical review, and Prof. Satoshi Hori, Department of Infection Control Science, Juntendo University for his critical review.

Funding

This trial was funded by a grant from the Japan Society for Surgical Infection, Tokyo, Japan, which is a non-profit organization established to control surgery-related infections, initiated and sponsored this study, but had no role in the study design or the collection, analysis, and interpretation of data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Ohyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan

    Tadatoshi Takayama & Osamu Aramaki

  2. Biostatistics Division, Center for Research Administration and Support, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104- 0045, Japan

    Taro Shibata

  3. Department of Digestive Surgery and Surgical Oncology, Faculty of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan

    Masaaki Oka

  4. Department of Gastroenterological and Transplant Surgery, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan

    Toshiyuki Itamoto

  5. Department of Digestive and Transplantation Surgery, Tokushima University School of Medicine, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan

    Mitsuo Shimada

  6. Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City, Mie, 514-8507, Japan

    Shuji Isaji

  7. Department of Surgery, Nagasaki University School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Takashi Kanematsu

  8. Department of Hepatobiliary Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka-City, Osaka, 545-8585, Japan

    Shoji Kubo

  9. Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Mie, Japan

    Masato Kusunoki

  10. Department of Surgery, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Hidetaka Mochizuki

  11. Chairman of the Board of Directors, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8510, Japan

    Yoshinobu Sumiyama

Authors
  1. Tadatoshi Takayama
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  2. Osamu Aramaki
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  3. Taro Shibata
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  4. Masaaki Oka
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  7. Shuji Isaji
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  8. Takashi Kanematsu
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  9. Shoji Kubo
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  10. Masato Kusunoki
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  11. Hidetaka Mochizuki
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  12. Yoshinobu Sumiyama
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Contributions

Concept and design: TT, MO, HM, and YS. Acquisition or interpretation of data: TT, MO, TI, MS, SI, TK, and SK. Drafting of the manuscript: TT, and OA. Critical revision of the manuscript: TT, MO, Shibata, MK, and YS. Statistical analysis: TS.

Corresponding author

Correspondence to Tadatoshi Takayama.

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All authors declare no conflicts of interest.

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This Study Was Registered With the University Hospital Medical Information Network (UMIN)-CTR (https://www.umin.ac.jp), Identification Number 000002852.

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Takayama, T., Aramaki, O., Shibata, T. et al. Antimicrobial prophylaxis for 1 day versus 3 days in liver cancer surgery: a randomized controlled non-inferiority trial. Surg Today 49, 859–869 (2019). https://doi.org/10.1007/s00595-019-01813-w

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  • DOI: https://doi.org/10.1007/s00595-019-01813-w

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