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Synbiotics reduce postoperative infectious complications: a randomized controlled trial in biliary cancer patients undergoing hepatectomy

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Abstract

Background and aims

The clinical value of synbiotics in surgical patients remains unclear. The aim of this study was to investigate the effect of synbiotics on intestinal integrity and microflora, as well as on surgical outcome, in patients undergoing high-risk hepatectomy.

Methods

Fifty-four patients with biliary cancer were randomly allocated to two groups before hepatectomy. One group received postoperative enteral feeding that included synbiotics; the other received enteral feeding only. Lactulose/mannitol (L/M) ratio, serum diamine oxidase (DAO) activity, and fecal microflora and organic acid concentrations were determined. Postoperative infectious complications were recorded.

Results

Of the 54 patients, 44 completed the trial (21 receiving synbiotics and 23 others as controls). Postoperative changes in L/M ratios and serum DAO activities were identical between the two groups. Numbers of beneficial bacteria increased in the synbiotics group after surgery but decreased in controls. Numbers of harmful microorganisms decreased in the synbiotics group but increased in controls. Total organic acid concentrations increased in the synbiotics group but decreased in controls. Incidence of infectious complications was 19% (4/21) in the synbiotics group and 52% (12/23) in controls (P<0.05). All study patients tolerated surgery (mortality 0%).

Conclusions

Synbiotics, combined with early enteral nutrition, can reduce postoperative infections. This beneficial effect presumably involves correction of an intestinal microbial imbalance induced by surgical stress.

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References

  1. Nagino M, Nimura Y, Hayakawa N, Kamiya J, Kondo S, Sasaki R, Hamajima N (1993) Logistic regression and discriminant analyses of hepatic failure after liver resection for carcinoma of the biliary tract. World J Surg 17:250–255

    Google Scholar 

  2. Pichlmayr R, Weimann A, Klempnauer J, Oldhafer KJ, Maschek H, Tusch G, Ringe B (1996) Surgical treatment in proximal bile duct cancer. A single-center experience. Ann Surg 224:628–638

    Google Scholar 

  3. Nimura Y, Kamiya J, Nagino M, Kanai M, Uesaka K, Kondo S, Hayakawa N (1998) Aggressive surgical treatment of hilar cholangiocarcinoma. J Hepatobiliary Pancreat Surg 5:52–61

    Google Scholar 

  4. Neuhaus P, Jonas S, Bechstein WO, Lohmann R, Radke C, Kling N, Wex C, Lobeck H, Hintze R (1999) Extended resection for hilar cholangiocarcinoma. Ann Surg 230:808–819

    Google Scholar 

  5. Nagino M, Kamiya J, Uesaka K, Sano T, Yamamoto H, Hayakawa N, Kanai M, Nimura Y (2001) Complications of hepatectomy for hilar cholangiocarcinoma. World J Surg 27:1277–1283

    Google Scholar 

  6. Sitzmann JV, Greene PS (1994) Perioperative predictors of morbidity following hepatic resection for neoplasms. Ann Surg 219:13–17

    Google Scholar 

  7. Shigeta H, Nagino M, Kamiya J, Uesaka K, Sano T, Yamamoto H, Hayakawa N, Kanai M, Nimura Y (2002) Bacteremia after hepatectomy: an analysis of single center, 10-year experience with 407 patients. Langenbecks Arch Surg 387:117–124

    Google Scholar 

  8. Wang X, Soltesz V, Andersson R, Bengmark S (1993) Bacterial translocation in acute liver failure induced by 90 per cent hepatectomy in the rat. Br J Surg 80:66–71

    Google Scholar 

  9. Tancrede CH, Andremont AO (1985) Bacterial translocation and gram-negative bacteremia in patients with hematological malignancies. J Infect Dis 152:99–103

    Google Scholar 

  10. Lilly D, Stillwell RJ (1965) Probiotics: growth promoting factors produced by microorganisms. Science 147:747–748

    Google Scholar 

  11. Fuller R (1991) Probiotics in human medicine. Gut 32:439–442

    Google Scholar 

  12. Gibson GR, Beatty ER, Wang X, Cummings JH (1995) Selective stimulation of Bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology 108:975–982

    CAS  PubMed  Google Scholar 

  13. Colins MD, Gibson GR (1999) Probiotics, prebiotics, and synbiotics: approaches for modulating the microbial ecology of the gut. Am J Clin Nutr 69 [Suppl]:1052S–1057S

    Google Scholar 

  14. McNaught CE, Woodcock NP, MacFie J (2002) A prospective randomized study of the probiotic Lactobacillus plantarum 299V on indices of gut barrier function in elective surgical patients. Gut 51:827–831

    Google Scholar 

  15. Rayes N, Seehofer D, Hansen S, Boucsein K, Muller AR, Serke S, Bengmark S, Neuhaus P (2002) Early enteral supply of lactobacillus and fiber versus selective bowel decontamination: a controlled trial in liver transplant recipients. Transplantation 74:123–128

    Google Scholar 

  16. Rayes N, Hansen S, Seehofer D, Muller AR, Serke S, Bengmark S (2002) Early enteral supply of fiber and Lactobacilli versus conventional nutrition: a controlled trial of patients with major abdominal surgery. Nutrition 18:609–615

    Article  PubMed  Google Scholar 

  17. Kamiya S, Nagino M, Kanazawa H, Komatsu S, Mayumi T, Takagi K, Asahara T, Nomoto K, Tanaka R, Nimura Y (2004) The value of bile replacement during external biliary drainage: an analysis of intestinal permeability, integrity, and microflora. Ann Surg 239:510–517

    Google Scholar 

  18. Jansen G, Muskiet FA, Schierbeek H, Berger R, van der Slik W (1986) Capillary gas chromatographic profiling of urinary, plasma and erythrocyte sugars and polyols as their trimethylsilyl derivatives, preceded by a simple and rapid prepurification method. Clin Chim Acta 157:277–293

    Google Scholar 

  19. Takagi K, Nakao M, Ogura Y, Nabeshima T, Kunii A (1994) Sensitive colorimetric assay of serum diamine oxidase. Clin Chim Acta 226:67–75

    Google Scholar 

  20. Azuma R, Suto T (1970) Validity of transfer of the taxonomical position of Corynebacterium pseudopyogenes from genus Corynebacterium to genus Actinomyces. In: Izuka H, Hasegawa T (eds) Proceeding of the first international conference on culture collection. University of Tokyo Press, Tokyo, pp 493–505

    Google Scholar 

  21. Tanaka R, Mutai M (1980) Improved medium for selective isolation and enumeration of Bifidobacterium. Appl Environ Microbiol 40:866–869

    Google Scholar 

  22. Petts DN (1984) Colistin–oxolinic acid–blood agar: a new selective medium for streptococci. J Clin Microbiol 19:4–7

    Google Scholar 

  23. Sonoike K, Mada M, Mutai M (1986) Selective agar medium for counting viable cells of bifidobacteria in fermented milk (in Japanese with English abstract). J Food Hyg Soc Jpn 27:238–244

    Google Scholar 

  24. Kitajima H, Sumida Y, Tanaka R, Yuki N, Takayama H, Fujimura M (1997) Early administration of Bifidobacterium breve to preterm infants: randomized controlled trial. Arch Dis Child 76:101–107

    Google Scholar 

  25. Kikuchi H, Yajima T (1992) Correlation between water-holding capacity of different types of cellulose in vitro and gastrointestinal retention time in vivo of rats. J Sci Food Agric 60:139–146

    Google Scholar 

  26. Mochizuki H, Trocki O, Dominioni L, Brackett KA, Joffe SN, Alexander JW (1984) Mechanism of prevention of postburn hypermetabolism and catabolism by early enteral feeding. Ann Surg 200:297–310

    Google Scholar 

  27. Gionotti L, Alexander JW, Nelson JL (1994) Role of early enteral feeding and acute starvation on postburn bacterial translocation and host defense: prospective, randomized trials. Crit Care Med 22:265–272

    Google Scholar 

  28. Kudsk KA, Croce MA, Fabian TC, Minard G, Tolley EA, Poret HA (1992) Enteral versus parenteral feeding: effects on septic morbidity after blunt and penetrating abdominal trauma. Ann Surg 215:503–513

    Google Scholar 

  29. Omura K, Hirano K, Kanehira E, Kaito K, Tamura M, Nishida S, Kawakami K, Watanabe Y (2000) Small amount of low-residue diet with parenteral nutrition can prevent decreases in intestinal mucosal integrity. Ann Surg 231:112–118

    Google Scholar 

  30. Yuki N, Watanabe K, Mike A, Tagami Y, Tanaka R, Ohwaki M, Morotomi M (1999) Survival of a probiotic, Lactobacillus casei Shirota, in the gastrointestinal tract: selective isolation from feces and identification using monoclonal antibodies. Int J Food Microbiol 48:51–57

    Google Scholar 

  31. Welsh FK, Ramsden CW, MacLennan K, Sheridan MB, Barclay GR, Guillou PJ, Reynolds JV (1998) Increased intestinal permeability and altered mucosal immunity in cholestatic jaundice. Ann Surg 227:205–212

    Google Scholar 

  32. Luk G, Bayless TM, Baylin SB (1983) Plasma postheparin diamine oxidase. J Clin Invest 71:1308–1315

    Google Scholar 

  33. Mitsuoka T (2000) Significance of dietary modulation of intestinal flora and intestinal environment. Biosci Microflora 19:15–25

    Google Scholar 

  34. Schneider SM, Le Gall P, Girard-Pipau F, Piche T, Pompei A, Nano JL, Hebuterne X, Rampal P (2000) Total artificial nutrition is associated with major changes in the fecal flora. Eur J Nutr 39:248–255

    Google Scholar 

  35. Guerrant GO, Lambert MA, Moss CW (1982) Analysis of short-chain acids from anaerobic bacteria by high-performance liquid chromatography. J Clin Microbiol 16:355–360

    Google Scholar 

  36. Takagi A, Matsuzaki T, Sato M, Nomoto K, Morotomi M, Yokokura T (1999) Inhibitory effect of oral administration of Lactobacillus casei on 3-methylcholanthrene-induced carcinogenesis in mice. Med Microbiol Immunol 188:111–116

    Google Scholar 

  37. Yasui H, Nagaoka N, Hayakawa K (1994) Augmentation of anti-influenza virus hemagglutinin antibody production by Peyer’s patch cells with Bifidobacterium breve YIT4064. Clin Diagn Lab Immunol 1:244–246

    Google Scholar 

  38. Kato I, Tanaka K, Yokokura T (1999) Lactic acid bacterium potently induces the production of interleukin-12 and interferon-gamma by mouse splenocytes. Int J Immunopharmacol 21:121–131

    Google Scholar 

  39. Yasui H, Nagaoka N, Mike A (1991) Enhancement of immune response in Peyer’s patch cells cultured with Bifidobacterium breve. J Dairy Sci 74:1187–1195

    Google Scholar 

  40. Takagi A, Matsuzaki T, Sato M, Nomoto K, Morotomi M, Yokokura T (2001) Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a probiotic microorganism. Carcinogenesis 22:599–605

    Article  CAS  PubMed  Google Scholar 

  41. Sakata T (1995) Effect of short-chain fatty acids on the proliferation of gut epithelial cells in vivo. In: Cummings JH, Rombeau JL, Sakata T (eds) Physiological and clinical aspects of short-chain fatty acids. Cambridge University Press, Cambridge, pp 289–305

    Google Scholar 

  42. Cherbut C (1995) Effects of short-chain fatty acids on gastrointestinal motility. In: Cummings JH, Rombeau JL, Sakata T (ed) Physiological and clinical aspects of short-chain fatty acids. Cambridge University Press, Cambridge, pp 191–208

    Google Scholar 

  43. Willemsen LE, Koetsier MA, van Deventer SJH, van Tol EA (2003) Short chain fatty acids stimulate epithelial mucin2 expression through differential effects on prostaglandin E1 and E2 production by intestinal myofibroblasts. Gut 52:1442–1447

    Google Scholar 

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Hidetoshi Kanazawa, Masato Nagino, Satoshi Kamiya, Shunichiro Komatsu & Yuji Nimura

  2. Department of Emergency and Critical Care Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Toshihiko Mayumi

  3. Nagoya University College of Medical Technology, Nagoya, Japan

    Kenji Takagi

  4. Yakult Central Institute for Microbiological Research, Tokyo, Japan

    Takashi Asahara, Koji Nomoto & Ryuichiro Tanaka

Authors
  1. Hidetoshi Kanazawa
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  2. Masato Nagino
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  3. Satoshi Kamiya
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  4. Shunichiro Komatsu
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  5. Toshihiko Mayumi
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  6. Kenji Takagi
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  7. Takashi Asahara
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  8. Koji Nomoto
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  9. Ryuichiro Tanaka
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  10. Yuji Nimura
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Corresponding author

Correspondence to Yuji Nimura.

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Kanazawa, H., Nagino, M., Kamiya, S. et al. Synbiotics reduce postoperative infectious complications: a randomized controlled trial in biliary cancer patients undergoing hepatectomy. Langenbecks Arch Surg 390, 104–113 (2005). https://doi.org/10.1007/s00423-004-0536-1

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  • DOI: https://doi.org/10.1007/s00423-004-0536-1

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