Skip to main content
SpringerLink
Log in

Impact of splenectomy and immunochemotherapy on survival following gastrectomy for carcinoma: Covariate interaction with immunosuppressive acidic protein, a serum marker for the host immune system

  • Original Articles
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

The role of the spleen in tumor immunology is still controversial in that it can either enhance or suppress the antitumor immune response depending on the tumor-bearing host. To clarify this biphasic effect of the spleen, a clinical evaluation of splenectomy in conjunction with immunotherapy and the host immune status was performed in gastric cancer patients. The effect of splenectomy and immunotherapy in 253 gastric cancer patients enrolled in a prospective randomized trial (SIP) was analyzed using the Cox’s proportional hazards model in terms of the covariate interaction of the preoperative immunosuppressive acidic protein (IAP) level. In patients with high IAP levels (>580 μg/ml) with predicted negative antitumor immune reactions splenectomy improved the prognosis. In patients with lower IAP values, conversely, the preservation of the spleen and immunotherapy demonstrated a significant benefit to survival. The spleen was shown to have a biphasic activity in terms of its antitumor immune response depending on the IAP level of the patient. The effect of immunotherapy is significantly influenced by the activity of spleen cells. The preoperative IAP level is therefore considered to be a possible indicator for the effectiveness of splenectomy and immunotherapy in curatively resected gastric cancer patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. The Gastrointestinal Tumor Study Group (1982) Controlled trial of adjuvant chemotherapy following curative resection for gastric cancer. Cancer 49:1116–1122

    Article  Google Scholar 

  2. Takahashi M, Fujimoto S, Kobayashi K, Takai M, Endoh F, Ohkubo H (1995) Indication for splenectomy combined with total gastrectomy for gastric cancer: analysis of data on 249, gastric cancer patients. Hepato-Gastroenterol 42:230–233

    CAS  Google Scholar 

  3. Okajima K, Isozaki H (1995) Splenectomy for treatment of gastric cancer: Japanese experience. World J Surg 19:537–540

    Article  CAS  PubMed  Google Scholar 

  4. Yasuna O, Hatayama Y, Yamaura Y (1984) Effects of surgical treatment and adjuvant chemotherapy studied by the depth of penetration in gastric cancer patients undergoing curative gastrectomy. Surgery 95:78–83

    CAS  PubMed  Google Scholar 

  5. Billiar TR, West MA, Hyland BJ, Simmons RL (1988) Splenectomy alters Kupffer cell response to endotoxin. Arch Surg 123:327–332

    CAS  PubMed  Google Scholar 

  6. King H, Shumacker HB (1952) Splenic studies 1. Susceptibility to infection after splenectomy performed in infancy. Ann Surg 136:239–242

    Article  CAS  PubMed  Google Scholar 

  7. Downey EC, Shackford SR, Fridlund PH, Ninnemann JL (1987) Long term depressed immune function in patients splenectomized for trauma. J Trauma 27:601–603

    Article  Google Scholar 

  8. Griffith JP, Sue-Ling HM, Martin I, Dixon MF, McMahon MJ, Axon ATR, Johnston D (1995) Preservation of the spleen improves survival after radical surgery for gastric cancer. Gut 36:684–690

    Article  CAS  PubMed  Google Scholar 

  9. Miwa T, Takezoe S, Moriya N, Iijima T, Gohchi A, Yamashita H, Kojima K, Ichikawa J, Matsumi A, Okamoto K, Orita K (1983) Effects of combined splenectomy and immunotherapy on survival (in Japanese). J Jpn Soc Cancer Ther 18:1815–1820

    CAS  Google Scholar 

  10. Honda R, Kobayashi K, Kase H, Sato Y, Yanagita K, Yoshio T (1989) Clinical evaluation of splenectomy for immunological influence in surgery of the gastric cancer (in Japanese). Jpn J Gastroenterol Surg 22:2606–2614

    Google Scholar 

  11. Toge T, Kameda A, Kuroi K, Seto Y, Yamada H, Arata S, Tomoda S, Hattori T (1985) Analysis of suppressor cell induction by the spleen in relation to splenectomy in gastric cancer patients (in Japanese). Oncologia 14:146–151

    Google Scholar 

  12. Toge T, Hattori T, Orita K, Ishibiki K, Yoshino K, Yamagishi H, Gohchi A, Okamura K, Nose Y, Miwa K, Inokuchi K (1990) Research on the meaning of splenectomy in gastric cancer operation: survival, postoperative complications and changes in immunological parameters (in Japanese). Proc Jpn Soc Cancer Ther 25:271

    Google Scholar 

  13. Maehara Y, Moriguchi S, Yoshida M, Takahashi I, Korenaga D, Sugimachi K (1991) Splenectomy does not correlate with length of survival in patients undergoing curative total gastrectomy for gastric carcinoma. Cancer 67:3006–3009

    Article  CAS  PubMed  Google Scholar 

  14. Clark JL, Saenz RH, Nava HR, Douglass HO (1991) Impact of splenectomy on survival following gastrectomy for adenocarcinoma. Am Surgeon 57:496–501

    CAS  PubMed  Google Scholar 

  15. Nakazato H, Koike A, Saji S, Ogawa N, Sakamoto J (1994) Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Lancet 343:1122–1126

    Article  CAS  PubMed  Google Scholar 

  16. Tamura K, Shibata Y, Matsuda Y, Ishida N (1981) Isolation and characterization of an immunosuppressive acidic protein from ascitic fluids of cancer patients. Cancer Res 41:3244–3252

    CAS  PubMed  Google Scholar 

  17. Shibata Y, Tamura K, Ishida N (1983) In vivo analysis of the suppressive effects of immunosuppressive acidic protein, a type of alpha-1 acid glycoprotein, in connection with its high level in tumor-bearing mice. Cancer Res 43:2889–2896

    CAS  PubMed  Google Scholar 

  18. Kennedy BJ (1987) The unified international gastric cancer staging classification. Scand J Gastroenterol 22 (suppl 133):11–13

    Article  Google Scholar 

  19. Sakamoto J, Teramukai S, Koike A, Saji S, Ohashi Y, Nakazato H (1996) Prognostic value of preoperative immunosuppressive acidic protein in patients with gastric carcinoma: findings from three independent clinical trials. Cancer 77:2206–2212

    Article  CAS  PubMed  Google Scholar 

  20. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 6:371–375

    Google Scholar 

  21. Cox DR (1972) Regression models and life tables. J R Statist Soc B 34:187–220

    Google Scholar 

  22. Ellison EC, Fabri PJ (1983) Complications of splenectomy. Surg Clin North Am 63:1313–1330

    CAS  PubMed  Google Scholar 

  23. Lockwood CM (1983) Immune functions of the spleen. Clin Lab Haematol 12:449–465

    CAS  Google Scholar 

  24. Llende M, Santiago-Delphin EA, Lavergne J (1986) Immunobiological consequences of splenectomy: a review. J Surg Res 40:85–94

    Article  CAS  PubMed  Google Scholar 

  25. Hellstrom I (1970) Serum mediated inhibition of cellular immunity to methylcholanthrene-induced murine sarcomas. Cell Immunol 1:18–30

    Article  CAS  PubMed  Google Scholar 

  26. Subramanian C, Mckhann CF (1978) Soluble suppressor factor from the spleens of tumor-bearing mice. Cancer Res 38:1996–2002

    CAS  PubMed  Google Scholar 

  27. Cuschieri A, Fayers P, Fielding J, Craven J, Bancewicz J, Joypaul V, Cook P (1996) Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomized controlled surgical trial. Lancet 347:995–999

    Article  CAS  PubMed  Google Scholar 

  28. Robertson CS, Chung SCS, Woods SDS, Griffin SM, Raimes SA, Lau JTF, Li AKC (1994) A prospective randomized trial comparing R1 subtotal gastrectomy with R3 total gastrectomy for antral cancer. Ann Surg 220:176–182

    Article  CAS  PubMed  Google Scholar 

  29. Standage BA, Gross JC (1982) Outcome and sepsis after splenectomy in adults. Am J Surg 143:545–548

    Article  CAS  PubMed  Google Scholar 

  30. Yamagishi H, Pellis NR, Kahan BD (1980) Effect of splenectomy upon tumor growth: characterization of splenic tumor-enhancing cells in vivo. Surgery 87:655–661

    CAS  PubMed  Google Scholar 

  31. Saji S, Oshita H, Yamamoto S, Takekoshi T, Sakata K (1983) Experimental study on merits and demerits of splenectomy in tumor bearers. J Surg Oncol 23:35–40

    Article  CAS  PubMed  Google Scholar 

  32. Orita K, Konaga E, Okada T, Kunisada K, Yumura M, Tanaka S (1977) Effect of splenectomy in tumor-bearing mice and gastric cancer patients. Gann 68:731–736

    CAS  PubMed  Google Scholar 

  33. Nordlund J, Gershon R (1975) Splenic regulation of the clinical appearance of small tumors. J Immunol 114:1486–1490

    CAS  PubMed  Google Scholar 

  34. Yashino K, Asanuma K, Haruyama F, Kubochi K, Suzuki K, Inada T, Konno H, Kurihara H, Okusawa S, Kubota T, Kumai K, Ishibiki K, Abe O (1983) Evaluation of splenectomy for possible metastasis from gastric cancer, with reference to nonspecific immunological parameters and postoperative survival. J Jpn Surg Soc 83:947–951

    Google Scholar 

  35. Honda R, Kobayashi K, Kato H, Sato Y, Yanagida K, Yoshio T (1989) Clinical evaluation of splenectomy for immunological influence in surgery of the gastric cancer. Jpn J Gastroenterol Surg 22:2606–2614

    Google Scholar 

  36. Sugimachi K, Kodama Y, Kumashiro R, Kanematsu T, Noda S, Inokuchi K (1980) Critical evaluation of prophylactic splenectomy in total gastrectomy for the stomach cancer. Gann 71:704–709

    CAS  PubMed  Google Scholar 

  37. Suehiro S, Nagasue N, Ogawa Y, Sasaki Y, Hirose S, Yukaya H (1984) The negative effect of splenectomy on the prognosis of gastric cancer. Am J Surg 148:645–648

    Article  CAS  PubMed  Google Scholar 

  38. Brady MS, Rogatko A, Dent LL, Shiu MH (1991) Effect of splenectomy on morbidity and survival following curative gastrectomy for carcinoma. Arch Surg 126:359–364

    CAS  PubMed  Google Scholar 

  39. Miwa H, Kojima K, Ono F, Kobayashi T, Tsurumi T, Hatosaki A, Iijima T, Orita K (1983) Effect of splenectomy and immunotherapy on advanced gastric cancer associated with total gastrectomy. Jpn J Surg 13:20–24

    Article  CAS  PubMed  Google Scholar 

  40. Ogoshi K, Miyaji M, Iwata K, Kondoh Y, Tajima T, Mitomi T (1992) Splenectomy, immunosuppressive acidic protein and postoperative immunotherapy in gastric cancer patients with total or proximal gastrectomy; a multivariate analysis. Ann Cancer Res Ther 1:61–66

    Google Scholar 

  41. Shibata Y, Tamura K, Ishida N (1983) In vivo analysis of the suppressive effects of immunosuppressive acidic protein, a type of alpha-1 acid glycoprotein, in connection with the high level in the tumor bearing mice. Cancer Res 43:2889–2896

    CAS  PubMed  Google Scholar 

  42. Gahmgerg CG, Anderson LC (1987) Leucocyte surface origin of human alpha-1 acid glycoprotein (orosomucoid). J Exp Med 148:507–521

    Article  Google Scholar 

  43. Beutler B, Cerami A. Cachectin and tumor necrosis factors as two sides of the same biological coin. Nature 320:584–588

Download references

Author information

Authors and Affiliations

  1. Second Department of Surgery, Gifu University, Gifu, Japan

    Shigetoyo Saji, Katsuyuki Kunieda & Yasuyuki Sugiyama

  2. Department of Surgery and Laboratory of Clinical Oncology, Aichi Prefectural Hospital, 18 Kuriyado, Kakemachi, 444, Okazaki, Japan

    Junichi Sakamoto

  3. Department of Health Science, University of Tokyo, Tokyo, Japan

    Satoshi Teramukai & Yasuo Ohashi

  4. Department of Surgery, Yokoyama Gastrointestinal Hospital, Nagoya, Japan

    Hiroaki Nakazato

Authors
  1. Shigetoyo Saji
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Junichi Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Satoshi Teramukai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katsuyuki Kunieda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasuyuki Sugiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yasuo Ohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroaki Nakazato
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saji, S., Sakamoto, J., Teramukai, S. et al. Impact of splenectomy and immunochemotherapy on survival following gastrectomy for carcinoma: Covariate interaction with immunosuppressive acidic protein, a serum marker for the host immune system. Surg Today 29, 504–510 (1999). https://doi.org/10.1007/BF02482344

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02482344

Key Words

Search

Navigation