Skip to main content

Advertisement

SpringerLink
Log in

Splenectomy and azygoportal disconnection decreases the risk of hepatocellular carcinoma for cirrhosis patients with portal hypertension bleeding: a 10-year retrospective follow-up study based on the inverse probability of treatment weighting method

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Liver cirrhosis is the highest risk factor for hepatocellular carcinoma (HCC) worldwide. However, etiological therapy is the only option in cirrhosis patients to decrease the HCC risk. The aim of this study was to explore whether laparoscopic splenectomy and azygoportal disconnection (LSD) decreases the risk of HCC for patients with cirrhotic portal hypertension (CPH).

Methods

Between April 2012 and April 2021, we identified 595 CPH patients in our hepatobiliary pancreatic center who were diagnosed with gastroesophageal variceal bleeding and secondary hypersplenism, and performed a 10-year retrospective follow-up. Inverse probability of treatment weighting (IPTW) was used to adjust for potential confounders, weighted Kaplan–Meier curves and logistic regression to estimate survival and risk differences.

Results

According to the method of therapy, patients were divided into LSD (n = 345) and endoscopic therapy (ET; n = 250) groups. Kaplan–Meier analysis revealed that patients who underwent LSD had higher survival benefit with those who underwent ET (P < 0.001). At the end of the follow-up, ET group was associated with a higher HCC incidence density compared with LSD group (28.1/1000 vs 9.6/1000 person-years; Rate ratio [RR] 2.922, 95% confidence intervals [CI] 1.599–5.338). In addition, logistic regression analyses weighted by IPTW revealed that, compared with ET, LSD was an independent protective predictor of HCC incidence (odds ratio [OR] 0.440, 95% CI 0.316–0.612; P < 0.001).

Conclusions

Considering the better postoperative survival and the ability to prevent HCC in CPH patients with gastroesophageal variceal bleeding and secondary hypersplenism, LSD is worth popularization in situations where liver donors are scarce.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1545–602.

    Article  Google Scholar 

  2. GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1459–544.

    Article  Google Scholar 

  3. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. The Lancet. 2018;391:1301–14.

    Article  Google Scholar 

  4. Chinese Society of Infectious Diseases, Chinese Medical Association. Chinese Society of Hepatology, Chinese Medical Association [The guidelines of prevention and treatment for chronic hepatitis B (2019 version)]. Zhonghua Gan Zang Bing Za Zhi. 2019;27:938–61.

    Google Scholar 

  5. Baffy G, Brunt EM, Caldwell SH. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. J Hepatol. 2012;56:1384–91.

    Article  PubMed  Google Scholar 

  6. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021;18:223–38.

    Article  PubMed  Google Scholar 

  7. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries. CA Cancer J Clin. 2021;71:209–49.

    Article  PubMed  Google Scholar 

  8. Sharma SA, Kowgier M, Hansen BE, et al. Toronto HCC risk index: a validated scoring system to predict 10-year risk of HCC in patients with cirrhosis. J Hepatol. 2018;68:92–9.

    Article  Google Scholar 

  9. Chen XP, Wu ZD, Huang ZY, et al. Use of hepatectomy and splenectomy to treat hepatocellular carcinoma with cirrhotic hypersplenism. Br J Surg. 2005;92:334–9.

    Article  PubMed  Google Scholar 

  10. Bai DS, Qian JJ, Chen P, et al. Modified laparoscopic and open splenectomy and azygoportal disconnection for portal hypertension. Surg Endosc. 2014;28:257–64.

    Article  PubMed  Google Scholar 

  11. Jiang GQ, Bai DS, Chen P, et al. Modified laparoscopic splenectomy and azygoportal disconnection combined with cell salvage is feasible and might reduce the need for blood transfusion. World J Gastroenterol. 2014;20:18420–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. McCaffrey DF, Griffin BA, Almirall D, et al. A tutorial on propensity score estimation for multiple treatments using generalized boosted models. Stat Med. 2013;32:3388–414.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bai DS, Zhou BH, Qian JJ, et al. Effects of laparoscopic splenectomy and azygoportal disconnection on liver synthesis function and cirrhosis: a 2-year prospective study. Surg Endosc. 2020;34:5074–82.

    Article  PubMed  Google Scholar 

  14. Yu H, Guo S, Wang L, et al. Laparoscopic splenectomy and esophagogastric devascularization for liver cirrhosis and portal hypertension is a safe, effective, and minimally invasive operation. J Laparoendosc Adv Surg Tech A. 2016;26:524–30.

    Article  PubMed  Google Scholar 

  15. Zhe C, Jian-wei L, Jian C, et al. Laparoscopic versus open splenectomy and esophagogastric devascularization for bleeding varices or severe hypersplenism: a comparative study. J Gastrointest Surg. 2013;17:654–9.

    Article  PubMed  Google Scholar 

  16. Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47(Suppl):S2-6.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zhang X, El-Serag HB, Thrift AP. Sex and race disparities in the incidence of hepatocellular carcinoma in the United States examined through age-period-cohort analysis. Cancer Epidemiol Biomarkers Prev. 2020;29:88–94.

    Article  PubMed  Google Scholar 

  18. Lesurtel M, Graf R, Aleil B, et al. Platelet-derived serotonin mediates liver regeneration. Science. 2006;312:104–7.

    Article  CAS  PubMed  Google Scholar 

  19. Murata K, Shiraki K, Sugimoto K, et al. Splenectomy enhances liver regeneration through tumor necrosis factor (TNF)-alpha following dimethylnitrosamine-induced cirrhotic rat model. Hepatogastroenterology. 2001;48:1022–7.

    CAS  PubMed  Google Scholar 

  20. Chen D, Liu W, Leng E, et al. Effect of splenectomy on CCl4-induced liver fibrosis in rats. Chin Med J (Engl). 1998;111:779–83.

    CAS  PubMed  Google Scholar 

  21. Morinaga A, Ogata T, Kage M, et al. Comparison of liver regeneration after a splenectomy and splenic artery ligation in a dimethylnitrosamine-induced cirrhotic rat model. HPB (Oxford). 2010;12:22–30.

    Article  PubMed  Google Scholar 

  22. Akahoshi T, Hashizume M, Tanoue K, et al. Role of the spleen in liver fibrosis in rats may be mediated by transforming growth factor beta-1. J Gastroenterol Hepatol. 2002;17:59–65.

    Article  CAS  PubMed  Google Scholar 

  23. Ueda S, Yamanoi A, Hishikawa Y, et al. Transforming growth factor-beta1 released from the spleen exerts a growth inhibitory effect on liver regeneration in rats. Lab Invest. 2003;83:1595–603.

    Article  CAS  PubMed  Google Scholar 

  24. Arakawa Y, Shimada M, Uchiyama H, et al. Beneficial effects of splenectomy on massive hepatectomy model in rats. Hepatol Res. 2009;39:391–7.

    Article  PubMed  Google Scholar 

  25. Ugel S, Peranzoni E, Desantis G, et al. Immune tolerance to tumor antigens occurs in a specialized environment of the spleen. Cell Rep. 2012;2:628–39.

    Article  CAS  PubMed  Google Scholar 

  26. Aoe T, Okamoto Y, Saito T. Activated macrophages induce structural abnormalities of the T cell receptor-CD3 complex. J Exp Med. 1995;181:1881–6.

    Article  CAS  PubMed  Google Scholar 

  27. Shimada M, Hashizume M, Shirabe K, et al. A new surgical strategy for cirrhotic patients with hepatocellular carcinoma and hypersplenism. Performing a hepatectomy after a laparoscopic splenectomy. Surg Endosc. 2000;14:127–30.

    Article  CAS  PubMed  Google Scholar 

  28. Karakantza M, Mouzaki A, Theodoropoulou M, et al. Th1 and Th2 cytokines in a patient with Evans’ syndrome and profound lymphopenia. Br J Haematol. 2000;110:968–70.

    Article  CAS  PubMed  Google Scholar 

  29. Nomura Y, Kage M, Ogata T, et al. Influence of splenectomy in patients with liver cirrhosis and hypersplenism. Hepatol Res. 2014;44:E100–9.

    Article  CAS  PubMed  Google Scholar 

  30. Hashimoto N, Shimoda S, Kawanaka H, et al. Modulation of CD4+ T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis. Clin Exp Immunol. 2011;165:243–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Voutsadakis IA. PD-1 inhibitors monotherapy in hepatocellular carcinoma: meta-analysis and systematic review. Hepatobiliary Pancreat Dis Int. 2019;18:505–10.

    Article  PubMed  Google Scholar 

  32. Voutsadakis IA. Immune ligands for cytotoxic T lymphocytes (CTLS) in cancer stem cells (CSCS). Front Biosci (Landmark Ed). 2018;23:563–83.

    Article  CAS  PubMed  Google Scholar 

  33. Han Y, Liu Q, Hou J, et al. Tumor-induced generation of splenicerythroblast-like ter-cells promotes tumor progression. Cell. 2018;173:634-48.e612.

    Article  CAS  PubMed  Google Scholar 

  34. Shi H, Han X, Sun Y, et al. Chemokine (C-X-C motif) ligand 1 and CXCL2 produced by tumor promote the generation of monocytic myeloid-derived suppressor cells. Cancer Sci. 2018;109:3826–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tian-Jiao Li, Hao Li, Zhang W-H, et al. Human splenic TER cells: a relevant prognostic factor acting via the artemin-GFRα3-ERK pathway in pancreatic ductal adenocarcinoma. Int J Cancer. 2021;148:1756–67.

    Article  Google Scholar 

  36. Jiang GQ, Chen P, Qian JJ, et al. Perioperative advantages of modified laparoscopic vs open splenectomy and azygoportal disconnection. World J Gastroenterol. 2014;20:9146–53.

    PubMed  PubMed Central  Google Scholar 

  37. Jiang XZ, Zhao SY, Luo H, et al. Laparoscopic and open splenectomy and azygoportal disconnection for portal hypertension. World J Gastroenterol. 2009;15:3421–5.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Garssen B, Goodkin K. On the role of immunological factors as mediators between psychosocial factors and cancer progression. Psychiatry Res. 1999;85:51–61.

    Article  CAS  PubMed  Google Scholar 

  39. Sklar LS, Anisman H. Stress and coping factors influence tumor growth. Science. 1979;205:513–5.

    Article  CAS  PubMed  Google Scholar 

  40. Moreno-Smith M, Lutgendorf SK, Sood AK. Impact of stress on cancer metastasis. Future Oncol. 2010;6:1863–81.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Scientific Research Subject of Jiangsu Province Health Department (No. H201661) and the Project of Invigorating Health Care through Science, Technology and Education: Jiangsu Provincial Medical Youth Talent (QNRC2016331).

Author information

Author notes

  1. Tian-Ming Gao, Jie Zhou, and Xiao-Xing Xiang contributed equally to this work.

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, 98 West Nantong Rd, Yangzhou, 225001, China

    Tian-Ming Gao, Jie Zhou, Xiao-Xing Xiang, Sheng-Jie Jin, Jian-Jun Qian, Chi Zhang, Bao-Huan Zhou, Dou-Sheng Bai & Guo-Qing Jiang

  2. Department of Hepatobiliary Surgery, The First Clinical College, Dalian Medical University, 9 West Section of South Port Arthur Rd, Dalian, 116027, Liaoning, China

    Jie Zhou

  3. Department of Digestive Diseases, Clinical Medical College, Yangzhou University, 98 West Nantong Rd, Yangzhou, 225001, China

    Xiao-Xing Xiang

  4. The Administration Office, Yangzhou Blood Center, Yangzhou, 225001, China

    Hua Tang

Authors
  1. Tian-Ming Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jie Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao-Xing Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sheng-Jie Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian-Jun Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bao-Huan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hua Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dou-Sheng Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Guo-Qing Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

T-MG: contributed to the study design, collected samples, and drafted the manuscript. JZ: contributed to the study design, collected samples, and assisted in drafting and revising the manuscript. X-XX: contributed to the study design and assisted in drafting and revising the manuscript. S-JJ: contributed to the study design and assisted in drafting and revising the manuscript. J-JQ: contributed to the study design and assisted in drafting and revising the manuscript. CZ: contributed to the study design and assisted in drafting and revising the manuscript. B-HZ: contributed to the study design and assisted in drafting and revising the manuscript. HT: contributed to the study design and assisted in drafting and revising the manuscript. D-SB: contributed to the study design, conducted analysis and interpretation of the data and assisted in drafting and revising the manuscript. G-QJ: contributed to the study design, conducted analysis and interpretation of the data and assisted in drafting and revising the manuscript.

Corresponding authors

Correspondence to Dou-Sheng Bai or Guo-Qing Jiang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the Ethics Committee of the Clinical Medical College of Yangzhou University. The Judgement’s reference number is No. 2022ky181.

Consent to participate

Written informed consent was obtained from the patient.

Unique identifying number (UIN)

Registry used. Name of the registry: researchregistery.com. Unique Identifying number or registration ID: researchregistry7777. Hyperlink to the registration (must be publicly accessible): https://www.researchregistry.com/browse-the-registry#home/.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 435 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gao, TM., Zhou, J., Xiang, XX. et al. Splenectomy and azygoportal disconnection decreases the risk of hepatocellular carcinoma for cirrhosis patients with portal hypertension bleeding: a 10-year retrospective follow-up study based on the inverse probability of treatment weighting method. J Gastroenterol 58, 503–512 (2023). https://doi.org/10.1007/s00535-023-01982-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-023-01982-z

Keywords

Search

Navigation