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Impact of Hepatic Pedicle Clamping on Long-Term Survival Following Hepatectomy for Hepatocellular Carcinoma: Stratified Analysis Based on Intraoperative Blood Transfusion Status

  • Hepatobiliary Tumors
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Abstract

Background

Hepatic pedicle clamping (HPC) is frequently utilized during hepatectomy to reduce intraoperative bleeding and diminish the need for intraoperative blood transfusion (IBT). The long-term prognostic implications of HPC following hepatectomy for hepatocellular carcinoma (HCC) remain under debate. This study aims to elucidate the association between HPC and oncologic outcomes after HCC resection, stratified by whether IBT was administered.

Patients and Methods

Prospectively collected data on patients with HCC who underwent curative resection from a multicenter database was studied. Patients were stratified into two cohorts on the basis of whether IBT was administered. The impact of HPC on long-term overall survival (OS) and recurrence-free survival (RFS) between the two cohorts was assessed by univariable and multivariable Cox regression analyses.

Results

Of 3362 patients, 535 received IBT. In the IBT cohort, using or not using HPC showed no significant difference in OS and RFS outcomes (5-year OS and RFS rates 27.9% vs. 24.6% and 13.8% vs. 12.0%, P = 0.810 and 0.530). However, in the non-IBT cohort of 2827 patients, the HPC subgroup demonstrated significantly decreased OS (5-year 45.9% vs. 56.5%, P < 0.001) and RFS (5-year 24.7% vs. 33.3%, P < 0.001) when compared with the subgroup without HPC. Multivariable Cox regression analysis identified HPC as an independent risk factor of OS and RFS [hazard ratios (HR) 1.16 and 1.12, P = 0.024 and 0.044, respectively] among patients who did not receive IBT.

Conclusions

The impact of HPC on the oncological outcomes following hepatectomy for patients with HCC differed significantly whether IBT was administered, and HPC adversely impacted on long-term survival for patients without receiving IBT during hepatectomy.

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References

  1. Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet. 2022;400:1345–62.

    Article  CAS  PubMed  Google Scholar 

  2. Chen H, Jia W. Progress in hepatectomy for hepatocellular carcinoma and peri-operation management. Genes Dis. 2020;7:320–7.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gunasekaran G, Bekki Y, Lourdusamy V, Schwartz M. Surgical treatments of hepatobiliary cancers. Hepatology. 2021;73(Suppl 1):128–36.

    Article  PubMed  Google Scholar 

  4. Katz SC, Shia J, Liau KH, Gonen M, Ruo L, Jarnagin WR, et al. Operative blood loss independently predicts recurrence and survival after resection of hepatocellular carcinoma. Ann Surg. 2009;249:617–23.

    Article  PubMed  Google Scholar 

  5. Rana A, Petrowsky H, Hong JC, Agopian VG, Kaldas FM, Farmer D, et al. Blood transfusion requirement during liver transplantation is an important risk factor for mortality. J Am Coll Surg. 2013;216:902–7.

    Article  PubMed  Google Scholar 

  6. Yang T, Liu K, Liu CF, Zhong Q, Zhang J, Yu JJ, et al. Impact of postoperative infective complications on long-term survival after liver resection for hepatocellular carcinoma. Br J Surg. 2019;106:1228–36.

    Article  CAS  PubMed  Google Scholar 

  7. Pringle JHV. Notes on the arrest of hepatic hemorrhage due to trauma. Ann Surg. 1908;48:541–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Simillis C, Li T, Vaughan J, Becker LA, Davidson BR, Gurusamy KS. A cochrane systematic review and network meta-analysis comparing treatment strategies aiming to decrease blood loss during liver resection. Int J Surg. 2015;23:128–36.

    Article  PubMed  Google Scholar 

  9. Chen GX, Qi CY, Hu WJ, Wang XH, Hua YP, Kuang M, et al. Perioperative blood transfusion has distinct postsurgical oncologic impact on patients with different stage of hepatocellular carcinoma. BMC Cancer. 2020;20:487.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Tai YH, Wu HL, Mandell MS, Tsou MY, Chang KY. The association of allogeneic blood transfusion and the recurrence of hepatic cancer after surgical resection. Anaesthesia. 2020;75:464–71.

    Article  CAS  PubMed  Google Scholar 

  11. Cata JP, Wang H, Gottumukkala V, Reuben J, Sessler DI. Inflammatory response, immunosuppression, and cancer recurrence after perioperative blood transfusions. Br J Anaesth. 2013;110:690–701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vamvakas EC, Blajchman MA. Transfusion-related immunomodulation (TRIM): an update. Blood Rev. 2007;21:327–48.

    Article  PubMed  Google Scholar 

  13. Farid SG, White A, Khan N, Toogood GJ, Prasad KR, Lodge JP. Clinical outcomes of left hepatic trisectionectomy for hepatobiliary malignancy. Br J Surg. 2016;103:249–56.

    Article  CAS  PubMed  Google Scholar 

  14. Khajeh E, Shafiei S, Al-Saegh SA, Ramouz A, Hammad A, Ghamarnejad O, et al. Meta-analysis of the effect of the pringle maneuver on long-term oncological outcomes following liver resection. Sci Rep. 2021;11:3279.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lin N, Li J, Ke Q, Xin F, Zeng Y, Wang L, et al. Does the intermittent Pringle maneuver affect the recurrence following surgical resection for hepatocellular carcinoma? A systematic review. PLoS One. 2020;15:e0229870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wei X, Zheng W, Yang Z, Liu H, Tang T, Li X, et al. Effect of the intermittent Pringle maneuver on liver damage after hepatectomy: a retrospective cohort study. World J Surg Oncol. 2019;17:142.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Famularo S, Giani A, Di Sandro S, Sandini M, Giacomoni A, Pinotti E, et al. Does the Pringle maneuver affect survival and recurrence following surgical resection for hepatocellular carcinoma? A western series of 441 patients. J Surg Oncol. 2018;117:198–206.

    Article  PubMed  Google Scholar 

  18. van der Bilt JD, Kranenburg O, Nijkamp MW, Smakman N, Veenendaal LM, Te Velde EA, et al. Ischemia/reperfusion accelerates the outgrowth of hepatic micrometastases in a highly standardized murine model. Hepatology. 2005;42:165–75.

    Article  PubMed  Google Scholar 

  19. van der Bilt JD, Kranenburg O, Borren A, van Hillegersberg R, Borel Rinkes IH. Ageing and hepatic steatosis exacerbate ischemia/reperfusion-accelerated outgrowth of colorectal micrometastases. Ann Surg Oncol. 2008;15:1392–8.

    Article  PubMed  Google Scholar 

  20. Agrawal S, Belghiti J. Oncologic resection for malignant tumors of the liver. Ann Surg. 2011;253:656–65.

    Article  PubMed  Google Scholar 

  21. Brown ZJ, Tsilimigras DI, Ruff SM, Mohseni A, Kamel IR, Cloyd JM, et al. Management of hepatocellular carcinoma: a review. JAMA Surg. 2023;158:410–20.

    Article  PubMed  Google Scholar 

  22. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Int J Surg. 2014;12:1495–9.

    Article  Google Scholar 

  23. Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, et al. Guidelines for the diagnosis and treatment of hepatocellular carcinoma (2019 Edition). Liver Cancer. 2020;9:682–720.

  24. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Bland JM, Altman DG. The logrank test. BMJ. 2004;328:1073.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Gill RD. Multistate life-tables and regression models. Math Popul Stud. 1992;3:259–76.

    Article  CAS  PubMed  Google Scholar 

  27. Xia F, Lau WY, Xu Y, Wu L, Qian C, Bie P. Does hepatic ischemia-reperfusion injury induced by hepatic pedicle clamping affect survival after partial hepatectomy for hepatocellular carcinoma. World J Surg. 2013;37:192–201.

    Article  PubMed  Google Scholar 

  28. Wassmer CH, Moeckli B, Berney T, Toso C, Orci LA. Shorter survival after liver pedicle clamping in patients undergoing liver resection for hepatocellular carcinoma revealed by a systematic review and meta-analysis. Cancers (Basel). 2021;13:637.

    Article  PubMed  Google Scholar 

  29. Hao S, Chen S, Yang X, Wan C. Adverse impact of intermittent portal clamping on long-term postoperative outcomes in hepatocellular carcinoma. Ann R Coll Surg Engl. 2017;99:22–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang CC, Iyer SG, Low JK, Lin CY, Wang SH, Lu SN, et al. Perioperative factors affecting long-term outcomes of 473 consecutive patients undergoing hepatectomy for hepatocellular carcinoma. Ann Surg Oncol. 2009;16:1832–42.

    Article  PubMed  Google Scholar 

  31. Tung-Ping Poon R, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg. 2000;232:10–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yang F, Zhang Y, Ren H, Wang J, Shang L, Liu Y, et al. Ischemia reperfusion injury promotes recurrence of hepatocellular carcinoma in fatty liver via ALOX12-12HETE-GPR31 signaling axis. J Exp Clin Cancer Res. 2019;38:489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chen H, Lu D, Yang X, Hu Z, He C, Li H, et al. One shoot, two birds: alleviating inflammation caused by ischemia/reperfusion injury to reduce the recurrence of hepatocellular carcinoma. Front Immunol. 2022;13:879552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kamel YA, Sasa NAG, Helal SM, Attallah HA, Yassen KA. Monitoring the effects of automated gas control of sevoflurane versus target-guided propofol infusion on hemodynamics of liver patients during liver resection. A randomized controlled trial. J Anaesthesiol Clin Pharmacol. 2023;39:74–83.

  35. Giustiniano E, Nisi F, Rocchi L, Zito PC, Ruggieri N, Cimino MM, et al. Perioperative management of complex hepatectomy for colorectal liver metastases: the alliance between the surgeon and the anesthetist. Cancers (Basel). 2021;13:2203.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Page AJ, Kooby DA. Perioperative management of hepatic resection. J Gastrointest Oncol. 2012;3:19–27.

    PubMed  PubMed Central  Google Scholar 

  37. Melendez JA, Arslan V, Fischer ME, Wuest D, Jarnagin WR, Fong Y, et al. Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction. J Am Coll Surg. 1998;187:620–5.

    Article  CAS  PubMed  Google Scholar 

  38. Jones RM, Moulton CE, Hardy KJ. Central venous pressure and its effect on blood loss during liver resection. Br J Surg. 1998;85:1058–60.

    Article  CAS  PubMed  Google Scholar 

  39. Chen H, Merchant NB, Didolkar MS. Hepatic resection using intermittent vascular inflow occlusion and low central venous pressure anesthesia improves morbidity and mortality. J Gastrointest Surg. 2000;4:162–7.

    Article  CAS  PubMed  Google Scholar 

  40. Liang L, Li C, Wang MD, Wang H, Zhou YH, Zeng YY, et al. Development and validation of a novel online calculator for estimating survival benefit of adjuvant transcatheter arterial chemoembolization in patients undergoing surgery for hepatocellular carcinoma. J Hematol Oncol. 2021;14:165.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Liang L, Li C, Diao YK, Jia HD, Xing H, Pawlik TM, et al. Survival benefits from adjuvant transcatheter arterial chemoembolization in patients undergoing liver resection for hepatocellular carcinoma: a systematic review and meta-analysis. Therap Adv Gastroenterol. 2020;13:1756284820977693.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Yang T, Lu JH, Zhai J, Lin C, Yang GS, Zhao RH, et al. High viral load is associated with poor overall and recurrence-free survival of hepatitis B virus-related hepatocellular carcinoma after curative resection: a prospective cohort study. Eur J Surg Oncol. 2012;38:683–91.

    Article  CAS  PubMed  Google Scholar 

  43. Zhu H, Xing H, Yu B, Yan WT, Zhang CW, Guan MC, et al. Long-term survival and recurrence after curative resection for hepatocellular carcinoma in patients with chronic hepatitis C virus infection: a multicenter observational study from China. HPB (Oxford). 2020;22:1793–802.

    Article  PubMed  Google Scholar 

  44. Yu JJ, Shen F, Chen TH, Liang L, Han J, Xing H, et al. Multicentre study of the prognostic impact of preoperative bodyweight on long-term prognosis of hepatocellular carcinoma. Br J Surg. 2019;106:276–85.

    Article  CAS  PubMed  Google Scholar 

  45. Chiu CC, Lee KT, Wang JJ, Sun DP, Lee HH, Huang CC, et al. Preoperative health-related quality of life predicts minimal clinically important difference and survival after surgical resection of hepatocellular carcinoma. J Clin Med. 2019;8:576.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgement

The authors thank all the surgeons and patients who participated in the study.

Funding

This study was supported by the National Natural Science Foundation of China (No. 62275050), the Major Research Projects for Young and Middle-aged Talent of Fujian Provincial Health Commission (no. 2021ZQNZD013), the Key Clinical Specialty Discipline Construction Program of Fuzhou, Fujian (Grant Number: 201912002), Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic Tumors (Grant Number: 2020Y2013), the Scientific Foundation of Fuzhou Municipal Health Commission (Grant Number: 2021-S-wp1), Dawn Project Foundation of Shanghai (No. 21SG36), Shanghai Health and Hygiene Discipline Leader Project (Grant Number: 2022XD001), and Shanghai Outstanding Academic Leader Program (Grant Number: 23XD1424900). Role of the funder/sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian Province, China

    Shi-Chuan Tang MD, Kong-Ying Lin MD, Hong-Zhi Liu MD, Yong-Yi Zeng MD & Tian Yang MD

  2. Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China

    Shi-Chuan Tang MD, Kong-Ying Lin MD & Yong-Yi Zeng MD

  3. Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University (Second Military Medical University), Shanghai, China

    Jia-Hao Xu MD, Feng Shen MD, PhD, Wan Yee Lau MD, FRCS, FACS, FRACS (Hon) & Tian Yang MD

  4. Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Jiangsu, China

    Yi-Fan Yang MD

  5. Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China

    Jia-Ning Shi MD

  6. Department of Hepatobiliary, Heze Municiple Hospital, Shandong, China

    Jie Kong MD

  7. Department of General Surgery, First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong, China

    Xian-Ming Wang MD

  8. Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, China

    Zhong-Qi Fan MD & Tian Yang MD

  9. The First Department of General Surgery, Fourth Hospital of Harbin, Heilongjiang, China

    Wei-Min Gu MD

  10. Department of Hepatobiliary Surgery, Pu’er People’s Hospital, Pu’er, China

    Ya-Hao Zhou MD

  11. Department of Hepatobiliary Surgery, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China

    Ying-Jian Liang MD

  12. Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China

    Wan Yee Lau MD, FRCS, FACS, FRACS (Hon)

  13. The Liver Disease Research Center of Fujian Province, Fuzhou, China

    Yong-Yi Zeng MD

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  1. Shi-Chuan Tang MD
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Contributions

Shi-Chuan Tang, Jia-Hao Xu, Yi-Fan Yang, Jia-Ning Shi, and Kong-Ying Lin contributed equally to this work. Drs Zeng and Yang had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conceptualization: Shi-Chuan Tang, Feng Shen, Yong-Yi Zeng, and Tian Yang. Acquisition, analysis, or interpretation of data: all authors. Drafting of the manuscript: Shi-Chuan Tang, Jia-Hao Xu, Yi-Fan Yang, Wan Yee Lau, Yong-Yi Zeng, and Tian Yang. Critical revision of the manuscript for important intellectual content: Shi-Chuan Tang, Wei-Min Gu, Ya-Hao Zhou, Hong-Zhi Liu, Ying-Jian Liang, Wan Yee Lau, and Tian Yang. Statistical analysis: Shi-Chuan Tang, Jia-Hao Xu, Jia-Ning Shi, Kong-Ying Lin, Jie Kong, Xian-Ming Wang, Zhong-Qi Fan, Hong-Zhi Liu, and Tian Yang. Obtained funding: Yong-Yi Zeng and Tian Yang. Administrative, technical, or material support: Xian-Ming Wang, Wei-Min Gu, Ya-Hao Zhou, Ying-Jian Liang, Feng Shen, Yong-Yi Zeng, and Tian Yang. Study supervision: Wan Yee Lau, Feng Shen, Yong-Yi Zeng, and Tian Yang. Final approval of manuscript: all authors.

Corresponding authors

Correspondence to Yong-Yi Zeng MD or Tian Yang MD.

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Tang, SC., Xu, JH., Yang, YF. et al. Impact of Hepatic Pedicle Clamping on Long-Term Survival Following Hepatectomy for Hepatocellular Carcinoma: Stratified Analysis Based on Intraoperative Blood Transfusion Status. Ann Surg Oncol 31, 1812–1822 (2024). https://doi.org/10.1245/s10434-023-14642-6

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