Excessive intraoperative blood loss independently predicts recurrence of hepatocellular carcinoma after liver transplantation

Abstract

BackgroundSeveral studies have investigated the effect of intraoperative blood loss (IBL) on recurrence of tumors. However, the independent effect of IBL on oncological outcome after liver transplantation (LT) for hepatocellular carcinoma (HCC) is unclear.MethodsA total of 479 patients who underwent LT for HCC from January 2001 to December 2012 at our institution were enrolled in this retrospective study. Kaplan–Meier and Cox regression methods were used to assess the recurrence rate, as well as its risk factors. Stratified analysis was performed to further examine the effect of IBL on HCC recurrence according to different characteristics of tumors. We also investigated the independent risk factors for excessive IBL using logistic regression analysis.ResultsThe median follow-up was 28 months (range, 1–131 months). Kaplan–Meier analysis with the log-rank test according to IBL at per liter intervals showed that IBL > 4 L was significantly associated with a higher recurrence rate (P < 0.001). Multivariate analysis identified that IBL > 4 L (P < 0.001; hazard ratio [HR] = 2.32, 95 % confidence interval [CI] = 1.60–3.36) was an independent risk factor for post-LT HCC recurrence, as well as age < 60 years, exceeding Milan criteria, α-fetoprotein levels > 400 ng/mL, and micro- and macrovascular invasion. IBL > 4 L (P < 0.001; HR = 2.45, 95 % CI = 1.64–3.66) was also independently associated with early (within 1 year) recurrence after LT. Furthermore, a significant correlation between IBL > 4 L and vascular invasion (P = 0.019) was found. IBL > 4 L was independently associated with HCC recurrence for patients with vascular invasion, but not for patients without vascular invasion. Finally, we found that the presence of ascites, model for end-stage liver disease score, and operation time were independent risk factors for IBL > 4 L.ConclusionsExcessive IBL is an independent predictor of HCC recurrence after LT, especially in patients with vascular invasion.

Prognostic Impact of Intraoperative Blood Loss in Liver Transplant Patients with Advanced Hepatocellular Carcinoma Blood Loss and HCC Recurrence

“…Teng et al demonstrated in 2014 that intraoperative bleeding was an independent risk factor of poor outcome in 223 LT patients with HCC, however, withou treporting on the tumor recurrence rate (33). Recently, Liu et al from the same transplant group found that excessive blood loss (>4 l) is associated with early HCC recurrence (34). Although we used a significantly lower cut-off value, our study supports what has been reported by Liu et al, namely that enhanced intraoperative bleeding portends oncological risk in LT patients with HCC.…”

“…Assuming occult tumor cells to be the trigger for promoting post-LT metastasis (18), an adverse prognostic impact of IOBL should be particularly evident in patients with vascular tumor invasion. Indeed, Liu et al have shown that excessive intraoperative bleeding is independently associated with HCC relapse in patients with, but not in those without, tumor infiltration into the vascular system (34). However, the clinical utility of this interesting finding was rather limited, since data were based on (post-transplant available) histopathological analysis not on (pretransplant available) radiographic staging (34).…”

Liver transplantation for hepatocellular carcinoma - non-cancer factors and implications for improving outcome beyond standard tumor criteria

“…The same group subsequently demonstrated in a series of 479 patients that, apart from recipients age, beyond MC status, AFP > 400 ng/mL and vascular invasion, IOBL > 4 L was an independent predictor of overall HCC recurrence and early post-LT (within 1 year) tumor relapse. In addition, IOBL was independently correlated with tumor recurrence in patients with but not in those without vascular invasion [126] .…”

“…Milan: HR = 1.039; 95%CI 1.021-1.057; P < 0.001 UCSF: HR = 1.039; 95%CI 1.002-1.057; P < 0.001 Fudan: HR = 1.035; 95%CI 1.018-1.052; P < 0.001 Hangzhou: HR = 1.020; 95%CI 1.000-1.040; P = 0.046 Liu et al . [126] 479 Cumulative 1-and 3-year RFS rates were 30.5% and 42.0% in IOBL ≤ 4 L, and 52.6% and 62.8% in IOBL > 4 L (P < 0.001). IOBL > 4 L was identified as an independent promoter of overall HCC recurrence (HR = 2.32; 95%CI 1.60-3.36; P < 0.001) and early post-LT (within 1 year) tumor relapse (HR = 2.45; 95%CI 1.64-3.66; P < 0.001).…”

“…Enhanced spread of occult cancer cells, aggravation of I/R injury to the graft and induction of proinflammatory and immunosuppressive mechanisms are currently discussed as underlying cancerogenic mechanisms [125][126][127][128][129] . Apart from that, IOBL increases the need of red blood cell transfusion, which in turn enhances the oncological risk by induction of pro-inflammatory and immunosuppressive mechanisms [130,131] .…”