scholarly journals Blood indices and circulating tumor cells for predicting metastasis of hepatocellular carcinoma after liver transplantation

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Li Zhuang ◽  
Xiang-Yan Liu ◽  
Heng-Kai Zhu ◽  
Zhuo-Yi Wang ◽  
Wu Zhang ◽  
...  

Abstract Objectives Liver transplantation (LT) can benefit the long-term survival of hepatocellular carcinoma (HCC) patients. We hypothesized that circulating tumor cell (CTC) levels and subtypes are intimately associated with metastasis status of HCC patients. This study was designed to test that compositive hematological indices including CTC can provide a prediction of post-LT metastasis. Methods Between 2017 and 2018, 37 HCC patients within Hangzhou criteria receiving LT were included for analysis. The 24-month follow-up was mainly conducted by outpatient and telephone. Blood samples were collected, and hematological indices were examined. The outcomes such as PFS, recurrence, metastasis, location of recurrence/metastasis, and number of metastases were recorded. Results The follow-up analysis showed that microvascular invasion (MVI) classification at the baseline is associated with metastasis. Next, α-fetoprotein (AFP) level was another useful indicator of postoperative metastasis, especially at the third or fourth month; the protein induced by vitamin K absence or antagonist-II (PIVKA-II) level three months after LT was significantly higher for those who had later metastasis. The mesenchymal CTC level at the 45th day was increased for in the metastasis group. Using two-ends Logistic regression, the calculated value MP (metastasis predictor, by above factors). Had an AUC of 0.858 in the ROC curve, with a cutoff value of 0.328. Conclusions In conclusion, microvascular invasion, AFP level at the third or fourth month, PIVKA-II level at the third month, and mesenchymal CTC level at day 45 were associated with post-LT metastasis. Using Logistic regression based on above variables, the two-year metastasis can be predicted with satisfactory sensitivity and accuracy.

2020 ◽  
Author(s):  
Li Zhuang ◽  
Xiang-yan Liu ◽  
Heng-kai Zhu ◽  
Zhuo-yi Wang ◽  
Wu Zhang ◽  
...  

Abstract Background: Liver transplantation (LT) can benefit the long-term survival of hepatocellular carcinoma (HCC) patients. We hypothesized that circulating tumor cell (CTC) levels and subtypes are intimately associated with metastasis status of HCC patients, and this study was designed to test that compositive hematological indices including CTC can provide sensitive and accurate prediction of post-LT metastasis. Methods: Between 2017 and 2018, HCC patients receiving LT were included for analysis. The 24-month follow-up was mainly conducted by outpatient and telephone. Blood samples were collected, and hematological indices were examined. The outcomes such as PFS, recurrence, metastasis, location of recurrence/metastasis, and number of metastases were recorded. Results: The follow-up analysis showed that microvascular invasion (MVI) classification at the baseline is associated with metastasis. Next, AFP level was another useful indicator of postoperative metastasis, especially at the third or fourth month; the PIVKA-II level 3 months after LT was significantly higher for those who had later metastasis. The mesenchymal CTC level at the 45th day was increased for in the metastasis group. Using two-ends Logistic regression, the calculated value MP (metastasis predictor, by above factors). Had an AUC of 0.858 in the ROC curve, with a cutoff value of 0.328. In conclusion, microvascular invasion, AFP level at the third or fourth month, PIVKA-II level at the third month, and mesenchymal CTC level at day 45 were associated with post-LT metastasis. Conclusion: Using Logistic regression based on above variables, the 2-year metastasis can be predicted with satisfactory sensitivity and accuracy.


2020 ◽  
Vol 20 (9) ◽  
pp. 720-727
Author(s):  
Jianguo Qiu ◽  
Wei Tang ◽  
Chengyou Du

Background: Immune checkpoint modulators, such as the programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor, cytotoxic T-Lymphocyte-associated antigen 4 (CTLA-4) inhibitor have been investigated with encouraging results for hepatocellular carcinoma (HCC). However, the safety of this strategy in patients with previous liver transplantation (LT) is not well studied. Objective: To explore the safety and feasibility of immune checkpoints inhibitors in recurrent and metastatic HCC patients on a background of LT. Methods: A case of recurrent, refractory, metastatic HCC after LT, where PD-1 inhibitor was initiated, was described and related literature was reviewed. Results: There was complete remission in lung metastases and the partial radiological response of metastatic retroperitoneal lymph node to the drug with no liver graft rejection after 13 cycles of PD- 1 inhibitor injection. PD-1inhibitor, at least in this patient, was verified to play an important role in controlling tumor progression and prolonging patient survival. Conclusions: This novel drug might be a useful method to allow doctors to guarantee a better chance for long-term survival in recurrent, metastatic HCC patients with the previous LT. However, it should be used with caution in allograft recipients due to the risk of acute graft rejection, further larger, prospective studies are needed to determine optimal immunomodulatory therapy to achieve optimal anti-tumor efficacy with transplant liver preservation.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3730
Author(s):  
Berend R. Beumer ◽  
Roeland F. de Wilde ◽  
Herold J. Metselaar ◽  
Robert A. de Man ◽  
Wojciech G. Polak ◽  
...  

For patients presenting with hepatocellular carcinoma within the Milan criteria, either liver resection or liver transplantation can be performed. However, to what extent either of these treatment options is superior in terms of long-term survival is unknown. Obviously, the comparison of these treatments is complicated by several selection processes. In this article, we comprehensively review the current literature with a focus on factors accounting for selection bias. Thus far, studies that did not perform an intention-to-treat analysis conclude that liver transplantation is superior to liver resection for early-stage hepatocellular carcinoma. In contrast, studies performing an intention-to-treat analysis state that survival is comparable between both modalities. Furthermore, all studies demonstrate that disease-free survival is longer after liver transplantation compared to liver resection. With respect to the latter, implications of recurrences for survival are rarely discussed. Heterogeneous treatment effects and logical inconsistencies indicate that studies with a higher level of evidence are needed to determine if liver transplantation offers a survival benefit over liver resection. However, randomised controlled trials, as the golden standard, are believed to be infeasible. Therefore, we suggest an alternative research design from the causal inference literature. The rationale for a regression discontinuity design that exploits the natural experiment created by the widely adopted Milan criteria will be discussed. In this type of study, the analysis is focused on liver transplantation patients just within the Milan criteria and liver resection patients just outside, hereby ensuring equal distribution of confounders.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Walid El Moghazy ◽  
Samy Kashkoush ◽  
Glenda Meeberg ◽  
Norman Kneteman

Background. We aimed to assess incidentally discovered hepatocellular carcinoma (iHCC) over time and to compare outcome to preoperatively diagnosed hepatocellular carcinoma (pdHCC) and nontumor liver transplants.Methods.We studied adults transplanted with a follow-up of at least one year. Patients were divided into 3 groups according to diagnosis of hepatocellular carcinoma.Results.Between 1990 and 2010, 887 adults were transplanted. Among them, 121 patients (13.6%) had pdHCC and 32 patients (3.6%) had iHCC; frequency of iHCC decreased markedly over years, in parallel with significant increase in pdHCC. Between 1990 and 1995, 120 patients had liver transplants, 4 (3.3%) of them had iHCC, and only 3 (2.5%) had pdHCC, while in the last 5 years, 263 patients were transplanted, 7 (0.03%) of them had iHCC, and 66 (25.1%) had pdHCC (P<0.001). There was no significant difference between groups regarding patient survival; 5-year survival was 74%, 75.5%, and 77.3% in iHCC, pdHCC, and non-HCC groups, respectively (P=0.702). Patients with iHCC had no recurrences after transplant, while pdHCC patients experienced 17 recurrences (15.3%) (P=0.016).Conclusions.iHCC has significantly decreased despite steady increase in number of transplants for hepatocellular carcinoma. Patients with iHCC had excellent outcomes with no tumor recurrence and survival comparable to pdHCC.


1996 ◽  
pp. 109-111 ◽  
Author(s):  
G. Colella ◽  
G. F. Rondinara ◽  
L. De Carlis ◽  
C. V. Sansalone ◽  
A. O. Slim ◽  
...  

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