Living donor liver transplantation for hepatocellular carcinoma: a special reference to a preoperative des-gamma-carboxy prothrombin value

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a sensitive marker related to vascular invasion of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence in living donor liver transplantation (LDLT) with special reference to preoperative DCP values. METHODS: Forty consecutive adult HCC patients who underwent LDLT were examined for a correlation between the DCP value and vascular invasion. Risk factors for recurrence were also investigated using clinicopathological variables including preoperative DCP levels. RESULTS: The incidence of positive histological vascular invasion in patients with DCP values above 300 mAU/mL was higher than that with those with DCP value below 300 mAU/mL. Other significant risk factors for recurrence were over 5 cm tumor diameter, not meeting the Milan criteria, AFP value >400 ng/mL, histological vascular invasion, poorly differentiated histology, and male gender. Among the patients who did not meet the Milan criteria, those with both no more than 5 cm of tumor diameter and no more than 300 mAU/mL DCP exhibited a good prognosis. CONCLUSIONS: A high DCP value, namely >300 mAU/mL correlated with histological vascular invasion and was one of the strongest prognostic variables. Therefore, special attention should be paid to HCC patients with high DCP values. No correlation between the number of tumor nodules and recurrence was found; therefore, the Milan criteria may require revision regarding the number of tumor nodules.     

Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation.

In the present study, the results of living donor liver transplantation (LDLT) for 125 hepatocellular carcinoma (HCC) patients were analyzed to determine optimal criteria exceeding the Milan criteria (MC) but still with predictably good outcomes. On the basis of pretransplant imaging studies, 70 patients met the MC, and 55 patients did not. Patients who exceeded the MC but presented with 相似文献   

Significance of Des-Gamma-Carboxy Prothrombin in Selection Criteria for Living Donor Liver Transplantation for Hepatocellular Carcinoma

Des-gamma-carboxy prothrombin (DCP) levels reportedly correlate with histological features of hepatocellular carcinoma (HCC). We examined serum DCP as a predictor of HCC recurrence in 144 patients who underwent living donor liver transplantation. Receiver operating characteristics (ROC) analysis revealed superiority of DCP and AFP over preoperative tumor size or number for predicting recurrence. Multivariate analysis revealed tumor size >5 cm, ≥11 nodules, and DCP >400 mAU/mL as significant independent risk factors for recurrence. Incidence of microvascular invasion (62% vs. 27%, p = 0.0003) and poor differentiation (38% vs. 16%, p = 0.0087) were significantly higher for patients with DCP >400 mAU/mL than for patients with DCP ≤400 mAU/mL. In ROC analysis for patients with ≤10 nodules all ≤5 cm to predict recurrence, area under the curve was much higher for DCP than for AFP (0.84 vs. 0.69). Kyoto criteria were thus defined as ≤10 nodules all ≤5 cm, and DCP ≤400 mAU/mL. The 5-year recurrence rate for 28 patients beyond-Milan but within-Kyoto criteria was as excellent as that for 78 patients within-Milan criteria (3% vs. 7%). The preoperative DCP level offers additional information regarding histological features, and thus can greatly improve patient selection criteria when used with tumor bulk information.     

Measurement of des-gamma-carboxy prothrombin levels in hemodialysis patients positive for anti-hepatitis virus C antibody

BACKGROUND: The prevalence of anti-hepatitis virus C (HCV) antibody is much higher in hemodialysis (HD) patients than in the normal population. Recently, blood des-gamma-carboxy prothrombin (PIVKA-II) has been demonstrated as a sensitive marker for the early detection of hepatocellular carcinoma (HCC). In this study, we measured blood PIVKA-II in HD patients positive for anti-HCV antibody or hepatitis B virus surface (HBs) antigen to examine if HD therapy may affect the measurement of PIVKA-II. PATIENTS AND METHODS: Ninety-four stable HD patients who had anti-HCV antibodies (n = 86) or HBs antigen (n = 8) without any evidence of HCC were enrolled in the study (age: 60 +/- 11 years, duration of HD: 17 +/- 10 years, male/female = 63/31). Five patients had liver cirrhosis and another 5 patients received warfarin treatment. We simultaneously measured serum PIVKA-II and alpha-fetoprotein (AFP), and compared the association between these markers and HCV RNA titer and laboratory parameters. RESULTS: Serum PIVKA-II became positive (> or = 40 mAU/ml) in only 5.6% (5/89) of patients without warfarin administration, ranging from 47 to 71 mAU/ml. Seventy out of 89 patients (78.7%) were below 20 mAU/ml. Serum PIVKA-II did not correlate with biochemical parameters including HCV RNA, while serum AFP was significantly correlated with serum AST (r = 0.21, p < 0.05), gamma-GTP (r = 0.21, p < 0.01) and platelet counts (r = -0.29, p < 0.01), respectively. In contrast, 5 patients receiving warfarin had an extremely high PIVKA-II value ranging from 1,930 to 19,900 mAU/ml. PIVKA-II was significantly and inversely correlated with the thrombotest value (r = -0.72, p = 0.01). CONCLUSION: The positivity of blood PIVKA-II in HD patients with hepatitis viremia was identical to that in patients without renal failure. Warfarin treatment dramatically increased serum PIVKA-II more than 1,000 mAU/ml. These findings suggested that HD treatment itself did not affect the measurement of PIVKA-II, but vitamin K deficiency can readily influence the PIVKA-II level in dialysis patients.     

Expression Pattern Analysis of Hepatocellular Carcinoma Tumor Markers in Viral Hepatitis B and C Patients Undergoing Liver Transplantation and Resection

Background

This study was conducted to compare the expression patterns of serum alpha-fetoprotein (AFP) and proteins induced by vitamin K absence or antagonist-II (PIVKA-II) in hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) and resection at a high-volume single institution.

Methods

First, 663 liver transplant recipients with HCC were selected. They were divided into hepatitis B virus (HBV) (n = 628) and hepatitis C virus (HCV) groups (n = 35). Their medical records were retrospectively reviewed. Second, another cohort of 2709 patients who underwent HCC resection included 2258 HBV, 143 HCV, and 308 non-HBV non-HCV (NBNC) patients.

Results

In the transplantation group, pretransplantation AFP level >20 ng/mL was observed in 42.5% of HBV patients and 60% of HCV patients (P = .042). PIVKA-II level >40 mAU/mL was observed in 30.6% of HBV patients and 42.9% of HCV patients (P = .127). In the resection group, a preoperative AFP level >20 ng/mL was observed in 51.7% of HBV patients and 43.3% of HCV patients (P = .052). PIVKA-II level >40 mAU/mL was observed in 59.7% of HBV patients and 56.6% of HCV patients (P = .47). Preoperative AFP level >20 ng/mL and PIVKA-II level >40 mAU/mL were observed in 35.7% and 61% of NBNC patients, respectively. Receiver-operator characteristic curve analyses revealed that the expression pattern of PIVKA-II in patients with elevated AFP level was not predictable and vice versa, regardless of background liver diseases.

Conclusions

This study indicates that serum AFP and PIVKA-II may be expressed variably regardless of the types of background liver disease. Further large-volume multicenter studies are needed to evaluate the possibility of the etiology-dependent expression of tumor markers.     

Usefulness of PIVKA-II After Living-donor Liver Transplantation for Hepatocellular Carcinoma

Objective

Prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) is a useful tumor marker for hepatocellular carcinoma (HCC). However, the usefulness of post-transplantation surveillance with PIVKA-II is not clear. We evaluated the clinical value of PIVKA-II in monitoring HCC recurrence after living-donor liver transplantation (LDLT).

Protein Induced by Vitamin K Antagonist-II (PIVKA-II) Is a Reliable Prognostic Factor in Small Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) <2 cm in diameter has a favorable prognosis. Therefore surgical resection of small HCC is associated with good outcomes. However, the predisposing factors of prognosis following resection of HCC remain ill-defined. The aims of the present study were to identify the clinicopathologic characteristics and outcomes of patients with small HCC and analyze the predisposing factors for tumor recurrence after surgery.

Methods

We retrospectively reviewed 180 patients with small HCC who underwent hepatectomy between 2006 and 2010. Independent predictors of tumor recurrence were identified with Cox regression analysis.

Results

The 1-year, 3-year, and 5-year disease-free survival rates and overall survival rates were 83.7, 68.0, 65.3, and 98.9, 96.5, 92.7 %, respectively. Multivariate analysis reported that protein induced by the vitamin K antagonist-II (PIVKA-II) ≥200 mAU/mL, alkaline phosphatase (ALP) ≥80 IU/mL, and microvascular invasion were important predisposing factors for tumor recurrence. Elevated serum PIVKA-II level was associated with microvascular invasion in small HCC, which was a powerful predisposing factor.

Conclusions

Although small HCC is generally associated with a good prognosis, serum PIVKA-II level ≥200 mAU/mL, ALP ≥ 80 IU/L, and microvascular invasion were predisposing factors for tumor recurrence. These factors can be used to stratify patients with respect to recurrence after resection. Elevated PIVKA-II was closely associated with microvascular invasion in small HCC. These data emphasize the importance of PIVKA-II in small HCC.     

Extended indication for living donor liver transplantation in patients with hepatocellular carcinoma

BACKGROUND: Liver transplantation is an accepted treatment option for patients with otherwise untreatable hepatocellular carcinoma (HCC). The present study assessed the outcome of living donor liver transplantation (LDLT) under extended selection criteria based on a single-center experience. METHODS: A total of 60 patients who underwent LDLT for HCC were included. Our indication for LDLT included HCC without extrahepatic spread or macroscopic vascular invasion. The size and number of HCC nodules were not limited. Recurrence-free survival rates according to various factors were compared to identify risk factors for recurrence. RESULTS: Forty patients (67%) preoperatively exceeded the Milan criteria. The median follow-up was 437 days (range: 23-1,385 days). The overall 1- and 3-year actuarial survival rates were 88.4 and 68.6%, respectively. HCC recurred in eight patients (14.3%) within a mean follow-up of 288 days; all were patients who exceeded the Milan criteria. The 1-, 2- and 3-year recurrence-free survival rates of patients who fulfilled the Milan criteria were 100%, 100%, and 100%, respectively, whereas those of patients who exceeded the criteria were 83.0%, 74.0%, and 74.0%, respectively. Tumor diameter >5 cm was significantly associated with worse prognosis, but the number of tumors was not. A preoperative des-gamma-carboxy prothrombin value >300 mAU/ml was strongly associated with the high recurrence rate. These two variables were significant in multivariate analysis. CONCLUSIONS: LDLT was shown to offer acceptable results in patients who exceeded the Milan criteria. The indication for LDLT can therefore be expanded beyond the Milan criteria, especially for patients with small multiple tumors <5 cm.     

异常凝血酶原对肝癌合并门静脉癌栓的预测价值

目的研究异常凝血酶原(PIVKA-Ⅱ)对肝癌合并门静脉癌栓(portal vein tumor thrombus,PVTT)的预测价值。方法回顾性分析2019年9月至2020年12月间宁波大学附属李惠利医院肝胆胰外科收治的191例肝细胞癌(HCC)患者的临床资料,采用内部验证方法将所有患者随机分为试验组和验证组,分别比较两组内部有PVTT与无PVTT的HCC患者临床资料特征。在试验组中采用受试者工作特征曲线(ROC)分析计算PIVKA-Ⅱ预测PVTT的最佳截断值,并在验证组中进行验证。Logistic回归分析HCC患者发生PVTT的危险因素,并采用Spearman等级相关检验分析PIVKA-Ⅱ与PVTT程氏分型等级的关系。结果伴有PVTT的HCC患者PIVKA-Ⅱ水平高于无PVTT的HCC患者(P<0.05),PIVKA-Ⅱ≥426.5 mAU/mL是预测PVTT的最佳截断值,敏感度为78.8%。多因素分析显示PIVKA-Ⅱ≥426.5 mAU/mL和D-二聚体≥286 μg/L是HCC患者发生PVTT的独立危险因素,PIVKA-Ⅱ升高水平与PVTT程氏分型等级呈线性相关联。结论...     

Two-step Selection Criteria for Living Donor Liver Transplantation in Patients With Hepatocellular Carcinoma

We have proposed risk factors for tumor recurrence, such as tumor nodule ≥5 cm and des-gamma-carboxy prothrombin ≥300 mAU/mL after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors for HCC recurrence and mortality within our criteria. We enrolled 152 adult recipients who had undergone LDLT for end-stage liver disease with HCC who met our criteria. The recurrence-free survival rates after LDLT were calculated. Risk factors for tumor recurrence were identified. On univariate analysis, factors affecting recurrence-free survival were pretransplant treatment for HCC, neutrophil-to-lumphocyte ratio (NLR) >4, alpha-fetoprotein ≥400 ng/mL, ≥5 nodules, and bilobar tumor distribution. Multivariate analysis identified that NLR >4 and ≥5 nodules were independent risk factors for tumor recurrence after LDLT (P = .003 and P = .002, respectively). Two-step selection criteria enable selection of patients who have high-risk of tumor recurrence.     

Living donor liver transplantation of the right lobe for hepatocellular carcinoma in cirrhosis in a European center.

Living donor liver transplantation of the right lobe might offer the possibility to extend the eligibility criteria of patients with hepatocellular carcinoma (HCC) in cirrhosis without penalizing patients who are waiting for a graft from a deceased donor. From 1988 to 2005, surgical treatment of HCC was performed in 580 patients (187 transplantation, 393 resection) in a European center. In the transplantation group, 21 patients with HCC in cirrhosis underwent LDLT (11% of all transplantations for HCC; 22% of 96 LDLT). Solitary HCC were accepted irrespective of their diameter unless vascular invasion was detectable. Multiple HCC nodes were considered acceptable up to a diameter of the largest node of 6 cm and a total tumor diameter of 15 cm. The median follow-up period was 26 months (range, 1-65 months). Vascular invasion had occurred in 12 patients (57%). One patient (4.8%) died within 60 days after transplantation from sepsis. Rates of 3-year survival and 3-year recurrence-free survival were 68% and 64%, respectively. Overall 3-year survival rates in patients with HCC in cirrhosis not meeting the Milan criteria (n = 13) or the San Francisco criteria (n = 8) were 62% and 53%, respectively. LDLT is a safe procedure. However, small sample sizes do not yet permit a definitive comparison to be made between the former results obtained after cadaveric donation. So far, the outcome of the patients is in favor of a careful extension of the selection criteria for HCC in cirrhosis.     

Liver transplantation for hepatocellular cancer: should the current indication criteria be changed?

Liver transplantation (LTx) is the best treatment for hepatocellular carcinoma (HCC), but should be offered only to selected patients. The usual procedure is to transplant only for small and unilobular tumors. The aim of this paper is to verify whether the actual indication criteria are still justified. The details of 121 patients with HCC who were submitted to LTx from 1985 to 2000 were analyzed. Age, gender, liver disease, Child class, alpha-fetoprotein (AFP) level, presence of tumor capsule, vascular invasion, size and number of nodules, histological grade, and pTNM were considered. The 5- and 10-year actuarial survival rates were 61.7% and 53.1%. Freedom from recurrence was 85.9% and 85.9%, respectively. At univariate analysis, size, presence of capsule, AFP levels, vascular invasion, grade, pTNM, transarterial chemoembolization (TACE), Child class, and age were all significantly related to survival and/or cancer recurrence. Presence of capsule, AFP levels, and viral cirrhosis were independent variables in Cox's analysis for survival, whereas histological grade, AFP levels, and vascular invasion were significant independent variables for recurrence. In conclusion, a strict selection should be made to optimize graft allocation while size and multifocality should probably no longer be considered a contraindication for LTx. Histological grade, AFP levels, and vascular invasion, as indicator of tumor behavior, more likely reflect the risk of recurrence.     

Spontaneous necrosis of hepatocellular carcinoma: a case report

BACKGROUND: Spontaneous regression of a malignant tumor is a rare phenomenon. So far, 13 cases of spontaneous regression of hepatocellular carcinoma (HCC) have been described in the English literature. We report a case of HCC, with spontaneous complete necrosis demonstrated by histological examination. METHODS: A 73-year-old male was admitted to our hospital complaining of general fatigue. CT and US revealed a huge mass measuring 9.5 cm at the left lobe. Angiographies showed hypovascular tumor stains. The levels of alpha-fetoprotein (AFP) and PIVKA-2 on admission were high, at 55 ng/ml and 62,300 mAU/ml, respectively. We diagnosed hypovascular HCC and performed a left lobectomy on October 16, 2000. RESULTS: In the histological examination, no viable cells were found. The levels of AFP and PIVKA-2 had already decreased to 14 ng/ml and 1,420 mAU/ml, before laparotomy. CONCLUSION: Changes in tumor markers and histological findings reveal that this phenomenon occurred without specific treatment.     

18F‐FDG‐PET/CT predicts early tumor recurrence in living donor liver transplantation for hepatocellular carcinoma

The prognosis including ¹⁸F‐fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F‐FDG‐PET/CT) for the early recurrence for hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) was not well established. Consecutive patients who underwent ¹⁸F‐FDG‐PET/CT and subsequent LDLT for HCC from March 2005 to June 2011 were enrolled. The 191 patients with a median follow‐up of 26.1 months were evaluated. There were 20 patients (10.5%) with early recurrence (≤6 months), 18 patients (9.4%) with late recurrence (>6 months), and 153 patients (80.1%) with no recurrence. Fifty‐five patients (28.8%) displayed increased PET/CT tumor uptake. Three‐year overall and disease‐free survival for PET/CT‐positive patients were 65.5% and 57.1%, respectively, while PET/CT‐negative patients showed respective values of 89.8% and 86.8% (P = 0.001 vs. P < 0.001). Tumor variables associated with PET/CT‐positive finding were preoperative AFP level, Milan, UCSF criteria, maximum tumor size, total tumor size, differentiation, vascular invasion, and serosal invasion. PET/CT‐positive status was identified as an independent prognostic factor for disease‐free survival influencing early recurrence in multivariable analysis (HR 3.945, 95% CI 1.196–13.016, P = 0.024). ¹⁸F‐FDG‐PET/CT is an independent and significant predictor of early tumor recurrence in LDLT for HCC.     

AFP mRNA detected in bone marrow by real-time quantitative RT-PCR analysis predicts survival and recurrence after curative hepatectomy for hepatocellular carcinoma

OBJECTIVE: To determine whether detection of hepatocellular carcinoma (HCC) cells by real-time quantitative RT-PCR targeting of alpha-fetoprotein mRNA (AFP mRNA) before or after curative hepatectomy predicts HCC recurrence and patient survival. SUMMARY BACKGROUND DATA: The presence of cancer cells in peripheral blood and/or bone marrow in patients with malignant disease has been reported to correlate with outcome. METHODS: Between July 2000 and June 2005, 136 consecutive HCC patients underwent primary curative hepatectomy. Bone marrow aspirated preoperatively, and peripheral blood samples collected before and after operation were subjected to real-time quantitative RT-PCR analysis using AFP mRNA as a target molecule. Median follow-up was 23 months (range, 6-54 months). Patient survival (PS), disease-free survival (DFS), and clinicopathologic features were compared between patients with positive and negative AFP mRNA. RESULTS: Twenty-four patients died (22 from HCC). HCC recurred in 66 patients (hepatic in 37 [56.1%]; hepatic and remote in 17 [25.8%], and remote alone in 12 [18.2%]). Bone marrow was positive for AFP mRNA in 38 patients (27.9%) and negative in 98 (72.1%). One- and 3-year PS was 96.6% and 91.4%, respectively, with negative AFP mRNA versus 86.2% and 55.5%, respectively, with positive AFP mRNA (P < 0.0001). One- and 3-year DFS were 73.2% and 44.8%, respectively, with negative AFP mRNA versus 54.5% and 25.8%, respectively, with positive AFP mRNA (P = 0.0399). Portal vascular invasion, tumor size, multiple tumors, and tumor differentiation correlated with inferior PS and DFS on univariate analysis. On multivariate analysis, positive AFP mRNA was the most important risk factor for PS (P = 0.001) and DFS (P = 0.0165). In addition, positive AFP mRNA in peripheral blood after operation tended to predict reduced DFS. CONCLUSION: AFP mRNA in the bone marrow and systemic circulation during the perioperative period predicts patient survival and recurrence after curative hepatic resection for HCC.     

Does preoperative fine needle aspiration-biopsy produce tumor recurrence in patients following liver transplantation for hepatocellular carcinoma?

INTRODUCTION: Liver transplantation (OLT) has been advocated for patients with carcinoma hepatocellular (HCC). A preoperative biopsy (fine needle aspiration biopsy) [FNA] facilitates preoperative diagnosis of adverse pathological factors: vascular invasion or histologicalic differentiation. But a biopsy may cause abdominal dissemination and be related to a higher incidence of recurrence. PATIENTS AND METHODS: From April 1986 to December 2003, we performed 95 OLT for HCC. We divided them in two groups: group A without FNA-biopsy (67.9%) and group B with FNA-biopsy (32.1%). RESULTS: We obtained the diagnosis of HCC in only 15 patients (57.6%). In two patients an OLT was avoided due to the presence of abdominal dissemination at the time of transplant. Recurrence incidence was higher among group B patients (5.9% vs 31.8%; P = .003) due to extrahepatic recurrence (2% vs 27.3%; P = .003). No differences were observed in morbidity or mortality. The two groups were homogeneous in epidemiological and pathological variables except: sex distribution, Child status, AFP level, tumor size, and pTNM stage. If we compare recurrence rates in the two groups attending to these nonhomogeneous variables, it was significantly higher among patients with tumors larger than 3 cm, pTNM I-III stage, Child B-C, AFP >200 ng/mL, and males or females. CONCLUSIONS: Preoperative liver biopsy is associated with a larger incidence of tumor recurrence, so we believe that it is not necessary prior to an OLT for HCC.     

Predictors of hepatic venous trunk invasion and prognostic factors in patients with hepatocellular carcinomas that had come into contact with the trunk of major hepatic veins

PURPOSE: In this study, we tried to identify the preoperative predictors of hepatic venous trunk invasion and the prognostic factors in patients with hepatocellular carcinoma (HCC) that had come into contact with the trunk of a major hepatic vein over a distance of 1.0 cm or more. METHODS: Forty patients who had such HCCs resected were entered into this study and predictors of hepatic venous trunk invasion and prognostic factors were evaluated by univariate and multivariate analyses. RESULTS AND CONCLUSIONS: A combined resection of the HCC and the venous trunk was performed in 29 patients. Hepatic venous trunk invasion was observed in 12 patients, including 2 with inferior vena cava tumor thrombus. A stepwise logistic regression analysis indicated that tumors larger than or equal to 7 cm in diameter and tumors showing a poorly differentiated histological grade were independent predictors of hepatic venous trunk invasion. The survival of patients without venous trunk invasion was significantly better than that for patients with venous trunk invasion (P = 0.048). A univariate analysis revealed that Child-Pugh classification B (P = 0.002), a high des-gamma-carboxy prothrombin concentration (> or =400 mAU/ml, P = 0.023), a large HCC (> or =5.0 cm in diameter, P = 0.002), the presence of portal vein invasion (P < 0.001), the presence of venous trunk invasion (P = 0.048), the presence of intrahepatic metastasis (P < 0.001), and poorly differentiated HCC (P = 0.006) correlated with a worse overall survival after hepatic resection. In a multivariate analysis, however, only the presence of intrahepatic metastasis (P = 0.037, relative risk 8.25) was an independent predictor of poor overall survival. CONCLUSIONS: Large tumors (> or =7 cm in diameter) and poorly differentiated HCCs were more likely to be associated with hepatic venous trunk invasion and intrahepatic metastasis was an independent prognostic factor in patients with HCC that had come into contact with the trunk of a major hepatic vein.