Number and Tumor Size Are Not Sufficient Criteria to Select Patients for Liver Transplantation for Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) is an indication for liver resection or transplantation (LT). In most centers, patients whose HCC meets the Milan criteria are considered for LT. The first objective of this study was to analyze whether there is a correlation between the pathologic characteristics of the tumor, survival and recurrence rate. Second, we focused our attention on vascular invasion (VI).

Methods

From January 1997 to December 2007, a total of 196 patients who had a preoperative diagnosis of HCC were included. The selection criteria for LT satisfied both the Milan and the San Francisco criteria (UCSF). Demographic, clinical, and pathologic information were recorded.

Results

HCC was confirmed in 168 patients (85.7%). The median follow-up was 74?months. The pathologic findings showed that 106 patients (54.1%) satisfied the Milan criteria, 134 (68.4%) the UCSF criteria of whom 28 (14.3%) were beyond the Milan criteria but within the UCSF criteria, and 34 (17.3%) beyond the UCSF criteria. VI was detected in 41 patients (24%). The 1-, 3-, and 5-year overall survival rates were 90%, 85%, and 77%, respectively, according to the Milan criteria and 90%, 83%, and 76%, respectively, according to the UCSF criteria (P?=?NS). In univariate and multivariate analyses, tumor size and VI were significant prognostic factors affecting survival (P?400?ng/ml and tumor grade G3.

Conclusions

Tumor size and VI were the only significant prognostic factors affecting survival of HCC patients. Primary liver resection could be a potential selection treatment before LT.     

Postoperative Serum Osteopontin Level is a Novel Monitor for Treatment Response and Tumor Recurrence after Resection of Hepatitis B–related Hepatocellular Carcinoma

Background

Presurgery serum osteopontin (OPN) level has been demonstrated to correlate to tumor recurrence and survival of hepatocellular carcinoma (HCC) patients. This study investigated the postoperative dynamic changes of serum OPN level and its clinical significance in HCC patients.

Methods

Presurgery serum OPN levels were measured by enzyme-linked immunosorbent assay in cohort A of 179 HCC patients and were compared with the multiple controls including different kinds of liver diseases and healthy individuals. In cohort B of 110 patients with resectable HCCs, besides preoperative assays, serum OPN was monitored at 1 week, 1, and ≥2 months after operation.

Results

The baseline presurgery serum OPN of HCC patients was significantly higher than that of the patients with the other kinds of liver diseases (p < 0.0001). The prognostic values of presurgery serum OPN level in HCC patients were further confirmed. The postsurgery OPN levels were significantly elevated within 1 week after HCC resection, then decreased at 1 month and reached the nadir later than 2 months after operations. It increased again at the time of tumor recurrence, then declined after the second removal of recurrent HCCs. Moreover, postoperative OPN in α-fetoprotein-negative and -positive HCC patients had the same changing pattern; it only correlated to liver function and C-reactive protein level.

Conclusions

After a transient fluctuation, serum OPN levels significantly decrease after curative resection of HCCs. Postoperative serum OPN could serve as a surrogate serologic biomarker for monitoring treatment response and tumor recurrence after HCC resection, including α-fetoprotein-negative ones.     

Decreased Expression and Prognostic Role of Mitogen-Activated Protein Kinase Phosphatase 4 in Hepatocellular Carcinoma

Purpose

This study aimed to investigate the potential role and prognostic significance of mitogen-activated protein kinase phosphatase 4 (MKP-4) in the pathology of hepatocellular carcinoma (HCC).

Methods

Western blot analysis and quantitative real-time polymerase chain reaction were performed to detect MKP-4 expression in HCC tissues, pericarcinomatous liver (PCL) tissues, and proliferating HCC cells. The detailed role of MKP-4 was further explored by MKP-4 downregulation in HepG2 cells using small interfering RNA (siRNA). Specimens of 134 HCC patients who had undergone hepatic resection were immunohistochemically evaluated for MKP-4 expression.

Results

MKP-4 protein and mRNA levels were significantly lower in HCC tissues than in PCL tissues. In vitro, its expression was gradually reduced following release of HepG2 cells from serum starvation. The cell counting kit-8 assay and Annexin-V-Fluos staining indicated that MKP-4 knockdown by siRNA in HCC cells enhanced cell survival and inhibited apoptosis. Univariate and multivariate analyses revealed that MKP-4 was a significant predictor for overall survival (OS) and time to recurrence (TTR). High MKP-4 expression was well correlated with prognosis independent of Edmondson grade and microvascular invasion (P?<?0.001).

Conclusions

MKP-4 expression was downregulated in HCC tissues and proliferating HCC cells and correlated with OS and TTR, which suggested that MKP-4 is a candidate prognostic marker for HCC.     

Liver Transplantation in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma: The Influence of Viral Characteristics on Clinical Outcome

Background

Hepatitis B virus (HBV) relapse and/or hepatocellular carcinoma (HCC) recurrence remains a major concern for patients who undergo liver transplantation (LT) because of HBV-related HCC. This study investigates the correlation between HBV relapse and HCC recurrence and it explores factors that affect patient outcomes after LT.

Methods

Between September 2002 and August 2009, 78 consecutive patients who underwent LT because of HBV-related HCC were enrolled in this study. Serum samples obtained before LT were assayed both for virological factors associated with HBV DNA and for genotypic characteristics of the virus. All patient clinicopathological features and virological factors were assessed further by univariate and multivariate analyses to determine prognostic factors.

Results

During a median follow-up period of 29.4 months, 13 (16.6 %) patients experienced HCC recurrence and 18 (23.1 %) patients experienced HBV relapse. HBV relapse exhibited a close association with HCC recurrence (p = 0.004) and led to unfavorable overall survival after LT. Multivariate analysis of prognostic factors showed that the basal core promoter (BCP) mutation independently predicted a shorter survival period free from HBV relapse (p = 0.036). Moreover, with the exception of unfavorable tumor characteristics, the BCP mutation was found to be an important prognostic factor that affected HCC recurrence after LT (p = 0.042).

Conclusions

In this study, the HBV–BCP mutation was identified as an important predictor of post-LT clinical outcomes in patients with HBV-related HCC. Therefore, we recommend that aggressive antiviral treatment may be considered for patients associated with this risk factor.     

Can we direct organ allocation based on predicted outcome? Hepatocellular carcinoma outside of UCSF criteria or retransplant?

Background

In this study, we ask between patients with graft failure listed for retransplant and patients with hepatocellular carcinoma (HCC) outside of UCSF criteria, who has the greater survival benefit with transplantation?

Methods

This is a retrospective analysis, of liver transplant (LT) patients, done between February 2002 and December 2009 at our center. Patients were included in the “extended HCC” group if their tumor was pathologically beyond UCSF criteria at LT and in the “redo” group if they underwent LT for graft failure occurring more than 3?months after the initial LT. Extended criteria donors (ECDs) were defined as donors above 70?years old, DCD, serology positive for HCV, and split grafts.

Results

There were 25 redos and 37 extended HCC patients. Use of ECDs or high donor risk index organs was associated with poor outcome in both groups (P?=?0.005). Overall, the extended HCC population had a much better survival than redos, both at 1 and 3?years.

Conclusion

These two very different but high risk patient populations have very different survival rates. At a time where regulatory agencies demand more and more with regards to transplant outcomes, we think the transplant community has to reflect on whether allocation justice and fair access to transplant are respected if we start allocating organs based on outcomes.     

Knockdown Survivin Expression Reduces the Efficacy of Curcumin Treatment in Hepatocellular Carcinoma Cells

Background

Survivin is a potential therapeutic target for cancer. Increased survivin expression promotes cell survival and therapeutic resistance. However, there is little information regarding whether the expression level of survivin affects curcumin treatment in hepatocellular carcinoma (HCC).

Methods

Survivin expression was suppressed in HCC cells using a short interfering RNA (siRNA) technique. The anticancer effects of curcumin were examined using a biosensor system, MTT assay, TUNEL assay, and cell cycle analysis.

Results

Curcumin resistance developed in cells with suppressed survivin, in contrast to the parental cells, as determined by survival assays. Cell cycle analysis and TUNEL assays revealed that the apoptotic cell population was increased in the scrambled-siRNA cells treated with curcumin compared with the survivin-siRNA cells. Suppression of survivin expression resulted in curcumin resistance via the modulation of Bcl-2 and Bax expression.

Conclusions

We conclude that the expression levels of survivin may mediate the therapeutic efficacy of curcumin in HCC cells.     

Influence of Nonclinical Factors on Choice of Therapy for Early Hepatocellular Carcinoma

Background

Initial therapy for early hepatocellular carcinoma (HCC) with well-compensated cirrhosis is controversial. While we previously reported on the effect of clinical factors and surgeon specialty on choice of therapy for early HCC, other nonclinical factors also may impact decision-making.

Methods

Surgeons who treat HCC were invited to complete a web-based survey that included ten case scenarios. Choice of therapy—liver transplantation (LT), liver resection (LR), or radiofrequency ablation (RFA)—was analyzed using regression models.

Results

There were 336 responses for analysis. Most respondents were in academic centers (86 %) that offered LT (71 %). The median number of patients annually evaluated for HCC was 30. Both practice type and HCC case volume were associated with choice of therapy, but these associations were not independent of surgeon specialty. LT surgeons who did not also perform RFA were less likely than those LT surgeons who did offer RFA to choose RFA over LT (relative risk ratios (RRR) 0.38, P < 0.001). Non-LT surgeons were more likely than LT surgeons who also offered RFA to choose RFA over LT (RRR 2.24, P < 0.001). Surgeons who worked at hospitals where LT was performed were much more likely to choose LT over LR and RFA even if they did not personally perform LT (RRR 1.27 and RRR 3.33, P < 0.001).

Conclusions

Surgeon- and institution-related factors impact choice of therapy for early HCC even after adjustment for differences in clinical presentation. These data suggest that choice of therapy for patients with early HCC varies across providers independent of case selection.     

Response to Therapy as a Criterion for Awarding Priority to Patients With Hepatocellular Carcinoma Awaiting Liver Transplantation

Background

How to prioritize patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) remains controversial. This study was designed to assess the effectiveness of a policy for prioritizing HCC patients according to their response to pre-LT therapy.

Methods

The study period was from 2000 to 2008. Dropout criteria included macroscopic vascular invasion, metastases, and poorly differentiated grade at pre-LT biopsy. A specific treatment algorithm was adopted to treat HCC before LT, and the effect of treatment was evaluated 3 months after listing or after the diagnosis of HCC for patients diagnosed while already on the waiting list. Patients were divided into two groups: group 1, patients with disease that completely or partially responded to therapy; and group 2, patients with stable, progressive, or untreatable disease. Group 2 patients were prioritized for LT unless full restaging and repeat biopsy identified dropout criteria.

Results

At the 3-month visit, 62 HCC patients (42%) were assigned to group 2 and 85 (58%) to group 1. Eleven of 12 dropouts due to tumor progression came from group 2 (P < 0.01). Response to therapy was the sole predictor of dropout probability, independent of tumor stage (competing risk analysis). The 42 patients in group 2 who were transplanted had much the same 3-year post-LT survival rate as the 57 transplanted patients in group 1 (with survival rates of 82% and 83%, respectively; P > 0.05), but a slightly higher risk of post-LT HCC recurrence (13% and 2%, respectively; P = 0.04).

Conclusions

Response to therapy is a potentially effective tool for prioritizing HCC patients for LT.     

Single HCC in Cirrhotic Patients: Liver Resection or Liver Transplantation? Long-term Outcome According to an Intention-to-treat Basis

Background

Compensated cirrhotic patients with single hepatocellular carcinoma (HCC) ≤5 cm may benefit from both liver resection (LR) and liver transplantation (LT); however, the better 10-year actuarial survival of the two treatments remains unclear. We aimed to assess the long-term outcome of cirrhotic patients with single HCC ≤5 cm treated either with LR or LT on an intention-to-treat basis.

Methods

A total of 217 cirrhotic patients with single HCC ≤5 cm were evaluated at our department: 95 were treated with LR (LR group), and 122 were included on the waiting list for LT (LT group). Patients in the LR group were divided into very early HCC (tumor size ≤2 cm) and early HCC (tumor size >2 cm). Median follow-up was 5.3 (range 0.1–18) years.

Results

Tumor recurrence was 72 % in the LR group versus 16 % in the LT group (p < 0.001). 1-, 5-, and 10-year cumulative risk of recurrence was 18, 69, and 83 % in the LR group versus 4, 18, and 20 % in the LT group (p < 0.001). Ten-year actuarial survival was 33 % in the LR group versus 49 % in the LT group (p = 0.002). At HCC recurrence, 27.3 % were included on the waiting list for salvage transplantation (very early HCC group) versus 15.1 % (early HCC group) (p = 0.2). After salvage transplantation, HCC recurrence was 0 % (very early HCC group) versus 40 % (early HCC group) (p = 0.2). No significant differences were observed in 1-, 5-, and 10-year actuarial survival between the very early HCC group and the LT group (95, 55, and 50 % vs. 82, 62, and 50 %).

Conclusions

LR should be the treatment of choice for cirrhotic patients with very early HCC.     

Clinical Decision-Making by Gastroenterologists and Hepatologists for Patients with Early Hepatocellular Carcinoma

Background

Choice of therapy in early hepatocellular carcinoma (HCC) is controversial, and no broad consensus exists as to how patient and tumor characteristics should be used to guide choice of therapy. We have previously reported on decision making in early HCC by liver surgeons. In the present study, we quantified the impact of clinical factors on choice of therapy for early HCC by gastroenterologists and hepatologists.

Methods

Physicians who treat HCC were invited to complete a web-based survey including ten case scenarios that systematically varied across seven clinical factors. Choice of therapy—liver transplantation (LT), liver resection (LR), radiofrequency ablation or intra-arterial therapy—was analyzed using multinomial logistic regression models.

Results

Tumor number and size, type of resection required, biological Model for End-Stage Liver Disease (MELD) score, and platelet count had the largest effects on choice of therapy. For example, LR was more likely to be recommended over LT for patients with small solitary tumors versus multiple tumors [relative risk ratio (RRR) 3.63], those who would require a minor versus major LR (RRR 3.39), those with lower biological MELD score (6 vs. 10; RRR 1.95), and those with a higher platelet count (150,000/μL vs. 70,000/μL; RRR 2.77). In contrast, serum α-fetoprotein level and etiology of cirrhosis were not associated with choice of therapy. No physician-related factors studied had an impact on choice of therapy.

Conclusion

The clinical factors weighed most heavily by gastroenterologists and hepatologists are quite similar to those considered important by surgeons. There was good consensus among gastroenterologists and hepatologists as to the factors used to choose therapy.     

Liver Transplantation and Liver Resection for Cirrhotic Patients with Hepatocellular Carcinoma: Comparison of Long-Term Survivals

Background

Both liver transplantation (LT) and liver resection (LR) represent curative treatment options for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. In this study, we have compared outcomes between historical and more recent patient cohorts scheduled either for LT or LR, respectively.

Methods

Clinicopathological data of all patients with HCC and cirrhosis who underwent LT or LR between 1989 and 2011 were evaluated. Overall survival of patients with HCC within the Milan criteria (MC) was analyzed focusing on changes between different time periods.

Results

In total, 364 and 141 patients underwent LT and LR for HCC in cirrhosis, respectively. Among patients with HCC within MC, 214 and 59 underwent LT and LR, respectively. Postoperative morbidity (37 vs. 11%, P?<?.0001), but not mortality (3 vs. 1%, P?=?.165), was higher after LR than after LT for HCC within MC. In the period 1989–2004, overall survival (OS) was significantly higher in patients who underwent LT compared to LR for HCC within MC (5-year OS: 77 vs. 36%, P?<?.0001). Interestingly, in the more recent period 2005–2011, OS was comparable between LT and LR for HCC within MC (5-year OS: 73 vs. 61%, P?=?.07).

Conclusion

We have noted an improvement of outcomes among patients selected for partial hepatectomy in recent years that were comparable to stable results after LT in cirrhotic patients with HCC. Whether those improvements are due to advances in liver surgery, optimized perioperative managament for patients with liver cirrhosis, and the development of modern multimodal treatment strategies for the recurrent lesions appears plausible.

     

Prediction of Disease-free Survival in Hepatocellular Carcinoma by Gene Expression Profiling

Background

Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis, which correlate with recurrence after surgical treatment and poor prognosis. The molecular prognostic model that could be applied to the HCC patient population in general is needed for effectively predicting disease-free survival (DFS).

Methods

A cohort of 286 HCC patients from South Korea and a second cohort of 83 patients from Hong Kong, China, were used as training and validation sets, respectively. RNA extracted from both tumor and adjacent nontumor liver tissues was subjected to microarray gene expression profiling. DFS was the primary clinical end point. Gradient lasso algorithm was used to build prognostic signatures.

Results

High-quality gene expression profiles were obtained from 240 tumors and 193 adjacent nontumor liver tissues from the training set. Sets of 30 and 23 gene-based DFS signatures were developed from gene expression profiles of tumor and adjacent nontumor liver, respectively. DFS gene signature of tumor was significantly associated with DFS in an independent validation set of 83 tumors (P = 0.002). DFS gene signature of nontumor liver was not significantly associated with DFS in the validation set (P = 0.827). Multivariate analysis in the validation set showed that DFS gene signature of tumor was an independent predictor of shorter DFS (P = 0.018).

Conclusions

We developed and validated survival gene signatures of tumor to successfully predict the length of DFS in HCC patients after surgical resection.     

The Clinical Behavior of Transplantable Recurrent Hepatocellular Carcinoma After Curative Resection: Implications for Salvage Liver Transplantation

Background

This study aimed to classify transplantable recurrent hepatocellular carcinoma (HCC) after resection into subgroups according to the pattern of progression and to identify risk factors for each subgroup to select optimal candidates for salvage liver transplantation (LT).

Methods

The patients that met the Milan criteria (MC) and were child-pugh class A at initial hepatectomy were included in the study. Of these patients, the patients with transplantable recurrence were identified and further divided into two groups according to the recurrent HCC progression pattern. Group 1 contained patients with controlled tumors within the MC. Group 2 contained patients with progressive tumors that spread beyond the MC. A controlled tumor was defined as the absence of tumor recurrence after locoregional treatment for ≥12 months or control of a recurrent tumor within the MC by active locoregional treatment.

Results

After curative resection of HCC, 114 patients with transplantable recurrence were identified: 70 were classified as group 1 and 44 as group 2. Overall survival after recurrence was significantly higher in group 1 compared to group 2 (65.4 vs 35.7 %, respectively; P < 0.003). Multiple logistic regression analysis showed that risk factors in group 1 were age >50 years and an indocyanine green retention at 15 min >10 %. The presence of a satellite nodule (SN) and/or microscopic portal vein invasion (mPVI) was the only independent risk factor identified in group 2. Among the 15 patients that underwent salvage LT, 2 of 3 patients (66.7 %) with SN and/or mPVI at initial hepatectomy developed extrahepatic recurrence.

Conclusions

The patients with SN and/or mPVI at initial hepatectomy may not be candidates for salvage LT, and an extended observation time is required to determine tumor biology.     

Sorafenib treatment is save and may affect survival of recurrent hepatocellular carcinoma after liver transplantation

Introduction

Recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) is a rare but challenging condition. In most cases, the recurrent tumor is presented with extrahepatic spread. Therefore, systemic treatment with sorafenib has to be assessed. Because of a plethora of possible drug interactions, e.g., with immunosuppressant or anti-infective therapy, safety and feasibility of sorafenib treatment requires special attention.

Materials and methods

We retrospectively analyzed 18 patients who suffered from recurrent advanced HCC after LT between January 2002 and December 2010 at the University Hospital Heidelberg regarding safety of sorafenib treatment and survival.

Results

Results showed that 8 patients were eligible for treatment with sorafenib showing a median time to progression (TTP) of 4.5 months and an overall survival of 9 months. Most common side effects were grades I and II diarrhea and hand–foot syndrome (HFS) which could be managed by sorafenib dose reduction. No grade III or IV adverse events (AEs) were noticed. No patient had to discontinue treatment due to AEs. The ten patients not amenable for sorafenib treatment, due to initial poor performance status or its deterioration after first line treatment, were treated with surgical resection (n?=?3), locoregional therapies (n?=?1), or palliative radiation therapy (n?=?1). They showed a median overall survival of 2.3 months.

Conclusion

Sorafenib may represent a therapeutic option for recurrent HCC after LT with manageable side effects. The clinical benefit of sorafenib in this setting is promising but needs to be confirmed in a prospective randomized trial.     

Child-Pugh A Hepatitis B-Related Cirrhotic Patients with a Single Hepatocellular Carcinoma Up to 5 cm: Liver Transplantation vs. Resection

Objective

This study aims to analyze the outcomes of patients with Child-Pugh A class cirrhosis and a single hepatocellular carcinoma (HCC) up to 5 cm in diameter who underwent liver transplantation vs. resection.

Methods

During 2007 to 2012, 282 Child-Pugh A cirrhotic patients with a single HCC up to 5 cm in diameter either underwent liver resection (N?=?243) or received liver transplantation (N?=?39) at our center. Patient and tumor characteristics and outcomes were analyzed.

Results

Patients who underwent liver transplantation had a better recurrence-free survival (RFS) vs. those who underwent liver resection. However, the 5-year survival rates after these two treatments were comparable. Similar results were observed when we analyzed patients with a HCC less than 3 cm, and for patients with portal hypertension. In the multivariate analysis, tumor differentiation, difference of primary treatment, and presence of microvascular invasion were associated with postoperative recurrence. However, only differentiation negatively impacted overall survival after operation.

Conclusion

Although more recurrences were observed in Child A cirrhotic patients with a single HCC up to 5 cm after liver resection, liver resection offers a similar 5-year survival to liver transplantation, even for patients with portal hypertension.     

Prognostic Significance of Alpha-fetoprotein Status in the Outcome of Hepatocellular Carcinoma after Treatment of Transarterial Chemoembolization

Background

Alpha-fetoprotein (AFP) has been used as a diagnostic biomarker for hepatocellular carcinoma (HCC), but its prognostic significance is not well defined. This study was performed to classify the prognostic significance of AFP status in HCC patients after transarterial chemoembolization (TACE).

Methods

Four hundred forty-one HCC patients from a prospective maintained database with pathologic confirmation including 139 with normal AFP levels and 302 with elevated AFP levels were retrospectively studied for prognostic significance of AFP in treatment response and survival after TACE. Univariate and multivariate analyses were used to identify the prognostic factors.

Results

There were significant differences in overall survival (OS) after TACE between AFP-negative and AFP-positive HCC patients when the AFP cutoff value was defined as 20?ng/ml (P?P?=?0.093). Multivariate analysis revealed that AFP status for AFP-negative or positive was an independent prognostic factor for HCC patients after TACE (P?=?0.001), along with ??-glutamyltransferase (GGT) level (P?=?0.004) and tumor diameter (P?Conclusions Compared with AFP-positive HCC patients, patients with AFP-negative status have a better treatment response and prognosis after TACE.     

Combination of Morphologic Criteria and α-Fetoprotein in Selection of Patients With Hepatocellular Carcinoma for Liver Transplantation Minimizes the Problem of Posttransplant Tumor Recurrence

Background

Serum α-fetoprotein concentration (AFP) might be a useful addition to morphologic criteria for selecting patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). The aim of this study was to evaluate the role of AFP in selecting HCC patients at minimal risk of posttransplant tumor recurrence in the setting of existing criteria.

Methods

This retrospective cohort study was based on 121 HCC patients after LT performed at a single institution. AFP was evaluated as a predictor of posttransplant tumor recurrence with respect to fulfillment of the Milan, University of California, San Francisco (UCSF), and Up-to-7 criteria.

Results

There was a nearly linear association between AFP and the risk of HCC recurrence (p < 0.001 for linear effect; p = 0.434 for nonlinear effect). AFP predicted HCC recurrence in patients (1) beyond the Milan criteria (p < 0.001; optimal cutoff 200 ng/ml); (2) within the UCSF criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.015; optimal cutoff 200 ng/ml); and (3) within the Up-to-7 criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.023; optimal cutoff 100 ng/ml) but not in patients within the Milan criteria (p = 0.834). Patients within either UCSF and Up-to-7 criteria with AFP level <100 ng/ml exhibited superior (100 %) 5-year recurrence-free survival—significantly higher than those within UCSF (p = 0.005) or Up-to-7 (p = 0.001) criteria with AFP levels higher than the estimated cutoffs or beyond with AFP levels less than the estimated cutoffs.

Conclusions

Combining the UCSF and Up-to-7 criteria with an AFP level <100 ng/ml is associated with minimal risk of tumor recurrence. Hence, this combination might be useful for selecting HCC patients for LT.     

Liver Transplantation for Unresectable Neuroendocrine Tumor Liver Metastases

Background

Liver transplantation (LT) is performed in selected patients with neuroendocrine hepatic metastases. Survival benefit and the risk of tumor recurrence after LT, also exacerbated by immunosuppressive therapy, remain important clinical issues. Whether patients with particular types of neuroendocrine tumors (NET) benefit more than others is unclear.

Methods

Bibliographical searches were performed in PubMed for the terms “liver transplantation and neuroendocrine tumors,” “liver transplant and neuroendocrine tumors,” “liver transplantation and immunosuppressive therapy,” “tumor recurrence.”

Results

Promising results have been reported for LT for NET metastases with 5-year survival of up to 90 % in patients with well-differentiated gastroenteropancreatic NETs, but only few patients are free of tumor 5 years after LT. Better outcomes have been reported for gastrointestinal tumors than for pancreatic NETs for both survival and risk or recurrence after LT. Selection criteria for LT are limited and include the 2007 Milan Criteria and the 2012 European Neuroendocrine Tumor Society guidelines, including: well-differentiated NET (Ki-67 <10 %), age <55 years, absence of extrahepatic disease, primary tumor removed before transplantation, stable disease for at least 6 months before LT, and <50 % liver involvement.

Conclusions

LT might be considered in carefully selected patients. The risk of tumor recurrence remains a significant clinical problem after LT, but data focused on immunosuppression issue are lacking, and there are no currently approved strategies for prevention of recurrence or follow-up protocols. Further studies are needed to define universally accepted inclusion criteria, reliable predictors of better outcome, and optimal timing for LT.