Early Detection of Hepatocellular Carcinoma Recurrence in the Posttransplant Population: A Comparison of RETREAT and Cleveland Clinic Florida Scoring System

BackgroundLiver transplantation (LT) for hepatocellular carcinoma (HCC) is curative in most cases; however, recurrence is observed in some patients. The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score is an externally validated scoring system for prediction of post-LT HCC recurrence. The Cleveland Clinic Florida Scoring System (CCFSS) is a potential new scoring system for prediction of HCC recurrence. Our study aimed to compare the RETREAT and CCFSS.MethodsWe conducted a retrospective cohort study of 52 adult patients with HCC who underwent LT at a tertiary care center. Mantel-Haenszel chi-square analyses were conducted to compare the RETREAT and CCFSS classifications for detecting HCC recurrence.ResultsA total of 52 patients underwent LT. The median follow-up period was 37 months. Four patients had post-LT HCC recurrence, with all recurrences occurring within 2 years of LT. The RETREAT score was better able to detect low, moderate, and high levels of risk (P < .001), compared to the CCFSS score (P = 0.480). Both risk scores had a sensitivity of 75%; the specificity of the RETREAT score was 95.8%, whereas the specificity of the CCFSS was 60.4%. Alpha-fetoprotein level at the time of LT was associated with HCC recurrence (P = .014).ConclusionsThis is the first study to evaluate the CCFSS as a potential new scoring system to predict HCC recurrence after LT. The RETREAT score is more specific than the CCFSS. The incorporation of alpha-fetoprotein level at the time of LT improves the estimation of HCC recurrence in the post-LT period.     

Tumor volume,surgical margin,and the risk of biochemical recurrence in men with organ-confined prostate cancer

ObjectivesWe proposed to investigate predictors of biochemical recurrence (BCR) in pT2 prostate cancer by identifying the interrelationship between the tumor volume and surgical margin status, and their impact on recurrence.Materials and methodsClinical, pathologic, and follow-up data of 404 consecutive patients who were treated with radical prostatectomy alone and were diagnosed as pT2 prostate cancer in our institution were reviewed. Percent tumor volume (PTV) was estimated from the cancer distribution map, and the surgical margin status was reviewed by a single pathologist (JYR). Clinicopathologic variables were analyzed with respect to the risk of BCR.Results and limitationsRecurrence was observed in 39 (9.7%) patients at a mean of 28.9 (5–47) months. Preoperative PSA, biopsy Gleason score, surgical Gleason score, PTV, and surgical margin status were significantly related to BCR in univariate analysis; in multivariate analysis, PTV (P < 0.001) and surgical Gleason score (P = 0.021) were independent predictors of BCR. PTV was also an independent determinant of positive surgical margin (P = 0.035, HR 1.026, 95% CI 1.002–1.050). By combining the 2 predictors 5-year recurrence-free survivals for PTV ≤ 14.5% and surgical Gleason score ≤ 7, PTV >14.5% or surgical Gleason score > 7, and PTV > 14.5% and surgical Gleason score > 7 were 97.5%, 88.7%, and 44.5%, respectively (log-rank test, P < 0.01). Retrospective study nature, use of PTV instead of actual volume, and intermediate follow-up length are the main limitations of the study.ConclusionsIn men with pT2 prostate cancer, percent tumor volume and the surgical Gleason score were independently prognostic of BCR and by combining the 2 factors, risk of BCR could be significantly stratified. Tumor volume further determined surgical margin status undermining its prognostic value as an independent variable.     

Everolimus-Based Immunosuppression in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Liver Transplantation: A Case Series

BackgroundLiver transplantation offers the most effective treatment in patients with hepatocellular carcinoma (HCC). However, transplant patients outside the Milan criteria have a high risk of tumor recurrence, which has been linked to standard immunosuppression regimens. Everolimus is a mammalian target of rapamycin inhibitor that has been used for immunosuppression, but its effect on recurrence and survival in HCC patients with a high risk of tumor recurrence has not been examined. We compared long-term survival and cumulative recurrence in high-risk patients receiving everolimus-based immunosuppression after liver transplantation for HCC with an historic control group.MethodsThe everolimus group comprised 21 patients receiving a liver transplant at our center from February 2005 to December 2010. The control group comprised 31 patients receiving a liver transplant from May 1994 to January 2005. All patients received cyclosporine or tacrolimus as initial post-transplant immunosuppression. Patients in the everolimus group switched to everolimus 2 weeks later.ResultsThere were no differences between the two groups in number of rejection episodes or of infectious or surgical complications. Five-year survival was 60.2% in the everolimus group and 32.3% in the control group (P = .05). Five-year cumulative recurrence rate was 61.3% in the control group and 41.3% in the everolimus group. Treatment with everolimus was identified as an independent predictor of longer survival (hazard ratio = 0.34; P = .02).ConclusionsPatients receiving liver transplantation for HCC with a high risk of tumor recurrence may well benefit from everolimus-based immunosuppression, with no added risks of rejection or other post-transplant complications.     

What is the optimal definition of misclassification in patients with very low-risk prostate cancer eligible for active surveillance? Results from a multi-institutional series

BackgroundThe risk of unfavorable prostate cancer in active surveillance (AS) candidates is nonnegligible. However, what represents an adverse pathologic outcome in this setting is unknown. We aimed at assessing the optimal definition of misclassification and its effect on recurrence in AS candidates treated with radical prostatectomy (RP).Materials and methodsOverall, 1,710 patients eligible for AS according to Prostate Cancer Research International: Active Surveillance criteria treated with RP between 2000 and 2013 at 3 centers were evaluated. Patients were stratified according to pathology results at RP: organ-confined disease and pathologic Gleason score ≤6 (group 1); organ-confined disease and Gleason score 3+4 (group 2); and non–organ-confined disease, Gleason score ≥4+3, and nodal invasion (group 3). Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen (PSA)≥0.2 ng/ml. Kaplan-Meier curves assessed time to BCR. Multivariable Cox regression analyses tested the association between pathologic features and BCR. Multivariable logistic regression analyses identified the predictors of adverse pathologic characteristics.ResultsOverall, 926 (54.2%), 653 (33.0%), and 220 (12.9%) patients were categorized in groups 1, 2, and 3, respectively. Median follow-up was 32.2 months. The 5-year BCR-free survival rate was 94.2%. Patients in group 3 had lower BCR-free survival rates compared with those in group 1 (79.1% vs. 97.0%, P<0.001). No differences were observed between patients included in group 1 vs. group 2 (97.0% vs. 94.7%, P = 0.1). These results were confirmed at multivariable analyses and after stratification according to margin status. Older age and PSA density≥10 ng/ml/ml were associated with higher risk of unfavorable pathologic characteristics (i.e., inclusion in group 3; all P<0.001).ConclusionsAmong patients eligible for AS treated with RP, only men with Gleason score≥4+3 or non–organ-confined disease at final pathology were at increased risk of BCR. These individuals represent the real misclassified AS patients, who can be predicted based on older age and higher PSA density.     

Related Factors of Hepatocellular Carcinoma Recurrence Associated With Hyperglycemia After Liver Transplantation

BackgroundRecurrence of hepatocellular carcinoma (HCC) is the main factor affecting the prognosis of patients with HCC undergoing liver transplantation (LT). In this study, we investigated the influencing factors of tumor recurrence and survival after LT for HCC, especially the long-term correlation with elevated fasting blood glucose (FBG).MethodsClinical data from 165 patients with HCC after LT in the General Hospital of Southern Theater Command of PLA between January 2013 and December 2016 were retrospectively analyzed. Disease-free survival (DFS) and overall survival (OS) rates, demographic characteristics, tumor characteristics, and surgical and postoperative data were evaluated.ResultsAmong 165 patients, 144 completed over 60 months of follow-up; the median follow-up period was more than 36 months. DFS rates were 76.97%, 51.52%, and 34.73% for 1, 3, and 5 years, respectively. The OS rate for 5 years was 40.28%. Independent risk factors for 1-year DFS were maximum tumor diameter >5 cm, age <49 years, and platelet transfusion. Independent risk factors for 3- and 5-year DFS were maximum tumor diameter >5 cm, capsular invasion, and FBG ≥6.1 mmol/L. Independent risk factors for OS were maximum tumor diameter >5 cm, capsular invasion, and FBG ≥6.1 mmol/L.ConclusionElevated FBG after LT for HCC may promote medium- to long-term tumor recurrence and affect OS. Age <49 years, platelet transfusion, maximum tumor diameter, capsular invasion, and microvascular invasion in patients with HCC also impact survival and tumor recurrence after LT.     

Transplantation in Hepatocellular Carcinoma: Observational Multivariate Analysis of Survival and Recurrence Factors in 414 Patients

BackgroundWe sought to identify the risk factors involved in survival of and tumor recurrence in patients with hepatocellular carcinoma (HCC) undergoing liver transplant (LTx).MethodsWe conducted a retrospective observational study and analyzed the medical records of 414 patients with HCC undergoing deceased donor LTx in São Paulo between January 2007 and December 2011. Multifactorial analysis of survival and recurrence was performed using clinical, laboratory, and pathology data.ResultsThe mortality rate was 27.5%; mean survival time was 68.1 months (95% confidence interval, 64.7-71.6); and estimated 1-, 3-, and 5-year survival probabilities were 83.8%, 75.8%, and 71.5%, respectively. Altered donor blood glucose, female sex, vascular invasion, advanced age, high Model for End‐Stage Liver Disease, and tumor size were the main risk factors determining survival in LTx recipients. Recurrence was noted in 7.2% of patients during the study period and was more frequent in women (hazard ratio, 2.6). Vascular invasion increased the chance of recurrence by 5.4 times. Each additional 1-year increase in recipient age increased the chance of recurrence by 5.6%, and each 1-mm increase in tumor size increased the chance of recurrence by 3%.ConclusionsRisk factors for reduced survival are donor blood glucose, female recipient, older age, increased Model for End‐Stage Liver Disease score, and nodule size. Tumor recurrence risk factors are vascular invasion, female sex, recipient age, and nodule size.     

Recurrent hepatocellular carcinoma after transplantation: use of a pathological score on explanted livers to predict recurrence.

Milan and University of California at San Francisco (UCSF) criteria are used to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). Recurrent HCC is a significant cause of death. There is no widely accepted pathological assessment strategy to predict recurrent HCC after transplantation. This study compares the pathology of patients meeting Milan and UCSF criteria and develops a pathological score and nomogram to assess the risk of recurrent HCC after transplantation. All explanted livers with HCC from our center over the 18-yr period 1985 to 2003 were assessed for multiple pathological features and relevant clinical data were recorded; multivariate analysis was performed to determine features associated with recurrent HCC. Using pathological variables that independently predicted recurrent HCC, a pathological score and nomogram were developed to determine the probability of recurrent HCC. Of 75 cases analyzed, 50 (67%) met Milan criteria, 9 (12%) met only UCSF criteria and 16 (21%) met neither criteria based on explant pathology. There were 20 cases of recurrent HCC and the mean follow-up was 8 yr. Recurrent HCC was more common (67 vs. 12%; P < 0.001) and survival was lower (15 vs. 83% at 5 yr; 15 vs. 55% at 8 yr; P < 0.001) with those who met only UCSF criteria, compared to those who met Milan criteria. Cryptogenic cirrhosis (25 vs. 5%; P = 0.015), preoperative AFP >1,000 ng/mL (20 vs. 0%; P < 0.001) and postoperative OKT3 use (40 vs. 15%; P = 0.017) were more common among patients with recurrent HCC. While microvascular invasion was the strongest pathological predictor of recurrent HCC, tumor size >or=3 cm (P = 0.004; odds ratio [OR] = 7.42), nuclear grade (P = 0.044; OR = 3.25), microsatellitosis (P = 0.020; OR = 4.82), and giant/bizarre cells (P = 0.028; OR = 4.78) also predicted recurrent HCC independently from vascular invasion. The score and nomogram stratified the risk of recurrent HCC into 3 tiers: low (<5%), intermediate (40-65%), and high (>95%). In conclusion, compared to patients meeting Milan criteria, patients who meet only UCSF criteria have a worse survival and an increased rate of recurrent HCC with long-term follow-up, as well as more frequent occurrence of adverse histopathological features, such as microvascular invasion. Application of a pathological score and nomogram could help identify patients at increased risk for tumor recurrence, who may benefit from increased surveillance or adjuvant therapy.     

Value of Imaging Findings in the Prediction of Microvascular Invasion in Hepatocellular Carcinoma

BackgroundThe purpose of this study was to determine the utility of some imaging findings in predicting microvascular invasion (MVI) and hepatocellular carcinoma (HCC) recurrence risk after liver transplantation.MethodThis retrospective study included 123 patients with histopathologically proven HCC at explant. All HCCs were classified as MVI positive (group I) or negative (group II) based on histopathological findings. In each group, multifocality, largest tumor size, bulging (tumor causing liver capsule expansion), beak sign (the acute angle between the tumor and liver parenchyma), and diffusion restriction on diffusion weighted images (DWI) were evaluated. These findings were compared between the groups by Student’s t test. The relation between the parameters and MVI was analyzed by using the Spearman’s correlation test.ResultsOf the total patients, 30.1% had MVI (group I) and 69.9% (group II) did not have MVI. Presence of beak sign (P ≤ .005), bulging sign (P = .002), and diffusion restriction (P = .045) were significantly more frequent in group I than group II. The beak sign, bulging sign, and diffusion restriction were correlated with presence of MVI. Largest tumor size and multifocality were higher in group I than group II, but the differences were not statistically significant.ConclusionRadiologists and transplant surgeons should be aware of some clue imaging findings, especially beak and bulging signs because these findings may predict the presence of MVI in HCC. These patients might benefit from histologic confirmation of the tumor characteristics through biopsy and subsequent bridging treatment options before liver transplantation to reduce the risk of recurrence.     

Pre‐transplant therapy for hepatocellular carcinoma is associated with a lower recurrence after liver transplantation

Abstract: Background: Hepatic transplantation has been advocated as an effective treatment for hepatocellular carcinoma (HCC). We seek to determine if pre‐transplant therapies can reduce post‐transplant recurrence. Methods: We conducted a retrospective review of prospective data in patients undergoing transplantation for HCC 2001–2006. Patients were followed for recurrence every six months with abdominal computerized tomography or magnetic resonance imaging. Logistic regression analyzed recipient factors such as prior treatment for HCC, donor, operative, and tumor factors in comparing patients developing HCC recurrence with those without recurrence. Results: During the study period, we performed 124 hepatic transplants for HCC [age: 55 ± 7.6 yr; 104 (85%) male, 81 (66%) white, and 32 (26%) Asian]. Recurrence was found in nine at a mean of 2.6 yr follow‐up. Thirty‐three patients (27%) had pre‐transplant treatment (radiofrequency ablation, transarterial chemoembolization or percutaneous ethanol injection). Univariable logistic regression identified nine factors [body mass index, Asian race, hepatitis B, prior HCC therapy, alpha‐fetoprotein (AFP), model for end‐stage liver disease (MELD) score, bilirubin, and international normalized ratio] predictive of HCC recurrence at a level of p < 0.1. Multiple logistic regression analysis of six of the nine selected factors demonstrated AFP level >1000, calculated pre‐transplant MELD score <14, and the lack of any pre‐transplant treatment were significantly associated with recurrence of HCC. No patient with prior HCC therapy had recurrence. Conclusions: In patients with HCC awaiting hepatic transplantation, there is a reduced rate of recurrence of HCC if tumors are pre‐treated with liver‐directed therapy. By treating HCC tumors with any type of treatment prior to transplant, we can significantly reduce the odds of HCC recurrence after transplant.     

Preoperative prediction score of hepatocellular carcinoma recurrence in living donor liver transplantation: Validation of SNAPP score developed at Asan Medical Center

The previously proposed scoring systems are not readily available because of the lack of simplicity for predicting hepatocellular carcinoma (HCC) recurrence. We aimed to develop and validate the new score system, which can predict HCC recurrence after living donor liver transplantation (LDLT) by using morphologic and biologic data. Predictors for HCC recurrence after LDLT were developed (n = 627) and validated (n = 806) in 1433 patients for whom we could collect information to date between 2007 and 2016 at Asan Medical center (AMC) to create the SNAPP score (tumor S ize and N umber, alpha-fetoprotein [A FP], vitamin K absence-II [P IVKA-II], positron emission tomography [P ET]). On logistic regression based on 3-year recurrence-free survival, the SNAPP factors were independently associated with HCC recurrence. The SNAPP score was highly predictive of HCC recurrence (C statistic, 0.920), and 5-year post-LT recurrence rates were significantly different between low, intermediate, and high SNAPP score groups. The performance of the SNAPP score (C-index [95% confidence interval], 0.840 [0.801-0.876]) on predicting tumor recurrence after LDLT was better than that of the New York/California, the Risk Estimation of Tumor Recurrence After Transplant (RETREAT), and the Model of Recurrence After Liver Transplant (MoRAL) score. The SNAPP score provides excellent prognostication after LDLT for HCC patients. Hence, we can help voluntary patients’ decisions about whether to undergo LDLT or not.     

Oncological Outcomes of Hepatic Resection vs Transplantation for Localized Hepatocellular Carcinoma

BackgroundScarce data are available comparing outcomes of hepatic resection vs orthotopic liver transplantation (OLT) for localized hepatocellular carcinoma (HCC) patients both meeting and exceeding the Milan criteria. This study compared the clinical and oncological outcomes of patients undergoing hepatic resection vs transplantation localized HCC.MethodBetween January 2005 and February 2017, clinical and oncological outcomes of patients who underwent liver resection (n = 38) vs OLT (n = 28) for localized HCC were compared using a prospectively maintained database.ResultsA total of 66 patients (with a median age of 62) who met the study criteria were analyzed. Comparable postoperative complications (13.2% vs 28.6%, P = .45) and perioperative mortality rates (7.9% vs 10.7%, P = .2) were noted for the resection vs OLT groups. While Child-Pugh Class A patients were more prevalent in the resection group (78.9% vs 7.1%, P = .0001), the rate of patients who met the Milan criteria was higher in the OLT group (89.3% vs 34.25, P = .0001). Recurrence rates were 36.8% in the resection group and 3.6% in the OLT group at the end of the median follow-up period (32 vs 39 months, respectively). The HCC-related mortality rate was significantly higher in the resection group (39.5% vs 10.7%, P = .034).However, a subgroup analysis of patients who met the Milan criteria revealed similar rates of recurrence and HCC-related mortality (15.4% vs 8%, P = .63). Based on logistic regression analysis, number of tumors (P = .034, odds ratio: 2.1) and “resection”-type surgery (P = .008, odds ratio: 20.2) were independently associated with recurrence.ConclusionCompared to liver transplantation, hepatic resection for localized hepatocellular carcinoma is associated with a higher rate of recurrence and disease-related mortality.     

Preoperative Alpha-Fetoprotein and Radiological Total Tumor Diameter as Predictors of Hepatocellular Carcinoma Recurrence After Liver Transplantation

BackgroundLiver transplantation is a unique treatment opportunity for patients with chronic liver disease and hepatocellular carcinoma (HCC). Selection of HCC patients for transplantation was revolutionized by Milan-based criteria, but tumor recurrence and shortage of organs are still a major concern. Nowadays, additional preoperative tumor parameters can help to refine the graft allocation process. The objective of this study was to evaluate the prognostic value and cut-off points of pretransplant serum alpha-fetoprotein (AFP) levels and radiological tumor parameters on liver transplantation outcomes.MethodsThis is a single-team retrospective cohort of 162 consecutive deceased donor liver transplants (DDLT) with pathologically confirmed HCC. Pretransplant serum AFP levels and radiological tumor parameters were retrieved from a preoperative follow-up. Receiver-operating characteristics (ROC) curves were used to evaluate cut-off points for each outcome. Multivariate Cox regression model was used to assess the predictors of HCC relapse and recipient mortality.ResultsTwelve recipients (7.4%) had HCC recurrence after transplantation, with median survival time of 5.8 months. Pretransplant AFP ≥30 ng/mL (hazard ratio [HR]: 13.84, P = .003) and radiological total tumor diameter (TTD) ≥5 cm (HR: 12.89, P = .005) were independent predictors for HCC relapse. Moreover, pretransplant AFP ≥150 ng/mL was independently associated with recipient mortality (HR: 4.45, P = .003).ConclusionsPretransplant AFP levels and radiological TTD were independently associated with HCC relapse and recipient mortality after DDLT, with different cut-off points predicting different outcomes. These findings may contribute to improving decision-making in the context of liver transplantation for HCC patients.     

Conditional cumulative incidence of postoperative complications stratified by complexity classification for laparoscopic liver resection: Optimization of in-hospital observation

BackgroundThe optimal in-hospital observation periods associated with minimal risks of complications and unplanned readmission after laparoscopic liver resection are unknown. The purpose of this study was to assess changes in the risks of postoperative complications over time.MethodsSurgical complexity of laparoscopic liver resection was stratified into grades I (low complexity), II (intermediate), and III (high) using our 3-level complexity classification. The cumulative incidence rate and conditional probability of postoperative complication and risk factors for complication Clavien-Dindo grade ≥II (defined as treatment-requiring complications) were assessed.ResultsThe cumulative incidence of treatment-requiring complications was higher in patients undergoing grade III resection than in patients undergoing grade I resection (32.3% vs 10.4%, P < .001) and grade II resection (32.3% vs 20.7%, P = .019). The conditional probability of postoperative complication stratified by our complexity classification decreased over time and was <10% for patients undergoing grade I resection on postoperative day 1, grade II resection on postoperative day 4, and grade III resection on postoperative day 10.ConclusionThe conditional cumulative incidence of treatment-requiring complications for patients undergoing laparoscopic liver resection is well stratified based on the 3-level complexity classification. Conditional complication risk analysis stratified by the 3 complexity grades may be useful for optimizing in-hospital observation after laparoscopic liver resection.     

Can the Dropout Risk of Candidates with Hepatocellular Carcinoma Predict Survival after Liver Transplantation?

In the last US national conference on liver transplantation for hepatocellular carcinoma (HCC), a continuous priority score, that incorporates model for end‐stage liver disease (MELD), alpha‐fetoprotein and tumor size, was recommended to ensure a more equitable liver allocation. However, prioritizing highest alpha‐fetoprotein levels or largest tumors may select lesions at a higher risk for recurrence; similarly, patients with higher degree of liver failure could have lower postoperative survival. Data from 300 adult HCC recipients were reviewed and the proposed HCC‐MELD equation was applied to verify if it can predict post‐transplantation survival. The 5‐year survival and recurrence rates after transplantation were 72.8 and 13.5%, respectively. Cox regression analysis confirmed HCC‐MELD as predictive of both postoperative survival and recurrence (p < 0.001). The 5‐year predicted survival and recurrence rates were plotted against the HCC‐MELD‐based dropout probability: the higher the dropout probability while on waiting list, the lower the predicted survival after transplantation, that is worsened by hepatitis C positivity; similarly, the higher the predicted HCC recurrence rate after transplantation. The HCC priority score could predict the postoperative survival of HCC recipients and could be useful in selecting patients with greater possibilities of survival, resulting in higher post‐transplantation survival rates of HCC populations.     

Efficacy of Tumor Markers After Liver Transplantation In Patients With Hepatocellular Carcinoma

ObjectiveThe most reliable treatment for hepatocellular carcinoma (HCC) is liver transplantation (LT). Recurrence of HCC after LT is the most serious problem; therefore, early diagnosis of recurrent HCC is very important. This study investigated the efficacy of tumor markers in patients with LT for HCC.Methods and MaterialsFrom January 2008 to December 2016, 242 patients underwent LT for HCC. The operation of LT and immunosuppressive methods were the same as those of general LT patients. All patients were followed up with alpha-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKA)-II. The 41 patients (16.9%) recurred during follow-up period.ResultsThe factors associated with recurrence were tumor markers (AFP, PIVKA-II), maximum tumor diameter, number, microvascular invasion, Milan criteria, and Edmondson–Steiner grade. In 41 patients with recurrent HCC, 14 patients (34.15%) were both elevated in 2 markers and 18 patients (43.9%) were elevated in 1 tumor marker. There was no relationship between tumor marker and recurrent site. The survival rate of patients with recurrence in 1, 3, and 5 years were 78.6%, 34.7%, and 23.7%, respectively. Curability of treatment and elevation of tumor marker before treatment were correlated with patient survival after recurrence. When the receiver operating characteristic curve was used, the area under the curve value using the sum of AFP and PIVKA-II before LT was 0.827.ConclusionsIn this study, tumor markers (AFP, PIVKA-II) for HCC were correlated with post-transplant recurrence factors and may be a useful tool for early diagnosis and to predict the prognosis after recurrence.     

Recurrence Patterns After Hepatectomy of Hepatocellular Carcinoma: Implication of Milan Criteria Utilization

Background  Bridge hepatectomy followed by salvage liver transplantation has been proposed for patients with hepatocellular carcinoma (HCC) and preserved liver function. Methods  Data were prospectively collected for 501 consecutive patients who underwent curative primary hepatectomy for HCC between 1990 and 2006. Patient survival, disease-free survival (DFS), recurrence patterns, and risk factors were analyzed in patients classified according to the Milan criteria. Results  Patients were divided into two groups on the basis of whether their disease was within the Milan criteria (group 1, n = 321) or not (group 2, n = 180). Group 1 patient survival and DFS rates were 73.6% and 40.6% at 5 years. Recurrence was observed in 160 group 1 patients (49.8%); in 42 (26.3%) of these 160 patients, the recurrence exceeded the Milan criteria. No recurrence was noted in 145 group 1 patients (45.2%). Group 2 patient survival and DFS rates were 52.2% and 23.2%, respectively, at 5 years. Recurrence was noted in 116 patients (64.4%); recurrence in 58 (50.0%) of these patients was within the Milan criteria. In group 2, no recurrence was noted in 55 patients (30.6%). In group 1, indocyanine green retention rate at 15 minutes of >15%, nonanatomical resection, and multiple tumors were statistically significant risk factors for survival; 10-year patient survival was 78.5% for patients with no risk factors and 64.9% for patients with a single risk factor. Conclusions  The Milan criteria should be used to recommend hepatectomy for patients with HCC; however, it is important to consider the high recurrence rate after hepatectomy and the possible requirement of salvage transplantation.     

External validation of the VENUSS prognostic model to predict recurrence after surgery in non-metastatic papillary renal cell carcinoma: A multi-institutional analysis

ObjectiveRecently, VENUSS (VEnous extension, NUclear Grade, Size, Stage), as a prognostic model, was defined to predict disease recurrence (DR) after curative surgery of non-metastatic papillary renal cell carcinoma (papRCC). This study aimed to validate the VENUSS prognostic model in a large multi-institutional European cohort of patients with histopathologically proven papRCC after curative surgery for non-metastatic disease.Patients and MethodsOverall, 980 patients undergoing partial or radical nephrectomy for sporadic, unilateral and non-metastatic papRCC between 1987 and 2020 were included from 7 European tertiary institutions. The primary outcome was the prediction of DR by VENUSS score and VENUSS risk groups. Chi-square, Kruskal-Wallis, Cox-regression and Kaplan-Meier survival analyses were used in statistical methods. The Concordance (C) Index was calculated to assess model's discriminatory power.ResultsThe median age was 64 (IQR:55–70) years and 82.6 % (n = 809) of patients were male. Median VENUSS score was 2 (IQR: 0–4), and 62.9 % (n = 617), 23.9 % (n = 234) and 13.2 % (n = 129) of patients was classified into low, intermediate and high risk according to the VENUSS model, respectively. At a median follow-up of 48 (IQR:23–88) months, the disease recurred in 6.6%, 18.8% and 63.8%, and the 5-year recurrence-free survival was 93.8%, 80.7% and 26.7% in low, intermediate and high-risk groups, respectively. (P < 0.001) Each increase in VENUSS score had 1.52-fold (95%CI:1.45–1.60, P < 0.001) DR risk. Compared with the VENUSS low risk, the intermediate risk had a 2.91-fold increased DR risk (95%CI:1.90–4.46, P < 0.001) and 17.9-fold (95%CI:12.25–26.25, P < 0.001) in high risk, while it was 6.07-fold greater in high risk vs. intermediate risk (95%CI:4.17–8.83, P < 0.001). The discrimination was 81.2% (95%CI:77.5%–84.8%) for the VENUSS score, and 78.6% (95%CI:74.8%–82.4%) for VENUSS risk groups, respectively. Both the VENUSS score and groups were well calibrated.ConclusionsThis contemporary multi-institutional European large dataset validated the use of VENUSS score and VENUSS risk groups on the prediction of DR after curative surgery in patients with non-metastatic papRCC. The VENUSS prognostic model can provide valuable information for patient counselling, follow-up and patient selection for adjuvant trials.     

Validation of the prognostic power of the RETREAT score for hepatocellular carcinoma recurrence using the UNOS database

Researchers in a recent multicenter study developed and validated a novel prognostic index, Risk Estimation of Tumor Recurrence After Transplant (RETREAT), which incorporates α‐fetoprotein (AFP) at liver transplantation (LT), microvascular invasion, and the sum of the largest viable tumor and number of tumors on explant. We now aim to evaluate RETREAT in the United Network for Organ Sharing (UNOS) database in patients with hepatocellular carcinoma (HCC) who meet Milan criteria by imaging and underwent LT between 2012 and ‐2014. On explantation (n = 3276), 13% had microvascular invasion, 30% had no viable tumor, and 15% exceeded Milan criteria. Post‐LT survival at 3 years decreased with increasing RETREAT score: 91% for a score of 0, 80% for a score of 3, and 58% for a score ≥5 (P < .001). Post‐LT HCC recurrence probability within 3 years increased from 1.6% with RETREAT score of 0% to 29% for a score ≥5 (P < .001). Increasing RETREAT score was also associated with a shorter time to HCC recurrence. RETREAT was superior to Milan criteria (explant) in predicting HCC recurrence by the net reclassification index (P < .001). This study validates the prognostic power of RETREAT, which may help standardize post‐LT surveillance, provide a framework for tumor staging and risk stratification, and select candidates for adjuvant therapies.     

Predictors of post-recurrence survival in hepatocellular carcinoma patients following liver transplantation: Systematic review and meta-analysis

BackgroundData on predictors of post-recurrence survival (PRS) of recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) have not been reviewed and analysed systematically. We aimed to systematically analyse all published data on the predictors for PRS.MethodsIn accordance with PRISMA and MOOSE guidelines, online search of PubMed and EMBASE databases was done for all reports that evaluate the predictors of PRS based on multivariate analyses. Cumulative analyses of hazard ratios (HRs) and their corresponding 95% CIs were conducted to assess the potential predictors of PRS.ResultsTwenty-three studies met the inclusion criteria. Among the 11,868 patients involved, 1921 (16%) had HCC recurrence within a median time of 16 months. The following were recurrence and tumour-related predictors: time to recurrence (<1 year; HR: 1.97; p < 0.001), AFP level at recurrence(≥100 ng/ml; HR: 1.82; p < 0.001), multiple recurrence (HR: 1.22; p < 0.001), bone recurrence (HR: 2.10; p < 0.001), poor differentiation (HR: 1.52; p < 0.001), intrahepatic recurrence (HR: 0.91; p = 0.03), extrahepatic recurrence (HR: 1.87; p < 0.001), Milan criteria at LT (HR: 1.34; p < 0.001), microvascular invasion (HR: 1.59; p < 0.001), multiorgan recurrence (HR: 1.28; p < 0.001), and recurrent HCV infection (HR: 1.21; p < 0.001). The treatment-related predictors were as follows: surgical resection (HR: 0.33; p < 0.001), mTOR inhibitors (HR: 0.63; p < 0.001), sorafenib (HR: 1.00; p = 0.01), palliative treatment (HR: 3.07; p < 0.001), RFA (HR: 0.47; p < 0.001), and radiotherapy (HR: 1.19; p < 0.001).ConclusionsSystematic evaluation of these predictors could guide surgeons to design risk-adapted algorithms for the management of post-LT HCC recurrence to construct reliable predictive models and to design future prospective studies or clinical trials.     

Excellent Outcome in 238 Consecutive Living Donor Liver Transplantations Using the Right Liver Graft in a Large Volume Single Center

Background

Using a right liver (RL) graft improves the outcomes in adult living donor liver transplantation (ALDLT). Here we report the recent excellent outcomes of 238 consecutive RL transplantations in ALDLT.

Methods

Between January 2005 and June 2009, 238 consecutive adult recipients underwent RL transplantation; The middle hepatic vein (MHV) was reconstructed using artificial vascular grafts in 209 cases. Among these study subjects, UNOS status 1 and 2A were 12 (5.0 %) and 20 (8.4 %) patients, and the mean medical MELD score, was 19.9. Hepatitis B virus was the most common original liver disease in 184 patients (77.3 %). Hepatocellular carcinoma was diagnosed in 133 patients (56.3 %), and 102 patients (76.1 %) met the radiologic Milan criteria. The mean graft-versus-recipient weight ratio was 1.14 %. The primary endpoint of this study was the patient and graft survival rate. The mean follow-up period was 32 (0–69) months.

Results

The most common major complication was biliary complication (n = 62; 26 %). The 1-, 2-, and 5-year patient survival rates were 96, 95, and 94 %, and the graft survival rates were 99, 99, and 98 %. There were 4 hospital deaths (1.6 %). Eighteen late mortalities were observed after recurrence of hepatocellular carcinoma (HCC, n = 17) and one case of lymphoma recurrence. One case of graft failure 33 months after ALDLT was attributed to cholestatic fibrosing hepatitis B saved by re-ALDLT. On multivariate analysis, no drainage of MHV branches and accompanying HCC beyond Milan criteria were the risk factors for poor patients’ survival rate (p < 0.05).

Conclusions

Further technical innovation would be required to overcome biliary complications. The technical innovation using right liver draining MHV branches improved both patient and graft survival outcomes of ALDLT. Despite these advances, selection criteria for HCC are still hurdles, even in RL transplantation.