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Purpose: Liver transplantation is curative for hepatocellular carcinoma (HCC). Checkpoint inhibitor therapy (CPIT) has been used in unresectable HCC, but recent advances have demonstrated CPIT as an innovative method of downstaging advanced HCC with the caveat that CPIT prior to transplantation has risks including irreversible graft rejection. We report the outcomes of Mayo Clinic Arizona patients who underwent downstaging with CPIT. Methods: This retrospective chart review was conducted for Mayo Clinic Arizona patients who were diagnosed with HCC who underwent downstaging with CPIT with the goal of meeting criteria for transplantation. Results: We present nine cases with HCC outside Milan who underwent CPIT. Four received a transplant; one was delisted due to his exceptional therapeutic response. All received liver-directed therapy. Peak alpha-fetoprotein pre-CPIT ranged from 8–29,523 ng/mL, which decreased to 2.2–19.6 ng/mL on CPIT. CPIT included atezolizumab/bevacizumab, ipilimumab/nivolumab, nivolumab, and pembrolizumab; one patient received two regimens. CPIT was held prior to transplant at a median of 3 months. Three patients received methylprednisolone for immunosuppression induction; one received thymoglobulin. One patient developed acute cellular rejection at 5 weeks, 9 weeks, and 5 months post-transplant; given the late onset, these were not attributed to CPIT and were successfully treated. During an average follow-up of 16.5 months, no tumor recurrence has occurred. Conclusion: We describe nine patients with HCC outside Milan with inadequate response with liver-directed therapy, who achieved marked responses with CPIT, allowing for consideration of successful liver transplantation. Our case series supports the consideration of locoregional therapies and CPIT for downstaging to within transplant criteria. [ABSTRACT FROM AUTHOR]

Background: Fine needle aspiration cytology (FNAC) is an integral part of the preoperative work-up of parotid tumours. Aim: To determine the rate of concordance between FNAC and histology following parotidectomy. Methods: A review of records of patients who had parotidectomy which was preceded FNAC was done. Data collected included patients' demography, presenting symptoms and clinical signs; cytology and post-operative histology results. Results: Seventy-seven records were found and 14 were excluded. Forty-five (71%: 45/63) of the tumours were benign, 21% (13/63) malignant and 8% (5/63) inflammatory lesions. Forty-one (91.1%: 41/45) of the benign tumours had concordance between FNAC and final histology. Seven (63.6%: 7/11) of FNAC diagnosed malignancies were confirmed on histology. Conclusion: Around 71% of parotid masses were benign. Painful masses are more likely to be malignant and FNAC is more reliable for the diagnosis of pleomorphic adenoma than rare benign and malignant tumours of the parotid gland. [ABSTRACT FROM AUTHOR]

Objectives: Liver transplant (LT) is an effective treatment for hepatocellular carcinoma (HCC) in appropriately selected patients. Locoregional therapy (LRT) is often performed to extend a patient’s eligibility for LT. Imaging has a modest sensitivity of approximately 40–77% for detecting pathologically viable HCC in post-LRT patients. The impact on overall survival (OS) and disease-free survival (DFS) is unclear. We hypothesize that Liver Imaging Reporting & Data Systems Treatment Response (LI-RADS TR) category is equivalently correlated with long-term survival and overall disease-free progression when compared to explant pathology findings. We additionally hypothesize that neoadjuvant LRT can improve OS and DFS in LT patients initially within MC.Patients found to have HCC on explant between January 2005 and December 2021 were included. A total of 167 patients were divided into treatment (any pre-LT LRT except for Y-90 therapy) and control (no pre-LT LRT) groups. Of the patients who received pre-LT LRT, imaging studies were reviewed by two abdominal radiologists using 2018 LI-RADS criteria. Statistical analysis was performed using Kaplan-Meier survival curves and Cox proportional hazard models to assess OS and DFS.No statistically significant difference in OS or DFS (p = 0.23 and p = 0.22 respectively) was initially found. Given significant difference in age between the groups (p < 0.0001), Cox proportional hazard models were used to adjust for age with statistical significance reached for better OS and DFS in the treatment group (p = 0.05 and p = 0.05 respectively). Contrary to our hypothesis, there was no difference between treatment response groups regarding overall survival or disease-free survival, presumably because of low number of HCC recurrences in our patient population (4%).Despite not reaching statistical significance, LI-RADS TR categorization demonstrates a good interreader agreement (Kappa 0.6), helping radiologists feel comfortable that modest sensitivity of the LI-RADS TR treatment response category for detecting pathologically active malignancy does not confer a negative clinical outcome.Methods: Liver transplant (LT) is an effective treatment for hepatocellular carcinoma (HCC) in appropriately selected patients. Locoregional therapy (LRT) is often performed to extend a patient’s eligibility for LT. Imaging has a modest sensitivity of approximately 40–77% for detecting pathologically viable HCC in post-LRT patients. The impact on overall survival (OS) and disease-free survival (DFS) is unclear. We hypothesize that Liver Imaging Reporting & Data Systems Treatment Response (LI-RADS TR) category is equivalently correlated with long-term survival and overall disease-free progression when compared to explant pathology findings. We additionally hypothesize that neoadjuvant LRT can improve OS and DFS in LT patients initially within MC.Patients found to have HCC on explant between January 2005 and December 2021 were included. A total of 167 patients were divided into treatment (any pre-LT LRT except for Y-90 therapy) and control (no pre-LT LRT) groups. Of the patients who received pre-LT LRT, imaging studies were reviewed by two abdominal radiologists using 2018 LI-RADS criteria. Statistical analysis was performed using Kaplan-Meier survival curves and Cox proportional hazard models to assess OS and DFS.No statistically significant difference in OS or DFS (p = 0.23 and p = 0.22 respectively) was initially found. Given significant difference in age between the groups (p < 0.0001), Cox proportional hazard models were used to adjust for age with statistical significance reached for better OS and DFS in the treatment group (p = 0.05 and p = 0.05 respectively). Contrary to our hypothesis, there was no difference between treatment response groups regarding overall survival or disease-free survival, presumably because of low number of HCC recurrences in our patient population (4%).Despite not reaching statistical significance, LI-RADS TR categorization demonstrates a good interreader agreement (Kappa 0.6), helping radiologists feel comfortable that modest sensitivity of the LI-RADS TR treatment response category for detecting pathologically active malignancy does not confer a negative clinical outcome.Results: Liver transplant (LT) is an effective treatment for hepatocellular carcinoma (HCC) in appropriately selected patients. Locoregional therapy (LRT) is often performed to extend a patient’s eligibility for LT. Imaging has a modest sensitivity of approximately 40–77% for detecting pathologically viable HCC in post-LRT patients. The impact on overall survival (OS) and disease-free survival (DFS) is unclear. We hypothesize that Liver Imaging Reporting & Data Systems Treatment Response (LI-RADS TR) category is equivalently correlated with long-term survival and overall disease-free progression when compared to explant pathology findings. We additionally hypothesize that neoadjuvant LRT can improve OS and DFS in LT patients initially within MC.Patients found to have HCC on explant between January 2005 and December 2021 were included. A total of 167 patients were divided into treatment (any pre-LT LRT except for Y-90 therapy) and control (no pre-LT LRT) groups. Of the patients who received pre-LT LRT, imaging studies were reviewed by two abdominal radiologists using 2018 LI-RADS criteria. Statistical analysis was performed using Kaplan-Meier survival curves and Cox proportional hazard models to assess OS and DFS.No statistically significant difference in OS or DFS (p = 0.23 and p = 0.22 respectively) was initially found. Given significant difference in age between the groups (p < 0.0001), Cox proportional hazard models were used to adjust for age with statistical significance reached for better OS and DFS in the treatment group (p = 0.05 and p = 0.05 respectively). Contrary to our hypothesis, there was no difference between treatment response groups regarding overall survival or disease-free survival, presumably because of low number of HCC recurrences in our patient population (4%).Despite not reaching statistical significance, LI-RADS TR categorization demonstrates a good interreader agreement (Kappa 0.6), helping radiologists feel comfortable that modest sensitivity of the LI-RADS TR treatment response category for detecting pathologically active malignancy does not confer a negative clinical outcome.Conclusion: Liver transplant (LT) is an effective treatment for hepatocellular carcinoma (HCC) in appropriately selected patients. Locoregional therapy (LRT) is often performed to extend a patient’s eligibility for LT. Imaging has a modest sensitivity of approximately 40–77% for detecting pathologically viable HCC in post-LRT patients. The impact on overall survival (OS) and disease-free survival (DFS) is unclear. We hypothesize that Liver Imaging Reporting & Data Systems Treatment Response (LI-RADS TR) category is equivalently correlated with long-term survival and overall disease-free progression when compared to explant pathology findings. We additionally hypothesize that neoadjuvant LRT can improve OS and DFS in LT patients initially within MC.Patients found to have HCC on explant between January 2005 and December 2021 were included. A total of 167 patients were divided into treatment (any pre-LT LRT except for Y-90 therapy) and control (no pre-LT LRT) groups. Of the patients who received pre-LT LRT, imaging studies were reviewed by two abdominal radiologists using 2018 LI-RADS criteria. Statistical analysis was performed using Kaplan-Meier survival curves and Cox proportional hazard models to assess OS and DFS.No statistically significant difference in OS or DFS (p = 0.23 and p = 0.22 respectively) was initially found. Given significant difference in age between the groups (p < 0.0001), Cox proportional hazard models were used to adjust for age with statistical significance reached for better OS and DFS in the treatment group (p = 0.05 and p = 0.05 respectively). Contrary to our hypothesis, there was no difference between treatment response groups regarding overall survival or disease-free survival, presumably because of low number of HCC recurrences in our patient population (4%).Despite not reaching statistical significance, LI-RADS TR categorization demonstrates a good interreader agreement (Kappa 0.6), helping radiologists feel comfortable that modest sensitivity of the LI-RADS TR treatment response category for detecting pathologically active malignancy does not confer a negative clinical outcome. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate the optimal radiologic method to determine Milan criteria (MC) for the prediction of recurrence in patients who underwent locoregional treatment (LRT) for hepatocellular carcinoma (HCC) and subsequent liver transplantation (LT). Methods: This retrospective study included 121 HCC patients who underwent LRT and had both liver dynamic CT and MRI. They were classified with MC using four cross combinations of two imaging modalities (CT and MRI) and two diagnostic criteria (modified Response Evaluation Criteria in Solid Tumors [mRECIST] and Liver Imaging Reporting and Data System treatment response algorithm [LI-RADS TRA]). Competing risk regression was performed to analyze the time to recurrence after LT. The predictive abilities of the four methods for recurrence were evaluated using the time-dependent area under the curve (AUC). Results: Competing risk regression analyses found that beyond MC determined by MRI with mRECIST was independently associated with recurrence (hazard ratio, 6.926; p = 0.001). With mRECIST, MRI showed significantly higher AUCs than CT at 3 years and 5 years after LT (0.597 vs. 0.756, p = 0.012 at 3 years; and 0.588 vs. 0.733, p = 0.024 at 5 years). Using the pathologic reference standard, MRI with LI-RADS TRA showed higher sensitivity (61.5%) than CT with LI-RADS TRA (30.8%, p < 0.001) or MRI with mRECIST (38.5%, p < 0.001). Conclusions: MRI with mRECIST was the optimal radiologic method to determine MC for the prediction of post-LT recurrence in HCC patients with prior LRT. Key Points: • MRI with modified RECIST (mRECIST) is the optimal preoperative method to determine Milan criteria for the prediction of post-transplant HCC recurrence in patients with prior locoregional treatment. • With mRECIST, MRI was better than CT for the prediction of post-transplant recurrence. [ABSTRACT FROM AUTHOR]

Background: Radiofrequency ablation (RFA) is considered as a convenient treatment with mild damage in treating recurrent hepatocellular carcinoma (RHCC). However, for patients with high risk of progression after RFA still needs new strategies to decrease the repeat recurrence.Methods: A total of 460 patients with RHCC within Milan criteria in four institutions were enrolled. 174 pairs were enrolled after propensity score matching (PSM). Overall survival (OS) and tumor-free survival (TFS) were compared between the two groups. A quantitative score system was established to screen out the beneficial population from RFA-sorafenib treatment.Results: The 1-, 3-, and 5-year OS rates were 97.7%, 83.7%, 54.7% for RFA-sorafenib group, and 93.1%, 61.3%, 30.9% for RFA group after PSM, respectively. Compared with the RFA group, the RFA-sorafenib group had significantly better OS (P < 0.001). The 1-, 3-, and 5-year TFS rates were 90.8%, 49.0%, 20.4% for RFA-sorafenib group, and 67.8%, 28.0%, 14.5% for RFA group after PSM. The difference was observed significantly between RFA-sorafenib group and RFA group (P < 0.001). A quantitative risk score system was established to precisely screen out the beneficial population from RFA-sorafenib treatment.Conclusions: Adjuvant sorafenib after RFA was superior to RFA alone in improving survival outcomes in patients with recurrent HCC within Milan criteria after initial hepatectomy. Subgroup analyses concluded that patients with high risk score had significantly longer survival from sorafenib administration. [ABSTRACT FROM AUTHOR]

The results of treatment for early stage recurrent hepatocellular carcinoma (HCC) remain controversial. This study aimed to analyze the clinical outcomes of recurrent HCC within the Milan criteria following different treatment modalities except liver transplantation. From January 2006 to December 2016, 272 consecutive HCC patients who developed intrahepatic recurrence after hepatectomy that satisfied the Milan criteria and Child–Pugh class A or B liver function were retrospectively enrolled. The outcomes of repeat resection (RR), local ablative therapy (LAT), or transarterial chemoembolization (TACE) were reported, and the prognostic factors of survival were investigated. Among the 272 patients, 136 (50.0%), 71 (26.1%), and 65 (23.9%) received TACE, LAT, and RR treatments, respectively. Treatment-related complications were 9.5%, 11.3%, and 10.7%, respectively, in the three groups. No patient died of treatment-related complication. The 1-, 3-, and 5-year overall survival rates after recurrence were 95.0%, 54.2%, and 45.8%, respectively, in the RR group; 86.6%, 51.7%, and 42.4%, respectively, in the LAT group; and 77.2%, 46.5%, and 38.4%, respectively, in the TACE group. On multivariate analysis, three independent factors related to survival after recurrences were identified. A single tumor nodule and AFP < 200 ng/mL predicted better survival, while a disease-free interval ≤ 1 year was associated with poor outcomes. RR and LAT could achieve good survival outcomes in well-selected patients with recurrent HCC within the Milan criteria, while TACE was the main form of treatment when curative therapy was not considered feasible and the clinical outcomes were satisfactory. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to apply the principles of the "Milan criteria" to patients undergoing hepatic resection for CRLM and to evaluate the efficacy of prognostic factors. Methods: The medical records of consecutive patients who underwent curative resection for CRLM from April 2007 to April 2019 were retrospectively reviewed. Time to aggressive treatment failure (TATF) was defined as the time interval from the initial surgery until the first unresectable recurrence or recurrence that could only be treated with doublet or lower dose chemotherapy, or death. The risk factors associated with recurrence-free survival (RFS), TSF, TATF, and overall survival (OS) were evaluated. Results: On univariate analysis, the Milan criteria significantly predicted long-term OS, TATF, TSF, and RFS. Moreover, the Milan criteria were able to stratify patients with CRLM into distinct prognostic groups with regard to long-term OS, TATF, TSF, and RFS. Conclusions: Milan criteria, a simple index, are a factor contributing to all the survival time and are a very important factor in discussing the prognosis of CRLM. [ABSTRACT FROM AUTHOR]

Purpose: The precise role of downstaging or bridge therapy for cirrhotic patients with hepatocellular carcinoma (HCC) beyond or within the Milan criteria (MC) before living donor liver transplantation (LDLT) remains undefined. Methods: We conducted a single-center, retrospective cohort study of 40 cirrhotic patients with HCC who underwent LDLT from 2000 to 2018. Dynamic computed tomography images at the initial presentation and immediately before LDLT as well as the final histopathological findings were reviewed to determine whether they met or exceeded MC. Results: Overall, 29 patients underwent various pre-transplant HCC treatments, including ablation and embolization (bridge therapy, n = 20; downstaging, n = 9). Of the 9 patients who were initially beyond the MC, 4 (44.4%) were successfully downstaged to within the MC. Five patients beyond the MC immediately before LDLT demonstrated a significantly worse 5-year overall survival rate than patients within the MC (16.7% vs. 82.2%, P = 0.004), regardless of the radiological HCC stage at presentation or the final pathological tumor status. All 3 recurrent patients had HCC beyond the MC immediately before transplant and died of their disease at 13, 24, and 50 months after transplantation. Conclusions: Successful downstaging for HCC cases beyond the MC provides similar outcomes to those within the MC at presentation, regardless of the histopathological findings. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths and the 7th most common cancer. It has two characteristic features: being advanced stage at diagnosis and association with liver cirrhosis. Liver transplantation (LT) offers the only curative option to treat both components of the disease. The Milan criteria have been extensively used for selecting patients with HCC for LT. However, using Milan criteria, we can only transplant 30% of the patients. The aim of the present review is to evaluate the role of LT in HCC beyond the Milan criteria. Methods: We evaluated the studies that have introduced extended criteria to select patients with HCC beyond the Milan criteria. We evaluated the outcomes in terms of disease-free survival rates and HCC recurrences. Results: There are patients with tumors that are beyond Milan criteria that could benefit from LT. Selection of these patients has paramount importance in the era of living donor liver transplantation. Current expanded criteria depend on either the bulk of the tumor or the additional surrogate markers of tumor biology such as alpha-fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP). Conclusion: There is no ideal marker or an extended criterion for selecting patients with HCC beyond the Milan criteria and it needs further research to find an effective biomarker that has prognostic significance to select patients with advanced tumors. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is common in patients with hepatocellular carcinoma (HCC) and may impact survival. Very few studies focused on the influence of DM in different clinical scenarios. We evaluated the prognostic impact of DM on HCC patients stratified by liver dysfunction, Milan criteria, and performance status defined in the Barcelona Clínic Liver Cancer staging parameters.Methods: A prospective dataset of 3573 HCC patients between 2002 and 2016 was retrospectively analyzed. The multivariate Cox proportional hazards model was used to identify independent prognostic predictors. The Kaplan-Meier method with a log-rank test was applied to compare the survival distributions between different patient groups.Results: Among all, DM was not an independent prognostic predictor in the Cox multivariate analysis (p = 0.1044). In the subgroup analysis, DM was not a significant prognostic predictor in Child-Turcotte-Pugh class A or class B/C patients. However, DM was associated with a decreased survival in patients within the Milan criteria (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.155-1.601, p = 0.0002) and in those with the performance status 0 (HR 1.213, 95% CI 1.055-1.394, p = 0.0067) in the multivariate Cox analysis, but not in those beyond the Milan criteria and poor performance status.Conclusions: DM is highly prevalent in HCC patients and has a distinct survival impact. DM is an independent survival predictor among patients within the Milan criteria and good performance status. These high-risk patients should be closely monitored, and aggressive anticancer treatment should be considered. [ABSTRACT FROM AUTHOR]

Purposes: The indication of endoscopic (laparoscopic and thoracoscopic) hepatic resection (HR) has been expanded in the past decade because of its low invasiveness. However, the indications of endoscopic HR and radiofrequency ablation (RFA) have not yet been determined. Methods: Among the 906 patients hospitalized for the initial treatment of hepatocellular carcinoma (HCC) between 2000 and 2017, 77 underwent endoscopic partial HR (E-pHR), and 94 underwent endoscopic RFA (E-RFA). We compared the short- and long-term outcomes between the E-pHR and E-RFA groups. Results: The patients in the E-RFA group were characterized primarily by an impaired liver function. Among the patients with liver damage B or C, the overall survival (OS) in the E-pHR group was significantly worse than in the E-RFA group (3-year OS: 36% vs. 82%, p = 0.003). Conclusion: E-RFA may be recommended for the initial treatment of HCC in patients with a severely impaired liver function. However, E-pHR should be avoided as the initial treatment of HCC in such patients. [ABSTRACT FROM AUTHOR]

Background: The survival of patients with advanced hepatocellular carcinoma (HCC) is highly variable due to heterogeneous tumoral characteristics. We proposed and validated an albumin-bilirubin (ALBI)-based model for HCC beyond Milan criteria, the ALBI-HOME, for these patients.Methods: A total of 2186 patients were enrolled and randomly assigned to the derivation cohort (n = 1093) and validation cohort (n = 1093). Multivariate Cox proportional hazards model was used to determine significant prognostic factors in the derivation cohort. The performance of ALBI-HOME was evaluated in the validation cohort.Results: In the Cox model, six factors were identified as independent predictors of poor survival: ALBI grade 2 [hazard ratio (HR) 1.848, 95% confidence incidence (CI) 1.556-2.195, p < 0.001], ALBI grade 3 (HR 3.266, 95% CI 2.531-4.215, p < 0.001), serum AFP ≥ 100 ng/ml (HR 1.482, 95% CI 1.279-1.717, p < 0.001), total tumor volume ≥ 250 cm3 (HR 1.503, 95% CI 1.294-1.746, p < 0.001), ascites (HR 1.400, 95% CI 1.187-1.561, p < 0.001), performance status 0-1 (HR 1.756, 95% CI 1.485-2.076 p < 0.001), and vascular invasion or metastasis (HR 2.110, 95% CI 1.809-2.0, p < 0.001). The ALBI-HOME is based on these six parameters, and the score ranges from 0 to 7. This model was associated with the best prognostic ability among different HCC staging systems to predict survival in patients beyond Milan criteria; its ability remained consistently stable in different treatment subgroups and viral etiologies.Conclusions: The proposed ALBI-HOME is a simple and feasible predictive model for HCC beyond Milan criteria. It demonstrates superior prognostic performance among the currently used staging systems and may help identify at-risk patients to undergo more aggressive treatments. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to establish a preoperatively available serological risk index using alpha-fetoprotein (AFP) and C-reactive protein (CRP) for predicting oncologically futile liver transplantation (LT) in hepatocellular carcinoma (HCC) patients.Methods: A total of 119 liver transplant patients with HCC were retrospectively analyzed. The prognostic impact of clinical and histopathologic factors including pre-LT serum AFP and CRP values was determined.Results: Apart from microvascular tumor invasion (MVI; odds ratio [OR] 15.77), pretransplant serum levels of AFP > 100 ng/ml (OR 13.31) and CRP > 0.8 mg/dl (OR 13.97) were identified as independent predictors of HCC recurrence. The cumulative risk of HCC relapse at 5 years post-LT was 2.3% in low serological tumor activity (STA) index (AFP ≤ 100 ng/ml + CRP ≤ 0.8 mg/dl), 17.1% in intermediate STA (AFP ≤ 100 ng/ml or CRP ≤ 0.8 mg/dl), and 91.6% in high STA index (AFP > 100 ng/ml + CRP > 0.8 mg/dl; p < 0.001), respectively. High STA index was identified as most powerful pre-LT available predictor of MVI (OR 15.31) and posttransplant HCC recurrence (OR 54.44). Five-year recurrence-free survival rate in Milan Out patients with high STA was 0%, compared to 91.7% and 83.6% in those with low or intermediate STA index (p < 0.001), respectively.Conclusion: Our proposed serological risk index based on pretransplant serum AFP and CRP values is able to predict oncologically futile LT among advanced HCC patients. [ABSTRACT FROM AUTHOR]

Over the last several years, liver transplantation has evolved to become a widely used treatment for hepatocellular carcinoma (HCC). The criteria used were developed in order to have acceptable outcomes for transplant with survival similar to other indications for transplant. These criteria are discussed in detail along with alternate options, including surgical resection and downstaging of HCC in cirrhotics. Technical considerations of liver transplantation must be considered, and living donor liver transplant is a possibility for treatment. [ABSTRACT FROM AUTHOR]

The aim of this work is to study the different factors that affect the outcome of living donor liver transplantation for patients with hepatocellular carcinoma (HCC). Between April 2003 to November 2014, 62 patients with liver cirrhosis and HCC underwent living donor liver transplantation (LDLT) in the National Liver Institute, Menoufia University, Egypt. The preoperative, operative, and postoperative data were analyzed. After studying the pathology of explanted liver; 44 (71 %) patients were within the Milan criteria, and 18 (29 %) patients were beyond Milan; 13 (21.7 %) of patients beyond the Milan criteria were also beyond the University of California San Francisco criteria (UCSF) criteria. Preoperative ablative therapy for HCC was done in 22 patients (35.5 %), four patients had complete ablation with no residual tumor tissues. Microvascular invasion was present in ten patients (16 %) in histopathological study. Seven (11.3 %) patients had recurrent HCC post transplantation. The 1, 3, 5 years total survival was 88.7, 77.9, 67.2 %, respectively, while the tumor-free survival was 87.3, 82.5, 77.6 %, respectively. Expansion of selection criteria beyond Milan and UCSF had no increased risk effect on recurrence of HCC but had less survival rate than patients within the Milan criteria. Microvascular invasion was an independent risk factor for tumor recurrence. [ABSTRACT FROM AUTHOR]

Benefits of liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) are well established. However, there is debate regarding optimal and equitable selection of patients best served by LT, particularly in the face of limited organ availability. Herein, we discuss topics regarding LT selection criteria for patients with HCC. Recent change in UNOS policy currently mandates a 6-month observation period prior to priority listing and institutes a cap of 34 MELD exception points for patients with HCC. Additionally, two further proposed changes to UNOS policy include (1) requiring locoregional therapy for those with small (2-3 cm) unifocal HCC prior to applying for exception points and (2) allowing downstaging in select patients with UNOS T3 lesions. These policies move beyond simply using tumor burden to using markers of tumor biology for selecting patients who have the lowest risk of post-transplant recurrence and best chance at long-term post-transplant survival. Given increasing time on transplant waiting lists and shortage of donor grafts, LT should be reserved for patients who may achieve significant benefit compared to non-transplant therapies. Potential benefit to HCC patients must be weighed against the harm from delaying or precluding LT for non-HCC patients on the waiting list, particularly in regions with limited donor availability. The relative benefit of LT in patients with small (<3 cm) HCC is likely limited; surgical resection (in absence of portal hypertension) and local ablative therapy (if portal hypertension present) are both efficacious and more cost-effective and should likely be regarded as first line therapies for these patients. Salvage LT can be considered as a rescue option for those with recurrent disease. Downstaging for selected patients with UNOS T3 lesions may identify those with good tumor biology and acceptable post-transplant outcomes; however, current studies have had a wide variation in reported outcomes. While awaiting more data, a standardized downstaging protocol including a priori inclusion criteria and a mandatory waiting time prior to LT to observe tumor biology likely yields the best outcomes. [ABSTRACT FROM AUTHOR]

Background and Aims: To evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.Methods: Our transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times. Survival analysis was conducted using Kaplan-Meier estimation and log-rank test.Results: Of 265 listed, 205 underwent OLT (mean follow-up 7.6 years). Of 205, 111 received bridging LRT (A), and 94 did not (B). Both were similar in demographics and tumor characteristics (p > 0.05). Median OS from HCC for A/B were 86.4 vs. 68.9 months (p = 0.01). Median OS from OLT for A/B were 74.6 vs. 63.6 months (p = 0.03). On multivariate analysis, independent predictors for survival from HCC were bridging LRT (p = 0.002) and high wait time (p = 0.008); independent predictors for survival from OLT were bridging LRT (p = 0.005) and high wait time (p = 0.005). Of 60 who were listed but did not undergo transplant, 44 received LRT (C) and 16 received best supportive care (D). Median OS from HCC for C/D were 37.1 vs. 24.8 months (p = 0.03).Conclusions: Bridging LRT and high wait times were independent positive prognostic factors for survival from HCC diagnosis and OLT. [ABSTRACT FROM AUTHOR]

Purpose of Review: The current review aims to provide an updated analysis on race/ethnicity-specific disparities in hepatocellular carcinoma (HCC) epidemiology in the USA with a focus on HCC incidence and prevalence, HCC stage at diagnosis, HCC treatment received, and overall HCC survival. Recent Findings: While the overall incidence of HCC in the USA has stabilized, race/ethnicity-specific disparities persist. HCC incidence remains the highest among Asians, but the burden of HCC among Hispanics is rising and may reflect the significant burden of nonalcoholic fatty liver disease (NAFLD)-related HCC among this group. Furthermore, disparate implementation of HCC screening and surveillance, which detrimentally affects ethnic minorities and underserved populations to the greatest extent, contributes to lower rates of potentially curative therapies and lower overall survival among these groups, especially African Americans with HCC. Summary: Despite improvements in clinical care of HCC patients, persistent race/ethnicity-specific disparities in HCC outcomes persist and reflect multifactorial barriers. Highlighting these disparities is the first step towards raising awareness to guide future education and research to improve HCC outcomes for all groups. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the fastest growing malignancy in the USA, and its prognosis remains poor with a 5-year survival around 12 %. Clinical data demonstrate that 85 % of cases occur in individuals with underlying cirrhosis and only 15 % develop in non-cirrhotic livers. Therefore, American and European guidelines recommend routine HCC screening for high-risk individuals (patients with cirrhosis) with abdominal ultrasound every 6 months. Once a lesion is identified or suspected on ultrasound, dynamic imaging is then indicated. The diagnosis of HCC is established in a patient with cirrhosis when a lesion measures at least 1 cm in diameter and demonstrates arterial enhancement and portal venous washout on contrast-enhanced computerized tomography or magnetic resonance imaging. Indeterminate lesions should be followed with surveillance imaging or further investigated with biopsy according to the level of suspicion for malignancy. Given the clinical, pathological, and molecular heterogeneity of HCC, there are multiple therapeutic modalities available. These may be curative, such as surgical resection, liver transplantation, and local ablation, or palliative, such as catheter-directed therapies (transarterial chemo, radio, or bland embolization), and systemic therapy (sorafenib). Patients with a single lesion, good performance status, and preserved liver synthetic function should be offered curative surgical resection or ablation therapy. Patients with HCC and decompensated liver disease should be evaluated and listed for liver transplantation. For unresectable disease or tumor burden precluding transplantation or curative ablation, palliative therapeutic modalities should be offered. Sorafenib is indicated for patients with vascular invasion and/or extra-hepatic metastasis if the estimated life expectancy is more than 3 months. Systemic internal radiation therapy using yttrium-90 microspheres in cases of multifocal bi-lobar disease and/or portal vein occlusion is an emerging therapy. Best supportive care is recommended for patients who lack the hepatic reserve to tolerate therapy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is an increasing problem in the USA and worldwide. Current treatments for HCC include chemoembolization, radioembolization, liver resection, and liver transplantation in the setting of selected cirrhotic patients. Liver transplantation for HCC was controversial initially, but is now widely accepted as a curative approach. Cirrhotic patients who meet standards for transplantation and have a tumor burden within Milan criteria are eligible for transplantation and receive Model for End-Stage Liver Disease (MELD) exception points once listed. Given the decline in availability of donor organs, rewarding MELD exception points and performing liver transplants in these patients remain controversial. Despite this, various guidelines propose expanding eligibility criteria for cirrhotics with HCC, due to post-transplant outcomes comparable to patients transplanted without HCC. Following the transplant, issues include optimizing the type and amount of immunosuppression and screening for and treating recurrence of HCC. [ABSTRACT FROM AUTHOR]

Background: We aimed to prospectively compare the diagnostic performance of gadoxetic acid-enhanced MRI (EOB-MRI) and contrast-enhanced Computed Tomography (CECT) for hepatocellular carcinoma (HCC) detection and liver transplant (LT) eligibility assessment in cirrhotic patients with explant histopathology correlation., Methods: In this prospective, single-institution ethics-approved study, 101 cirrhotic patients were enrolled consecutively from the pre-LT clinic with written informed consent. Patients underwent CECT and EOB-MRI alternately every 3 months until LT or study exclusion. Two blinded radiologists independently scored hepatic lesions on CECT and EOB-MRI utilizing the liver imaging reporting and data system (LI-RADS) version 2018. Liver explant histopathology was the reference standard. Pre-LT eligibility accuracies with EOB-MRI and CECT as per Milan criteria (MC) were assessed in reference to post-LT explant histopathology. Lesion-level and patient-level statistical analyses were performed., Results: Sixty patients (49 men; age 33-72 years) underwent LT successfully. One hundred four non-treated HCC and 42 viable HCC in previously treated HCC were identified at explant histopathology. For LR-4/5 category lesions, EOB-MRI had a higher pooled sensitivity (86.7% versus 75.3%, p <  0.001) but lower specificity (84.6% versus 100%, p <  0.001) compared to CECT. EOB-MRI had a sensitivity twice that of CECT (65.9% versus 32.2%, p <  0.001) when all HCC identified at explant histopathology were included in the analysis instead of imaging visible lesions only. Disregarding the hepatobiliary phase resulted in a significant drop in EOB-MRI performance (86.7 to 72.8%, p <  0.001). EOB-MRI had significantly lower pooled sensitivity and specificity versus CECT in the LR5 category with lesion size < 2 cm (50% versus 79%, p = 0.002 and 88.9% versus 100%, p = 0.002). EOB-MRI had higher sensitivity (84.8% versus 75%, p <  0.037) compared to CECT for detecting < 2 cm viable HCC in treated lesions. Accuracies of LT eligibility assessment were comparable between EOB-MRI (90-91.7%, p = 0.156) and CECT (90-95%, p = 0.158)., Conclusion: EOB-MRI had superior sensitivity for HCC detection; however, with lower specificity compared to CECT in LR4/5 category lesions while it was inferior to CECT in the LR5 category under 2 cm. The accuracy for LT eligibility assessment based on MC was not significantly different between EOB-MRI and CECT., Trial Registration: ClinicalTrials.gov Identifier: NCT03342677 , Registered: November 17, 2017., (© 2023. The Author(s).)

Purpose: To establish a prognostic prediction system for patients with hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation (LT). Methods: A total of 130 patients undergoing LT for HCC exceeding Milan criteria were enrolled into the study. Independent predictors for relapse-free survival (RFS) were adopted to establish a grading system to predict the risk of post-LT tumor recurrence. Results: Multivariate Cox analysis revealed that tumor size >10 cm [vs. ≤5 cm: relative risk (RR) = 4.214, P < 0.001], preoperative alpha fetoprotein > 400 ng/ml (vs. ≤400 ng/ml: RR = 1.657, P < 0.001), extrahepatic invasion (RR = 2.407, P = 0.005) and vascular invasion (RR = 1.917, P = 0.013) were independent predictors for RFS. The risk index of each patient was defined as the sum of the RR obtained in the Cox analysis for RFS. The risk of tumor recurrence was classified into four grades: grade I-risk index equal to 0, grade II-risk index from 0 to 2, grade III-risk index from 2 to 6 and grade IV-risk index >6. RFS rates of patients with grade I-IV ( n = 35, 46, 30 and 19) were 87.5, 57.8, 34.7 and 0 % in 1 year; and 74.4, 41.7, 14.4 and 0 % in 5 years. Both of overall survival (OS) and RFS correlated well with the risk index grade. Patients with grade I achieved comparable prognostic outcomes with the Milan group patients ( n = 119) (5-year OS = 73.7 vs. 74.7 %, P = 0.748; 5-year RFS = 74.4 vs. 85.7 %, P = 0.148). Conclusions: The new grading system was proved to be a promising system in predicting the patient prognosis after LT for HCC exceeding Milan criteria. [ABSTRACT FROM AUTHOR]

The worldwide incidence of hepatocellular carcinoma (HCC) continues to rise and liver transplantation (LT) represents an established curative treatment for early stage disease. As a result of organ shortage, guidelines have restricted transplantation to HCC patients with an expected 5-year post transplantation survival greater than 70 %. The Milan criteria (MC) remain a reliable and noninvasive instrument for selecting patients with 5-year survival meeting this criteria. Since the adoption of the MC by United Network for Organ Sharing (UNOS), attempts have been made to expand MC to account for the projected increase in the incidence of HCC over the next 20 years. An area of active debate focuses on identifying a subgroup of patients outside of MC with similar or better outcomes through either new expanded criteria or identifying other prognostic factors to enhance MC. [ABSTRACT FROM AUTHOR]

Objectives: To compare the diagnostic performance of international hepatocellular carcinoma (HCC) guidelines with gadoxetic acid-enhanced MRI (EOB-MRI) and contrast-enhanced Computed tomography (CECT) and their impact on liver transplant (LT) allocation in cirrhotic patients with explant histopathology correlation., Methods: In this prospective single-centre ethics-approved study, 101 cirrhotic patients were consecutively enrolled with informed consent from the pre-LT clinic. They underwent CECT and EOB-MRI alternately at three monthly intervals until LT or removal from LT list. Two abdominal radiologists, blinded to explant histopathology, independently recorded liver lesions visible on CECT and EOB-MRI. Imaging-based HCC scores were assigned to non-treated liver lesions utilizing Liver Imaging Reporting and Data System (LI-RADS), European Association for the Study of the Liver (EASL), Asian-Pacific Association for the Study of the Liver (APASL) and Korean Liver Cancer Association-National Cancer Center (KLCA) guidelines. Liver explant histopathology was the reference standard. Simulated LT eligibility was assessed as per Milan criteria (MC) in reference to explant histopathology., Results: One hundred and three non-treated HCC and 12 non-HCC malignancy were identified at explant histopathology in 34 patients (29 men, 5 women, age 55-73 years). Higher HCC sensitivities of statistical significance were observed with EOB-MRI for LI-RADS 4 + 5, APASL and KLCA compared to LI-RADS 5 and EASL with greatest sensitivity obtained for LIRADS 4 + 5 lesions. HCC sensitivities by all guidelines with both EOB-MRI and CECT were significantly lower if all histopathology-detected HCCs were included in the analysis, compared to imaging-visible lesions only. A significantly greater variation in HCC sensitivity was noted across the guidelines with EOB-MRI compared to CECT. No significant differences in simulated LT eligibility based on MC were observed across the HCC scoring guidelines with EOB-MRI or CECT., Conclusion: HCC sensitivities are variable depending on scoring guideline, lesion size and imaging modality utilised. Prior studies that included only lesions visible on pre-operative imaging overestimate the diagnostic performance of HCC scoring guidelines. Per-lesion differences in HCC diagnosis across these guidelines did not impact patient-level LT eligibility based on MC., (© 2022. The Author(s).)

The optimum strategy, hepatic resection (HR) or liver transplantation (LT), for treatment of early hepatocellular carcinoma (HCC) associated with liver diseases of Child–Pugh A is far from established. The aim of this study was to compare and determine which strategy is optimal for HCC fulfilling the Milan criteria. Consecutive data were collected in 1,018 HCC patients treated with HR and 89 HCC patients listed for LT (1 drop out for HCC progression) between January of 2003 and December of 2007. The independent prognostic factors identified by multivariate analysis were tumor size-plus-number, microscopic venous invasion, and operation type (LT or HR). When tumor size-plus-number was ≤4 or microscopic venous invasion was absent, there was no significant difference in overall survival (OS) between the LT and HR group. When tumor size-plus-number was >4 or microscopic venous invasion was present, OS was higher in the LT group. Since the pathological microscopic venous invasion was not easily available before operation which is limitation for widespread clinical use, thus in practice, we concluded that, for early HCC associated with Child–Pugh A cirrhosis, when tumor size-plus-number is >4, LT provides the best cure; when it is ≤4, HR remains the initial treatment of choice. [ABSTRACT FROM AUTHOR]

Hepatectomy is feasible for patients with hepatocellular carcinoma (HCC) who are eligible for liver transplantation according to the Milan criteria if they have good hepatic function. This retrospective study investigates the prognostic factors of hepatectomy in HCC patients meeting the Milan criteria. Between 1991 and 2005, 175 patients underwent hepatectomy for HCC at our institute; 111 met and 64 exceeded the Milan criteria. The prognostic factors for hepatectomy were investigated using a Cox regression model. Operative mortality and morbidity were significantly lower in the patients who met the criteria than in those who exceeded the criteria. After a median follow-up of 51.5 months, the 5-year survival rate was significantly better for the patients who met the criteria than for those who exceeded the criteria (77.8% vs 35.7%; P < 0.0001). The factors predictive of poor prognosis were poor differentiation, microscopic vasculobiliary invasion, and a high serum des-gamma-carboxy prothrombin (DCP) level (>100 mAU/ml) for the patients who met the Milan criteria; and only the presence of a microsatellite lesion for the patients who did not meet the Milan criteria. Hepatectomy is safe and beneficial for HCC patients who meet the Milan criteria, but a high preoperative serum DCP level may be predictive of a poor prognosis. [ABSTRACT FROM AUTHOR]

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The reported survival after liver transplantation (OLT) for early hepatocellular carcinoma (HCC) is superior to the results of liver resection (LR), but few analyses have considered long waiting times and patient drop-offs due to tumor progression. From 1995–2005, 347 patients with HCC were evaluated at our institution and underwent either LR ( n = 174) or placed on the OLT waiting list ( n = 173). Patients who only underwent ablation were not included. After eliminating patients with 1) incidental tumors after OLT, 2) tumors outside of Milan criteria, 3) preoperative vascular invasion prior to LR and 4) Child-Pugh Class C cirrhosis prior to OLT, 261 patients (LR = 121; OLT = 140) were included in this analysis. Median follow-up time was 35 months. Median waiting time for OLT was 7.7 months; during this time, 30 patients were taken off the waiting list. Overall survival (OS) from time of listing or LR was not different between the two groups; 1, 3, and 5 year OS after LR was 89%, 75%, and 56% compared with 90%, 70%, and 64% for OLT ( P = .84). Only patients who waited <4 months for OLT ( n = 67) had better survival than those who underwent LR ( P = .05). Patients who waited longer that four months for OLT had a 2.5× higher risk of death in a Cox multivariate model [odds ratio (OR) 2.5; 95% confidence interval (CI): 1.3–5; P = .007]. Unless waiting time is short (<4 months), the survival of patients with early HCC is similar between LR and LT. [ABSTRACT FROM AUTHOR]

The model for end-stage liver disease (MELD) is useful for assessing the recipients of liver transplants, namely, deceased-donor transplantation. The application of MELD for living donor liver transplantation (LDLT) is under investigation. Thus, the aim of this study was to analyze the impact of the MELD score in LDLT in Japan. Seventeen adult cases of LDLT during 2001 to 2005 were enrolled. Indications for LDLT were primary biliary cirrhosis, seven; liver cirrhosis, two; hepatocellular carcinoma (HCC), three; metabolic liver disease, one; primary sclerosing cholangitis, two; Caroli's disease, one; and biliary atresia, one. Total medical charges during the operative periods were retrospectively evaluated. The united network of organ sharing (UNOS) modified was obtained using preoperative clinical data. The average medical expense of the 17 cases was approximately $97 901. The UNOS-modified MELD score was 22.1. A statistically significant positive correlation was found between the MELD score and medical expense ( P = 0.0086, ρ = 0.657), and between the MELD score and the length of stay in the intensive care unit (ICU) ( P = 0.0396, ρ = 0.515). The cause of the liver disease leading to transplantation was not related to MELD score, medical expense, or length of ICU stay. Although not originally designed for the application to LDLT, the MELD score is useful for predicting medical expenses in LDLT. Similar to those of deceased-donor liver transplantation, the disadvantage of high medical expenses associated with a high MELD score allow consideration of an earlier elective operation in suitable cases. [ABSTRACT FROM AUTHOR]

The role of living-donor liver transplantation (LDLT) in the surgical treatment of patients with hepatocellular carcinoma (HCC) has not been established as yet. Preliminary experience gained from 24 patients who underwent LDLT for HCC between March 2002 and November 2004, and the results of the 131 patients who underwent hepatic resection (HR) for HCC between January 1990 and December 2003 were retrospectively analyzed. The exclusion criteria for LDLT for HCC included extrahepatic metastasis and major vascular invasion. (1) LDLT: the median age of the patients was 57 years and the Child-Pugh grades (A/B/C) of the patients were 6, 12, and 6, respectively. The tumor size was 3 cm or less in 15 patients, multinodular tumors were present in 23 patients, and 11 patients (45.8%) met the Milan Criteria. The overall 2-year survival rate was 72.3%, without a significant difference as to whether or not patients met the Milan criteria. (2) HR: on multivariate analysis, the Child-Pugh grade, the presence of cirrhosis, and the number of tumor nodules were considered as independent risk factors for unfavorable survival ( P < 0.05). The 84 patients who met the Milan criteria and were Child-Pugh grade A had a 5-year survival rate of 71.3%; this was significantly better than those of the other patients ( P < 0.005). Among the 57 patients with intrahepatic recurrence, 18 patients who were Child-Pugh grade A, met the Milan criteria, and were treated by re-resection or ablation therapy achieved a significantly better 5-year survival rate, of 73.1%, as compared to 19.7% in the other 39 patients ( P < 0.0045). HR could be a first-line treatment with a favorable prognosis for patients who have resectable HCC, preserved liver function, and who meet the Milan criteria. Salvage LDLT could be employed in patients with recurrent tumors that cannot be controlled by conventional treatment or in patients in whom liver function has deteriorated to Child-Pugh grade B or C. [ABSTRACT FROM AUTHOR]