A novel nomogram to predict the recurrence of hepatocellular carcinoma after liver transplantation using extended selection criteria.

BACKGROUND: Liver transplantations (LTs) with extended criteria have produced surgical results comparable to those obtained with traditional standards. However, it is not sufficient to predict hepatocellular carcinoma (HCC) recurrence after LT according to morphological criteria alone. The present study aimed to construct a nomogram for predicting HCC recurrence after LT using extended selection criteria. METHODS: Retrospective data on patients with HCC, including pathology, serological markers and follow-up data, were collected from January 2015 to April 2020 at Huashan Hospital, Fudan University, Shanghai, China. Logistic least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were performed to identify and construct the prognostic nomogram. Receiver operating characteristic (ROC) curves, Kaplan-Meier curves, decision curve analyses (DCAs), calibration diagrams, net reclassification indices (NRIs) and integrated discrimination improvement (IDI) values were used to assess the prognostic capacity of the nomogram. RESULTS: A total of 301 patients with HCC who underwent LT were enrolled in the study. The nomogram was constructed, and the ROC curve showed good performance in predicting survival in both the development set (2/3) and the validation set (1/3) (the area under the curve reached 0.748 and 0.716, respectively). According to the median value of the risk score, the patients were categorized into the high- and low-risk groups, which had significantly different recurrence-free survival (RFS) rates (P < 0.01). Compared with the Milan criteria and University of California San Francisco (UCSF) criteria, DCA revealed that the new nomogram model had the best net benefit in predicting 1-, 3- and 5-year RFS. The nomogram performed well for calibration, NRI and IDI improvement. CONCLUSIONS: The nomogram, based on the Milan criteria and serological markers, showed good accuracy in predicting the recurrence of HCC after LT using extended selection criteria.

Utilization of Immunotherapy as a Neoadjuvant Therapy for Liver Transplant Recipients with Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for unresectable HCC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era to enhance outcomes in patients with HCC. Here, we report our experience with patients with HCC who had received Immune Checkpoint Inhibitors (ICPI) prior to curative OLT. Methods: This was a retrospective cohort that included patients with HCC who received ICPI prior to OLT at a single institution from January 2019 to August 2023. Graft rejection was assessed and reported along with the type of ICPI, malignancy treated, and the timing of ICPI in association with OLT. Results: During this cohort period, six patients with HCC underwent OLT after neoadjuvant ICPI. All patients were male with a median age of 61 (interquartile range: 59-64) years at OLT. Etiology associated with HCC was viral (N = 4) or Non-alcoholic steatohepatitis, NASH (N = 2). Tumor focality was multifocal (N = 4) and unifocal (N = 2). Lymphovascular invasion was identified in four patients. No perineural invasion was identified in any of the patients. All patients received ICPI including atezolizumab/bevacizumab (N = 4), nivolumab/ipilimumab (N = 1), and nivolumab as monotherapy (N = 1). All patients received either single or combined liver-directed/locoregional therapy, including transarterial chemoembolization (TACE), Yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 5 months. All patients responded to ICPI and achieved a safe and successful OLT. All patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT and one patient received prednisone as additional IS. No patient had clinical evidence of rejection. Conclusions: This cohort emphasizes the success of tumor downstaging by ICPI for OLT when employed as the neoadjuvant therapy strategy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, we believe that our study lays the groundwork for prospective trials to further examine the impact of ICPI prior to OLT.

Radiofrequency ablation with or without transarterial chemoembolization for hepatocellular carcinoma meeting Milan criteria: a focus on tumor progression and recurrence patterns.

Background/objective: The aim of this study was to evaluate tumor progression and recurrence patterns of radiofrequency ablation (RFA) with or without transarterial chemoembolization (TACE) for treating hepatocellular carcinoma (HCC) that meets Milan criteria. Methods: This retrospective study included consecutive HCC patients meeting Milan criteria who underwent percutaneous RFA with or without TACE as initial treatment at a tertiary academic center between December 2017 and 2022. Technical success rate, local recurrence-free survival (LRFS), progression-free survival (PFS) and recurrence patterns were recorded. Results: A total of 135 HCC patients (109 male [80.7%]) with a mean age of 62 years and 147 target lesions were retrospectively enrolled. The technical success rate was 99.3%. The median LRFS was 60 months, and the cumulative 1-, 3-, and 5-year LRFS were 88.9%, 70.1%, and 30.0%, respectively. Additionally, the median PFS was 23 months, with cumulative 1-, 3-, and 5-year PFS of 74%, 30%, and 0%, respectively. Multivariate analysis confirmed that age > 60, alpha-fetoprotein (AFP) (> 10), and albumin were associated with PFS (2.34, p = 0.004; 1.96, p = 0.021; 0.94, p = 0.007, respectively). Six recurrence patterns were identified: local tumor progression (LTP) alone (n = 15, 25.0%), intrahepatic distant recurrence (IDR) alone (n = 34, 56.7%), extrahepatic recurrence (ER) alone (n = 2, 3.3%), IDR + ER (n = 2, 3.3%), LTP + IDR (n = 5, 8.8%), and LTP + IDR + ER (n = 2, 3.3%). IDR occurred most frequently as a sign of good local treatment. Conclusions: RFA in combination with TACE does not appear to provide an advantage over RFA alone in improving tumor progression in patients with HCC meeting the Milan criteria. However, further prospective studies are needed to confirm these findings and to determine the optimal treatment approach for this patient population.

Liver transplant versus liver resection in patients with multifocal hepatocellular carcinoma.

BACKGROUND: The optimal surgical option in patients with multifocal hepatocellular carcinoma (MHCC) is an area of active research. The preference varies based on geographic variations and institutional policies. We sought to determine long-term outcomes in patients with MHCC based on surgical treatment-liver transplant (LT) vs resection (LR). METHODS: We performed a retrospective analysis of the National Cancer Database (2004-2015) and identified patients with MHCC within Milan criteria. Patients with α-fetoprotein ≥ 1000 ng/mL and those who underwent ablation were excluded. The primary outcome measure was long-term survival in patients undergoing LT vs LR. The secondary aim of our study was to determine clinicodemographic factors associated with the receipt of LT and LR. RESULTS: A total of 1546 patients were included, of whom 1211 received LT and 335 underwent LR. Patients who were non-Hispanic White (70.8% vs 54.9%; P < .01), privately insured (53.7% vs 36.7%; P < .01), and treated at academic centers (85.4% vs 71.6%; P < .01) were more likely to receive an LT. Multivariable Cox analysis revealed LT was associated with improved survival compared with LR (hazard ratio, 0.34; 95% CI, 0.28-0.42). CONCLUSION: We described clinical and sociodemographic differences in LT and LR patients and found LT to be associated with a decreased mortality risk compared with LR. The study's findings should be interpreted in the context of several limitations, including the selection of MHCC criteria within Milan criteria.

Tumor Thrombus of Hepatocellular Carcinoma: A Direct Extension From the Liver to the Right Atrium.

Hepatocellular carcinoma (HCC) is a very aggressive type of cancer and can either invade or spread distantly through the portal vein to the inferior vena cava (IVC) and the right atrium (RA). The presentation varies based on the stage of the cancer at the time of diagnosis. Liver transplantation or surgical resection is the ideal management of small lesions without metastases, while systemic therapy can help in extensive cases to decrease the tumor burden to allow surgical resection of the tumor. We present a rare case of HCC with a tumor thrombus (TT) extending to the RA. Unfortunately, the patient did not survive the cancer. We hope that this case report can contribute to saving the lives of future patients with HCC.

Downstaging Hepatocellular Carcinoma with Checkpoint Inhibitor Therapy Improves Access to Curative Liver Transplant.

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.

Liver Transplantation for Hepatocellular Carcinoma beyond the Milan Criteria: A Specific Role for Living Donor Liver Transplantation after Neoadjuvant Therapy.

PURPOSE: This study was designed to elucidate the various new classifications and the use of LDLT and bridging therapy for HCC in this context beyond the Milan criteria (MC). METHODS: The clinical data of patients with HCC outside the MC who underwent LT at Jena University between January 2007 and August 2023 were retrospectively analysed. Eligible patients were classified according to various classification systems. Clinicopathological features, overall and disease-free survival rates were compared between LT and LDLT within the context of bridging therapy. THE RESULTS: Among the 245 patients analysed, 120 patients did not meet the MC, and 125 patients met the MC. Moreover, there were comparable overall survival rates between patients outside the MC for LT versus LDLT (OS 44.3 months vs. 28.3 months; 5-year survival, 56.4% vs. 40%; p = 0.84). G3 tumour differentiation, the presence of angioinvasion and lack of bridging were statistically significant risk factors for tumour recurrence according to univariate and multivariate analyses (HR 6.34; p = 0.0002; HR 8.21; p < 0.0001; HR 7.50; p = 0.0001). Bridging therapy before transplantation provided a significant survival advantage regardless of the transplant procedure (OS: p = 0.008; DFS: p < 0.001). CONCLUSIONS: Patients with HCC outside the MC who underwent LT or LDLT had worse outcomes compared to those of patients who met the MC but still had a survival advantage compared to patients without transplantation. Nevertheless, such patients remain disadvantaged on the waiting list, which is why LDLT represents a safe alternative to LT and should be considered in bridged HCC patients because of differences in tumour differentiation, size and tumour marker dynamics.

Long-term survival analysis of ultrasound-guided percutaneous microwave ablation for hepatocellular carcinoma conforming to the Milan criteria: primary versus recurrent HCC.

BACKGROUND: This study compared long-term outcomes between patients with initial hepatocellular carcinoma (IHCC) and those with recurrent HCC (RHCC) treated with microwave ablation (MWA). METHODS: This retrospective study included 425 patients with HCCs (294 IHCCs and 131 RHCCs) within the Milan criteria who were treated with ultrasound-guided percutaneous MWA between January 2008 and November 2021. All patients with RHCC had previously undergone MWA for initial HCC. Overall survival (OS) and recurrence-free survival (RFS) rates were compared between the IHCC and RHCC groups before and after propensity score matching (PSM). RESULTS: Before matching, the 1-, 3-, 5-, and 10-year OS rates in the IHCC group were 95.9%, 78.5%, 60.2%, and 42.5%, respectively, which were significantly higher than those in the RHCC group (93.8%, 70.0%, 42.0%, and 6.6%, respectively). This difference remained significant after PSM. However, subgroup analyses suggested that there were no significant differences in OS rates between IHCC and RHCC in patients with solitary HCC ≤3.0 cm, AFP ≤200 ng/mL, ablative margins ≥0.5 cm, or Albumin-Bilirubin (ALBI) grade 1. RFS was significantly higher in IHCC than in RHCC before and after PSM, as well as in subgroup analyses. ALBI grade (hazard ratio (HR), 2.38; 95% CI: 1.46-3.86; p < 0.001), serum AFP level (HR, 2.07; 95% CI: 1.19-3.62; p = 0.010) and ablative margins (HR, 0.18; 95% CI: 0.06-0.59; p = 0.005) were independent prognostic factors for OS of RHCC. Serum AFP(HR, 1.29; 95% CI: 1.02-1.63, p = 0.036) level was the only factor associated with RFS in RHCC. CONCLUSIONS: MWA yielded comparable OS in IHCC and RHCC patients with solitary HCC ≤3.0 cm, AFP ≤200 ng/mL, ablative margins ≥0.5 cm, or ALBI grade 1.

Prognostic Factors for Mortality in Hepatocellular Carcinoma at Diagnosis: Development of a Predictive Model Using Artificial Intelligence.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 75% of primary liver tumors. Controlling risk factors associated with its development and implementing screenings in risk populations does not seem sufficient to improve the prognosis of these patients at diagnosis. The development of a predictive prognostic model for mortality at the diagnosis of HCC is proposed. METHODS: In this retrospective multicenter study, the analysis of data from 191 HCC patients was conducted using machine learning (ML) techniques to analyze the prognostic factors of mortality that are significant at the time of diagnosis. Clinical and analytical data of interest in patients with HCC were gathered. RESULTS: Meeting Milan criteria, Barcelona Clinic Liver Cancer (BCLC) classification and albumin levels were the variables with the greatest impact on the prognosis of HCC patients. The ML algorithm that achieved the best results was random forest (RF). CONCLUSIONS: The development of a predictive prognostic model at the diagnosis is a valuable tool for patients with HCC and for application in clinical practice. RF is useful and reliable in the analysis of prognostic factors in the diagnosis of HCC. The search for new prognostic factors is still necessary in patients with HCC.

Validation of Japanese indication criteria for deceased donor liver transplantation for hepatocellular carcinoma: Analysis of US national registry data.

AIM: The Japanese indication criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC) have been updated based on living donor LT data to include either the Milan criteria (MC) or the 5-5-500 rule, which requires a nodule size of ≤5 cm, ≤5 nodules, and an alpha-fetoprotein (AFP) level ≤500 ng/mL. We aimed to validate the 5-5-500 rule and the MC for deceased donor LT (DDLT). METHODS: Using national registry data from the United States from 2010 to 2014, we separated DDLT patients into four groups based on the MC and the 5-5-500 rule. The AFP values were stratified into categories: ≤100, 101-300, 301-500, and >500 ng/mL. RESULTS: The 5-year survival rate was significantly lower for patients in the groups within MC/beyond 5-5-500 (56.3%) or beyond MC/5-5-500 (60.7%) than for patients in the groups within MC/5-5-500 (76.2%) and beyond MC/within 5-5-500 (72.3%) (p < 0.01). Hepatocellular carcinoma recurrence at 5 years was highest for the within MC/beyond 5-5-500 (25.4%) group, followed by the beyond MC/within 5-5-500 (13.1%), beyond MC/5-5-500 (9.6%), and within MC/5-5-500 (7.4%) groups. The stratified 5-year survival rates after DDLT were 76.5%, 72.4%, 58.4%, and 55.6% in the AFP ≤100, 101-300, 301-500, and >500 categories, respectively (p < 0.01). CONCLUSION: The 5-5-500 rule guides the appropriate selection of patients with HCC for DDLT. Patients with AFP levels from 300 to 500 ng/mL had inferior outcomes even when they met the 5-5-500 rule, so further investigation is needed to guide their treatment.

The adverse characteristics of hepatocellular carcinoma in the non-cirrhotic liver disproportionately disadvantage Black patients.

BACKGROUND: Black patients have higher hepatocellular carcinoma (HCC)-related mortality than White patients and more often develop HCC in non-cirrhotic liver. HCC surveillance is primarily directed toward cirrhotic patients. We aimed to characterize HCC in non-cirrhotic patients and to identify factors associated with HCC beyond Milan criteria. METHODS: Demographic, imaging, laboratory, and pathology data of HCC patients at our institution, 2003-2018, were reviewed, retrospectively. Race/ethnicity were self-reported. Cirrhosis was defined as a Fibrosis-4 score ≥3.25. RESULTS: Compared to 1146 cirrhotic patients, 411 non-cirrhotic patients had larger tumors (median 4.7 cm vs. 3.1 cm, p < 0.01) and were less likely to be within Milan criteria (42.6% vs. 57.7%, p < 0.01). Among non-cirrhotic patients, Black patients had larger tumors (4.9 cm vs. 4.3 cm, p < 0.01) and a higher percentage of poorly differentiated tumors (39.4% vs. 23.1%, p = 0.02). Among cirrhotic patients, Black patients had larger tumors (3.3 cm vs. 3.0 cm, p = 0.03) and were less likely to be within Milan criteria (52.3% vs. 83.2%, p < 0.01). In multivariable analysis, lack of commercial insurance (OR 1.45 [CI 95% 1.19-1.83], p < 0.01), male sex (OR 1.34 [CI 95% 1.05-1.70], p < 0.01), absence of cirrhosis (OR 1.58 [CI 95% 1.27-1.98], p < 0.01) and Black race/ethnicity (OR 1.34 [CI 95% 1.09-1.66], p = 0.01) were associated with HCC beyond Milan criteria. Black patients had lower survival rates than other patients (p < 0.01). CONCLUSIONS: Non-cirrhotic patients had more advanced HCC than cirrhotic patients. Black patients (with or without cirrhosis) had more advanced HCC than comparable non-Black patients and higher mortality rates. Improved access to healthcare (commercial insurance) may increase early diagnosis (within Milan criteria) and reduce disparities.

Optimal Liver Transplantation Criteria for Hepatocellular Carcinoma.

Liver transplantation continues to be the optimal treatment for hepatocellular carcinoma (HCC). Given the limited organ supply, patient selection for liver transplant must carefully balance tumor progression with risk of recurrence posttransplant. There are several pretransplant selection criteria that incorporate biomarkers as well as imaging modality to risk-stratify patients as we continue to look for the optimal transplant cutoff for patients with HCC, which should be transplant-center specific, and account for organ availability and dynamic response to locoregional therapy.

Changes in the Liver Transplant Waiting List after Expanding to the 'Up-to-Seven' Criteria for Hepatocellular Carcinoma.

We aimed to assess changes in the composition of the waiting list for liver transplantation (LT) after expanding from Milan to "up-to-seven" criteria in patients with hepatocellular carcinoma (HCC). A consecutive cohort of 255 LT candidates was stratified in a pre-expansion era (2016-2018; n = 149) and a post-expansion era (2019-2021; n = 106). The most frequent indication for LT was HCC in both groups (47.7% vs. 43.4%; p = 0.5). The proportion of patients exceeding the Milan criteria in the explanted liver was nearly doubled after expansion (12.5% vs. 21.1%; p = 0.25). Expanding criteria had no effect in drop-out (12.3% vs. 20.4%; p = 0.23) or microvascular invasion rates (37.8% vs. 38.7%; p = 0.93). The length on the waiting list did not increase after the expansion (172 days [IQR 74-282] vs. 118 days [IQR 67-251]; p = 0.135) and was even shortened in the post-expansion HCC subcohort (181 days [IQR 125-232] vs. 116 days [IQR 74-224]; p = 0.04). Tumor recurrence rates were reduced in the post-expansion cohort (15.4% vs. 0%; p = 0.012). In conclusion, expanding from Milan to up-to-seven criteria for LT in patients with HCC had no meaningful impact on the waiting list length and composition, thus offering the opportunity for the adoption of more liberal policies in the future.

The Usefulness of Fine Needle Aspiration Cytology in the Management of Parotid Gland Masses at a Tertiary Academic Hospital.

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.

Combination Therapy of Bland Transarterial Embolization and Microwave Ablation for Hepatocellular Carcinoma within the Milan Criteria Leads to Significantly Higher Overall Survival.

A comparison of the combination therapy consisting of microwave ablation (MWA) after bland lipiodol-based transarterial embolization (TAE) with MWA alone in the treatment of hepatocellular carcinoma (HCC) within the Milan criteria. Forty-nine patients in the TAE-MWA group (12 women and 37 men; mean age: 63.3 ± 9.6 years) with 55 tumors and 63 patients in the MWA group (18 women and 45 men; mean age: 65.9 ± 10.5 years) with 67 tumors were retrospectively enrolled in this study. For the investigation of treatment protocols based upon both safety and efficacy, patients' cases were analyzed with regard to complications, local tumor progression (LTP), intrahepatic distant recurrence (IDR), overall survival (OS), and progression-free survival (PFS). There were no cases of major complications in either group. The LTP rate was 5.5% in the MWA-TAE group and 7.5% in the MWA group (p = 0.73). The rate of IDR was 42.9% in the MWA-TAE group and 52.4% in the MWA group (p = 0.42). The 12-, 24-, and 36-month OS rates starting at the date of tumor diagnosis were 97.7%, 85.1%, and 78.8% in the TAE-MWA group, and 91.9%, 71.4%, and 59.8% in the MWA group, respectively (p = 0.004). The 6-, 12-, and 24-month PFS rates were 76.5%, 55%, and 44.6% in the TAE-MWA group, and 74.6%, 49.2%, and 29.6% in the MWA group, respectively (p = 0.18). The combination therapy of TAE-MWA was significantly superior to MWA monotherapy according to OS in treating HCC within the Milan criteria.

Risk of Recurrence of Hepatocarcinoma after Liver Transplantation: Performance of Recurrence Predictive Models in a Cohort of Transplant Patients.

Liver transplantation (LT) is a curative treatment for early-stage hepatocellular carcinoma (HCC) unsuitable for surgical resection. However, tumor recurrence (TR) rates range from 8% to 20% despite strict selection criteria. The validation of new prognostic tools, such as pre-MORAL or RETREAT risks, is necessary to improve recurrence prediction. A retrospective study was conducted at Marqués de Valdecilla University Hospital in Cantabria, Spain, between 2010 and 2019 to determine the rate of TR in LT patients and identify associated factors. Patients with liver-kidney transplantation, re-transplantation, HIV infection, survival less than 90 days, or incidental HCC were excluded. Data on demographic, liver disease-related, LT, and tumor-related variables, as well as follow-up records, including TR and death, were collected. TR was analyzed using the Log-Rank test, and a multivariate Cox regression analysis was performed. The study was approved by the IRB of Cantabria. TR occurred in 13.6% of LT patients (95% CI = 7.3-23.9), primarily as extrahepatic recurrence (67%) within the first 5 years (75%). Increased TR was significantly associated with higher Body Mass Index (BMI) (HR = 1.3 [95% CI = 1.1-1.5]), vascular micro-invasion (HR = 8.8 [1.6-48.0]), and medium (HR = 20.4 [3.0-140.4]) and high pre-MORAL risk (HR = 30.2 [1.6-568.6]). TR also showed a significant correlation with increased mortality. Conclusions: LT for HCC results in a 13.6% rate of tumor recurrence. Factors such as BMI, vascular micro-invasion, and medium/high pre-MORAL risk are strongly associated with TR following LT.

Is hepatectomy feasible for hepatocellular carcinoma patients with clinically significant portal hypertension and beyond the Milan criteria?

BACKGROUND: Hepatocellular carcinoma (HCC) patients with clinically significant portal hypertension (CSPH) and beyond the Milan criteria undergoing hepatectomy were previously considered to be at high risk and to have a poor prognosis, especially for major hepatectomy. The aim of this study was to investigate the safety and efficacy of hepatectomy in those patients. METHODS: Data were collected on HCC patients with CSPH treated at a single centre from January 2010 to October 2021. Propensity score-matched (PSM) analysis was used to balance the bias between groups. RESULTS: Of the included patients, 556 underwent hepatectomy and 172 underwent transcatheter arterial chemoembolization (TACE). Comparison of patients beyond the Milan criteria and those with Milan criteria underwent hepatectomy, the 90-day mortality and complication rates were similar in the two groups. However, the overall survival (OS) and recurrence-free survival (RFS) of patients within the Milan criteria were significantly better than those beyond the Milan criteria (p < 0.001). In HCC patients beyond the Milan criteria, OS of performing hepatectomy was significantly longer than TACE (p < 0.001). Within HCC patients beyond the Milan criteria underwent hepatectomy, there was no significant difference in 90-day mortality and complications between minor and major hepatectomy in patients beyond the Milan criteria and no significant difference in RFS and OS after PSM. CONCLUSIONS: Hepatectomy for HCC patients with CSPH and beyond the Milan criteria is safe and feasible, with an acceptable prognosis and no significant difference between minor and major hepatectomy.

An MRI-Based Prognostic Stratification System for Medical Decision-Making of Multinodular Hepatocellular Carcinoma Patients Beyond the Milan Criteria.

BACKGROUND: The suitability of hepatectomy among patients with multinodular hepatocellular carcinoma (MHCC) beyond the Milan criteria remains controversial. There is a need for a reliable risk stratification tool among these patients for the selection of ideal candidates of curative resection. PURPOSE: To determine the clinicoradiological prognostic factors for patients with MHCC beyond the Milan criteria to further develop a stratification system. STUDY TYPE: Retrospective. SUBJECTS: 176 patients with pathologically confirmed MHCC beyond the Milan criteria. FIELD STRENGTH/SEQUENCE: The 1.5 T scanner, including T1-, T2-, diffusion-weighted imaging, in/out-phase imaging, and dynamic contrast-enhanced imaging. ASSESSMENT: Conventional MRI features and preoperative laboratory data including aspartate aminotransferase (AST) and α-fetoprotein (AFP) were collected and analyzed. Two nomograms incorporating clinicoradiological variables were independently constructed to predict recurrence-free survival (RFS) and overall survival (OS) with Cox regression analyses and verified with 5-fold cross validation. Based on the nomograms, two prognostic stratification systems for RFS and OS were further developed. STATISTICAL TESTS: The Cohen's kappa/intraclass correlation coefficient, C-index, calibration curve, Kaplan-Meier curve, log-rank test. A P value <0.05 was considered statistically significant. RESULTS: AST > 40 U/L, increased tumor burden score, radiological liver cirrhosis and nonsmooth tumor margin were independent predictors for poor RFS, while AST > 40 U/L, AFP > 400 ng/mL and radiological liver cirrhosis were independent predictors for poor OS. The two nomograms demonstrated good discrimination performance with C-index of 0.653 (95% confidence interval [CI], 0.602-0.794) and 0.685 (95% CI, 0.623-0.747) for RFS and OS, respectively. The 5-fold cross validation further validated the discrimination capability of the nomograms. Based on the nomogram models, MHCC patients beyond the Milan criteria were stratified into low-/medium-/high-risk groups with significantly different RFS and OS. DATA CONCLUSION: The proposed MRI-based prognostic stratification system facilitates the refinement and further subclassification of patients with MHCC beyond the Milan criteria. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: 2.

Bridging and downstaging with TACE in early and intermediate stage hepatocellular carcinoma: Predictors of receiving a liver transplant.

Background and Aims: In patients with surgically unresectable early and intermediate stage hepatocellular carcinoma (HCC), only liver transplant (LT) offers a cure. Locoregional therapies, such as transarterial chemoembolization (TACE), are widely used to bridge patients waiting for an LT or downstage tumors beyond Milan Criteria (MC). However, there are no formal guidelines on the number of TACE procedures patients should receive. Our study explores the extent to which repeated TACE might offer diminishing gains toward LT. Approach: We retrospectively analyzed 324 patients with BCLC stage A and B HCC who had received TACE with the intention of disease downstaging or bridging to LT. In addition to baseline demographics, we collected data on LT status, survival, and the number of TACE procedures. Overall survival (OS) rates were estimated using the Kaplan-Meier method, and correlative studies were calculated using chi-square or Fisher's exact test. Results: Out of 324 patients, 126 (39%) received an LT, 32 (25%) of whom had responded favorably to TACE. LT significantly improved OS: HR 0.174 (0.094-0.322, P < .001). However, the LT rate significantly decreased if patients received ≥3 vs < 3 TACE procedures (21.6% vs 48.6%, P < .001). If their cancer was beyond MC after the third TACE, the LT rate was 3.7%. Conclusions: An increased number of TACE procedures may have diminishing returns in preparing patients for LT. Our study suggests that alternatives to LT, such as novel systemic therapies, should be considered for patients whose cancers are beyond MC after three TACE procedures.