UNASSIGNED: We aimed to investigate risk factors for early postoperative recurrence in patients with hepatocellular carcinoma (HCC) and determine the effect of surgical methods on early recurrence to facilitate predicting the risk of early postoperative recurrence in such patients and the selection of appropriate treatment methods.
UNASSIGNED: We retrospectively analyzed clinical data concerning 428 patients with HCC who had undergone radical surgery at Mianyang Central Hospital between January 2015 and August 2022. Relevant routine preoperative auxiliary examinations and regular postoperative telephone or outpatient follow-ups were performed to identify early postoperative recurrence. Risk factors were screened, and predictive models were constructed, including patients\' preoperative ancillary tests, intra- and postoperative complications, and pathology tests in relation to early recurrence. The risk of recurrence was estimated for each patient based on a prediction model, and patients were categorized into low- and high-risk recurrence groups. The effect of anatomical liver resection (AR) on early postoperative recurrence in patients with HCC in the two groups was assessed using survival analysis.
UNASSIGNED: In total, 353 study patients were included. Multifactorial logistic regression analysis findings suggested that tumor diameter (≥5/<5 cm, odds ratio [OR] 2.357, 95% confidence interval [CI] 1.368-4.059; P = 0.002), alpha fetoprotein (≥400/<400 ng/L, OR 2.525, 95% CI 1.334-4.780; P = 0.004), tumor number (≥2/<2, OR 2.213, 95% CI 1.147-4.270; P = 0.018), microvascular invasion (positive/negative, OR 3.230, 95% CI 1.880-5.551; P < 0.001), vascular invasion (positive/negative, OR 4.472, 95% CI 1.395-14.332; P = 0.012), and alkaline phosphatase level (>125/≤125 U/L, OR 2.202, 95% CI 1.162-4.173; P = 0.016) were risk factors for early recurrence following radical HCC surgery. Model validation and evaluation showed that the area under the curve was 0.813. Hosmer-Lemeshow test results (X 2 = 1.225, P = 0.996 > 0.05), results from bootstrap self-replicated sampling of 1,000 samples, and decision curve analysis showed that the model also discriminated well, with potentially good clinical utility. Using this model, patients were stratified into low- and high-risk recurrence groups. One-year disease-free survival was compared between the two groups with different surgical approaches. Both groups benefited from AR in terms of prevention of early postoperative recurrence, with AR benefits being more pronounced and intraoperative bleeding less likely in the high-risk recurrence group.
UNASSIGNED: With appropriate surgical techniques and with tumors being realistically amenable to R0 resection, AR is a potentially useful surgical procedure for preventing early recurrence after radical surgery in patients with HCC.

OBJECTIVE: Liver transplantation is the optimal treatment for patients with early hepatocellular carcinoma and cirrhosis. However, hepatocellular carcinoma recurs in approximately 15 % of individuals. This study aimed to assess the efficacy of predictive models for hepatocellular carcinoma recurrence after liver transplantation.
METHODS: This retrospective study included 381 patients with HCC and evaluated the performance of the following models: R3-AFP score, alpha-fetoprotein (AFP) model, University of California, Los Angeles (UCLA) nomogram, Pre-Model of Recurrence after Liver Transplantation (MORAL), Post-MORAL, and Combo MORAL models, Risk Estimation of Tumor Recurrence (RETREAT) model and Platelet to Lymphocyte Ratio (PLR) model.
RESULTS: The R3-AFP score, UCLA nomogram, AFP model, RETREAT, Combo MORAL, and Post-MORAL models exhibited comparable AUROCs, ranging from 0.785 to 0.733. The AUROCs for the R3-AFP model and AFP model were superior to those of the Pre-MORAL and PLR models. The UCLA nomogram, RETREAT score, Combo MORAL model, and Post-MORAL model performed similarly to the first two models, but were only superior to the PLR model.
CONCLUSIONS: The R3-AFP model, UCLA nomogram, AFP model, RETREAT, Combo MORAL, and Post-MORAL models demonstrated a moderate predictive capacity for hepatocellular carcinoma recurrence following transplantation. No significant differences were observed among these models in their ability to predict recurrence.

OBJECTIVE: This study aimed to evaluate the therapeutic outcomes of transarterial chemoembolization combined with radiofrequency ablation (TACE + RFA) for hepatocellular carcinomas (HCC) measuring ≤3 cm infeasible for ultrasound (US)-guided percutaneous RFA.
METHODS: Twenty-four patients who underwent fluoroscopy-guided TACE + RFA for single HCC between January 2012 and December 2016 were screened. To evaluate the TACE + RFA outcomes compared with those of US-guided RFA, 371 patients who underwent US-guided RFA during the same period were screened. We compared local tumor progression (LTP) and intrahepatic distant recurrence (IDR) between the two groups before and after propensity score (PS) matching, and performed univariable and multivariable Cox proportional hazard regression analyses for all patients.
RESULTS: PS matching yielded 21 and 42 patients in the TACE + RFA and US-guided RFA groups, respectively. Cumulative LTP rates after PS matching were not significantly different between the two groups at 1 (0.0% vs. 7.4%, p = 0.072), 2 (10.5% vs. 7.4%, p = 0.701), and 5 years (16.9% vs. 10.5%, p = 0.531). IDR rates did not differ significantly between the two groups at 1 (20.6% vs. 10%, p = 0.307), 2 (25.9% vs. 25.9%, p = 0.999), or 5 years (49.9% vs. 53%, p = 0.838). Multivariable analysis showed that treatment type was not a significant factor for LTP or IDR.
CONCLUSIONS: The outcomes of TACE + RFA for HCC were similar to those of general US-guided RFA. Fluoroscopy-guided TACE + RFA may be an effective treatment when US-guided RFA is not feasible.

UNASSIGNED: The aim of curative-intent treatment for hepatocellular carcinoma (HCC) is to restore the patients\' survival to what it would have been, had they not developed HCC. We examined the chances of such \'statistical cure\' from HCC in patients with cirrhosis due to alcohol-related liver disease (ALD cirrhosis).
UNASSIGNED: Using nationwide Danish healthcare registries, all patients with ALD cirrhosis who were treated for HCC in 2004-2018 were identified and included in cohorts based on initial HCC treatment. We used cure fraction analyses to estimate the chance of being statistically cured by each HCC treatment.
UNASSIGNED: We included 1087 patients with HCC due to ALD cirrhosis, of whom 51 (4.7%) were treated with resection and 215 (19.8%) were treated with ablation. The cure fraction, ie the fraction of patients who experienced no excess mortality from HCC, was 31.8% (95% CI: 0.0-67.5) following resection and 22.9% (95% CI: 2.6-43.2) following ablation. In patients who were still alive five years after the initial HCC treatment, the likelihood of having been statistically cured at that time was 69.0% after resection and 60.2% after ablation. For both treatments, a 90% chance of having been statistically cured was reached after seven years.
UNASSIGNED: Based on cure fraction analyses, resection for HCC statistically cures 31.8% of patients with HCC and underlying ALD cirrhosis, while ablation statistically cures 22.9% of patients. Seven years after curative-intent treatments for HCC, surviving patients are 90% likely to be statistically cured of HCC. This information is valuable to patients and the clinicians caring for them.

There is scant literature on primary nonhematopoietic malignant liver tumours (PMLT) in cats. In this retrospective study, medical data of 40 cats diagnosed with PMLT were reviewed over a period of 22 years (2000-2021). The most frequent epithelial tumours were hepatocellular (42.5%) and bile duct carcinomas (32.5%), only six (15%) cats had mesenchymal tumours. The median age was 13 years and clinical signs commonly included ano-/hyporexia (62.5%), apathy/lethargy (52.5%), weight loss (42.5%) and vomiting (35%). At initial diagnosis, metastases were confirmed in 1 (2.5%) and suspected in three (7.5%) cats. Massive was the most frequent morphology (75%). Most intrahepatic tumours were left-sided (54.2%) with the left medial lobe being primarily affected (25%). Extrahepatic tumours were rare (5%). In 34 (85%) cats, liver lobectomy was performed (surgery group), four (10%) were treated palliatively (non-surgery group), and two (5%) received no treatment. Intraoperative complications occurred in 11.8% with four (15.4%) postoperative deaths. Recurrence was detected in 28.6% at a median of 151 days (range, 79-684 days), while postoperative metastases were suspected in 21.4% at a median of 186 days (range, 79-479 days). The median survival time (MST) was significantly longer in cats of the surgery group (375 days) than in the non-surgery group (16 days) (p = .002). MST was 868 days for hepatocellular compared to 270 days for bile duct carcinomas (p = .06). In summary, liver lobectomy is associated with prolonged survival times and good prognosis in cats with hepatocellular, and an acceptable prognosis in cats with bile duct carcinoma.

OBJECTIVE: Cabozantinib showed a favorable benefit-risk profile in Japanese patients with advanced hepatocellular carcinoma (HCC) in an open-label, phase II study (NCT03586973). This analysis presents cumulative data to final database lock.
METHODS: Patients with previously treated, advanced HCC received cabozantinib 60 mg/day. Progression-free survival (PFS) and tumor response rates in prior-sorafenib and sorafenib-naïve cohorts were assessed by independent radiology committee (IRC) and an investigator. Liver function was evaluated by albumin-bilirubin (ALBI) score.
RESULTS: Median cabozantinib exposure was 5.6 months. In the prior-sorafenib cohort (n = 20), median PFS was 7.4 months per IRC assessment and 5.6 months per investigator assessment. In the sorafenib-naïve cohort (n = 14), median PFS was 3.6 and 4.4 months per IRC and investigator assessment, respectively. Six-month PFS rate per IRC and investigator assessment in the prior-sorafenib cohort was 59.8% and 49.5%, respectively, and in the sorafenib-naïve cohort was 16.7% and 35.7%, respectively. Disease control rate by both IRC and investigator assessment was 85.0% in the prior-sorafenib cohort and 64.3% in the sorafenib-naïve cohort. Median overall survival (Kaplan-Meier estimate) was 19.3 and 9.9 months in the prior-sorafenib and sorafenib-naïve cohort, respectively. Mean ALBI score remained relatively constant in patients able to continue treatment. The most frequent adverse events were palmar-plantar erythrodysesthesia syndrome, diarrhea, hypertension, and decreased appetite. No new safety concerns were identified.
CONCLUSIONS: Cabozantinib showed efficacy and a manageable safety profile in Japanese patients with advanced HCC.

Portal vein infiltration (PVI) is a typical complication of HCC. Once diagnosed, it leads to classification as BCLC C with an enormous impact on patient management, as systemic therapies are henceforth recommended. Our aim was to investigate whether radiomics analysis using imaging at initial diagnosis can predict the occurrence of PVI in the course of disease. Between 2008 and 2018, we retrospectively identified 44 patients with HCC and an in-house, multiphase CT scan at initial diagnosis who presented without CT-detectable PVI but developed it in the course of disease. Accounting for size and number of lesions, growth type, arterial enhancement pattern, Child-Pugh stage, AFP levels, and subsequent therapy, we matched 44 patients with HCC who did not develop PVI to those developing PVI in the course of disease (follow-up ended December 2021). After segmentation of the tumor at initial diagnosis and texture analysis, we used LASSO regression to find radiomics features suitable for PVI detection in this matched set. Using an 80:20 split between training and holdout validation dataset, 17 radiomics features remained in the fitted model. Applying the model to the holdout validation dataset, sensitivity to detect occurrence of PVI was 0.78 and specificity was 0.78. Radiomics feature extraction had the ability to detect aggressive HCC morphology likely to result in future PVI. An additional radiomics evaluation at initial diagnosis might be a useful tool to identify patients with HCC at risk for PVI during follow-up benefiting from a closer surveillance.

To develop a radiomics-based hepatocellular carcinoma (HCC) grade classifier model based on data from gadoxetic acid-enhanced MRI.
This retrospective study included 137 patients who underwent hepatectomy for a single HCC and gadoxetic acid-enhanced MRI within 60 days before surgery. HCC grade was categorized as low or high (modified Edmondson-Steiner grade I-II vs. III-IV). We used the hepatobiliary phase (HBP), portal venous phase, T2-weighted image(T2WI), and T1-weighted image(T1WI). From the volume of interest in HCC, 833 radiomic features were extracted. Radiomic and clinical features were selected using a random forest regressor, and the classification model was trained and validated using a random forest classifier and tenfold stratified cross-validation. Eight models were developed using the radiomic features alone or by combining the radiomic and clinical features. Models were validated with internal enrolled data (internal validation) and a dataset (28 patients) at a separate institution (external validation). The area under the curve (AUC) of the validation results was compared using the DeLong test.
In internal and external validation, the HBP radiomics-only model showed the highest AUC (internal 0.80 ± 0.09, external 0.70 ± 0.09). In external validation, all models showed lower AUC than those for internal validation, while the T2WI and T1WI models failed to predict the HCC grade (AUC 0.30-0.58) in contrast to the internal validation results (AUC 0.67-0.78).
The radiomics-based machine learning model from gadoxetic acid-enhanced liver MRI could distinguish between low- and high-grade HCCs. The radiomics-only HBP model showed the best AUC among the eight models, good performance in internal validation, and fair performance in external validation.

OBJECTIVE: The objectives of this study are to define the specificity of the DNAJB1-PRKACA fusion transcript for the fibrolamellar subtype of hepatocellular carcinoma (FL-HCC) by testing a targeted sampling of other hepatic neoplasms/proliferations and extrahepatic neoplasms seen in children and young adults and to develop a FISH assay using a commercially available PRKACA break apart probe for use in a CLIA-certified clinical laboratory.
METHODS: Formalin fixed paraffin embedded tissue sections from 12 FL-HCC cases, 142 cases of other hepatic neoplasms/proliferations (conventional HCC, focal nodular hyperplasia (FNH), hepatocellular adenoma (HA) and hepatoblastoma (HB)) and extrahepatic neoplasms (neuroblastoma (NB), Wilms tumor (WT) and Gastrointestinal neuroendocrine tumor (GNET)) and 60 matched background normal control tissues underwent fluorescence in situ hybridization (FISH) testing using a break apart probe targeting the PRKACA gene locus on chromosome 19 using standard techniques.
RESULTS: The PRKACA gene rearrangement was detected in 11/12 (92%) FL-HCC cases and 1/94 (1%) of conventional HCC cases. All other cases and background control tissues were negative for the PRKACA gene rearrangement. These findings establish a test sensitivity of 91.7% and specificity of 99.5%.
CONCLUSIONS: This study shows that, using standard techniques, FISH testing with a commercially available break apart probe targeting the PRKACA gene can be used as a surrogate for the DNAJB1-PRKACA fusion commonly found in FL-HCC. Also, the PRKACA gene rearrangement is not expressed in other hepatic neo-plasms/proliferations or extrahepatic neoplasms seen in children and young adults. Finally, FISH testing can be used as a diagnostic tool to confirm the diagnosis of FL-HCC, in the appropriate clinical setting.

OBJECTIVE: Tyrosine kinase inhibitors target transarterial chemoembolization (TACE)-mediated vascular endothelial growth factor to inhibit tumor revascularization and to slow tumor progression. The present study aimed to compare the clinical outcomes of TACE combined with lenvatinib (TACE-lenvatinib) and TACE combined with sorafenib (TACE-sorafenib) in patients with unresectable hepatocellular carcinoma (HCC).
METHODS: The clinical data of patients diagnosed with unresectable HCC who received TACE-lenvatinib or TACE-sorafenib between January 2018 and April 2021 were retrospectively reviewed. The tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups.
RESULTS: A total of 112 patients were enrolled and classified into the TACE-lenvatinib group (n = 53) and the TACE-sorafenib group (n = 59). The objective response rates of patients in the TACE-lenvatinib and TACE-sorafenib groups were 54.7% and 44.1%, respectively (p = 0.260), and the disease control rates (DCRs) were 81.1% and 61.0% (p = 0.020). The median PFS time was significantly longer in the TACE-lenvatinib group than in the TACE-sorafenib group (10.7 vs. 6.0 months; p = 0.002). The median OS time between the TACE-lenvatinib and TACE-sorafenib groups also showed a significant difference (30.5 vs. 20.5 months, p = 0.018). All treatment-related AEs and grade 3/4 AEs were comparable between the two groups (p > 0.05).
CONCLUSIONS: Compared to TACE-sorafenib, TACE-lenvatinib was associated with better DCR, PFS and OS outcomes in patients with unresectable HCC. In subgroups of Barcelona Clinic Liver Cancer B stage or TACE-refractory patients, TACE-lenvatinib also showed a trend of superiority.