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Background: Currently, the effectiveness of TACE, Lenvatinib, and PD-1/L1 inhibitors used alone or in combination has been thoroughly reported. However, the differences in effectiveness between these treatment protocols require further verification. To this end, this study employs a Bayesian network meta-analysis to compare the efficacy and safety of TACE, Lenvatinib, and PD-1/L1 inhibitors, whether administered by monotherapy or in combination, providing evidence-based medicine for the treatment of unresectable HCC. Purpose: This study employed a network meta-analysis to evaluate the efficacy and safety of trans-arterial chemoembolization (TACE), Programmed Cell Death Protein/Ligand 1 (PD-1/L1) inhibitors, and Lenvatinib in the treatment of advanced HCC. Methods: Literature on the treatment of advanced HCC with TACE, PD-1/L1 inhibitors, and Lenvatinib was searched for in both Chinese and English databases, including PubMed, EMBASE, ClinicalTrials.gov, Cochrane Library, CNKI, and Wanfang. Two researchers conducted independent screening and data extraction, and the meta-analysis was performed using R language with the gemtc package. Results: After retrieval and screening, a total of 21 articles were included, involving 2052 participants and six treatment modalities: Lenvatinib (L), TACE (T), TACE + Lenvatinib (TL), Lenvatinib + PD-1/L1 inhibitors (LP), TACE + Lenvatinib + PD-1/L1 inhibitors (TLP), and TACE + PD-1/L1 inhibitors (TP). In terms of objective response rate (ORR), the TLP regimen provided the optimal effect. In predicting the best ORR, TLP had the highest (75.5%) probability. In terms of disease control rate (DCR), the TLP regimen showed the best effect. In predicting the best DCR, the TLP again offered the highest (76.1%) probability. In terms of overall survival (OS), the best outcome was observed in the TLP protocol. In predicting the best OS, the TLP holds the highest (86.00%) probability. Furthermore, the best outcome in progression-free survival (PFS) was found in the TLP regimen. In predicting the best PFS, the TLP still holds the highest (97.0%) result. Conclusion: The combination of TACE, Lenvatinib, and PD-1/L1 inhibitors appears to provide the maximum benefit for inoperable HCC patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a disease with a poor prognosis, often diagnosed at an advanced stage. Therapeutic options have developed considerably in recent years, particularly with trans-arterial treatments. Systemic treatments have also evolved significantly, with the rise of immune checkpoint inhibitors (ICI) as first-line treatment for advanced HCC. The combination of loco-regional treatments and ICI is opening up new prospects and is the subject of numerous clinical trials. Recently, two global phase 3 trials investigating ICI-based adjuvant combinations have demonstrated improvements in recurrence-free survival or progression-free survival in patients treated with resection, ablation, or trans-arterial chemoembolization. However, mature data and overall survival results are still awaited but will be difficult to interpret. We are at the start of a new era of combinations of loco-regional treatments and immunotherapy. The identification of the best therapeutic strategies and predictive biomarkers is a crucial issue for future standards in clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Background Systemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy. Materials We retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups. Results In total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed. Conclusion The combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.

Backgrounds: It is unclear which patients benefit from resection in intermediate-stage-hepatocellular carcinoma (HCC). The authors aimed to identify high-risk patients for early recurrence among patients with resectable intermediate-stage HCC. Methods: This multicenter retrospective study included patients who underwent resection or trans-arterial chemoembolization (TACE) for intermediate-stage HCC (2008-2019). Multivariable Cox proportional analysis was performed to identify high-risk patients when treated with resection. A prediction score for 2-year recurrence-free survival (RFS) was developed using the training cohort and validated. The 2-year RFS in each risk group was compared with that in TACE group, after propensity score matching (PSM). Results: A total of 1686 patients were included (480 and 1206 patients in the resection and TACE groups). During a median followup of 31.4 months, the 2-year RFS was significantly higher in the resection (47.7%) than in the TACE group (19.8%) [adjusted hazard ratio (aHR)= 1.471, 95% CI: 1.199-1.803, P< 0.001). On multivariate analysis, alpha-fetoprotein = 5.0 ng/ml (aHR =0.202), ALBI grade =2 (aHR =0.709), tumor number =3 (aHR =0.404), and maximal tumor size =5 cm (aHR =0.323) were significantly associated with the lower risk of 2-year RFS in the resection group. The newly developed Surgery Risk score in BCLC-B (SR-B score) with four significant risk factors showed an area under the curve of 0.801 for the 2-year RFS and was validated. Based on the SR-B score, low-risk patients had a significantly higher 2-year RFS (training: aHR = 5.834; validation: aHR =5.675) than high-risk patients (all P <0.001) did. In a PSM cohort, a low-risk resection group had a significantly higher (aHR =3.891); a high-risk resection group had a comparable 2-year RFS to those treated with TACE (aHR =0.816). Conclusions: Resection may be beneficial for resectable intermediate-stage HCC based on the SR-B score. [ABSTRACT FROM AUTHOR]

Background and objectives: Trans Arterial Chemo Embolisation (TACE) is the treatment choice for most unresectable hepatocellular carcinoma (HCC) patients. Post-embolisation syndrome (PES) is the most common complication. PES definition was a constellation of fever, nausea/vomiting, and abdominal pain within the first 72 hours post-TACE regardless of the need for systemic medication. This study aims to identify the risk factors of PES and its association with patients' survival. Variables included demographic, clinical characteristics, tumour characteristics and procedure characteristics were identified. Study design and method: This is a retrospective study in a single centre, Hospital Universiti Sains Malaysia, Kelantan. This study showed that 90 HCC patients underwent TACE procedures between 1st January 2016 and 31st December 2019. Variables included demographic, clinical characteristics, tumour characteristics and procedure characteristics were collected. Data were entered and analysed using Statistical Package for the Social Sciences (SPSS) version 22. Results: The prevalence of PES among 90 patients was 25.6% (n = 23). There was a significant association between related variables towards PES, such as the number of tumours (p = 0.039), lobar involvement (p = 0.024) and chemotherapy type (p = 0.035) when adjusted for other variables. Also, there was a significant association between PES and survival duration (p = 0.001). Majority of the patients with no PES found highest in the group of survival duration of more and equal to 12 months (n = 56, 62.2%). Conclusion: We found that PES is a clinically significant event in HCC patients. There were few risk factors identified in this study. PES is associated with a worse prognosis in terms of survival rate for patients who experience it. [ABSTRACT FROM AUTHOR]

Purpose: To explore the safety and efficacy of lenvatinib in combination with trans-arterial chemoembolization (TACE) and programmed death receptor 1 (PD-1) antibody in the treatment of unresectable recurrent hepatocellular carcinoma (urHCC). Patients and methods: The clinical data of 16 patients with unresectable recurrent hepatocellular carcinoma admitted to the Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, and received the conversion therapy of lenvatinib + TACE + PD-1 antibody between January 2019 and January 2022 were retrospectively analyzed. Results: There were 25% (4/16) patients suffering from grade 3 adverse events and no patients suffering from grade 4 or higher adverse events. After 4 months of treatment of 16 patients, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), two, five, three, and six cases were in complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively, and the objective response rate (ORR) was 43.8% (7/16). The 1-year overall survival (OS) rate and 1-year progressionfree survival (PFS) rate were 86.2% and 46.9%, respectively. In our subgroup analysis, the ORR of patients with multiple lesions reached up to 60%, which was higher than that of patients with single lesions. Conclusions: Lenvatinib in combination with TACE and PD-1 antibody is safe and effective in the treatment of unresectable recurrent hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: Textbook Outcome (TO) is inclusive of quality indicators and it not been provided for trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Materials and Methods: Data on treatment-naïve HCC patients receiving TACE from 10 centers were reviewed. TO was defined as "no post-TACE grade 3–4 complications, no prolonged hospital stay (defined as a post-procedure stay ≤ 75th percentile of the median values from the total cohort), no 30-day mortality/readmission and the achievement of an objective response (OR) at post-TACE imaging." Grade of adverse event was classified according to the Common Terminology Criteria for Adverse Events and short-term efficacy was assessed by response. Pooled estimates were calculated to account for hospital's effect and risk-adjustment was applied to allow for diversity of patients in each center. Results: A total of 1124 patients (2014–2018) fulfilling specific inclusion criteria were included. Baseline clinical features showed considerable heterogeneity (I2 > 0.75) across centers. TACE-related mortality was absent in 97.6%, readmission was not required after 94.9% of procedures, 91.5% of patients had no complication graded 3–4, 71.8% of patients did not require prolonged hospitalization, OR of the target lesion was achieved in 68.5%. Risk-adjustment showed that all indicators were achieved in 43.1% of patients, and this figure was similar across centers. The median overall survival for patients who achieved all indicators was 33.1 months, 11.9 months longer than for patients who did not. Conclusions: A useful benchmark for TACE in HCC patients has been developed, which provides an indication of survival and allows for a comparison of treatment quality across different hospitals. [ABSTRACT FROM AUTHOR]

Abstract Background Heterogeneity of liver function and tumor burden in intermediate-stage hepatocellular carcinoma (HCC) results in different outcomes after transarterial chemoembolization (TACE). Easy albumin-bilirubin (EZ-ALBI), a simplified albumin-bilirubin (ALBI) score, has recently been proposed as a new prognostic score for HCC. This study aimed to validate the EZ-ALBI score and evaluate the impact of dynamic changes in patients with intermediate-stage HCC undergoing TACE. Methods All patients with HCC treated with TACE at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between January 2015 and December 2019 were prospectively enrolled. Intermediate-stage HCC was defined as Barcelona Clinic Liver Cancer (BCLC) stage B or unresectable single HCC with size > 5 cm in BCLC stage A. EZ-ALBI and ALBI scores were calculated and stratified into three different grades. Overall survival (OS) and prognostic factors were assessed using the Kaplan–Meier curve and Cox proportional hazard model. Decision analysis curves were used to evaluate the clinical utility of the predictive scores. Results Among 672 patients with HCC treated with TACE, 166 patients with intermediate-stage HCC who met the eligibility criteria were enrolled. The median OS of all patients in the cohort was 21 months. A good correlation between the EZ-ALBI and ALBI scores was observed (correlation coefficient 1.000, p 20 ng/ml were significantly associated with OS [hazard ratio (HR) 2.20 (95% confidence interval [CI] 1.24–3.88, p = 0.007), 3.26 (95% CI 1.24–8.57, p = 0.016), and 1.77 (95% CI 1.10–2.84, p = 0.018), respectively]. Following TACE, 42 (29.6%) patients had a worsening EZ-ALBI grade. However, the EZ-ALBI grade migration was not significantly correlated with OS. EZ-ALBI and ALBI score provided improved discriminatory ability (Harrell’s concordance index 0.599 and 0.602, respectively) and better net benefit compared with Child-Turcotte-Pugh and Model for End-stage Liver Disease scores. Conclusions The baseline EZ-ALBI score demonstrated good predictive performance for survival and a strong correlation with conventional ALBI scores. Both the EZ-ALBI and ALBI scores outperformed other prognostic models in patients with intermediate-stage HCC receiving TACE. However, the dynamic change in the EZ-ALBI grade after TACE was not associated with postprocedural survival.

Simple Summary: Hepatocellular carcinoma (HCC) is one of the most prevalent and devastating malignancies worldwide. An ongoing phase-II clinical trial assesses the efficacy of a novel sequential trans-arterial chemoembolization (TACE) plus stereotactic body radiotherapy (SBRT) plus immunotherapy strategy as an induction therapy for unresectable HCC patients. This study aims to investigate the potential association between radiomic features extracted from pre-treatment multi-phasic MR images and treatment response following the novel intervention strategy. In this study, Four DeltaP-derived radiomics that characterize the temporal change in intratumoral randomness and uniformity were identified as the contributors to the treatment response for a 3-month timepoint. Additional arterial phase (AP)-derived radiomic features and tumor morphology were also shown to have strong associations with treatment response for a 6-month timepoint. The success of this study would demonstrate the feasibility of pre-treatment identification of responsive HCC patients, paving the way toward effective and personalized oncology for HCC management. This study aims to investigate the association of pre-treatment multi-phasic MR-based radiomics and dosimetric features with treatment response to a novel sequential trans-arterial chemoembolization (TACE) plus stereotactic body radiotherapy (SBRT) plus immunotherapy regimen in unresectable Hepatocellular Carcinoma (HCC) sub-population. Twenty-six patients with unresectable HCC were retrospectively analyzed. Radiomic features were extracted from 42 lesions on arterial phase (AP) and portal-venous phase (PVP) MR images. Delta-phase (DeltaP) radiomic features were calculated as AP-to-PVP ratio. Dosimetric data of the tumor was extracted from dose-volume-histograms. A two-sided independent Mann–Whitney U test was used to assess the clinical association of each feature, and the classification performance of each significant independent feature was assessed using logistic regression. For the 3-month timepoint, four DeltaP-derived radiomics that characterize the temporal change in intratumoral randomness and uniformity were the only contributors to the treatment response association (p-value = 0.038–0.063, AUC = 0.690–0.766). For the 6-month timepoint, DeltaP-derived radiomic features (n = 4) maintained strong clinical associations with the treatment response (p-value = 0.047–0.070, AUC = 0.699–0.788), additional AP-derived radiomic features (n = 4) that reflect baseline tumoral arterial-enhanced signal pattern and tumor morphology (n = 1) that denotes initial tumor burden were shown to have strong associations with treatment response (p-value = 0.028–0.074, AUC = 0.719–0.773). This pilot study successfully demonstrated associations of pre-treatment multi-phasic MR-based radiomics with tumor response to the novel treatment regimen. [ABSTRACT FROM AUTHOR]

Background and Objectives: Post-embolization syndrome (PES), characterized by pain, fever, nausea, and vomiting, is a common but non-serious adverse event following arterial embolization, negatively impacting patient satisfaction with the procedure. This study aimed to evaluate the efficacy of dexamethasone-based prophylactic therapy in preventing PES, as well as to assess the effects of its dosage and timing of administration., Methods: A systematic search was conducted across three databases, two trial registries, and citation searches to identify relevant studies. Data related to postoperative pain, fever, nausea, and vomiting were extracted and meta-analyzed using a random-effects model and the Mantel-Haenszel method. Meta-regression was performed to examine the role of dexamethasone dose and timing of administration as mediators., Results: Dexamethasone-based prophylactic therapy significantly reduced the risk of postoperative pain (RR=0.58, 95% CI: 0.48-0.69; P<0.00001), fever (RR=0.36, 95% CI: 0.22-0.61; P<0.00001), nausea (RR=0.52, 95% CI: 0.41-0.67; P<0.00001), and vomiting (RR=0.54, 95% CI: 0.36-0.82; P=0.004) compared to placebo or no treatment. A higher dose of dexamethasone was associated with a significantly lower incidence of postoperative pain (P=0.038). Regarding timing, postoperative and continuous (extending throughout the perioperative period) administration, was more effective than preoperative administration (P=0.024; P=0.007). A dosage of 6-12 mg was particularly effective in reducing the risk for all four symptoms., Conclusion: Dexamethasone effectively prevents PES in patients undergoing arterial embolization. An optimal protocol may involve a divided dose regimen within the range of 6-12 mg, extending throughout the recovery period for maximum benefit., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Sihang Cheng,1,2 Xiang Yu,2 Siyun Liu,3 Zhengyu Jin,1 Huadan Xue,1 Zhiwei Wang,1 Ping Xie2 1Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Radiology, Sichuan Provincial People’s Hospital, Sichuan Academy of Medical Sciences, Chengdu, People’s Republic of China; 3Pharmaceutical Diagnostics, GE Healthcare, Beijing, People’s Republic of ChinaCorrespondence: Zhiwei Wang; Ping Xie Tel +8610 69159562; +8628 87393976Email zhiweiwang1981@sina.com; haoyanx@163.comObjective: To develop and validate a prognostic nomogram in eastern patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) receiving trans-arterial chemoembolization with drug-eluting beads (DEB-TACE).Methods: This retrospective study included 200 patients with training cohort (n = 118) from institution 1 and test cohort (n = 82) from institution 2. All these patients received first-line DEB-TACE between October 2016 and October 2018. Multivariate Cox proportional hazard regression analysis was performed on the training cohort to reveal the independent prognostic factors, and then prognostic nomograms were developed. In order to evaluate the performance of the nomogram comprehensively in both the training and test cohorts, C-index, Kaplan–Meier curve with Log rank test, receiver operating characteristic curve (ROC), calibration plot, and decision curve analysis (DCA) were performed.Results: Tumor number, serum γ-glutamyl transferase (GGT) level, and level of PVTT were independent risk factors of prognosis. A nomogram was constructed to predict 6-, 12- and 18-month overall survival (OS) based on these identified prognostic factors. C-indexes of the nomogram were 0.88 (95% confidence interval [CI], 0.79– 0.97) in the training cohort and 0.87 (95% CI, 0.75– 0.99) in the test cohort. The Kaplan–Meier curve analysis showed that the nomogram was able to separate patients into low- and high-risk subgroups. ROC curves for the nomogram at 6-, 12- and 18-month showed satisfied discrimination, with an AUC of 0.765, 0.803 and 0.809 in the training cohort, respectively, and 0.772, 0.724 and 0.746 in the test cohort, respectively. The calibration curve demonstrated good agreement between predicted and actual survival rates in the training and test cohorts. The decision curve showed good performance of the nomogram in terms of clinical application.Conclusion: We developed and validated a nomogram that was accurate and clinically useful in eastern patients with HBV-associated HCC with PVTT who underwent DEB-TACE.Keywords: hepatocellular carcinoma, portal vein tumor thrombus, trans-arterial chemoembolization, drug-eluting beads, nomogram

Background: Heterogeneity of liver function and tumor burden in intermediate-stage hepatocellular carcinoma (HCC) results in different outcomes after transarterial chemoembolization (TACE). Easy albumin-bilirubin (EZ-ALBI), a simplified albumin-bilirubin (ALBI) score, has recently been proposed as a new prognostic score for HCC. This study aimed to validate the EZ-ALBI score and evaluate the impact of dynamic changes in patients with intermediate-stage HCC undergoing TACE.Methods: All patients with HCC treated with TACE at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between January 2015 and December 2019 were prospectively enrolled. Intermediate-stage HCC was defined as Barcelona Clinic Liver Cancer (BCLC) stage B or unresectable single HCC with size > 5 cm in BCLC stage A. EZ-ALBI and ALBI scores were calculated and stratified into three different grades. Overall survival (OS) and prognostic factors were assessed using the Kaplan-Meier curve and Cox proportional hazard model. Decision analysis curves were used to evaluate the clinical utility of the predictive scores.Results: Among 672 patients with HCC treated with TACE, 166 patients with intermediate-stage HCC who met the eligibility criteria were enrolled. The median OS of all patients in the cohort was 21 months. A good correlation between the EZ-ALBI and ALBI scores was observed (correlation coefficient 1.000, p < 0.001). The baseline EZ-ALBI grades 1, 2, and 3 were 24.5%, 70%, and 5.5%, respectively. EZ-ALBI grade can stratify patients with significantly different prognoses (p = 0.002). Baseline EZ-ALBI grade 2, 3, and serum alpha-fetoprotein > 20 ng/ml were significantly associated with OS [hazard ratio (HR) 2.20 (95% confidence interval [CI] 1.24-3.88, p = 0.007), 3.26 (95% CI 1.24-8.57, p = 0.016), and 1.77 (95% CI 1.10-2.84, p = 0.018), respectively]. Following TACE, 42 (29.6%) patients had a worsening EZ-ALBI grade. However, the EZ-ALBI grade migration was not significantly correlated with OS. EZ-ALBI and ALBI score provided improved discriminatory ability (Harrell's concordance index 0.599 and 0.602, respectively) and better net benefit compared with Child-Turcotte-Pugh and Model for End-stage Liver Disease scores.Conclusions: The baseline EZ-ALBI score demonstrated good predictive performance for survival and a strong correlation with conventional ALBI scores. Both the EZ-ALBI and ALBI scores outperformed other prognostic models in patients with intermediate-stage HCC receiving TACE. However, the dynamic change in the EZ-ALBI grade after TACE was not associated with postprocedural survival. [ABSTRACT FROM AUTHOR]

Purpose of Review: The surgical management of metastatic colorectal cancer (CRC) has evolved over time. Most often, the management of asymptomatic primary CRC with simultaneous liver metastases (LM) proceeds with neoadjuvant chemotherapy followed by surgical resection. Although the timing of surgical resection has remained controversial, the ability to achieve R0 resection and the importance of patient selection remain widely accepted. Recent Findings: Preoperative novel modalities such as portal vein ligation (PVL) or portal vein embolization (PVE) have allowed for improved surgical outcomes and decreased post-surgical morbidity. Combination or hybrid management has also seen increased utility by associating ablation therapies with surgical resection. Finally, patients with significant comorbidities and surgically unresectable disease have benefited greatly from locoregional salvage therapies such as percutaneous ablation and radioembolization. Summary: Here we will review pertinent literature associated with surgical management for resectable disease and explore newly developed locoregional salvage therapies for unresectable disease. [ABSTRACT FROM AUTHOR]

Multiphase MRI liver is the gold-standard imaging modality for staging hepatocellular carcinoma (HCC) in patients with cirrhosis. Often, small HCCs diagnosed on multiphase MRI are occult on B-mode ultrasound and multiphase CT (MPCT) and thus pose a challenge for loco-regional therapy. We adapted the technique of lipiodol CT in treating two such patients of small HCC. Lipiodol-CT involved an intra-arterial lipiodol injection through the hepatic artery followed by a noncontrast CT liver. CT delineated small, hyperdense, lipiodol-laden hepatic nodules, which served as a target for executing ablation of the nodule and also revealed the true disease stage by depicting the additional number of tumors in the liver. Case one was a 51-year female, known case of chronic hepatitis C who presented with ascites for two months. She was diagnosed with a small HCC (LI-RADS-4) in a cirrhotic liver on multiphase MRI. Percutaneous radiofrequency ablation was planned, but the mass was not located on ultrasound or multiphase CT. Lipiodol-CT was undertaken, which delineated the lipiodol-laden small HCC, which served as a target for executing ablation. Case 2 was a 55-year male, Child-Pugh A cirrhotic, who had undergone right extended hepatectomy for hepatitis B-related HCC. Follow-up MRI revealed a 5 mm segment III nodule, which had increased in size on repeat MRI at 3 months (LI-RADS-4). This nodule, too, was occult on both ultrasound and MPCT. Lipiodol CT revealed additional multiple, variable-sized lipiodol-laden nodules in the liver remnant. Treatment of trans-arterial chemoembolization was performed at one month. Both patients showed complete response to treatment. Conclusion: Lipiodol CT can be safely used in a new role of facilitating treatment of small HCCs diagnosed on MRI but occult on ultrasonography and MPCT. [ABSTRACT FROM AUTHOR]

Abstract Background Transarterial chemoembolization (TACE) is the recommended treatment modality for non-resectable intermediate-stage hepatocellular carcinoma; however, this stage has wide variable levels of liver functions and tumor burden making a challenge as regards the tolerability of the functioning residual liver to this type of therapy. Further stratification of this intermediate stage may help the clinical decision for the suitability of TACE, so we tried to derive a clinical decision support tool to predict the tolerability of the functioning residual liver to TACE using pre-intervention liver reserve function and liver residual volume as well as tumor burden. Results Two hundred and fifty-two patients with non-resectable intermediate-stage hepatocellular carcinoma (HCC) were consecutively included in this cohort study; all patients were blindly followed up for 6 weeks after TACE for manifestation of liver decompensation. For univariate logistic regression analysis, the significant predictors were age, s.albumin, s.bilirubin, prothrombin concentration (PC), tumor volume (TV), residual liver volume (RLV), and residual to liver volumetric ratio (RLVR) (sig, 0.007, 0.000, 0.000, 0.000, 0.000, 0.002, and 0.000, respectively). Multivariate logistic regression analysis illustrated that s.albumin, s.bilirubin, PC, and RLVR were the most independent significant predictors (sig, 0.000 for all with adjusted OR 0.002, 22.692, 0.827, and 0.000, respectively). The discriminatory performance of our proposed decision support score (liver tolerability score) was evaluated using the receiver operating characteristics that identified two cutoff points (≤ 0.30 and ≥ 0.83) to rule out or rule in the possibility of liver decompensation after TACE, respectively (AUC, 0.942 and sig. 0.000). Liver tolerability score stratified the intermediate stage of HCC to 3 risk grades (low, medium, and high) with significant difference as regards hazard distribution. Conclusion Computed tomography image-based assessment of RLVR may have a possible role in predicting future tolerability of the functioning residual tissue to TACE of HCC. Liver tolerability score (LTS) could stratify the intermediate stage HCC to 3 risk grades, so LTS may have a role in clinical decision for the suitability of TACE for intermediate stage HCC.

Aim: Trans-arterial chemoembolization (TACE) in combination with tyrosine kinase inhibitor (TKI) has been evidenced to improve outcomes in a portion of patients with hepatocellular carcinoma (HCC). Developing biomarkers to identify patients who might benefit from the combined treatment is needed. This study aims to investigate the efficacy of radiomics/deep learning features-based models in predicting short-term disease control and overall survival (OS) in HCC patients who received the combined treatment.Materials and Methods: A total of 103 HCC patients who received the combined treatment from Sep. 2015 to Dec. 2019 were enrolled in the study. We exacted radiomics features and deep learning features of six pre-trained convolutional neural networks (CNNs) from pretreatment computed tomography (CT) images. The robustness of features was evaluated, and those with excellent stability were used to construct predictive models by combining each of the seven feature exactors, 13 feature selection methods and 12 classifiers. The models were evaluated for predicting short-term disease by using the area under the receiver operating characteristics curve (AUC) and relative standard deviation (RSD). The optimal models were further analyzed for predictive performance on overall survival.Results: A total of the 1,092 models (156 with radiomics features and 936 with deep learning features) were constructed. Radiomics_GINI_Nearest Neighbors (RGNN) and Resnet50_MIM_Nearest Neighbors (RMNN) were identified as optimal models, with the AUC of 0.87 and 0.94, accuracy of 0.89 and 0.92, sensitivity of 0.88 and 0.97, specificity of 0.90 and 0.90, precision of 0.87 and 0.83, F1 score of 0.89 and 0.92, and RSD of 1.30 and 0.26, respectively. Kaplan-Meier survival analysis showed that RGNN and RMNN were associated with better OS (p = 0.006 for RGNN and p = 0.033 for RMNN).Conclusion: Pretreatment CT-based radiomics/deep learning models could non-invasively and efficiently predict outcomes in HCC patients who received combined therapy of TACE and TKI.

Background and Aims: Trans-arterial chemoembolization (TACE) has become a widely accepted treatment in unresectable hepatocellular carcinoma (HCC). We aimed at comparing the efficacy of Degradable Starch Microspheres (DSMs)-TACE with 50 ± 7µmversus 300–500 μm Drug Eluting Beads (DEB)-TACE in terms of initial clinical and radiological treatment response parameters. Material and Methods: A total of 54 patients with unresectable HCC who underwent DEB-TACE (n = 25) or DSMs-TACE (n = 29) were included in this retrospective study. Baseline demographic and clinical characteristics, duration of follow-up, local recurrence and survival status, as well as treatment outcome including treatment response via modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, viable and total tumor diameter and serum alpha-fetoprotein (AFP) levels were analyzed in both study groups. Results: No significant difference was noted between the two groups in terms of local recurrence (31.6 vs. 16.7%) or mortality (73.9 vs. 85.7%) rates after 36-month and 12-month follow-up, respectively. DSMs-TACE vs. DEB-TACE was associated with significantly higher complete response rate (27.6 vs. 0.0%, p = 0.011) and significant decrease in serum AFP levels (p = 0.013). Conclusion: Both DSMs-TACE with 50 ± 7µmmicrospheres and 300–500 μm DEB-TACE are effective for local control of unresectable HCC. Our findings revealed superiority of DSMs-TACE over DEB-TACEnin terms of initial clinical and radiological tumor response; though no significant difference was noted between the two patient groups in terms of local recurrence or mortality during follow up.

Despite careful selection for liver transplantation (LT) of patients with hepatocellular carcinoma (HCC), HCC may still recur after LT and is frequently associated with dismal outcome. Tumor factors, including serum alpha-fetoprotein (AFP), the presence of microvascular invasion, tumor grade/differentiation, and largest tumor size are amongst the most important predictors of recurrence after transplantation. The nature of recurrence can be highly variable, but often presents with extra-hepatic involvement. As such, management of patients with HCC can be challenging, and consensus guidelines are lacking. Curative options, with surgery or ablation, which may be applicable in patients with isolated intra-or extrahepatic metastases, offer the best chance for improved long-term outcome in patients with HCC recurrence after transplantation. Most patients with recurrence have unresectable disease, and may benefit from palliative treatments, including intra-arterial therapies and/or systemic therapy.

Purpose: The aim of this study was to describe changes in contrast agent kinetics in HCC following incomplete trans-arterial chemoembolization (TACE) on contrast-enhanced ultrasound (CEUS) and MRI/CT. Methods: Patients with residual HCC proven by biopsy, retreatment angiography, or 4–8 month MRI demonstrating tumor progression were identified. Pre-treatment and 4–6-week follow-up CE-MRI/CT and CEUS exams were collected for blinded reads by two experienced readers for each modality to evaluate arterial phase hyper-enhancement (APHE) and washout within the residual HCC. A third reader provided tie-breaking decisions for any disagreements. Results: Contrast-enhanced imaging data were collected from 29 patients with residual HCC post-TACE. On CEUS, 84.2% of patients with baseline APHE demonstrated APHE post-TACE (p = 0.25). On CE-MRI/CT, 57.1% of patients with baseline APHE later demonstrated APHE (p = 0.004). As for washout, on CEUS 33.3% of patients with baseline washout retained washout post-TACE (p = 0.01), while on CE-MRI/CT only 18.8% of patients with baseline washout later demonstrated washout (p < 0.001). Among CEUS readers, reader agreement was 100% for baseline APHE, 66.7% for baseline washout (K = 0.35), 84.2% for post-TACE APHE (K = 0.35), and 57.9% for post-TACE washout (K = − 0.09). On CE-MRI/CT, reader agreement was 65.5% for baseline APHE (K = 0.19), 55.2% for baseline washout (K = 0.12), 48.3% for post-TACE APHE (K = − 0.07), and 58.6% for post-TACE washout (K = 0.04). Conclusion: Common diagnostic features of treatment-naïve HCC like APHE and washout can be substantially altered by TACE and should be considered when diagnosing residual disease on contrast-enhanced imaging. [ABSTRACT FROM AUTHOR]

Background and Aims: Trans-arterial chemoembolization (TACE) has become a widely accepted treatment in unresectable hepatocellular carcinoma (HCC). We aimed at comparing the efficacy of Degradable Starch Microspheres (DSMs)-TACE with 50 ± 7 µm versus 300-500 µm Drug Eluting Beads (DEB)-TACE in terms of initial clinical and radiological treatment response parameters. Material and Methods: A total of 54 patients with unresectable HCC who underwent DEB-TACE (n = 25) or DSMs-TACE (n = 29) were included in this retrospective study. Baseline demographic and clinical characteristics, duration of follow-up, local recurrence and survival status, as well as treatment outcome including treatment response via modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, viable and total tumor diameter and serum alpha-fetoprotein (AFP) levels were analyzed in both study groups. Results: No significant difference was noted between the two groups in terms of local recurrence (31.6 vs. 16.7%) or mortality (73.9 vs. 85.7%) rates after 36-month and 12-month follow-up, respectively. DSMs-TACE vs. DEB-TACE was associated with significantly higher complete response rate (27.6 vs. 0.0%, p = 0.011) and significant decrease in serum AFP levels (p = 0.013). Conclusion: Both DSMs-TACE with 50 ± 7 µm microspheres and 300-500 µm DEB-TACE are effective for local control of unresectable HCC. Our findings revealed superiority of DSMs-TACE over DEB-TACEnin terms of initial clinical and radiological tumor response; though no significant difference was noted between the two patient groups in terms of local recurrence or mortality during follow up. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to investigate the effectiveness and safety of the combination of immune checkpoint inhibitor, local interventional therapy, and anti-angiogenic therapy in patients with metastatic soft-tissue sarcoma (mSTS).Settings and Design: We retrospectively evaluated the medical records of patients with mSTS who started treatment between September 2018 and June 2020 at our hospital.Materials and Methods: Overall, 33 patients with different subtypes of mSTS were included. Most primary tumors originated from the lungs, and the rest were scattered throughout the body. All patients were treated with camrelizumab combined with apatinib within 5 days of local interventional therapy using transarterial chemoembolization (TACE) or radiofrequency ablation (RFA). Primary end point was progression-free survival (PFS), and secondary end points were objective response rate (ORR), disease control rate (DCR), and patient safety.Results: The median PFS, median overall survival (OS), ORR, and DCR were 8.8 months, 18.5 months, 36.4%, and 75.8%, respectively. Patients (n = 20) treated with RFA combined with TACE showed better responses than those treated with RFA alone (n = 13), with mPFS of 9.3 and 7.9 months (P = 0.044) and mOS of 19.0 and 16.2 months (P = 0.043), respectively. Patients (n = 8) with alveolar soft part sarcomas showed excellent efficacy, with ORR, DCR, mPFS, and mOS of 62.5%, 87.5%, 11.5 months, and 22.5 months, respectively. Grades 3 or 4 treatment-related adverse events occurred in 12 of 33 patients.Conclusions: Local intervention therapy combined with camrelizumab and apatinib is effective and safe for patients with mSTS and should be investigated in future clinical trials. [ABSTRACT FROM AUTHOR]

Background: The combination therapy of trans-arterial chemoembolization (TACE) and sorafenib were proved to be one of the effective methods for intermediate and advanced hepatocellular carcinoma (HCC). Although it has been confirmed that the combination therapy can prolong survival for advanced HCC effectively, the therapeutic efficacy and safety are still controversial and the clinical value has not been determined. This meta-analysis aims to evaluate the efficacy and safety of combination therapy and discuss the optimal timing of combination for better clinical benefits. Data sources: PubMed, EMBASE, the Cochrane Library, MEDLINE, and Web of Science were systematically reviewed to search for relevant studies published before May 15, 2021. Studies comparing the efficacy and safety of TACE + sorafenib with TACE + placebo / alone were adopted. Two reviewers independently extracted study outcomes. The data were analyzed through fixed/random-effect meta-analysis models with Review Manager (Version 5. 3) software. Results: 7 randomized controlled trials (RCTs) were included with 1464 patients with unresectable HCC (734 in TACE + sorafenib group and 730 in TACE + placebo or alone group). Meta-analysis showed that objective response rate (ORR) and disease control rate (DCR) were slightly improved in TACE + sorafenib group (ORR: risk ratio = 1.24; 95% confidence interval: 1.08–1.42; P = 0.002; DCR: risk ratio = 1.09; 95% confidence interval: 1.01–1.18; P = 0.02). The combination therapy obviously improved time to progression (TTP) (hazard ratio: 0.73; 95% confidence interval: 0.55–0.96; P = 0.03) and progression-free survival (PFS) (hazard ratio 0.62; 95% confidence interval: 0.52–0.73, P

Abstract Background The ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE. Methods From January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT. Results Eighty nine TACE procedures (1.35 ± 0.67; 1–4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P = 0.002), “typical tumor enhancement” (P = 0.010) and smooth tumor margins (p = 0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis. Conclusions The well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation.

Abstract Background Hepatoma arterial-embolization prognostic (HAP) score and its modifications (modified HAP [mHAP] and mHAP-II), consisting of some or all of the following factors of tumor size, number, alpha-fetoprotein, bilirubin, and serum albumin, have been found to predict outcomes after trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We investigated the feasibility of using HAP-related risk scores for dynamic risk assessment during repeated TACE. Methods A total of 619 HCC patients treated with TACE from two institutions between 2003 and 2010 were included. Results Patients with A-B class risk scores showed significantly better survival than those with C-D class risk scores at the first (median 43.7 vs. 21.5 months for mHAP-II, 35.2 vs. 10.2 months for mHAP, and 39.8 vs. 18.6 months for HAP; all P

PurposeThis study aimed to evaluate the efficacy and safety of trans-arterial chemoembolization (TACE) followed by stereotactic body radiation therapy (SBRT) in treating Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) not amenable to resection and radiofrequency ablation (RFA).MethodsFrom February 2012 to January 2017, a total of 57 BCLC stage B HCC patients who were unsuitable candidates for resection and RFA treated with TACE combined with CyberKnife SBRT were included in this retrospective study. Patients underwent TACE for a median of two times (1–5 times) before SBRT. SBRT prescription doses ranged from 30 Gy to 50 Gy in 3–5 fractions.ResultsThe median follow-up time was 42 months. The objective response rate (CR + PR) was 85.9%, and the disease control rate (CR + PR + SD) was 96.5%. The local control (LC) rates were 91.1% and 84.3% at 1 and 2 years, respectively. The 1-, 2-, 3-year overall survival (OS) and the median survival time were 73.2%, 51.4%, 32.4% and 26.6 months, respectively. The 1-, 2-, and 3-year progression-free survival (PFS) were 34.2%, 21.6%, and 9%, respectively, with a median PFS time of 9.7 months. A subgroup analysis was conducted in 32 patients with AFP ≥ 200 ng/ml before TACE. OS was significantly prolonged in those with AFP that decreased by more than 75% than those with AFP that decreased by less than 75% (P = 0.018) after SBRT. The treatment was well tolerated with only one patient (1.8%) developed grade 3 gastrointestinal toxicity, and another patient developed non-classical RILD. In multivariate analysis, tumor length ≥ 10 cm and AFP ≥ 200 ng/ml were independent poor prognostic factors for OS.ConclusionThe combination of TACE and Cyberknife SBRT showed optimal efficacy with acceptable toxicity for BCLC stage B HCC.

Purpose: This study aimed to evaluate the efficacy and safety of trans-arterial chemoembolization (TACE) followed by stereotactic body radiation therapy (SBRT) in treating Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) not amenable to resection and radiofrequency ablation (RFA). Methods: From February 2012 to January 2017, a total of 57 BCLC stage B HCC patients who were unsuitable candidates for resection and RFA treated with TACE combined with CyberKnife SBRT were included in this retrospective study. Patients underwent TACE for a median of two times (1–5 times) before SBRT. SBRT prescription doses ranged from 30 Gy to 50 Gy in 3–5 fractions. Results: The median follow-up time was 42 months. The objective response rate (CR + PR) was 85.9%, and the disease control rate (CR + PR + SD) was 96.5%. The local control (LC) rates were 91.1% and 84.3% at 1 and 2 years, respectively. The 1-, 2-, 3-year overall survival (OS) and the median survival time were 73.2%, 51.4%, 32.4% and 26.6 months, respectively. The 1-, 2-, and 3-year progression-free survival (PFS) were 34.2%, 21.6%, and 9%, respectively, with a median PFS time of 9.7 months. A subgroup analysis was conducted in 32 patients with AFP ≥ 200 ng/ml before TACE. OS was significantly prolonged in those with AFP that decreased by more than 75% than those with AFP that decreased by less than 75% (P = 0.018) after SBRT. The treatment was well tolerated with only one patient (1.8%) developed grade 3 gastrointestinal toxicity, and another patient developed non-classical RILD. In multivariate analysis, tumor length ≥ 10 cm and AFP ≥ 200 ng/ml were independent poor prognostic factors for OS. Conclusion: The combination of TACE and Cyberknife SBRT showed optimal efficacy with acceptable toxicity for BCLC stage B HCC. [ABSTRACT FROM AUTHOR]

Purpose: Data from common clinical practice were used to generate balanced cohorts of patients receiving either sorafenib or lenvatinib, for unresectable hepatocellular carcinoma, with the final aim to investigate their declared equivalence. Methods: Clinical features of lenvatinib and sorafenib patients were balanced through inverse probability of treatment weighting (IPTW) methodology, which weights patients' characteristics and measured outcomes of each patient in both treatment arms. Overall survival was the primary endpoint and occurrence of adverse events was the secondary. Results: The analysis included 385 patients who received lenvatinib, and 555 patients who received sorafenib. In the unadjusted cohort, lenvatinib did not show a survival advantage over sorafenib (HR: 0.85, 95% CI 0.70‐1.02). After IPTW adjustment, lenvatinib still not returned a survival advantage over sorafenib (HR: 0.82, 95% CI: 0.62‐1.07) even in presence of balanced baseline characteristics. Lenvatinib provided longer survival than sorafenib in patients previously submitted to TACE (HR: 0.69), with PS of 0 (HR: 0.73) or without extrahepatic disease (HR: 0.69). Conclusion: Present results confirmed randomized controlled trial in the real‐life setting, but also suggests that in earlier stages some benefit can be expected. [ABSTRACT FROM AUTHOR]

Purpose: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, when unresectable; therefore, intra-arterial therapies (IAT) such as trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE) have been employed. With the present systematic review and meta-analysis, we aimed to analyse published studies to understand if one IAT can be superior to the alternative.Materials and Methods: A systematic search of PubMed and Web of Science databases was performed for articles published until 1 March 2020 relevant to IAT for ICC. Overall survival was the primary end point. Occurrence of clinical adverse events and tumour overall response were secondary outcome measures.Results: A total of 31 articles (of 793, n.1695 patients) were selected for data extraction, 13 were on TACE (906 patients) and 18 were on TARE (789 patients). Clinical and tumour characteristics showed moderate heterogeneity between the two groups. The median survival after TACE was 14.2 months while after TARE was 13.5 months (95%C.I.: 11.4-16.1). The survival difference was small (d = 0.112) at 1 year and negligible at 2 years (d = 0.028) and at 3 years (d = 0.049). The radiological objective response after TACE was 20.6% and after TARE was 19.3% (d = 0.032). Clinical adverse events occurred in 58.5% after TACE, more frequently than after TARE (43.0%, d = 0.314).Conclusion: In conclusion, IATs are promising treatments for improving outcomes for patients with unresectable ICC. To date, TACE and TARE provide similar good outcomes, except for adverse events. Therefore, the decision about techniques is determined by ability to utilize these resources and patient specific factors (liver function or lesion dimension). [ABSTRACT FROM AUTHOR]

Background: To date there is no therapy consensus in patients with multifocal hepatocellular carcinoma (mHCC). Purpose: To compare outcome of trans-arterial chemoembolization (TACE) with degradable starch microspheres (DSM-TACE) versus selective internal radiation therapy (SIRT) in mHCC. Material and Methods: In this single-center study, 36 patients without portal vein invasion, treated between May 2014 and May 2018, were enrolled retrospectively. Eighteen consecutive patients received DSM-TACE and were matched by age, gender, BCLC stage, Child-Pugh status, and tumor volume and 18 patients underwent SIRT. Overall survival (OS), progression-free survival (PFS), and local tumor control (LTC) were evaluated. Toxicity profiles for both therapies were also evaluated and compared. Results: In the entire collective, median OS was 9.5, PFS 5.0, and LTC 5.5 months. Subgroup analysis revealed an OS of 9.5 months in both groups (P = 0.621). PFS was 6 months for the SIRT and 4 months for the DSM-TACE cohort (P = 0.065). Although not significantly, LTC was lower (4 months) in the SIRT compared to the DSM-TACE cohort (7 months; P = 0.391). When DSM-TACE was performed ≥3 times (n = 11), OS increased, however without statistical difference compared to SIRT, to 11 months, PFS to 7 months, and LTC to 7 months. When DSM-TACE was performed <3 times (n = 7), OS, PFS, and LTC decreased (5 months, P = 0.333; 2 months, P = 0.047; 2 months, P = 0.47). Toxicity profiles and adverse event analysis only revealed a significant difference for nausea and vomiting (more frequent in the SIRT cohort, P = 0.015), while no other parameter showed a significant difference (P > 0.05). Conclusion: DSM-TACE might be an alternative to SIRT in multifocal HCC patients as OS, PFS, and LTC did not differ significantly and toxicity profiles seem to be comparable. [ABSTRACT FROM AUTHOR]

Background: Transarterial chemoembolization (TACE) is the recommended treatment modality for non-resectable intermediate-stage hepatocellular carcinoma; however, this stage has wide variable levels of liver functions and tumor burden making a challenge as regards the tolerability of the functioning residual liver to this type of therapy. Further stratification of this intermediate stage may help the clinical decision for the suitability of TACE, so we tried to derive a clinical decision support tool to predict the tolerability of the functioning residual liver to TACE using pre-intervention liver reserve function and liver residual volume as well as tumor burden. Results: Two hundred and fifty-two patients with non-resectable intermediate-stage hepatocellular carcinoma (HCC) were consecutively included in this cohort study; all patients were blindly followed up for 6 weeks after TACE for manifestation of liver decompensation. For univariate logistic regression analysis, the significant predictors were age, s.albumin, s.bilirubin, prothrombin concentration (PC), tumor volume (TV), residual liver volume (RLV), and residual to liver volumetric ratio (RLVR) (sig, 0.007, 0.000, 0.000, 0.000, 0.000, 0.002, and 0.000, respectively). Multivariate logistic regression analysis illustrated that s.albumin, s.bilirubin, PC, and RLVR were the most independent significant predictors (sig, 0.000 for all with adjusted OR 0.002, 22.692, 0.827, and 0.000, respectively). The discriminatory performance of our proposed decision support score (liver tolerability score) was evaluated using the receiver operating characteristics that identified two cutoff points (≤ 0.30 and ≥ 0.83) to rule out or rule in the possibility of liver decompensation after TACE, respectively (AUC, 0.942 and sig. 0.000). Liver tolerability score stratified the intermediate stage of HCC to 3 risk grades (low, medium, and high) with significant difference as regards hazard distribution. Conclusion: Computed tomography image-based assessment of RLVR may have a possible role in predicting future tolerability of the functioning residual tissue to TACE of HCC. Liver tolerability score (LTS) could stratify the intermediate stage HCC to 3 risk grades, so LTS may have a role in clinical decision for the suitability of TACE for intermediate stage HCC. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the histological findings in both tumor and surrounding non-tumoral liver parenchyma after trans-arterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC) in patients who subsequently underwent hepatectomy. Material and methods: This study included six patients with an HCC (size 15–61 mm). DEB-TACE was performed using polyvinyl alcohol-based hydrogel microspheres loaded with epirubicin. Radiological tumor response was evaluated after DEB-TACE and before hepatectomy, according to the Modified Response Evaluation Criteria in Solid Tumors. Surgical specimens were histologically evaluated with hematoxylin and eosin, and elastic Van Gieson's staining. Results: Segmental, sub-segmental, or partial hepatectomy were performed 14–58 days after DEB-TACE. There was no remarkable destructive change and minimal to absent inflammatory cell infiltration in the surrounding non-tumoral liver parenchyma. There was no evidence of biliary tract or arterial wall impairment. Complete and partial histological tumor necrosis were found in three cases, respectively, in agreement with the complete and partial responses seen during the radiological evaluation. Conclusion: Histological examination of resected liver specimens after DEB-TACE showed substantial tumor necrosis without any severe inflammatory or destructive changes in the non-tumoral liver parenchyma. [ABSTRACT FROM AUTHOR]

Despite careful selection for liver transplantation (LT) of patients with hepatocellular carcinoma (HCC), HCC may still recur after LT and is frequently associated with dismal outcome. Tumor factors, including serum alpha-fetoprotein (AFP), the presence of microvascular invasion, tumor grade/differentiation, and largest tumor size are amongst the most important predictors of recurrence after transplantation. The nature of recurrence can be highly variable, but often presents with extra-hepatic involvement. As such, management of patients with HCC can be challenging, and consensus guidelines are lacking. Curative options, with surgery or ablation, which may be applicable in patients with isolated intra-or extrahepatic metastases, offer the best chance for improved long-term outcome in patients with HCC recurrence after transplantation. Most patients with recurrence have unresectable disease, and may benefit from palliative treatments, including intra-arterial therapies and/or systemic therapy. [ABSTRACT FROM AUTHOR]

Background: The ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE.Methods: From January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT.Results: Eighty nine TACE procedures (1.35 ± 0.67; 1-4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P = 0.002), "typical tumor enhancement" (P = 0.010) and smooth tumor margins (p = 0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis.Conclusions: The well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation. [ABSTRACT FROM AUTHOR]

Although different treatment methods have been introduced to treat advanced pancreatic carcinoma, the median overall survival rate remains unsatisfactory. Theoretically, combining different treatment methods should work in synergy to enhance locoregional disease control and improve survival. Therefore, the aim of the present retrospective study was to analyze the effectiveness of combined interventional therapy compared with trans-arterial chemoembolization (TACE) or chemotherapy alone for the treatment of unresectable pancreatic carcinoma. A total of 266 patients who were undergoing treatment for unresectable pancreatic carcinoma between July 2012 and November 2015 were included in the current study. The tumor responses and 3-year overall survival rates of patients treated with combined interventional therapy (TACE combined with iodine-125 seed implantation and/or radiofrequency ablation; CIT group; n=84) were compared with those of patients treated with TACE alone (TACE group; n=59), as well as patients treated with systemic chemotherapy alone (control group; n=123). Patients in the CIT group exhibited significantly improved tumor responses compared with patients in the TACE group (51.89 vs. 30.61%; P=0.028) or control group (51.89 vs. 17.20%; P<0.001). The 3-year overall survival rate of the CIT group was also significantly higher compared with that of the TACE and control groups (P=0.0116 and P=0.0001, respectively). Furthermore, the CIT group exhibited a significantly higher overall survival rate for patients with unresectable metastatic pancreatic cancer compared with the TACE and control groups (P=0.0088 and P<0.0001, respectively), which suggests that a combination of different interventional techniques increases the survival of patients with unresectable pancreatic cancer. No life-threatening complications were observed in any treatment group. In conclusion, combined interventional therapy exhibits a good efficacy and an improved survival rate for unresectable pancreatic cancer compared with TACE alone. [ABSTRACT FROM AUTHOR]

Background: Hepatoma arterial-embolization prognostic (HAP) score and its modifications (modified HAP [mHAP] and mHAP-II), consisting of some or all of the following factors of tumor size, number, alpha-fetoprotein, bilirubin, and serum albumin, have been found to predict outcomes after trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We investigated the feasibility of using HAP-related risk scores for dynamic risk assessment during repeated TACE.Methods: A total of 619 HCC patients treated with TACE from two institutions between 2003 and 2010 were included.Results: Patients with A-B class risk scores showed significantly better survival than those with C-D class risk scores at the first (median 43.7 vs. 21.5 months for mHAP-II, 35.2 vs. 10.2 months for mHAP, and 39.8 vs. 18.6 months for HAP; all P < 0.001) and the second rounds of TACE (38.6 vs. 17.2 months for mHAP-II, 30.0 vs. 8.5 months for mHAP, and 32.6 vs. 17.3 months for HAP; all P < 0.001). Sequential assessment of risk scores at the second TACE round was applied for patients with A-B class risk scores at the first TACE round, which further identified two subgroups of A-B and C-D class risk scores with different outcomes (median survival 40.6 vs. 19.6 months for mHAP-II, 31.2 vs. 16.9 months for mHAP, and 35.8 vs. 21.0 months for HAP; all P < 0.001). Compared with mHAP and HAP, mHAP-II showed the highest likelihood ratio (22.61 vs. 14.67 and 13.97, respectively), highest linear trend (24.43 vs. 19.67 and 14.19, respectively), and lowest Akaike information criteria value (1432.51 vs. 3412.29 and 2296.98, respectively).Conclusions: All HAP-related risk scores dynamically predicted outcomes during repeated TACE. Sequential risk assessment using mHAP-II best identified optimal candidates for repeated TACE. [ABSTRACT FROM AUTHOR]

Objective: To evaluate MDCT perfusion role in HCC local therapy response. Patients and methods: Post radiofrequency ablation and trans-arterial chemoembolization 14 (88%) male and 2 (12%) female HCC patients; with the mean age, 55.75 ± 10.6 years underwent follow-up hepatic CT perfusion. The hepatic arterial and portal venous perfusions (HAP and HPP, ml/min/100 ml) and hepatic perfusion index (HPI%) were indicated using the color coded maps to assess the effects of local therapy on hepatic perfusion values. Results: The post local treatment CTP of the recurrent tumor confirmed relative increased HAP and HPI and reduced PVP relative to the background values of the cirrhotic hepatic parenchyma. The recurrent HCC post-treatment CTP including HAP is 71 ± 12.19, the PVP is 25.5 ± 8.66 and HPI is 52.5 ± 11.9. The post local-treatment CTP of the necrosis confirmed relative decreased HAP and HPI and increased PVP. The post-treatment necrosis CTP including HAP is 23 ± 10.39, the PVP is 34.75 ± 11.5 and HPI is 29 ± 16.51. The CTP sensitivity is 75%, specificity 50% and P-value

Aim: To identify the role of serum MicroRNA-335 (miR-335) in determining the treatment response to Trans-arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and their prognosis after TACE. Methods: A total of 125 HCC patients were enrolled in this study. All these patients underwent TACE and the treatment response was evaluated. All patients were followed for prognosis analyses. Serum miR-335 levels immediate before and 30 days after TACE were determined. Results: HCC patients had significantly lower miR-335 levels than hepatitis patients and healthy controls. Lower serum miR-335 levels were closely associated with more progressive clinical features, including a higher mean serum AFP level, more vascular invasion, cirrhosis and larger tumor size. Response rates were higher in patients with high miR-335 compared to those with low miR-335 level. Patients with lower serum miR-335 levels had significantly poorer prognosis than patients with higher serum miR-335 levels. Conclusion: Our data suggest that serum miR-335 can be used as a molecular marker to predict the treatment response and clinical outcome in HCC patients receiving TACE.

Blockage of blood supply while administering chemotherapy to tumors, using trans-arterial chemoembolization (TACE), is the most common treatment for intermediate and advanced-stage unresectable Hepatocellular carcinoma (HCC). However, HCC is characterized by a poor prognosis and high recurrence rates (≈30%), partly due to a hypoxic pro-angiogenic and pro-cancerous microenvironment. This study investigates how modifying tissue stress while improving drug exposure in target organs may maximize the therapeutic outcomes. Porous degradable polymeric microspheres (MS) are designed to obtain a gradual occlusion of the hepatic artery that nourishes the liver, while enabling efficient drug perfusion to the tumor site. The fabricated porous MS are introduced intrahepatically and designed to release a combination therapy of Doxorubicin (DOX) and Tirapazamine (TPZ), which is a hypoxia-activated prodrug. Liver cancer cell lines that are treated with the combination therapy under hypoxia reveal a synergic anti-proliferation effect. An orthotopic liver cancer model, based on N1-S1 hepatoma in rats, is used for the efficacy, biodistribution, and safety studies. Porous DOX-TPZ MS are very effective in suppressing tumor growth in rats, and induction tissue necrosis is associated with high intratumor drug concentrations. Porous particles without drugs show some advantages over nonporous particles, suggesting that morphology may affect the treatment outcomes., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Purpose: To compare the diagnostic accuracy of extracellular gadolinium-based contrast-enhanced MRI (Gd-MRI) and gadoxetic acid-enhanced MRI (EOB-MRI) for the assessment of hepatocellular carcinoma (HCC) response to locoregional therapy (LRT) using explant correlation as the reference standard.Methods: Forty-nine subjects with cirrhosis and HCC treated with LRT who underwent liver MRI using either Gd-MRI (n = 26) or EOB-MRI (n = 23) within 90 days of liver transplantation were included. Four radiologists reviewed the MR images blinded to histology to determine the size and percentage of viable residual HCC using a per-lesion explant reference standard. Sensitivities, specificities, accuracies, and agreement with histology for the detection residual HCC were calculated.Results: Gd-MRI had greater agreement with histology (ICC: 0.98 [0.95-0.99] vs. 0.80 [0.63-0.90]) and greater sensitivity for viable HCC (76% [13/17 50-93%] vs. 58% [7/12; 28-85%]) than EOB-MRI; specificities were similar (84% [16/19; 60-97%] vs. 85% [23/27; 66-96%]). Areas under ROC curves for detecting residual viable tumor were 0.80 (0.64-0.92) for Gd-MRI and 0.72 (0.55-0.85) for EOB-MRI. Gd-MRI had greater inter-rater agreement than EOB-MRI for determining the size of residual viable HCC (ICC: 0.96 [0.92-0.98] vs. 0.85 [0.72-0.92]).Conclusion: Gd-MRI may be more accurate and precise than EOB-MRI for the assessment of viable HCC following LRT. [ABSTRACT FROM AUTHOR]

The majority of patients with unresectable hepatocellular carcinoma (HCC) undergo trans-arterial chemoembolization (TACE). However, the prognosis of HCC remains poor. In the present study, five staging systems were compared to predict the survival rate of patients with HCC undergoing TACE treatment. A total of 220 patients with HCC were examined according to the model to estimate survival for hepatocellular carcinoma (MESH), hepatoma arterial embolization prognostic score (HAP), modified HAP (mHAP), performance status combined Japan Integrated Staging system (PSJIS) and tumor-node-metastasis (TNM) staging systems. The endpoints of the study were 3-month survival, 6-month survival, 1-year survival and overall survival (OS) rates. Receiver operating characteristic curve analysis indicated that the area under the curve of MESH, HAP, mHAP, PSJIS and TNM was 0.858, 0.728, 0.690, 0.688 and 0.699, respectively, in predicting 3-month survival rates; 0.822, 0.747, 0.720, 0.722 and 0.715, respectively, in predicting 6-month survival rates and 0.725, 0.664, 0.672, 0.645 and 0.654, respectively, in predicting 1-year survival rates. Discriminatory ability, homogeneity, monotonicity and prognostic stratification ability was evaluated using a likelihood ratio test and Akaike information criterion values among the five staging systems, and revealed that the MESH system was the optimal prognostic staging system for HCC. In conclusion, the results of the present study suggest that the MESH system is the most accurate prognostic staging system of 3-month survival, 6-month survival, 1-year survival and OS rates among the five systems analyzed in patients with HCC who have received TACE treatment. [ABSTRACT FROM AUTHOR]

In patients with AFP-negative hepatocellular carcinoma (HCC), des-γ-carboxyprothrombin (DCP) is an important prognostic indicator for the preoperative assessment of transarterial chemoembolization (TACE). However, the association between the serum DCP levels and the degree of progression and prognosis of patients with AFP-negative HCC treated with TACE has not been thoroughly investigated to date, and the molecular mechanism is also unclear. The present study retrospectively analyzed the clinical data of 107 patients with AFP-negative HCC treated with TACE and divided them into two groups based on the median serum DCP levels. The association between DCP and the clinical characteristics of the patients was analyzed, and the survival data were analyzed using Kaplan-Meier curves and Cox regression models. The results demonstrated that the median follow-up time was 755 days (range, 64–1,556 days), and patients in the low-DCP group (n=11; 20.8%) had a lower mortality rate than those in the high-DCP group (n=20; 37.0%). Cox multivariate regression analysis suggested that preoperative lymph node metastasis [hazard ratio (HR), 3.903; 95% CI, 1.778-8.519; P=0.001] and DCP group (HR, 2.465; 95% CI, 1.038-5.854; P=0.041) were independent risk factors. Furthermore, the Gene Expression Omnibus database was utilized to screen differentially expressed mRNAs. Enrichment analyses were then performed, and a protein-protein interaction (PPI) network was constructed to identify hub genes. A total of 169 differentially expressed genes were screened. Enrichment analyses revealed that cancer-related and ribosomal pathways were significantly enriched. Furthermore, 10 hub genes were identified in the PPI network by counting the number of gene interactions, the majority of which belonged to the ribosomal protein (RPS) family, and the top three significant genes were RPS23, RPS11 and RPS3A. In patients with AFP-negative HCC, higher serum DCP levels were associated with poor prognosis after TACE. This may be associated with genes such as those belonging to the RPS family, which may contribute to future personalized therapy for this disease. [ABSTRACT FROM AUTHOR]

Background & Aims: The hepatoma arterial-embolization prognostic (HAP) score predicts survival outcome in patients with hepatocellular carcinoma (HCC) treated with trans-arterial chemoembolization (TACE). We validated the HAP score in Korean subjects with HCC and investigated whether its prognostic performance is improved with additional parameters. Methods: A total of 280 patients with HCC treated with TACE between 2003 and 2009 were included. Validation and modification of HAP score were performed based on multivariate Cox regression models. Results: The median age of the study population (211 men, 69 women) was 60 years. Viral etiology of HCC accounted for 80.4% (n = 181 for hepatitis B, 44 for hepatitis C). The median overall survival (OS) was 40.5 months. On multivariate analysis, together with the original components of the HAP score (serum albumin <3.6 g/dl, total bilirubin >0.9 mg/dl, alpha-foetoprotein >400 ng/ml, and tumor size >7 cm), tumor number =2 was selected as an independent unfavorable prognostic factor for OS (hazard ratio 2.3; P < 0.001). Accordingly, a modified HAP-II (mHAP-II) score was established by adding tumor number =2. Although both HAP and mHAP-II scores discriminated the four different risk groups (log-rank test, all P < 0.001), the mHAP-II score performed significantly better than the HAP score, as per the areas under receiver-operating curves predicting OS at 3 years (0.717 vs. 0.658) and 5 years (0.728 vs. 0.645), respectively (all P < 0.05). Conclusions: Although the HAP score predicted OS for Korean subjects with HCC undergoing TACE, the addition of tumor number significantly improved the prognostic performance. The mHAP-II score can be used for accurate prognostication and selection of optimal candidates for TACE. [ABSTRACT FROM AUTHOR]