Clinical efficacy of lenvatinib, trans-arterial chemoembolization, and PD-1/L1 inhibitors in advanced hepatocellular carcinoma: a systematic review and network meta-analysis.

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.

Hepatocellular Carcinoma in Ceará: Epidemiology and Treatment in a Reference Liver Transplant Center in Northeast Brazil.

Hepatocellular carcinoma remains a significant worldwide malignancy and an important cause of cancer-related death. The incidence is increasing globally. In Latin America, there is no consistent data on the epidemiology of hepatocellular carcinoma. However, Brazil is considered a country with an intermediate incidence of this liver neoplasm. In the state of Ceará, situated in the northeast region of Brazil, there are no consistent clinical and epidemiologic data on the actual incidence and the treatment of hepatocellular carcinoma. The purpose of this article is to describe epidemiologic characteristics and treatment forms of patients with hepatocellular carcinoma who were treated in a Liver Transplant Center. A retrospective observational study was conducted using the database from the register of 299 patients with hepatocellular carcinoma between June 2004 and February 2022. Only patients born in Ceará were included. Therefore, most patients were eligible, based on the Milan Criteria, to undergo liver transplantation with a Model End Stage Liver Disease score of 12.48 ± 4.66 points, and the waiting list time was approximately 7 months with 8.7% hepatocellular carcinoma recurrence after liver transplant. A total of 38.5 % of cases were outside the Milan criteria at the time of cancer diagnosis, and transarterial chemoembolization was the main treatment choice. In conclusion, the diagnosis of hepatocellular carcinoma in Ceará mainly occurs in male patients with hepatitis C or alcoholism, with a mean age of 61.55 years and a previous diagnosis of liver disease. Liver transplantation was the best curative therapeutic form in patients with cirrhosis and hepatocellular carcinoma in Ceará, where a significant number of patients were diagnosed with intermediate and advanced-stage hepatocellular carcinoma, so public health policies are important for the screening and monitoring of liver disease.

Radiological characteristics of hepatocellular carcinoma that achieved complete response after chemoembolization with drug-eluting beads for liver transplantation planning.

OBJECTIVE: To describe the radiological characteristics of hepatocellular carcinoma (HCC) lesions that achieved a complete response following drug-eluting bead transarterial chemoembolization (DEB-TACE) preceding liver transplantation. METHODS: This single-center case-control study enrolled patients with hepatocellular carcinoma who underwent neoadjuvant DEB-TACE therapy, were followed up with contrast-enhanced magnetic resonance imaging or computed tomography, and were successively evaluated according to the modified Response Evaluation Criteria in Solid Tumors. The HCCs were divided into two groups based on their diameter (Group A: ≤3cm; Group B: 3cm). Viability was assessed using the Kaplan-Meier method according to tumor size categories. The relationship between tumor variables was analyzed using bivariate Cox regression. RESULTS: Three-hundred and twenty-eight patients with 667 hepatocellular carcinomas who underwent their first DEB-TACE session were enrolled. A total of 105 hepatocellular carcinomas in 59 patients exhibited complete response after the initial DEB-TACE session and were divided into Group A (92 HCCs) and Group B (13 HCCs). The diameter in Group A decreased significantly compared to the pre-procedure size until the second assessment (p<0.001), with no subsequent reduction in diameter, despite maintaining a complete response. In Group B, the reduction in diameter remained significant compared with the initial value until the sixth imaging evaluation (p=0.014). The average reduction was 45.1% for Group B and a maximum of 14.9% in Group A. CONCLUSION: HCCs >3cm exhibited a greater reduction in size and a longer time to recurrence. HCCs ≤3cm had a shorter relapse time. The recurrence rates were similar. These findings may aid in planning for liver transplantation.

Liver decompensation is a frequent cause of treatment discontinuation and prognostic factor in intermediate-advanced HCC.

INTRODUCTION AND OBJECTIVES: With the advent of new therapeutic options for patients with hepatocellular carcinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real-world data regarding prognostic survival factors are of significant importance. PATIENTS AND METHODS: A multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic variables and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, estimating hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: Overall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enrollment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was independently associated with increased mortality [HR 3.22 (CI 1.64;6.33); P<.001]. Systemic treatment was initiated in 48.2% of the cohort (n=188), with a median survival of 15.7 months. Of these, 48.9% presented first-line treatment discontinuation (44.4% tumor progression, 29.3% liver decompensation, 18.5% symptomatic deterioration, and 7.8% intolerance), and only 28.7% received second-line systemic treatments. Liver decompensation [HR 2.9 (1.64;5.29); P<.0001], and symptomatic progression [HR 3.9 (1.53;9.78); P=0.004] were independently associated with mortality after first-line systemic treatment discontinuation. CONCLUSIONS: The complexity of these patients, with one-third presenting liver decompensation after systemic therapies, underlines the need for multidisciplinary team management and the central role of hepatologists.

Percutaneous ethanol injection is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation.

PURPOSE: Locoregional therapies (LRT) are employed for bridging patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). Although the main LRT options include transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) is an alternative with considerably lower costs. This study is a pioneering evaluation of the natural history of PEI bridging to OLT as compared to TACE. METHODS: All consecutive cirrhotic patients with HCC enlisted for OLT (2011-2020) at a single center were analyzed. Patients were divided into three LRT modality groups: PEI, TACE, and PEI+TACE. The primary study outcome was waitlist dropout due to tumor progression beyond Milan criteria. A comparison of post-transplant outcomes of patients as stratified by LRT modality also was performed. RESULTS: One hundred twenty-nine patients were included (PEI=56, TACE=43, PEI+TACE=30). The dropout rate due to tumor progression was not different among the three groups: PEI=8.9%, TACE=14%, PEI+TACE=16.7% (p=0.54). Thirteen (76.4%) patients underwent OLT after successful downstaging (3 [75%] in the PEI group, 5 [83.3%] in the TACE group, and 5 [71.4%] in the PEI+TACE group). For the 96 patients undergoing OLT, 5-year post-transplant recurrence-free survival was PEI=55.6% vs. TACE=55.1% vs. PEI+TACE=71.4% (p=0.42). Complete/near-complete pathological response rate was similar among groups (p=0.82). CONCLUSION: Dropout rates and post-transplant recurrence-free survivals related to PEI were comparable to those of TACE. This study supports the use of PEI alone or in combination with TACE for HCC patients awaiting OLT whenever RFA is not an option.

Comparison of surgical resection and transcatheter arterial chemoembolization for large hepatocellular carcinoma: a systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Large primary hepatocellular carcinoma (HCC) has a high mortality rate and a variety of treatments. Surgery and transcatheter arterial chemoembolization (TACE) are important treatments. Which could be better remain debatable. The objective of the study is to compare the long-term overall survival of surgical resection (SR) and the use of TACE in patients with large hepatocellular carcinoma. MATERIALS AND METHODS: We assessed clinical trials through PubMed, Medline, Embase, and the Cochrane Library up to March 2022. Two researchers independently screened articles, extracted data, and assessed the study quality according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses)guidelines. The primary outcome was overall survival (OS). The secondary outcomes were OS after propensity scores matching (PSM) and progression-free survival (PFS). RESULTS: A total of 14 studies, including 3609 patients, were enrolled in the meta-analysis. The meta-analysis indicated a significant improvement in the 1-year OS, 3-year OS, and 5-year OS favoring SR over TACE (OR = 2.19, 95% CI 1,60-3.00; OR = 3.47, 95% CI 2.47-4.88; OR = 2.72, 95% CI 2.03-3.64, p < 0.001, random model). The results were consistent across subgroups of tumor size and tumor numbers (p > 0.05). The pooled outcome indicated that 1-year OS, 3-year OS, and 5-year OS after PSM were higher in the SR group than in the TACE group (p < 0.001). CONCLUSIONS: This meta-analysis indicates that among patients with large primary hepatocellular carcinoma, the overall survival rate of patients undergoing surgical resection was higher than that of patients undergoing TACE.

Bloqueio epidural torácico comparado a morfina endovenosa no tratamento da dor na síndrome pós-embolização hepática: ensaio clínico randomizado controlado / Thoracic epidural block compared to intravenous morphine in the treatment of pain in hepatic post-embolization syndrome: a randomized controlled clinical trial

Introdução: A embolização e a quimioembolização transarterial hepática são procedimentos cirúrgicos usados para tratar pacientes com tumores hepáticos de origem primária e metastática, entretanto causam dor importante no período pós-operatório. O objetivo do estudo foi comparar o bloqueio epidural torácico à morfina endovenosa no tratamento da dor na síndrome pós-embolização hepática. Métodos: Foram randomizados 50 casos de pacientes submetidos a embolização transarterial hepática, os quais foram alocados em dois grupos: grupo morfina endovenosa (GV), submetido a uma dose de morfina na sala operatória; e o grupo bloqueio epidural torácico (GE), submetido a bloqueio epidural de injeção única. Todos os pacientes utilizaram analgesia endovenosa controlada pelo paciente no período pós-operatório. Foram analisados no estudo o consumo de morfina endovenosa no período pós-operatório, a dor aferida pela escala numérica verbal (ENV), o tempo de internação hospitalar, a incidência de náuseas, vômitos, prurido, retenção urinária, depressão respiratória e sonolência. Resultados: Não houve diferença do consumo médio de morfina e da ENV no período pós-operatório imediato. No primeiro dia pós-operatório o consumo médio de morfina no GV foi de 6.3 mg vs. 0.45 mg no GE, p < 0.01. A ENV no GV foi de 3.77 vs. 0.82 no GE, p<0.01. O consumo médio de morfina no período pós-operatório no GV foi de 6.91mg vs. 0.5mg no GE, p<0.01. Apenas dois pacientes do GE ficaram internados por mais de um dia, enquanto no GV oito pacientes receberam alta hospitalar a partir do segundo dia pós-operatório, entretanto não houve diferença estatisticamente significativa do tempo de internação hospitalar. Prurido foi observado em 18.2% dos pacientes do GE, e não houve ocorrência no GV, p=0.04. Conclusões: O bloqueio epidural torácico foi superior à morfina endovenosa no tratamento da dor na síndrome pós-embolização hepática.

Background: Hepatic transarterial embolization and chemoembolization are surgical procedures used to treat patients with hepatic tumors of primary and metastatic origin, however they cause significant pain in the postoperative period. The objective of the study was to compare thoracic epidural block with intravenous morphine in the treatment of pain in hepatic post-embolization syndrome. Methods: A total of 50 patients undergoing hepatic transcatheter arterial embolization were randomized and allocated into two groups: intravenous morphine group (IG) underwent to a morphine dose in the operating room; and thoracic epidural block group (EG) underwent to a single-shot epidural injection. All patients used intravenous patient-controlled analgesia (PCA) in postoperative period. Intravenous morphine consumption in the postoperative period, pain measured by the numerical rating scale (NRS), length of hospital stay, nausea, vomiting, pruritus, urinary retention, respiratory depression and drowsiness were analyzed. Results: There was no difference in the mean morphine consumption and NRS in the immediate postoperative (IPO) period. On postoperative day 1, the IG mean morphine consumption was 6.3 mg vs. 0.45 mg in EG, p<0.01. NRS in IG was 3.77 vs. 0.82 in EG, p<0.01. Morphine consumption in post-operative period in IG was 6.91 mg vs. 0.5 mg in EG, p<0.01. Only two patients in the EG were hospitalized for more than one day, while in the GV eight patients were discharged from the second postoperative day, however there was no statistically significant difference in the length of hospital stay. Pruritus was observed in 18.2% of EG patients and none in the IG, p = 0.04. Conclusions: Thoracic epidural block was superior to intravenous morphine in the treatment of pain in hepatic post embolization syndrome.

Clinical efficacy and safety of external radiotherapy combined with sorafenib in the treatment of hepatocellular carcinoma: a systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Both external radiotherapy and sorafenib are promising treatments for hepatocellular carcinoma (HCC). Nevertheless, the combined treatment of external radiotherapy and sorafenib has not been widely applied clinically due to potentially adverse effects. This meta-analysis aimed to evaluate the clinical efficacy and safety of external radiotherapy combined with sorafenib in the treatment of HCC. METHODS: Pubmed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched. The primary and secondary observation endpoints were the end of survival and incidence of adverse events, respectively. 11 studies involving 664 patients were included in this meta-analysis. RESULTS: The results demonstrated that median overall survival (mOS) and median progression-free survival (mPFS) of the external radiotherapy combined with sorafenib (RS) group were 19.45 months and 8.20 months. The one- and two-year survival rates were 0.65 (95%CI: 0.55-0.76) and 0.40 (95%CI: 0.24-0.56). The incidence of adverse events was 0.34 (95%CI: 0.25-0.44). CONCLUSIONS: The findings demonstrated that the survival of the RS group was significantly improved and few severe adverse events were observed. Hence, it can be concluded that external radiotherapy combined with sorafenib is a safe, effective, and promising therapeutic option for HCC.

Ytrrium-90 transarterial radioembolization in patients with gastrointestinal malignancies.

Transarterial radioembolization (TARE) with yttrium-90 (Y90) is a promising alternative strategy to treat liver tumors and liver metastasis from colorectal cancer (CRC), as it selectively delivers radioactive isotopes to the tumor via the hepatic artery, sparring surrounding liver tissue. The landscape of TARE indications is constantly evolving. This strategy is considered for patients with hepatocellular carcinoma (HCC) with liver-confined disease and preserved liver function in whom neither TACE nor systemic therapy is possible. In patients with liver metastases from CRC, TARE is advised when other chemotherapeutic options have failed. Recent phase III trials have not succeeded to prove benefit in overall survival; however, it has helped to better understand the patients that may benefit from TARE based on subgroup analysis. New strategies and treatment combinations are being investigated in ongoing clinical trials. The aim of this review is to summarize the clinical applications of TARE in patients with gastrointestinal malignancies.

Efficacy comparison of optimal treatments for hepatocellular carcinoma patients with portal vein tumor thrombus.

INTRODUCTION AND OBJECTIVES: Optimal treatment of hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) remains controversial. MATERIALS AND METHODS: A total of 627 HCC patients with PVTT after initial treatment with one of the following at Affiliated Tumor Hospital of Guangxi Medical University: liver resection (LR, n = 225), transarterial chemoembolization (TACE, n = 298) or sorafenib (n = 104) were recruited and randomly divided into the training cohort (n = 314) and internal validation cohort (n = 313). Survival analysis were repeated after stratifying patients by Cheng PVTT type. RESULTS: Resection led to significantly higher OS than the other two treatments among patients with type I or II PVTT. TACE worked significantly better than the other two treatments for patients with type III. All three treatments were associated with similar OS among patients with type IV. These findings were supported by the internal validation cohort. CONCLUSIONS: Our results suggest that the optimal treatment for HCC involving PVTT depends on the type of PVTT. LR may be more appropriate for type I or II PVTT; TACE, for type III Sorafenib may be more appropriate than invasive treatments for patients with type IV PVTT.

Standardization of conventional chemoembolization for hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: Conventional transarterial chemoembolization (cTACE) has several limitations due to the lack of standardization. The aim of this study was to evaluate the chemical and physical characteristics and behaviors over time of emulsions for cTACE and to assess intra- and inter-operator variabilities in the preparation processes. MATERIALS AND METHODS: This in vitro study involved evaluation of emulsions for cTACE prepared using two methods: water-in-oil (WiO) and chemotherapeutic-in-oil (CiO). Three emulsions were prepared with each method and obtained after 20, 50, and 100 pumping exchanges. A drop from each final mixture was analyzed via light microscopy (time 1) and after 5, 10, 15, and 20min since the end of preparation. After 20min, all preparations were re-mixed and new drops were re-evaluated. The intra- and inter-operator variabilities were analyzed. RESULTS: The mean droplet diameter decreased non-significantly when the number of pumping exchanges increased and increased significantly over time for both WiO and CiO. The droplets returned to their initial diameters after re-mixing. There were no significant differences in the intra- and inter-operator variabilities (P>0.01). CONCLUSIONS: Any interventional radiologist, regardless of their experience, may prepare these emulsions. These data may represent a set of instructions to standardize cTACE.

Recurrence of hepatocellular carcinoma after liver transplantation: Prognostic and predictive factors of survival in a Latin American cohort.

BACKGROUND & AIM: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has a poor prognosis, and the adjusted effect of different treatments on post-recurrence survival (PRS) has not been well defined. This study aims to evaluate prognostic and predictive variables associated with PRS. METHODS: This Latin American multicenter retrospective cohort study included HCC patients who underwent LT between the years 2005-2018. We evaluated the effect of baseline characteristics at time of HCC recurrence diagnosis and PRS (Cox regression analysis). Early recurrences were those occurring within 12 months of LT. To evaluate the adjusted treatment effect for HCC recurrence, a propensity score matching analysis was performed to assess the probability of having received any specific treatment for recurrence. RESULTS: From a total of 1085 transplanted HCC patients, the cumulative incidence of recurrence was 16.6% (CI 13.5-20.3), with median time to recurrence of 13.0 months (IQR 6.0-26.0). Factors independently associated with PRS were early recurrence (47.6%), treatment with sorafenib and surgery/trans-arterial chemoembolization (TACE). Patients who underwent any treatment presented "early recurrences" less frequently, and more extrahepatic metastasis. This unbalanced distribution was included in the propensity score matching, with correct calibration and discrimination (receiving operator curve of 0.81 [CI 0.72;0.88]). After matching, the adjusted effect on PRS for any treatment was HR of 0.2 (0.10;0.33); P < .0001, for sorafenib therapy HR of 0.4 (0.27;0.77); P = .003, and for surgery/TACE HR of 0.4 (0.18;0.78); P = .009. CONCLUSION: Although early recurrence was associated with worse outcome, even in this population, systemic or locoregional treatments were associated with better PRS.

Effect of prophylactic transcatheter arterial chemoembolization on hepatocellular carcinoma with microvascular invasion after R0 resection. A case-control study.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is thought to prevent recurrence of hepatocellular carcinoma (HCC), but its efficacy is a matter of controversy. OBJECTIVES: We investigated the effect of preventive TACE on the tumor, nodes, metastasis (TNM) classification in cases of stage II HCC (T2N0M0) after R0 resection. DESIGN AND SETTING: Case-control study conducted in a tertiary-level public hospital. METHODS: We analyzed recurrence rates and mortality rates over time for 250 consecutive cases of HCC in TNM classification cases of stage II HCC (T2N0M0) after R0 resection. These cases were divided into patients who underwent TACE (TACE+) and presented microvascular invasion (MVI+; n = 80); TACE+ but did not present MVI (MIV-; n = 100); MVI+ but did not undergo TACE (TACE-, n = 30); and TACE-/MVI- (n = 40). RESULTS: MVI+ patients in the TACE+ group had significantly lower recurrence rates and mortality rates at one, two and three years than those in the TACE- group (all P < 0.05). Among MVI- patients, the TACE+ group did not have significantly lower recurrence rates and mortality rates at one, two and three years than the TACE- group (all P > 0.05). Regardless of whether TACE was performed or not, MVI- patients had significantly lower recurrence rates and mortality rates at two and three years after their procedures than did MVI+ patients (all P < 0.05). CONCLUSION: Recurrence rates and mortality rates for MVI+ patients were significantly higher than for MVI- patients, beyond the first year after TACE. Postoperative adjuvant TACE may be beneficial for HCC patients with MVI.

Transarterial radioembolization for liver tumors as neoadjuvant therapy: three case reports.

Transarterial radioembolization (TARE) with yttrium-90 microspheres is a palliative locoregional treatment, minimally invasive for liver tumors. The neoadjuvant aim of this treatment is still controversial, however, selected cases with lesions initially considered unresectable have been enframed as candidates for curative therapy after hepatic transarterial radioembolization. We report three cases in which the hepatic transarterial radioembolization was used as neoadjuvant therapy in an effective way, allowing posterior potentially curative therapies.

Expanding TACTICS trial into a different setting in hepatocellular carcinoma.

Systemic treatment for hepatocellular carcinoma (HCC) is recommended for patients with advanced stage and for those who progressed on locoregional modalities. The first agent approved for advanced HCC was sorafenib, and it remains one of the cornerstones of systemic treatment. In the past years, immunotherapy has shown promising results and has been incorporated into the treatment armamentarium. The rates of recurrence and progression after locoregional therapies are significant, what highlights the need to explore systemic agents for preventing or delaying these negative outcomes. Recently, sorafenib was shown to benefit patients with unresectable HCC under transarterial chemoembolization (TACE) by delaying tumor progression and prolonging time to vascular invasion and extrahepatic spread. Although this result was reported in patients with intermediate stage, it provides background to test the strategy of combining systemic treatment plus TACE as a bridge therapy to HCC patients awaiting liver transplantation, for which the risk of dropout due to tumor progression impairs the possibility of cure.

Effect of prophylactic transcatheter arterial chemoembolization on hepatocellular carcinoma with microvascular invasion after R0 resection. A case-control study

ABSTRACT BACKGROUND: Transcatheter arterial chemoembolization (TACE) is thought to prevent recurrence of hepatocellular carcinoma (HCC), but its efficacy is a matter of controversy. OBJECTIVES: We investigated the effect of preventive TACE on the tumor, nodes, metastasis (TNM) classification in cases of stage II HCC (T2N0M0) after R0 resection. DESIGN AND SETTING: Case-control study conducted in a tertiary-level public hospital. METHODS: We analyzed recurrence rates and mortality rates over time for 250 consecutive cases of HCC in TNM classification cases of stage II HCC (T2N0M0) after R0 resection. These cases were divided into patients who underwent TACE (TACE+) and presented microvascular invasion (MVI+; n = 80); TACE+ but did not present MVI (MIV−; n = 100); MVI+ but did not undergo TACE (TACE−, n = 30); and TACE−/MVI− (n = 40). RESULTS: MVI+ patients in the TACE+ group had significantly lower recurrence rates and mortality rates at one, two and three years than those in the TACE- group (all P < 0.05). Among MVI- patients, the TACE+ group did not have significantly lower recurrence rates and mortality rates at one, two and three years than the TACE- group (all P > 0.05). Regardless of whether TACE was performed or not, MVI− patients had significantly lower recurrence rates and mortality rates at two and three years after their procedures than did MVI+ patients (all P < 0.05). CONCLUSION: Recurrence rates and mortality rates for MVI+ patients were significantly higher than for MVI− patients, beyond the first year after TACE. Postoperative adjuvant TACE may be beneficial for HCC patients with MVI.

25-OH-vitamin D deficiency identifies poor tumor response in hepatocellular carcinoma treated with transarterial chemoembolization.

PURPOSE: Vitamin D is implicated linked to liver cancer and chronic liver diseases, but its association with tumor response in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE) remains unclear. This study aimed to determine whether vitamin D levels influence tumor response in HCC patients treated with TACE. METHODS: A total of 58 HCC patients undergoing TACE were enrolled in the study. Serum 25-hydroxyvitamin D (25-OHD) levels were determined at baseline and 1 day after TACE using electrochemiluminescence immunoassay. Response to TACE was evaluated after a 4-6 week interval. Univariate and multivariate analyses with Cox regression model were performed to determine the risk factors associated with tumor response. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of baseline 25-OHD levels on tumor response in HCC patients undergoing TACE. RESULTS: 43.1% of HCC patients showed 25-OHD deficiency. Baseline 25-OHD level was associated with liver cirrhosis (P = 0.025), vascular invasion (P = 0.031), Barcelona Clinic Liver Cancer stage (P = 0.002) and an alanine aminotransferase increase after TACE (P = 0.021). Serum 25-OHD level was significantly decreased 1 day after TACE (P = 0.045). Multiple tumor numbers (P = 0.034) and low baseline 25-OHD levels (P = 0.040) were independently correlated with poor tumor response after TACE. ROC curve analysis showed that baseline 25-OHD levels present better predictive performance for OR in those patients, compared with other current clinical test pointers. CONCLUSION: Our study suggested that 25-OHD deficiency at baseline is a prognostic indicator for a poor tumor response in hepatocellular carcinoma treated with TACE.

Transarterial radioembolization for liver tumors as neoadjuvant therapy: three case reports / Radioembolização transarterial hepática como terapia neoadjuvante: relato de três casos

ABSTRACT Transarterial radioembolization (TARE) with yttrium-90 microspheres is a palliative locoregional treatment, minimally invasive for liver tumors. The neoadjuvant aim of this treatment is still controversial, however, selected cases with lesions initially considered unresectable have been enframed as candidates for curative therapy after hepatic transarterial radioembolization. We report three cases in which the hepatic transarterial radioembolization was used as neoadjuvant therapy in an effective way, allowing posterior potentially curative therapies.

RESUMO A radioembolização transarterial hepática com microesferas de ítrio-90 é uma modalidade paliativa de tratamento locorregional minimamente invasiva. O objetivo neoadjuvante deste tratamento ainda é controverso, mas casos selecionados de lesões consideradas inicialmente irressecáveis reenquadram-se como candidatos à terapia curativa após a radioembolização transarterial hepática. Relatamos três casos em que a radioembolização transarterial hepática foi utilizada como terapia neoadjuvante de forma efetiva possibilitando aplicação posterior de terapias potencialmente curativas.