Combined transarterial chemoembolization and tislelizumab for patients with unresectable hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)often presents as unresectable,necessitating effective treatment modalities.Combining transarterial chemoembolization(TACE)with immunotherapy and targeted therapy has shown promise,yet real-world evidence is needed.AIM To investigate effectiveness and safety of TACE with tislelizumab±targeted therapy for unresectable HCC in real-world setting.METHODS This retrospective study included patients with unresectable HCC receiving combined treatment of TACE and tislelizumab.The clinical outcomes included progression-free survival(PFS),overall survival(OS),objective response rate(ORR),and disease control rate(DCR).All patients were evaluated according to the mRECIST criteria.The adverse event(AE)was also assessed.RESULTS In this study of 56 patients with median follow-up of 10.9 months,7 had previous immunotherapy.Tislelizumab was administered before TACE in 21(37.50%)and after in 35(62.50%)patients,with 91.07%receiving concurrent targeted therapy.Median PFS was 14.0(95%CI:7.0-18.00)months,and OS was 28(95%CI:2.94-53.05)months.Patients with prior immunotherapy had shorter PFS(6 vs.18 months,P=0.006).Overall ORR and DCR were 82.14%and 87.50%.Grade≥3 treatment-related AEs included increased alanine aminotransferase(8.93%),aspartate aminotransferase(10.71%),and total bilirubin(3.57%).CONCLUSION The combination of TACE and tislelizumab,with or without targeted therapy,demonstrated promising efficacy and safety in unresectable HCC,especially in immunotherapy-naive patients,warranting further prospective validation studies.

Tumor lysis syndrome after transarterial chemoembolization of hepatocellular carcinoma: Case reports and literature review

Tumor lysis syndrome (TLS) is a potentially lethal complication in cancer therapy. It may occur in highly sensitive tumors, especially in childhood cancer and leukemia, whereas, it is rare in the treatment of solid tumors in adults. TLS results from a sudden and rapid release of nuclear and cytoplasmic degradation products of malignant cells. The release of these can lead to severe alterations in the metabolic prof ile. Here, we present two cases of large hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) that resulted in TLS. Although TLS rarely happens in the treatment of adult hepatic tumor, only a few cases have been reported. We should keep in mind that all patients with HCC, particularly those with large and rapidly growing tumors, must be closely watched for evidence of TLS after TACE.

Influence of preoperative transcatheter arterial chemoembolization on liver resection in patients with resectable hepatocellular carcinoma

Objective: To assess the influence of preoperative transcatheter arterial chemoembolization (TACE) on liver resection in patients with resectable hepato- cellular carcinoma (HCC). Methods: Of 126 patients with resectable HCC, 62 received preoperative TACE (TACE group) and the remaining 64 patients were selected as controls (non- TACE group). Perioperative risk factors including liver function alteration, mean blood loss during op- eration, mean time of clamping the porta hepatis, length of operation, postoperative abdominal drain- age at day 1, 2 and 3, morbidity and mortality were compared between the two groups. Results: Neither significant difference in liver func- tion alteration nor mortality was observed between the two groups. More severe hepatic cirrhosis, lon- ger operation time, more blood loss and postopera- tive abdominal drainage were noted in the TACE group than in the non-TACE group. There was no significant difference in postoperative morbidity be- tween the two groups. Conclusions: Preoperative TACE for resectable HCC increases surgical difficulty and risk, and therefore should be considered prudently according to the indi- viduality of patients.

Molecular targeting agents associated with transarterial chemoembolization or radiofrequency ablation in hepatocarcinoma treatment

Hepatocellular carcinoma(HCC)is the fifth most common cause of cancer in the world.According to Barcelona Clinic Liver Cancer modified criteria,patients with early stage disease are candidate to radiofrequency ablation(RFA),while patients with intermediate stage HCC are usually treated by transarterial chemoembolization(TACE).TACE and RFA induce a transient devascularisation effect followed by strong neoangiogenic stimulus.In fact,after these procedures,it has been demonstrated an up-regulation of pro-angiogenic and growth factors such as vascular endothelial growth factor-A,which might contribute to accelerated progression in patients with incomplete response.Several studies have demonstrated that MAP-kinase and AKT pathways,in addition to neo-angiogenesis,have an important role in the development of HCC.In advanced HCC,anti-angiogenic therapy and tyrosine kinases inhibitors showed potential clinical benefit.Actually,a number of clinical studies are ongoing testing these agents in combination with TACE or RFA.In this paper,we have reviewed the most recent preclinical and clinical results of such trials.

Study on the Changes in Microvessel Density in Hepatocellular Carcinoma Following Transcatheter Arterial Chemoembolization

To study the changes in intratumoral microvessel density (MVD) in hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE), MVD in 42 HCC specimens histologically verified was studied by using immunohistochemical method. Of all the specimens, 20 were obtained from the patients treated with surgical resection alone, 22 from those with second stage surgical resection after TACE. The results showed that the MVD in HCC tissues was 53.4±21 9 in the TACE group and 27.6±9.2 in the single operating group, respectively, with the difference being significant between them ( P <0.001). It was suggested that TACE might contribute to angiogenesis of HCC, possibly due to anoxic stress and ischemia reperfusion injury.

Arterial chemoembolization for hepatocellular carcinoma

IM To study the therapeutic effects of transcatheter arterial threesegment chemoembolization for hepatocellular carcinoma (HCC).METHODS According to the anatomy of vessels, the tumor capillary networks, muscular arterioles and feeding arteries were successively occluded using lipiodol ultrafluid (LUF), sinobufagin microsphere (SBMs) and particles of gelatin sponge (PGS). In this series of 80 cases, therapeutic effects were evaluated in 76 cases.RESULTS There were 22 cases (289%) with partial response and 41 (539%) with minor response in the 76 evaluated patients. The 6month, 1year, 2year and 3year survival rates were 974%, 868%, 461% and 276% respectively.CONCLUSION This regimen was a rational chemoembolization method for HCC patients.

Recent trends in the treatment of well-differentiated endocrine carcinoma of the small bowel

Well-differentiated endocrine carcinomas of the small bowel are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that may cause carcinoid syndrome. However, many are clinically silent until late presentation with major effects. Initial treatment aims to control carcinoid syndrome with somatostatin analogs. Even if there is metastatic spread, surgical resection of the primitive tumor should be discussed in cases of retractile mesenteritis, small bowel ischemia or subocclusive syndrome in order to avoid any acute complication, in particular at the beginning of somatostatin analog treatment. The choice of treatment depends on the symptoms, general health of the patient, tumor burden, degree of uptake of radionuclide, histological features of the tumor, and tumor growth. Management strategies include surgery for cure (which is rarely achieved) or for cytoreduction, radiological interventions (transarterial embolization or radiofrequency ablation), and chemotherapy (interferon and somatostatin analogs). New biological agent and radionuclide targeted therapies are under investigation. Diffuse and non-evolving lesions should also be simplymonitored. Finally, it has to be emphasized that it is of the utmost importance to enroll these patients with a rare disease in prospective clinical trials assessing new therapeutic strategies.

Multimodality treatment in hepatocellular carcinoma patients with tumor thrombi in portal vein

AIM: To compare the therapeutic effect and significances of multimodality treatment for hepatocellular carcinoma (HCC) with tumor thrombi in portal vein (PVTT). METHODS: HCC patients (n=147) with tumor thrombi in the main portal vein or the first branch of portal vein were divided into four groups by the several therapeutic methods. There were conservative treatment group in 18 out of patients (group A); and hepatic artery ligation(HAL) and/or hepatic artery infusion (HAI) group in 18 patients (group B), in whom postoperative chemoembolization was done periodically; group of removal of HCC with PVTT in 79 (group C) and group of transcatheter hepatic arterial chemoembolization (TACE) or HAI and/or portal vein infusion (PVI) after operation in 32 (group D). RESULTS: The median survival period was 12 months in our series and the 1-,3-, and 5-year survival rates were 44.3%, 24.5% and 15.2%, respectively. The median survival times were 2, 5, 12 and 16 months in group A, B, C and D, respectively. The 1-, 3- and 5-year survival rates were 5.6%, 0% and 0% in group A; 22.2%, 5.6% and 0% in group B; 53.9%, 26.9% and 16.6% in group C; 79.3%, 38.9% and 26.8% in group D, respectively. Significant difference appeared in the survival rates among the groups (P 【 0.05). CONCLUSION: Hepatic resection with removal of tumor thrombi and HCC should increase the curative effects and be encouraged for the prolongation of life span and quality of life for HCC patients with PVTT, whereas the best therapeutic method for HCC with PVTT is with regional hepatic chemotherapy or chemoembolization after hepatic resection with removal of tumor thrombi.

Radiofrequency ablation combined with transarterial chemoembolization for unresectable primary liver cancer

Background Radiofrequency ablation （RFA） followed by transarterial chemoembolization （TACE） for unresectable primary liver cancer （PLC） has not been widely discussed. In this study, the outcome of the combination of RFA with TACE was retrospectively evaluated. Methods From May 2003 to March 2008, 127 consecutive PLC patients with a median age of 56.4＋8.8 years underwent RFA plus TACE. All patients were deemed to have unresectable PLC based on their tumor characteristics. The maximal diameter of the tumor was between 1.5 cm and 10.0 cm. Twenty-six cases with small （〈3.0 cm）, 33 with medium （3.1-5.0 cm）, and 68 with large （〉5.0 cm） tumors were included in this study. RFA was performed using a RITA Medical Systems expandable electrode device, which was followed by first-time TACE administration one to two months later. Results Technical success of RFA was achieved in all 127 patients with no severe treatment-related complications. RFA was performed percutaneously in 16 （13.5%） cases, by laparoscopic approach in 19 （15.7%）, and through laparotomy in the remaining 92 （72.4%）. RFA response was classified as complete ablation in 48 cases, nearly complete ablation in 28, and partial ablation in 51. The total 1-, 2-, and 3-year survival rates after RFA were 83.1%, 55.7%, and 43.7%, respectively. The survival rates at 3 years were 78.6%, 28.1%, and 0 for complete ablation, nearly complete ablation, or partial ablation groups, respectively. Three-year disease-free survival rates for the complete ablation and nearly complete ablation groups were 50.3% and 21.3%, respectively. RFA response and liver function were significant variables influencing survival time as analyzed using the Cox regression model. Conclusion RFA could be the first-line exterminate treatment for unresectable PLC, and TACE following RFA may assist in eradicatinq the peripheral viable tissue and micro-metastasis.

A Case Series of Liver Abscess Formation after Transcatheter Arterial Chemoembolization for Hepatic Tumors

Background： Liver abscess is a serious complication following transcatheter arterial chemoembolization （TACE）. Much attention has been paid to this condition as it may interfere with the treatment process and result in a poor prognosis of the patient. This study aimed to analyze the causes of liver abscess, a complication, after TACE for hepatic tumors and to summarize management approaches. Methods： From June 2012 to June 2014, of 1480 consecutive patients who underwent TACE at our hospital, five patients developed liver abscess alier TACE procedures for hepatic tumors. Of the five patients, each receiving conventional TACE, one underwent three sessions, two underwent two sessions, and the remaining two underwent one session of TACE. Demographic and clinical characteristics, together with management approaches and prognosis, were collected through a review of medical records. Results： These five patients were confirmed to have post-TACE liver abscess through clinical manifestations, laboratory, and imaging tests. Aiier percutaneous drainage and anti-inflammatory treatments, the symptoms present in four patients with liver abscess significantly improved as evidenced by shrinkage or disappearance of the abscess cavity, and the patients recovered completely after sufficient drainage. The remaining patient experienced recurrent symptoms and abdominal abscess, achieved no significant improvement after treatment, and eventually died of severe infection and multiple organ failures. Conclusions： TACE must be implemented with extreme caution to avoid liver abscess. An effective management relies on an early diagnosis, prompt use of sufficient doses of appropriate antibiotics, and active implementation of abscess incision, drainage, and aspiration.

Comparative efficacy and safety of Chinese herbal injections combined with transcatheter hepatic arterial chemoembolization in treatment of liver cancer: a bayesian network Meta-analysis

OBJECTIVE: To address the optimal Chinese herbal injections(CHIs) against liver cancer, the present network Meta-analysis is designed to investigate the comparative efficacy and safety of different CHIs.METHODS: Several electronic databases were searched up to June 1 st, 2017. The quality assessment was conducted and network Meta-analysis was performed to compare the efficacy and safety of different CHIs plus transcatheter hepatic arterial chemoembolization(TACE). Primary outcomes were 1-year and 2-year survival rate, the secondary outcomes includes the clinical effective rate, performance status and the adverse reactions(ADRs). Data analysis was applied Stata 13.0 and Win BUGS 1.4 software.RESULTS: A total of 105 randomized controlled trials(RCTs) were identified for inclusion in this analysis, with data for 7683 patients and 13 CHIs. The results suggested that Javanica oil emulsion,Huachansu injection plus TACE were more favorable for 1-year and 2-year survival rate than other CHIs. Kanglaite, Astragalus polysaccharide injection plus TACE showed superiority in the clinical effective rate and performance status over other CHIs.And Shenmai injection plus TACE was superior to reducing ADRs than other CHIs for patients with liver cancer.CONCLUSION: Our findings indicated that receiving CHIs combined with TACE may have therapeutic benefits for patients with liver cancer in improving survival rate, clinical effective rate, the performance status and alleviating the ADRs.

Delayed cerebral lipiodol embolism after transcatheter arterial chemoembolization of hepatocellular carcinoma

Transcatheter arterial chemoembolization （TACE） has been an effective mean in treating hepatocellular carcinoma for nearly 30 years. The reported complications associated with TACE mainly include acute hepatic failure （accounting for 0.26%）, liver abscess （0.22%）, multiple intrahepatic aneurysms （0.17%）, hepatic artery occlusion （1.52%）, spontaneous rupture of tumor （0.15%）, gallbladder infarction （0.3%）, perforation of duodenum （0.05%）, acute renal failure （0.05%）,

Prognostic analysis of transarterial chemoembolization combined with a traditional Chinese herbal medicine formula for treatment of unresectable hepatocellular carcinoma

Background Transarterial chemoembolization （TACE） is the most widely used primary treatment for unresectable hepatocellular carcinoma （HCC） due to its survival benefit, though its clinical effect is still far from satisfactory. Jiedufang （JDF） granule preparation is a commonly used Chinese herbal medicine formula for HCC. The aim of this study was to evaluate the effect of combined therapy with TACE and JDF granule preparation in treatment of unresectable HCC on survival. Methods A retrospective study of TACE was performed in 165 patients with unresectable HCC who were admitted between January 2002 and December 2007 in Changhai Hospital, Shanghai, China. Of the 165 patients, 80 patients （study group） received combined therapy consisting of TACE and a long-term maintenance treatment with oral JDF granule preparation, and the remaining 85 patients （control group） received TACE alone. The survival rates of both groups were calculated by the Kaplan-Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model, such as maximum tumor size, number of lesions, portal vein invasion, and etc. Results The median overall survival was 9.2 months （95% CI： 6.94-11.46） in the study group versus 5.87 months （95% CI： 4.21-7.52） in the control group. In the study group,survival rates of the 1-, 2- and 3-year follow-up were 41.2%, 18.4%, and 9.6%, respectively. Significant independent prognostic factors identified by the Cox regression analysis were as follows： serum hepatitis B surface antigen （HBsAg） （P=0.014）, maximum tumor size （P=0.027）, number of lesions （P 〈0.001）, portal vein invasion （P 〈0.001）, and the therapy model （P=-0.006）. Conclusion Combination therapy of TACE and JDF granule preparation may significantly prolong survival of patients with unresectable HCC.

Effect of decoction of Fuzheng Jiedu Xiaoji formula(扶正解毒消积方) plus chemoembolization on primary liver cancer in patients

OBJECTIVE:To investigate the effect of the decoction of Fuzheng Jiedu Xiaoji formula(扶正解毒消积方,FJXF)plus chemoembolization(TACE)on primary liver cancer(PLC)in patients,and study the underlying mechanism.METHODS:Patients with PLC who met the inclusion criteria were randomized into case group and control group.The case group was treated with FJXF combined with TACE.The control group was treated with TACE alone.The short-term clinical effect was evaluated;liver biochemistry,liver function index and multidrug resistance-associated indicators were detected.RESULTS:FJXF combined with TACE in the case group significantly increased the disease control rate than TACE alone in the control group(83.3%vs 61.1%).There was a reduction in the serum alpha-fetoprotein at 8 weeks after treatment in each group,while no difference between the two groups.The same trend can be observed for transaminase and direct bilirubin in both groups.In the case group,it showed a significant increase for albumin at 8 weeks after treatment,while no change in the control group.Multidrug resistanceassociated indicators for multidrug resistance protein 1 and p-glycoprotein were upregulated in the case group but remained stable in the control group.CONCLUSIONS:FJXF combined TACE had a better short-term effect than TACE alone in patients with PLC.The potential mechanism was probably associated with alleviated multidrug resistance induced by FJXF.Additionally,FJXF didn’t increase the risk of liver damage in the combined therapy.

Global similarities: comparison of the Korean Liver Cancer Association chemoembolization guidelines for hepatocellular carcinoma to the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and Barcelona Clinic Liver Cancer recommendations

Hepatocellular carcinoma(HCC)remains the third most common cause of cancer-related deaths worldwide(1).Transarterial chemoembolization(TACE)has been established as a therapeutic option in those patients who are outside of surgical resection or transplant criteria for over four decades(2).Multiple expert panels have outlined the appropriate use criteria and recommendations for HCC treatment(3-5).These documents have focused on multiple treatment modalities including interventional radiology intra-arterial and ablative treatments as well as resection,transplant and systemic therapy.In their recently published practice recommendations for the use of TACE in HCC patients,the Korean Liver Cancer Association(KLCA)has developed a comprehensive list of recommendations for this specific modality(6).The recommendations are a combination of evidence-based,expert consensus decisions and surveys of Korean experts in TACE for HCC.Comparing and contrasting this focused guideline on TACE to the recent HCC guidelines from the National Comprehensive Cancer Network(NCCN),American Association for the Study of Liver Diseases(AASLD)and Barcelona Clinic Liver Cancer(BCLC)is valuable to understand where methods are truly global and also to understand differences in treatment approach by region.