Transcatheter Hepatic Arterial Chemoembolization Research Articles

Retraction Note to: Circ-DENND4C up-regulates TCF4 expression to modulate hepatocellular carcinoma cell proliferation and apoptosis via activating Wnt/\u03b2-catenin signal pathway

Hepatocellular carcinoma (HCC) is a common malignant tumor in China. Advanced treatment like transcatheter hepatic arterial chemoembolization (TACE) has prolonged the lives of many HCC patients. However, the prognosis of most HCC patients remains unsatisfactory. Recently, circular RNAs (circRNAs) have been gradually unveiled to exert considerable functions in cancer. Promising circRNAs in HCC remains to be further elucidated. Gene expression was assessed by qRT-PCR and western blot. The function of circ-DENND4C in HCC was estimated by both in vitro and in vivo experiments. The location of circ-DENND4C in HCC cells was determined by subcellular fractionation and FISH assays. The association among molecules were analyzed through RNA pull down, RIP and luciferase reporter assays. circ-DENND4C (DENN domain containing 4C), an oncogene identified in breast cancer, was overexpressed in HCC cells. Also, circ-DENND4C exerted pro-tumor functions in HCC through activating Wnt/β-catenin pathway. Importantly, circ-DENND4C could augment transcription factor 4 (TCF4) expression to activate Wnt/β-catenin signaling via sequestering miR-195-5p. Moreover, following rescue assays disclosed that circ-DENND4C mediated malignant phenotypes in HCC cells via up-regulating TCF4 through sponging miR-195-5p. circ-DENND4C boosted TCF4 expression to modulate malignant behaviors of HCC cells via activating Wnt/β-catenin pathway, which might offer a promising target for HCC treatment.

Transcatheter hepatic arterial chemoembolization in cirrhotic patients with hepatocellular carcinoma before liver transplantation: the prognostic value of alpha-fetoprotein concentrations

Objective : to study liver transplantation (LT) outcomes in cirrhotic patients with hepatocellular carcinoma (HCC), who underwent transcatheter hepatic arterial chemoembolization (THACE). Materials and methods. From January 1998 to April 2020, we performed 245 orthotopic liver transplantation (OLTs) in 229 patients of which 25 (10.2%) had HCC in cirrhosis. In 9 (36%) patients, LT was performed without neoadjuvant therapy (Group 1). Group 2 consisted of 16 (66%) patients who underwent 49 THACE cycles before LT. 10 (62.5%) patients fell within the Milan criteria, while 6 (37.5%) were outside. According to the BCLC (Barcelona Clinic Liver Cancer) classification, 10 patients had A 1 –A 4 stage, while 6 were in B stage. In 11 (68.5%) of 16 patients, increased serum alpha-fetoprotein (AFP) concentrations from 20 to 2463 (on average 493.8) ng/mL was revealed before treatment. In performing THACE, both the classical method (with lipiodol and hemostatic sponge) and the method with drug-eluting beads were performed 1 to 7 (on average 3) times. Doxorubicin was used in all cases. Results . Group 2 recorded a 100% technical success. There were no complications. We performed radiofrequency ablation (RFA) in three patients as an adjunct. In two patients, we performed laparoscopic RFA-assisted atypical liver resection, and in one – sequential resection and RFA. Under the m-Recist criteria, complete response was observed in 6 (37.5%), partial response in 7 (43.75%), and stabilization in 3 (18.75%) patients. Change in AFP concentrations were as follows: in 5 out of 11 patients with increased concentrations, we were able to reduce their AFP concentrations to the reference values, their long-term outcomes are comparable to those of Group 1. Four patients showed a 13–84% decrease; a directly proportional relationship between the degree of AFP decrease and the time to tumor progression was revealed. In 2 patients, there were 42% and 320% increase in AFP concentrations, the time to tumor progression was 3 and 1 month, both did not live up to 12 months. Among 9 (56%) of the living 16 patients, a maximum of 156 months and a minimum of 4 months (60.2 average) have elapsed since the surgery. Two of these nine have tumor progression (cases 4 and 14). Seven (44%) patients died within 9 to 54 months. The 1, 3, 5-year actuarial survival rates were 93, 50, 32%, two patients lived more than 10 years. The average life expectancy was 28.0 ± 3.0 months. Conclusion . Serum AFP concentration is an important prognostic factor influencing the long-term outcomes of LT. Good biological response to THACE can be a positive predictor; LT outcomes in these patients are comparable to those in patients who meet the Milan criteria. A decrease in AFP concentrations by less than 50% after neoadjuvant THACE is an unfavorable factor, and its increase is extremely adverse.

Continuous elevation of procalcitonin in cirrhosis combined with hepatic carcinoma: a case report

BackgroundSerum levels of procalcitonin (PCT) are considered a useful biomarker for the diagnosis of bacterial infection or inflammation. There are few reports of high PCT levels in end-stage liver disease regardless of bacterial infection. Here, we present a case of extremely high PCT levels (> 100 ng/mL) in a patient with severe cirrhosis combined with hepatic carcinoma.Case presentationA 65-year-old man developed end-stage cirrhosis with hepatic carcinoma. Radiographic imaging showed a massive hepatocellular carcinoma with multiple loci lack of indications of resection. Hence, transcatheter hepatic arterial chemoembolization was performed three times over a period of 4 months. Before and after interventional therapies, the biochemistry laboratory results were only slightly abnormal except for persistently high PCT concentrations (> 100 ng/mL), irrespective of the evidence for bacterial infection or sepsis.ConclusionsThis case suggests that continuously high levels of PCT (> 100 ng/mL) may be present in advanced liver disease, particularly in complex situations such as decompensated cirrhosis and liver cancer, in the absence of severe infection or sepsis. This knowledge could expand the significance of PCT in liver disease.

Transcatheter hepatic arterial chemoembolization combined with Kangai injection for hepatitis B virus-related hepatocellular carcinoma: A protocol for a PRISMA-compliant meta-analysis.

Kangai injection, a well-known insect-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy and safety of Kangai injection for patients with HBV-related HCC through the meta-analysis. All available randomized controlled trials (RCTs) and high-quality prospective cohort studies that investigated the efficacy and safety of Kangai injection for patients with HBV-related HCC were searched from ten electronic databases including Google Scholar, PubMed, Excerpt Medica Database (Embase), Cochrane Library, Medline, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (CSJ) Chinese, Biomedical Literature Database (CBM) and Wanfang Database. Papers in Chinese or English published from January 2000 to September 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 researchers. The clinical outcomes including overall response rate (ORR), disease control rate (DCR), quality of life (QoL), clinical symptoms, virological indicators, immune function and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the literatures was also evaluated. The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HBV-related HCC patients. Our study will draw an objective conclusion of the efficacy of Kangai injection on curative effect (ORR and DCR), clinical symptoms, virological indicators, QoL, and immune function in patients with HBV-related HCC. INPLASY202090014.

Elevated procalcitonin levels in primary hepatic neuroendocrine carcinoma

Rationale:Procalcitonin (PCT) has been identified as a tumor biomarker in medullary thyroid carcinoma. Other neuroendocrine carcinomas with elevated PCT levels are relatively rare, and are mainly reported in the lung, digestive tract, and pancreas. No studies in the literature have reported a case of primary hepatic carcinoma complicated with unexpectedly elevated PCT levels.Patient concerns:A 78-year-old man with persistent fatigue and mild fever was complicated with an extremely high PCT level. Radiological examination revealed a single hypodense lesion in the left lobe of the liver with a “rapid enhancement and rapid washout” pattern. Pathological analysis showed a poorly differentiated neuroendocrine carcinoma (grade 3) with multiple genetic mutations.Diagnosis:Primary hepatic neuroendocrine carcinoma.Interventions:The patient received antibiotic therapy and subsequent transcatheter hepatic arterial chemoembolization; a PCT assessment and computed tomography were performed during the follow-up.Outcomes:The PCT level did not decline after antibiotic therapy but greatly declined in response to effective transcatheter hepatic arterial chemoembolization. The patient survived and is still being followed up.Lessons:An extremely elevated PCT level may raise a suspicion of a neuroendocrine carcinoma and plays an indicative role as a biomarker during therapy.

RETRACTED ARTICLE: Circ-DENND4C up-regulates TCF4 expression to modulate hepatocellular carcinoma cell proliferation and apoptosis via activating Wnt/\u03b2-catenin signal pathway

BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor in China. Advanced treatment like transcatheter hepatic arterial chemoembolization (TACE) has prolonged the lives of many HCC patients. However, the prognosis of most HCC patients remains unsatisfactory. Recently, circular RNAs (circRNAs) have been gradually unveiled to exert considerable functions in cancer. Promising circRNAs in HCC remains to be further elucidated.MethodsGene expression was assessed by qRT-PCR and western blot. The function of circ-DENND4C in HCC was estimated by both in vitro and in vivo experiments. The location of circ-DENND4C in HCC cells was determined by subcellular fractionation and FISH assays. The association among molecules were analyzed through RNA pull down, RIP and luciferase reporter assays.Resultscirc-DENND4C (DENN domain containing 4C), an oncogene identified in breast cancer, was overexpressed in HCC cells. Also, circ-DENND4C exerted pro-tumor functions in HCC through activating Wnt/β-catenin pathway. Importantly, circ-DENND4C could augment transcription factor 4 (TCF4) expression to activate Wnt/β-catenin signaling via sequestering miR-195-5p. Moreover, following rescue assays disclosed that circ-DENND4C mediated malignant phenotypes in HCC cells via up-regulating TCF4 through sponging miR-195-5p.Conclusioncirc-DENND4C boosted TCF4 expression to modulate malignant behaviors of HCC cells via activating Wnt/β-catenin pathway, which might offer a promising target for HCC treatment.

Prognosis for intrahepatic cholangiocarcinoma patients treated with postoperative adjuvant transcatheter hepatic artery chemoembolization

Objective: We used meta-analysis to evaluate the efficacy of transcatheter hepatic arterial chemoembolization (TACE) for the treatment of intrahepatic cholangiocarcinoma (ICC). Methods: We performed the meta-analysis using the R 3.12 software and the quality evaluation of data using the Newcastle-Ottawa Scale. The main outcomes were recorded as 1-year overall survival (OS), 3-year OS, 5-year OS, and hazard ratio (HR) of TACE treatment or non-TACE treatment. The heterogeneity test was performed using the Q-test based on chi-square and I2 statistics. Egger's test was used to test the publication bias. The odds ratio or HR and 95% confidence interval (CI) were used to represent the effect index. Results: Nine controlled clinical trials involving 1724 participants were included in this study; patients came mainly from China, Italy, South Korea, and Germany. In the OS meta-analysis, the 1-year and 3-year OS showed significant heterogeneity, but not the 5-year OS. TACE increased the 1-year OS (odds ratio = 2.66, 95% CI: 1.10-6.46) of the patients with ICC, but the 3- and 5-year OS rates were not significantly increased. The results had no publication bias, but the stability was weak. The HR had significant heterogeneity (I2 = 0%, P= 0.54). TACE significantly decreased the HR of ICC patients (HR = 0.59, 95% CI: 0.48-0.73). The results had no publication bias, and the stability was good. Conclusions: Treatment with TACE is effective for patients with ICC. Regular updating and further research and analysis still need to be carried out.

The blooming intersection of transcatheter hepatic artery chemoembolization and nanomedicine

Transcatheter hepatic artery chemoembolization (TACE) is a universal treatment for patients with hepatocellular carcinoma (HCC) that inhibits tumor growth by cutting off the blood supply and provides chemotherapeutics locally to the tumor. The strategy of combining TACE formulation with image-guided ablation holds tremendous potential, but patient tolerance and undesired toxicity/immunosuppression remains a challenge. The application of nanotechnology in TACE opens new doors for the treatment of HCC. Strikingly, nanomaterials or nano-drugs dispersed in the TACE formulation can effectively improve the delivery efficiency of drugs by achieving both controlled and continuous release. In addition, the utilization of multifunctional nanoparticles can provide guidance and monitoring for various advanced imaging methods for TACE treatment, and can realize the combination therapy of thermal ablation, microwave ablation, in situ radiotherapy, and other therapies, greatly expanding the therapeutic strategies available for HCC treatment. Here, the current exploration of nanotechnology in TACE of HCC is briefly summarized and the challenges of TACE with nanoformulations for clinical translation are comprehensively discussed.

Chemotherapy for breast cancer progresses to liver metastases after surgery and systemic treatment.

BackgroundThis study aims to evaluate the effectiveness of hepatic arterial infusion chemotherapy/portal vein infusion chemotherapy (HAIC/PVIC), transcatheter hepatic arterial chemoembolization (TACE) and transcatheter arterial embolization (TAE) for unresectable breast cancer liver metastases (UBCLM).MethodsThe present study included 57 patients. These patients were randomly divided into three groups (n=19, each): HAIC/PVIC group, TACE group and TAE group. Patients in the HAIC/PVIC group were treated with the same systemic chemotherapy regimen previously received by infusion through an intra-arterial and portal vein catheter. Patients in the TACE group received cyclophosphamide, epirubicin and 5-fluorouracil, and embolization. Patients in the TAE group were only treated with embolization.ResultsThe median number of treatments was 6 (range, 3–13) in the HAIC/PVIC group, 5 (range, 4–9) in the TACE group, and 6 (range, 4–8) in the TAE group. The 1-, 2- and 3-year survival rates for these groups were 18/19 (94.7%), 14/19 (73.7%) and 11/19 (57.9%), 14/19 (73.7%), 9/19 (47.4%) and 8/19 (42.1%), and 8/19 (42.1%), 4/19 (21.1%) and 0/19 (0%), respectively. The median overall survival from the original breast cancer diagnosis was 88 (range, 11–133), 75 (range, 9–115), and 49 (range, 10–64) months in the HAIC/PVIC, TACE and TAE groups, respectively. Grade I–II and grade III–IV bone marrow suppression was observed in 12/19 (63.2%) and 3/19 (15.8%) patients in the HAIC/PVIC group, respectively, in 17/19 (89.5%) and 5/19 (26.3%) patients in the TACE group, respectively, and in 0/19 (0%) and 0/19 (0%) patients in the TAE group, respectively.ConclusionsHAIC/PVIC with the same regional chemotherapy regimen of the original systemic treatment is feasible, and can benefit patients with UBCLM, who have progressed on prior systemic therapies.

Clinical characteristics and prognostic factors of primary hepatic neuroendocrine tumor: a study of 21 patients

Objective To analyze the clinical characteristics, diagnosis, treatment and prognostic factors of primary hepatic neuroendocrine tumor (PHNET). Methods To analyze the clinical data of 21 patients with PHNET who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2012 to January 2019. There were 11 males and 10 females, with ages which ranged from 36 to 75 years. Log-rank test was used for single-factor analysis of the relationship between clinical and pathological indicators and prognosis. Cox proportional risk model was used for multi-factor analysis. Results Among the 21 PHNET patients, 10 presented with central and upper abdominal pain, 3 abdominal pain accompanied by nausea and vomiting, 5 abdominal distension, and 3 were asymptomatic. Carbohydrate antigen (CA) 19-9 was elevated in 6 patients and CA125 in 7 patients. Abdominal enhanced CT showed solid liver space occupying lesions. Four patients had solitary and 17 had multiple lesions. The mean diameter was 58 mm. Fourteen patients had lymph node metastasis. Five patients underwent radical hepatectomy, 2 transcatheter hepatic arterial chemoembolization + chemotherapy, 12 chemotherapy, and 2 supportive treatment. Factors which were associated with prognosis of PHNET patients were surgery, tumor grading, cytokeratin positivity and lymph node metastasis. Multivariate Cox regression analysis showed that inoperability (HR=8.99, 95%CI: 1.13-71.80) was an independent risk factor of prognosis of PHNET patients. The prognosis in patients who underwent surgical resection was better. Conclusion Patients with PHNET had no specific clinical manifestations. Surgical resection gave the best results in treatment. As surgical resection affected prognosis, it should be carried out if technically feasible. Key words: Diagnosis; Primary liver neuroendocrine tumor; Clinical characteristics; Influencing factor

Safety and Short-term Efficacy of Licartin Combined with Conventional Transcatheter Hepatic Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma

To evaluate the safety and short-term efficacy of Licartin combined with conventional transcatheterheaptic arterial chemoembolization for patients with unresectable hepatocellular carcinoma, 13 patients with unresectable primary liver cancer treated with Licartin combined with conventional transcatheter arterial chemoembolization at the First Affiliated Hospital from January 2012 to December 2014, were retrospectively analyzed. Licartin was infused via hepatic artery at a dose of 27.75 MBq/kg prior to conventional transcatheter arterial chemoembolization (pirarubicin 20 mg and iodized oil), supplemented with poly vinyl alcohol particles. Here, the iodized oil is used as an embolic agent and carrier of anticancer drugs. After entering into the small arteries and peritumoral sinusoid of hepatocellular carcinoma through a catheter, the iodized oil gets retained there to block the terminal blood flow. According to mRECIST evaluation criteria, the remission and control rates after 1, 3, 6, and 9 mo were 69.3 and 100; 69.3 and 84.6; 61.5 and 76.9 and 60 % and 80 %, respectively. The survival rate was 100 % after 6 mo. The 1 y and 2 y survival rates estimated with Life Tables were 68 and 45 %, respectively. Liver and kidney function showed no significant difference pre- and posttreatment. No serious infections, jaundice, gastrointestinal bleeding or bone marrow suppression occurred. Licartin combined with conventional transcatheter arterial chemoembolization showed short-term efficacy and minimal side-effects in patients afflicted with unresectable primary liver cancer. Long-term follow-up involving large cohorts is needed to determine the long-term efficacy of the intervention.

The TACE’s role in the management of primary liver cancer

Objective: Identify the most effective and safe method of transcatheter hepatic artery chemoembolization (TACE) in patients with primary liver cancer. Methods: Overall, 139 patients, who underwent 558 TACE procedures were included in the study. Gender in the group of patients was distributed approximately equally and amounted to 72 men (52%) and 67 women (48%), the average age was 57.8 (9.9) years (range from 23 to 92 years). In most patients, the underlying disease for the development of hepatocellular carcinoma was cirrhosis of the liver in the outcome of hepatitis C or B. Characteristics of liver tumors were examined by magnetic resonance imaging or computed tomography and ultrasound. For verification of the diagnosis, a percutaneous liver biopsy was performed under ultrasound guidance, and the level of alpha-fetoprotein was also determined. All patients were considered unresectable due to cirrhosis and / or local spread of the tumor. Chemoembolization was performed by following scheme: one procedure in 2 months, not less than 3 procedures. Doxorubicin was used for chemotherapy. As a carrier of chemotherapy, Lipiodol (Guerbet, France) or saturable Hepaspheres (Merit Medical, USA) were used. Each patient received from 3 to 13 procedures. Results: Postembolization syndrome occurred in all cases, but was effectively treated. One patient died due to acute liver failure with the borderline stage of the disease according to the BCLC classification (EASL 2012) and the multinodular form of HCC. There were no serious complications in the treatment process. In two patients in the area of the puncture of the femoral artery, pseudoaneurysm was formed, which was eliminated by compression under ultrasound guidance. About 10% of patients developed subacute cholecystitis in the postoperative period and were associated with non-targeted chemoembolization in the cystic artery. In all patients, the symptoms of cholecystitis at the time of discharge were relieved conservatively. Survival median – 19 months. Dynamics of tumors was assessed by RECIST criteria. In the group of patients with hepatocellular carcinoma after first 3 TAСEs partial response and stabilization were observed in 83%, progression in 17%. In 18 cases (13%), histologically proved tumor necrosis after TAСE was achieved, without progression during follow-up. Three patients after reducing of tumor size was resected, 32 patients continue treatment. Conclusion: Transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma shows high efficacy, low mortality and the development of postoperative complications in patients with concomitant liver cirrhosis and locally advanced tumor lesion.

Liver Transplantation After Downstagings of Ruptured Advanced Hepatocellular Carcinoma in Cirrhotic Liver: Is It Advisable? A Case Report

Spontaneous rupture of hepatocellular carcinoma (HCC), defined as T4 in TNM stage by the American Joint Committee on Cancer (eighth edition), is a serious life-threatening complication. Effective treatment remains challenging because of a high 1-month mortality, a short median survival, and the potential of peritoneal metastasis. We reported on a case that received a living related donor liver transplantation (LDLT) after successful consecutive downstaging therapies. A 63-year-old man with alcohol-related liver cirrhosis and multiple HCC developed spontaneous rupture and hemoperitoneum. He received 3 sessions of transcatheter hepatic arterial chemoembolization and target therapy with sorafenib. Computed tomography scans and magnetic resonance imaging after 11 months of treatment showed that the patient's HCCs fulfilled the Milan criteria and the University of California San Francisco criteria prior to LDLT. The perioperative course was rather smooth. After discharge, interval follow-up computed tomography studies of chest and liver and a whole-body bone scan showed no tumor recurrence or metastasis up to 20 months post-operation. Successful downstaging therapies of ruptured HCC to fulfill Milan criteria to receive liver transplantation is advisable in highly selected patients.

Liver transplantation for advanced hepatocellular carcinoma combined with portal vein tumor thrombus

Summary: Background: The advanced hepatocellular carcinoma combined with portal vein tumor thrombus(PVTT)once has been the contraindications of liver transplantation which has been changed recently attribute to the development of vascular surgery. However, PVTT confining the entire portal vein and cavernomatous transformation of PV (CTPV) remains a challenge for liver transplantation. This video shows our experience with removal of PVTT and anastomosis of the portal vein in liver transplantation with PVTT. Methods: A 53-year-old female patient with hepatitis B cirrhosis, Transcatheter Hepatic Arterial Chemoembolization has applied four months ago and Radiotherapy was applied one month ago. The CT scan demonstrated portal vein tumor thrombus as well as an arteriovenous fistula. This patient was successfully treated with orthotopic modified piggyback liver transplantation. The distal PV was clamped and then the transection of PV was performed to remove the PVTT after the PV was exposed completely. After that, IVC was partly clamped and the outflow of the graft was reconstructed in a side to side anastomosis. Then, we reconstructed the portal vein by end-to-end anastomosis. The hepatic artery was reconstructed at last. Results: The patient stayed for 7 days in ICU. The immunosuppression used were methylprednisolone, Fk506, and CellCept. The patient recovered smoothly and 15-day discharge after the operation. She has tumor-free survived for two years and survived now. Conclusion: Despite advanced hepatocellular carcinoma combined with portal vein tumor thrombus is not the indication for liver transplantation, this therapy can also give these end-stage patients a flash of hope.

Transcatheter hepatic arterial chemoembolization plus cinobufotalin injection adjuvant therapy for advanced hepatocellular carcinoma: a meta-analysis of 27 trials involving 2,079 patients.

ObjectiveThe aim of this study was to systematically investigate the safety and efficacy of the combination of transcatheter hepatic arterial chemoembolization (TACE) and cinobufotalin injection for advanced hepatocellular carcinoma (HC).MethodsClinical trials were searched from Web of Science, Cochrane Library, PubMed, Embase, Chinese Medical Citation Index (CMCI), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wanfang database. Outcome measures including therapeutic efficacy, quality of life, liver function, immune function, and adverse events were extracted and evaluated.ResultsAfter final assessment, 27 studies including 2,079 advanced HC patients were involved in this study. Compared with TACE alone, the combination of TACE with cinobufotalin injection adjuvant therapy significantly prolonged the patients’ 1-, 1.5-, 2-, and 3-year overall survival (OS) rate (1-year OS, OR=2.84, 95% CI=2.20–3.67, P<0.00001; 1.5-year OS, OR=3.57, 95% CI=1.92–6.66, P<0.0001; 2-year OS, OR=3.17, 95% CI=2.36–4.25, P<0.00001; 3-year OS, OR=2.88, 95% CI=1.82–4.57, P<0.00001). The combined therapy also improved patients’ overall response rate (ORR; OR=1.86, 95% CI=1.54–2.24, P<0.00001), disease control rate (DCR; OR=2.05, 95% CI=1.59–2.64, P<0.00001), and quality of life improved rate (QIR; OR=3.45, 95% CI=2.52–4.72, P<0.00001). Moreover, the immune function and liver function of HC patients were all significantly enhanced after the combined therapy of TACE and cinobufotalin injection (CD3+, P=0.001; CD4+, P=0.0006; CD4+/CD8+, P=0.03; natural killer [NK] cell, P=0.01; total bilirubin [TBIL], P=0.003; alanine aminotransferase [ALT], P<0.00001; aspartate aminotransferase [AST], P<0.00001). No serious adverse events occurred during cinobufotalin injection-mediated therapy.ConclusionThe combination of TACE and cinobufotalin injection adjuvant therapy is safe and more effective for end-stage HC treatment than TACE alone.

Transplantation After Successful Downstaging by Multimodal Treatments of American Joint Committee on Cancer Stage IIIB Hepatocellular Carcinoma With Portal Vein Thrombi: A Case Report

The effective treatment for hepatocellular carcinoma (HCC) with American Joint Committee on Cancer stage IIIB remains controversial and challenging because of the high recurrence rate after resection and low survival rate. The median survival of those with macroscopic portal vein tumor thrombus (PVTT) is short. We reported such a case which received liver transplantation (LT) after successful consecutive downstaging therapies. A 40-year-old man with alcohol related liver cirrhosis and repeated esophageal varices bleeding had HCC with tumor thrombi in right main portal vein and the second portal branch of segment VI (stage IIIB). The received percutaneous alcohol injection, radiofrequency ablation, 8 sessions of transcatheter hepatic arterial chemoembolization, radiotherapy, and target therapy with sorafenib. Computed tomography (CT) scan and magnetic resonance imaging after treatments showed no viable fragments in the tumor and revealed both the right main portal vein and V1 branch were patent. One month later, the patient received a deceased LT. The perioperative course was rather smooth. After discharge, the interval follow-up CT studies of the chest and liver and whole body bone scan showed no tumor recurrence or metastasis up to 20 months postoperation.

Efficacy of dexmedetomidine mixed with sufentanil for patient-controlled intravenous analgesia in patients undergoing transcatheter hepatic arterial chemoembolization

Objective To evaluate the efficacy of dexmedetomidine mixed with sufentanil for patient-controlled intravenous analgesia(PCIA)in the patients undergoing transcatheter hepatic arterial chemoembolization(TACE). Methods One hundred and twenty patients of both sexes, aged 40-65 yr, weighing 45-80 kg, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, scheduled for elective TACE under monitored anesthesia care, were divided into 2 groups(n=60 each)using a random number table: sufentanil group(S group)and dexmedetomidine mixed with sufentanil group(DS group). At 15 min prior to surgery, 0.1 μg/kg sufentanil and 5 mg tropisetron were intravenously injected in both groups.In addition, dexmedetomidine 0.6 μg/kg was intravenously infused for 15 min in DS group, while the equal volume of normal saline was given instead in S group.PCIA solution contained sufentanil 2 μg/kg and tropisetron 5 mg in 100 ml of normal saline in S group.PCIA solution contained sufentanil 2 μg/kg, dexmedetomidine 2 μg/kg and tropisetron 5 mg in 100 ml of normal saline in DS group.The PCIA pump was programmed to deliver a 0.5 ml bolus dose with a lockout interval of 15 min and background infusion of 2 ml/h.Observer′s Assessment of Alertness/Sedation Scale scores and scores for patient′s satisfaction with analgesia were recorded at 30 min and 2, 6, 12, 24 and 48 h after surgery.The pressing times of PCIA, total consumption of sufentanil and requirement for morphine as rescue analgesics were recorded.The development of requirement for antiemetics, nausea and vomiting, bradycardia, respiratory depression and agitation was also recorded during analgesia. Results Compared with S group, the pressing times of PCIA, total consumption of sufentanil and requirement for morphine were significantly reduced, scores for satisfaction with analgesia were increased, and Observer′s Assessment of Alertness/Sedation Scale scores were decreased(P 0.05). Conclusion Dexmedetomidine mixed with sufentanil produces better efficacy than sufentanil alone when used for PCIA in the patients undergoing TACE. Key words: Dexmedetomidine; Sufentanil; Hepatic artery; Embolization, therapeutic; Analgesia, patient-controlled

Short-term efficacy of 125I seed implantation combined with transcatheter arterial chemoembolization in the treatment of advanced primary hepatocellular carcinoma

Objective To evaluate the efficacy and safety of 125I seed implantation combined with transcatheter arterial chemoembolization (TACE) in the treatment of primary hepatocellular carcinoma (PHC). Methods 156 patients who had unresectable PHC seen from January 2012 to December 2015 in our unit were randomly assigned into the study group (76 patients) and the control group (80 patients). The study group of patients were treated with intra-hepatic implantation of 125I seed + TACE, and the control group of patients were treated with three dimensional conformal radiotherapy (3DCRT) + TACE. After radiotherapy the two groups of patients underwent 2 to 3 times TACE treatment. The biomarker levels were compared between the two groups before and after treatment, and the short-term efficacy, clinical safety and 1 year survival rates were assessed. Results The success rates of the treatment for the two groups were both 100%. Patients in the study group were implanted with 1 016 125I seeds, with an average of (13.7±2.5) seeds per patient. The two groups had no significant difference on short-term efficacy (P>0.05). The DCR, ORR and 1 year survival rates in the study group were 63.2%, 92.1%, 55.5%, and they were 61.3%, 90.0%, 58.1% in the control group, respectively. There were no significant differences between these 2 groups (P>0.05). At 1 month after treatment, the two groups had no significant differences on AFP, IGF-II and IGFBP-2 [(5.08±0.85) μg/L vs. (5.12±0.79) μg/L, (4.77±0.58) μg/L vs. (4.86±0.53) μg/L, (4.98±0.67) μg/L vs. (5.04±0.71) μg/L] (P>0.05). There were no significant differences on chemotherapy drug toxicities between the two groups (P>0.05). The incidence of radiation hepatitis in the study group was 1.3%, while the incidences of radiation dermatitis, hepatitis, gastric ulcer in the control group were 5.0%, 8.8%, 2.5%, respectively. The radiation dermatitis incidence in the study group was significantly lower than that of the control group (P<0.05). In the study group, 2 patients (2.6%) had their 125I seed slightly moved. Conclusion The short-term efficacy of 125I seed implantation plus TACE in the treatment of PHC is no less than the 3DCRT + TACE regimen, but with less radiation side effects. Key words: Primary hepatocellular carcinoma; Tumor thrombus; Transcatheter hepatic arterial chemoembolization; 125I seed implantation; Three dimensional conformal radiotherapy; Clinical efficacy

Efficient Suppression of Liver Metastasis Cancers by Paclitaxel Loaded Nanoparticles in PDLLA-PEG-PDLLA Thermosensitive Hydrogel Composites.

Breast and colonic carcinomas are two main origins of metastatic liver cancer. Chemotherapy, which introduces various anticancer drugs such as paclitaxel, is an important cure for patients who are not suitable for surgery and transcatheter hepatic arterial chemoembolization. However, the poor water solubility and serious side effects have limited the use of paclitaxel. Nanoparticles are promising carriers for paclitaxel to overcome these limitations. Besides, relatively consistent drug absorption by peritoneum into the liver through the portal system can be obtained if paclitaxel is given through intraperitoneum, which is beneficial to the therapy of metastatic liver cancer. In this study, we used our newly synthetic copolymer thermogels, PDLLA-PEG-PDLLA hydrogel as a carrier of paclitaxel-loaded nanoparticles. This novel injectable thermosensitive hydrogel is able to transfer into physically cross-linked non-flowing gel structure in body temperature with acceptable biocompatibility and biodegradability. The results showed that paclitaxel nanoparticle carried by PDLLA-PEG-PDLLA gel illustrated good liver metastatic cancer suppression efficacy. We also discussed the alterations of inflammatory cells (MDSCs and TAMs) and several inflammatory factors during the treatments. Nano-PTX-GEL led to more obvious reduction of infiltration of MDSCs in metastatic liver cancers, compared with free paclitaxel and Nano-PTX treated groups. In addition, we revealed that free paclitaxel treatment resulted in higher levels of IL-6, IL-10, PDL-1, TGF-β1, TNF-α and VEGF, while the expression levels of these inflammatory factors were much lower in the other two groups, especially in the Nano-PTX-GEL treated groups. These results suggested that utilization of PDLLA-PEG-PDLLA hydrogel as a carrier for paclitaxel could reduce inflammatory reaction induced by paclitaxel in liver metastatic cancers treatment. Besides, in this study, we used a simpler method to build liver metastatic cancer model through surgery, which can control the bias of results.

Transcatheter hepatic arterial chemoembolization and sorafenib for hepatocellular carcinoma: a meta-analysis of randomized, double-blind controlled trials.

We performed a meta-analysis of transcatheter hepatic arterial chemoembolization (TACE) combined with sorafenib for hepatocellular carcinoma (HCC), which included 4 double-blind, randomized controlled trials (RCTs) that investigated the effects of TACE combined with sorafenib (experimental groups) on time to disease progression (TTP), overall survival (OS), and various sorafenib-related adverse events, compared to those in the placebo (control) groups. A total of 877 HCC cases from 14 countries, including China and the USA, were included in our meta-analysis. The TTP increased significantly in the experimental groups (hazard ration [HR]: 0.82; 95% CI: 0.69–0.97; p = 0.02), but OS did not improve significantly (HR: 0.97; 95% CI: 0.72–1.29; p = 0.82), compared with the control groups. The risks of hand and foot skin reactions (HFSR), rash, fatigue, and diarrhea were significantly greater in the experimental groups (p < 0.05 for all), compared to those in the control groups, whereas the risk of nausea was statistically similar (p > 0.05). Among these, the risk of HFSR was highest (risk ratio [RR]: 5.93; 95% CI: 2.00–17.53; p = 0.001), and a subgroup analysis of studies that lacked significant heterogeneity in the HFSR data showed a higher risk of HFSR (RR: 10.96; 95% CI: 5.54–21.69; p < 0.05). In conclusion, although TACE plus sorafenib increases TTP, it does not improve OS. Therefore, the risk of the adverse events of TACE plus sorafenib should be considered as a potential therapeutic limitation.