Portal vein embolization for closure of marked arterioportal shunt of hepatocellular carcinoma to enable radioembolization: A case report.

BACKGROUND: Marked arterioportal shunt (APS) can be a contraindication for transarterial radioembolization (TARE) because of the risk of radiation-induced liver toxicity or pneumonitis. To date, the best method to close marked APS to reduce intrahepatic shunt (IHS) and hepatopulmonary shunt (HPS) before TARE has not been elucidated. CASE SUMMARY: This case report describes a novel strategy of embolization of the portal venous outlet to reduce IHS and HPS caused by marked APS before TARE in a patient with advanced hepatocellular carcinoma (HCC). The patient had a significant intratumoral shunt from the tumor artery to the portal vein and had already been suspected based on pre-interventional magnetic resonance angiography, and digital subtraction angiography (DSA) confirmed the shunt. Selective right portal vein embolization (PVE) was performed to close the APS outlet and DSA confirmed complete closure. Technetium-99m macroaggregated albumin was administered and single photon emission computed tomography revealed a low HPS with 8.4%. Successful TARE was subsequently performed. No major procedure-related complication occurred. CONCLUSION: Closure of APS with PVE during mapping angiography of advanced-stage HCC to enable reduction of HPS and subsequent TARE is feasible.

Associating liver partition and portal vein ligation for staged hepatectomy versus sequential transarterial chemoembolization and portal vein embolization in staged hepatectomy for HBV-related hepatocellular carcinoma: a randomized comparative study.

Background: Both portal vein embolization (PVE) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) have merits and demerits when used in patients with unresectable liver cancers due to insufficient volumes in future liver remnant (FLR). Methods: This study was a single-center, prospective randomized comparative study. Patients with the diagnosis of hepatitis B related hepatocellular carcinoma (HCC) were randomly assigned in a 1:1 ratio to the 2 groups. The primary endpoints were tumor resection and three-year overall survival (OS) rates. Results: Between November 2014 to June 2016, 76 patients with unresectable HBV-related HCC due to inadequate volume of FLR were randomly assigned to ALPPS groups (n=38) and TACE + PVE groups (n=38). Thirty-seven patients (97.4%) in the ALPPS group compared with 25 patients (65.8%) in the TACE + PVE group were able to undergo staged hepatectomy (risk ratio 1.48, 95% CI: 1.17-1.87, P<0.001). The three-year OS rate of the ALPPS group (65.8%) (95% CI: 50.7-80.9) was significantly better than the TACE + PVE group (42.1%) (95% CI: 26.4-57.8) (HR 0.50, 95% CI: 0.26-0.98, two-sided P=0.036). However, no significant difference in the OS rates between patients who underwent tumor resection in the 2 groups of patients was found (HR 0.80, 95% CI: 0.35-1.83, two-sided P=0.595). Major postoperative complications rates after the stage-2 hepatectomy were 54.1% in the ALPPS group and 20.0% in the TACE + PVE group (risk ratio 2.70, 95% CI: 1.17-6.25, P=0.007). Conclusions: ALPPS resulted in significantly better intermediate-term OS outcomes, at the expenses of a significantly higher perioperative morbidity rate compared with TACE + PVE in patients who had initially unresectable HBV-related HCC.

Recurrent undifferentiated embryonal sarcoma of the liver in adult patient treated by pembrolizumab: A case report.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a neoplasm that rarely develops in adults. The main treatments for UESL are upfront gross total surgical resection and adjuvant multiagent chemotherapy. Here, we report a case of recurrent UESL in an adult treated with pembrolizumab and discuss a method to identify proper candidates for antibody of programmed cell death protein 1 (anti-PD-1) treatment. CASE SUMMARY: A 69-year-old woman was admitted for abdominal pain that developed for 1 wk. Computed tomography showed a 16 cm mass in the right lobe of the liver. Right hemihepatectomy and lymphadenectomy were performed, and histological diagnosis was UESL. Six months later, the patient suffered from painless obstructive jaundice, and positron emission tomography-computed tomography revealed multiple metastases. Then, percutaneous transhepatic cholangial drainage was applied to reduce jaundice, and radiofrequency ablation was used to control the lesion near the hepatic hilum. However, the patient suffered from a serious fever caused by the tumor. The patient received treatment with pembrolizumab, and the prescribed dosage was 2 mg/kg every 3 wk. After the seventh dose, positron emission tomography-computed tomography revealed that the multiple metastases had nearly disappeared. Radiologic exam was used to evaluate the disease state, and no new lesions were found. Next-generation sequencing and immunohistology were applied to determine the reason why the patient had such a favorable response to pembrolizumab. Tumor mutation burden, microsatellite instability, and programmed death ligand 1 expression can be combined to predict the effect of PD-1 antibodies. When every one of these biomarkers are detected in a tumor patient, the patient may be a proper candidate for PD-1 antibodies. CONCLUSION: Anti-PD-1 treatment for tumors needs further research to identify indications and proper biomarkers.

Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition).

BACKGROUND: Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. SUMMARY: This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. KEY MESSAGES: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Small Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma in Cirrhotic Livers May Share Similar Enhancement Patterns at Multiphase Dynamic MR Imaging.

Purpose To assess the accuracy of magnetic resonance (MR) imaging-based differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in a cohort of patients with focal liver lesions and cirrhosis. Materials and Methods This study was institutional review board approved, and the requirement for informed consent was waived. Between January 2009 and December 2014, a cohort of cirrhotic patients, including 71 with ICC and 612 with HCC, underwent unenhanced T1- and T2-weighted MR imaging, gadolinium-based contrast material-enhanced dynamic phase imaging, and partial hepatectomy. Results of pathologic examinations were obtained for all patients. Clinical, radiologic, and pathologic results in these patients were analyzed and compared comprehensively. Differences in signal intensity on baseline and contrast material-enhanced images and dynamic enhancement patterns were evaluated and compared by using the χ(2) test or the Fisher exact test. Results The preoperative diagnoses of 517 of 683 lesions were confirmed pathologically. Five ICCs and 481 HCCs displayed contrast material washout in delayed phases (P < .001). Thirty-six ICCs and 23 HCCs displayed a progressive enhancement pattern (P < .001). Twenty-six ICCs and 63 HCCs displayed a stable enhancement pattern (P < .001). ICCs displayed significantly different enhancement patterns according to size (P = .022). Conclusion The accurate discrimination of small ICCs from HCCs in the setting of cirrhosis at MR imaging is difficult, as substantial proportions of ICCs and HCCs have similar enhancement patterns. Absence of contrast material washout at MR imaging is not a factor that prevents the misdiagnosis of HCC. (©) RSNA, 2016 Online supplemental material is available for this article.

Evolving Role of Radiopharmaceuticals in Hepatocellular Carcinoma Treatment.

The global incidence of primary liver cancer has been increased during recent decades. Among the primary liver malignancies, hepatocellular carcinoma (HCC) is recognized as the most prevalent and aggressive. Although HCC has come to be regarded as a radioresponsive tumor during the last decade, it has also been noted that the ability to deliver destructive radioactive doses exclusively to HCC is limited with conventional external irradiation techniques. This review examines a number of radiotherapeutic techniques used to treat HCC, and the radiopharmaceuticals associated with those techniques. Selective internal radiotherapy (SIRT) is a powerful therapeutic technique developed during recent decades that is increasingly used in HCC treatment due to its superior ability to target and destroy cancer cells while sparing normal tissue. The radiopharmaceuticals used in SIRT are usually comprised of a simple ion and a complex or a carrier. Transarterial radioembolization (TARE) is a technique that is increasingly used in adjuvant or neoadjuvant therapy following the surgical treatment of HCC, as well as the treatment of unresectable or untransplantable HCC. The primary radiopharmaceuticals used in TARE include Iodine- 131-labeled Lipiodol and Yttrium-90 microspheres. Radioimmunotherapy (RAIT) is currently used as targeted procedure for adjuvant therapy and combination therapy of HCC. The primary radiopharmaceutical used in RAIT is 131I-metuximab. Interstitial brachytherapy has also been the subject of recent HCC treatment investigations. The primary radiopharmaceuticals used in interstitial brachytherapy are implanted iodine-125 seed strands. This review surveys the important milestones in the development and clinical implementation of the radiopharmaceuticals used in HCC therapy and critically examines new and emerging trends for the delivery of radiopharmaceuticals to HCC tissues.

Multimodality Treatment for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Large-Scale, Multicenter, Propensity Mathching Score Analysis.

The optimal treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains controversial. We aimed to investigate the best treatment for patients with HCC with PVTT. From January 2002 to January 2014, the data from all consecutive patients with HCC with PVTT who underwent surgical treatment (ST),TACE,TACE combined with sorafenib (TACE-Sor), or TACE combined with radiotherapy (TACE-RT) in the 4 largest tertiary hospitals in China were analyzed retrospectively. The patients were divided into 3 subtypes according to the extent of PVTT in the portal vein (type I-III). The primary endpoint was overall survival (OS). A total of 1580 patients with HCC with PVTT were included in the study. The median survival times (MST) for ST (n = 745) for type I, II, and III patients (95% CI) were 15.9 (13.3-18.5), 12.5 (10.7-14.3), and 6.0 (4.3-7.7) months, respectively. The corresponding figures for patients after TACE (n = 604) were 9.3 (5.6-12.9), 4.9 (4.1-5.7), and 4.0 (3.1-4.9), respectively; for patients after TACE-Sor (n = 113) 12.0 (6.6-17.4), 8.9 (6.7-11.1), and 7.0 (3.0-10.9), respectively; and for patients after TACE-RT (n = 118) 12.2 (0-24.7), 10.6 (6.8-14.5), and 8.9 (5.2-12.6), respectively. Comparison among the different treatments for the 3 subtypes of PVTT patients after propensity score (PS) matching showed the effectiveness of ST to be the best for type I and type II PVTT patients, and TACE-RT was most beneficial for type III patients. Treatment was an independent risk factor of OS. ST was the best treatment for type I and II PVTT patients with Child-Pugh A and selected B liver function. TACE-RT should be given to type III PVTT patients.

Genetic Variants in ASCT2 Gene are Associated with the Prognosis of Transarterial Chemoembolisation-Treated Early- Stage Hepatocelluar Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. Transarterial chemoembolisation (TACE) is the standardized therapy for intermediate stage HCC. However, the prognosis for HCC patients treated by TACE greatly varies. Thus, there is a critical need for finding biomarkers to predict the prognosis of HCC patients. The amino acid transporter-2 (ASCT2) is involved in tumorigenesis and progression of many malignancies. This study aimed to evaluate the predictive role of two single nuclear polymorphisms (SNPs, rs3826793 and rs2070246) in the ASCT2 gene in HCC patients treated by TACE. MATERIALS AND METHODS: Two functional SNPs (rs3826793 and rs2070246) in the ASCT2 gene were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 448 unresectable Chinese HCC patients treated by TACE. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier curves were used for the prognosis analyses. RESULTS: There was no significant association between two SNPs (rs3826793 and rs2070246) in the ASCT2 gene and overall survival of TACE treated HCC patients. However, we demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype (P=0.023). CONCLUSIONS: We demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype.

Hepatic artery injection of ¹³¹I-labelled metuximab combined with chemoembolization for intermediate hepatocellular carcinoma: a prospective nonrandomized study.

PURPOSE: Hepatocellular carcinoma (HCC) is the fifth and seventh most common cause of cancer in men and women, respectively. Transcatheter arterial chemoembolization (TACE) is the standardized therapy for the intermediate stage of HCC. However, the 3-year overall survival remains low (<30 %) in these patients. Thus, there is a critical need for the development of treatment modalities to improve the survival rate. This study aimed to evaluate whether the combination of (131)I-metuximab with chemoembolization could improve treatment efficiency. METHODS: Between January 2009 and January 2010, a prospective two-arm nonrandomized study was performed in patients with intermediate HCC. Of 138 patients, 68 (combination therapy group) received 132 courses of intraarterial (131)I-metuximab injections combined with chemoembolization (mean 1.94 per patient, median 2, range 1-2), followed by 152 sessions of TACE (mean 2.24 per patient, median 2, range 0-4). The remaining 70 patients (monotherapy group) received 296 sessions of TACE (mean 4.23 per patient, median 4, range 1-7). RESULTS: The overall median survival times for the combination therapy group and the group treated only with TACE were 26.7 months (95 % CI 20.7-31.3 months) and 20.6 months (95 % CI 15.3-24.7 months), respectively. The combination therapy group had a significantly higher survival rate than the TACE-only group (P = 0.038). Age ≥65 years, serum albumin ≤35 g/l, and treatment category (combination therapy or TACE only) were independent prognostic factors for survival according to multivariate analysis. CONCLUSION: The combination of (131)I-metuximab and chemoembolization extended survival in patients with intermediate HCC compared with TACE only, and was well tolerated by patients with Child-Pugh class A or B disease. This combination seems to be a promising treatment modality for patients with intermediate HCC.

Leukocyte telomere length predicts overall survival in hepatocellular carcinoma treated with transarterial chemoembolization.

Previous studies have reported that telomere length in peripheral blood leukocytes can predict the clinical outcome of several cancers. However, whether leukocyte telomere length is associated with the prognosis of hepatocellular carcinoma (HCC) remains to be determined. In this study, relative telomere length (RTL) in peripheral blood leukocytes was measured using a real-time PCR-based method for 269 HCC patients treated with transarterial chemoembolization (TACE) from two independent hospitals. The association between RTL and the overall survival (OS) of HCC was analyzed. The immunological function of the HCC patients with different leukocyte RTLs was evaluated. Multivariate analyses indicated that long leukocyte RTL was significantly associated with poor OS of HCC patients, with a hazard ratio of 2.04 (95% confidence interval, 1.46-2.86; P < 0.001). Kaplan-Meier analyses showed a significant difference of median survival time between patients with long and short RTL (log rank P < 0.001). Fluorescence-activated cell sorting analyses showed that the long RTL group had a significantly increased percentage of CD4(+)CD25(+)FOXP3(+) Treg in CD4(+) T cells compared with short RTL group (P = 0.002). In conclusion, our results suggest that leukocyte RTL may serve as an independent prognostic marker for HCC patients treated with TACE.

Isolation of circulating tumor cells in patients with hepatocellular carcinoma using a novel cell separation strategy.

PURPOSE: To establish a sensitive and specific isolation and enumeration system for circulating tumor cells (CTC) in patients with hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: HCC cells were bound by biotinylated asialofetuin, a ligand of asialoglycoprotein receptor, and subsequently magnetically labeled by antibiotin antibody-coated magnetic beads, followed by magnetic separation. Isolated HCC cells were identified by immunofluorescence staining using Hep Par 1 antibody. The system was used to detect CTCs in 5 mL blood. Blood samples spiked with Hep3B cells (ranging from 10 to 810 cells) were used to determine recovery and sensitivity. Prevalence of CTCs was examined in samples from HCC patients, healthy volunteers, and patients with benign liver diseases or non-HCC cancers. CTC samples were also analyzed by FISH. RESULTS: The average recovery was 61% or more at each spiking level. No healthy, benign liver disease or non-HCC cancer subjects had CTCs detected. CTCs were identified in 69 of 85 (81%) HCC patients, with an average of 19 ± 24 CTCs per 5 mL. Both the positivity rate and the number of CTCs were significantly correlated with tumor size, portal vein tumor thrombus, differentiation status, and the disease extent as classified by the TNM (tumor-node-metastasis) classification and the Milan criteria. HER-2 gene amplification and TP53 gene deletion were detected in CTCs. CONCLUSION: Our system provides a new tool allowing for highly sensitive and specific detection and genetic analysis of CTCs in HCC patients. It is likely clinically useful in diagnosis and monitoring of HCC and may have a role in clinical decision making.

Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein as a marker of prognosis and a monitor of recurrence of hepatocellular carcinoma after curative liver resection.

BACKGROUND: The aim of this study was to determine the role of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) as a prognostic marker and a monitor marker of recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: From December 2002 to May 2004, 395 consecutive patients with HCC who underwent curative partial hepatectomy were included in the study. The tumor characteristics and clinical outcomes of patients with positive preoperative and postoperative AFP-L3 were compared with those with negative results. RESULTS: A high ratio of AFP-L3 to total AFP was an indicator of pathologic aggressiveness. Patients with positive preoperative AFP-L3 had significantly earlier recurrence (median time to recurrence 22.0 ± 2.4 months vs 45.0 ± 6.9 months, P < .001) when compared with those with negative preoperative results. Significantly more patients with continuously positive or negative-turn-positive AFP-L3 results after surgery developed recurrence, particularly distant metastases, when compared with patients with continuously negative AFP-L3 results. The overall and disease-free survivals were significantly shorter in the positive than the negative preoperative AFP-L3 group. The overall and disease-free survivals were significantly shorter in the continuously positive and the negative-turn-positive than the continuously negative postoperative AFP-L3 group. CONCLUSION: Positive preoperative AFP-L3 and continuously positive or negative-turn-positive AFP-L3 results after surgery predicted a more aggressive tumor behavior, higher tumor recurrence, and poorer clinical outcomes. HCC patients with an increased proportion of AFP-L3 to total AFP should be more aggressively treated and closely followed-up.

Cerebral lipiodol embolism following transcatheter arterial chemoembolization for hepatocellular carcinoma.

Cerebral lipiodol embolism (CLE) is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma (HCC). The authors present a case of CLE that occurred after the second hepatic arterial chemoembolization for HCC, and attempt to introduce several plausible mechanisms of CLE, after reporting the clinical and radiological findings and reviewing the medical literature.

Hepatic arterial iodine-131-labeled metuximab injection combined with chemoembolization for unresectable hepatocellular carcinoma: interim safety and survival data from 110 patients.

Few options are available to treat patients with hepatocellular carcinoma (HCC). It was tested whether the combination of iodine-131(¹³¹I)-metuximab with chemoembolization could improve outcomes in patients with intermediate HCC. Between April 2008 and April 2009, 110 patients with unresectable HCC were treated with 113 intra-arterial ¹³¹I-metuximab injections combined with chemoembolization (mean, 1.03 per patient; median, 1; range, 1-2), followed by 264 sessions of transcatheter arterial chemoembolization (mean, 2.4 per patient; median, 3; range, 1-6). The survival rates at 6, 12, and 18 months were 88.2%, 79.1%, and 57.4%, respectively, by the Kaplan-Meier method. Of these patients, 12% exhibited grade 3/4 bilirubin toxicity, 5% exhibited grade 3/4 white blood count toxicity, and 7% exhibited grade 3/4 platelet toxicity. Response rates based on World Health Organization and European Association for the Study of the Liver criteria were 42.73% and 61.82%, respectively. The combination of ¹³¹I-metuximab and chemoembolization appeared to extend survival in patients with unresectable HCC compared with historical controls, as well as being well tolerated by patients with Child-Pugh A and B. This combination may represent a promising treatment modality for patients with intermediate HCC.

[Evaluation of transcatheter arterial chemoembolization in the prevention of postoperative recurrence in 1630 patients with hepatocellular carcinoma].

OBJECTIVE: To evaluate postoperative transcatheter arterial chemoembolization (TACE) in the prevention of postoperative recurrence of hepatocellular carcinoma (HCC). METHODS: In TACE group, 987 HCC patients without any evidence of recurrence at the first TACE were treated by prophylactic TACE postoperatively within one or two months. In the control group, 643 HCC patients were not treated by prophylactic TACE for comparison. The correlation between the first recurrence and prophylactic TACE was analyzed. RESULTS: Recurrence rate in the TACE and control group was 22.2% (219/987) and 61.6% (396/643) within 6 months (P < 0.01); 78% (770/987) and 74.7% (480/643) within 12 months (P > 0.05); 88.6% (874/987) and 80.1% (515/643) within 18 months (P < 0.01), respectively. CONCLUSION: Postoperative prophylactic TACE may be able to suppress the recurrence formation for HCC patients with or without definite residual lesion within 6 months.