Personalized neoantigen vaccine prevents postoperative recurrence in hepatocellular carcinoma patients with vascular invasion

Abstract Background Clinically, prophylactic anti-recurrence treatments for hepatocellular carcinoma (HCC) patients after radical surgery are extremely limited. Neoantigen based vaccine can generate robust anti-tumor immune response in several solid tumors but whether it could induce anti-tumor immune response in HCC and serve as a safe and effective prophylactic strategy for preventing postoperative HCC recurrence still remain largely unclear. Methods Personalized neoantigen vaccine was designed and immunized for 10 HCC patients with high risk of postoperative recurrence in a prime-boost schedule. The safety and immune response were assessed through adverse events, tissue sequencing, ELISpot, TCR sequencing. The clinical response was evaluated by recurrence-free survival (RFS) and personalized circulating tumor DNA (ctDNA) sequencing. Results In the 10 enrolled patients, no obvious adverse events were observed during neoantigen vaccinations. Until the deadline of clinical trial, 8 of 10 patients were confirmed with clinical relapse by imaging, the other 2 patients remained relapse-free. From receiving first neoantigen vaccination, the median RFS of 10 patients were 7.4 months. Among 7 patients received all planned neoantigen vaccinations, 5 of them demonstrated neoantigen-induced T cell responses and have significantly longer RFS after radical surgery than other 5 patients without responsive neoantigens or only with prime vaccination and propensity scores matching control patients (p = 0.035). Moreover, tracking personalized neoantigen mutations in ctDNA could provide real-time evaluation of clinical response in HCC patients during neoantigen vaccination and follow up. Conclusion Personalized neoantigen vaccine is proved as a safe, feasible and effective strategy for HCC anti-recurrence, and its progression could be sensitively monitored by corresponding neoantigen mutations in ctDNA, and thus provided solid information for individualized medicine in HCC. Trial registration This study was registered at Chinese Clinical Trial Registry; Registration number: ChiCTR1900020990.

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A Comparison of the Efficacy, Tolerability and Safety of Azithromycin and Co-Amoxiclav in the Treatment of Sinusitis in Adults

Journal of International Medical Research ◽

10.1177/030006059802600202 ◽

1998 ◽

Vol 26 (2) ◽

pp. 66-75 ◽

Cited By ~ 22

Author(s):

PAR Clement ◽

J-B de Gandt

Keyword(s):

Clinical Trial ◽

Streptococcus Pneumoniae ◽

Adverse Events ◽

Haemophilus Influenzae ◽

Clinical Response ◽

Persistent Infection ◽

Single Daily Dose ◽

Adult Patients ◽

Daily Dose

The efficacy, tolerability and safety of azithromycin and co-amoxiclav in the treatment of non-severe acute maxillary/ethmoidal sinusitis were compared in a randomized, open clinical trial in 254 adult patients. The predominant pathogens were Streptococcus pneumoniae and Haemophilus influenzae (83 patients). Azithromycin was administered orally to 165 patients at a single daily dose of 500 mg for 3 days, and co-amoxiclav (4:1) to 89 patients, at a dose of 500 mg three times daily for 10 days. The overall clinical response rates were 87.5% for azithromycin and 83.7% for co-amoxiclav at follow-up (day 21–28). Microbiological responses to both drugs were good, with only five patients in each group having a persistent infection after treatment. Both drugs were well tolerated and produced similar incidences of adverse events, which were mostly gastrointestinal. Azithromycin was as effective, and as well tolerated as co-amoxiclav, and its shorter simpler dosing regime may offer advantages in compliance and cost.

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Hepatic arterial infusion of oxaliplatin plus raltitrexed in patients with unresectable hepatocellular carcinoma (HAIROX): A phase II, single-arm, prospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4574 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4574-4574

Author(s):

Shiguang Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trial ◽

Adverse Events ◽

Phase Ii ◽

Objective Response ◽

Hepatic Arterial Infusion ◽

Arterial Infusion ◽

Intention To Treat ◽

Unresectable Hepatocellular Carcinoma ◽

Treat Population

4574 Background: Chemoembolisation and oral sorafenib are the recommended treatment for unresectable hepatocellular carcinoma (HCC); however, some patients respond poorly to these. Hepatic arterial infusion (HAI) chemotherapy may have potential benefit in these patients. We aimed to investigate the efficacy and safety of HAI of oxaliplatin plus raltitrexed in patients with unresectable HCC. Methods: In this phase II, single-arm clinical trial, we enrolled patients aged 18–70 years with unresectable HCC at the Fujian Cancer Hospital (China). We performed HAI with oxaliplatin (100 mg/m2 for 4 hours) and raltitrexed (3 mg/m2 for 1 hour). Treatment was repeated every 3 weeks and was discontinued either because of disease progression, unacceptable toxicity levels, or refusal of further treatment. We used Simon’s two-stage design. The primary endpoint was the objective response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results: Fifty-one patients were screened between January 5, 2018 and August 7, 2019. Of these, 39 patients (34 men and 5 women; median age, 53 years) were enrolled and included in the intention-to-treat population. Objective response was achieved in 18 (51.4%) of 35 patients in the per-protocol population and in 18 (46.2%) of 39 patients in the intention-to-treat population. Treatment-related grade 4 adverse events or deaths were not reported, and the observed grade 3 adverse events were elevated aspartate aminotransferase levels (5[12.8%]), elevated alanine aminotransferase levels (1 [2.6%]), leukopenia (1 [2.6%]), thrombocytopenia (1 [2.6%]), and abdominal infection (1 [2.6%]). Conclusions: HAI of oxaliplatin plus raltitrexed showed promising efficacy and acceptable toxicity levels in patients unresectable HCC, and further evaluation is warranted. Clinical trial information: ChiCTR-OOC-17014182 . [Table: see text]

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Neoadjuvant transarterial infusion chemotherapy with FOLFOX could improve outcomes of resectable BCLC stage A/B hepatocellular carcinoma patients beyond Milan criteria: An interim analysis of a multi-center, phase 3, randomized, controlled clinical trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4008 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4008-4008

Author(s):

Shaohua Li ◽

Chong Zhong ◽

Qiang Li ◽

Jingwen Zou ◽

Qiaoxuan Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trial ◽

Adverse Events ◽

Milan Criteria ◽

Controlled Clinical Trial ◽

Efficacy And Safety ◽

Phase 3 ◽

Free Survival ◽

Infusion Chemotherapy ◽

Transarterial Infusion

4008 Background: The efficacy of operation, as the only radical option for resectable BCLC stage A/B hepatocellular carcinoma (HCC) patients beyond Milan criteria, is still unsatisfactory. This study aimed to investigate to efficacy and safety of preoperative neoadjuvant transarterial infusion chemotherapy (TAI) with FOLFOX regimen for these patients. Methods: In this multi-center, prospective, phase 3, randomized, open-labeled, controlled clinical trial, resectable BCLC stage A/B HCC patients beyond Milan criteria were randomly assigned (1:1) before hepatectomy to receive either neoadjuvant TAI (NT group) or operation directly without any neoadjuvant treatment (OP group). The primary endpoint was overall survival (OS), the secondary endpoints are progression-free survival (PFS), recurrence free survival (RFS), and safety. Results: Between March, 2016 and July, 2020, 208 patients enrolled from five Chinese hospitals were randomly assigned to NT group (n=104) or OP group (n=104)， with 99 patients in NT group and 100 patients in OP group included in the efficacy and safety analysis. Clinicopathological characteristics were balanced between the two groups. The 1-, 2-, and 3-year OS rates for NT group were 92.9%, 78.6%, and 63.5%, and were 79.5%, 62.0%, and 46.3% for OP group, respectively. The 6-, 12-, and 18-month PFS rates for NT group were 77.6%, 50.4%, and 47.4%, and were 52.7%, 42.8%, and 34.8% for OP group, respectively. The OS and PFS were significantly better in NT group than in OP group (p=0.016 and 0.017, respectively). The 6-, 12-, and 18-month RFS rates for NT group were 63.8%, 47.3%, and 47.3%, and were 52.7%, 42.8%, and 34.8% for OP group, respectively. The RFS between the two group had no difference (p=0.385). No patients in NT group experienced grade 3 or more severe TAI related adverse events. The operation related adverse events were similar between two groups (p=0.300). Conclusions: Neoadjuvant TAI before hepatectomy may bring survival benefits for resectable BCLC stage A/B HCC patients beyond Milan criteria. Trial number: NCT03851913. Clinical trial information: NCT03851913.

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Accuracy of Endoscopic Transpapillary Gallbladder Drainage with Liquid-Based Cytology for Gallbladder Disease

Digestion ◽

10.1159/000519250 ◽

2021 ◽

pp. 1-10

Author(s):

Soichiro Kawahara ◽

Takeshi Tomoda ◽

Hironari Kato ◽

Toru Ueki ◽

Yutaka Akimoto ◽

...

Keyword(s):

Clinical Trial ◽

Adverse Events ◽

Diagnostic Accuracy ◽

Success Rate ◽

Cystic Duct ◽

Gallbladder Disease ◽

Drainage Tube ◽

Clinical Trial Registry ◽

Gallbladder Drainage ◽

Gallbladder Diseases

Introduction: Gallbladder carcinoma is often difficult to distinguish from benign gallbladder diseases. While the diagnostic accuracy of endoscopic transpapillary gallbladder drainage (ETGD) has been reported, these results were obtained retrospectively. This prospective study aimed to evaluate the cytological diagnostic accuracy of ETGD in patients with gallbladder disease. Methods: This single-arm prospective clinical trial included a total of 35 patients scheduled to undergo ETGD between March 2017 and September 2019. A 5F pigtail nasobiliary drainage tube was inserted into the gallbladder, and bile was collected over 5 times; if ETGD failed, a drainage tube was placed into the bile duct. The endpoints were, first, the cytological diagnostic accuracy of ETGD and, second, technical success rates and adverse events. Results: Of the 35 patients, 19 were finally diagnosed with gallbladder cancer. The success rate of ETGD tube insertion was 85.7%, and the morphological pattern of the cystic duct with the angle down and located on the right side had a significantly lower success rate for ETGD than that of other cystic duct patterns (odds ratio, 13.5; 95% confidence interval, 1.7–143.7; p = 0.02). Cytological samples were collected 5 times on median. The sensitivity, specificity, and accuracy in all patients were 78.9%, 100%, and 88.6%, respectively, while those in 30 patients with successful ETGD were 87.5%, 100%, and 93.3%, respectively. Adverse events occurred in 3 patients: mild pancreatitis in 1 patient and obstructive jaundice in 2 patients; all complications were resolved with conservative therapy. Discussion/Conclusions: Cytology using an ETGD tube is useful in differentiating benign and malignant gallbladder diseases (Clinical Trial Registry No. UMIN000026929).

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Bioequivalence of a Generic Nateglinide Formulation in Healthy Chinese Volunteers under Fasting and Fed Conditions: A Randomized, Open-Label, Double-Cycle, Double-Crossover Study

Pharmacology ◽

10.1159/000512851 ◽

2021 ◽

pp. 1-8

Author(s):

Ming Yu ◽

Xiaobin Li ◽

Hao Jin ◽

Lu Chen ◽

Nan Wang ◽

...

Keyword(s):

Clinical Trial ◽

Adverse Events ◽

Vital Signs ◽

Reference Formulation ◽

Clinical Trial Registry ◽

Open Label ◽

Laboratory Test Results ◽

Liquid Chromatography Tandem Mass ◽

Healthy Chinese

Introduction: Nateglinide or N-(trans-4-isopropylcyclohexyl-1-carbonyl)-D-phenylalanine is a drug with a rapid hypoglycemic effect that is mainly used in the treatment of type 2 diabetes. Very few studies have assessed bioequivalence based on feeding status. This study aimed to assess the pharmacokinetic bioequivalence and safety of nateglinide-containing tablets (0.12 g) in healthy Chinese volunteers under fasting and fed conditions. Methods: The studies were performed in 2017–2018 in the Phase I Clinical Trial Ward of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, China. Eligible Chinese volunteers received a single 0.12-g dose of the test or reference formulation, followed by a 7-day washout period and administration of the alternate formulation. Blood samples were collected at various time intervals, and plasma nateglinide concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Then, the adverse events, laboratory test results, vital signs, and physical exam findings were compared between the 2 groups. Results: The ratios of the geometric means of Cmax, AUC0-t, and AUC0-inf of the tested to reference preparations under fasting conditions were 105.03% (90% confidence interval [CI]: 99.53–110.83%), 104.02% (90% CI: 101.37–106.74%), and 104.04% (90% CI: 101.38–106.77%), respectively. The same ratios under fed conditions were 96.55% (90% CI: 85.80–108.65%), 103.08% (90% CI: 100.07–106.18%), and 103.07% (90% CI: 100.21–106.01%), respectively. The 90% CI values for Cmax, AUC0-t, and AUC0-inf fell within the accepted range of bioequivalence (80.00–125.0%). Common adverse events included hypoglycemia, heart rate increase, palpitation, sweating, dizziness, and diarrhea. Conclusions: The test formulation (0.12 g) met the CFDA’s regulatory definition for bioequivalence to the reference formulation. Both formulations were well tolerated by healthy Chinese subjects. Trial Registration: This trial has been registered in the Chinese Clinical trial registry (ChiCTR2000030694), March 10, 2020.

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Physician-and patient-reported barriers to hepatocellular carcinoma surveillance: a nationwide survey

10.21203/rs.3.rs-255177/v1 ◽

2021 ◽

Author(s):

Tongluk Teerasarntipan ◽

Yingluk Sritunya ◽

Parinda Prathyajuta ◽

Palada Pitakkitnukun ◽

Chonlada Phathong ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trial ◽

Social Networks ◽

Nationwide Survey ◽

Physician Education ◽

Trial Registry ◽

Clinical Trial Registry ◽

Patient Reported ◽

Risk Patients ◽

Main Barrier

Abstract Background Hepatocellular carcinoma (HCC) surveillance rates are suboptimal. We aimed to identify HCC surveillance barriers from both physician and patient perspectives and assess the effectiveness of physician education using social networks. Methods A nationwide survey with 513 physicians and another single-center survey with 315 HCC-risk patients were conducted. Regression analysis was used to identify surveillance barriers. We educated 143 physicians by sending brief notes on HCC surveillance guidelines via social networks and re-evaluated their knowledge at 60 days using paired T-test.Results Surveys showed 458 (86.3%), 254 (47.8%) and 225 (42.4%) physicians recommended surveillance in patients with cirrhosis, at-risk HBV and HCV infection, respectively. Only 228 (42.9%) and 241 (38.0%) respondents adhered to recommended surveillance tools and interval, respectively. The main surveillance barriers among physicians were the lack of knowledge and resource limitations. The lack of a doctor’s prescription was identified as main barrier by patients (relative risk 1.4, 95%CI 1.1-1.8, p=0.024). Social networks education enhanced physicians’ knowledge pre-and post-education scores for guideline awareness: (63.0%vs.84.3%, p<0.001) and surveillance indication (40.0%vs.63.0%, p=0.001). Conclusions Physicians’ knowledge gap was primary barrier for adherence to HCC surveillance protocols. Brief education via social networks showed effectiveness at increasing knowledge of HCC surveillance with medical residents.Clinical trial registry: This study was registered to the Thai clinical trial registry (TCTR number 20210127006). Registered 22 July 2021- Retrospectively registered. http://www.clinicaltrials.in.th/

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Thalidomide Plus Prednisone and Methotrexate for Symptomatic Large Granular Lymphocyte Leukemia: A Prospective, Single-Center, Pilot Study

Blood ◽

10.1182/blood-2020-139481 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 23-24

Author(s):

Shuhua Yi ◽

Jun Du ◽

Ying Yu ◽

Yang Jiao ◽

Yi Wang ◽

...

Keyword(s):

Clinical Trial ◽

Adverse Events ◽

Clinical Response ◽

Conflicts Of Interest ◽

Complete Response ◽

Lymphocytic Leukemia ◽

Large Granular Lymphocyte ◽

Control Treatment ◽

Phase 2 ◽

Large Granular Lymphocyte Leukemia

Background: Large granular lymphocyte leukemia (LGLL) is one type of chronic lymphocytic proliferative disorders, which commonly manifests as infiltration of large granular lymphocytes in both peripheral blood and bone marrow. LGLL now includes two entities with similar clinical course, treatment strategy and outcomes: T-cell large granular lymphocytic leukemia and chronic lymphoproliferative disorder of NK cells. The standard therapy for LGLL is still elusive. Here, we presented the efficacy and safety of combinatorial oral immunoregulatory regimen thalidomide, prednisone, and methotrexate (TPM regimen) in a prospective phase 2 clinical trial. Methods: We designed this phase 2 investigator-initiated clinical trial (NCT04453345) to evaluate the clinical response and safety of the combination of thalidomide, prednisone, and methotrexate in symptomatic treatment naïve LGLL patients. The TPM regimen includes thalidomide 50-100mg per night, prednisone 0.5-1.0mg/kg qod and methotrexate 10mg/m2 per week. This regimen will be administrated for up to 12 months until disease progression or intolerable. Then, thalidomide maintenance will continue for another year or until intolerance. Meanwhile, we set Cyclosporin A (CsA) alone or plus steroids as control. Treatment dosage for CsA was 3-5mg/Kg/day with or without steroids (prednisone) 0.5-1 mg/Kg/day. The primary endpoint of this study was the complete response rate. Results: From Aug 2013, to Jan 2020, twenty-eight patients were enrolled in this study. The median follow-up time was 26 months (range: 7-96). Twenty-five patients (89%) achieved hematologic and symptomatic response. Among them, 21 patients (75%) achieved complete response (CR) and four patients achieved partial response. The median time to best clinical response was 6 months (2-18). The 3-years progression-free-survival (PFS) rate was 90%, and 3-years overall survival (OS) rate was 92%. The median PFS time was not reached in TPM group. The curative effect was better for TPM treatment group, both for overall response (OR) (TPM 89% (25/28) vs CsA 49% (49/99), P=0.000) and CR (TPM 75% (21/28) vs CsA 20% (20/99), P=0.000). Adverse events were uncommon, two patients had grade 1-2 nausea and one had grade 3 nausea. Two patients had grade 1-2 constipation and one patient experienced grade 1-2 peripheral neuritis. Conclusion: The efficacy of this TPM regimen is higher than the history reports with limited adverse events. The multiple-center clinical trial has been initiated to validate this conclusion. Disclosures No relevant conflicts of interest to declare.

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A Prospective, Double-Blind, Randomized, Placebo-Controlled, Crossover Study Using an Orally Administered Oxalate Decarboxylase (OxDC)

Kidney360 ◽

10.34067/kid.0001522020 ◽

2020 ◽

Vol 1 (11) ◽

pp. 1284-1290

Author(s):

Emily Quintero ◽

Victoria Yvonne Bird ◽

Howard Liu ◽

Gary Stevens ◽

Alan S. Ryan ◽

...

Keyword(s):

Clinical Trial ◽

Adverse Events ◽

Healthy Volunteers ◽

Urinary Oxalate ◽

Oxalate Decarboxylase ◽

Clinical Trial Registry ◽

Serious Adverse Events ◽

Double Blind ◽

Registration Number ◽

Urinary Parameters

BackgroundHyperoxaluria is typically associated with excessive oxalate intake in the diet, decreased dietary calcium, hyperabsorption of oxalate, or increased endogenous production of oxalate. The disorder spectrum extends from recurrent kidney stones to ESKD. This clinical trial sought to evaluate the effectiveness of an acid stable oxalate decarboxylase (OxDC) to reduce urinary oxalate in healthy subjects on a high-oxalate diet.MethodsIn this prospective, double-blind, randomized, placebo-controlled, crossover clinical trial, 33 healthy volunteers were randomized into two crossover sequences separated by a 2-day washout period. A controlled high-oxalate diet (750–800 mg oxalate, 500–550 mg calcium daily) was utilized, and six 24-hour urine collections were measured. Subjects were given approximately 1000 U (micromoles per minute per milligram) of OxDC or placebo with meals three times daily during the 4 days of treatment.ResultsUrinary oxalate significantly decreased with OxDC treatment. The baseline corrected within-subject mean reduction in 24-hour urinary excretion (after OxDC dosing versus high-oxalate baseline preceding treatment) was 12.5 mg or 29% (P<0.001). OxDC treatment was effective (>5% reduction) in 31 of 33 subjects (94%). Compared with placebo, OxDC produced a 24% reduction (P<0.001) in 24-hour oxalate excretion. Other urinary parameters (creatinine, uric acid, citrate, magnesium, calcium) were not affected by OxDC. No serious adverse events and no product-related adverse events occurred.ConclusionsAn orally administered OxDC is capable of significantly reducing urinary oxalate levels in healthy volunteers on a high-oxalate diet without affecting creatinine clearance, urine creatinine, or other solutes related to supersaturation of calcium oxalate.Clinical Trial registry name and registration number:Evaluation of Nephure, and the Reduction of Dietary Oxalate, in Healthy Volunteers, NCT03661216

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Real-world efficacy and safety of immune checkpoint inhibitors in advanced hepatocellular carcinoma: Experience of a tertiary Asian center.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.559 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 559-559

Author(s):

Kennedy Ng ◽

Lawrence Wen Jun Wong ◽

Su Pin Choo ◽

David Wai-Meng Tai ◽

Sze Huey Tan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trial ◽

Adverse Events ◽

Real World ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Advanced Hepatocellular Carcinoma ◽

Efficacy And Safety ◽

Advanced Hcc ◽

Increased Risk

559 Background: Immune checkpoint inhibitor (ICI) use in advanced hepatocellular carcinoma (HCC) is increasing. Real-world data on efficacy and safety however is lacking, more so when used in patients who fall out of standard clinical trial criteria. Methods: We conducted a retrospective review of all patients with advanced HCC seen at our centre who received at least one dose of an ICI between May 2015 - June 2018. Data cutoff was 31 Dec 2018. Responses were evaluated using RECIST v1.1 criteria. Results: 114 patients fulfilled inclusion criteria. Median age was 66 years and 88.6% were male. 96.5% had an ECOG PS of 0 – 1. 64.9% received an ICI within a clinical trial setting. 62.3% received monotherapy ICI. 19.6% of patients had Child-Pugh B disease on initiation of ICI, and 69.3% had an ALBI Grade of 2. 50.0% were known to have hepatitis B and 11.4% had hepatitis C. Baseline HBV VL ranged from undetectable to 8210000 IU/mL. 30.7% received prior systemic treatment, most commonly sorafenib (82.9%). Over a median follow-up duration of 5.7 months (0.03 - 42.4), ORR was 18.4%, and disease control rate (DCR) was 51.8%. Median PFS was 2.6 months (1.7 - 3.9), and median OS was 13.9 months (7.0 - 16.2). 5 patients (23.8%) had response duration of more than 18 months. 35.1% received further systemic therapy after ICI. On multivariable analyses, age ≥ 65 years, higher albumin level and lower bilirubin level were associated with increased OS. 68.0% of patients experienced adverse events (AEs) of any grade, 12.0% of these being grade 3 - 4. No grade 5 adverse events were observed. Use of antiviral therapy was associated with a lower risk of hepatic AEs (p = 0.04) whilst high baseline HBV VL was not associated with an increased risk of reactivation or hepatic AEs. Conclusions: In the real-world setting, responses and adverse event profiles to ICI use are comparable to those observed in clinical trials despite a more heterogenous population base. The expansion of indications for ICI use in advanced HCC beyond current approvals warrants greater study.

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Analysis of monitoring adverse events and problems in the treatment with sorafenib for hepatocellular carcinoma

Kanzo ◽

10.2957/kanzo.54.249 ◽

2013 ◽

Vol 54 (4) ◽

pp. 249-256

Author(s):

Keiko Komori ◽

Chie Mochizuki ◽

Yoshie Masu ◽

Noriko Hasegawa ◽

Akio Ishihara ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events

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