Masahiro Kanayama

Sorafenib Prevents Escape from Host Immunity in Liver Cirrhosis Patients with Advanced Hepatocellular Carcinoma

Purpose. It has been reported that Th2 cytokines downregulate antitumor immunity, while activation of type T cells promotes antitumor immunity. The aim of this paper was to evaluate host immunity in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) receiving sorafenib therapy. Methods. Forty-five adult Japanese LC patients received sorafenib for aHCC between 2009 and 2011 at our hospital. Sorafenib was administered at a dose of 200–800 mg/day for 4 weeks. Blood samples were collected before and after treatment. Results. Eleven patients were treated with sorafenib at 200 mg/day (200 group), 27 patients received sorafenib at 400 mg/day (400 group), and 7 patients were given sorafenib at 800 mg/day (800 group). There was no significant change in the percentage of Th1 cells after treatment in any group. However, the percentages of Th2 cells and regulatory T cells were significantly decreased after treatment in the 400 group and 800 group compared with before treatment, although there was no significant change after treatment in the 200 group. Conclusions. These results indicate that treatment with sorafenib might induce Th1 dominance and prevent the escape of tumor cells from the host immune system in LC patients with aHCC.

Sustained complete response of hepatocellular carcinoma with portal vein tumor thrombus following discontinuation of sorafenib: A case report.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-associated mortality worldwide. No effective treatment has been established for unresectable advanced HCC, and the prognosis is poor. Sorafenib is an oral multi-targeted tyrosine kinase inhibitor for unresectable advanced HCC that significantly improves progression-free and overall survival. However, in the two large phase III clinical trials (the SHARP and Asia-Pacific trials), no cases of complete response (CR) were reported. The present study reports the case of a 68-year-old male with hepatitis C virus-related cirrhosis and multiple recurrent HCCs, with a tumor thrombus of the third portal vein following resection. The patient received 400 mg once daily (half the standard dose) of sorafenib for two years and achieved a CR. At the most recent follow-up examination at one year after the cessation of treatment, the patient was observed to be in remission without clinical or imaging evidence of disease recurrence.

A Case of Sclerosing Angiomatoid Nodular Transformation of the Spleen: Correlations Between Contrast-enhanced Ultrasonography and Histopathologic Findings

Sclerosing angiomatoid nodular transformation (SANT) is a recently recognized benign vascular lesion of the spleen. Detection of SANT as an incidentaloma has increased due to improvements in imaging techniques. However, a definitive diagnosis of SANT on CT or MRI remains difficult. We report the use of contrast‐enhanced ultrasonography with Sonazoid in a case of SANT in a 50‐year‐old woman, with gross and microscopic pathologic correlations.

Changes of cytokines in cirrhosis patients with advanced hepatocellular carcinoma treated by intra-arterial chemotherapy.

IntroductionTumor necrosis factor (TNF) induces cancer cell-specific apoptosis by binding to a TNF-related apoptosis-inducing ligand. Binding of the Fas ligand on cytotoxic T lymphocytes to the Fas receptor on hepatocytes is also known to induce apoptosis. The aim of this study was to clarify changes of cytokines in patients with liver cirrhosis (LC) and advanced hepatocellular carcinoma (aHCC) receiving intra-arterial combination chemotherapy.MethodsTwenty-one adult Japanese LC patients with aHCC received intra-arterial combination chemotherapy. The serum levels of TNF-alpha, soluble TNF receptor-I (sTNFr-I), soluble Fas ligand (sFas L), and soluble Fas (sFas) were evaluated.ResultsThirteen of the 21 patients (group R) showed an objective response, while the other eight patients (group N) showed no response. The serum level of TNF-alpha was lower after chemotherapy than before chemotherapy in group N, but there was no difference of serum sTNFr-I levels between before and after chemotherapy and there were also no differences between the two groups. The serum sFas levels were higher after chemotherapy than before chemotherapy in group N, while there was no difference among groups.ConclusionsThese results indicate that a high serum TNF-alpha level and a low serum sFas level might be important for successful combined arterial chemotherapy in LC patients with aHCC.

Duct of Luschka diagnosed by sonography in a patient with bile duct carcinoma and intrahepatic bile duct dilatation

The bile duct of Luschka (BDL) is an anatomic anomaly that is an important cause of bile leakage after bile duct surgery. We report a case of bile duct carcinoma with dilated BDL that was diagnosed by ultrasonography (US). An 83‐year‐old man presented with an obstructive jaundice. US on admission revealed the presence of a solid hypoechoic mass in the bile duct at the hepatic duct confluence and a branch of the bile duct, about 2–4 mm in diameter, distinct from the dilated right anterior hepatic duct slightly upstream of the tumor. This branch had a spiral structure, extended along the gallbladder bed on the surface of segment 5 (S5) of the liver, and emanated small branches that entered the hepatic parenchyma. There has been no previous report of delineation of BDL by preoperative US.

Su2039 Changes of Cytokines in Cirrhosis Patients With Advanced Hepatocellular Carcinoma Treated by Sorafenib

PURPOSE:Sorafenib is multi-kinase inhibitor against RAF, involved in the growth of cancer cells and VEGFR(Vascular Endotherial Growth Factor Receptor), involved in angiogenesis around cancer. It is known that tumor stain is reduced by the administration of sorafenib. We retrospectively evaluated whether the decrease of blood flow after the administration of sorafenib affect the overall survival (OS) or not. METHODS:From May 2009 to November 2011, 127 patients out of 201 patients with advanced hepatocellular carcinoma (HCC) were treated with sorafenib and included in the present study. Patients received CE-CT or GdEOB-DTPA-MRI before treatment and every 4~6 weeks were evaluated to find the therapeutic effect. Patients were divided into 3 groups (No change group, partially decrease group, partially disappearance group) of tumor vascularity. We calculated OS of these 3 groups. RESULT:In the decrease group (85 cases, partially decrease group and partially disappearance group), the median OS was 19.6 months (95%C.I. 14.7-24.9). In the no change group (42 cases), the median OS was 8.6 months (95%C.I. 5.6-12.0). There were statistically significant differences between the two groups (p<0.001). In the partially disappearance group (51 cases), the median OS was 19.9 months (95%C.I. 11.3-28.6). In the partially decrease group (34 cases), the median OS was 22.0months (95%C.I. 12.2-32.0). There were no statistically significant differences between the two groups (p=0.59). CONCLUSION:In the treatment of sorafenib for advanced HCC, even if there is no necrosis, decrease of blood flow improves the OS.

Su2043 Serum VEGF Level and the Response to Combined Intra-Arterial Chemotherapy in Patients With Advanced Hepatocellular Carcinoma

A S L D A b st ra ct s 40.1±19.9kPa, p=0.01) and patients with nodules in the right liver lobe compared to the left lobe (46±20.4kPa vs 27.3±10.8kPa, p 15), patients with nodules >50mm had a significantly higher LSM value (71.8 ±4.8kPa vs 42.2±16.1kPa, p=0.001). Conclusion: There is a good correlation between liver stiffness assessed by Fibroscan® and HCC nodule size, in cirrhotic patients. Our data suggests that higher LSM values are registered in the presence of nodules >50mm in patients with low MELD score (< 15). Aggressive screening for HCC in cirrhotic patients with low MELD score and high LSM is mandatory, in order to early detect patients within Milan criteria for liver transplantation.

Su2041 Sorafenib Cancels Mechanisms to Escape From the Host Immune System in Cirrhosis Patients With Advanced Hepatocellular Carcinoma

A S L D A b st ra ct s 40.1±19.9kPa, p=0.01) and patients with nodules in the right liver lobe compared to the left lobe (46±20.4kPa vs 27.3±10.8kPa, p 15), patients with nodules >50mm had a significantly higher LSM value (71.8 ±4.8kPa vs 42.2±16.1kPa, p=0.001). Conclusion: There is a good correlation between liver stiffness assessed by Fibroscan® and HCC nodule size, in cirrhotic patients. Our data suggests that higher LSM values are registered in the presence of nodules >50mm in patients with low MELD score (< 15). Aggressive screening for HCC in cirrhotic patients with low MELD score and high LSM is mandatory, in order to early detect patients within Milan criteria for liver transplantation.

A case of type II c itrullinemia diagnosed 3 years after right lobectomy for hepatocellular carcinoma

シトルリン血症は尿素サイクルの一つであるアルギニノコハク酸合成酵素 (ASS) の欠損, あるいは活性低下により高シトルリン血症および高アンモニア血症を呈して意識障害を発現する, 常染色体劣性遺伝を示す疾患である. 本症例は幼児期から学業成績不良で, 青年期にはナルコレプシーやてんかんと診断され, 平成12年に刑事事件を起こし, 精神鑑定で精神病と認定された. その後に肝硬変・肝細胞癌が発見され, 右葉切除を受けていた. 今回, 他医でブドウ糖7.5%加アミノ酸製剤の輸液を契機に昏睡状態となり当院救命救急センターに搬入され, 血漿アンモニア値の著増から血漿アミノ酸分析を行い, シトルリンが高値であったため分子遺伝学的検索を行った. その結果, SLC25A13遺伝子の変異を認め成人発症II型シトルリン血症(CTLN2)と診断された.