Showing papers by "Hiroshi Yoshida published in 2011"

Impact of nodal involvement on surgical outcomes of intrahepatic cholangiocarcinoma: a multicenter analysis by the Study Group for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Abstract: The aim of this study was to clarify the prognostic factors of intrahepatic cholangiocarcinoma (ICC) following hepatectomy and to examine the impact of lymph node metastasis on survival. This study was therefore carried out as a Project Study of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. Three hundred and forty-one patients who underwent hepatectomy for ICC between 1995 and 2004 at the 9 institutions of the Medical University Hospitals were analyzed retrospectively. Multivariate regression analyses and a Kaplan–Meyer analysis were performed to identify prognostic factors. Pathological lymph node metastasis was one of the significant factors affecting overall survival (hazard ratio 2.10, p < 0.001) based on the multivariate analysis. Among the patients who underwent extended lymphadenectomy beyond the hepatoduodenal ligament, the median survival of 121 patients with nodal involvement was 12.2 months. Only seven patients with nodal involvement have survived for more than 4 years. In the present study, preoperative carbohydrate antigen (CA) 19-9, intrahepatic metastasis, and nodal involvement were the significant independent predictors of poor prognosis by multivariate analysis. Further prospective studies may thus be needed to confirm these findings, because this study has a limitation in that it was a retrospective study with multicenter data collection.

Phase I trial of neoadjuvant chemoradiation with gemcitabine and surgical resection for cholangiocarcinoma patients (NACRAC study).

Abstract: Background/aims The feasibility of neoadjuvant chemoradiation therapy for cholangiocarcinoma, followed by conventional resection, has not been determined yet. Here, a phase I study of neoadjuvant chemoradiation therapy, named NACRAC, was performed to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of gemcitabine when combined with external beam radiation therapy for resectable cholangiocarcinoma. Methodology From August 2007 to June 2008, 12 patients provided informed consent. Preoperative radiation was administered in 1.8Gy daily fractions up to a total dose of 45Gy. Gemcitabine was administered at day 1 and 8 every three weeks. The initial dose of gemcitabine was started from 400mg/m2. Results One patient was not able to start treatment because of bleeding caused by a duodenal ulcer and cholangitis. At 800mg/m2 of gemcitabine, one patient out of three failed to complete the treatment because of Grade 3 hematological toxicity. In another three cases of 800mg/m2, the second case could not complete the treatment because of cholangitis. Then, 600mg/m2 was determined to be the MTD, and the RD dose decided as 600mg/m2. Conclusions The RD of gemcitabine in NACRAC study was determined to be 600mg/m2. NACRAC study should proceed to a phase II trial to evaluate the effectiveness.

In vitro and in vivo antitumor effects of recombinant bispecific antibodies based on humanized anti-EGFR antibody.

Abstract: We performed in vitro and in vivo experiments of the anti-epidermal growth factor receptor (EGFR) x anti-CD3 bispecific diabody (hEx3-Db) with the IgG-like bispecific antibodies (BsAbs) (hEx3-scFv-Fc and hEx3-scDb-Fc) and the anti-EGFR therapeutic antibody cetuximab to assess the effect of BsAbs on cancer growth inhibition. In vitro, efficacy of the BsAbs and cetuximab were compared by growth inhibition assays of human cell lines of bile duct (TFK-1, HuCC-T1, OCUCh-LM1), epidermoid (A431), gastric (Kato-III), colon (DLD-1, SW480), and breast (SK-BR-3, MCF-7) cancer. In vivo, in three mouse models, we evaluated the anti-tumor activity of hEx3-Db and cetuximab, assessed the effect of hEx3-Db alone, and compared the antitumor activity of hEx3-Db with the IgG-like BsAbs. In vitro, hEx3-scFv-Fc showed nearly 100% killing activity for all cell lines. Both in vitro and in vivo, hEx3-Db needed CD3-positive phenotypes to induce a growth inhibitory effect. In contrast, IgG-like BsAbs showed monotherapeutic effects in vivo by inducing antibody-dependent cellular cytotoxicity (ADCC) similar to cetuximab. However, enhancement was not observed when lymphokine-activated killer cells with the T-cell phenotype were co-injected. Results suggest that IgG-like BsAbs could not efficiently direct T lymphocytes toward tumor cells to induce ADCC due to steric hindrance on binding to CD3- and Fc-receptor-positive phenotypes. Although hEx3-scFv-Fc showed high cytotoxicity in vitro, its high molecular weight limits its usefulness. With an in vivo effect comparable to hEx3-scFv-Fc and its realistic molecular weight, hEx3-scDb-Fc shows promise as a novel recombinant therapeutic antibody and may be modified to enhance its potency by prevention of steric hindrance.

Fulminant type of emphysematous pancreatitis has risk of massive hemorrhage

Abstract: Emphysematous pancreatitis (air in the parenchyma) was previously considered an indication for surgery, but some recent studies have reported good clinical outcomes with non-operative management. As a step toward establishing a better treatment strategy, we report a case of fulminant pancreatitis with massive hemorrhage into the emphysematous space. A 75-year-old man was admitted with worsening abdominal pain with obstructive jaundice and renal failure 28 h after the onset. He was diagnosed as having emphysematous pancreatitis with slight pancreatic necrosis. Despite conservative treatment with intensive care, sudden cardiac and respiratory failure occurred, and he died 53 h after onset. The autopsy findings revealed biliary sludge and massive bleeding in the retroperitoneal space around the pancreas, suggesting that temporary obstruction of the bile duct with sludge induced emphysema and the hemorrhage rapidly spread into the broadened emphysematous space. Whereas conservative management has been thought to be appropriate in selected cases of emphysematous pancreatitis, when there is pancreatic emphysema in the early phase, a fulminant course tends to develop. Since there is a risk of massive bleeding into the emphysematous space, endoscopic or invasive drainage performed to collapse the emphysematous space could benefit the outcome.

A Single-Chip RF Tuner/OFDM Demodulator for Mobile Digital TV Application

Abstract: This paper presents a single-chip RF tuner/OFDM demodulator for a mobile digital TV application called “1-segment broadcasting.” To achieve required performances for the single-chip receiver, a tunable technique for a low-noise amplifier (LNA) and spurious suppression techniques are proposed in this paper. Firstly, to receive all channels from 470MHz to 770MHz and to relax distortion characteristics of following circuit blocks such as an RF variable-gain amplifier and a mixer, a tunable technique for the LNA is proposed. Then, to improve the sensitivity, spurious signal suppression techniques are also proposed. The single-chip receiver using the proposed techniques is fabricated in 90nm CMOS technology and total die size is 3.26mm × 3.26mm. Using the tunable LNA and suppressing undesired spurious signals, the sensitivities of less than -98.6dBm are achieved for all the channels.