Chūō-ku, Japan
Chūō-ku, Japan

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Kitayama H.,Tonan Hospital
Clinical Medicine Insights: Therapeutics | Year: 2016

Serotonin-type 3 receptor antagonists have been available as intravenous and oral formulations. Recently, granisetron transdermal system has won a firm position in the antiemesis of cancer chemotherapy. Its pharmacokinetic profile has been shown by pooled population analysis incorporation data. The 52 cm2 patch, which contains 34.3 mg granisetron, releases 3.3 mg daily and reaches the maximal plasma concentration after 48 hours, maintaining a 2.2 ng/mL stable average concentration over six days. This level is similar to the one obtained with daily oral 2 mg of granisetron. Three randomized clinical studies evaluating its efficacy have been published. Transdermal granisetron showed noninferiority to other formulations of serotonin-type 3 receptor antagonists for highly and moderately emetogenic – including multiday – chemotherapy. The adverse effects were not significantly different from other formulations. The system has possible applications in oral chemotherapy, radiotherapy, dexamethasone sparing, palliative care, and refractory emesis due to benign disease. © 2016; the authors, publisher and licensee Libertas Academica Limited.


Oda I.,National Cancer Center Hospital | Shimazu T.,Research Center for Cancer Prevention and Screening | Ono H.,Shizuoka Cancer Center | Tanabe S.,Kitasato University | And 3 more authors.
Gastric Cancer | Year: 2012

A Japanese multicenter prospective cohort study is currently being conducted on endoscopic resection (ER) for early gastric cancer (EGC) using a Web registry system developed to determine short-term and long-term outcomes based on the absolute and expanded indications. All consecutive patients with EGC or suspected EGC undergoing ER at the 41 participating institutions from July 2010 to June 2012 are being enrolled in the study cohort using the Web registry system, and each patient will be followed up for a minimum of 5 years. The study investigation includes baseline patient and lesion characteristics as well as short-term and long-term outcomes. A survey program to collect information on long-term outcomes is also being introduced for patients subsequently followed up in institutions other than their original participating institutions, as well as patients for whom the original participating institutions have been losing track of their follow-up. The primary endpoint is 5-year overall survival, with en bloc resection, curative resection, complication, local recurrence, distant metastasis, metachronous EGC, and recurrence-free survival being secondary endpoints in addition to the successful collection of longterm outcome data on enrolled patients utilizing the survey program. © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2011.


PubMed | Sapporo Kiyota Hospital, Hokkaido Gastroenterology Hospital, Tonan Hospital, Obihiro Kosei General Hospital and 2 more.
Type: | Journal: Langenbeck's archives of surgery | Year: 2017

Despite its spread and advances, laparoscopic gastrectomy (LG) for advanced gastric cancer (AGC) remains controversial. The aim of this study was to evaluate the oncologic outcomes and to identify the potential risk factors for recurrence and survival after LG in AGC patients.The medical records of patients who underwent radical LG for histopathologically diagnosed stage IB or more advanced gastric cancer from 2004 to 2012 were collected. The clinicopathologic factors and outcomes were evaluated retrospectively.LG was performed for 300 patients, with a median operative time of 278min and blood loss of 46ml. Postoperative morbidity was defined as Clavien-Dindo grades III and IV and occurred in 13 patients (6.3%) in the laparoscopic distal gastrectomy group. The pathologic stage was IB in 109 patients (36.3%), IIA in 77 patients (25.7%), IIB in 48 patients (16.0%), IIIA in 31 patients (10.3%), IIIB in 19 patients (6.3%), and IIIC in 16 patients (5.3%). Median follow-up period was 55.2months. The 3-year relapse-free survival (RFS) rate was 92.7% for stage IB, 87.0% for IIA, 68.8% for IIB, 64.5% for IIIA, 47.4% for IIIB, and 43.8% for IIIC. The 5-year actual overall survival rate was 91.1% for stage IB, 72.7% for II, and 62.5% for III. Multivariate analysis revealed postoperative complication as an independent risk factor for RFS.LG for AGC was feasible and provided comparable oncologic outcomes with those previously reported. Postoperative complications correlated with poor prognosis. Randomized control trials should be conducted to confirm these results of LG for AGC in the general population.


Kato K.,National Cancer Center Hospital | Chin K.,Cancer Institute Hospital Tokyo | Yoshikawa T.,Kanagawa Cancer Center | Yamaguchi K.,Saitama Cancer Center | And 8 more authors.
Investigational New Drugs | Year: 2012

Purpose NK105 is a new drug delivery system formulation for paclitaxel (PTX) whose recommended dose (RD) is 150 mg PTX equivalent/m 2 administered every 3 weeks, as determined in a phase I trial. This study aimed to evaluate the efficacy and safety of NK105 in patients with advanced gastric cancer after failure of first-line chemotherapy. Experimental design Eligible patients had measurable disease and one chemotherapeutic regimen except taxane. NK105 (150 mg PTX equivalent/m 2) was administered by a 30-minute intravenous infusion every 3 weeks without antiallergic premedication until disease progression, unacceptable toxicity or patient refusal. The primary efficacy endpoint was best overall response rate (ORR) post baseline. The secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF) and overall survival (OS). All adverse events were reported using CTCAE v3.0. Results Between November 2007 and July 2009, 57 patients were enrolled and 56 were evaluable for efficacy. Two complete responses and 12 partial responses were observed for an ORR of 25%. The median PFS was 3.0 months, the median TTF was 2.8 months, and the median OS was 14.4 months. Drug related toxicity was mainly mild (grades 1-2) to severe (grades 3-4); other data: neutropenia (64.9%); leukopenia (17.5%); lymphopenia (8.8%); neuropathysensory (1.8%); fatigue (3.5%); and stomatitis (1.8%). There were no treatment-related deaths. Conclusions This study of NK105 (150 mg PTX equivalent/m 2) proves the concept for the modest activity and tolerability of a new drug delivery system formulation for PTX. A phase III trial will be evaluated to clarify survival benefit. © Springer Science+Business Media, LLC 2011.


Aikawa N.,Keio University | Shimazaki S.,Kyorin University | Yamamoto Y.,Tokyo Rinkai Hospital | Saito H.,Nagoya Central Hospital | And 5 more authors.
Shock | Year: 2011

To investigate treatment effects of thrombomodulin alfa (TM-α) in patients with disseminated intravascular coagulation (DIC) having infection as the underlying disease, retrospective subanalysis of a double-blind, randomized controlled phase 3 trial was conducted. In the phase 3 trial, 227 DIC patients (full-analysis set) having infection and/or hematologic malignancy as the underlying disease received either TM-α (0.06 mg·kg-1 for 30 min once daily) or heparin (8 U·kg-1·h -1 for 24 h) for 6 days using the double-dummy method. Among these patients, 147 patients with noninfectious comorbidity leading to severe thrombocytopenia (e.g., hematologic malignancy, or aplastic anemia) were excluded from the present analysis, and 80 patients with infectious disease and DIC were extracted and subjected to the present retrospective subanalysis. Disseminated intravascular coagulation resolution rates were determined using the DIC diagnostic criteria for critically ill patients at 7 days, and mortality rates were evaluated at 28 days. In the TM-α and heparin groups, DIC resolution rates were 67.5% (27/40) and 55.6% (20/36), and 28-day mortality rates were 21.4% (9/42) and 31.6% (12/38), respectively. Mortality rates of patients who recovered from DIC were 3.7% (1/27) in the TM-α group and 15% (3/20) in the heparin group. These results suggest TM-α may be valuable in the treatment of DIC associated with infection. Copyright © 2011 by the Shock Society.


Oyamada M.,Fuji Women's University | Takebe K.,Fuji Women's University | Oyamada Y.,Tonan Hospital
Biochimica et Biophysica Acta - Biomembranes | Year: 2013

Gap junctions are specialized cell-cell junctions that directly link the cytoplasm of neighboring cells. They mediate the direct transfer of metabolites and ions from one cell to another. Discoveries of human genetic disorders due to mutations in gap junction protein (connexin [Cx]) genes and experimental data on connexin knockout mice provide direct evidence that gap junctional intercellular communication is essential for tissue functions and organ development, and that its dysfunction causes diseases. Connexin-related signaling also involves extracellular signaling (hemichannels) and non-channel intracellular signaling. Thus far, 21 human genes and 20 mouse genes for connexins have been identified. Each connexin shows tissue- or cell-type-specific expression, and most organs and many cell types express more than one connexin. Connexin expression can be regulated at many of the steps in the pathway from DNA to RNA to protein. In recent years, it has become clear that epigenetic processes are also essentially involved in connexin gene expression. In this review, we summarize recent knowledge on regulation of connexin expression by transcription factors and epigenetic mechanisms including histone modifications, DNA methylation, and microRNA. This article is part of a Special Issue entitled: The communicating junctions, roles and dysfunctions. © 2011 Elsevier B.V.


Ebihara Y.,Tonan Hospital | Okushiba S.,Tonan Hospital | Kawarada Y.,Tonan Hospital | Kitashiro S.,Tonan Hospital | Katoh H.,Tonan Hospital
Langenbeck's Archives of Surgery | Year: 2013

Purpose: Totally laparoscopic total gastrectomy (TLTG) is unpopular because reconstruction is difficult. In fact, esophagojejunostomy is the most difficult surgical technique in TLTG. We adopted functional end-to-end anastomosis for esophagojejunostomy to simplify the procedure. The present study assesses the feasibility and surgical outcomes of TLTG with functional end-to-end esophagojejunostomy. Methods: We assessed the intraoperative and postoperative outcomes of 65 consecutive patients who underwent TLTG with functional end-to-end esophagojejunostomy at Tonan Hospital between January 2006 and August 2011. Results: The mean surgical duration was 271.5 ± 64.7 min, and the mean blood loss was 85.2 ± 143.2 g. One patient (1.5 %) was converted to open surgery, and two patients (3.1 %) required reoperation due to ileus because of an internal hernia and jejunojejunostomy leakage. No reoperation was associated with functional end-to-end esophagojejunostomy. The mean hospital stay was 21.4 ± 13.5 days. Ten patients (15.4 %) developed postoperative complications, of which three (4.6 %) were anastomotic stenosis associated with functional end-to-end esophagojejunostomy. All of these were resolved by endoscopic dilation. Conclusion: Functional end-to-end esophagojejunostomy in TLTG is safe and feasible. © 2013 The Author(s).


Ukau K.,Tonan Hospital | Hisa N.,Tonan Hospital
Acta Hepatologica Japonica | Year: 2016

Aim: We assessed the safety and effectiveness of drug-eluting beads transarterial chemoembolization (DEB TACE) with 5-fluorouracil (5FU) loaded Hepa-Sphere for classical hepatocellular carcinoma (HCC). Regimen: A: 5FU 250 mg/5 ml, non-ionic contrast medium (CM) 5 ml, HepaSphere 25 mg, B: 5FU 400 mg/8 ml, CM 2 ml, HepaSphere 25 mg, C: 5FU 300 mg/6 ml, CM 2 ml, 10% NaCl 2 ml, HepaSphere 25 mg D: The regimen C is diluted from 10 times. Results: There was no CTCAE Grade 2-5 adverse reaction. The response (CR/PR/SD/PD, CR + PR rate) was as follows; A; 0/1/3/0, 25%, B; 0/1/5/0, 16.7%, C; 1/ 1/2/0, 50%, D; 1/2/3/0, 50%. Conclusion: DEB TACE with 5FU loaded HepaSphere for classical HCC is safe. It seems to be more favorable with well-tolerated and effective method uses 10% NaCl. © 2016 The Japan Society of Hepatology.


PubMed | Tonan Hospital
Type: Journal Article | Journal: Molecular and clinical oncology | Year: 2017

Intravenous and intraperitoneal paclitaxel with S-1 is showing promising results in gastric cancer with peritoneal metastases. We herein report a successful conversion of unresectable to resectable disease using combination chemotherapy with trastuzumab. The patient was a 39-year-old woman with human epidermal growth factor receptor 2-positive gastric cancer with peritoneal, pulmonary and bilateral ovarian metastases. After 6 cycles of S-1 plus cisplatin with trastuzumab, followed by 15 cycles of intravenous and intraperitoneal paclitaxel with S-1 and trastuzumab, the pulmonary and peritoneal metastases exhibited complete response and no evidence of malignancy was found on diagnostic laparoscopy. We performed metastasectomy of the bilateral sizeable ovaries, followed by total gastrectomy. The patient had no recurrence for 16 months after the gastrectomy. Therefore, satisfactory response to systemic and intraperitoneal chemotherapy may convert unresectable to resectable disease, and primary tumor resection with ovarian metastasectomy may prolong survival. This combination chemotherapy has the potential of becoming a conversion therapy for gastric cancer with peritoneal metastases, even if ascites and ovarian metastases are extensive.


PubMed | Tonan Hospital and Hokkaido University
Type: Journal Article | Journal: Molecular and clinical oncology | Year: 2017

Combination chemotherapy consisting of systemic and intraperitoneal agents against peritoneal metastases from several types of cancer has shown promising results. We herein report a case in which combination therapy with intravenous and intraperitoneal paclitaxel with S-1 converted an unresectable pancreatic cancer with peritoneal metastases into a resectable one. The patient was a 65-year old woman with recurrent pancreatitis for 5 months. Endoscopic ultrasonography-guided fine-needle aspiration revealed minute epithelial masses composed of cells with irregular nuclei in the pancreatic body. The patient underwent abdominal surgery, but no excision was performed, as two peritoneal metastases in the bursa omentalis were detected. Combination therapy was initiated, consisting of intravenous and intraperitoneal paclitaxel with S-1 as a single-center clinical trial. The regimen consisted with 2-week administration of S-1 (80 mg per day) followed by 1 week of rest, intravenous paclitaxel 50 mg/m

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