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Atagi S.,Kinki chuo Chest Medical Center | Kawahara M.,Otemae Hospital | Yokoyama A.,Niigata Cancer Center Hospital | Okamoto H.,Yokohama Municipal Citizens Hospital | And 8 more authors.
The Lancet Oncology | Year: 2012

Background: It is unknown whether combined chemoradiotherapy improves overall survival in elderly patients with locally advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess whether radiotherapy plus carboplatin results in longer survival than radiotherapy alone in elderly patients with NSCLC. Methods: This was a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Patients older than 70 years with unresectable stage III NSCLC were randomly assigned to chemoradiotherapy (60 Gy plus concurrent low-dose carboplatin [30 mg/m2 per day, 5 days a week for 20 days]) or radiotherapy alone, using a minimisation method with biased-coin assignment balancing on Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1 vs 2), stage (IIIA vs IIIB), and institution. The primary endpoint was overall survival, which was analysed for the eligible population and stratified by ECOG performance status, stage, and institution. The trial was stopped early as a result of the second planned interim analysis. This study is registered with UMIN Clinical Trials Registry, number C000000060, and ClinicalTrials.gov, number NCT00132665. Findings: 200 patients were enrolled from Sept 1, 2003 to May 27, 2010: 100 in the chemoradiotherapy group and 100 in the radiotherapy group. The second planned interim analysis was done 10 months after completion of patient accrual. At this time, median follow-up for censored cases was 19·4 months (IQR 10·3-33·5). In accordance with the prespecified stopping rule, the JCOG data and safety monitoring committee recommended early publication of this trial because the difference in overall survival favoured the chemoradiotherapy group. Median overall survival for the chemoradiotherapy and radiotherapy alone groups were 22·4 months (95% CI 16·5-33·6) and 16·9 months (13·4-20·3), respectively (hazard ratio 0·68, 95·4% CI 0·47-0·98, stratified log-rank test one-sided p value=0·0179). More patients had grade 3-4 haematological toxic effects in the chemoradiotherapy group than in the radiotherapy alone group, including leucopenia (61 [63·5%] vs none), neutropenia (55 [57·3%] vs none), and thrombocytopenia (28 [29·2%] vs two [2·0%]). Grade 3 infection was more common with chemoradiotherapy (12 patients [12·5%]) than with radiotherapy (four patients [4·1%]). Incidences of grade 3-4 pneumonitis and late lung toxicity were similar between groups. There were seven treatment-related deaths: three of 100 patients (3·0%) in the chemoradiotherapy group and four of 100 (4·0%) in the radiotherapy group. Interpretation: For a select group of elderly patients with locally advanced NSCLC, combination chemoradiotherapy provides a clinically significant benefit over radiotherapy alone, and should be considered for this population. Funding: Ministry of Health, Labour, and Welfare of Japan. © 2012 Elsevier Ltd.


Tsuburaya A.,Yokohama City University | Yoshida K.,Gifu University | Yoshino S.,Yamaguchi University | Takahashi M.,Yokohama Municipal Citizens Hospital | And 14 more authors.
The Lancet Oncology | Year: 2014

Background: The prognosis for locally advanced gastric cancer is poor despite advances in adjuvant chemotherapy. We did the Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) to assess the superiority of sequential treatment (paclitaxel then tegafur and uracil [UFT] or paclitaxel then S-1) compared with monotherapy (UFT or S-1) and also the non-inferiority of UFT compared with S-1. Methods: We did this randomised phase 3 trial with a two-by-two factorial design at 230 hospitals in Japan. We enrolled patients aged 20-80 years with T4a or T4b gastric cancer, who had had D2 dissection and a ECOG performance score of 0-1. Patients were randomly assigned to one of four treatment groups with minimisation for tumour size, lymph node metastasis, and study site. Patients received UFT only (267 mg/m2 per day), S-1 only (80 mg/m2 per day) for 14 days, with a 7-day rest period or three courses of intermittent weekly paclitaxel (80 mg/m2) followed by either UFT, or S-1. Treatment lasted 48 weeks in monotherapy groups and 49 weeks in the sequential treatment groups. The primary endpoint was disease-free survival assessed by intention to treat. We assessed whether UFT was non-inferior to S-1 with a non-inferiority margin of 1·33. This trial was registered at UMIN Clinical Trials Registry, number C000000082. Findings: We randomly assigned 1495 patients between Aug 3, 2004, and Sept 29, 2009. 374 patients were assigned to receive UFT alone, 374 to receive S-1 alone, 374 to received paclitaxel then UFT, and 373 to receive paclitaxel then S-1. We included 1433 patients in the primary analysis after at least 3 years of follow-up (359, 364, 355, and 355 in each group respectively). Protocol treatment was completed by 215 (60%) patients in the UFT group, 224 (62%) in the S-1 group, 242 (68%) in the paclitaxel then UFT group, and 250 (70%) in the paclitaxel then S-1 group. 3-year disease-free survival for monotherapy was 54·0% (95% CI 50·2-57·6) and that of sequential treatment was 57·2% (53·4-60·8; hazard ratio [HR] 0·92, 95% CI 0·80-1·07, p=0·273). 3-year disease-free survival for the UFT group was 53·0% (95% CI 49·2-56·6) and that of the S-1 group was 58·2% (54·4-61·8; HR 0·81, 95% CI 0·70-0·93, p=0·0048; pnon-inferiority=0·151). The most common grade 3-4 haematological adverse event was neutropenia (41 [11%] of 359 patients in the UFT group, 48 [13%] of 363 in the S-1 group, 46 [13%] of 355 in the paclitaxel then UFT group, and 83 [23%] of 356 in the paclitaxel then S-1 group). The most common grade 3-4 non-haematological adverse event was anorexia (21 [6%], 24 [7%], seven [2%], and 18 [5%], respectively). Interpretation: Sequential treatment did not improve disease-free survival, and UFT was not non-inferior to S-1 (and S-1 was superior to UFT), therefore S-1 monotherapy should remain the standard treatment for locally advanced gastric cancer in Japan. Funding: Epidemiological and Clinical Research Information Network. © 2014 Elsevier Ltd.


Yoshimura Y.,Yokohama Municipal Citizens Hospital | Tachikawa N.,Yokohama Municipal Citizens Hospital | Komiya T.,Japan National Institute of Infectious Diseases | Yamamoto A.,Japan National Institute of Infectious Diseases
Epidemiology and Infection | Year: 2014

A human immunodeficiency virus-1 (HIV-1)-positive male undergoing antiretroviral therapy was diagnosed with an axillary lymph node abscess caused by Corynebacterium ulcerans, and an environmental survey revealed that the patient's cat as the source of infection. Copyright © Cambridge University Press 2013.


Nakazato T.,Yokohama Municipal Citizens Hospital | Nakazato T.,Keio University | Sagawa M.,Keio University | Sagawa M.,Saitama University | Kizaki M.,Saitama University
International Journal of Oncology | Year: 2014

Triptolide, a diterpenoid trioxide purified from the Chinese herb Tripterygium wilfordii Hook F, has been used as a natural medicine in China for hundreds of years. Several reports have demonstrated that triptolide inhibits the proliferation of cancer cells in vitro and reduces the growth of several types of tumors in vivo. To address the potential of triptolide as a novel therapeutic agent for patients with multiple myeloma, we investigated the effects of triptolide on the induction of apoptosis in human multiple myeloma cells in vitro. Triptolide rapidly induces apoptotic cell death in various myeloma cell lines. Triptolide-induced apoptosis in myeloma cells is associated with the loss of mitochondrial transmembrane potential (ΔΨ m), the release of cytochrome c and Smac/DIABLO from mitochondria into the cytosol, and the activation of caspase-3 and caspase-9. Furthermore, triptolide induces a rapid decline in the levels of Mcl-1 protein that correlates with caspase activation and induction of apoptosis. Inhibition of Mcl-1 synthesis by triptolide occurs at the level of mRNA transcription and is associated with an inhibition of phosphorylation of RNA polymerase II CTD. These results indicate that Mcl-1 is an important target for triptolide-induced apoptosis in myeloma cells that occurs via inhibition of Mcl-1 mRNA transcription coupled with rapid protein degradation through the ubiquitin-proteasome pathway.


Kamiya K.,Yokohama Municipal Citizens Hospital
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2013

Vascular-type Ehlers-Danlos syndrome(vEDS) is a rare autosomal dominant inherited disorder of the connective tissue, which often causes arterial ruptures and surgical complications. We report the case of a vEDS patient who was incidentally diagnosed at surgical treatment for hemothorax. A 64-year-old woman with a past history of hysterectomy due to excessive bleeding during childbirth visited our hospital complaining of chest pain. Chest computed tomography revealed right pleural effusion suspected of hemothorax and a high density area behind the right anterior chest wall. Emergency thoracoscopy revealed bloody spots throughout the mediastinal pleura, suggestive of bleeding from the right internal thoracic artery. During thoracoscopy, easy bruising of the tissue by surgical manipulation was noted which led us to suspect connective tissue disease. A biochemical analysis by cultured dermal fibroblasts and molecular biological examination established the diagnosis of vEDS.


Kamiya K.,Yokohama Municipal Citizens Hospital
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2011

Differential diagnosis of lung abscess from lung cancer is sometimes difficult. In February 2009, a 57-year-old man consulted our hospital complaining of bloody sputum. Chest computed tomography (CT) demonstrated a 2.5 cm nodule with pleural indentation, spicula and vascular involvement in the right S(3). Bronchofiberscope could not establish a definitive diagnosis. Blood test showed no abnormality. Three months later, progression of the nodule to the adjacent middle lobe was demonstrated by follow-up CT, and F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed isotope accumulation in the nodule and hilar lymph node. A diagnosis of lung cancer was suspected and surgery was performed. The diagnosis of possible lung cancer was made by needle biopsy, and the patient underwent right upper lobectomy and partial resection of middle lobe with standard nodal dissection. The final pathological diagnosis was lung abscess. Lung abscess must be kept in mind as a possible differential diagnosis when abnormal shadow suspected of lung cancer is observed.


Yoshizu A.,Yokohama Municipal Citizens Hospital
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2011

Diaphragmatic hernia complicating pregnancy is rare and results in a high mortality rate, if early surgical intervention is not undertaken. We report a case of a woman at 32 week's gestation who was admitted to our hospital due to severe epigastralgia. Diaphragmatic relaxation had been pointed out since her birth. The patient was initially diagnosed with acute gastritis, but she developed acute respiratory insufficiency on day 3 of hospitalization. Chest X-ray and computed tomography showed niveau in the left pleural cavity. She was treated with chest tube drainage and an emergency caesarean was performed. The next day, gastric fiberscope demonstrated perforation of gastric ulcer in the left hemithorax. She was diagnosed as having diaphragmatic hernia complicated by a perforated stomach. Emergency thoracotomy was carried out and primary repair of both stomach and diaphragma was performed.


Fukutomi T.,Keio University | Hayashi Y.,Keio University | Emoto K.,Keio University | Kamiya K.,Yokohama Municipal Citizens Hospital | And 2 more authors.
Human Pathology | Year: 2013

Small-sized lung adenocarcinomas often contain a lepidic growth component in part. The term lepidic growth has recently been used to represent a growth pattern of neoplastic cells along preexisting alveolar structures. We reviewed 91 small-sized (≤3 cm) invasive lung adenocarcinomas with a lepidic component to study the histopathologic and clinicopathologic characteristics. In the lepidic component of invasive adenocarcinoma, we have identified a morphologically unique structure characterized by proliferation of low papillae, consisting of neoplastic cells piling up toward the alveolar space, and we defined this architecture as "low papillary structure." There were 18 cases with the low papillary structure in the lepidic components, whereas 73 cases did not have the structure. In the lepidic component, the cases with the low papillary structure had higher Ki-67 labeling index (15.7%) and more frequent p53 overexpression (50.0%) than did those without the structure (9.4% and 16.4%, respectively). Based on clinicopathologic findings, the presence of low papillary structure was significantly associated with lymphatic invasion (P =.023) and lymph node metastasis (P =.001). Furthermore, the patients with the low papillary structure in the lepidic components demonstrated significantly shorter disease-free and overall survival than did those without the structure (P =.001 and P =.010, respectively). We conclude that the low papillary structure is a significant histologic feature in a lepidic component and is associated with aggressive cancer behavior in lung adenocarcinoma. © 2013 Elsevier Inc.


Tachikawa N.,Yokohama Municipal Citizens Hospital
Nihon rinsho. Japanese journal of clinical medicine | Year: 2012

These are six different classes of antiretroviral drugs that are nucleoside/nucleotide reverse transcriptase inhibitors(NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors, CCR5 inhibitors and integrase inhibitors. NRTIs are thought as backbone of HAART(highly active antiretroviral therapy) and tenofovir/emtricitabine is one of the most important combinations in NRTIs. Efavirenz has been one of the most effective key drugs of HAART but rilpivirine and etravirine have been options recently. PIs have been also effective key drugs. Lopinavir/ritonavir (LPV/RTV) had been a last option to virological failures but adverse events such as diarrhea, nausea and hypertriglycemia of these drugs were severe. Darunavir/ritonavir is more virologically effective PIs with milder adverse events than LPV/RTV.


Okamoto H.,Yokohama Municipal Citizens Hospital
Japanese Journal of Lung Cancer | Year: 2015

In Japan, the number of elderly patients with lung cancer is increasing along with the prolongation of life. In the 2012 Japan cancer registry, 73% of lung cancer deaths occurred in patients ≥70 years of age. The Japanese guidelines recommend monotherapy with third-generation agents as grade A treatment and carboplatin-based doublets as grade C1 treatment for elderly patients with an epidermal growth factor receptor (EGFR) wild-type status or unknown advanced non-squamous non-small cell lung cancer (NSCLC) and recommend the same regimen for elderly patients with advanced squamous cell lung cancer. However, three metaanalyses reported conflicting results regarding the use of monotherapy vs. doublet chemotherapy in elderly patients with advanced NSCLC. Therefore, no clear-cut consensus for optimal chemotherapy for this population exists. In Japan, a phase III trial evaluating the inferiority of carboplatin-pemetrexed doublet chemotherapy to docetaxel monotherapy is ongoing among elderly patients with advanced non-squamous NSCLC. Although no comparative trials in elderly patients with EGFR mutation-positive disease have been reported, the use of EGFR tyrosine kinase inhibitors (TKIs) in this population has been widely accepted based on several phase II trials in Japan. A Japan Clinical Oncology Group (JCOG) phase III trial demonstrated the superiority of daily carboplatin plus thoracic radiotherapy over radiotherapy alone for elderly patients with locally advanced stage III NSCLC. In elderly patients with extensive disease small cell lung cancer (ED-SCLC), carboplatin plus etoposide (CE) is considered to be a standard regimen, and a JCOG phase II/III study comparing carboplatin plus irinotecan with CE for elderly patients with ED-SCLC is ongoing. Although the use of a simple and effective comprehensive geriatric assessment (CGA) has been warranted for a long time, no standard CGA methods have been established to date. Additional clinical trials of elderly lung cancer patients are thus needed. © 2015 The Japan Lung Cancer Society.

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