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Aoki J.,Komagome Hospital | Aoki J.,Tokyo Metropolitan Otsuka Hospital | Aoki J.,Kanagawa Cancer Center | Ishiyama K.,Komagome Hospital | And 14 more authors.
Biology of Blood and Marrow Transplantation | Year: 2014

Central nervous system (CNS) involvement in adult acute myeloid leukemia (AML) is rare and associated with poor outcomes. Therefore, CNS involvement in AML is an indicator for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the impact of CNS involvement in AML on the outcome of allo-HSCT remains unclear. We performed a large-scale nationwide retrospective analysis to elucidate the outcomes of allo-HSCT on AML with CNS involvement (CNS+AML). Clinical data were collected from a registry database of the Japan Society for Hematopoietic Cell Transplantation. CNS involvement was defined as the infiltration of leukemia cells into the CNS or myeloid sarcoma in the CNS identified at any time from diagnosis to transplantation. One hundred fifty-seven patients with CNS+AML underwent allo-HSCT between 2006 and 2011. The estimated overall survival, cumulative incidence of relapse and nonrelapse mortality at 2 years for CNS+AML (51.2%, 30.2%, and 14.5%, respectively) were comparable with those for AML without CNS involvement (48.6%, 27.4%, and 22.0%, respectively). Univariate and multivariate analyses indicated that the development of chronic graft-versus-host disease, disease status, and cytogenetic risk category were independent prognostic factors for overall survival for CNS+AML. These results suggest that allo-HSCT may improve outcomes in patients with CNS+AML. © 2014 American Society for Blood and Marrow Transplantation.

PubMed | Oita University, Hamamatsu University School of Medicine, Miyagi Cancer Center, Saiseikai Maebashi Hospital and 15 more.
Type: | Journal: Blood cancer journal | Year: 2014

The superiority of the pediatric protocol for adolescents with acute lymphoblastic leukemia (ALL) has already been demonstrated, however, its efficacy in young adults remains unclear. The ALL202-U protocol was conducted to examine the efficacy and feasibility of a pediatric protocol in adolescents and young adults (AYAs) with BCR-ABL-negative ALL. Patients aged 15-24 years (n=139) were treated with the same protocol used for pediatric B-ALL. The primary objective of this study was to assess the disease-free survival (DFS) rate and its secondary aims were to assess toxicity, the complete remission (CR) rate and the overall survival (OS) rate. The CR rate was 94%. The 5-year DFS and OS rates were 67% (95% confidence interval (CI) 58-75%) and 73% (95% CI 64-80%), respectively. Severe adverse events were observed at a frequency that was similar to or lower than that in children treated with the same protocol. Only insufficient maintenance therapy significantly worsened the DFS (hazard ratio 5.60, P<0.001). These results indicate that this protocol may be a feasible and highly effective treatment for AYA with BCR-ABL-negative ALL.

PubMed | National Hospital Organization Shikoku Cancer Center, Sapporo Medical University, National Cancer Center Research Institute, National Cancer Center Hospital and 10 more.
Type: Journal Article | Journal: BMC gastroenterology | Year: 2016

Evidence supporting the associations between folate metabolizing gene polymorphisms and pancreatic cancer has been inconclusive. We examined their associations in a case-control study of Japanese subjects.Our case-control study involved 360 newly diagnosed pancreatic cancer cases and 400 frequency-matched, non-cancer control subjects. We genotyped four folate metabolizing gene polymorphisms, including two polymorphisms (rs1801133 and rs1801131) in the methylenetetrahydrofolate (MTHFR) gene, one polymorphism (rs1801394) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene and one polymorphism (rs1805087) in the 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) gene. Genotyping was performed using Fluidigm SNPtype assays. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between folate metabolizing gene variants and pancreatic cancer risk.Overall we did not observe a significant association between these four genotypes and pancreatic cancer risk. For rs1801133, compared with individuals with the CC genotype of MTHFR C677T, the OR for those with the CT genotype and TT genotype was 0.87 (0.62-1.22) and 0.99 (0.65-1.51), respectively. For rs1801131, individuals with the CC genotype had approximately 1.2-fold increased risk compared with those with the AA genotype, but the association was not statistically significant. In analyses stratified by smoking and drinking status, no significant associations were noted for C677T genotypes. No significant interactions were observed with smoking and drinking with respect to pancreatic cancer risk.Our data did not support the hypothesis that MTHFR polymorphisms or other polymorphisms in the folate metabolizing pathway are associated with pancreatic cancer risk.

Miyauchi J.,Tokyo Dental College | Ito Y.,National Center for Child Health and Development | Tsukamoto K.,National Center for Child Health and Development | Takahashi H.,Tokyo Metropolitan Otsuka Hospital | And 3 more authors.
British Journal of Haematology | Year: 2010

Mutations of GATA1, leading to aberrant expression of a truncated form of GATA1 (called GATA1s), are present in transient leukaemia (TL) in neonates with Down syndrome. Using these molecular markers of TL, we investigated the growth and differentiation potential of TL blasts in the presence of hematopoietic growth factors (HGFs). Interleukin-3, stem cell factor and granulocyte- macrophage colony-stimulating factor potently stimulated the growth of TL blast progenitors and induced differentiation towards basophil/mast cell lineages, whereas thrombopoietin induced differentiation towards megakaryocytes. GATA1s was expressed in TL blasts in all five patients examined but was down-regulated during differentiation induced by these HGFs, while full-length GATA1 was not expressed throughout the culture. GATA1 mutations were detected in TL blasts in four patients, including one patient with two distinct mutations. The cells of this patient exhibited identical and only mutated sequences both before and after culture with HGFs, confirming the leukemic cell origin of these differentiated cells. Erythroid differentiation of TL blasts was not evident with any HGFs. These data indicate that TL blasts have the potential to grow and differentiate towards particular hematopoietic lineages in the presence of specific HGFs and that the down-regulation of GATA1s might be involved in blast cell differentiation. © 2010 Blackwell Publishing Ltd.

Kikuchi A.,Tokyo Metropolitan Otsuka Hospital
Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2012

Here, we present the case of a 73-year-old woman in whom abdominal computed tomography showed an abdominal tumor (13 cm in diameter) in the backspace of the posterior gastric wall. Its feeding artery was detected to be the left gastric artery by abdominal angiography. We diagnosed it as a gastrointestinal stromal tumor (GIST) of the stomach and performed an operation. Peritoneal dissemination was observed and the tumor was connected to the gastric wall by a stalk. Histologically, the tumor consisted of spindle-shaped cells. Immunohistochemical staining showed positive c-kit and CD34 expression and negative SMA and S100 protein expression. Therefore, we diagnosed this as a case of extragastric pedunculated GIST of the stomach with peritoneal dissemination. After surgery, internal use of imatinib was started. The patient is still followed up 15 months after the operation. Combination therapy of tumor resection and imatinib chemotherapy might improve the prognosis of patients with GIST of the stomach with pedunculated growth.

Kakimoto M.,Tokyo Metropolitan Otsuka Hospital
Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2012

This is a case of a 58-year-old woman who underwent mastectomy for advanced right breast cancer (T2N2M0, stage IIIA, ER+, PR+, and HER2 0) at another hospital 13 years ago. Tamoxifen was administered after the operation. Two years later, bone and lung metastases appeared and she was transferred to our hospital. Hormonal therapies, epirubicin- cyclophosphamide-5-FU, doxifluridine, paclitaxel, vinorelbine, and capecitabine were ineffective. We planned a sixth-line chemotherapy comprising gemcitabine combined with docetaxel, but not paclitaxel. Partial response was obtained by treatment with 3 courses of gemcitabine-docetaxel. The same treatment was continued and the patient is alive in a good condition without progression for 14 months.

Koshiishi H.,Tokyo Metropolitan Otsuka Hospital
Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2011

The case is a 60-year-old female who underwent an operation as a right lobectomy of the thyroid and the resection of neck enlarged cystic lymph nodes in 2006. Pathological results were adenomatous goiter and the metastatic lymph nodes of papillary thyroid carcinoma. The primary lesion of thyroid carcinoma was not found. In four years after the operation, the local recurrence with anaplastic formation of the tumor occurred and tracheobronchial expandable metallic stent( EMS) therapy was performed to the tracheal stenosis. But she died of rapidly enlargement of the anaplastic thyroid carcinoma in two months after stent therapy. It was necessary to observe this case severely after the first operation because the primary lesion of the thyroid carcinoma was not resected. The tracheobronchial EMS therapy was effective to the respiratory failure for a short-term caused by the tracheal stenosis of the thyroid anaplastic carcinoma.

PubMed | Tokyo Metropolitan Otsuka Hospital
Type: Journal Article | Journal: Journal of anesthesia | Year: 2013

Since repeated noxious stimuli may sensitize neuropathic pain receptors of the spinal cord, we tested the hypothesis that the appropriate blockade of surgical stimuli with epidural anesthesia during upper abdominal surgery would be beneficial for postoperative analgesia. Thirty-six adult patients undergoing either elective gastrectomy or open cholecystectomy were randomly allocated to receive either inhalational general anesthesia alone (group G) or epidural anesthesia along with light general anesthesia (group E) throughout the surgery. Postoperative pain management consisted of patient-controlled analgesia (PCA) with bupivacaine accompanied by the continuous infusion of buprenorphine. To assess postoperative pain, a visual analogue scale (VAS) was employed at 2, 24, and 48 h postoperatively. While there was no significant difference in the bupivacaine dose, more patients undergoing gastrectomy in group G required supplemental analgesics than those in group E, and the VAS scores in group E demonstrated significantly better postoperative analgesia compared to group G after both types of surgery. Thus, an appropriate epidural blockade during upper abdominal surgery likely provides better postoperative pain relief.

PubMed | Tokyo Metropolitan Otsuka Hospital
Type: Journal Article | Journal: Journal of anesthesia | Year: 2013

To examine the adverse effects of peritoneal carbon dioxide (CO2) insufflation during laparoscopic cholecystectomy, both hemodynamic and respiratory alterations were continously monitored in 17 adult patients using noninvasive Doppler ultrasonography and a continuous spirometric monitoring device. During the surgery, which was performed under inhalational general anesthesia, intraabdominal pressure was maintained automatically at 10mmHg by a CO2 insufflator, and a constant minute ventilation, initially set to 30-33 mmHg of end-tidal CO2 (ETCO2), was maintained. Despite considerable depth of anesthesia, peritoneal CO2 insufflation induced a significant and immediate increase of mean blood pressure (+42%) and systemic vascular resistance (+62%), accompanied by a slight depression of cardiac index (-12%, nonsignificant), while the ETCO2 gradually increased and maximized around 30min following the initial CO2 insufflation. The stress of 10mmHg pneumoperitoneum was a major cause of hemodynamic changes during laparoscopic cholecystectomy. Some clinical strategies such as deliberate intraabdominal insufflation at the initial phase might be required to minimize these hemodynamic changes.

PubMed | Tokyo Metropolitan Otsuka Hospital
Type: Journal Article | Journal: Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2017

We report 2 cases of obstructive colorectal cancer that were successfully treated with a self-expanding metallic stent (SEMS). They were both diagnosed with obstructive colorectal cancer. Colonoscopy was performed to make a definitive and qualitative diagnosis and to relieve the stenosis using a SEMS. The SEMSs were inserted without complications. A few days later, the patients underwent laparoscope-assisted sigmoidectomy with lymph node resection. Despite the colon obstruction, a primary anastomosis was performed. They were both discharged without complications. Obstructive colorectal cancer is an oncological emergency commonly observed in our daily clinical practice. Conventional treatments such as stoma creation or insertion of a trans-analdrainage tube have been performed. However, these treatments significantly reduce the patients QOL. On the other hand, colonic stent placement plays a satisfactory role in improvement of the patients QOL by paying scrupulous attention to retaining the colonic stent.

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