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Ohkubo H.,Yokohama City University | Kessoku T.,Hiratsuka City Hospital | Fuyuki A.,Chigasaki Municipal Hospital | Iida H.,Yokohama City University | And 11 more authors.
American Journal of Gastroenterology | Year: 2013

OBJECTIVES:Chronic intestinal pseudo-obstruction (CIPO) is a rare, serious motility disorder, with life-threatening complications over time. However, lack of an established, non-invasive diagnostic method has caused delays i. The diagnosis of this intractable disease. Cine-magnetic resonance imaging (MRI) is an emerging technique, with a potential to evaluat. The motility o. The entire bowel. We compared small bowel motility in healthy volunteers, patients with irritable bowel syndrome (IBS), and those with CIPO, using cine-MRI, and evaluate. The usefulness of cine-MRI as a novel diagnostic method for CIPO.METHODS:Twelve healthy volunteers, IBS patients, and CIPO patients prospectively underwent cine-MRI at 1.5 T. Luminal diameter, contraction ratio, and contraction cycle were measured and compared betwee. The groups.RESULTS:Cine-MRI provided sufficient dynamic images to asses. The motility o. The entire small bowel. Luminal diameter (mean±s.d.) in CIPO patients was significantly higher than that in healthy volunteers and IBS patients (43.4±14.1, 11.1±1.5, and 10.9±1.9 mm, respectively), and contraction ratio was significantly lower in CIPO patients than that in healthy volunteers and IBS patients (17.1±11.0%, 73.0±9.3%, and 74.6±9.4%, respectively). No significant differences were observed i. The contraction cycle.CONCLUSIONS:This study i. The first to asses. The clinical utility of cine-MRI in CIPO patients. Cine-MRI clearly detected contractility impairments in CIPO patients. Cine-MRI is noninvasive, radiation-free, and can directly evaluat. The entire small bowel peristalsis, and can detec. The affected loops at a glance; therefore, it might be extremely useful fo. The diagnosis and follow-up of CIPO patients in clinical practice.


PubMed | Red Cross, Nippon Telegraph and Telephone, National Cancer Center Hospital, Nippon Medical School and 2 more.
Type: Journal Article | Journal: Leukemia | Year: 2016

We conducted a comprehensive analysis of 28 recurrently mutated genes in acute myeloid leukemia (AML) in 271 patients with de novo AML. Co-mutations were frequently detected in the intermediate cytogenetic risk group, at an average of 2.76 co-mutations per patient. When assessing the prognostic impact of these co-mutations in the intermediate cytogenetic risk group, overall survival (OS) was found to be significantly shorter (P=0.0006) and cumulative incidence of relapse (CIR) significantly higher (P=0.0052) in patients with complex molecular genetic abnormalities (CMGAs) involving three or more mutations. This trend was marked even among patients aged 65 years who were also FLT3-ITD (FMS-like tyrosine kinase 3 internal tandem duplications)-negative (OS: P=0.0010; CIR: P=0.1800). Moreover, the multivariate analysis revealed that CMGA positivity was an independent prognostic factor associated with OS (P=0.0007). In stratification based on FLT3-ITD and CEBPA status and simplified analysis of co-mutations using seven genes that featured frequently in CMGAs, CMGA positivity retained its prognostic value in transplantation-aged patients of the intermediate cytogenetic risk group (OS: P=0.0002. CIR: P<0.0001). In conclusion, CMGAs in AML were found to be strong independent adverse prognostic factors and simplified co-mutation analysis to have clinical usefulness and applicability.


PubMed | Red Cross, Nippon Telegraph and Telephone, National Cancer Center Hospital, Nippon Medical School and 2 more.
Type: Journal Article | Journal: Haematologica | Year: 2016

In recent years, it has been reported that the frequency of DNA-methylation regulatory gene mutations - mutations of the genes that regulate gene expression through DNA methylation - is high in acute myeloid leukemia. The objective of the present study was to elucidate the clinical characteristics and prognosis of acute myeloid leukemia with associated DNA-methylation regulatory gene mutation. We studied 308 patients with acute myeloid leukemia. DNA-methylation regulatory gene mutations were observed in 135 of the 308 cases (43.8%). Acute myeloid leukemia associated with a DNA-methylation regulatory gene mutation was more frequent in older patients (P<0.0001) and in patients with intermediate cytogenetic risk (P<0.0001) accompanied by a high white blood cell count (P=0.0032). DNA-methylation regulatory gene mutation was an unfavorable prognostic factor for overall survival in the whole cohort (P=0.0018), in patients aged 70 years, in patients with intermediate cytogenetic risk, and in FLT3-ITD-negative patients (P=0.0409). Among the patients with DNA-methylation regulatory gene mutations, 26.7% were found to have two or more such mutations and prognosis worsened with increasing number of mutations. In multivariate analysis DNA-methylation regulatory gene mutation was an independent unfavorable prognostic factor for overall survival (P=0.0424). However, patients with a DNA-methylation regulatory gene mutation who underwent allogeneic stem cell transplantation in first remission had a significantly better prognosis than those who did not undergo such transplantation (P=0.0254). Our study establishes that DNA-methylation regulatory gene mutation is an important unfavorable prognostic factor in acute myeloid leukemia.


PubMed | Red Cross, Saga University, Nippon Telegraph and Telephone, Kitano Hospital and 7 more.
Type: | Journal: Leukemia research | Year: 2016

The risk of complication of polycythemia vera (PV) and essential thrombocythemia (ET) by thrombosis in Japanese patients is clearly lower than in western populations, suggesting that genetic background such as race may influence the clinical features. This study aimed to clarify the relationship between genetic mutations and haplotypes and clinical features in Japanese patients with PV and ET. Clinical features were assessed prospectively among 74 PV and 303 ET patients. There were no clinical differences, including JAK2V617F allele burden, between PV patients harboring the various genetic mutations. However, CALR mutation-positive ET patients had a significantly lower WBC count, Hb value, Ht value, and neutrophil alkaline phosphatase score (NAP), and significantly more platelets, relative to JAK2V617F-positive ET patients and ET patients with no mutations. Compared to normal controls, the frequency of the JAK246/1 haplotype was significantly higher among patients with JAK2V617F, JAK2Ex12del, or MPL mutations, whereas no significant difference was found among CALR mutation-positive patients. CALR mutation-positive patients had a lower incidence of thrombosis relative to JAK2V617F-positive patients. Our findings suggest that JAK2V617F-positive ET patients and CALR mutation-positive patients have different mechanisms of occurrence and clinical features of ET, suggesting the potential need for therapy stratification in the future.


Izumi K.,Yokohama City University | Taguri M.,Yokohama City University | Miyamoto H.,Johns Hopkins University | Hara Y.,Odawara Municipal Hospital | And 18 more authors.
Oncotarget | Year: 2014

Although accumulating preclinical evidence indicates the involvement of androgen receptor signals in bladder cancer (BC) development, its clinical relevance remains unclear. We aimed to evaluate the predictive role of androgen deprivation therapy (ADT) in BC recurrence in prostate cancer (PC) patients. We retrospectively reviewed 20,328 patients with PC diagnosed during 1991-2013 and identified 239 (1.2%) men having primary BC. After excluding ineligible patients, 162 patients made up a final cohort. With a median follow-up of 62 months, 38 (50%) of 76 control patients without ADT experienced BC recurrence, while 19 (22%) of 86 did in ADT group. Thus, patients having received ADT for their PC showed a significantly lower risk of BC recurrence (5-year actuarial recurrence-free survival: 76% v 40%; P < 0.001) and also had a significantly smaller number of recurrence episodes (5-year cumulative recurrence: 0.44 v 1.54; P < 0.001), compared to the control patients. A multivariable analysis revealed ADT as an independent prognosticator (hazard ratio, 0.29; 95% confidence interval, 0.17-0.49) for BC recurrence. This is the first clinical study showing that ADT significantly reduces the risk of BC recurrence.


Ng K.,Macquarie University | Higurashi M.,Yokohama Minami Kyousai Hospital | Uemiya N.,Saitama University | Qian Y.,Macquarie University
PLoS ONE | Year: 2014

Haemodynamic changes in cerebral circulation are associated with the natural ageing process and associated pathology, leading to the development of incapacitating neurological and neurovascular diseases. Due to inherent biological limitations, current literatures mostly aimed at studying the correlation descriptively or quantifying the relationship in vitro or using computational models. In this paper, a model of a carotid-jugular fistula in the rat was used to create a haemodynamic insult to the intracranial arterial circulation and subsequent venous drainage. An arterial-venous (AV) fistula was created in 12 rats, 6 of which are normotensive Wistar-Kyoto strain (WKY) and the rest spontaneously hypertensive strain (SHR) with an additional 6 in each strains designed as controls without previous surgery. After 4 weeks of convalescence, all 24 rats were euthanised and their cerebral circulation was examined histomorphologically. We confirmed an intrinsic morphological difference between normotensive WKY and hypertensive SHR and found a modest but significant arterial shrinkage in both strains induced with AV fistula. We also reported that alterations in blood flow are also associated with marked extracellular matrix changes. We concluded that the model was suitable for studying the relative contributions of altering haemodynamic patterns and venous drainage on cerebrovascular changes. We also found that hypertension modulated cerebral vascular changes in addition to disrupted blood flow. © 2014 Ng et al.


Uemura H.,Yokohama City University | Yanagisawa M.,Yokohama Minami Kyousai Hospital | Ikeda I.,Yokohama Minami Kyousai Hospital | Fujinami K.,Chigasaki City Hospital | And 4 more authors.
International Journal of Clinical Oncology | Year: 2013

Background: To ascertain the anti-tumor effect of zoledronic acid (ZOL) treatment on clinical outcomes in patients with bone metastatic prostate cancer, we examined the effect of ZOL started simultaneously with hormonal therapy as initial treatment in these patients. Methods: Forty-seven patients with bone-metastatic prostate cancer who received a luteinizing hormone releasing-hormone (LHRH) analogue and an anti-androgen [maximal androgen blockade (MAB)] were assigned to receive ZOL (4 mg intravenous administration every month for 2 years). The time to progression (TTP) of the prostate-specific antigen (PSA), the overall survival (OS), and the rate of PSA decrease in patients with MAB and ZOL treatment (ZOL group) were compared with these parameters in patients who received only MAB at one institute as a control group (non-ZOL group). Results: Although the nadir PSA level and the rate of PSA normalization showed no significant differences between the ZOL and non-ZOL groups, the time to nadir PSA in the ZOL group was significantly shorter than that in the non-ZOL group (P < 0.05, Mann-Whitney U-test). There was a significant difference in TTP (P = 0.017, log-rank test) between the ZOL and non-ZOL groups, and statistically significant differences in TTP and OS between the ZOL and non-ZOL groups (P = 0.044 and 0.035, log-rank test) were recognized particularly in patients with advanced disease (extension of disease, grade 3 and 4). Conclusions: Simultaneous administration of ZOL and MAB as initial treatment delayed TTP in bone-metastatic prostate cancer patients. Initial treatment with ZOL has the possibility of anti-tumor activity to delay disease progression. © 2012 Japan Society of Clinical Oncology.


PubMed | Yokohama Minami Kyousai Hospital and Yokohama City University
Type: Case Reports | Journal: Clinical journal of gastroenterology | Year: 2015

Fatty changes are frequently observed in small, well-differentiated hepatocellular carcinomas (HCCs), but are rarely observed in large (over 30 mm in diameter) lesions. Here, we report a 76-year-old man who developed a large (58 mm in diameter), well-differentiated HCC with diffuse extensive fatty changes in the right lobe of the liver. He had no history of alcohol abuse, obesity, or hepatitis B or C infection, and no autoantibodies, but he did have type 2 diabetes. The serum alpha-fetoprotein level was within the normal range, and ultrasonography showed a round hyperechoic lesion. Dynamic contrast-enhanced computed tomography revealed a tumor with inhomogeneous low attenuation in the arterial, portal, and venous phases, mimicking an angiomyolipoma. The patient underwent central bisegmentectomy of the liver, and the histological diagnosis was well-differentiated HCC with diffuse extensive fatty changes. The surrounding non-cancerous area was normal. A review of the published literature found six published cases of large, well-differentiated HCC with extensive fatty changes. Unlike the patients in most previous reports, our patient did not have any underlying liver disease and had no history of alcohol abuse.


Ideguchi H.,Yokohama City University | Suda A.,Yokohama City University | Suda A.,Yokohama Minami Kyousai Hospital | Takeno M.,Yokohama City University | And 3 more authors.
Clinical and Experimental Rheumatology | Year: 2011

Objective. We analysed the clinical vascular characteristics of Behçet's disease (BD) patients in Japan. Methods. We retrospectively reviewed the clinical charts of 412 patients who fulfilled the 1987 Japanese criteria for BD and were treated in two University hospitals from July 1991 to December 2007. Patients with superficial thrombophlebitis were excluded, since it is categorised as a skin manifestation according to the Japanese criteria. Results. Twenty-six patients (6%) had large-vessel involvement. Mean ages at BD diagnosis and onset of vascular episodes were 39.7 and 41.6 years, respectively. Males predominated (62%). Arterial and venous lesions were found in 8 (31%) and 21 patients (81%), respectively, including 3 (12%) with both types. Pulmonary artery occlusion was the most common arterial lesion (n=5, 19%), followed by ascending aortic aneurysm (n=2, 8%). Limb deep vein thrombosis was the leading venous lesion (n-20, 77%). Cardiac complications (angina pectoris)'aortic regurgitation) occurred in two patients. Gastrointestinal involvement was more frequent than in patients without vascular involvement (p<0.001); ocular involvement was less frequent (p<0.05). Only 3 patients (12%) required surgery. Patients received prednisone and immunosuppressants, including infliximab, for vascular and! or concurrent gastrointestinal involvement. Nine patients received warfarin, without bleeding complications. One patient died during the observation period, 4 days after surgery for an aortic aneurysm. Conclusion. Frequency of vascular involvement in BD in Japan is lower than in other ethnic populations. Although one patient died during the observation, there was no fatal haemoptysis, even in patients receiving warfarin. © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2011.


Hirakawa T.,Nippon Medical School | Yamaguchi H.,Nippon Medical School | Yokose N.,Nippon Medical School | Gomi S.,Yokohama Minami Kyousai Hospital | And 2 more authors.
Annals of Hematology | Year: 2010

CHOP-like regimen combined with rituximab is a standard chemotherapy for diffuse large B-cell lymphoma (DLBCL). The relative dose intensity (RDI) was proposed as an index of the dose and administration interval of agents. Previous studies reported that the maintenance of the RDI during CHOP therapy improved the treatment results. However, few studies regarding RDI have reviewed patients receiving combination therapy with CHOP and rituximab. We investigated the influence of RDI maintenance, involving combination therapy with rituximab, on therapeutic effects in patients with DLBCL. We retrospectively examined 152 DLBCL patients who were treated with CHOP-like regimen combined with rituximab in whom the RDI could be followed up. Multivariate analysis revealed that international prognosis index (IPI) high intermediate-high (HI-H) (p=0.005) and RDI of less than 70% (p=0.007) were independent prognostic factors for low progression free survival. Concerning overall survival, IPI HI-H (p=0.027) and an RDI of less than 70% (p=0.002) were involved in an unfavorable prognosis. In addition, age over 60 years (p=0.003), R-THPCOP (p=0.034), or the presence of febrile neutropenia (p=0.004) made RDI maintenance difficult, and prophylactic G-CSF therapy (p=0.026) was useful for maintaining the RDI. Maintaining the RDI is important even in the era of rituximab-combined chemotherapy for DLBCL. © 2010 Springer-Verlag.

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