Takano Hospital

Kumamoto-shi, Japan

Takano Hospital

Kumamoto-shi, Japan

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Ueno H.,National Defense Medical College | Hase K.,National Defense Medical College | Hashiguchi Y.,Teikyo University | Shimazaki H.,National Defense Medical College | And 13 more authors.
American Journal of Surgical Pathology | Year: 2014

The study aimed to determine the value of a novel site-specific grading system based on quantifying poorly differentiated clusters (PDC; Grade PDC) in colorectal cancer (CRC). A multicenter pathologic review involving 12 institutions was performed on 3243 CRC cases (stage I, 583; II, 1331; III, 1329). Cancer clusters of ≥5 cancer cells and lacking a gland-like structure (PDCs) were counted under a ×20 objective lens in a field containing the maximum clusters. Tumors with <5, 5 to 9, and ≥10 PDCs were classified as grades G1, G2, and G3, respectively. According to Grade PDC, 1594, 1005, and 644 tumors were classified as G1, G2, and G3 and had 5-year recurrence-free survival rates of 91.6%, 75.4%, and 59.6%, respectively (P<0.0001). Multivariate analysis showed that Grade PDC exerted an influence on prognostic outcome independently of TNM staging; approximately 20% and 46% of stage I and II patients, respectively, were selected by GradePDC as a population whose survival estimate was comparable to or even worse than that of stage III patients. Grade PDC surpassed TNM staging in the ability to stratify patients by recurrence-free survival (Akaike information criterion, 2915.6 vs. 2994.0) and had a higher prognostic value than American Joint Committee on Cancer (AJCC) grading (GradeAJCC) at all stages. Regarding judgment reproducibility of grading tumors, weighted κ among the 12 institutions was 0.40 for GradeAJCC and 0.52 for GradePDC. GradePDC has a robust prognostic power and promises to be of sufficient clinical value to merit implementation as a site-specific grading system in CRC. Copyright © 2013 by Lippincott Williams & Wilkins.


PubMed | Red Cross, Tokyo Women's Medical University, Iwate Medical University, Takano Hospital and 15 more.
Type: Journal Article | Journal: Oncotarget | Year: 2015

Our previous study showed that administering oxaliplatin as first-line chemotherapy increased ERCC1 and DPD levels in liver colorectal cancers (CRCs) metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this multicenter observational study to validate our previous findings on ERCC1 and DPD, and clarify the response of VEGFA expression to bavacizumab administration. 346 CRC patients with liver metastases were enrolled at 22 Japanese institutes. Resected liver metastases were available for 175 patients previously treated with oxaliplatin-based chemotherapy (chemotherapy group) and 171 receiving no previous chemotherapy (non-chemotherapy group). ERCC1, DPYD, and VEGFA mRNA levels were measured by real-time RT-PCR. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group (P = 0.033), and were significantly correlated (Spearmans correlation coefficient = 0.42; P < 0.0001). VEGFA expression level was higher in patients receiving bevacizumab (n = 51) than in those who did not (n = 251) (P = 0.007). This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPYD expression levels, potentially enhancing chemosensitivity to subsequent therapy. We also found that bevacizumab induces VEGFA expression in tumor cells, suggesting a biologic rationale for extending bevacizumab treatment beyond first progression.


Ueno H.,National Defense Medical College | Hase K.,National Defense Medical College | Hashiguchi Y.,Teikyo University | Shimazaki H.,National Defense Medical College | And 14 more authors.
Journal of Gastroenterology | Year: 2014

Background Novel risk factors for lymph node metastasis (LNM) in T1 colorectal cancer (CRC) have been recently proposed, but most have not been implemented because of the lack of validation. Here we determined the value of poorly differentiated clusters (PDCs) in a multi-institutional cohort of T1 CRC cases. Methods A pathology review involving 30 institutions was conducted for 3556 T1 CRCs. PDC was defined as malignant clusters comprising ≥5 cells and lacking a glandular formation. The ability to identify LNM risk was compared using Akaike’s information criterion (AIC). Results PDC was observed in 1401 tumors (39.4 %), including 94 (17.8 %) with <1000 μm submucosal invasion and 1307 (43.2 %) with ≥1000 μm submucosal invasion (P<0.0001). The incidence of LNM was higher in PDC-positive tumors (17.4 %) than in PDC-negative tumors (6.9 %; P<0.0001), and PDCs had an adverse impact on LNM irrespective of the degree of submucosal invasion. Grade 3, vascular invasion, budding, and submucosal invasion depth were also significant factors (all, P<0.0001). AIC of risk factor to identify LNM risk was most favorable for vascular invasion (2273.4), followed by PDC (2357.4); submucosal invasion depth (2429.1) was the most unfavorable. Interinstitutional judgment disparities were smaller in PDC (kappa, 0.51) than vascular invasion (0.33) or tumor grade (0.48). Conclusions PDC is a promising new parameter with good ability to identify LNM risk. Use of its appropriate judgment criteria will enable us determine whether an observational policy can be safely applied following local tumor excision in T1 CRC cases. © 2013, Springer Japan.


Tsunoda A.,Kameda Medical Center | Yamada K.,Takano Hospital | Kano N.,Kameda Medical Center | Takano M.,Takano Hospital
Surgery Today | Year: 2013

Purpose: The aim of the study was to conduct a psychometric evaluation of the fecal incontinence quality of life scale (FIQL) in the Japanese language using rigorous methodologies. Methods: The FIQL was translated into Japanese. After being linguistically validated, the Japanese version of the FIQL was administered to a sample of 119 patients who completed the questionnaire at baseline and again after 2 weeks. The patients filled out a general questionnaire regarding health (the Short-Forum 36 Health Survey), and the severity of incontinence was assessed at baseline (Wexner scale). Results: Internal consistency was good/excellent for all scales (Cronbach's alpha >0.70, between 0.72 and 0.94). Stability over time was good for all scales (Intra-class correlation >0.80, between 0.86 and 0.93). The four scales of the FIQL were significantly correlated with the scales of the generic questionnaire on health (P < 0.0001) and the Wexner scale (P < 0.0001). The mean FIQL score improved significantly after treatment in the 22 patients whose Wexner scale scores decreased >4 points, thus indicating good sensitivity in all four scales and the total scale. Conclusions: The linguistic and psychometric evaluation demonstrated the validity of the Japanese version of the FIQL. © 2012 Springer Japan.


Masahiro T.,Takano Hospital
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2010

To characterize the symptoms of neurogenic intrapelvic syndrome and the pathogenic mechanisms. A total of 537 patients with neurogenic intrapelvic syndrome were treated in the Takano Hospital between 2001 and 2005. Clinical data were analyzed retrospectively. The mean age was 58.5 years old. There were 205 males and 332 females. There were 80 patients(14.9%) who presented with only one symptom with anorectal pain being the most common one (43.8%, 35/80). One hundred and fifty-six(29.1%) patients had two symptoms with anorectal pain and difficult evacuation being the most common combination (26.3%, 41/156). There were 144 patients (26.8%) complained of 3 symptoms and the most common combination was anorectal pain, difficult evacuation, and abdominal discomfort (30.0%, 43/144). A combination of 4 symptoms was reported in 105 patients(19.6%) with the combination of anorectal pain, incontinence, abdominal discomfort, and lumbar discomfort being the most often(65.7%, 69/105). In addition, there were 52 patients(9.7%) who had above 5 symptoms simultaneously. The frequencies of the 5 symptoms were 73.6% for anorectal pain, 27.9% for incontinence, 69.6% for difficult evacuation, 55.3% for abdominal discomfort, and 53.6% for lumbar discomfort. Symptomatology of neurogenic intrapelvic syndrome is complicated. The pathogenic mechanism may be related to concurrent dysfunction of sacral nerve and pelvic splanchnic nerve.


Fukudo S.,Tohoku University | Hongo M.,Kurokawa Hospital | Kaneko H.,Hoshigaoka Maternal Hospital | Takano M.,Takano Hospital | Ueno R.,Sucampo AG
Clinical Gastroenterology and Hepatology | Year: 2015

Background and Aims: Lubiprostone is an activator of the type 2 chloride channel that facilitates spontaneous bowel movement (SBM). We performed phase 3 studies to determine whether lubiprostone increases the frequency of SBM in patients with chronic idiopathic constipation (CIC) in Japan, and whether long-term administration of lubiprostone increases the quality of life of patients with CIC. Methods: We performed a randomized, double-blind, placebo-controlled, phase 3 trial of lubiprostone. Patients with CIC (n= 124) were assigned randomly to groups given placebo (n= 62) or lubiprostone (48 μg/day; n= 62) for 4 weeks. The primary efficacy end point was the change from baseline in the weekly average number of SBMs after 1 week of administration. In a long-term study of efficacy and safety, 209 patients with CIC were given lubiprostone (24 μg twice daily) for 48 weeks. Results: Daily administration of lubiprostone induced a significantly greater change, from baseline, in the weekly average number of SBMs at week 1 (increase of 3.7 ± 2.8), compared with placebo (increase of 1.3 ± 1.8; P < .001). The frequency of SBMs during each week of the study period was significantly higher after subjects began receiving lubiprostone than at baseline (. P < .0001 at all weeks). Long-term administration of lubiprostone significantly increased scores from the Short-Form health survey and irritable bowel syndrome quality-of-life questionnaire, compared with baseline. We did not observe any severe adverse reactions to lubiprostone. Conclusions: In phase 3 studies in Japan, lubiprostone increased the weekly average number of SBMs and increased the quality of life of patients with CIC. Clinical Trial Notification of the Japanese Regulatory Authorities: 20-3296 and 20-3300. © 2015 AGA Institute.


Kobayashi N.,Takano Hospital | Tajiri J.,Tajiri Clinic | Takano M.,Takano Hospital
Journal of Medical Case Reports | Year: 2011

Introduction. There are few reports on thyrotoxic psychosis caused by diseases other than Graves' disease or toxic nodular goiter. Case presentation. A 64-year-old Japanese woman was treated for anxiety disorder in our clinic for 10 years. She had five episodes of transient psychosis during the first five years. When she developed psychosis without neck pain 10 years after her first visit, a laboratory reexamination revealed that she had subclinical hyperthyroidism, and tested positive for antithyroid autoantibodies, negative for thyroid stimulating hormone receptor antibody and had decreased radioactive iodine uptake. She was diagnosed as having painless thyroiditis. The hyperthyroidism disappeared within a month, and the psychosis lasted for three months. Conclusion: To the best of our knowledge, this is the first report of psychosis due to painless thyroiditis-induced hyperthyroidism. Physical symptoms of painless thyroiditis are often so mild that careful differential diagnosis is necessary in the cases of transient psychosis. © 2011 Kobayashi et al; licensee BioMed Central Ltd.


Hirai F.,Fukuoka University | Ishihara H.,Fukuoka University | Yada S.,Kyushu University | Esaki M.,Kyushu University | And 9 more authors.
Digestive Diseases and Sciences | Year: 2013

Background: One of the problems associated with infliximab (IFX) treatment for Crohn's disease (CD) is loss of response during maintenance therapy. Aims: The aim of this multicenter, retrospective, cohort study was to determine whether enteral nutrition (EN) added to the IFX therapy regimen is effective for maintaining remission in adult CD patients. Methods: Patients with CD who had started IFX therapy between April 2003 and March 2008 at any one of the seven participating medical centers and who met the following inclusion criteria were enrolled in the study: remission after triple infusions of IFX followed by IFX maintenance therapy every 8 weeks, and follow-up data available for ≥1 year. Remission was defined as a C-reactive protein (CRP) level of <0.3 mg/dL, and recurrence was defined as an increase in CRP to ≥1.5 mg/dL or shortening of the IFX interval. Patients were classified by EN dosage into two groups (EN group and non-EN group). The cumulative remission period and related factors were analyzed. Results: Of the 102 adult CD patients who met the inclusion criteria, 45 were in the EN group and 57 were in the non-EN group. The cumulative remission rate was significantly higher in the EN group than in the non-EN group (P = 0.009). Multivariate analysis revealed that EN was the only suppressive factor for disease recurrence (P = 0.01). Conclusions: The results demonstrate that among this CD patient cohort, EN combined with IFX maintenance treatment was clinically useful for maintaining remission. © 2012 The Author(s).


PubMed | Hoshigaoka Maternal Hospital, Tohoku University, Sucampo AG, Kurokawa Hospital and Takano Hospital
Type: Journal Article | Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | Year: 2015

Lubiprostone is an activator of the type 2 chloride channel that facilitates spontaneous bowel movement (SBM). We performed phase 3 studies to determine whether lubiprostone increases the frequency of SBM in patients with chronic idiopathic constipation (CIC) in Japan, and whether long-term administration of lubiprostone increases the quality of life of patients with CIC.We performed a randomized, double-blind, placebo-controlled, phase 3 trial of lubiprostone. Patients with CIC (n= 124) were assigned randomly to groups given placebo (n= 62) or lubiprostone (48 g/day; n= 62) for 4 weeks. The primary efficacy end point was the change from baseline in the weekly average number of SBMs after 1 week of administration. In a long-term study of efficacy and safety, 209 patients with CIC were given lubiprostone (24 g twice daily) for 48 weeks.Daily administration of lubiprostone induced a significantly greater change, from baseline, in the weekly average number of SBMs at week 1 (increase of 3.7 2.8), compared with placebo (increase of 1.3 1.8; P < .001). The frequency of SBMs during each week of the study period was significantly higher after subjects began receiving lubiprostone than at baseline (P < .0001 at all weeks). Long-term administration of lubiprostone significantly increased scores from the Short-Form health survey and irritable bowel syndrome quality-of-life questionnaire, compared with baseline. We did not observe any severe adverse reactions to lubiprostone.In phase 3 studies in Japan, lubiprostone increased the weekly average number of SBMs and increased the quality of life of patients with CIC. Clinical Trial Notification of the Japanese Regulatory Authorities: 20-3296 and 20-3300.


PubMed | Red Cross, Takano Hospital, Beppu University, Kurume University and 10 more.
Type: Journal Article | Journal: PLoS genetics | Year: 2016

Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation. To this end, we profiled the genome and epigenome in multiple regions within each of nine colorectal tumors. Extensive intertumor heterogeneity is observed, from which we inferred the evolutionary history of the tumors. First, clonally shared alterations appeared, in which C>T transitions at CpG site and CpG island hypermethylation were relatively enriched. Correlation between mutation counts and patients ages suggests that the early-acquired alterations resulted from aging. In the late phase, a parental clone was branched into numerous subclones. Known driver alterations were observed frequently in the early-acquired alterations, but rarely in the late-acquired alterations. Consistently, our computational simulation of the branching evolution suggests that extensive intratumor heterogeneity could be generated by neutral evolution. Collectively, we propose a new model of colorectal cancer evolution, which is useful for understanding and confronting this heterogeneous disease.

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