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Mizuno Y.,Tokyo West Tokushukai Hospital | Fuchikami H.,Tokyo West Tokushukai Hospital | Takeda N.,Tokyo West Tokushukai Hospital | Iwai M.,Tokyo West Tokushukai Hospital | Sato K.,Tokyo West Tokushukai Hospital
Japanese Journal of Clinical Oncology | Year: 2017

Background: This retrospective study aimed to evaluate the efficacy of a 3.6-mg dose of pegfilgrastim for primary prophylaxis in Japanese breast cancer patients receiving dose-dense chemotherapy. Methods: Patients treated with adjuvant or neoadjuvant chemotherapy for early-stage breast cancer at the Tokyo-West Tokushukai Hospital were included in this analysis. Because 6mg pegfilgrastim has not yet been approved for use in Japan, we compared the outcomes of a dose-dense doxorubicin and cyclophosphamide regimen plus 3.6 mg pegfilgrastim support with a conventional dose epirubicin and cyclophosphamide regimen. The incidence of febrile neutropenia, relative dose intensity, dose delay, dose reduction, regimen change and hospitalization because of neutropenia were assessed. Results: From November 2013 to March 2016, 97 patients with stage I-III invasive breast cancer were analyzed (dose-dense doxorubicin and cyclophosphamide plus 3.6-mg pegfilgrastim group, n = 41; epirubicin and cyclophosphamide group, n = 56; median ages, 49.0 and 48.5 years, respectively). Febrile neutropenia occurred during the first chemotherapy cycle in 7 of 56 patients (12.5%) in the epirubicin and cyclophosphamide group and 0 of 41 patients in the dose-dense doxorubicin and cyclophosphamide group (P = 0.02). The average relative dose intensities were 97.9% and 96.8%, respectively (P = 0.28), with corresponding dose delay rates of 4.9% (2/41) and 16.1% (9/56), respectively (P = 0.11) and dose reduction rates of 0% (0/41) and 7.1% (4/56), respectively (P = 0.16). Conclusions: Our results indicate the efficacy of a 3.6-mg pegfilgrastim dose for the primary prevention of febrile neutropenia in dose-dense doxorubicin- and cyclophosphamide-treated Japanese breast cancer patients. © The Author 2016.


Takahashi S.,University of Tokyo | Haramoto Y.,University of Tokyo | Onuma Y.,Japan National Institute of Advanced Industrial Science and Technology | Nagamine K.,Hiroshima International University | And 4 more authors.
International Journal of Developmental Biology | Year: 2010

Ras guanyl nucleotide-releasing protein 2 (RASGRP2), one of the Ras guanine exchange factors, is implicated as a critical regulator of inside-out integrin activation in human lymphocytes, neutrophils and platelets. However, the activities of this protein in endothelial cells remain unclear. In the current study, we identify a physiological function in blood vessel formation for XRASGRP2, which is the Xenopus ortholog of mammalian RASGRP2. XRASGRP2 over-expression induced ectopic vascular formation, and XRASGRP2-knockdown embryos showed delayed vascular development. We also investigated the upstream signaling of XRASGRP2 in endothelium formation. XRASGRP2 expression was up-regulated in the presence of VEGF-A and down-regulated following VEGF-A depletion. XRASGRP2 knockdown abolished the ectopic induction of endothelial cells by VEGFA in the posterior ventral blood island. These results suggest that XRASGRP2 is essential for vascular formation during Xenopus development. © 2009.


PubMed | Inoue Ladies Clinic, Seto Hospital, Tokyo West Tokushukai Hospital and Utsunomiya Memorial Hospital
Type: Journal Article | Journal: Breast cancer (Tokyo, Japan) | Year: 2016

Partial breast irradiation (PBI) is an alternative to whole breast irradiation (WBI) for breast-conserving therapy (BCT). A randomised phase 3 trial demonstrated that PBI using multicatheter brachytherapy had an equivalent rate of local recurrence, disease-free survival, and overall survival as compared to WBI. However, limited data are available on PBI efficacy for young patients with breast cancer.We evaluated consecutive patients with Tis-2(3cm)N0-1 breast cancer who underwent BCT. For PBI, patients received radiotherapy using multicatheter brachytherapy in an accelerated manner with a dose of 32Gy in eight fractions over 5-6days. For WBI, patients received an external beam radiation therapy that was applied to the entire breast with a total dose of 50Gy in fractions of 2Gy for 5weeks. Two hundred seventy-four patients with 278 lesions received PBI; 190 patients with 193 lesions received WBI.Patients aged <50years including 98 women with 99 lesions receiving PBI and 85 women with 85 lesions receiving WBI were selected. Ipsilateral breast tumor recurrence rate was 3.0 and 2.4% by PBI and WBI, respectively (P=0.99). There was no significant difference in 4-year probability of disease-free survival (97.6 and 91.4% for PBI and WBI, respectively; P=0.87).This is the first report of PBI efficacy in young patients in Asia. Although it is a nonrandomized retrospective chart review of a small cohort of patients with a relatively short follow-up period, PBI may be a better option than WBI following BCS in some young patients with breast cancer.


PubMed | Inoue Ladies Clinic, Seto Hospital, Tokyo West Tokushukai Hospital and Utsunomiya Memorial Hospital
Type: Journal Article | Journal: Journal of contemporary brachytherapy | Year: 2015

Breast conserving surgery (BCS) followed by whole breast irradiation (WBI) is the standard of care for breast cancer patients. However, there is a risk of coronary events with WBI therapy. In this study, we compared the radiation dose in the left anterior descending artery (LAD) in patients receiving partial breast irradiation (PBI) with WBI.We evaluated consecutive patients who underwent adjuvant radiotherapy after BCS between October 2008 and July 2014. Whole breast irradiation patients received 50 Gy in fractions of 2 Gy to the entire breast. Partial breast irradiation was performed using multicatheter brachytherapy at a dose of 32 Gy in eight fractions. The mean and maximal cumulative doses to LAD were calculated. The radiotherapeutic biologically effective dose of PBI was adjusted to WBI, and radiation techniques were compared.Of 379 consecutive patients with 383 lesions receiving radiotherapy (151 WBI and 232 PBI lesions), 82 WBI and 100 PBI patients were analyzed. In WBI patients, the mean and maximal cumulative doses for left-sided breast cancer (2.13 0.11 and 8.19 1.21 Gy, respectively) were significantly higher than those for right-sided (0.37 0.02 and 0.56 0.03 Gy, respectively; p < 0.0001). In PBI patients with left-sided breast cancer, the doses for tumors in inner quadrants or central location (2.54 0.21 and 4.43 0.38 Gy, respectively) were significantly elevated compared to outer quadrants (1.02 0.17 and 2.10 0.29 Gy, respectively; p < 0.0001). After the adjustment, the doses in PBI patients were significantly reduced in patients with tumors only in outer quadrants (1.12 0.20 and 2.43 0.37 Gy, respectively; p = 0.0001).Tumor control and dose to LAD should be considered during treatment since PBI may reduce the risk of coronary artery disease especially in patients with lateral tumors in the left breast.


Woottisin S.,University of Ryukyus | Hossain R.Z.,University of Ryukyus | Hossain R.Z.,Tokyo West Tokushukai Hospital | Yachantha C.,University of Ryukyus | And 3 more authors.
Journal of Urology | Year: 2011

Purpose We evaluated the antilithic effect of Orthosiphon grandiflorus, Hibiscus sabdariffa and Phyllanthus amarus extracts on known risk factors for calcium oxalate stones in rats. Materials and Methods We divided 30 male Wistar rats into 5 equal groups. Controls were fed a standard diet and the remaining groups received a 3% glycolate diet for 4 weeks to induce hyperoxaluria. One glycolate fed group served as the untreated group and the others were given oral extracts of Orthosiphon grandiflorus, Hibiscus sabdariffa or Phyllanthus amarus at a dose of 3.5 mg daily. We collected 24-hour urine and blood samples. Kidneys were harvested for histological examination. We measured the renal tissue content of calcium and oxalate. Results The Hibiscus sabdariffa group showed significantly decreased serum oxalate and glycolate, and higher oxalate urinary excretion. The Phyllanthus amarus group showed significantly increased urinary citrate vs the untreated group. Histological examination revealed less CaOx crystal deposition in the kidneys of Hibiscus sabdariffa and Phyllanthus amarus treated rats than in untreated rats. Those rats also had significantly lower renal tissue calcium content than untreated rats. All parameters in the Orthosiphon grandiflorus treated group were comparable to those in the untreated group. Conclusions Hibiscus sabdariffa and Phyllanthus amarus decreased calcium crystal deposition in the kidneys. The antilithic effect of Hibiscus sabdariffa may be related to decreased oxalate retention in the kidney and more excretion into urine while that of Phyllanthus amarus may depend on increased urinary citrate. In contrast, administering Orthosiphon grandiflorus had no antilithic effect. © 2011 American Urological Association Education and Research, Inc.


Fukumura Y.,Juntendo University | Takase M.,Juntendo University | Mitani K.,Juntendo University | Suda K.,Juntendo University | And 6 more authors.
Pancreas | Year: 2012

Objectives: Infiltration of many IgG4-positive plasma cells (G4-Ps) is seen in IgG4-related diseases and in several "non-IgG4-related diseases," such as pilonidal sinus (PS) as well. The involvement of CD4 +CD25+ regulatory T cells (CD4+CD25+ Tregs) in IgG4-related diseases has been reported. To see whether CD4 +CD25+ Tregs are involved in autoimmune pancreatitis (AIP)/non-IgG4-related diseases with many G4-Ps, we investigated the amount of G4-Ps and CD4+CD25+ Tregs histologically in AIP/PS. Methods: Four AIP and 10 PS were immunostained with IgG4/Foxp3, a specific marker for CD4+CD25+ Tregs. Double immunohistochemistry and dual fluorescent immunohistochemistry were conducted to see the amount of CD4+CD25+ Tregs. Results: All AIP and 30% of PS showed abundant G4-Ps. G4-Ps infiltrated diffusely for all AIPs and in a patchy pattern for PS at the abscess/granulation foci. Foxp3 immunostaining/double immunohistochemistry showed moderate to abundant CD4+CD25+ Tregs in AIP and abscess of PS, but few to moderate in granulation of PS. Dual fluorescent immunohistochemistry also showed many CD4+CD25 + Tregs in AIP. Conclusions: Many CD4+CD25+ Tregs were seen in AIP lesions, abscess of PS, but not in granulation of PS, suggesting that the amount of CD4+CD25+ Tregs sometimes do not synchronize with that of G4-Ps and might relate to the inflammatory activity of both AIP and PS. Copyright © 2012 Lippincott Williams & Wilkins.


Yuzawa Y.,Tokyo West Tokushukai Hospital
Archives of Orthopaedic and Trauma Surgery | Year: 2011

Introduction: Retrospective clinical study has done concerning the outcomes of lumbar spinal stenosis (LSS) patients treated with trans-interspinous ligament approach method. The object is to determine the efficacy of this procedure and to confirm that the interspinous ligament could be removed for the decompression surgery. Method: Seventy patients were treated with this method and 63 patients were followed up for more than 4 years. Operative time, blood loss, complications of surgery and further surgery were checked out. During the follow-up period, JOA score and lumbar spine X-ray were evaluated. Results: The average operative time was 51 min, average operative time per one level was 32 min, and the average blood loss was 57 ml. The recovery rate was excellent in 26, good in 24, fair in 8 and poor in 5 patients. Four of 63 patients (6.3%) needed further surgery and among them only 2 cases (3.2%) needed reoperation because of the instability of the operative levels. Conclusion: The trans-interspinous ligament procedure is a simple decompression method completed quickly and accomplishes absolute decompression for LSS. The interspinous ligament should be removed for decompression with a case of lumbar spinal canal stenosis. © 2010 Springer-Verlag.


PubMed | Tokyo West Tokushukai Hospital
Type: Journal Article | Journal: Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2014

The long-term use of hormonal therapy is important for the treatment of patients with breast cancer. Therefore, we evaluated the methods used for measuring adherence and examined factors that influence compliance. Our goal was to improve overall adherence to the treatment.Retrospective analyses by using electronic medical records and questionnaires were performed on 294 patients with breast cancer. The patients were classified into 2 groups based on the mean number of days when a dose was missed over a period of 28 days: group A(range, 0-3 days, n=272)and group B (range, B4 days, n=22). Factors that may influence adherence, including age, duration of hormonal therapy, the drug administered in hormonal therapy, the surgical method, axillary lymph node dissection, and adjuvant chemotherapy, were compared between both groups.The adherence rates calculated from electronic medical records and questionnaires were similar. The proportion of patients younger than 50 years was 30% in group A and 50% in group B(p<0.05). Additionally, there was a difference in the duration of hormone therapy(752 days vs 981 days in groups A and B, respectively; p< 0.05). Additional factors that are related to low-risk cancer-related procedures, such as breast conserving surgery, may also be linked to poor adherence.Young age and long duration of hormonal therapy are possibly related to poor adherence. Therefore, pharmacists should identify and manage these patients to increase adherence.


PubMed | Tokyo West Tokushukai Hospital
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

e11550 Background: The efficacy of an accelerated partial breast irradiation (APBI) has been investigated compared with whole-breast irradiation (WBI). APBI starting just after surgery might give more benefit by intra-operative insertion of catheters. Although balloon catheter-based APBI is available in the US, it would not be adapted for Japanese women with small breast. When the applicators are implanted during operation for the tumor, APBI can start just after surgery. The aim of this study is an assessment of the efficacy and safety of APBI using intra-operative open-cavity implant (IOCI) technique.Patients (40yrs) with invasive breast cancer (3 cm) were enrolled. Before the lumpectomy, the insertion of applicators and delivery doses were simulated with CT. After the confirmation of the free margin and negative SNs for metastasis using frozen section analysis, applicators were inserted. Dose distribution analysis, using dose-volume histograms, was achieved based on a postoperative CT. APBI was started the same day of the operation. APBI therapy delivered 32 Gy in 8 fractions over 5-6 days with coverage of 2 cm tumor margins.From October 2008 to Jan 2011, 107 women were enrolled (55.0 y/o, <40:10, sn+:19, for patients request). The mean number of applicators was 6.8 (2-15). The mean PTV was 36.7cmAlthough this study is a small number of participants and short follow-up period, this convenient technique should be needed to establish clinical efficacy and safety.


PubMed | Tokyo West Tokushukai Hospital
Type: Case Reports | Journal: Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2015

A 62-year-old man with lower rectal cancer underwent abdominoperineal resection and dissection of the lateral pelvic lymph nodes. The cancer was staged at pT3pN0cM0, pStage II and did not show recurrence. Two years later, the patient had dysphagia and was diagnosed with esophageal cancer based on upper gastrointestinal endoscopy. Positron emission tomography-computed tomography (PET/CT) performed to detect distant metastasis revealed fluorodeoxyglucose (FDG) uptake in the left obturator lymph nodes, indicating rectal cancer recurrence. The patient received radiation therapy (60.4 Gy) for the recurrence. A PET/CT scan obtained 2 years 6 months after the initial rectal cancer resection revealed no FDG uptake. Uraciltegafur plus Leucovorin (UFT+LV) was started and continued for 6 months, but tumor enlargement was noted. Treatment was changed to LV, 5-fluorouracil, and irinotecan (FOLFIRI), but after 4 courses, the patients carcinoembryonic antigen (CEA) levels rose. The patient then received 4 courses of bevacizumab plus FOLFIRI. A CT scan revealed tumor shrinkage, so the patient received 4 more courses of this regimen. Five years postoperatively, the patients CEA levels rose again. A PET/CT scan 4 months later revealed FDG uptake in the left obturator lymph nodes, indicative of rectal cancer recurrence. One month later, the lymph nodes were resected. The patient was subsequently recurrence free. Tumor marker measurement and PET/CT helped to assess the patients condition. When cancer recurs in the lateral pelvic lymph nodes with no involvement of the pelvis and R0 resection is possible, resection should be considered if the patient is capable of undergoing surgery.

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