Masahiro Kashiwaba

Iwate Medical University, Morioka, Iwate, Japan

Are you Masahiro Kashiwaba?

Claim your profile

Publications (35)69.43 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Postoperative hyperglycemia is associated with infectious complications after various types of surgery. Our objective was to determine whether postoperative blood glucose levels up to 1 week after highly invasive esophageal cancer surgery are associated with the incidence of postoperative infections (POIs).
    Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: A dose escalation study of biweekly irinotecan (CPT-11) combined with capecitabine was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) for metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes. Methods: Escalating doses of CPT-11 (80-120 mg/m(2)) were administered on days 1 and 15. Capecitabine was administered at a fixed dose of 1,657 mg/m(2)/day for 21 consecutive days, followed by 7 days of rest. We treated 3-6 patients at a particular dose level until the MTD was determined. Results: Twenty patients were treated. The MTD was determined to be 100 mg/m(2), as 3 of 6 patients developed dose-limiting toxicities, grade 3 leukopenia, neutropenia, photophobia, fatigue and diarrhea. The RD for the phase II study was thus determined to be 90 mg/m(2). The response rate was 41.7%. Conclusions: Combination therapy with CPT-11 and capecitabine was well tolerated with a promising response rate for MBC that had been treated previously with anthracyclines and taxanes. A multi-center phase II study is warranted to evaluate the efficacy and safety of this combination therapy with pharmacokinetic assessment. © 2014 S. Karger AG, Basel.
    Oncology 05/2014; 86(4):206-211. · 2.17 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patient: Female, 56 Final Diagnosis: Breast cancer Symptoms: Solid mass in the right breast Medication: Exemestane Clinical Procedure: - Specialty: Oncology. Unusual clinical course. The efficacy of third-generation aromatase inhibitors for hormone receptor-positive postmenopausal metastatic breast cancer is well established. Although several clinical trials have reported incomplete cross-resistance between different aromatase inhibitors, few cases of complete responses of recurrent metastatic breast cancer occurring after substituting a second aromatase inhibitor have been reported. We here present a rare case of non-steroidal aromatase inhibitor-tolerant metastatic breast cancer with long-term complete remission following substitution of a steroidal aromatase inhibitor. We present the case of a 56-year-old Japanese woman who underwent right breast-conserving surgery for breast cancer, TNM staging T1, N0, M0, Stage I. She received adjuvant chemotherapy with 6 cycles of FEC100 and radiation therapy, and then began hormonal therapy with anastrozole. Twelve months postoperatively, computed tomography (CT) revealed multiple lung metastases. Exemestane was substituted for anastrozole. After 3 months of exemestane, CT showed that all lung metastases had completely resolved. Her complete response was maintained for 5 years: she died during a tsunami 6 years after the initial surgery. Substitution of a steroidal for a non-steroidal aromatase inhibitor produced a sustained complete remission in a patient with hormonal receptor-positive postmenopausal recurrent breast cancer. Achieving complete response after switching from a non-steroidal to a steroidal aromatase inhibitor in a hormonal receptor-positive postmenopausal recurrent breast cancer contributed to a higher quality of life for the patient. Further investigation is needed to identify the predictors of long-term remission following such a switch.
    The American journal of case reports. 01/2014; 15:85-9.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This randomized, multicenter study compared the efficacy of docetaxel with or without capecitabine following fluorouracil/epirubicin/cyclophosphamide (FEC) therapy in operable breast cancer and investigated the role of Ki67 as a predictive biomarker. Patients were randomized to 4 cycles of docetaxel/capecitabine (docetaxel: 75 mg/m(2) on day 1; capecitabine: 1,650 mg/m(2) on days 1-14 every 3 weeks) or docetaxel alone (75 mg/m(2) on day 1 every 3 weeks) after completion of 4 cycles of FEC (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2) on day 1 every 3 weeks). The primary endpoint was the pathological complete response (pCR) rate. Predictive factor analysis was conducted using clinicopathological markers, including hormone receptors and Ki67 labeling index (Ki67LI). A total of 477 patients were randomized; the overall response in the docetaxel/capecitabine and docetaxel groups was 88.3 and 87.4 %, respectively. There were no significant differences in the pCR rate (docetaxel/capecitabine: 23 %; docetaxel: 24 %; p = 0.748), disease-free survival, or overall survival. However, patients with mid-range Ki67LI (10-20 %) showed a trend towards improved pCR rate with docetaxel/capecitabine compared to docetaxel alone. Furthermore, multivariate logistic regression analysis showed pre-treatment Ki67LI (odds ratio 1.031; 95 % CI 1.014-1.048; p = 0.0004) to be a significant predictor of pCR in this neoadjuvant treatment setting. Docetaxel/capecitabine (after 4 cycles of FEC) did not generate significant improvement in pCR compared to docetaxel alone. However, exploratory analyses suggested that assessment of pre-treatment Ki67LI may be a useful tool in the identification of responders to preoperative docetaxel/capecitabine in early-stage breast cancer.
    Breast Cancer Research and Treatment 10/2013; · 4.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study included patients who were prescribed pregabalin, vitamin B12, amitriptyline, clonazepam, or carbamazepine to improve oxaliplatin(L-OHP)- or paclitaxel(PTX)-induced peripheral neuropathy at Iwate Medical University Hospital between April 2011 and July 2012. The efficacy and safety of pregabalin was evaluated by comparing 27 patients with L-OHP-induced peripheral neuropathy and 28 with PTX-induced peripheral neuropathy prescribed pregabalin(pregabalin group) with 20 patients with L-OHP-induced peripheral neuropathy and 25 with PTX-induced peripheral neuropathy prescribed other drugs(non-pregabalin group). Response was defined as a decrease in neuropathy of at least 1 grade from baseline. The response rates were 40.7% and 10.0% for L-OHP-induced peripheral neuropathy patients and 28.6% and 12.0% for PTX-induced peripheral neuropathy patients in the pregabalin and non-pregabalin groups, respectively. The severity of peripheral neuropathy before and after the administration of pregabalin differed significantly[L-OHP, 1.33±0.48(mean±SD) vs. 1.00±0.78 and PTX, 1.46±0.69 vs. 1.21±0.88]. In 28-37% of patients, pregabalin was associated with adverse events, with drowsiness and dizziness being frequently observed. In conclusion, pregabalin was efficacious in reducing the severity of L-OHP- and PTX-induced peripheral neuropathy.
    Gan to kagaku ryoho. Cancer & chemotherapy 09/2013; 40(9):1189-93.
  • [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated the outcome of esophageal stenting for esophagorespiratory fistula in patients with advanced esophageal cancer. Six patients with such fistula underwent esophageal stenting at our department from January 2000 to May 2012. Intraoral ingestion improved in all patients. Cough decreased immediately after stenting in 3 patients, and pneumonia detected by chest radiography improved within 1 week in 2 patients. Ventilation was weaned 2 days after stenting in 1 patient. The median survival duration after stenting was 31 days, and the cause of death was cancer in all patients. The following background factors were identified at the time of death: bleeding(n=3), mediastinitis(n=1), and pneumonia(n=1). Esophageal stenting, which should always be performed with the informed consent of the patient, improves respiratory symptoms, intraoral ingestion, and quality of life. Therefore, it is one of the best palliative therapies for patients with esophagorespiratory fistula associated with advanced esophageal cancer.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2012; 39(12):1849-51.
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The outcome in patients with human epidermal growth factor receptor-2 (HER-2)-positive locally advanced breast cancer may be improved by integrating trastuzumab with primary systemic therapy (PST). METHODS: The efficacy and safety of PST comprising EC (epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2), four cycles every 3 weeks) followed by docetaxel (75 mg/m(2), four cycles every 3 weeks) and concurrent trastuzumab (loading dose 4 mg/kg followed by 2 mg/kg, 12 cycles every week) was investigated in a multicenter, prospective, phase II study in patients with HER-2-positive stage IIIB/IIIC/IV breast cancer. The primary endpoint was pathologic complete response (pCR) including the tumor intraductal component confirmed by central pathologic review. RESULTS: In total, 38 patients were enrolled (stage IIIB, 63.2 %; IIIC, 23.7 %; IV, 13.2 %; estrogen receptor- and/or progesterone receptor-positive, 47.4 %). The pCR rate was 16.2 % in the primary tumor (six of 37 patients in the Full Analysis Set) and 56.8 % (21/37) in the ipsilateral axillary lymph nodes. Treatment was given according to protocol in 28 of 37 patients; six of 28 in the Per-Protocol Set achieved pCR (21.4 %). The clinical response rate was 67.6 % (25/37 patients; complete response, 13.5 %; partial response, 54.1 %). No patients developed congestive heart failure; however, three patients had a non-symptomatic decrease of >10 % of left ventricular ejection fraction. CONCLUSIONS: PST including concurrent use of trastuzumab combined with docetaxel is effective and well-tolerated in HER-2-positive advanced breast cancer patients, including those patients requiring mastectomy for local control.
    International Journal of Clinical Oncology 07/2012; · 1.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite extensive evaluation of first-line bevacizumab-containing therapy in randomized trials in locally recurrent/metastatic breast cancer (LR/mBC), data from Japanese populations are limited. We conducted a phase II study exclusively in Japanese patients to evaluate bevacizumab combined with weekly paclitaxel. Patients with HER2-negative measurable LR/mBC who had received no prior chemotherapy for LR/mBC received bevacizumab 10 mg/kg, days 1 and 15, in combination with paclitaxel 90 mg/m(2), days 1, 8, and 15, repeated every 4 weeks, until disease progression, unacceptable toxicity, or patient/physician decision. Co-primary endpoints of this single-arm open-label phase II study were progression-free survival (PFS) and safety. A total of 120 patients (median age 55 years) received study therapy. At the time of data cut-off, the median duration of therapy was 11.1 months (range 0.5-24.7 months). Median PFS was 12.9 months (95% CI: 11.1-18.2) according to Independent Review Committee assessment and 14.9 months by investigator assessment. Median PFS was 9.6 months in the subgroup of 38 patients with triple-negative LR/mBC. The overall response rate was 74% (95% CI: 64.5-81.2%). Median overall survival (OS) was 35.8 months (95% CI: 26.4-not estimated) and the 1-year OS rate was 88.9% (95% CI: 83.2-94.6). The regimen was well tolerated and the safety profile was generally consistent with previous reports of bevacizumab-paclitaxel combination therapy. Grade 3 hypertension was reported in 17% of patients. Grade 4 hypertension, grade 3/4 proteinuria, and gastrointestinal perforation were absent. There were no new bevacizumab safety signals. In 50 patients (42%), treatment was continued for ≥ 1 year. Conclusion: The high activity of first-line bevacizumab in combination with weekly paclitaxel observed in our study confirms the results of the E2100 trial. Our results suggest that the activity and tolerability of first-line bevacizumab-containing regimens demonstrated in E2100 can be reproduced in Japanese populations.
    Breast Cancer Research and Treatment 07/2011; 129(3):829-38. · 4.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Notch signaling is often and aberrantly activated by hypoxia during tumor progression; however, the exact pathological role of hypoxia-induced Notch signaling in tumor metastasis is as yet poorly understood. In this study, we aimed to define the mechanism of Notch-ligand activation by hypoxia in both primary tumor and bone stromal cells in the metastatic niche and to clarify their roles in tumor progression. We have analyzed the expression profiles of various Notch ligands in 779 breast cancer patients in GEO database and found that the expression of Jagged2 among all five ligands is most significantly correlated with the overall- and metastasis-free survival of breast cancer patients. The results of our immunohistochemical (IHC) analysis for Jagged2 in 61 clinical samples also revealed that both Jagged2 and Notch signaling were strongly upregulated at the hypoxic invasive front. Activation of Jagged2 by hypoxia in tumor cells induced EMT and also promoted cell survival in vitro. Notably, a γ-secretase inhibitor significantly blocked Notch-mediated invasion and survival under hypoxia by promoting expression of E-cadherin and inhibiting Akt phosphorylation. Importantly, Jagged2 was also found to be upregulated in bone marrow stroma under hypoxia and promoted the growth of cancer stem-like cells by activating their Notch signaling. Therefore, hypoxia-induced Jagged2 activation in both tumor invasive front and normal bone stroma has a critical role in tumor progression and metastasis, and Jagged2 is considered to be a valuable prognostic marker and may serve as a novel therapeutic target for metastatic breast cancer.
    Oncogene 04/2011; 30(39):4075-86. · 7.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report surgical techniques for single-incision laparoscopy-assisted surgery (SILAS) in the treatment of pediatric acute appendicitis. We performed SILAS in 15 cases of acute appendicitis between January and September of 2009. SILAS is a surgical method that involves making the incision at the umbilicus, inserting a wound retractor XS, suspending the abdominal wall with a hook, and appendectomy with the same procedures as conventional appendectomy. SILAS appendectomy was performed in all 15 cases with the exception of one case where one 3-mm port was added. Compared to open appendectomy, blood loss was significantly lower and postoperative hospitalization time was shorter, although there was no significant decrease in operative time, or postoperative fasting time. No postoperative complications, such as wound infection, intestinal obstruction, intra-abdominal abscess, or bleeding, were encountered. SILAS was safely performed and is superior to open appendectomy with regard to cosmetic outcome.
    Asian Journal of Endoscopic Surgery 02/2011; 4(1):11-5.
  • [Show abstract] [Hide abstract]
    ABSTRACT: This trial is conducted to investigate the benefit of trastuzumab monotherapy compared with a combination therapy of trastuzumab and chemotherapy in women over 70 years with human epidermal growth factor receptor type-2-positive primary breast cancer. Inclusion criteria are the following: histologically diagnosed as invasive breast cancer and received curative operation for primary breast cancer; Stage I, IIA, IIB or IIIA/M0; and baseline left ventricular ejection fraction is ≥55%. Patients are randomized to receive either trastuzumab (8 mg/kg loading dose, 6 mg/kg every 3 weeks for 1 year) plus chemotherapy selected from regimens specified on the protocol or trastuzumab monotherapy. The primary endpoint is disease-free survival. Secondary endpoints are overall survival, relapse-free survival, safety, health-related quality of life, comprehensive geriatric assessment and cost effectiveness. Patients recruitment has been commenced in October 2009. Enrollment of 300 patients is planned during the 4-year recruitment period. We hereby report the study concept.
    Japanese Journal of Clinical Oncology 02/2011; 41(5):709-12. · 1.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Resveratrol is a natural polyphenolic compound and has been shown to exhibit cardio-protective as well as anti-neoplastic effects on various types of cancers. However, the exact mechanism of its anti-tumor effect is not clearly defined. Resveratrol has been shown to have strong hypolipidemic effect on normal adipocytes and as hyper-lipogenesis is a hallmark of cancer cell physiology, the effect of resveratrol on lipid synthesis in cancer stem-like cells (CD24(-)/CD44(+)/ESA(+)) that were isolated from both ER+ and ER- breast cancer cell lines was examined. The authors found that resveratrol significantly reduced the cell viability and mammosphere formation followed by inducing apoptosis in cancer stem-like cells. This inhibitory effect of resveratrol is accompanied by a significant reduction in lipid synthesis which is caused by the down-regulation of the fatty acid synthase (FAS) gene followed by up-regulation of pro-apoptotic genes, DAPK2 and BNIP3. The activation of apoptotic pathway in the cancer stem-like cells was suppressed by TOFA and by Fumonisin B1, suggesting that resveratrol-induced apoptosis is indeed through the modulation of FAS-mediated cell survival signaling. Importantly, resveratrol was able to significantly suppress the growth of cancer stem-like cells in an animal model of xenograft without showing apparental toxicity. Taken together, the results of this study indicate that resveratrol is capable of inducing apoptosis in the cancer stem-like cells through suppression of lipogenesis by modulating FAS expression, which highlights a novel mechanism of anti-tumor effect of resveratrol.
    Breast Cancer Research and Treatment 12/2010; 130(2):387-98. · 4.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The 21-gene signature has been intensively studied and incorporated into major guidelines for treatment decision in early breast cancer. However, it remains to be examined whether this system is applicable to Asian populations. The authors collected 325 tumor tissues from estrogen receptor (ER)-positive primary breast cancer patients who had undergone surgery and were treated with tamoxifen between 1992 and 1998. The tissues were analyzed for the 21-gene signature, and the patients were classified into groups of low, intermediate, or high risk based on the Recurrence Score. A total of 280 patients were eligible, with adequate reverse transcription polymerase chain reaction profiles for the Recurrence Score. Of those, 200 and 80 patients had lymph node-negative and lymph node-positive disease, respectively. The proportions of lymph node-negative patients categorized as being at low, intermediate, or high risk were 48%, 20%, and 33%, respectively. In lymph node-negative patients, the Kaplan-Meier estimates of the distant recurrence rate at 10 years were 3.3% (95% confidence interval [95% CI], 1.1-10.0%), 0%, and 24.8% (95% CI, 15.7-37.8%) for those in the low-risk, intermediate-risk, and high-risk groups, respectively. The risk of distant recurrence in the low-risk group was significantly lower than that in the high-risk group when the entire Kaplan-Meier plots were compared (P < .001, log-rank test). There was a significant difference for overall survival between the low-risk and the high-risk groups (P = .008, log-rank test). This is the first report to show that the 21-gene signature has value in providing prognostic information in Asian populations with ER-positive, lymph node-negative breast cancer.
    Cancer 07/2010; 116(13):3112-8. · 5.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The study aimed to assess our newly devised CDDP delivery system designed to provide targeting potential and a sustained release of the anticancer agent. Seventy percent deacetylated chitin was applied as a drug carrier. We prepared two different types of systems with two different procedures: namely, system A with direct method and system B with indirect method. The targeting property of the system was evaluated ex vivo with measuring adhesive force between each system and human colonic mucosa. The release behavior of the CDDP from the system was examined in vitro. The anticancer activities of the released CDDP were also examined in vitro using human gastric cancer cell line, MKN-45. Each system was a viscose elastic solution. The adhesive forces of the novel systems were stronger at 37 degrees C than that of 25 degrees C. Each system provided a sustained release of CDDP. The released CDDP demonstrated effective growth suppression activity against the MKN-45 cancer cells. The novel systems basically showed a favorable targeting function and a sustained release of CDDP, which effectively provided a growth inhibition potential against human cancer cell line. Our newly devised CDDP delivery systems are promising as a novel approach to cancer chemotherapy.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2009; 36(12):2294-6.
  • [Show abstract] [Hide abstract]
    ABSTRACT: With the increase in breast cancer patients in Japan, therapy for breast cancer has progressed with evidence-based medicine (EBM), and most of it has shifted to outpatient clinics (OPC) except for surgery. With the specialization of surgical techniques and pharmacological treatments, i. e. sentinel node biopsy and advanced medical treatment, many patients now visit specialized cancer clinics, and the congestion has resulted in difficulty in follow-up after surgery, and the reconsideration of how to follow-up is under way. Although the clinical guideline issued by the Japanese Breast Cancer Society recommends performing a careful history, physical examination and annual mammography, each clinic has its own follow-up program with additional modalities different approaches in EBM. Here we investigate the recommendations of the clinical guideline, how they discuss evidence, and we attempt to pinpoint the problems when used at the daily clinical level while considering the characteristics of current breast cancer practice. Then, we considered the specific characteristics of breast cancer revealed by meta-analyses, the effect of long-term adjuvant endocrine therapy after surgery, and reflecting the patient's intent in follow-up in order to conduct an ideal follow-up with a view to cooperation between cancer specialized hospitals and community clinics.
    Gan to kagaku ryoho. Cancer & chemotherapy 09/2009; 36(9):1423-7.
  • [Show abstract] [Hide abstract]
    ABSTRACT: We examined 51 patients treated with Capecitabine for metastatic breast cancer. 51 patients achieved a 30.8% response rate, 59.6% a clinical benefit rate(59.6%)and 7.2 M of time to disease progression, as previously reported. Capecitabine therapy, single agent or combination therapy, should be considered a treatment of choice for metastatic breast cancer with certain response and general tolerability.
    Gan to kagaku ryoho. Cancer & chemotherapy 06/2009; 36(5):769-72.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Papillary thyroid carcinoma (PTC) generally has a good prognosis but may have an aggressive course, particularly in the elderly. Standard treatment consists of radioactive iodine and thyrotropin suppression with superphysiological doses of thyroid hormone. Other modalities are less commonly used. We report perhaps the first patient with PTC who was treated with Mohs chemosurgery. The patient was a 94-year-old woman who was diagnosed at age 67 with PTC and underwent a near-total thyroidectomy. The PTC recurred in the cervical nodes and reached the size of 8 x 5.5 cm by age 89. The tumor had become exposed and was hemorrhaging. By age 92 it measured 10 cm, encompassed the right common carotid artery, and was invading the trachea and larynx. In order to implement local control, we applied Mohs ointment. She also required blood transfusions. After approximately 1 month, the tumor had flattened, and the hemorrhaging stopped, and the patient was able to be discharged from the hospital to home nursing. Treatment with Mohs chemosurgery should be considered in the rare patient with exposed locally aggressive PTC for palliation and improved quality of life.
    Thyroid: official journal of the American Thyroid Association 06/2009; 19(6):657-9. · 2.60 Impact Factor
  • Breast. 01/2009; 18.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose This multicenter phase II study examined the impact of pathological effect on survival after preoperative chemotherapy in Japanese women with early stage breast cancer. Patients and methods Prior to surgery, patients received four cycles of FEC (fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2) q3w) followed by four cycles of docetaxel (75 mg/m(2) q3w). Primary endpoint was 3 year disease free survival (DFS) stratified by the absence or presence of Quasi-pCR (QpCR; absence of invasive tumor or only focal residual tumor cells). Secondary endpoints were predictors for QpCR, clinical response, breast conservation rate, and safety. Results Between June 2002 and June 2004, 202 women were enrolled. Among 191 assessable patients, 25% achieved QpCR. With 40 months median follow-up, 3 year DFS was estimated at 91% for all patients. 3 year DFS for patients with QpCR was 98% vs. 89% without QpCR (hazard ratio 0.38 [95% Confidence Interval 0.09-0.84], P = 0.0134). HER2 status and response to FEC were independent predictors of QpCR. The overall clinical response was 75%; 85% of patients achieved breast conservation. Grade 3/4 neutropenia was the most common adverse event, observed in 44% and 35% of patients during FEC and docetaxel, respectively. Treatment related side effects were manageable; there were no treatment related fatalities. Conclusion FEC followed by docetaxel is an active and manageable preoperative regimen for women with early stage breast cancer. QpCR following preoperative chemotherapy predicts favorable DFS. HER2 overexpression and clinical response to FEC predict QpCR.
    Breast Cancer Research and Treatment 09/2008; 110(3):531-9. · 4.47 Impact Factor