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Miura D.,Nippon Medical School | Miura D.,Toranomon Hospital | Yoneyama K.,National Cancer Center East | Furuhata Y.,Red Cross | Shimizu K.,Nippon Medical School
Journal of Nippon Medical School | Year: 2014

Materials and Methods: The subjects were 20 patients with HER2-positive breast cancer: 9 received the combination of trastuzumab (4 mg/kg as a loading dose and 2 mg/kg weekly) and paclitaxel (80 mg/m2 weekly) and 19 received monotherapy with trastuzumab. In blood samples (mononuclear cells) obtained before and 10 minutes after administration of chemotherapy, ADCC and the number of effector cells, including natural killer (NK) cells, monocytes, and CD64+ cells, were compared in each case. The ADCC was analyzed with a 51 Cr releasing assay using the SK-BR-3 cell line, and the fractions of NK cells (both CD16+ [FcγRIII] and CD56+) and CD64+ (FcγRI) cells were analyzed with flow cytometry.Introduction: An important mechanism by which trastuzumab inhibits the growth of human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells is the activation of a host tumor response via antibody-dependent cell-mediated cytotoxicity (ADCC). Although paclitaxel has a synergistic effect in combination with trastuzumab, whether ADCC is enhanced by paclitaxel is not known. In the present study we examined whether adding paclitaxel to trastuzumab enhances ADCC and also investigated the kinetics of effector cells in ADCC.Results: The mean ADCC level increased 20% after trastuzumab monotherapy and 126% (p<0.05) after combination therapy with trastuzumab and paclitaxel. All 9 patients receiving combination therapy had increased ADCC levels. The number of NK cells increased 51% after trastuzumab monotherapy and 112% (p<0.05) after combination therapy. No significant changes were found in monocytes (39% increase) or CD64+ cells (53% increase) after trastuzumab monotherapy, but monocytes decreased 40% (p<0.05) and CD64+ cells decreased 24% after combination therapy.Conclusions: Adding paclitaxel to trastuzumab significantly enhances ADCC, with levels twice as great as with trastuzumab monotherapy, through a rapid recruitment of NK cells. This finding suggests that the combination of trastuzumab and paclitaxel has a stronger-thanexpected synergistic effect in HER2-positive breast cancer. © The Medical Association of Nippon Medical School.


Giasuddin N.A.,S Z Medical College Hospital | Chowdhury N.F.,University of Dhaka | Hashimoto N.,Hokkaido University | Fujisawa D.,National Cancer Center East | Waheed S.,Dhaka Medical College Hospital
Social Psychiatry and Psychiatric Epidemiology | Year: 2012

Introduction The pattern of care seeking of psychiatric patients is important for service and policy issues. We conducted a study in 2008 in Bangladesh to find out the referral patterns, delays to reach mental health professional (MHP), diagnoses and treatment received before reaching psychiatric care etc. Materials and methods We interviewed 50 consecutive new patients at the Psychiatry outpatient department of a tertiary hospital using the translated version of WHO pathway encounter form. Results 84% of the patients we interviewed consulted other carers before they arrived at a MHP (2.5-3.1 steps were needed to reach MHP) and the range of delay was 8-78 weeks (indirect pathway). 16% of the patients came directly to a MHP with mean delay of 10.5 weeks from onset of mental illness (direct pathway). Among the patients who took the indirect pathway 44% first visited the Individual Private practitioners (PP), 22% first visited native or religious healers (NRH) and 12% rural medical practitioners (RMP). Patients reaching NRH or RMP made the least delay (2-2.5 weeks) and the shortest pathway to MHP (4.5-7 weeks). Most delay occurred from PP to MHP/General Hospital (22-31 weeks). About a third of patients were informed of diagnosis with poor concordance with the diagnosis made by MHP. 70 and 40% of patients with mental illness who attended General Hospital and PP were referred to MHP, respectively. Conclusion In the study we found four major pathways to mental health care in Bangladesh. They are direct pathway and referrals from PP, general hospitals and NRH. PP did not play a pivotal role in reaching MHP. Family members had a significant role on the decision to seek help from health service. © Springer-Verlag 2010.


Fujisawa D.,National Cancer Center East | Fujisawa D.,Keio University | Miyashita M.,Tohoku University | Nakajima S.,National Institute of Mental Health | And 4 more authors.
Journal of Affective Disorders | Year: 2010

Background: Few epidemiological studies have examined complicated grief in the general population, especially in Asian countries. Therefore, this study aimed to explore the prevalence and predictors of complicated grief among community dwelling individuals in Japan. Methods: A questionnaire survey regarding grief and related issues was conducted on community dwelling individuals aged 40-79 who were randomly sampled from census tracts. Complicated grief was assessed using the Brief Grief Questionnaire. Stepwise logistic regression analysis was conducted in order to identify predictors of complicated grief. Results: Data from 969 responses (response rate, 39.9%) were subjected to analysis. The analysis revealed 22 (2.4%) respondents with complicated grief and 272 (22.7%) with subthreshold complicated grief. Respondents who were found to be at a higher risk for developing complicated grief had lost their spouse, lost a loved one unexpectedly, lost a loved one due to stroke or cardiac disease, lost a loved one at a hospice, care facility or at home, or spent time with the deceased everyday in the last week of life. Limitations: Limitations of this study include the small sample size, the use of self-administered questionnaire, and the fact that the diagnoses of complicated grief were not based on robust diagnostic criteria. Conclusions: The point prevalence of complicated grief within 10 years of bereavement was 2.4%. Complicated grief was maintained without significant decrease up to 10 years after bereavement. When subthreshold complicated grief is included, the prevalence of complicated grief boosts up to a quarter of the sample, therefore, routine screening for complicated grief among the bereaved is desired. Clinicians should pay particular attention to the bereaved families with abovementioned risk factors in order to identify people at risk for future development of complicated grief. © 2010 Elsevier B.V. All rights reserved.


Sugimoto M.,The Surgical Center | Sugimoto M.,Toho University | Gotohda N.,The Surgical Center | Gotohda N.,National Cancer Center East | And 7 more authors.
Journal of Hepato-Biliary-Pancreatic Sciences | Year: 2013

Background: Postoperative pancreatic fistula (POPF) is a major, intractable complication after distal pancreatectomy (DP). Risk factor evaluation and prevention of this complication are important tasks for pancreatic surgeons. Methods: One hundred and six patients who underwent DP using a stapler for pancreatic division were retrospectively investigated. The relationship between clinicopathological factors and the incidence of POPF was statistically analyzed. Results: Clinically relevant, Grade B or C POPF by International Study Group of Pancreatic Fistula criteria occurred in 52 patients (49.1 %). Age, American Society of Anesthesiologists score, body mass index, and concomitant gastrointestinal tract resection did not influence the incidence of POPF. Use of a double-row stapler and a thick pancreatic stump were significant risk factors for POPF in multivariate analysis. Compression index was also shown to be an important factor in cases in which the pancreas was divided by a stapler. Conclusions: The most important risk factor for POPF after DP was suggested to be the thickness of the pancreatic stump, reflecting the volume of remnant pancreas. A triple-row stapler seemed to be superior to a double-row stapler in preventing POPF. However, triple-row stapler use in a thick pancreas is considered to be a future problem to be solved. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery and Springer Japan.


Suzuki C.,Karolinska University Hospital | Torkzad M.R.,Uppsala University Hospital | Jacobsson H.,Karolinska University Hospital | Astrom G.,Uppsala University Hospital | And 4 more authors.
Acta Oncologica | Year: 2010

Background. Response Evaluation Criteria In Solid Tumors (RECIST) and WHO-criteria are used to evaluate treatment effects in clinical trials. The purpose of this study was to examine interobserver and intraobserver variations in radiological response assessment using these criteria. Material and methods. Thirty-nine patients were eligible. Each patient's series of CT images were reviewed. Each patient was classified into one of four categories according RECIST and WHO-criteria. To examine interobserver variation, response classifications were independently obtained by two radiologists. One radiologist repeated the procedure on two additional different occasions to examine intraobserver variation. Kappa statistics was applied to examine agreement. Results. Interobserver variation using RECIST and WHO-criteria were 0.53 (95% CI 0.33-0.72) and 0.60 (0.39-0.80), respectively. Response rates (RR) according to RECIST obtained by reader A and reader B were 33% and 21%, respectively. RR according to WHO-criteria obtained by reader A and reader B were 33% and 23% respectively. Intraobserver variation using RECIST and WHO-criteria ranged between 0.760.96 and 0.860.91, respectively. Conclusion. Radiological tumor response evaluation according to RECIST and WHO-criteria are subject to considerable inter- and intraobserver variability. Efforts are necessary to reduce inconsistencies from current response evaluation criteria. © 2010 Informa UK Ltd.


Yoneyama Y.,National Cancer Center East | Ito M.,National Cancer Center East | Sugitou M.,National Cancer Center East | Kobayashi A.,National Cancer Center East | And 2 more authors.
Japanese Journal of Clinical Oncology | Year: 2011

Objective: The aim of this study is to examine the relationship between postoperative laboratory parameters of inflammation and the disease-free survival in patients undergoing resection for colorectal cancer. Methods: Six hundred seventy-five consecutive patients who underwent an elective resection for primary colorectal cancer from October 1999 to March 2004 were included in this study. We examined the associations between cancer recurrence and white blood cell count, lymphocyte percentage, neutrophil percentage and C-reactive protein. Results: Lymphocyte percentage on postoperative days 3 and 7 was significantly higher in patients without recurrence than in those with recurrence. Lymphocyte percentage on postoperative day 7 differed the most between the two groups. On postoperative day 7, Stage II patients with lymphocyte percentage >15% had significantly longer survival compared with the patients with lymphocyte percentage ≤15%. A multivariate analysis showed lymphocyte percentage ≤15% on postoperative day 7 to be an independent prognostic factor, along with lymph node metastases and serosal invasion. Logistic regression analysis showed that blood loss (>250 ml) and postoperative complications were significant independent predictors of lymphocyte percentage ≤15% on postoperative day 7. Conclusions: Lymphocyte percentage ≤15% on postoperative day 7 is an independent prognostic factor for the patients undergoing a resection for colorectal cancer. © The Author (2011). Published by Oxford University Press. All rights reserved.


Yoshida T.,National Cancer Center Hospital East | Niho S.,National Cancer Center Hospital East | Toda M.,National Cancer Center East | Goto K.,National Cancer Center Hospital East | And 5 more authors.
Japanese Journal of Clinical Oncology | Year: 2014

Objective: Magnesium supplementation has been reported to have a nephroprotective effect on cisplatin-induced renal dysfunction, but little evidence exists regarding the effect of magnesium preloading before cisplatin administration. We started to include magnesium preloading (8 mEq) in cisplatin-containing treatment regimens in January 2011. The aim of the present study was to evaluate whether magnesium preloading reduces cisplatin-induced nephrotoxicity. Methods: We retrospectively reviewed 496 thoracic malignancy patients treated with cisplatin (≥60 mg/m2)-containing regimens as a first-time chemotherapy between January 2009 and December 2011. We compared the incidence of Grade ≥2 serum creatinine elevation according to the Common Terminology Criteria for Adverse Events, version 4.0, between magnesium preloading group (n = 161 [32%]) and non-magnesium preloading group (n = 335 [68%]) during the first cycle and all cycles. Results: The median number of administered cycles was four in both groups. The incidence of Grade ≥2 serum creatinine elevation in magnesium preloading group was significantly lower during both the first cycle and all cycles than in the non-magnesium preloading group (4.9 versus 19.1% during the first cycle, and 14.2 versus 39.7% during all the cycles). A multivariate analysis indicated that magnesium preloading significantly reduced cisplatin-induced nephrotoxicity throughout the entire period from after the first administration (odds ratio: 0.262, 95% confidence interval: 0.106-0.596 during the first cycle, and odds ratio: 0.234, 95% confidence interval: 0.129-0.414 during all cycles). Conclusions: Magnesium preloading before cisplatin administration significantly reduced cisplatin-induced nephrotoxicity. © The Author 2014. Published by Oxford University Press. All rights reserved.


Deno M.,Musashino University | Miyashita M.,Tohoku University | Fujisawa D.,National Cancer Center East | Nakajima S.,National Institute of Mental Health | And 2 more authors.
Journal of Affective Disorders | Year: 2011

Background: The present research investigated whether the relationship between alexithymia and complicated grief was different from the relationship between alexithymia and general depressive symptom according to the seriousness of complicated grief in the Japanese general population. Methods: In the Japanese general population sample, 948 participants between 40 and 79 years old (effective response rate, 48.0%) completed a cross-sectional anonymous questionnaire about alexithymia, depression, and complicated grief. To compare the high risk (n = 243) and low risk (n = 705) of complicated grief groups, simultaneous analysis of two groups with standard maximum likelihood estimation was performed and six hypothesized models were verified. Results: The model (RMSEA = 0.047, AIC = 71.520) that showed that the path coefficients of the latent variable of alexithymia to the observed variables were equal and that the path coefficient of alexithymia to psychological distress was equal was adopted. The contribution ratios from alexithymia to complicated grief were apparently smaller (2-4%) than those to depression (37-38%). Conclusions: Our findings showed that alexithymia scarcely contributed to complicated grief compared to depression and that the contribution ratio in the high risk group was lower than that in the low risk group. The contribution of the latent variable of psychological distress to complicated grief and depression was lower in the high risk group than in the low risk group. The lack of a correlation between alexithymia and complicated grief might indicate that there are different mechanisms underlying the symptoms of alexithymia and complicated grief. © 2011 Elsevier B.V. All rights reserved.


Kamizono K.,National Cancer Center Hospital East | Sakuraba M.,National Cancer Center Hospital East | Sakuraba M.,National Cancer Center East | Nagamatsu S.,National Cancer Center Hospital East | And 2 more authors.
Annals of Surgical Oncology | Year: 2014

Background: Surgical site infections (SSIs) occur at a rate exceeding 40 % after head and neck reconstruction and are due in part to the clean-contaminated surgical field, in which cutaneous fields interact with oral or pharyngeal fields. The aim of this study was to clarify the most important risk factors for SSI and to identify effective strategies for preventing SSI. Methods: In 2011 and 2012, 197 patients who underwent head and neck reconstructive surgery were studied at National Cancer Center Hospital East, Japan. The SSI rate, risk factors for SSI, and biological aspects of SSI were evaluated prospectively. Results: A total of 42 patients (21.3 %) had SSIs, and 62 bacterial species were identified at infection sites. Significant risk factors for SSI identified with multivariate analysis were hypoalbuminemia [P = 0.002, odds ratio (OR) = 3.37], reconstruction with vascularized bone transfer (P = 0.006, OR = 3.99), and a poor American Society of Anesthesiologists Physical Status score (P = 0.041, OR = 3.00). Most bacteria identified were species that persist around cutaneous and pharyngeal fields, but multidrug-resistant bacteria were rare. Conclusions: The SSI rate at our hospital is lower than rates in previous studies. To minimize SSI, intervention to improve the patient's perisurgical nutritional status and a more appropriate mandible reconstructive strategy should be considered. © 2014 Society of Surgical Oncology.


PubMed | Komagome Hospital, International University of Japan, National Cancer Center East and St Lukes International Hospital
Type: Journal Article | Journal: Anticancer research | Year: 2016

To examine the relationship between symptomatic radiation pneumonitis and lung dose-volume parameters for patients receiving accelerated partial breast irradiation (APBI) using three dimensional-conformal radiotherapy (3D-CRT).The prescribed radiation dose was 30 Gy in 5 fractions over 10 days. Toxicity was graded according to the Common Terminology Criteria for Adverse Events (version 4.0).Fifty-five patients were enrolled from August 2010 to October 2013 and the median follow-up time was 30 months (range=18-46 months). Three patients (5%) developed grade 2 symptomatic radiation pneumonitis after 3D-CRT APBI. Among 16 patients with ILV10Gy (% ipsilateral lung receiving 10 Gy) of 10% or higher, three patients (19%) developed symptomatic radiation pneumonitis. This trend was not observed in any of the patients with ILV10Gy less than 10% (p=0.005).High ILV10Gy might be associated with symptomatic radiation pneumonitis after 3D-CRT APBI.

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