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Umezawa S.,Tokyo Medical and Dental University | Umezawa S.,Research Center for Innovative Oncology | Fujimori M.,Research Center for Innovative Oncology | Fujimori M.,National Institute of Mental Health | And 6 more authors.
Cancer | Year: 2015

BACKGROUND The objective of this study was to clarify the communication preferences of patients with advanced cancer regarding discussions about ending anticancer treatment and transitioning to palliative care and to explore the variables associated with those preferences. METHODS Participants were 106 Japanese patients with cancer who had been informed at least 1 week earlier about the cessation of their anticancer treatment. They completed a survey measuring their preferences for communication about ending anticancer treatment and transitioning to palliative care as well as their demographic characteristics. Medical records were also examined to investigate medical characteristics. RESULTS Results of the descriptive analysis indicated that patients strongly preferred their physicians to listen to their distress and concerns (96%), to assure them that their painful symptoms would be controlled (97.1%), and to explain the status of their illness and the physical symptoms that would likely occur in the future (95.1%). Multiple regression analyses identified the factors associated with these preferences: telling patients to prepare mentally and informing them of their expected life expectancy were associated with cancer site; sustaining hope was associated with cancer site and children; and empathic paternalism was associated with duration since cancer diagnosis. CONCLUSIONS The majority of patients preferred their physicians to be realistic about their likely future and wanted to be reassured that their painful symptoms would be controlled. For patients with cancer at certain sites, those with children, and those more recently diagnosed, physicians should communicate carefully and actively by providing information on life expectancy and mental preparation, sustaining hope, and behaving with empathic paternalism. © 2015 American Cancer Society.


Tagami K.,National Cancer Center Research Institute | Tagami K.,National Cancer Center Hospital East | Tagami K.,Juntendo University | Kashiwase Y.,National Cancer Center Research Institute | And 13 more authors.
Neuropeptides | Year: 2015

The growth hormone secretagogue receptor (GHS-R) belongs to Gαq-coupled G protein-coupled receptor (GPCR) that mediates growth hormone release, food intake, appetite, glucose metabolism and body composition. Ghrelin has been identified as an endogenous ligand for GHS-R, and it is the only orexigenic peptide found in the peripheral organs. Olanzapine, an atypical antipsychotic agent that binds to and inhibits the activation of GPCR for several neurotransmitters, has metabolic side effects such as excessive appetite and weight gain. Recently, studies have revealed that the orexigenic mechanism of olanzapine is mediated via GHS-R signaling, although the precise mechanisms have not been clarified.In this study, we investigated the effect of olanzapine on ghrelin-mediated GHS-R signaling by using an electrical impedance-based receptor biosensor assay system (CellKey™). Olanzapine at concentrations of 10-7 and 10-6 mol/L enhanced ghrelin-induced (10-10-10-8 mol/L) GHS-R activation. A Ca2+ imaging assay revealed that olanzapine (10-7 and 10-6 mol/L) enhanced ghrelin (10-7 M)-induced GHS-R activity. In contrast, haloperidol (an antipsychotic agent) failed to enhance this ghrelin-mediated GHS-R activation, as demonstrated by both the CellKey™ and Ca2+ imaging assays. Together, these results suggest that olanzapine, but not haloperidol, promotes appetite by enhancing ghrelin-mediated GHS-R signaling. © 2015 Elsevier Ltd.


Zenda S.,National Cancer Center Hospital East | Zenda S.,Innovation Center for Supportive | Ota Y.,Hyogo Cancer Center | Tachibana H.,Aichi Cancer Center Hospital | And 6 more authors.
Journal of Radiation Research | Year: 2016

Radiation dermatitis is one of the most common acute toxicities of both radiotherapy and chemoradiotherapy. Many clinical trials have evaluated the level of toxicity using the Common Terminology Criteria for Adverse Events ver. 4.03. This criterion accounts for severity in a single sentence only, and no visual classification guide has been available. Thus, there is a risk of subjective interpretation by the individual investigator. This contrasts with the situation with hematologic toxicities, which can be interpreted objectively. The aim of this prospective picture collection study was to develop a grading tool for use in establishing the severity of radiation dermatitis in clinical trials. A total of 118 patients who were scheduled to receive definitive or postoperative radiotherapy or chemoradiotherapy were enrolled from the four participating cancer centers. All researchers in our group used the same model of camera under the same shooting conditions to maintain consistent photographic quality. In all, 1600 photographs were collected. Of these, 100 photographs qualified for the first round of selection and were then graded by six experts, basically in accordance with the CTCAE ver. 4.03 (JCOG ver. in Japanese). After further study, 38 photographs were selected as representing typical models for Grade 1-4 radiation dermatitis; the radiation dermatitis grading atlas was produced from these photographs. The atlas will play a major role in ensuring that the dermatitis rating system is consistent between the institutions participating in trials. We hope that this will contribute to improving the quality of clinical trials, and also to improving the level of routine clinical practice. © The Author 2016.


Wada S.,National Cancer Center Hospital | Wada S.,Tokyo Medical and Dental University | Shimizu K.,National Cancer Center Hospital | Inoguchi H.,National Cancer Center Hospital | And 12 more authors.
Journal of Pain and Symptom Management | Year: 2015

Context There is controversy around the association between depressive symptoms and age in adult cancer patients. Objectives The aim of this study was to evaluate the following hypotheses: 1) cancer patients' depressive symptoms decrease with age, and 2) in individuals aged 65 years or older, depressive symptoms increase because of the effect of somatic symptoms. Methods We retrospectively analyzed a database of 356 cancer patients who were consecutively recruited in a previous multicenter cross-sectional study. Depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9), and correlations with age and other factors were assessed by hierarchical multivariate regression analysis. Age was entered as the dependent variable in the first step, patient characteristics and cancer-related variables were entered in the second step, and somatic symptoms were entered in the last step. We analyzed this model for both the total sample and the subpopulation aged 65 years or older. Results In the total sample, the PHQ-9 score was significantly associated with lower age, fatigue, and shortness of breath (adjusted R2 14.2%). In the subpopulation aged 65 years or older, no factor was associated with the PHQ-9 score (adjusted R2 7.3%). Conclusion The finding that depressive symptoms in cancer patients decreased with age was concordant with our first hypothesis, but the second hypothesis was not supported. Younger cancer patients were vulnerable to depressive symptoms and should be monitored carefully. Further studies using more representative samples are needed to examine in detail the association between depressive symptoms and age in older cancer patients. © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.


Murakami S.,Seirei Sakura Citizen Hospital | Sudo Y.,Tokyo University of Science | Sudo Y.,National Cancer Center Research Institute | Miyano K.,National Cancer Center Research Institute | And 9 more authors.
Journal of Pharmacological Sciences | Year: 2015

Non-selective transient receptor potential vanilloid (TRPV) cation channels are activated by various insults, including exposure to heat, acidity, and the compound capsaicin, resulting in sensations of pain in the skin, visceral organs, and oral cavity. Recently, TRPV1 activation was also demonstrated in response to basic pH elicited by ammonia and intracellular alkalization. Tris-hydroxymethyl aminomethane (THAM) is widely used as an alkalizing agent; however, the effects of THAM on TRPV1 channels have not been defined. In this study, we characterized the effects of THAM-induced TRPV1 channel activation in baby hamster kidney cells expressing human TRPV1 (hTRPV1) and the Ca2+-sensitive fluorescent sensor GCaMP2 by real-time confocal microscopy. Notably, both capsaicin (1 μM) and pH 6.5 buffer elicited steep increases in the intracellular Ca2+ concentration ([Ca2+]i), while treatment with THAM (pH 8.5) alone had no effect. However, treatment with THAM (pH 8.5) following capsaicin application elicited a profound, long-lasting increase in [Ca2+]i that was completely inhibited by the TRPV1 antagonist capsazepine. Taken together, these results suggest that hTRPV1 pre-activation is required to provoke enhanced, THAM-induced [Ca2+]i increases, which could be a mechanism underlying pain induced by basic pH. © 2015.

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