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Purpose To clarify the bereaved family's perceptions about the appropriateness of timing when physicians first referred patients to palliative care units, and to identify the factors contributing to family-perceived late referrals. Subjects and Methods A multicenter questionnaire survey was conducted on 630 bereaved family members of cancer patents who were admitted to palliative care units in Japan. A total of 318 responses were analyzed (effective response rate, 62%). Results Half of the bereaved family members regarded the timing of referrals to palliative care units as late or very late, while less than 5% of families reported early referrals (very late [19%, n = 59], late [30%, n = 96], appropriate [48%, n = 151], early [1.6%, n = 5], and very early [2.2%, n = 7]). Multiple regression analyses revealed that the independent determinants of family-perceived late referrals were: family belief before admission that palliative care shortens the patient's life, insufficient in-advance discussion about preferred end-of-life care between patients/families and physicians, families' insufficient preparation for changes of patient conditions, and hospital admission before referrals. Conclusion In Japan, the timing of referrals to palliative care units was late or very late from the families' perspectives. The independent determinants of family-perceived late referrals were: family misconception about palliative care, inadequate communication with physicians, and families' insufficient preparation for deterioration of patients' conditions. Systematic strategies to overcome these barriers would contribute to providing appropriate palliative care at all stages of cancer.

Symptomatic sedation is often required in terminally ill cancer patients and could cause significant distress to their families. The aim of this study was to gather vivid family descriptions about their experiences in palliative sedation therapy.This report is an additional analysis of a multicenter questionnaire survey. We performed content analysis on 48 statements described by 185 bereaved family members of patients who received palliative sedation therapy.Family members reported guilt, helplessness, and physical and emotional exhaustion when patients received palliative sedation therapy. They were concerned about whether sedated patients experienced distress, wished to know that the maximum efforts had been made, wished to prepare for patient death, wished to tell important things to patients before sedation, wished to understand patients' suffering, and wanted medical professionals to treat patients with dignity.To alleviate family distress, clinicians should understand families' emotional distress, ensure that unconscious patients feel no distress, reassure family members that the symptoms are truly refractory despite maximum efforts for symptom relief, give information and coordinate the situation to enable families to prepare for patient death and to tell important things to patients before sedation, help families to share patients' suffering, and treat patients the same as when they remained conscious.

The CD34+ hematopoietic stem cells have been shown to be able to reconstitute hematopoiesis in vivo. We concentrated CD34+ cells from bone marrow (BM) of normal adults or mobilized peripheral blood (PB) of patients with breast cancer using the MicroCELLector (Applied Immune Sciences). The purified BM CD34+ fractions were enriched in CFU-GM (9.6-153-fold, average 64-fold) and BFU-E (25-61-fold, average 44-fold), with 7-95% recovery of these colony-forming cells in the CD34+ fraction. Similar results were observed for PB CD34+ fractions. CD34 phenotypic analysis using the FITC-conjugated CD34 monoclonal antibody 8G12 showed that the purifed CD34+ fractions were 18-93% (average, 71%) positive using lymphoblast gate. These preclinical data form part of the basis for future clinical studies of stem cell transplantation and gene transfer.

Objective: Hormonal imbalance characterized by excessive production of growth hormone (GH) and a low circulating concentration of insulin-like growth factor (IGF)-1 has been demonstrated in individuals with various serious conditions. However, little is known about changes in the GH–IGF-1 axis in cancer patients. Methods: We prospectively examined the circulating levels of several hormones in 58 patients with solid tumors who were classified according to Eastern Cooperative Oncology Group performance status (PS): PS 0–1, n ¼ 15; PS 2, n ¼ 15; PS 3, n ¼ 15; and PS 4, n ¼ 13. The relations of hormone concentrations, with a focus on the GH –I GF-1 system, to PS were evaluated by Spearman’s rank correlation test and regression analysis. Results: The circulating levels of IGF-1, IGF-binding protein-3 and thyroid hormones (total T3 and T4) were inversely correlated with PS score. The concentration of GH was increased irrespective of PS but not statistically significant. The ratio of IGF-I to GH was inversely correlated with PS. The levels of GH and IGF-1 in all patients were also inversely correlated. Conclusions: The present study suggests that the GH –I GF-1 axis is disturbed in patients with cancer.

Selecting a place for end-of-life care is an important issue for patients with cancer. In this study we conducted a retrospective analysis on the prevalence of discharge from a palliative care unit (PCU) and explored factors related to discharge based on individual-level data from 5 years of experience at the Tokyo Metropolitan Toshima Hospital PCU.We retrospectively collected information on patients and families from the admission database of the PCU. We calculated the prevalence of patients discharged from the PCU and explored the factors related to discharge using bivariate and multivariate analysis.The subjects were 498 terminal patients with cancer. The overall discharge rate was 33%. For subjects who were admitted for symptom control, the discharge rate was 54%. The duration of the period from referral to death (odds ratio [OR] = 4.98, p0.001), Eastern Cooperative Oncology Group Performance States [ECOG PS]_OR = 0.51, p = 0.003), problems with oral intake (OR = 0.41, p = 0048), presence of nausea (OR = 0.41, p = 0.046), experience of radiation therapy (OR = 0.27, p = 0.003), and patient's anxiety for family (OR = 0.35, p = 0.029) were independent related factors for discharge from the PCU, according to logistic regression.Early referral to the PCU and development of alleviation methods for symptoms such as nausea and anxiety and depression are important for promoting discharge and would contribute to the patient's quality of life at the end of life.

Symptomatic sedation is often required in terminally ill cancer patients, and could cause significant distress to their family. The aims of this study were to clarify the family experience during palliative sedation therapy, including their satisfaction and distress levels, and the determinants of family dissatisfaction and high-level distress. A multicenter questionnaire survey assessed 280 bereaved families of cancer patients who received sedation in 7 palliative care units in Japan. A total of 185 responses were analyzed (response rate, 73%). The families reported that 69% of the patients were considerably or very distressed before sedation. Fifty-five percent of the patients expressed an explicit wish for sedation, and 89% of families were clearly informed. Overall, 78% of the families were satisfied with the treatment, whereas 25% expressed a high level of emotional distress. The independent determinants of low levels of family satisfaction were: poor symptom palliation after sedation, insufficient information-giving, concerns that sedation might shorten the patient's life, and feelings that there might be other ways to achieve symptom relief. The independent determinants of high levels of family distress were: poor symptom palliation after sedation, feeling the burden of responsibility for the decision, feeling unprepared for changes in the patient's condition, feeling that the physicians and nurses were not sufficiently compassionate, and shorter interval to patient death. Palliative sedation therapy was principally performed to relieve severe suffering based on family and patient consent. Although the majority of families were comfortable with this practice, clinicians should minimize family distress by regular monitoring of patient distress and timely modification of sedation protocols, providing sufficient information, sharing the responsibility of the decision, facilitating grief, and providing emotional support.

Background Communication about the ending of anticancer treatment and transition to palliative care is a difficult task for oncologists. The primary aims of this study were to clarify family-reported degree of emotional distress and the necessity for improvement in communication methods when communicating about the ending of anticancer treatment, and to identify factors contributing to the levels of emotional distress and the necessity for improvement. Methods A multi-center questionnaire survey was conducted on 630 bereaved family members of cancer patents who received specialized palliative care in Japan. A total of 318 responses were analyzed (effective response rate, 62%). Results Thirty-nine percent of the bereaved family members reported that they were ‘very distressed’ in receiving information about the ending of anticancer treatment, and 19% reported ‘considerable’ or ‘much’ improvement was necessary in the communication methods. High-level emotional distress was significantly associated with younger patient age, female family gender, the experience of the physician stating she/he could do nothing for the patient, the physician's unwillingness to explore their feelings, and prognostic disclosure of definite survival periods without probabilities or ranges. High levels of perceived necessity for improvement in the communication methods were significantly associated with the experience of the physician stating she/he could do nothing for the patient, physicians not explaining treatment goals in specific terms, physicians not pacing the explanation with the state of family preparation, physicians not being knowledgeable about the most advanced treatments, and the atmosphere not being relaxing enough to ask questions. Conclusions In receiving the information about ending anticancer treatment, a considerable number of families experienced high levels of emotional distress and felt a need for improvement of the communication methods. The strategies to alleviate family distress could include: (i) assuring that physicians will do their best to achieve specific goals, without saying that they can do nothing for the patient; (ii) providing information, including estimated prognosis, in careful consideration of families' preparation and the uncertainty for each patient; (iii) exploring families' emotions and providing emotional support; (iv) acquiring knowledge about advanced treatments; and (v) making the atmosphere relaxing enough to allow families to ask questions.

Purpose: Conventional chemotherapy for metastatic breast cancer results in very few long-term survivors. With a view to overcoming this problem, we hypothesized that a higher rate of complete response (CR) would lead to more long-term survivors. Therefore, we conducted a phase II study of epirubicin-containing high-dose chemotherapy (HDC) followed by autologous hematopoietic progenitor cell transfusion in patients who were sensitive to induction chemotherapy. Methods: The induction chemotherapy consisted of doxorubicin 60 mg/m2, cyclophosphamide 750 mg/m2 and fluorouracil 750 mg/m2 on day 1. Supported by G-CSF, this chemotherapy was repeated for at least three cycles at intervals of 2 weeks until the achievement of >50% tumor regression. The HDC comprised epirubicin 120 mg/m2 on day 1, cyclophosphamide 60 mg/kg on days 1 to 3 and thiotepa 6 mg/kg on days 1 to 3, followed by autologous bone marrow transplantation and peripheral blood stem cell transfusion. Results: Of 25 patients who achieved a partial response to the induction chemotherapy, 17 were treated with the HDC. Of the 15 patients evaluable for response, 10 achieved a CR (67%), giving an overall CR rate of 43% (10/25). The disease-free survival rate at 5 years was 27%. The median duration of overall survival was 21 months and the overall survival rate at 5 years was 31%. However, the survival curves were not significantly different from those of the historical controls who achieved a CR or PR to conventional chemotherapy. There were three early deaths, one as a consequence of disease progression and two treatment-related (sepsis and heart failure). Diarrhea (grade 3, 76%) and stomatitis (grade 3–4, 29%) were the dose-limiting toxicities. Conclusions: The present study suggests that epirubicin-containing HDC is able to induce a high rate of CR, but its benefit in terms of survival is still unclear. To determine whether HDC can achieve a cure in some patients, further studies in a larger number of patients, with a longer follow-up, are necessary.