Cancer Rehabilitation Provided by Designated Cancer Hospitals in Japan: The Current State of Outpatient Setting and Coordination after Discharge.

Objectives: The aim of the present study was to clarify the current state of outpatient cancer rehabilitation and coordination systems provided by designated cancer hospitals in Japan. Methods: A questionnaire was sent to 427 designated cancer hospitals in Japan to investigate the status of outpatient cancer rehabilitation and whether it was sufficiently conducted. The status of regional coordination with post-discharge rehabilitation facilities was surveyed. Results: Responses were received from 235/427 facilities (55.0%). Outpatient cancer rehabilitation was implemented in 92 (39.1% of responding facilities), and of these facilities, 83.7% answered that the provision of rehabilitation was insufficient. The reasons were ineligibility for reimbursement of medical fees, a lack of human resources, a lack of awareness of the need, and a lack of education. Regional coordination was conducted by 39.1% of responding facilities, yet a regional alliance path had been established in only 9.8% of centers. The absence of coordination was associated with large facility size, the absence of physiatrists, and few rehabilitation professionals who had completed the training program; an insufficient framework for regional coordination was also given as a reason. Conclusions: To provide adequate outpatient cancer rehabilitation, sufficient human resources, the reimbursement of medical fees in the outpatient setting, and education and a framework to promote regional coordination are necessary.

A Support System for Adolescent and Young Adult Patients with Cancer at a Comprehensive Cancer Center.

Cancer patients in adolescents and young adults (AYA) generation aged 15-39 years have various psychosocial needs during their treatment course such as school enrollment, finding employment, marriage, and fertility. It is difficult for medical professionals to gain experience related to providing medical care and consultation support to these kinds of AYA generation cancer patients. There is a need to provide information and establish both support and medical care systems that are able to meet the diverse needs unique to this generation. This review will explain how to launch an AYA support team (AST). We have worked and established the AST since 2016, which is medical care teams that provide support according to the life stage of each individual patient and build a multidisciplinary AYA generation patient support system. The team-building process consisted of two main projects: building and enlarging multidisciplinary team and establishing screening process of psychosocial needs of AYA generation patients. Multidisciplinary healthcare professionals got involved in the AST with already-existing patient support functions in our center: the patient support center, which is an outpatient department and the palliative care team, which is an inpatient interdepartmental team. The AST systematically finds patients in need of assistance and offers them support as a multidisciplinary team. The AST also established a procedure that systematically gathers information about the needs of patients by using a screening tool. In addition, the AST provides the following specialized services: reproductive medicine, supporting cancer patients with children, employment support, and peer support. The AST has been established and sophisticatedly worked. It can flexibly provide various psychosocial support services. This review will explain how to launch an AST.

The current status of inpatient cancer rehabilitation provided by designated cancer hospitals in Japan.

OBJECTIVE: This survey was conducted to clarify the current status of inpatient cancer rehabilitation provided by designated cancer hospitals in Japan. METHODS: A survey questionnaire was sent to 427 designated cancer hospitals in Japan. Information was sought regarding whether inpatient cancer rehabilitation was provided by the center, and if so, whether respondents regarded such provision as satisfactory. RESULTS: Responses were obtained from 235/427 surveyed institutions (55.0%). Cancer rehabilitation was provided in inpatient settings by 97.4%. Two-thirds of respondents (67.7%) regarded inpatient cancer rehabilitation provision as still inadequate. The primary reasons claimed for this inadequacy were a lack of human resources, a lack of rehabilitation professionals with the requisite knowledge/skills and patients who would benefit from cancer rehabilitation present but not prescribed. The total number of rehabilitation staff was identified as associated factor of inadequate inpatient cancer rehabilitation in multivariate analysis (odds ratio = 0.979, 95% confidence interval = 0.96-1.00, P = 0.009). CONCLUSIONS: In order to provide adequate cancer rehabilitation, a sufficient supply of rehabilitation staff, education and recognition of the need for cancer rehabilitation within oncology units are necessary.

The endoplasmic reticulum stress transducer BBF2H7 suppresses apoptosis by activating the ATF5-MCL1 pathway in growth plate cartilage.

BBF2H7 (box B-binding factor 2 human homolog on chromosome 7) is a basic leucine zipper transmembrane transcription factor that belongs to the cyclic AMP-responsive element-binding protein (CREB)/activating transcription factor (ATF) family. This novel endoplasmic reticulum (ER) stress transducer is localized in the ER and is cleaved in its transmembrane region in response to ER stress. BBF2H7 has been shown to be expressed in proliferating chondrocytes in cartilage during the development of long bones. The target of BBF2H7 is Sec23a, one of the coat protein complex II components. Bbf2h7-deficient (Bbf2h7(-/-)) mice exhibit severe chondrodysplasia, with expansion of the rough ER in proliferating chondrocytes caused by impaired secretion of extracellular matrix (ECM) proteins. We observed a decrease in the number of proliferating chondrocytes in the cartilage of Bbf2h7(-/-) mice. TUNEL staining of the cartilage showed that apoptosis was promoted in Bbf2h7(-/-) chondrocytes. Atf5 (activating transcription factor 5), another member of the CREB/ATF family and an antiapoptotic factor, was also found to be a target of BBF2H7 in chondrocytes. ATF5 activated the transcription of Mcl1 (myeloid cell leukemia sequence 1), which belongs to the antiapoptotic B-cell leukemia/lymphoma 2 family, to suppress apoptosis. Finally, we found that the BBF2H7-ATF5-MCL1 pathway specifically suppressed ER stress-induced apoptosis in chondrocytes. Taken together, our findings indicate that BBF2H7 is activated in response to ER stress caused by synthesis of abundant ECM proteins and plays crucial roles as a bifunctional regulator to accelerate ECM protein secretion and suppress ER stress-induced apoptosis by activating the ATF5-MCL1 pathway during chondrogenesis.

Unfolded protein response, activated by OASIS family transcription factors, promotes astrocyte differentiation.

OASIS is a member of the CREB/ATF family of transcription factors and modulates cell- or tissue-specific unfolded protein response signalling. Here we show that this modulation has a critical role in the differentiation of neural precursor cells into astrocytes. Cerebral cortices of mice specifically deficient in OASIS (Oasis(-/-)) contain fewer astrocytes and more neural precursor cells than those of wild-type mice during embryonic development. Furthermore, astrocyte differentiation is delayed in primary cultured Oasis(-/-) neural precursor cells. The transcription factor Gcm1, which is necessary for astrocyte differentiation in Drosophila, is revealed to be a target of OASIS. Introduction of Gcm1 into Oasis(-/-) neural precursor cells improves the delayed differentiation of neural precursor cells into astrocytes by accelerating demethylation of the Gfap promoter. Gcm1 expression is temporally controlled by the unfolded protein response through interactions between OASIS family members during astrocyte differentiation. Taken together, our findings demonstrate a novel mechanism by which OASIS and its associated family members are modulated by the unfolded protein response to finely control astrocyte differentiation.

The endoplasmic reticulum stress transducer OASIS is involved in the terminal differentiation of goblet cells in the large intestine.

OASIS is a basic leucine zipper transmembrane transcription factor localized in the endoplasmic reticulum (ER) that is cleaved in its transmembrane region in response to ER stress. This novel ER stress transducer has been demonstrated to express in osteoblasts and astrocytes and promote terminal maturation of these cells. Additionally, OASIS is highly expressed in goblet cells of the large intestine. In this study, we investigated the roles of OASIS in goblet cell differentiation in the large intestine. To analyze the functions of OASIS in goblet cells, we examined morphological changes and the expression of goblet cell differentiation markers in the large intestine of Oasis(-/-) mice. By disrupting the Oasis gene, the number of goblet cells and production of mucus were decreased in the large intestine. Oasis(-/-) goblet cells showed abnormal morphology of mucous vesicles and rough ER. The expression levels of mature goblet cell markers were lower, and conversely those of early goblet cell markers were higher in Oasis(-/-) mice, indicating that differentiation from early to mature goblet cells is impaired in Oasis(-/-) mice. To determine the association of OASIS with other factors involved in goblet cell differentiation, in vitro experiments using a cell culture model were performed. We found that OASIS was activated in response to mild ER stress that is induced in differentiating goblet cells. Knockdown of the Oasis transcript perturbed goblet cell terminal differentiation. Together, our data indicate that OASIS plays crucial roles in promoting the differentiation of early goblet cells to mature goblet cells in the large intestine.

Six-year experience of permanent prostate brachytherapy for clinically localized prostate cancer.

This report presents the outcome of prostate permanent brachytherapy (PPB). One hundred and seventy-two patients with clinically localized prostate cancer were treated with permanent brachytherapy using iodine-125 seeds (125-I) at Hiroshima University Hospital from July 2004 to June 2010. This study evaluated the efficacy of PPB in these patients. The median patient age was 69 years (range 53 to 82 years), the median prostate-specific antigen (PSA) value before biopsy was 6.75 ng/ml (range 3.5 to 47.9 ng/ml), and the median prostate volume was 23.1 ml (range 10.1 to 57 ml). The median follow-up was 37 months (range 1 to 72 months). The serum PSA levels decreased continuously after PPB throughout the entire follow-up period in 97% of patients without neoadjuvant hormonal therapy. No relapse occurred during the follow-up period in patients at low risk. Our 6-year experience suggests that PPB is effective for localized prostate cancer. Patients with prostate cancer that does not require combined external beam radiation therapy (EBRT) have the best chance of responding to treatment.