[Automatic Quantification of Breast Density from Mammography Using Deep Learning].

BACKGROUND: In the field of breast screening using mammography, announcing to the examinees whether they are dense or not has not been deprecated in Japan. One of the reasons is a shortage of objectivity estimating their dense breast. Our aim is to build a system with deep learning algorithm to calculate and quantify objective breast density automatically. MATERIAL AND METHOD: Mammography images taken in our institute that were diagnosed as category 1 were collected. Each processed image was transformed into eight-bit grayscale, with the size of 2294 pixels by 1914 pixels. The "base pixel value" was calculated from the fatty area within the breast for each image. The "relative density" was calculated by dividing each pixel value by the base pixel value. Semantic segmentation algorithm was used to automatically segment the area of breast tissue within the mammography image, which was resized to 144 pixels by 120 pixels. By aggregating the relative density within the breast tissue area, the "breast density" was obtained automatically. RESULT: From each but one mammography image, the breast density was successfully calculated automatically. By defining a dense breast as the breast density being greater than or equal to 30%, the evaluation of the dense breast was consistent with that by a computer and human (76.6%). CONCLUSION: Deep learning provides an excellent estimation of quantification of breast density. This system could contribute to improve the efficiency of mammography screening system.

[Elements that cancer peer supporters working in Japanese hospitals consider to be important in helping them perform their role].

Objectives　The purpose of this study was to identify elements that cancer peer supporters working in Japanese hospitals consider to be important in helping them perform their role.Methods　A qualitative inductive research was conducted. Introductions to potential participants were obtained from a patient association that agreed to help with the study. Interviews were conducted from July through October 2014, using an interview guide, with cancer peer supporters who consented to participate in the study. Elements they perceived as important to the performance of their role were inductively identified from interview transcripts. The analysis consisted of coding phrases in the text and organizing the codes generated into categories and subcategories.Results　The study participants consisted of 10 cancer peer supporters (2 men, 8 women), in the age range of 40 to 70 years, who provided private counseling and worked in cancer support groups in hospitals. The analysis generated 129 codes, 11 subcategories, and 5 categories. These 5 categories were: [1.Help service users determine their own paths by listening to and accepting what they say with a non-judgmental attitude]; [2.Offer a perspective distinct from that of the medical staff]; [3.Think of ways to achieve a good balance between one's personal life and cancer peer support work while maintaining a stable state of mind]; [4.Ensure that one maintains the necessary knowledge and skills, and continually improve oneself]; and [5.Build relationships of trust with medical staff and the hospital].Conclusion　Category [1] and category [2] were behaviors regarded as important when interacting with users. They were "matters regarded as important during the practice of cancer peer support working for users," and comprised the core of matters that were regarded as important. Next, as for matters regarded as important in relation to the supporters themselves, the categories were [3] and [4]. These were "matters regarded as important for continuity and qualitative improvement of cancer peer support working." Areas that call for improvement in relation to this are preparation of support systems and learning environments. Another matter regarded as important was category [5]. This was a "matter regarded as important to smoothen and facilitate cancer peer support working." Placing importance on relationships of trust with medical staff and hospitals could be considered a distinctive characteristic of cancer peer supporters working at hospitals.

[Support that cancer peer supporters working at medical institutions currently receive and the support they actually need].

Objectives　This research aims to ascertain the kinds of support cancer peer supporters at medical institutions currently receive and the support they actually need.Methods　Participants in the study were ten cancer peer supporters who were recommended by a patient association and who agreed to participate in the study. Using a qualitative descriptive method, interviews were conducted using an interview guide from July to October 2014. Codes were extracted from the interview transcript and divided into categories and subcategories. Accuracy was ensured by checking the data with the participants. The study was conducted with the approval of the Ethics Committee of Mejiro University.Results　Research participants consisted of two men and eight women aged forty to seventy years, who were private counselors, telephone counselors, or members of cancer salons at hospitals. Four categories were generated on the basis of the support that cancer peer supporters are currently receiving: mutual learning and support among peer supporters, learning and encouragement from patients, self-improvement in peer supporters, and cooperation with hospitals and the government. Seven categories were generated on the basis of the support that cancer peer supporters need: opportunities for peer supporters to learn from and support each other, further studies on cancer peer support, reliable and up-to-date information, society's understanding and cooperation regarding cancer, financial support for support activities and patient associations, improvement of cancer peer support system, and quality assurance of peer supporter training courses.Conclusion　Cancer peer supporters were supporting each other, gaining encouragement from patients, improving themselves, and gaining support from others. However, they also needed additional assistance such as opportunities for supporters to learn from and support each other and reliable and up-to-date information. Moreover, peer supporters needed advice and emotional support from hospital staff as they experienced difficulties during consultation. Various other types of support were needed, such as society's understanding and cooperation regarding cancer, financial support for support activities and patient associations, institutionalization of peer supporter placement in hospitals, and quality assurance of peer supporter training courses. Overall, support for cancer peer supporters is still not sufficient; thus, further help is necessary.

Efficacy and safety of an amino acid jelly containing coenzyme Q10 and L-carnitine in controlling fatigue in breast cancer patients receiving chemotherapy: a multi-institutional, randomized, exploratory trial (JORTC-CAM01).

PURPOSE: Cancer-related fatigue (CRF) is one of the most common symptoms reported by cancer patients. This randomized trial investigated the efficacy of the amino acid jelly Inner Power(®) (IP), a semi-solid, orally administrable dietary supplement containing coenzyme Q10 and L-carnitine, in controlling CRF in breast cancer patients in Japan. METHODS: Breast cancer patients with CRF undergoing chemotherapy were randomly assigned to receive IP once daily or regular care for 21 days. The primary endpoint was the change in the worst level of fatigue during the past 24 h (Brief Fatigue Inventory [BFI] item 3 score) from day 1 (baseline) to day 22. Secondary endpoints were change in global fatigue score (GFS; the average of all BFI items), anxiety and depression assessed by the Hospital Anxiety and Depression Scale (HADS), quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC Breast Cancer-Specific QLQ (EORTC QLQ-BR23), and adverse events. RESULTS: Fifty-nine patients were enrolled in the study, of whom 57 were included in the efficacy analysis. Median patient age was 50 years. Changes in the worst level of fatigue, GFS, and current feeling of fatigue were significantly different between the intervention and control groups, whereas the change in the average feeling of fatigue was not significantly different between groups. HADS, EORTC QLQ-C30, and EORTC QLQ-BR23 scores were not significantly different between the two groups. No severe adverse events were observed. CONCLUSION: IP may control moderate-severe CRF in breast cancer patients. TRIAL REGISTRATION: The registration number of this study in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) is UMIN000008646.

Missing memories of death: Dissociative amnesia in the bereaved the day after a cancer death.

OBJECTIVE: The death of a loved one is one of the most stressful events of life, and such stress affects the physical and psychological well-being of the bereaved. Dissociative amnesia is characterized by an inability to recall important autobiographical information. Dissociative amnesia in the bereaved who have lost a loved one to cancer has not been previously reported. We discuss herein the case of a patient who developed dissociative amnesia the day after the death of here beloved husband. METHOD: A 38-year-old woman was referred for psychiatric consultation because of restlessness and abnormal behavior. Her 44-year-old husband had died of pancreatic cancer the day before the consultation. On the day of the death, she looked upset and began to hyperventilate. The next day, she behaved as if the deceased were still alive, which embarrassed her family. At her initial psychiatric consultation, she talked and behaved as if her husband was still alive and in the hospital. RESULTS: Her psychiatric features fulfilled the DSM-V criteria for dissociative amnesia. The death of her husband had been very traumatic for her and was considered to have been one of the causes of this dissociation. SIGNIFICANCE OF RESULTS: This report adds to the list of psychiatric symptoms in the bereaved who have lost a loved one to cancer. In an oncology setting, we should consider the impact of death, the concomitant defense mechanisms, and the background of the families.

Detection of circulating tumor cells in peripheral blood of heavily treated metastatic breast cancer patients.

BACKGROUND: Circulating tumor cells (CTCs) are detected in peripheral blood of breast cancer patients, and they may play an important role as a prognostic and predictive marker. We conducted this study to determine the presence of CTCs with the CellSearch System™ and the clinical significance in treatment of metastatic breast cancer (MBC). METHOD: Twenty-eight MBC patients were enrolled. These patients were followed by assessing CTCs, imaging studies, and serum tumor markers. Blood samples were collected before starting a new treatment and at the treatment evaluation period (2-3 months after starting chemotherapy). The cutoff for CTC level was 5. RESULTS: At baseline, 9 of 28 patients (32%) had ≥5 CTCs per 7.5 mL of blood. At the evaluation period, 5 of 23 patients (22%) had ≥5 CTCs. The baseline CTC number did not contribute to determine their overall survival (OS); however, CTCs at the evaluation period were available to predict their OS (p < 0.001). In two cases, both CTCs and tumor markers were available as predictors of treatment efficacy. In two other cases, although alterations of tumor markers might not reflect disease condition, CTC alteration corresponded to their condition. One patient who had multiple skeletal metastasis only, experienced a decrease in her CTCs in spite of tumor marker alteration. CONCLUSIONS: We suggest that monitoring the number of CTCs may be helpful in predicting the efficacy of the treatment and the prognosis. CTCs might be especially useful with patients whose lesions are difficult to assess.

Long-term efficacy of imatinib in a practical setting is correlated with imatinib trough concentration that is influenced by body size: a report by the Nagasaki CML Study Group.

Imatinib has dramatically improved long-term survival of chronic myelogenous leukemia (CML) patients. To analyze its efficacy in a practical setting, we registered most of CML patients in Nagasaki Prefecture of Japan. Of these, 73 patients received imatinib as an initial therapy. The overall survival rate of these patients was 88.7% at 6 years, and the cumulative complete cytogenetic response rate was 82.5% at 18 months. These results are comparable with the data of other reports including the IRIS study; however, the administered imatinib dose was smaller in our study than that in other reports. To address these discrepancies, we measured the trough concentration of imatinib among 35 patients. Although 39% of the patients were administered less than 400 mg/day, the trough level was comparable to those of previous reports. The trough level of imatinib showed a significant relationship with its efficacy, and was clearly related to dose of imatinib administrated and dose of imatinib divided by body surface area (BSA). Considering the smaller BSA of Japanese patients as compared to those of foreign origin, the results suggest that a lower dose of imatinib could maintain enough trough level and provided excellent results for the treatment of CML in our registry.

Imatinib provides durable molecular and cytogenetic responses in a practical setting for both newly diagnosed and previously treated chronic myelogenous leukemia: a study in nagasaki prefecture, Japan.

To evaluate the efficacy of imatinib in a practical setting, we registered 43 patients with newly diagnosed chronic myelogenous leukemia (CML) (group I) and 56 patients with previously diagnosed CML (group II) at 11 hematology centers in Nagasaki prefecture, Japan, from December 2001 to July 2005 and analyzed the molecular responses. Cytopenia, fluid retention, and skin rash were major adverse events, along with elevation in creatine phosphokinase levels. With a follow-up of approximately 3.5 years, imatinib treatment led to 88.7% overall survival (OS) and 85.2% progression-free survival (PFS) rates for group I, and 79.8% OS and 76.6% PFS rates for group II; the rates were not significantly different despite a lower average imatinib dose in group II. The rates of complete cytogenetic response at 30 months and major molecular response at 24 months were 86.1% and 62.5%, respectively, in group I, and 77.9% and 58.3% in group II; the rates were not significantly different. As has been reported by other groups, these results demonstrate that imatinib treatment can provide excellent clinical and molecular effects for not only newly diagnosed but also previously treated CML patients in practical settings that cover a wider variety of patients than clinical trials.

Expression of the myeloperoxidase gene in AC133 positive leukemia cells relates to the prognosis of acute myeloid leukemia.

We previously reported that the percentage of myeloperoxidase (MPO) positive blasts had a prognostic impact on survival of patients with acute myeloid leukemia (AML). To extend this observation, we quantitatively measured the level of the MPO gene in AC133 positive leukemia cells that would contain a putative AML stem/progenitor compartment. AML cases were divided into the MPO gene high (MPOg-H) and MPO gene low (MPOg-L) groups. Only patients belonging to the MPOg-H group had a favorable chromosomal translocation, t(8;21), and having no morphological dysplasia that was associated with MPOg-L. The difference in the survival of MPOg-H and MPOg-L was statistically meaningful, demonstrating the possible prognostic impact of the expression of MPO gene in AC133 positive leukemia cells.

Chemokine expression in human erythroid leukemia cell line AS-E2: macrophage inflammatory protein-3alpha/CCL20 is induced by inflammatory cytokines.

OBJECTIVE: Normal and malignant hematopoietic cells are shown to express and secrete various cytokines and chemokines, some of which are believed to play an important role in normal and abnormal hematopoiesis in an autocrine/paracrine manner. To explore the possibility of a cytokine/chemokine network participating in the pathophysiology of anemic disorders, we evaluated the ability of inflammatory cytokines to induce chemokine expression using erythroid progenitor cells. METHODS: Erythropoietin-dependent human leukemia cell line AS-E2 was used as a model of erythroid colony-forming unit (CFU-E) cells. The expression of mRNA of 8 chemokines was examined using RT-PCR, before and after TNF-alpha, IFN-gamma, and IL-1beta stimulation. For MIP-3alpha, the promoter activity was analyzed by luciferase assay and secretion was confirmed by ELISA. The expression of CCR6, the specific receptor for MIP-3alpha, was analyzed by RT-PCR and flow cytometry. RESULTS: Unstimulated AS-E2 cells constitutively expressed transcripts for MCP-4, IP-10, PF-4, IL-8, and MIP-3alpha. Stimulation with TNF-alpha, IFN-gamma, and IL-1beta upregulated MIP-3alpha mRNA expression and induced its protein secretion. Luciferase assay revealed that these cytokines could upregulate promoter activity of the MIP-3alpha gene, possibly through the NF-kappaB pathway. CCR6 mRNA was detected and its intracellular expression was confirmed. CONCLUSION: These data suggest that inflammatory cytokine-stimulated erythroid progenitors secrete MIP-3alpha, which may function in an autocrine/paracrine manner. Furthermore, the existence of intracellular CCR6 suggests the involvement in cytokine signaling of a MIP-3alpha-dependent internal autocrine mechanism. These mechanisms may play a role in pathophysiology of anemic disorders, such as secondary anemia and bone marrow failure syndromes.

Gene Expression Profiles of CD133-positive Fractions Predict the Survival of Individuals with Acute Myeloid Leukemia.

BACKGROUND: The current classification of acute myeloid leukemia (AML) is based predominantly on the cytogenetic abnormalities and morphology of the malignant blasts and is not always helpful for optimization of the treatment strategy. Gene expression profiles of AML blasts were obtained and a gene expression-based means of predicting the outcome of AML patients was developed. MATERIALS AND METHODS: CD133-positive hematopoietic stem cell-like fractions were purified from the bone marrow of 99 individuals with AML-related disorders and the expression profiles of ~33,000 human transcripts in these cells were characterized with the use of DNA microarray analysis. RESULTS: The comparison of the expression data between individuals with short- or long-term survival by application of Cox's proportional hazard model led to the identification of four genes, whose expression patterns discriminated between the two groups. The gene expression-based stratification (GES) system, based on a combination of the karyotype approach and the risk index calculated from the expression levels of the four outcome predictor genes, was developed to separate the patients into subgroups with distinct prognoses. CONCLUSION: DNA microarray analysis of purified fractions provides novel stratification schemes for AML based on the expression profiles of a handful of genes.

DNA microarray analysis of dysplastic morphology associated with acute myeloid leukemia.

OBJECTIVE: Acute myeloid leukemia (AML) develops de novo or secondarily to either myelodysplastic syndrome (MDS) or anticancer treatment (therapy-related leukemia, TRL). Prominent dysplasia of blood cells is apparent in individuals with MDS-related AML as well as in some patients with TRL or even with de novo AML. The clinical entity of AML with multilineage dysplasia (AML-MLD) is likely to be an amalgamation of MDS-related AML and de novo AML-MLD. The aim of this study was to clarify, by the use of high-density oligonucleotide microarrays, whether these subcategories of AML are intrinsically distinct from each other. MATERIALS AND METHODS: The AC133+ hematopoietic stem cell-like fractions were purified from the bone marrow of individuals with de novo AML without dysplasia (n = 15), AML-MLD (n = 11), MDS-related AML (n = 11), or TRL (n = 2), and were subjected to the synthesis of cRNA which was subsequently hybridized to microarray harboring oligonucleotide corresponding to more than 12,000 probe sets. RESULTS: We could identify many genes whose expression was specific to these various subcategories of AML. Furthermore, with the correspondence analysis/three-dimensional projection strategy, we were able to visualize the independent, yet partially overlapping, nature of current AML subcategories on the basis of their transcriptomes. CONCLUSION: Our data indicate the possibility of subclassification of AML based on gene expression profiles of leukemic blasts.

Membranous nephropathy after allogeneic stem cell transplantation: report of 2 cases.

Nephrotic syndrome (NS) is a rare complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The cases of 2 patients who developed NS after receiving allo-HSCT for chronic myelogenous leukemia and acute lymphoblastic leukemia are described. In both cases, renal biopsy revealed membranous nephropathy (MN), and the patients achieved remission after treatment with prednisolone. Previously reported cases and our experience suggest that most NS patients show MN in histologic tests after allo-HSCT and that its development is related to graft-versus-host disease. Early treatment with steroids seems effective for resolving symptoms of NS and improving renal function.

The level of MEF but not ELF-1 correlates with FAB subtype of acute myeloid leukemia and is low in good prognosis cases.

ETS proteins (such as PU.1, Fli-1 and ETS-1) have been shown to play important roles in normal and abnormal hematopoiesis. We examined the expression of the ELF subfamily of ETS genes (ELF-1, MEF and NERF) in acute myeloid leukemia (AML) cells using Northern blot analysis. ELF-1 and MEF were expressed in all samples, whereas NERF was not. The relative expression (RE) of MEF, but not ELF-1, was significantly lower (P<0.0001) in AML with t(8;21) and t(15;17) compared with AML with normal karyotype. The pattern of MEF expression was not uniform among cells with CD34(+)/CD33(+). It is suggested that the low RE of MEF might be part of a gene expression profile characterizing AML with a good prognosis.

Matrix metalloproteinase-9 and vascular endothelial growth factor: a possible link in adult T-cell leukaemia cell invasion.

Plasma from a total of 57 patients with adult T-cell leukaemia (ATL) (acute ATL, 39 patients; lymphoma ATL, one patient; chronic ATL, 15 patients; smouldering ATL, two patients) and 20 healthy controls was analysed for the presence of type IV gelatinase activity with clinical features. A significant elevation of plasma matrix metalloproteinase-9 (MMP-9) was observed in some ATL patients, particularly in the patients with malignant cell infiltration. MMP-9 was found to be secreted into the conditioned medium from all ATL cell lines examined. Moreover, the corresponding mRNA was detectable both in all ATL cell lines examined and in the majority of primary acute ATL cells, indicating that ATL cells are capable of synthesizing and secreting MMP-9. We previously demonstrated that a high incidence of ATL cell infiltration was closely related to a high plasma level of vascular endothelial growth factor (VEGF) produced by ATL cells themselves. This present study showed that the presence of increased plasma MMP-9 was closely associated with elevated plasma VEGF in ATL patients. Furthermore, we showed that both increased plasma MMP-9 and VEGF were significantly related to high ATL cell infiltration. All these findings strongly suggest that MMP-9 and VEGF act co-operatively in the process of ATL cell invasion.