Status and prognostic value of immunological biomarkers of breast cancer.

The immune response to cancer serves an important role in disease progression and patient prognosis. For triple-negative breast cancer showing aggressive behavior, immunotherapy has a good efficacy because of the potent immunogenicity of this type of cancer. However, the dominant subtype, luminal human epidermal growth factor receptor-2 (HER2)-negative breast cancer, is less immunogenic. To determine whether luminal HER2-negative cancer reacts to the anticancer immune response, the present study analyzed the status and prognostic value of the principal immunological biomarkers of breast cancer, including tumor-infiltrating lymphocytes (TILs), CD8+ T lymphocytes, the major histocompatibility complex and programmed cell death ligand-1 (PD-L1). The biomarkers were compared between patients with luminal HER2-negative breast cancer and those with immunogenic subtypes including triple-negative and HER2-overexpressed breast cancer. A total of 71 patients with primary breast cancer were classified into the immunogenic non-luminal (n=23) and less immunogenic luminal HER2-negative groups (n=48) based on immunogenicity. In the luminal HER2-negative group, compared with patients with low TIL levels, those with high TIL levels were at an advanced stage of cancer (P=0.024) and showed worse relapse-free survival (P=0.057); however, the remaining biomarkers exhibited no association with cancer progression or prognosis. In the non-luminal group, patients with high TIL levels showed significantly better RFS than those with low TIL levels (P=0.014). Compared with non-luminal patients negative for PD-L1, those positive for PD-L1 exhibited better overall survival (P=0.064). Notably, TIL status was found to exhibit contrasting prognostic predictions based on immunogenicity. In conclusion, TILs are a strong candidate for prognostic prediction in breast cancer, regardless of the subtype. PD-L1 is a potential candidate for prognostic prediction in immunogenic breast cancers, but not in the luminal HER2-negative subtype.

NANDA-I, NOC, and NIC linkages to SARS-CoV-2 (COVID-19): Part 3. Family response.

PURPOSE: To provide guidance to nurses caring for families with COVID-19, we developed linkages using interoperable standardized nursing terminologies: NANDA International (NANDA-I) nursing diagnoses, Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC). In addition, we wanted to identify gaps in the terminologies and potential new nursing diagnoses, outcomes, and interventions for future development related to nurse roles in family care during a pandemic. METHODS: Using a consensus process, seven nurse experts created the linkages focused on families during the COVID-19 pandemic using the following steps: (1) creating an initial list of potential nursing diagnoses, (2) selecting and categorizing outcomes that aligned with all components of each nursing diagnosis selected, and (3) identifying relevant nursing interventions. FINDINGS: We identified a total of seven NANDA-I nursing diagnoses as the basis for the linkage work. These are distributed in three NANDA-I Domains and based in the psychosocial dimension of the Nursing Care in Response to Pandemics model. Eighty-nine different NOC outcomes were identified to guide care based on the nursing diagnoses, and 54 different NIC interventions were suggested as possible interventions. Fifteen new proposed concepts were identified for future development across the three classifications. CONCLUSIONS: The linkages of nursing diagnoses, outcomes, and interventions provide a guide to enhance nursing practice and care documentation that could quantify the impact of nursing care to patient outcomes for families at risk for or infected by COVID-19. IMPLICATIONS FOR NURSING PRACTICE: NANDA-I, NOC, and NIC linkages identified in this paper provide resources to support clinical decisions and guide critical thinking for nurses encountering care needs of families with COVID-19. Documentation of these linkages provides data that can create new knowledge to enhance the care of families impacted by COVID-19.

The association between resilience and academic performance among nursing students: a cross-sectional study in Japan.

Objective: Medical science students, especially nursing students, are more likely to experience academic stress; therefore, resilience helps them focus on their lessons attentively. However, the results of a few existing studies regarding how resilience impacts the academic performance of medical science students are incongruent. This study aimed to investigate whether resilience impacts the academic performance of Japanese nursing students. Methods: We conducted a cross-sectional, self-administered questionnaire survey from September to November 2020. A total of 229 undergraduate nursing students participated in this study; here, resilience was measured using the Bidimensional Resilience Scale, which includes innate factors (optimism, control, sociability, and vitality) and acquired factors (problem-solving, self-understanding, and understanding others). Academic performance was measured using the functional grade point average (f-GPA). Covariates were demographics, pre-entry academic performance levels, medical history, time spent walking, psychological distress, subjective economic status, and part-time jobs. Multivariate regression analyses were performed. Results: Among the 229 participants, the f-GPA mean (standard deviation) was 2.93 (0.46). Only vitality was significantly associated with a higher f-GPA after multiple imputations (ß = 0.06; 95% confidence interval = 0.03-0.09; P<0.01). The Poisson regression analysis of 212 participants with all data indicated that vitality was associated with the fourth quartile f-GPA (prevalence ratio, 1.05; 95% confidence interval, 1.03-1.08; P<0.01). Conclusion: There was a significant association between the vitality of resilience components and academic performance among Japanese nursing students. This study suggests that an approach that develops resilience is necessary for the academic success of nursing students.

NANDA-I, NOC, and NIC Linkages to SARS-Cov-2 (Covid-19): Part 1. Community Response.

PURPOSE: We developed linkages using interoperable standardized nursing terminologies, NANDA International (NANDA-I) nursing diagnoses, Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC), to present initial guidance for the development of care plans focused on COVID-19 for nurses practicing in community or public health roles. METHODS: Seven nurse experts identified the linkages of NANDA-I, NOC and NIC for our work related to the COVID-19 pandemic. A model was developed to guide the project. The first step in creating linkages focused on the identification of nursing diagnoses. Then, for each nursing diagnosis, outcomes aligned with all components of the diagnosis were categorized and a list of nursing interventions was selected. The experts used their clinical judgment to make final decisions on the linkages selected in this study. FINDINGS: Two community level nursing diagnoses were identified as key problems appropriate for a pandemic related to COVID-19: Deficient Community Health and Ineffective Community Coping. For the nursing diagnosis Deficient Community Health, eight nursing outcomes and 12 nursing interventions were selected. In comparison for the nursing diagnosis, Ineffective Community Coping, nine nursing outcomes and 18 nursing interventions were identified. A total of40 concepts were identified for future development across the three classifications. CONCLUSIONS: The nursing diagnoses, outcomes and interventions selected during this linkage process provide knowledge to support the community challenged with responding to the COVID-19 pandemic, provide the opportunity to quantify the impact of nursing care, and enhance nursing practice by promoting the use of three standardized terminologies. IMPLICATIONS FOR NURSING PRACTICE: NANDA-I, NOC and NIC linkages identified in this manuscript provide resources to support clinical decisions and care plan development for nurses practicing in the community.

NANDA-I, NOC, and NIC linkages to SARS-CoV-2 (COVID-19): Part 2. Individual response.

PURPOSE: To provide guidance to nurses caring for individuals with COVID-19, we developed linkages using interoperable standardized nursing terminologies: NANDA International (NANDA-I) nursing diagnoses, Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC). We also identified potential new NANDA-I nursing diagnoses, NOC outcomes, and NIC interventions for future development related to nurses' role during a pandemic. METHODS: Using a consensus process, seven nurse experts created the linkages for individuals during the COVID 19 pandemic using the following steps: (a) creating an initial list of potential nursing diagnoses, (b) selecting and categorizing outcomes that aligned with all components of each nursing diagnosis selected, and (c) identifying relevant nursing interventions. FINDINGS: A total of 16 NANDA-I nursing diagnoses were identified as the foundation for the linkage work, organized in two dimensions, physiological and psychosocial. A total of 171 different NOC outcomes were identified to guide care based on the nursing diagnoses and 96 NIC interventions were identified as suggested interventions. A total of 13 proposed concepts were identified for potential future development across the three classifications. CONCLUSIONS: The linkages of nursing diagnoses, outcomes, and interventions developed in this article provide a guide to enhance nursing practice and determine the effectiveness of nurses' contribution to patient outcomes for individuals at risk for or infected by COVID-19. IMPLICATIONS FOR NURSING PRACTICE: NANDA-I, NOC, and NIC linkages identified in this paper are an important example of the value of using standardized nursing terminologies to guide and document nursing care. When included in electronic health record databases and used widely, the data generated from the care plans can be used to create new knowledge about how to better improve outcomes for patients with COVID-19.

NANDA-I, NOC, and NIC Linkages for Nutritional Problems.

PURPOSE: To determine nursing outcomes and interventions for problem-focused nursing diagnoses related to nutritional problems. METHODS: Judgment of linkages among nursing diagnoses, outcomes, and interventions using a multiple review process. Five nursing diagnoses were selected, and then outcomes and interventions were determined, based on clinical expertise and scientific literature. FINDINGS: Nursing outcomes and interventions were determined for the resolution or improvement of the nursing diagnoses, with selection of interventions that could influence the progression of the outcomes. CONCLUSIONS: This study provides knowledge for developing care plans for patients with nutritional problems and evaluating the response to the interventions. IMPLICATIONS FOR NURSING PRACTICE: NANDA-I, Nursing Outcomes Classification (NOC), and Nursing Interventions Classification (NIC) linkages facilitate nurses' ability to select nursing outcomes and interventions for patients with nutritional problems.

Maintenance antisepsis in reducing the rate of late-onset central venous catheter-related bloodstream infection: A comparison of 0.05% and 1% chlorhexidine.

BACKGROUND: Bundled measures have been recommended to reduce the risk of central venous catheter (CVC)-related bloodstream infection. However, the importance of each procedure involved in CVC insertion/management for preventing catheter-related bloodstream infection (CRBSI) has not been thoroughly assessed. We aimed to analyze the effectiveness of maintenance antisepsis at the CVC insertion site in reducing the CRBSI risk through comparing the use of 0.05% chlorhexidine to 1% chlorhexidine. PATIENTS AND METHODS: In the South Miyagi Medical Center, Japan, 372 patients with a CVC who had undergone antisepsis maintenance using 0.05% chlorhexidine swabs 12 months prior to implementing 1% chlorhexidine swabs, and 344 patients at 12 months post-implementation of 1% chlorhexidine swabs, were followed prospectively for the development of CRBSI and signs of infection, and their data compared. RESULTS: Post-implementation of the 1% chlorhexidine swabs, the CRBSI rate decreased from 3.64/1000 catheter-days to 1.77/1000 catheter-days. The risk of CRBSI decreased to 0.465 (95% confidence interval [CI]: 0.216-1.001). Furthermore, the risk of CRBSI ≥20 days after CVC insertion decreased to 0.200 (95% CI: 0.049-0.867); however, we found no difference between 0.05% and 1% chlorhexidine use within 19 days of CVC insertion. The increased number of patients with insertion site tenderness after implementing 1% chlorhexidine indicated a possible adverse effect of chlorhexidine. CONCLUSION: Maintenance antisepsis with 1% chlorhexidine decreased the risk of developing CRBSI ≥20 days after CVC insertion, indicating the effectiveness of antisepsis with 1% chlorhexidine. Our data highlight the importance of maintenance antisepsis in reducing the rate of late-phase CRBSI.

Cluster of differentiation 8 and programmed cell death ligand 1 expression in triple-negative breast cancer combined with autosomal dominant polycystic kidney disease and tuberous sclerosis complex: a case report.

BACKGROUND: Autosomal dominant polycystic kidney disease is defined as an inherited disorder characterized by renal cyst formation due to mutations in the PKD1 or PKD2 gene, whereas tuberous sclerosis complex is an autosomal dominant neurocutaneous syndrome caused by mutation or deletion of the TSC2 gene. A TSC2/PKD1 contiguous gene syndrome, which is caused by a chromosomal mutation that disrupts both the TSC2 and PKD1 genes, has been identified in patients with tuberous sclerosis complex and severe early-onset autosomal dominant polycystic kidney disease. The tumor tissue of patients with breast cancer with contiguous gene syndrome has a high mutation burden and produces several neoantigens. A diffuse positive immunohistochemistry staining for cluster of differentiation 8+ in the T cells of breast cancer tissue is consistent with neoantigen production due to high mutation burden. CASE PRESENTATION: A 61-year-old Japanese woman who had been undergoing dialysis for 23 years because of end-stage renal failure secondary to autosomal dominant polycystic kidney disease was diagnosed as having triple-negative breast cancer and underwent mastectomy in 2015. She had a history of epilepsy and skin hamartoma. Her grandmother, mother, two aunts, four cousins, and one brother were also on dialysis for autosomal dominant polycystic kidney disease. Her brother had epilepsy and a brain nodule. Another brother had a syndrome of kidney failure, intellectual disability, and diabetes mellitus, which seemed to be caused by mutation in the CREBBP gene. Immunohistochemistry of our patient's breast tissue showed cluster of differentiation 8 and programmed cell death ligand 1 positivity. CONCLUSIONS: Programmed cell death ligand 1 checkpoint therapy may be effective for recurrence of triple-negative breast cancer in a patient with autosomal dominant polycystic kidney disease and tuberous sclerosis complex.

Prognostic impact of interleukin-6 and C-reactive protein on patients with breast cancer.

The prognostic impacts of preoperative C-reactive protein (CRP) and interleukin (IL)-6 expression levels in patients with breast cancer remain controversial. A total of 55 female patients with invasive breast cancer were enrolled, and preoperative prognostic parameters including IL-6 and CRP were analyzed. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method, and candidates' prognostic factors were examined using a Cox proportional hazard model. Using receiver operating characteristic curve analysis, IL-6 at 10.0 pg/ml and CRP at 0.12 mg/dl were determined as threshold values to predict OS and RFS, respectively. Patients with IL-6 ≥10.0 pg/ml had poorer OS compared with those with IL-6 <10.0 pg/ml (P=0.003), and patients with CRP ≥0.12 mg/dl had poorer RFS compared with those with CRP <0.12 mg/dl (P<0.001). Serum IL-6 level (hazard ratio, 13.230; 95% confidence interval, 1.285-136.214; P=0.030) and triple-negative subtype (hazard ratio, 11.739; 95% confidence interval, 1.415-97.362; P=0.023) were independent prognostic factors for OS, and CRP expression level was an independent prognostic factor for RFS in patients with breast cancer (hazard ratio, 18.571; 95% confidence interval, 2.240-153.949; P=0.007). In patients with invasive breast cancer, preoperative serum IL-6 and triple-negative subtype may be independent prognostic factors for OS, while for RFS, preoperative CRP may be a more accurate prognostic factor compared with those currently established.

Expression profile of CADM1 and CADM4 in triple negative breast cancer with primary systemic therapy.

Triple negative breast cancer (TNBC) is defined by a lack of ER, PgR, and HER2 expression, and to date there have been no significant advances in treatment by targeted therapies against those molecules. Therefore, primary systemic therapy (PST) followed by surgery is the standard therapy for patients with advanced TNBC. According to gene expression analysis, TNBC has a distinct profile when compared with non-TNBC, suggesting that a unique gene affects the treatment efficacy of PST. Cell adhesion molecule (CADM) genes encode an immunoglobulin superfamily molecule involved in cell-to-cell adhesion in a variety of human epithelial cells. While it has been reported that inactivation of CADM1 and CADM4 serves a pivotal role in the progression of breast cancer, a full analysis has not been completed for TNBC. Previous studies have reported that CADM1 and CADM4 expression is less likely to be decreased in TNBC than in non-TNBC. In the present study, CADM1 and CADM4 expression was evaluated in patients with TNBC who had received PST. The present study revealed that loss or weak expression of CADM1 was frequently observed in non-pathological complete response patients. Furthermore, while the majority of TNBC cases exhibited high CADM1 expression, a small number of cases exhibited low CADM1 expression and low therapeutic response of PST for TNBC. These results suggest that CADM1 has a pivotal role in anti-PST efficacy in patients with TNBC.

To Be Supported, or Not to Be: Images of Older People in Policy and the Reality in Local Communities in Japan.

Social innovation is not only about tangible new products, services, policies, and laws, but also about changes in societal perceptions, values, and norms. In Japan, current policies for older people, including Long-Term Care Insurance, tend to focus on medical and long-term care and other forms of "support" for older adults such as a pension. Naturally, these policies depict older adults as the "beneficiaries," or the ones in need of support. However, when we look back at pre-modern Japan, it was not always like that. Although older adults did depend on support from family and community members, they also played an active role as a laborer and caretaker as well as providing useful knowledge for their family and community. Moreover, currently, in different areas suffering from a sharp decline in population, such as Okayama prefecture in western Japan, older people are actually playing the role of the supporter for groups of people who are in need, not only the aged population but also other demographics including young children and parents. Based on this historic "tradition" and the present reality, this paper argues that we need to reestablish the image of (at least some) older people as capable of taking a more active and responsible role in society, and position them as such in the new "welfare society" systems in order to replace the conventional "welfare state" model.

[A Case of Synchronous Bilateral Neuroendocrine Ductal Carcinoma In Situ].

Neuroendocrine ductal carcinoma in situ(NE-DCIS)is a unique subtype of ductal carcinoma in situ(DCIS)that is not described in the general rules for clinical and pathological recording of breast cancer. NE-DCIS is described as an unusual variant of DCIS in the 2012 World Health Organization(WHO)classification. The chief complaint in NE-DCIS is hemorrhagic nipple discharge. The histological characteristics of NE-DCIS are solid growth of cancer cells with granular and spindle-shaped nuclei. Histologically, NE-DCIS is suggestive of low malignancy but a poor prognosis of neuroendocrine carcinoma of the breast has been reported. The report by Honami et al was the only other report of synchronous bilateral neuroendocrine ductal carcinoma in situ. We report the second case of NE-DCIS diagnosed synchronously in both breasts in a patient who had visited our outpatient clinic with hemorrhagic nipple discharge.

Decreased expression of CADM1 and CADM4 are associated with advanced stage breast cancer.

Cell adhesion molecule (CADM) genes encode immunoglobulin superfamily molecules, which are involved in cell-cell adhesion in a number of human epithelia. Through the maintenance of epithelia, CADM genes protect against malignant conversion and metastasis. Whilst numerous in vitro studies have investigated the molecular characteristics of CADM1 and CADM4 and in vivo studies have investigated CADM1 and CADM4 expression in a number of tumor types, the roles of CADM1 and CADM4 have yet to be elucidated. Therefore, in the present study, CADM1 and CADM4 expression levels were evaluated using immunohistochemistry staining in 208 patients with breast cancer and compared with clinicopathological factors. CADM1 and CADM4 expression levels were negative in 160 (76.9%) and 166 (79.8%) of the 208 cases, respectively. The lack of expression in these cases was associated with advanced tumor stage, suggesting that inactivation of CADM1 and CADM4 promotes breast cancer development. The prognostic role of CADM1 and CADM4 in breast cancer was also evaluated and the expression of CADM1 and CADM4 were not associated with cancer-specific survival or overall survival rate in the cohort of patients in the present study. Whilst these results suggested that CADM1 and CADM4 possess tumor suppressive roles, further functional experiments are required to address the important mechanisms involving CADM1 and CADM4.

[A Case of Encapsulated Papillary Carcinoma of the Breast].

An 84-year-old woman was revealed to have focal asymmetric density(FAD)based on mammography, and ultrasonography showed a 0.5 cm sized cyst in the left breast. It gradually increased in size and contained solid components. A core needle biopsy revealed an intracystic papillary carcinoma of the breast. Partial mastectomy and sentinel lymph node biopsy were performed. Histopathological examination revealed an encapsulated papillary carcinoma and a papillary lesion surrounded by a thick fibrous capsule. Myoepithelial cells were not found at the periphery of the lesion or within fibrovascular cores. Currently, it is classified as non-invasive carcinoma, and the patient has a good prognosis.

Immunogenic tumor cell death induced by chemotherapy in patients with breast cancer and esophageal squamous cell carcinoma.

It has been reported that chemo-radiotherapy can induce immunogenic tumor cell death (ICD), which triggers T-cell immunity mainly mediated by high-mobility group box 1 protein (HMGB1) and calreticulin. However, there is still limited information to support this theory relating to chemotherapy alone. In the present study, the expression of HMGB1 and calreticulin was evaluated by immunohistochemistry in pre-treatment biopsy specimens and surgically resected specimens, which were obtained from patients with breast cancer (n=52) and esophageal squamous cell carcinoma (ESCC) (n=8) who had been treated with neoadjuvant chemotherapy (NAC). We also analyzed HMGB1 and calreticulin expression in breast cancer cell lines treated with chemotherapeutic drugs. As a result, both HMGB1 and calreticulin expression levels were significantly upregulated after NAC in both breast cancer and ESCC tissues. However, no significant correlation was observed between HMGB1 expression and pathological response after NAC or between HMGB1 expression and patient survival. Furthermore, although overall survival in the high infiltration group of CD8-positive T cells was significantly superior to that in the low infiltration group in breast cancer patients, there were no correlations between the number of CD8-positive T cells and HMGB1 or calreticulin expression levels. In addition, chemotherapeutic drugs induced upregulation of HMGB1 and calreticulin in all tested cell lines. Our findings indicate that chemotherapy alone can significantly induce ICD regardless of the degree of pathological response after chemotherapy.

Myeloid-derived suppressor cells are increased and correlated with type 2 immune responses, malnutrition, inflammation, and poor prognosis in patients with breast cancer.

Myeloid-derived suppressor cells (MDSCs) have been identified in the majority of patients and experimental mice with tumors by their suppression of T cell activation. MDSCs have also been reported to be associated with chronic inflammation. In advanced cancer, the T helper (Th) cell balance tends to shift from Th1 to Th2 predominance, and immune function, including cell-mediated immunity, is impaired by cytokines produced by Th2 cells. The present study examined the correlations between MDSC levels and inflammation, immune suppression, malnutrition, and poor prognosis in 155 patients with breast cancer. The levels of MDSCs in preoperative patients and in patients with recurrent breast cancer were significantly higher compared with postoperative patients, patients with recurrent breast cancer who received chemotherapy and healthy volunteers. The MDSC levels of preoperative patients were significantly positively correlated with interleukin (IL)-6 production by peripheral blood mononuclear cells (PBMCs), the neutrophil/lymphocyte ratio and C-reactive protein, and were negatively correlated with the production of interferon-γ and IL-12, serum concentration of rapid turnover protein, and the stimulation index. These patients were divided into two groups based on the levels of MDSCs. In preoperative patients with MDSC levels >1.0% of total PBMCs, the overall survival of patients with stage IV disease was significantly shorter compared with other disease stages, and was also significantly shorter compared with patients with MDSC levels <1.0% of total PBMCs. Thus, the MDSC levels of preoperative patients may function as a good prognostic indicator, particularly in patients with advanced breast cancer.

[A Case of Occult Breast Cancer].

We report a case of occult breast cancer. A 61-years-old woman underwent tumorectomy of right axillary mass. Pathological diagnosis was adenocarcinoma. Two years after, right axillary mass was discovered again. Wide local excision, axillary lymph node dissection and radiation therapy of the breast was performed. Pathological findings showed lymph node metastasis of breast cancer, or primary cancer of the axially tail of the breast. Ten months after second operation, she presented an axillary mass again. She underwent resection of the axillary tumor. The pathological findings showed lymph node metastasis of breast cancer. There was no evidence of primary tumor of the breast during the period. We suspected lymph node metastasis of occult breast cancer. Irradiation was administered to the right axilla, and she is receiving endocrine therapy.

[A Case of Breast Carcinoma Associated with Osteoclast-Like Giant Cells].

Mammary carcinoma with osteoclast-like giant cells is uncommon, and its onset mechanism and malignancy are unknown. We report a case of mammary carcinoma with osteoclast-like giant cells. A 41-year-old woman noticed a lump in her left breast. Ultrasound sonography findings suggested breast cancer. A core needle biopsy revealed invasive ductal carcinoma of the breast. Modified radicalmastectomy and sentinell ymph node biopsy were performed. Histopathologicalexamination revealed papillotubular carcinoma with osteoclast-like giant cells. Cells were positive for estrogen receptor and progesterone, and negative for HER2. MIB-1 index was under 5%. The giant cells were generally associated with an inflammatory, fibroblastic, hyper-vascular stroma. The carcinomatous part of the lesion was most frequently a well-to moderately differentiated invasive ductalcarcinoma. Immunohistochemicaland ultrastructuralstudies suggested that the osteoclast-like giant cells were of stromalhistiocytic origin. To understand biochemicalfindings of this carcinoma, more case studies are required to be reported.

Clinicopathological significance of lymphangiogenesis detected by immunohistochemistry using D2-40 monoclonal antibody in breast cancer.

To elucidate the association between the lymphangiogenesis and clinicopathological factors including the survival in breast cancer, 91 Japanese patients with breast cancer were investigated.　The lymphangiogenesis was evaluated by the count of lymph vessel density (LVD) with immunohistochemical method using D2-40 monoclonal antibody, a specific marker for lymphatic endothelial cells.D2-40-positive lymph vessels were detected in 87 of 91 cases, and were mainly distributed in the peritumoral lesions or around the tumor edge.　There was a significant difference in disease-free survival (DFS) and overall survival (OS) between patients with high LVD and with low LVD (p=0.02, 0.01, respectively, log-rank test).　In addition, LVD significantly correlated with the following clinicopathological factors: menopausal status (p<0.01), tumor size (p<0.01), lymph-node status (p=0.01) lymphatic vessel invasion (LVI) (p<0.01), blood vessel invasion (BVI) (p=0.03) and estrogen receptor status (ER) (p=0.02).Those data suggest that D2-40 monoclonal antibody is a useful marker for evaluating the LVD and its evaluation is helpful to predict the survival in breast cancer.

[A Case of Primary Poorly Differentiated/Small Cell Carcinoma of the Breast in a Patient with Von Recklinghausen's Disease].

We report a case of neuroendocrine carcinoma and poorly differentiated/small cell carcinoma ofthe breast in a patient with von Recklinghausen's disease. The patient was a 46-year-old woman who was diagnosed with von Recklinghausen's disease when she was 22 years old. She presented with left breast pain, and physical examination revealed a firm mass in the left breast. A core needle biopsy of the tumor revealed triple negative breast cancer with neuroendocrine features. We performed a simple mastectomy with lymph node dissection. We did not plan neoadjuvant chemotherapy because the tumor would be possibly inoperative if neoadjuvant chemotherapy was not effective for this neuroendocrine cancer. The tumor was diagnosed as a neuroendocrine carcinoma and poorly differentiated/small cell carcinoma. The patient was treated with CDDP and CPT- 11, which is a regimen often used to treat small cell lung cancer.