FDG uptake reflects breast cancer immunological features: the PD-L1 expression and degree of TILs in primary breast cancer.

BACKGROUND: High F18-fluorodeoxyglucose (FDG) uptake has been reported to be a predictor of poor prognosis in patients with breast cancer. We investigated the relationship between FDG uptake and immunological factors, including the data of programmed cell death-ligand 1 (PD-L1), CD8, and tumor-infiltrating lymphocytes (TILs). METHODS: Breast cancer tissues of 97 patients who underwent surgery without preoperative therapy were examined. The grade of stromal TILs was immunohistochemically evaluated using the criteria of the International TILs Working Group in breast cancer. PD-L1 positivity and CD8 positivity were immunohistochemically evaluated. The FDG uptakes were evaluated based on the standardized uptake value max (SUVmax). The relationships between SUVmax and TIL grade and expression of PD-L1 and CD8 were investigated. RESULTS: Among the 97 patients, 41 (42.3%) had a high SUVmax in their primary tumor, based on the SUVmax cut-off value 3 yielded by receiver operating characteristic curves. PD-L1 was positive in 17 patients (17.5%). Our analyses revealed that large tumor size, high nuclear grade, high degree of TILs and positive expression of PD-L1 were significantly associated with high SUVmax in the primary tumor. There were significant associations between SUVmax and the degree of TILs (r = 0.428, p < 0.001) and between SUVmax and the PD-L1 positivity (r = 0.413, p < 0.001). All cases with a high degree of TILs showed high CD8 expression. CONCLUSION: Our results indicate that the FDG uptake may be predictive of immunological features including TILs and PD-L1 expression in breast cancer patients. Additional research is necessary to further evaluate FDG-PET as a biomarker of immune checkpoint therapy in breast cancer.

Phase II study of sequential S-1 and cyclophosphamide therapy in patients with metastatic breast cancer.

BACKGROUND: S-1 and cyclophosphamide (CPA) can be given orally, and their combination may have great potential for treating metastatic breast cancer (MBC). A phase I study of sequential S-1 and CPA therapy was conducted in patients with MBC; the recommended doses that were determined for this regimen were 80 mg/m2/day for S-1 and 100 mg/m2/day for CPA. We then conducted a phase II study of this oral S-1 and CPA regimen. METHODS: This was a single-arm, open-label, single-center prospective phase II study to evaluate the efficacy of a sequential S-1 and CPA regimen for MBC. S-1 was administered orally 2×/day for 14 consecutive days, and then CPA was administered orally 2×/day for 14 consecutive days in a repeating 4-week cycle (S-1 for 2 weeks, CPA for 2 weeks). The primary endpoint was the overall response rate (ORR). Secondary endpoints included the overall survival (OS), progression-free survival (PFS), clinical benefit rate (CBR) and safety. RESULTS: Thirty-six patients were enrolled in this study. The overall response was complete response in 0 (0%), partial response in 12 (33.3%), stable disease in 12 (33.3%), and progressive disease in 11 (30.1%) patients. The ORR was 33.3% (12/36). The CBR was 66.7% (24/36). The median PFS was 9.5 months (95%CI: 7.8-12.6 months). The median OS was 20.2 months (95%CI: 15.0-25.4 months) Grade 3/4 adverse events included leukopenia in seven patients (19.4%). Dose reductions because of adverse events occurred in 12 patients (33.3%). There was no treatment-related mortality. CONCLUSION: The combination of sequential therapy with S-1 and CPA was tolerable and had efficacy with good disease control. Sequential therapy with S-1 and CPA may be a feasible new treatment option for patients with MBC; however, further study is warranted to explore the efficacy of this therapy. TRIAL REGISTRATION: JRCT, JRCTs031180296 . Registered 2 December 2019 - Retrospectively registered.

[A Case of Solitary Metastasis to the Small Intestine from Sigmoid Colon Cancer after Treatment of Seven Multiple Cancers].

A 75-year-old woman who had undergone a Hartmann's operation for sigmoid colon cancer 2 years ago was hospitalized because she experienced small bowel obstruction several times. She had a treatment history of 6 other cancers, including 5 gastrointestinal tract cancers. However, the obstruction was relieved by conservative therapy each time. In September 2015, she was hospitalized for ileus. Abdominal computed tomography revealed that the lumen of intestine was partially dilated. Subsequently, a long tube was inserted, but the dilatation of the small intestine was not fully recovered. She was diagnosed with small intestinal obstruction due to adhesion, and she underwent an operation in October 2015. During the laparotomy, she was diagnosed with adhesion due to an intestinal tumor, and a partial intestinal resection, including the entire tumor, was performed. Because the tumor appearance and histological findings were very similar to those of sigmoid colon cancer, the tumor was diagnosed as a solitary metastasis of sigmoid colon cancer to the small intestine. Generally, peritoneal dissemination causes metastasis of colon cancer to the small intestine. However, this is a rare case because the lymphatic system or extra-wall invasion was the most likely cause of metastasis. Ileus repeating the improvement exacerbation, an examination must be performed while considering possible intestinal tumors, especially for a patient previously treated for multiple gastrointestinal cancers.

[A new role of nursing in violence: a reconsideration of nursing of victims].

Forensic nursing is the application of forensic science to nursing. It provides direct patient care with relation to violence, abuse, crime, victimization and exploitation. Forensic nurses integrate forensic and nursing sciences in their assessment and care of victims and perpetrators. In the U.S.A., Canada and Europe, forensic nursing practice involves advocating for the collection of evidence and reporting of crimes. Additionally, forensic nurses treat victims and perpetrators for their trauma, their families, communities and the systems that respond to them. Through its practice, forensic nursing contributes to public health by preventing health hazards caused by violence and crime. This report considers the possibility of the development of forensic nursing in Japan. We propose that the development of forensic nursing is necessary.

[Possibilities and problems in the development of forensic nursing in Japan: a questionnaire survey of clinical nurses].

Forensic nursing scientifically obtains and preserves the criminal damage from victims of domestic violence, child abuse, elder abuse, sexual violence and other related forms of violence. This was developed in North America in the 1980s, and has carried out appropriate nursing care while protecting the human rights of victims. Serious crime in Japan has been increasing, and it would seem that forensic nursing opportunities should expand as well. However, in Japan, there hasn't been much discussion about forensic nursing. Theorizing that support for clinical forensic nursing should be recognized and relevant, we carried out a survey of 581 clinical nurses to investigate the development of forensic nursing in Japan. 93 clinical nurses (16.0%) had a low level of familiarity with forensic nursing; however, 324 nurses (56.3%) had encountered patients who had suffered violence. 264 nurses (45.4%) had a feeling of wanting to be involved in forensic nursing, but were not confident with the knowledge and technology, while 144 nurses (24.8%) were concerned about the larger responsibility they would have. 400 nurses (68.8%) hoped to receive specialized knowledge and technical education. It is necessary to establish an education system for forensic nursing in accordance with the educational status-quo while considering the present state of forensic nursing education.

[Achievements in the objectives of a practicum as seen through changes in awareness of nursing and care techniques in a basic nursing practice].

This study aims to elucidate the level of achievement and the challenges in a basic nursing practicum for second-year nursing students through the association method. Analysis revealed various descriptions of learning through the practicum training experiences in terms of understanding the healthcare environment, planning and implementing daily life assistance, and involvement in building a supportive relationship with a care recipient. In this sense, we can assume that the goal of the practicum was achieved. The students' attitude toward learning showed an emphasis on knowledge, basics, reasoning, and acquisition of knowledge through experience. At the same time, however, we did not observe descriptions of developing the healthcare environment, understanding the methods of developing healthcare plans, or respect for privacy, thus not indicating whether the goal was achieved. In the future, it is necessary to additionally examine specific details of students' learning through analyzing their reports.

Ethical Issues Encountered by Forensic Psychiatric Nurses in Japan.

BACKGROUND: Criminals in Japan with mental disorders face penal servitude in prison or treatment under the Medical Treatment and Supervision Act, depending on their ability to take responsibility for their criminal acts. Forensic psychiatric nurses caring for this group may face various ethical issues. OBJECTIVE: This study aimed to identify ethical issues forensic psychiatric nurses in Japan encountered. METHOD: We used the Ethical Issues Scale to conduct a survey among forensic healthcare ward nurses and analyzed the data using descriptive statistics. We also conducted semistructured interviews with individual nurses who provided signed consent and responded to the initial survey on ethical issues they encountered. These data were analyzed using Berelson's content analysis. RESULTS: Of 175 nurses, 131 answered our survey. The most frequently encountered ethical issue was "protecting patients' rights and human dignity," and the most disturbing ethical issue was "providing nursing care with possible health risks." Seventy-seven percent of the nurses chose to discuss with peers when resolving the ethical issues. Seventeen nurses who were interviewed described these forensic psychiatric nursing-related ethical distresses and conflicts: difficulty in discharge management, prevention of violence and self-harm, compulsory treatment, patient care, and negative emotions toward patient. CONCLUSION: Forensic psychiatric nurses in Japan face difficulties regarding respecting patients' rights. They strive to respect patients' rights by using their expertise as nurses while sharing their difficulties with colleagues. It is important to develop a support system for social reintegration to solve ethical issues.

Identification and characterization of glucocorticoid receptor-binding sites in the human genome.

Glucocorticoids regulate gene expression via binding of the ligand-activated glucocorticoid receptor (GR) to glucocorticoid-responsive elements (GRE). To identify GR-binding sites, we developed a modified yeast one-hybrid system which enables rapid and efficient identification of genomic targets for DNA-binding proteins. The human GR expression vector was transformed into yeast cells containing a library of human genomic fragments cloned upstream of the reporter gene URA3. The genomic fragments with GR-binding sites were identified by growth of yeast clones in media lacking uracil but containing dexamethasone. DNA fragments were recovered by colony-direct PCR and GRE sequences were predicted by in silico analysis. Using electrophoretic mobility shift assay and fluorescence correlation spectroscopy, we demonstrated that 314 predicted GREs could directly interact with recombinant human GR proteins. In addition, when the genomic fragments were inserted in front of the heterologous SV40 promoter, at least 150 fragments could function as GREs in HEK293 cells. Furthermore, we identified four functional regulatory polymorphisms which may influence individual variation in sensitivity to glucocorticoids. These results provide insights into the molecular mechanisms underlying the physiological and pathological actions of glucocorticoid.

[The role of law in protection from violent and abusive patients].

What counter-measures can medical professionals take against violent and abusive patients in Japan? The aim of this article is to consider the role of law for protecting medical professionals from such patients in Japan, comparing it with its role in the UK. Medical professionals need to have legal knowledge for avoiding trouble after using such measures as "verbal defense" or "negotiation". When they use their body or objects for defense, they must use them within the limits of the law. Patients sometimes have violent and abusive behavior because of disease or depression from their condition or the environment. If a medical professional fights back against such a patient, is (s)he legally or morally responsible? This is a very important problem. Professional discretion is concerned with balancing patient healthcare and the safety of medical professionals.

Relationship Between FDG Uptake and Neutrophil/Lymphocyte Ratio in Patients with Invasive Ductal Breast Cancer.

BACKGROUND: 18F-Fluorodeoxyglucose-positron-emission tomography (FDG-PET) is used to evaluate the glucose metabolic rates of tumors. Several studies have reported that high FDG uptake is predictive of poor prognosis and aggressive features in patients with breast cancer. FDG uptake is influenced by many factors, including inflammation. In this study, the relationship between FDG uptake and neutrophil/lymphocyte ratio (NLR), which is an indicator of systemic inflammation, was investigated. PATIENTS AND METHODS: A retrospective investigation of the cases of 143 consecutive patients with invasive ductal carcinoma who had undergone surgery and FDG-PET preoperatively. PET was evaluated using standardized uptake value max (SUVmax). The median SUVmax was 2.5 (range=0-10.5). The cases were divided into two groups based on the value of SUVmax: low (<2.5) and high (≥2.5). The relationships between SUVmax and clinicopathological features, including NLR, were investigated. RESULTS: Among the 143 patients, 73 (51.0%) had high SUVmax in the primary tumor. The analysis revealed that large tumor size (p<0.001), high nuclear grade (p<0.001), the presence of lymphovascular invasion (p<0.001), high C-reactive protein (p=0.046) and high NLR (p<0.001) were significantly associated with high SUVmax in the primary tumor. SUVmax and NLR were significantly positively correlated (r=0.323, p<0.001). Among the 70 cases with low SUVmax, there was no recurrent disease, while out of the 73 cases with high SUVmax had disease recurrence. It is interesting to note that the group with high SUVmax and low NLR had no recurrent disease. CONCLUSION: The present study demonstrated that the finding of high preoperative FDG uptake in breast cancer may be reflective of poor prognosis and that a high NLR may be predictive of aggressive features among patients with breast cancer. On the other hand, among patients with breast cancer with high SUVmax in the primary tumor, it will be useful to identify those with a low NLR in order to improve prognostic accuracy.

Clinicopathological Features of Ductal Carcinoma In Situ from 18F-FDG-PET Findings.

AIM: The presence of ductal carcinoma in situ (DCIS) can increase the risk of developing an invasive ductal carcinoma (IDC), but it is difficult to predict what will occur if a DCIS is left untreated. We reported the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for DCIS, and that the presence of FDG uptake in the tumor could be considered a predictor of invasive potential in patients with DCIS. In this study, we retrospectively evaluated the clinicopathological features of DCIS by using FDG-PET findings, and we evaluated the possibility of using FDG-PET in DCIS cases as a biomarker of which lesions will go on to become invasive. PATIENTS AND METHODS: We investigated the cases of 185 consecutive patients with primary breast cancer who were diagnosed as having DCIS or IDC and underwent FDG-PET preoperatively. RESULTS: We divided the cases into two groups on the basis of histology; DCIS vs. IDC (n=171). The DCIS cases were divided into two groups on the basis of FDG uptake in the primary tumor. Fourteen of the 185 patients (7.4%) were revealed to have a DCIS. The analysis revealed that the SUVmax and the number of cases not detected by FDG-PET were significantly different between the DICS and IDC groups. The extent of the primary tumor was not significantly different between the two groups. In six cases (42.9%) of the 14 DCIS cases, no FDG uptake was detected by FDG-PET. The extent of tumor did not significantly differ between the two groups. In addition, all six cases without FDG uptake were of the diffuse-spread type, without mass formation. All eight cases with mass formation had FDG uptake. CONCLUSION: Our present findings suggest that the FDG-PET uptake reflects tumor burden or tumor density, which should be considered to be associated with the presence of invasion.

Linkage disequilibrium grouping of single nucleotide polymorphisms (SNPs) reflecting haplotype phylogeny for efficient selection of tag SNPs.

Single nucleotide polymorphisms (SNPs) have been proposed to be grouped into haplotype blocks harboring a limited number of haplotypes. Within each block, the portion of haplotypes is expected to be tagged by a selected subset of SNPs; however, none of the proposed selection algorithms have been definitive. To address this issue, we developed a tag SNP selection algorithm based on grouping of SNPs by the linkage disequilibrium (LD) coefficient r(2) and examined five genes in three ethnic populations--the Japanese, African Americans, and Caucasians. Additionally, we investigated ethnic diversity by characterizing 979 SNPs distributed throughout the genome. Our algorithm could spare 60% of SNPs required for genotyping and limit the imprecision in allele-frequency estimation of nontag SNPs to 2% on average. We discovered the presence of a mosaic pattern of LD plots within a conventionally inferred haplotype block. This emerged because multiple groups of SNPs with strong intragroup LD were mingled in their physical positions. The pattern of LD plots showed some similarity, but the details of tag SNPs were not entirely concordant among three populations. Consequently, our algorithm utilizing LD grouping allows selection of a more faithful set of tag SNPs than do previous algorithms utilizing haplotype blocks.