End-of-Life Preference Lists as an Advance Care Planning Tool for Japanese People.

Advance care planning (ACP) is important to determine the wishes of patients before they lose decision-making capacity. However, Japanese people are often reluctant to have end-of-life discussions. This study aims to develop and categorize an end-of-life preference list in the Japanese context to encourage dialog about ACP for healthcare providers and patients. A questionnaire was developed with end-of-life choices prioritized by a sample of Japanese subjects. Data were collected either in person or by mail. The list of Japanese preferences was compiled and categorized into four domains: medical care, life and care, relationships, and values, with 11-12 items in each domain. The highest-ranking items chosen by >70% of participants were in the relationships and values domains. Subjects with two cohabitants tended to be biased toward the "with others" group, focused on spending time with others, whereas those with older age and higher clinical frailty scale scores tended to be biased toward the "how to live" group.

2(3H)-Dihydrofranolactone metabolites from Pleosporales sp. NUH322 as anti-amyotrophic lateral sclerosis drugs.

Amyotrophic lateral sclerosis (ALS) is a devastating motor disease with limited treatment options. A domestic fungal extract library was screened using three assays related to the pathophysiology of ALS with the aim of developing a novel ALS drug. 2(3H)-dihydrofuranolactones 1 and 2, and five known compounds 3-7 were isolated from Pleosporales sp. NUH322 culture media, and their protective activity against the excitotoxicity of ß-N-oxalyl-L-α,ß-diaminopropionic acid (ODAP), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamatergic agonist, was evaluated under low mitochondrial glutathione levels induced by ethacrynic acid (EA) and low sulfur amino acids using our developed ODAP-EA assay. Additional assays evaluated the recovery from cytotoxicity caused by transfected SOD1-G93A, an ALS-causal gene, and the inhibitory effect against reactive oxygen species (ROS) elevation. The structures of 1 and 2 were elucidated using various spectroscopic methods. We synthesized 1 from D-ribose, and confirmed the absolute structure. Isolated and synthesized 1 displayed higher ODAP-EA activities than the extract and represented its activity. Furthermore, 1 exhibited protective activity against SOD1-G93A-induced toxicity. An ALS mouse model, SOD1-G93A, of both sexes, was treated orally with 1 at pre- and post-symptomatic stages. The latter treatment significantly extended their lifespan (p = 0.03) and delayed motor deterioration (p = 0.001-0.01). Our result suggests that 1 is a promising lead compound for the development of ALS drugs with a new spectrum of action targeting both SOD1-G93A proteopathy and excitotoxicity through its action on the AMPA-type glutamatergic receptor.

Ovarian fibromatosis associated with large pedunculated fibroma in a 30-year-old woman: A rare coincidence or variant?

A 30-year-old nulligravida was referred under suspicion of large subserosal myoma. T2-weighted magnetic resonance imaging revealed multilobulated solid mass in the left lower abdomen measuring 16 cm in longitudinal diameter. The ovarian surface was covered with a marked T2-hypointense thick rim called "black garland sign," forming multiple nodular masses ranging from 1 to 5 cm in diameter in some portions of the bilateral ovaries. By laparoscopic-assisted minilaparotomy, the stalk of pedunculated mass originating from the left ovarian hilum was excised, followed by carrying out of the body after in-bag morcellation using a surgical scalpel. Right ovarian exophytic nodular masses larger than 1 cm were excised using monopolar electrode needle. Pathological examination of excised right and left masses showed fibroblast-like spindle cell proliferation with collagenous stroma; however, differences between right and left masses cannot be distinguished on a histological level. Postoperative diagnosis was ovarian fibromatosis coexisting with large pedunculated fibroma.

Ovarian high-grade serous carcinoma with estrogenic manifestations in a postmenopausal woman: A case report.

Background: Hormonally active ovarian tumors include a variety of pathologies such as sex-cord-stromal tumors, germ cell tumors, tumors with neuroendocrine differentiation, and tumors with functioning stroma. In addition, although the precise mechanism is unknown, epithelial ovarian cancers can be associated with elevated serum estrogen levels on rare occasions. Case: A 56-year-old postmenopausal woman (gravida 3, para 3) with a history of hyperlipidemia was referred due to the discovery of a heterogenous right adnexal mass after presenting to her physician with genital bleeding and nipple discharge associated with breast tension. Her serum cancer antigen 125 (CA125) level was 136.5 U/mL at the initial examination, and serum estradiol and testosterone levels were 214.8 pg/mL and 236.3 ng/dL, respectively. Endometrial thickening was also observed. The diagnosis was a mixed cystic and solid right adnexal mass, implying malignant ovarian tumor but not completely ruling out sex-cord-stromal tumor. Laparoscopic-assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy were performed. Cancer cells were detected in the peritoneal cytology of pooled ascites. Histological examination revealed high-grade serous carcinoma of the right ovary. Six cycles of paclitaxel and carboplatin chemotherapy were administered postoperatively. At three-year follow-up, there was no evidence of disease recurrence, including re-elevation of CA125, or of serum estradiol, or of testosterone. Conclusions: Epithelial ovarian cancer should be considered in postmenopausal women presenting with a pelvic mass and raised hormonal profile, and these patients should be managed according to an epithelial ovarian cancer treatment paradigm.

Effects of dance video game training on cognitive functions of community-dwelling older adults with mild cognitive impairment.

BACKGROUND: Some patients with minor cognitive impairment can revert to normal cognition if intervention is implemented early. Dance video games as multi-task training have shown beneficial effects on cognitive and physical functions in older adults. AIMS: This study aimed to elucidate the effects of dance video game training on cognitive functions and prefrontal cortex activity in older adults with and without mild cognitive impairment. METHODS: A single-arm trial was used for this study. The participants were divided based on the Japanese version of Montreal Cognitive Assessment scores into the mild cognitive impairment (n = 10) and normal cognitive function (n = 11) groups. Dance video game training was performed 60 min/day, 1 day/week, for a total of 12 weeks. Neuropsychological assessments, prefrontal cortex activity using functional near-infrared spectroscopy, and step performance of dance video game were recorded at pre- and post-intervention. RESULTS: Dance video game training significantly improved the Japanese version of Montreal Cognitive Assessment score (p < 0.05), and tendency toward improvement was observed in the trail making test in the mild cognitive impairment group. The dorsolateral prefrontal cortex activity in the Stroop color word test was significantly increased in the mild cognitive impairment group (p < 0.05) after dance video game training. CONCLUSIONS: Dance video game training improved cognitive function and increased prefrontal cortex activity in the mild cognitive impairment group.

Paraganglioma of the Fallopian Tube Presenting as Isolated Fallopian Tube Torsion.

A 32-year-old woman with no previous disease history was presented with worsening right-lower abdominal pain, which lasted for 4 days. On magnetic resonance imaging, a solid mass measuring 48 mm in longitudinal diameter connected with a tortuous structure that appeared to be a fallopian tube was identified in the right-lower abdomen. Because the right ovary was identified at a slightly distant location, isolated fallopian tube torsion with heterogeneous mass was suspected. The isolated fallopian tube torsion without ovarian involvement was laparoscopically confirmed. After detorsion, solid necrotized mass in the distal portion of the right fallopian tube near the fimbrial end became evident, followed by uneventful right salpingectomy with ovarian preservation. The pathological diagnosis was paraganglioma of the fallopian tube with positive cells for neural cell adhesion molecule, neuron-specific enolase, and S-100 protein in the viable peripheral foci of the massively necrotized hemorrhagic mass. Recurrence was not observed after 1.5 years.

Rapid regression of microsatellite instability-high/programmed cell death ligand 1-negative recurrent endometrial carcinoma by immune checkpoint blockade with pembrolizumab: A case report and literature review.

In a 53-year-old woman who had a surgical diagnosis of grade 3 endometrioid carcinoma (pT1aN0M0, FIGO 1A), adjuvant chemotherapy with paclitaxel and carboplatin was initiated. However, after the completion of fourth cycle, the patient refused to continue the treatment. At 12 months after surgery, local recurrence was noted near the left posterior portion of the vaginal stump. External radiotherapy to the pelvic cavity achieved marked reduction of the tumor. At 12 months after radiotherapy, regrowth of the tumor was noted. Although the tumor was negative for programmed cell death ligand 1, after the identification of a high level of microsatellite instability, treatment with pembrolizumab, an immune checkpoint inhibitor, was initiated. After 2 cycles of treatment, the recurrent tumor markedly regressed. Four months later, a complete metabolic response was confirmed by positron emission tomography, without any immune-related adverse events; at the time of writing, this has been maintained for 9 months.

Calculating the Tumor Nuclei Content for Comprehensive Cancer Panel Testing.

Comprehensive genetic panel testing generally requires that the analyzed tissues have a percent tumor nuclei (%TN) content of 20% or more to achieve assay performance comparable to the validated specifications. Pathologists play a crucial role in ensuring that the optimal results are achieved by accurately assigning %TN content of the available specimens and selecting the best material to submit for sequencing. This study addresses the issues in evaluating %TN, such as intraobserver variability, and examines whether focused training and feedback can improve pathologist performance. Nine referring institution pathologists (all board-certified and working at the core institute and the alignment hospitals under the National Cancer Genome scheme) evaluated 18 tumors that had been subjected to comprehensive genetic panel testing with the FoundationOne CDx assay. The %TN estimates provided by referring institution pathologists were compared with two standards: %TN assigned by the tumor sequencing institution's pathologist (a board-certified pathologist at Foundation Medicine, Inc.) and the computational %TN estimated from the mutant allele frequencies after sequencing was completed. The pathologists generally overestimated %TN in the first pretraining round of the evaluation, and the differences in the averaged %TN from the tumor sequencing institution and computational standards were statistically significant. However, the posttraining second-round results became significantly concordant with the standards. This study suggests that %TN content is empirically overestimated but the evaluation skill can be improved by providing a training and feedback program.

Dramatic response to nivolumab after local radiotherapy in pulmonary pleomorphic carcinoma with rapid progressive post-surgical recurrence.

Pulmonary pleomorphic carcinoma (PPC) is resistant to anticancer drug treatment, outcomes are poor, and no standard therapy has been established. High PD-L1 expression has been found in PPCs, suggesting the possible efficacy of an immune checkpoint inhibitor (ICI) in cancer immunotherapy; however, this approach requires further investigation through case accumulation. Herein, we report a case of rapid recurrence and progression of PPC early after surgery in a 70-year-old male ex-smoker. Surgery was performed for lung cancer of the right lower lobe, and a pathological examination indicated primary PPC with high PD-L1 expression (tumor proportion score: 90%). Because systemic metastasis recurred only six weeks after surgery, nivolumab was administered as second-line treatment. Marked tumor regression was observed on imaging after three cycles, revealing a near complete response. Palliative radiotherapy was applied to the bone metastasis region for pain relief before nivolumab was administered. This case suggests that an ICI can have an effect on PPC and that the efficacy of ICIs may be enhanced by radiotherapy-induced abscopal effects.

Sudden Death Due to Recent Hemorrhage From an Intrathoracic Chronic Expanding Hematoma.

Chronic expanding hematoma (CEH) is a rare disease that can develop in any region of the body, but it most frequently develops in the thorax. When intrathoracic CEH is left untreated, gradually expanding hematoma can be life-threatening, leading to respiratory failure or hemoptysis. We encountered an 89-year-old man with cardiopulmonary arrest on arrival. He had been healthy, and it was unclear whether CEH had previously been detected. A very large mass was observed on chest computed tomography (CT), but the cause of death could not be determined. In the autopsy, this mass was identified as CEH and no malignant findings were noted. A fresh hemorrhage had occurred in the hematoma and perforated the bronchial lumen, which caused airway obstruction/asphyxia and resulted in sudden death. CEH should be suspected when a very large tumorous lesion occupying the entire hemithorax is observed on chest imaging, and it is important to recognize that sudden death can occur in the natural course of CEH.

Chronic tubal pregnancy manifesting as a heterogeneous adnexal mass with prominent neovascularization in a woman with a negative serum ß-human chorionic gonadotropin level.

A 41-year-old woman (gravida 2, para 1) underwent elective termination of pregnancy at approximately 7 weeks of gestation. At 1 month after the elective abortion, she was referred due to abnormal results in a cervical cytological examination. Transvaginal ultrasonography showed a heterogeneous mass of 16 mm in diameter in the left adnexal region. At 3 months after her referral, the asymptomatic left adnexal mass had increased to 55 mm in diameter. Prominent vascular flow was detected in the solid portion by color Doppler ultrasonography. Magnetic resonance imaging showed suspected hemorrhage in the left adnexal cystic mass. Three-dimensional computerized tomographic angiography showed the prominent development of tortuous blood vessels in the left adnexal region, which originated from the left ovarian artery. The patient had a negative ß-human chorionic gonadotropin (hCG) level. Left salpingectomy was performed by a single-port laparoscopic approach. A pathological examination revealed degenerated villous tissue with ß-hCG-positive syncytiotrophoblasts.

Identification of Leiomyoma Cell Sheets in Peritoneal Washings Retrieved by an Intraoperative Red Blood Cell Salvage Device during Laparoscopic-Assisted Myomectomy with in-Bag Manual Tissue Extraction: A Pilot Study.

STUDY OBJECTIVE: To examine whether peritoneal washings during laparoscopic-assisted myomectomy with in-bag manual tissue extraction can contain spilled leiomyoma cell sheets. DESIGN: Retrospective observational study (Canadian Task Force classification II-2). SETTING: Departments of Obstetrics and Gynecology and Diagnostic Pathology at a general hospital. PATIENTS: Twenty-four women. INTERVENTIONS: Hysterotomy followed by complete enucleation by blunt and sharp dissection was performed. Enucleated myomas were placed into a retriever bag and extracted through a suprapubic or umbilical mini-laparotomic incision by manual morcellation with a surgical scalpel. A histological examination was performed to identify the dispersed leiomyoma cell sheets in trapped tissues on the surface of a defoaming sponge equipped in the reservoir of an intraoperative red blood cell salvage device, which was used to collect peritoneal washing fluid along with blood. MEASUREMENTS AND MAIN RESULTS: Bag rupture was not observed in any case; however, apparent leiomyoma cell sheets were identified in 20 of 24 cases (83.3%). No devices or procedures that were used for myomectomy could completely prevent leiomyoma cells from appearing in the peritoneal washing fluid. CONCLUSION: Even when careful in-bag tissue extraction of myomas was performed in laparoscopic-assisted myomectomy, dispersion of leiomyoma cell was identified in most cases. Further study is needed to show that the feasibility of rigorous washing to reduce the potential risk of leiomyoma cell dissemination.

Multimodal imaging for diagnosis and management of parasitic peritoneal myoma with myxoid degeneration after laparoscopic-assisted myomectomy with electric power morcellation.

A 45-year-old multipara woman was referred due to the rapid enlargement of an asymptomatic pelvic mass that was detected during a regular check up. She had undergone laparoscopic-assisted myomectomy 15 years previously. At the time, the uncontained extraction of an intraligamental myoma with electric power morcellation had been performed. Multimodal imaging revealed a heterogeneous mass in the vesicouterine pouch that was found to be supplied by the left gastro-omental and superior vesical arteries. Although malignancy could not be completely denied, parasitic peritoneal myoma with myxoid degeneration was the most probable diagnosis. Single-port laparoscopic excision of the peritoneal mass was performed along with laparoscopic-assisted vaginal hysterectomy and bilateral salpingo-oophorectomy. The excised peritoneal mass was placed into a retrieval bag and extracted through the vagina. The pathological diagnosis was a parasitic peritoneal myoma with myxoid degeneration. The postoperative course was uneventful, and there was no recurrence of parasitic myoma in the 1-year follow up after surgery.

Microsatellite instability-high endocervical serous carcinoma manifesting as pulmonary thromboembolism: A case report and review of the literature.

A 53-year-old obese woman was referred because of sudden onset of dyspnea and chronic vaginal bleeding. In addition to severe anemia, multiple pulmonary emboli were identified. Pelvic imaging showed an irregular-shaped mass in the region of the endocervix extending to the lower uterine segment. After successful anticoagulant therapy, followed by placement of an inferior vena cava filter, transabdominal hysterectomy and bilateral salpingo-oophorectomy were performed. An immunopathological study resulted in the diagnosis of endocervical serous carcinoma. After the identification of a high level of microsatellite instability (MSI), an immunohistochemical analysis of mismatch repair (MMR) proteins showed the isolated loss of PMS2. Germline testing of MMR genes showed no mutations, indicating that the high MSI had occurred as a result of sporadic isolated loss of the PMS2 gene expression.

Sudden Death from Cardiopulmonary Arrest on Arrival of a Patient with Pulmonary Tuberculosis: A Case Diagnosed by Postmortem CT and Autopsy.

Sudden death due to massive hemoptysis during management of tuberculosis occurs in a considerable number of patients. However, when massive airway hemorrhage occurs in a patient in whom tuberculosis has not been confirmed and a blood is not apparent externally on the face/body, it is difficult to immediately identify the cause of death as airway obstruction by tuberculous bleeding in the airway. We encountered an 83-year-old Japanese woman with her medical history included treatment of tuberculosis in her 20s who was in cardiopulmonary arrest on arrival (CPAOA), and the cause of sudden death could not initially be identified. Postmortem CT (PMCT) and autopsy revealed that the cause of sudden death was airway obstruction/asphyxia by tuberculous massive airway hemorrhage. Identification of the cause of death facilitated a subsequent active contact investigation and led to prevention of secondary tuberculosis infection.

Uterine metastasis of lung adenocarcinoma under molecular target therapy with epidermal growth factor receptor tyrosine kinase inhibitors: A case report and review of the literature.

A 63-year-old woman presented with abnormal vaginal bleeding. Her disease history was significant, and included advanced lung adenocarcinoma with a deletion mutation in exon 19 of the epidermal growth factor receptor (EGFR) gene, which was managed by concurrent chemoradiotherapy, followed by molecular targeted therapy with tyrosine kinase inhibitors (TKIs) for a two-year period. Contrast-enhanced computed tomography showed the enlargement of a previously suspicious myoma node, with peripheral enhancement. Hemorrhagic necrosis was also observed on magnetic resonance imaging. Transabdominal hysterectomy and bilateral salpingo-oophorectomy showed solitary intramyometrial metastatic lung adenocarcinoma with a second-site T790M gatekeeper mutation in exon 20 of the EGFR gene. In conclusion, uterine metastasis from lung adenocarcinoma can present a diagnostic challenge. The possibility of lung cancer metastasis should be considered when a uterine mass increases in size during treatment. Molecular analysis of the EGFR gene to detect mutations could provide useful information for planning the treatment strategy.

Gynandroblastoma with a Juvenile Granulosa Cell Component in an Adolescent: Case Report and Literature Review.

BACKGROUND: Gynandroblastoma is an extremely rare ovarian sex cord tumor with malignant potential. CASE: An 18-year-old adolescent experienced intermittent vaginal bleeding. A year later, a right adnexal mass with a heterogeneous imaging appearance was identified. Laparoendoscopic single-site ovarian tumorectomy was performed. A histopathological examination showed gynandroblastoma composed of juvenile granulosa and Sertoli-Leydig cells. Because the tumor was upstaged to stage Ic because of cyst rupture during surgery, three cycles of adjuvant chemotherapy with carboplatin and paclitaxel were added. Three years after surgery, no signs of recurrence have been noted. SUMMARY AND CONCLUSION: The present findings can help clinicians make an accurate preoperative imaging diagnosis of gynandroblastoma with a juvenile granulosa cell component and plan an adequate treatment strategy for this rare, potentially malignant neoplasm.

[Feasibility Study of a One-Day Educational Program to Train Advance Care Planning Facilitators(ACPFs)in Regional Areas].

Promoting advance care planning in regional areas is important. Education For Implementing End-of-Life Discussion(EFIELD) is a two-day educational program for Advance Care Planning Facilitators(ACPFs)developed by the National Center for Geriatrics and Gerontology. Unfortunately, some trainers experience difficulties implementing the content of the program, and some trainees feel the program is too long for implementation in many regional areas. The purpose of the research is to clarify the feasibility of ACPFs education using a one-day program in regional areas. The methods involved documenting the process of a one-day program from implementation to evaluation from May of 2015 to March of 2016 and then evaluating the effectiveness of the program 3 months after the implementation using meeting minutes from 7 local hospitals. The results indicated a need for 5 steps from program implementation to evaluation as well as 5 categories for final evaluation. The most important finding is that E-FIELD challenged trainers to shorten and simplify their expressions in order to teach the content more efficiently. The second finding is that Group for Promoting Advance Care Planning & End Of Life Discussion in Chita(GACPEL) activities encouraged ACPimplementation within each hospital. The limitations of this research are related to small regional areas. In conclusion, a one-day regional ACPFs educational program is feasible.