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Bladder cancer is the most common urinary tract cancer. Patients diagnosed with advanced T-stage/muscle-invasive bladder cancer through transurethral resection of bladder tumors (TURBT) are treated with total radical cystectomy; however, there is a high chance of recurrence. Nevertheless, markers for predicting this recurrence are not currently available. Here, we evaluated the chronological change of ephrin type-A receptor 2 (EPHA2) expression, a molecule known for its role in cell adhesion, to predict bladder cancer recurrence after cystectomy, using TURBT and cystectomy specimens.An immunostaining evaluation method that combines whole-slide images and image analysis software was developed to quantify and evaluate stainability objectively. We assessed the correlation between EPHA2 expression and bladder cancer recurrence using this novel immunostaining method and chronological changes in target protein expression in TURBT and radical cystectomy samples.In TURBT specimens, the number of cases with a high N-terminal/C-terminal EPHA2 ratio in the group with recurrence was significantly higher than in the non-recurrent group (p=0.019). The number of cases with a high level of C-terminal EPHA2 positivity in the radical cystectomy specimen when compared to the TURBT specimen obtained from the same patient was significantly higher in the recurrent group than in the non-recurrent group (p=0.0034).EPHA2 appears to be a promising marker for bladder tumor recurrence after cystectomy and its evaluation may enable the selection of appropriate cases for adjuvant therapy among patients undergoing radical cystectomy. Further studies, including mass-scale analysis, are required to confirm these results.

Background: Analytical information obtained from clinical tissue samples has recently become more important due to recent advancements in the clinical practice of medicine, for example, gene panel testing. However, acquiring and managing the sample quality, which greatly influences the analyses, are not sufficient and hence requires immediate attention. We introduced time stamp (TS) recording and documentation using the Standard PREanalytical Code (SPREC) for breast cancer surgery samples to monitor and control their quality. Materials and Methods: The TS recording used SPREC for quality control of each sample by recording seven factors: type of sample, type of collection, warm ischemia time (WIT), cold ischemia time (CIT), fixation type, fixation time (FT), and long-term storage. The responsibilities to record each factor were assigned among group members (breast surgeons, anesthesiologists, pathologists, operating room nurses, and medical technologists in pathology). Results: Records based on SPREC were recorded for 393 surgical cases of first-time breast cancer patients performed at the Kanagawa Cancer Center from May 2018 to April 2019. The vascular clamp time was defined as when skin flap formation was completed, regardless of the surgical procedure. An anesthesiologist recorded the vascular clamp time and sample collection time, and the pathologist recorded the fixation start time and fixation end time. WIT was 23 (3-116) minutes (breast-conserving surgery, 11 [3-38] minutes; mastectomy, 26 [5-116] minutes; and nipple-sparing mastectomy, 39 [31-43] minutes), CIT was 37 (3-1052) minutes, and FT was 43 (17-115) hours. The median CIT and FT were significantly shortened after introducing the TS system, and the variabilities were reduced. Conclusion: A TS system for quality control of breast cancer surgical sample functions well due to the establishment of highly versatile WIT and a working group consisting of multiple members of different occupations who shared roles.

A 46-year-old woman presented with discomfort in her right lateral gaze, right-sided headache, and facial numbness 17 days after concurrent chemoradiotherapy(CCRT)for a Stage ⅢB cervical cancer. The initial imaging investigations, maxillofacial and otolaryngology reviews did not reveal a diagnosis. After 54 days of CCRT, her symptoms deteriorated. Magnetic resonance imaging(MRI)showed a tumor in the right infratemporal fossa and its biopsy confirmed a metastatic cervical cancer. In view of the rapid deterioration and the potential visual loss, palliative intensity-modulated radiotherapy(IMRT) was given. Although the symptoms improved temporarily, multiple metastases were subsequently found. Despite chemotherapy, the patient died 11 months after developing the symptoms of infratemporal fossa metastasis.

A 71-year-old woman became aware of a 25-mm mass in her right breast as identified by her previous doctor. Needle biopsy findings suggested malignant lymphoma, and she was referred to our hospital for further evaluation. She was diagnosed with diffuse large B-cell lymphoma (DLBCL) at our hospital. Positron emission tomography-computed tomography (PET-CT) revealed an elevated SUVmax (maximum standardized uptake value; 10.3), with the mass localized in the right breast, but magnetic resonance imaging findings revealed that the mass had shrunk to 10 mm. Needle biopsy was repeated in our hospital, and lymphoma cells were absent. Two months later, CT scan revealed complete disappearance of the mass, and, since then, the patient has been free of recurrence. Although there are reports of spontaneous remission of nonHodgkin's lymphoma, it is rare in the case of high-grade B-cell lymphoma. The mechanism of spontaneous remission is unclear; however, advancing age, localized stage, activated B-cell (ABC) or nongerminal center B-cell (GCB) type, and a history of infection are the associated factors. The findings from this case suggest that DLBCL can be cured without therapeutic intervention; however, careful followup may be needed.

Low-grade adenosquamous carcinoma (LGASC) is a rare type of metaplastic carcinoma of the breast (MBC) with an indolent clinical course. A few cases with high-grade transformation have been reported; however, their genetic alterations remain unclear. This study was designed to explore the somatic genetic characteristics of LGASC with transformation to high-grade MBC. Whole-genome sequencing analysis was performed on five MBCs from four patients, including one case with matching primary LGASC and lymph node metastatic tumor consisting of high-grade MBC with a predominant metaplastic squamous cell carcinoma pattern (MSC) that has progressed from LGASC, and three de novo MSC. Both LGASC and its associated MSC, unlike de novo MSC, had no TP53 mutation and tended to have fewer structural variants than de novo MSC. Both LGASC and its associated MSC had common mutations and copy number alterations, including GNAS R844C, which shows an increase in its allele frequency in MSC. These results indicated that LGASC and its associated MSC were ancestry clonal and that clonal selection occurred during progression. MSC associated with LGASC had additional pathogenic deletions of multiple tumor suppressor genes caused by, for example, SMAD4–DCC fusion. Reverse transcription polymerase chain reaction, followed by Sanger sequencing, confirmed this fusion transcript in both LGASC and its associated MSC; however, chimera proteins were not detected by Western blotting. SMAD4 protein expression had already decreased at the stage of LGASC, which may have contributed to the tumorigenesis of LGASC. In conclusion, not only LGASC but also its associated high-grade MBC may be genetically different from de novo high-grade MBC. The progression from LGASC to high-grade MBC may concern the concentration of the driver mutation caused by clonal selection and inactivation of tumor suppressor genes.

Background: Uterine adenosarcoma is a rare malignant tumor that accounts for 8% of all uterine sarcomas, and less than 0.2% of all uterine malignancies. However, it is frequently misdiagnosed in clinical examinations, including pathological diagnosis, and imaging studies owing to its rare and non-specific nature, which is further compounded by the lack of specific diagnostic markers. Case Presentation: We report a case of uterine adenosarcoma for which a comprehensive genomic profiling (CGP) test provided a chance to reach the proper diagnosis. The patient, a woman in her 60s with a history of uterine leiomyoma was diagnosed with an intra-abdominal mass post presentation with abdominal distention and loss of appetite. She was suspected to have gastrointestinal stromal tumor (GIST), and the laparotomically excised mass was found to comprise uniform spindle-shaped cells that grew in bundles with a herringbone architecture, and occasional myxomatous stroma. Immunostaining revealed no specific findings, resulting in the tumor being diagnosed as a spindle cell tumor/suspicious adult fibrosarcoma. The tumor relapsed during postoperative follow-up, and showed size reduction with chemotherapy, prior to regrowing. CGP was performed to identify a possible treatment, which resulted in detection of a JAZF1-BCORL1 rearrangement. Since the rearrangement has been reported in uterine sarcomas, we reevaluated specimens of the preceding uterine leiomyoma, which revealed the presence of adenosarcoma components in the corpus uteri. Further, both the uterine adenosarcoma and intra-abdominal mass were partially positive for CD10 and BCOR staining. Conclusions: These results conclusively identified the abdominal tumor as a metastasis of the uterine adenosarcoma. The JAZF1-BCORL1 rearrangement is predominantly associated with uterine stromal sarcomas, and ours is the second report of the same in an adenosarcoma thus far. Adenosarcomas are rare and difficult to diagnose, especially in atypical cases with scarce glandular epithelial components. Identification of rearrangements involving BCOR or BCORL1, will encourage BCOR staining analysis, thereby potentially resulting in better diagnostic outcomes. Given that platinum-based chemotherapy was proposed as the treatment choice for this patient post diagnosis with adenosarcoma, CGP also indirectly contributed to designing the best suited treatment protocol.

Objectives Molecular profiling of marker mutations has become an essential aspect in the treatment planning for colorectal cancer (CRC). Anaplastic lymphoma kinase (ALK) mutations could be used as markers in CRC molecular profiling. However, the extremely low frequency of these mutations makes their confirmation in all patients inefficient. Thus, to determine whether ALK positivity could be indicated by morphological features, we have analyzed ALK positivity in CRC tissues with a signet-ring cell carcinoma (SRCC) component. Methods We screened cases of patients who underwent CRC surgical resection at the Department of Gastrointestinal Surgery of the Kanagawa Cancer Center between January 2015 and December 2019. The selected samples were then assessed immunohistochemically using an antibody against p80 ALK. Results In total, we were able to retrieve 29 cases of CRC with the SRCC component from the database; however, 5 cases were excluded owing to the absence of formalin-fixed paraffin-embedded tissue sections or the absence of the SRCC component when the tissues were observed. In the immunohistochemical analysis, two cases showed diffused positive immunoreactivity for ALK and were defined as ALK-positive CRC. Thus, the ALK positivity rate in CRC with SRCC was determined to be 8.3%. Conclusions This present study sheds light on the morphological features of ALK-positive CRC. Our findings could contribute to the effective screening and improvement of front-line therapy for CRC.

Aim: To clarify students’ stress factors, sense of coherence, stress-coping behavior, and stress reactions during nursing practice, and develop recommendations for educational support. Method: We conducted a search of literature published in the period 2009-2020, using the Igaku Chuo Zasshi, MEDLINE, and CINAHL, and the keywords “nursing student,” “stress,” and “nursing practice.” Results: Twenty articles were included in the review. As a result, the stress factors were a nursing process and record common to all grades. Sense of coherence tended to be higher among nursing students than for students in other faculties. As for stress-coping behavior, students selected “Avoidance and suppression” in specialty I. In nursing integration, students chose “Active solution.” Regarding stress reaction, students’ mental health was low during nursing practice, and their thinking and concentration abilities continued to decline even after practice. Conclusion: As teachers develop a better understanding of stress factors and their contexts, students will assess trends in stress-coping behavior to guide lessons and reflect on coping with stress.

This study aims to clarify what kinds of resilience and coping strategies students employ to successfully complete their clinical practicum and provide suggestions for instruction that will allow students to carry out effective learning activities. The study subjects were 86 students enrolled at Nursing University A for the 2019 school year and planning to take the integrated nursing practicum. The survey was conducted using an anonymous, self-administered questionnaire. The Wilcoxon signed-rank test was used to determine the amount of change in resilience factors from the surveys before and after the practicum. Subsequently, multiple regression analysis was carried out with stress coping behaviors that were significantly associated with resilience factors in univariate analysis as independent variables and the amount of change in resilience factors before and after the practicum as dependent variables. A total of 56 responses were received (response rate 65.8%) from the 85 survey subjects. Innate resilience factors increased significantly from 41 pre-practicums to 44 post-practicums. Acquired resilience factors also increased significantly from 32 pre-practicums to 35 post-practicums (p < 0.01). The results of multiple regression analysis found that the stress coping behavior of “changing point of view” (β = 0.361, p < 0.01) and pre-practicum innate resilience factors (β = −0.456, p < 0.01) were significantly associated with innate resilience factors. Examining the relationship between the amount of change in student resilience and stress coping behaviors revealed that the stress coping behavior of “changing point of view” was associated with innate resilience. This finding suggests that resilience may be increased by changing one’s perspective on an event by taking on a new way of thinking. The results suggested that helping students transform realizations made during reflection into learning and create a sense of meaning may lead to fostering innate resilience during integrated nursing practicums.

Objectives: With rapid advancements in medical care, nurses are confronted with ethical issues on a daily basis. If new nurses are introduced to the clinical setting without having acquired sufficient ethical judgment skills in basic nursing education, they are unable to respond to the ethical dilemmas they face. This results in learned helplessness, which can lead to burnout and turnover. Therefore, it is imperative to develop educational programs where there is a natural progression from basic to continuing nursing. Therefore, in this study, we conducted a nationwide survey using the Nursing Student Care Ethical Competence Scale to present a benchmark for the assessment of this skill and facilitate continuity in nursing education. Methods: From February to March 2019, we conducted a questionnaire survey of 4930 final-year nursing students enrolled in nursing colleges, junior colleges, and technical schools nationwide. The survey consisted of 29 items on ethical behavior, 26 items on ethics knowledge, and seven items on personal attributes. For the analysis, we calculated percentiles for the five standards of nursing students’ ethical care competence: safe care provision, respecting self-determination, protecting personal information, providing the best care, and upholding patients’ dignity. Results: Responses were obtained from 1505 nursing students (collection rate 30.5%, valid response rate 30.5%). The 80th percentile (minimum value-maximum value) was 128 (38 - 145) points for the ethical competence of nursing students, 37 (11 - 40) points for safe care provision, 28 (4 - 31) points for respect for self-determination, 23 (5 - 25) points for protection of personal information, 23 (5 - 25) points for best care provision, and 13 (3 - 15) points for respect for personal dignity. Discussion: The 80th percentile was established as the benchmark for ethical care competence. Conclusion: Based on these criteria, nursing students can objectively assess their ethical behavior, allowing them to understand their strengths and weaknesses, articulate their challenges, and learn autonomously.

In prostate cancer, accurate diagnosis and grade group (GG) decision based on biopsy findings are essential for determining treatment strategies. Diagnosis by experienced urological pathologists is recommended; however, their contribution to patient benefits remains unknown. Therefore, we analyzed clinicopathological information to determine the significance of reassessment by experienced urological pathologists at a high-volume institution to identify factors involved in the agreement or disagreement of biopsy and surgical GGs. In total, 1325 prostate adenocarcinomas were analyzed, and the GG was changed in 452/1325 (34.1%) cases (359 cases were upgraded, and 93 cases were downgraded). We compared the highest GG based on biopsy specimens, with the final GG based on surgical specimens of 210 cases. The agreement rate between the surgical GG performed and assessed in our institute and the highest biopsy GG assessed by an outside pathologist was 34.8% (73/210); the agreement rate increased significantly to 50% (105/210) when biopsy specimens were reevaluated in our institute (chi-square test, P P

Differentiating small cell neuroendocrine (NE) carcinoma (SCNC) of the prostate from adenocarcinoma with NE differentiation based on morphological features alone sometimes can be challenging. Given that treatment strategies vary depending on histological type, an accurate diagnosis is critical. This study aimed to identify the accurate diagnostic factors for SCNC of the prostate. Furthermore, the possibility of novel treatment strategies through genetic analysis was also investigated. Prostate biopsies conducted in our hospital between January 2017 and May 2020 were included. Consequently, seven cases of SCNC and four cases of adenocarcinoma with NE differentiation were identified. No significant differences in the serum neuron-specific enolase, pro-gastrin-releasing peptide, and prostate-specific antigen (PSA) levels were observed between both tumors. The Ki-67 labeling index was significantly higher, and PSA immunoreactivity tended to be lower in SCNC. Although the morphology was undetectable, genetic analysis confirmed several mutations, including those of PIK3CA and TP53. The fact that morphological findings are not apparent indicates that genetic investigation rather than only morphological findings would be important in the future. In conclusion, given the heterogeneity of serum NE markers in SCNC, diagnosis based on these markers alone is challenging. A high Ki-67 labeling index and low PSA immunoreactivity may be useful for diagnosis, but p53 immunoreactivity is insufficient in distinguishing. Although further studies are required to interpret the results of the genetic analysis involving ALK, PIK3CA, and TP53 mutations, the results of our genetic analysis suggest that PIK3CA mutations in SCNC of the prostate may provide a novel therapeutic strategy.

Differentiating small cell neuroendocrine carcinoma (SCNC) of the prostate from prostatic cancer with diffuse neuroendocrine (NE) differentiation based on morphological features alone can be challenging. Given that treatment strategies vary depending on histological type, accurate diagnosis is critical. This study firstly aimed to identify the accurate diagnostic factors for primary prostate NE tumors. Furthermore, the possibility of novel treatment strategies through genetic analysis is also an aim. Specifically, prostate biopsies conducted in our hospital between January 2017 and May 2020 were included. As a result seven cases of SCNC and four cases of prostatic cancer with diffuse NE differentiation were identified. No significant differences in serum neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), and prostate-specific antigen (PSA) levels were observed between SCNC and adenocarcinoma with diffuse NE differentiation. The Ki-67 labeling index was significantly higher and PSA immunoreactivity tended to be lower in SCNC. Genetic analysis did not detect any ALK mutations but confirmed several other mutations, including those of PIK3CA and TP53. In conclusion, given the heterogeneity in serum NE markers in SCNC, diagnosis based on these markers alone is difficult. A high Ki-67 labeling index and low PSA immunoreactivity may be useful for diagnosing, but p53 immunoreactivity is insufficient to distinguish these tumors. Although further studies are required to interpret the results of the genetic analysis involving ALK, PIK3CA, and TP53 mutations, the results of our genetic analysis suggest that PIK3CA mutations in SCNC of the prostate may provide a novel therapeutic strategy.

An important method to improve the sensitivity of a nuclear magnetic resonance (NMR) system is to increase the quality factor ( Q ) of the pickup coils. In this paper, we focus on the following three items: 1) effect of the surface resistance ( R s) of the YBa2Cu3O7-δ (YBCO) films on the Q of the NMR pickup coil; 2) relationship between coil line width and current flowing through coil; and 3) effect of Si-ion irradiation to YBCO films on the Q of the NMR pickup coils. In the study of 1), we examined the Q of the NMR pickup coils made by YBCO films with different R s and found that reduction of R s is useful in increasing the Q of the NMR pickup coils. In the study of 2), we simulated the current flowing in the NMR coils by an electromagnetic simulator, and found that wider microstrip lines of the NMR pickup coil increase the current. In the study of 3), we examined Si-ion irradiation effect to reduce R s of YBCO films, and found low irradiation energy and low irradiation density of Si-ion is useful to decrease R s and useful to obtain the high Q NMR pickup coils.

A high-temperature superconducting (HTS) radio frequency (RF) probe has been designed for nuclear magnetic resonance spectroscopy that is constructed of two newly developed HTS elliptical–coupled resonators that are placed on either side of the sample. The probe has a higher quality factor and a more uniform magnetic field along the z -axis than one with square resonators. The measured unloaded quality factor ( Qu ) of a pair of elliptical–coupled resonators fabricated using YBa2Cu3Oy thin films on an Al2O3 substrate was about 30 000 at 15 K, which is about 82 times higher than the simulated Qu of a copper counterpart at room temperature. Measurement of the input power dependence of Qu showed that a Qu of over 20 000 was obtained up to 16 dBm. Measurement of the RF magnetic field profile along the z -axis showed that the RF magnetic field was more than 85% uniform around the sample region.

The aim of this study was to reveal the level of ethical competence acquired through basic nursing education, to report on the present state of ethics education, and to consider future directions for ethics education. The medical databases ICHUSHI, MEDLINE, and CINAHL were searched using the search terms “nursing ethics,” “nursing practice,” “ethics education,” and “nursing students.” Of the total results, 25 research articles (original papers, research reports, practical reports, documents) were used for this study. Ethical competence covered in basic nursing education corresponded to points 1 - 11 of the Code of Ethics, and the competencies acquired included cognizance and judgement. Ethics education included methods such as case studies in Japan and blended learning in other countries. At present, ethical competence education does not comprehensively cover the Code of Ethics, and the judgement level of competence is not acquired during basic nursing education. It is thus necessary henceforth to progressively put an educational program in place to develop ethics education that persists from basic nursing education through to continuing nursing education.

[Aim] This study aimed to conduct a concept analysis and clarification of ethical competence of nursing students and nurses, and further clarify the components. [Method] Rodger’s concept analysis method was used. A literature search was conducted using the ICHUSHI database, MEDLINE, and CINAHL databases. The keywords included in the search were ethical competence. A total of 24 published articles were analyzed. [Results] As a concept of ethical competence among nursing students and nurses, five categories of [ethical sensitivity], [ethical reasoning], [ethical decision making], [ethical practice], [ethical reflection], obviously became. As a component, two categories of antecedent factors and three categories of consequences were identified. I defined ethical competence in nursing students and nurses, “including nursing students and nurses thinking processes and nursing practice and reflection to solve ethical problems Behavioral characteristics”. [Conclusion] Review of nursing practice from an ethical perspective [ethical reflection] is indispensable for clarifying self-tasks and deepening better nursing practice.

Background Fetal adenocarcinoma of the lung is a rare variant of lung adenocarcinoma and is subcategorized into low-grade and high-grade (H-FLAC) fetal adenocarcinoma. We previously reported poor prognosis in pulmonary adenocarcinomas with an H-FLAC component; however, the genetic abnormalities involved in H-FLAC remain unclear. Therefore, this study aimed to elucidate molecular abnormalities as potential therapeutic targets for H-FLACs. Methods We performed immunohistochemical analysis and comprehensive genetic analyses using whole-exome sequencing in 16 lung cancer samples with an H-FLAC component. DNA was extracted from formalin-fixed paraffin-embedded tissues after macrodissection of the H-FLAC component. Results Cancer-related mutations were identified in TP53 (7/16 cases), KMT2C (6/16 cases), KRAS (4/16 cases), NF1 (3/16 cases), STK11 (3/16 cases), CTNNB1 (2/16 cases), and EGFR (1/16 cases). A high tumor mutation burden of ≥10 mutations per megabase was observed in 3/16 cases. A high microsatellite instability was not detected in any case. Based on the cosine similarity with the Catalogue of Somatic Mutations in Cancer mutational signatures, H-FLACs were hierarchically clustered into three types: common adenocarcinoma-like (five cases), surfactant-deficient (ten cases), and signatures 2 and 13-related (one case). All common adenocarcinoma-like cases presented thyroid transcription factor-1 (TTF-1) expression, whereas surfactant-deficient cases often presented loss of TTF-1 and surfactant protein expression and included cases with mutations in the surfactant system genes NKX2-1 and SFTPC. H-FLACs displayed low programmed death ligand-1 (PD-L1) expression (1-49% of tumor cells) in 5/16 cases, and no case displayed high PD-L1 expression (≥50% of tumor cells). Conclusions This study indicates that lung cancers with an H-FLAC component rarely harbor currently targetable driver gene mutations for lung cancer but display a high frequency of KMT2C mutations. The microsatellite instability, tumor mutation burden, and PD-L1 expression status suggest a poor response to immune checkpoint therapy.

Ovarian clear cell carcinoma(OCCC)shows a poor response to standard chemotherapy, and it is often difficult to choose a regimen for patients with recurrent OCCC. Several reports have suggested a synergistic effect between gemcitabine and cisplatin; another report suggested that gemcitabine, platinum, and bevacizumab are efficacious against recurrent ovarian cancer. We treated patients with OCCC using a combination chemotherapy regimen consisting of gemcitabine(1,000 mg/ m2)and cisplatin(40 mg/m2)on days 1 and 15, and bevacizumab(15 mg/kg)on day 1, with the cycle repeated every 4 weeks. Six patients received this therapy after informed consent, and 2 evaluable patients showed a partial response. Adverse events were mild, with Grade 3 anemia, leukopenia, and neutropenia occurring in 67%, 33%, and 17% of cases, respectively. No Grade 4 events were observed, including hematological or non-hematological toxicities. This suggests that a regimen of combined gemcitabine, platinum, and bevacizumab can be efficacious and feasible for the treatment of OCCC.

Purpose: Diagnosis of breast preneoplastic and neoplastic lesions is difficult due to their similar morphology in breast biopsy specimens. To diagnose these lesions, pathologists perform immunohistochemical analysis and consult with expert breast pathologists. These additional examinations are time-consuming and expensive. Artificial intelligence (AI)-based image analysis has recently improved, and may help in ordinal pathological diagnosis. Here, we showed the significance of machine learning-based image analysis of breast preneoplastic and neoplastic lesions for facilitating high-throughput diagnosis.Methods: Images were obtained from normal mammary glands, hyperplastic lesions, preneoplastic lesions and neoplastic lesions, such as usual ductal hyperplasia (UDH), columnar cell lesion (CCL), ductal carcinoma in situ (DCIS), and DCIS with comedo necrosis (comedo DCIS) in breast biopsy specimens. The original enhanced convoluted neural network (CNN) system was used for analyzing the pathological images. Results: The AI-based image analysis provided the following area under the curve values (AUC): normal lesion vs. DCIS, 0.9902; DCIS vs. comedo DCIS, 0.9942; normal lesion vs. CCL, 0.9786; and UDH vs. DCIS, 1.000. Multiple comparison analysis showed precision and recall scores similar to those of single comparison analysis. Based on the Gradient-weighted Class Activation Mapping (Grad-CAM) used to visualize the important regions reflecting the result of CNN analysis, the ratio of stromal tissue in the whole weighted area was significantly higher in UDH and CCL than that in DCIS. Conclusions: These analyses may provide a more accurate and rapid pathological diagnosis of patients. Moreover, Grad-CAM identifies uncharted important histological characteristics for newer pathological findings and targets of research for understanding diseases.

Diagnosis of breast preneoplastic and neoplastic lesions is difficult due to their similar morphology in breast biopsy specimens. To diagnose these lesions, pathologists perform immunohistochemical analysis and consult with expert breast pathologists. These additional examinations are time-consuming and expensive. Artificial intelligence (AI)-based image analysis has recently improved, and may help in ordinal pathological diagnosis. Here, we showed the significance of machine learning-based image analysis of breast preneoplastic and neoplastic lesions for facilitating high-throughput diagnosis. Images were obtained from normal mammary glands, hyperplastic lesions, preneoplastic lesions and neoplastic lesions, such as usual ductal hyperplasia (UDH), columnar cell lesion (CCL), ductal carcinoma in situ (DCIS), and DCIS with comedo necrosis (comedo DCIS) in breast biopsy specimens. The original enhanced convoluted neural network (CNN) system was used for analyzing the pathological images. The AI-based image analysis provided the following area under the curve values (AUC): normal lesion versus DCIS, 0.9902; DCIS versus comedo DCIS, 0.9942; normal lesion versus CCL, 0.9786; and UDH versus DCIS, 1.000. Multiple comparison analysis showed precision and recall scores similar to those of single comparison analysis. Based on the gradient-weighted class activation mapping (Grad-CAM) used to visualize the important regions reflecting the result of CNN analysis, the ratio of stromal tissue in the whole weighted area was significantly higher in UDH and CCL than that in DCIS. These analyses may provide a more accurate and rapid pathological diagnosis of patients. Moreover, Grad-CAM identifies uncharted important histological characteristics for newer pathological findings and targets of research for understanding diseases.

We reviewed our clinical experience of olaparib treatment for patients with platinum-sensitive recurrent ovarian, fallopian tube, and peritoneal cancer. Of the 10 cases, the primary sites of cancer were the ovaries, fallopian tubes, and peritoneum in 7, 1 and 2 cases, respectively. The median period of treatment administration was 10 months. The observed Grade 3 or 4 adverse events as per the Common Terminology Criteria for Adverse Events version 4.0 were: anemia, leukopenia and neut r openia in 4, 4 and 3 cases, respectively. Eight cases needed treatment to be interrupted, and 5 cases required a reduction in dose. Three patients were treated for more than 12 months, while the others had to discontinue due to disease progression. However, none of the patients had to discontinue treatment due to adverse events. Therefore, it appears that olaparib can be safely used despite some patients requiring a withdrawal or reduction in treatment.

We report a rare case of liver recurrence of gastric cancer 14 years and 3 months after curative gastrectomy. An 81-yearold man underwent total gastrectomy, D2 lymphadenectomy, Roux-en-Y reconstruction, and cholecystectomy for advanced gastric cancer in November 2002. H e was diagnosed pathologically with M, Type 5, 53×42 mm, tub2tub1, pT4a, ly2, v2, pN1, pPM0, pDM0, M0, pStage ⅢA(JGCA 15th). Postoperative adjuvant therapy was not administered. He was followed up for 5 years after surgery without adjuvant therapy, and he did not exhibit recurrence. In February 2017, he experienced difficulties in swallowing and visited our hospital. Abdominal contrast-enhanced CT showed an 8×5 cm liver tumor in the lateral segment. Part of the tumor protruded to outside of the liver, and the tumor invaded and pushed the jejunum in the Roux limb. We performed liver biopsy and diagnosed him with liver metastasis of recurrent gastric cancer. Late relapse after gastrectomy, especially after 10 years or more, is very rare.

Background: The present paper elucidates the current status of ethical judgment capacity and nursing ethics in relation to continuous nursing education, while further examining the ideal direction for future educational ventures. Method: We searched the Igaku Chuo Zasshi, MEDLINE, and CINAHL databases for the time period between 2008 and 2018. The keywords used were “nursing ethics,” “nursing practice,” “ethical education,” and “nurses,” restricting the search to research articles focusing on nurses working in hospital wings (excluding nursing managerial positions). Results: A total of 22 papers were extracted. The capacity to make ethical judgments during continuous nursing education corresponds to Article 1 through 11 of the Code of Ethics from the Japanese Nursing Association. Assessed levels included awareness, judgment, and action. In terms of the clinical ladder for nurses, ladders I, II, and IV were observed. In Japan, literature on ethics education for nurses primarily comprised case studies, while papers in foreign countries carried out education through expert knowledge, namely by placing nursing ethics scholars in the hospital. Conclusion: Currently, the capacity for nurses to make ethical judgments does not cover the entire Code of Ethics, and ethics education is not being provided according to all clinical ladder stages. Thus, future work will need to devise a step-wise educational program that can continuously provide adequate ethics training.

Modified radical hysterectomy (MRH) is thought to be equivalent to class II (Piver classification) or type B (Querleu classification) radical hysterectomy (RH) and identical to the original method of the Wertheim operation. MRH is a method of hysterectomy defined as being intermediate between simple hysterectomy and RH and enabling almost full preservation of the pelvic splanchnic nerves and hypogastric plexus. This surgical procedure entails the cutting of the anterior leaf, not the posterior one, of the vesicouterine ligament of the uterus. The ureter is mobilized laterally, part of the parametrial tissue is transected at the level of the ureteral tunnel, and at least 10 mm of the vaginal wall from the uterine cervix is removed. The indication of MRH (with pelvic lymphadenectomy) in cervical cancer is International Federation of Gynecology and Obstetrics stage IA1 with lymphovascular space invasion or stage IA2. MRH is associated with a very low (≤1%) rate of significant postoperative complications, and compared with RH, it reduces the rate of adverse effects on the urinary tract, such as fistula formation and severe voiding dysfunction. The mortality rate for those undergoing this procedure is 0.4–0.5%. The possibility of MRH for low-risk FIGO stage IB1 patients has been considered, and clinical trials are ongoing.

A 41-year-old female smoker presented with a vaginal mass. Gynecological examination showed a mass filling the uterine corpus, cervix, and vagina. A total abdominal hysterectomy was performed. Macroscopic findings included a large fragile mass involving the uterine cavity, cervix, and vagina. Histology revealed atypical ducts admixed with solid components consisting of large atypical cells. The initial pathological diagnosis was grade 3 endometrioid adenocarcinoma. The patient was designated as stage II according to the 2008 International Federation of Gynecology and Obstetrics (FIGO) staging. Two years later, two nodules were found in the upper lobe of the left lung, and the patient underwent an upper lobectomy. The masses, which exhibited solid and organoid growth patterns of large atypical cells, had histological characteristics of large cell neuroendocrine carcinoma (LCNEC) of the lung. However, the tumor was immunohistochemically positive for neuroendocrine markers, such as synaptophysin in addition to estrogen receptor and progesterone receptor, and the tumor was negative for thyroid transcription factor-1. These immunohistochemical results were almost identical to those of the solid portions of the uterine carcinoma. The final diagnosis was LCNEC combined with endometrioid adenocarcinoma of the uterine corpus and lung metastasis of the LCNEC component of the endometrial carcinoma. LCNEC often arises in the lung, but it rarely arises in other organs. Some patients with metastatic components exhibited only a LCNEC pattern although the primary tumor was a mixed carcinoma consisting of LCNEC and other histology, like the present case. LCNEC is often poorly differentiated, especially in extrapulmonary primary organ LCNEC. Therefore, pathologists should consider metastatic carcinoma when they encounter lung LCNEC in a patient with a preceding extrapulmonary carcinoma composed of a poorly differentiated component or LCNEC component, and they should clarify tumor immunohistochemical characteristics to confirm the diagnosis.

Gangliocytic paraganglioma (GP) has been regarded as a rare benign tumor that commonly arises from the second part of the duodenum. As GP does not exhibit either prominent mitotic activity or Ki-67 immunoreactivity, it is often misdiagnosed as neuroendocrine tumor (NET) G1. However, the prognosis might be better in patients with GP than in those with NET G1. Therefore, it is important to differentiate GP from NET G1. Moreover, our previous study indicated that GP accounts for a substantial, constant percentage of duodenal NETs. In the present article, we describe up-to-date data on the clinicopathological characteristics of GP and on the immunohistochemical findings that can help differentiate GP from NET G1, as largely revealed in our new and larger literature survey and recent multi-institutional retrospective study. Furthermore, we would like to refer to differential diagnosis and clinical management of this tumor and provide intriguing information about the risk factors for lymph node metastasis on GP.

Background: Although gangliocytic paraganglioma (GP) is considered a rare benign neuroendocrine tumor, cases of mortality have been reported. Occasionally, GP is misdiagnosed as neuroendocrine tumor G1, which is associated with a poorer prognosis than GP. To avoid such misdiagnoses, it is important to understand the clinicopathological characteristics of GP. Thus, herein, we discuss the current literature on the clinicopathological characteristics of GP. Methods: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed and Japana Centra Revuo Medicina searches were used to identify papers describing GP. Inclusion criteria included confirmation of epithelioid, spindle-shaped, and ganglion-like cells in the main article and/or figures and whether the paper was cited in other studies of GP. Data were collected on age, sex, site of the primary lesion, tumor size, treatment, prognosis, lymph node metastasis (LNM), depth of tumor invasion, rate of preoperative diagnosis, and clinical symptoms. Results: In total, 162 papers containing 263 cases of GP met the criteria. The mean age at diagnosis was 53.5 years. The male-to-female ratio was 157:104. The mean tumor size was 25.7 mm. The predominant site of the primary tumor was the duodenum (89.7%). The most common clinical sign of GP was gastrointestinal bleeding (47.9%). Other signs and symptoms of GP included abdominal pain (44.7%), anemia (20.3%), incidental findings (12.9%), nausea (6.9%), weight loss (5.5%), general fatigue (5.1%), jaundice (4.6%), and incidental autopsy findings (5.1%). LNM was observed in 11.4% of patients. Liver metastasis was observed in 1.1% of patients. Depth of tumor invasion (penetrating beyond the submucosal layer or sphincter of Oddi) was by far the most significant risk factor for LNM in patients with GP. This suggests, along with histological heterogeneity, that GP may have hamartomatous characteristics. Furthermore, immunohistochemical expression of progesterone receptor and pancreatic polypeptide were useful in distinguishing between GP and neuroendocrine tumor G1, even in small biopsy specimens. Conclusions: We reveal the clinicopathological characteristics of GP, including risk factors for LNM, differential diagnostic approaches, and improvements in the clinical management of this tumor.In addition, GP may have hamartomatous characteristics.

Fetal adenocarcinoma is a rare variant of lung adenocarcinoma, which is subcategorized into low-grade and high-grade forms. High-grade fetal adenocarcinoma confers worse prognosis than low-grade fetal adenocarcinoma, but the prognostic differences between high-grade fetal adenocarcinoma and conventional lung adenocarcinoma are unknown. We reviewed tissue sections of 3719 cases of surgically resected primary lung cancers and found 53 lung cancers with a high-grade fetal adenocarcinoma component. We analyzed their clinicopathological and immunohistochemical features, and performed a prognostic analysis of adenocarcinomas with the fetal-type component. We further analyzed the prognostic differences between adenocarcinomas with the fetal-type component and conventional adenocarcinomas without the fetal-type component. Lung cancers with the fetal-type component predominantly occurred in elderly men with a smoking history. Twenty-nine patients had stage I disease, 13 patients had stage II, and 11 patients had stage III. The fetal-type histology was combined with conventional-type adenocarcinoma (41 cases), squamous cell carcinoma (5 cases), large cell neuroendocrine carcinoma (5 cases), enteric adenocarcinoma (2 cases), and small cell carcinoma (1 case). The fetal-type component showed immunopositivity for α-fetoprotein (39%), glypican-3 (37%), and SALL4 (17%). The 5-year overall survivals of fetal-type-predominant and fetal-type-nonpredominant patients were 44 and 56%, respectively (P = 0.962). The 5-year overall survivals of lepidic-, acinar-, papillary-, solid-, and micropapillary-predominant adenocarcinomas, invasive mucinous adenocarcinomas, and adenocarcinomas with the fetal-type component were 94, 82, 77, 69, 57, 83, and 41%, respectively (P

Background The worldwide incidence of neuroendocrine tumors (NETs) has increased remarkably, with the hindgut being the second most common site for such tumors. However, the mechanisms underlying progression and metastasis of hindgut NETs are unclear. A retrospective study was conducted to elucidate these mechanisms. Methods Clinicopathological data of cases of hindgut NET between April 1996 and September 2015 were analyzed, retrospectively. Patients with neuroendocrine carcinoma were excluded. Formalin-fixed paraffin-embedded tissues of hindgut NET cases were subjected to detailed morphometric and immunohistochemical analyses. Statistical analyses were performed using the non-parametric Mann-Whitney U test, Spearman’s correlation coefficient, and chi-squared test. Multivariate logistic regression analysis was conducted as appropriate for the data set. Results Fifty-six hindgut NET cases were considered. Microvessel density and lymphatic microvessel density were identified as significant risk factors for venous and lymphatic invasion. There was a positive correlation between microvessel density and the maximum tumor diameter. Multivariate logistic regression analysis revealed that the maximum tumor diameter alone was an independent predictor of lymph node metastasis, whereas lymphovascular invasion and MVD was not the predictor of lymph node metastasis. There were no significant correlations between the Ki-67 labeling index and any of the parameters evaluated including age, sex, the maximum tumor diameter, venous invasion, lymphatic invasion, microvessel density, lymphatic microvessel density, and lymph node metastasis. Conclusions Angiogenic mechanisms may play important roles in the progression of hindgut NET. Otherwise, the maximum tumor diameter alone was an independent predictor of lymph node metastasis in hindgut NETs. Moreover, our study raises the question of whether the presence of lymphovascular invasion, in endoscopically obtained hindgut NET tissues, is an absolute indication for additional surgery or not.

Background As the World Health Organization grading system for gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) may not always correlate with tumor progression, it is imperative that other independent predictors of tumor progression be established. To identify such predictors, we conducted a retrospective histopathological study of hindgut NETs, obtained from endoscopic procedures, and used statistical analyses to evaluate predictive factors. Methods We first obtained clinicopathological data of cases of hindgut NETs. Tissue sections from tumor samples were prepared and subjected to pathological examination. In particular, we calculated the microvessel density (MVD) and lymphatic microvessel density (LMVD) values, and performed appropriate statistical analyses. Results A total of 42 cases of hindgut NETs were selected for the study, 41 from the rectum and 1 from the sigmoid colon. Based on the Ki-67 labeling index, 34 cases were classified as NET G1 tumors and 8 as NET G2 tumors. MVD values ranged from 1.4/mm2 to 73.9/mm2 and LMVD values from 0/mm2 to 22.9/mm2. MVD and LMVD were identified as risk factors for venous and lymphatic invasion of hindgut NETs. Moreover, MVD positively correlated with the maximum diameter of the tumor. Conclusions Tumor progression of NETs may cause angiogenesis and lymphangiogenesis, via an unknown mechanism, as well as lymphovascular invasion. Angiogenesis likely plays an important role in occurrence and progression in the initial phase of hindgut NETs.

We encountered a case of uterine leiomyosarcoma with multiple lung metastases. The patient was a 52-year-old woman who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by chemotherapy with gemcitabine and docetaxel. After 1 cycle of chemotherapy, the lung metastasis was reduced, but at the same time, she developed bilateral pneumothorax. Chemical pleurodesis using talc was performed. The lungs were expanded and stabilized in 7 days. After 5 cycles of chemotherapy were administered, no recurrence of pneumothorax and adverse effects were observed.

A 53-year-old patient with recurrent ovarian clear cell adenocarcinoma developed fever (39°C) and cough on day 28 of liposomal doxorubicin chemotherapy, the 4th cycle of the 4th regimen since initial treatment. Drug-induced interstitial pneumonia was suspected from a chest CT image showing diffuse ground-glass opacities; however, we deduced pneumocystis pneumonia from the elevated serum beta-D-glucan levels. After effective treatment with sulfamethoxazole and amphotericin B, the patient's symptoms and radiological findings improved. Pneumocystis pneumonia is an opportunistic infection that poses a risk not only for patients undergoing aggressive immunosuppressive therapy, those infected with HIV, and those with transplants, but also for patients undergoing chemotherapy. When pneumonia is diagnosed during chemotherapy, it is essential to consider the possibility of pneumocystis pneumonia.