Excellent concordance of the molecular classification between preoperative biopsy and final hysterectomy in endometrial carcinoma.

OBJECTIVE: The 2023 International Federation of Gynecology and Obstetrics classification with molecular classification shows superior discriminatory ability compared to staging systems lacking molecular data. However, the accuracy of endometrial biopsy data in molecular classification remains uncertain. This study aimed to assess the concordance of molecular classifications between preoperative biopsy and hysterectomy to predict prognosis before surgical staging. METHODS: Endometrial biopsies and corresponding hysterectomy specimens were collected at the National Cancer Center Hospital between 2012 and 2023. Immunohistochemistry for p53 and mismatch repair (MMR) proteins and next-generation sequencing of all exons of polymerase epsilon (POLE) were performed. Given the limited number of POLE mut cases in prior studies, we prepared a POLE mut-enriched cohort. Cohen's kappa estimates were used to determine concordance for molecular and clinicopathological subgroup assignments. RESULTS: Among 70 patients classified into four molecular subtype groups, 33 exhibited POLE mutations, 15 showed loss of MMR protein expression, 13 had p53-abnormality, and 9 had no specific molecular profile. Concordance between biopsy and hysterectomy specimens was 100% (κ = 1.000). In contrast, histological types and grades between biopsy and surgical specimens showed moderate and substantial agreement (κ = 0.420 and κ = 0.780, respectively). CONCLUSIONS: Molecular subtypes were completely consistent with those derived from surgical specimens, demonstrating high concordance between preoperative and postoperative molecular classifications. This suggests that endometrial biopsies could reliably predict prognosis. Future studies should investigate how biopsy-based molecular profiling influences treatment planning and patient outcomes.

Genomic profiles of Japanese patients with vulvar squamous cell carcinoma.

The incidence of vulvar carcinoma varies by race; however, it is a rare disease, and its genomic profiles remain largely unknown. This study examined the characteristics of vulvar squamous cell carcinoma (VSCC) in Japanese patients, focusing on genomic profiles and potential racial disparities. The study included two Japanese groups: the National Cancer Center Hospital (NCCH) group comprised 19 patients diagnosed between 2015 and 2023, and the Center for Cancer Genomics and Advanced Therapeutics group comprised 29 patients diagnosed between 2019 and 2022. Somatic mutations were identified by targeted or panel sequencing, and TP53 was identified as the most common mutation (52-81%), followed by HRAS (7-26%), CDKN2A (21-24%), and PIK3CA (5-10%). The mutation frequencies, except for TP53, were similar to those of Caucasian cohorts. In the NCCH group, 16 patients of HPV-independent tumors were identified by immunohistochemistry and genotyping. Univariate analysis revealed that TP53-mutated patients were associated with a poor prognosis (log-rank test, P = 0.089). Japanese VSCC mutations resembled those of Caucasian vulvar carcinomas, and TP53 mutations predicted prognosis regardless of ethnicity. The present findings suggest potential molecular-targeted therapies for select VSCC patients.

Efficacy of a Combination Therapy for Difficulties Waking Up in Non-School-Attending Students.

School non-attendance due to difficulties waking up is increasing in Japan, and affected students are commonly diagnosed with orthostatic dysregulation (OD); however, OD-associated sleep problems are overlooked. To date, no sleep-medicine-based treatment for wake-up difficulties in non-school-attending students has been established. This study aimed to assess the efficacy of a novel combination therapy for these students. We assessed the combined effect of sleep hygiene guidance, low-dose aripiprazole administration (3 mg/day), and blue-light exposure on wake-up difficulty in 21 non-school-attending teenage patients. The patients were evaluated using sleep studies and questionnaires before and after treatment. The average subjective total sleep time calculated from sleep diaries before treatment in the patients was 10.3 h. The therapy improved wake-up difficulty by 85.7% and further improved school non-attendance by 66.7%. The subjective sleep time significantly decreased by 9.5 h after treatment (p = 0.0004). The self-rating Depression Scale and mental component summary of the 36-item Short-Form Health Survey significantly improved after treatment (p = 0.002 and p = 0.01, respectively). Wake-up difficulties were caused by the addition of a delayed sleep phase to the patients' long sleep times. The novel combination therapy was effective in improving wake-up difficulty and mental quality of life in non-school-attending teenage students.

Case of leiomyosarcoma arising from subserosal leiomyoma.

Uterine leiomyosarcoma (LMS) is a rare tumor. It has not been established if these tumors arise de novo or from pre-existing leiomyomas (LM). We report a case herein of LMS arising from a subserosal LM. A 47-year-old nulliparous woman was diagnosed with a uterine tumor measuring 30 cm in diameter by pelvic magnetic resonance imaging. Serum CA-125 level was 369 U/mL, and the lactate dehydrogenase level was elevated (565 IU/L, respectively). Positron emission tomography-computed tomography revealed abnormal uptake (SUVmax = 25.29) of the abdominal tumor. Upon laparotomy, a large tumor with solid and cystic components was shown to arise from a subserosal LM, with invasion into the greater omentum and small intestine. Abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and small intestine resection were performed. Macroscopic findings showed that the LMS was adherent to a subserosal LM, without continuity between the tumor and the uterus. Our case supports the hypothesis that LMS can arise from a pre-existing LM.

A Retrospective Study of the Effects of Oncology Pharmacist Participation in Treatment on Therapeutic Outcomes and Medical Costs.

Specialist oncology pharmacists are being trained in Japan to assist cancer treatment teams. These specialized pharmacists address patients' physical and mental problems in pharmacist-managed cancer care clinics, actively participate in formulating treatment policies, and are beneficial in offering qualitative improvements to patient services and team medical care. However, the effect of outpatient treatment by oncology pharmacists on therapeutic outcomes and medical costs is still unknown. A retroactive comparative analysis of the treatment details and clinical course was conducted among three groups of patients: patients who underwent adjuvant chemotherapy managed by a gynecologic oncologist only (S arm), patients managed by a non-oncologist (general practice gynecologist) only (NS arm), and patients managed by both a non-oncologist and a specialist oncology pharmacist (NS+Ph arm). The medical cost per course was significantly lower for patients in the NS+Ph arm than for those in the other two arms. Surprisingly, the outpatient treatment rate in the NS+Ph arm was overwhelmingly high. The involvement of an oncology pharmacist did not make a significant difference in therapeutic outcomes such as recurrence rate and survival. The participation of oncology pharmacists in the management of cancer patients undergoing chemotherapy enables safe outpatient treatment and also reduces medical costs.

Parathyroid hormone-related protein (PTHrP) and Ca levels in the milk of lactating cows.

To investigate the roles of mammary PTHrP in calcium uptake and/or release in the mammary gland of cows, plasma PTHrP and Ca levels, and their arterial-venous differences were examined in a Jersey cow during the periparturient period. Levels of Ca in both abdominal aorta and abdominal subcutaneous vein blood slightly decreased around the parturition and at 24 days after the parturition, however, no remarkable arterial-venous differences were observed. Plasma PTHrP levels in both arterial and venous samples were below the detection limit (0.57 pmol/l) during the experimental period. Milk PTHrP and Ca levels were measured in 9 Holstein dairy cows. Although plasma PTHrP levels in all arterial and venous samples were also below the detection limit, milk PTHrP and Ca levels were remarkably high, ranging from 14,900 pmol/l to 41,200 pmol/l and from 772 mg/l to 1,200 mg/l, respectively. In addition, a significant positive correlation (P<0.01) was observed between milk PTHrP and Ca levels. These results suggested that mammary PTHrP is closely related to Ca concentration in the milk.