Published papers

Fallopian tube carcinoma is frequently detected at an advanced stage, and its imaging findings and tumor marker profiles are often indistinguishable from those of ovarian or peritoneal carcinoma. Nontuberculous mycobacteria (NTM) are environmental acid-fast bacilli with increasing clinical significance in both immunocompromised and immunocompetent individuals. Infection of gynecologic organs is extremely rare. This report describes a case of fallopian tube NTM infection caused by Mycobacterium abscessus that mimicked fallopian tube carcinoma. An 87-year-old woman underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during routine surveillance, which revealed focal FDG uptake in the right adnexal region. Serum CA125 was elevated, and magnetic resonance imaging demonstrated findings suspicious for fallopian tube carcinoma. Primary debulking surgery was performed. Intraoperative frozen-section examination of the right adnexa revealed necrotizing granulomas without evidence of malignancy, raising suspicion of mycobacterial infection. Fresh specimens were submitted for microbiological evaluation. Culture identified Mycobacterium abscessus, establishing the diagnosis of fallopian tube NTM infection. The patient was asymptomatic and had no abscess formation. Complete surgical resection was achieved, and no antimicrobial therapy was administered. The patient remained recurrence-free at 1-year follow-up. This case highlights the difficulty of differentiating infectious granulomatous disease from malignancy based on imaging findings alone. Intraoperative frozen-section examination played a crucial role in prompting microbiological investigation and establishing the correct diagnosis.

Aim: To assess the impact of COVID-19 on cervical cancer screening. Method: The Japanese Society of Gynecologic Oncology launched COVID-19 Task Force surveyed the municipalities in urban areas of Japan. Questionnaires were sent to 20 ordinance-designated cities and 23 wards of Tokyo metropolitan area in Japan via telephone and mail in January 2021. An additional survey was conducted in March and April 2021, counted the monthly checkups in 2020 and, as a control data, the number of monthly checkups in 2019. “The State of Emergency” between April 7 and May 25, 2020, included 13 prefectures. The data collected in this research involved the number of screenings only. The chi-square test was performed for statistical analysis. Results: The number of cancer screenings from March to August, with May being the month with the lowest number of screenings, was less than 50% of that in the previous year. In particular, the drop in the number of cancer screenings in the “Prefectures operating under special safety precautions” was remarkable and significantly lower than that in other Prefectures. However, after August, the number recovered to the usual level, despite the second wave of the pandemic occurring nationwide. The initial “the State of Emergency” caused a significant decrease in the number of people receiving population-based screenings, but the recovery has been remarkable, and the total number is expected to be the same as in previous years. Conclusion: The initial “the State of Emergency” caused a significant decrease in the number of people receiving population-based screenings.

Objective: As coronavirus disease 2019 (COVID-19) rages on, it is a challenging task to balance resources for treatment of COVID-19 and malignancy-based treatment. For the development of optimal strategies, assessing the conditions and constrains in treatment during the COVID-19 pandemic is pertinent. This study reported about a nationwide survey conducted by the Japan Society of Gynecologic Oncology. Methods: We interviewed 265 designated training facilities about the state of their clinical practice from the time period between March and December 2020. We asked the facility doctors in charge to fill a web-based questionnaire. Results: A total of 232 facilities (87.5%) responded. A decrease in the number of outpatient visits was reported, and the major reason attributed was reluctance of patients to visit hospitals rather than facility restrictions. The actual number of surgeries decreased by 3.9%, compared to 2019. There was a significant difference when the variable of “Prefectures operating under special safety precautions” or not was introduced. There was no increase in the rate of advanced stages in the three cancer types studied. However, 34.1% participants perceived COVID-19 affected management and prognosis. Conclusion: Refraining from visiting hospitals based on the patient's judgment may be expected to be an issue in the future. No significant decrease in surgeries was observed, and it would seem that there were few forced changes in treatment plans, but “the State of Emergency” had an impact. There was no increase in the rate of advanced cancers, but this will need to be monitored.

While the fallopian tube epithelium (FTE) is known to be composed of various differentiated cells such as secretory and ciliated cells, the upstream regulatory mechanisms of cell differentiation that are essential for tissue homeostasis remain under investigation. In this study, we established human FTE organoids and identified quiescent cells within the early organoid formation by observing cellular proliferation heterogeneity. We also analyzed two single-cell transcriptomic data to trace the differentiation trajectory in human FTE, and found that the gene LCN2 serves as a marker gene of early stage of the trajectory. Genetically manipulated FTE organoids indicated that LCN2 inhibits ferroptosis and promotes cell survival under oxidative stress. In addition, the FTE organoids introduced p53 dysfunction, the common genetic characteristics of high-grade serous carcinoma, showed upregulated LCN2 expression and enhanced ferroptosis resistance. This study provides insights into the LCN2-mediated protective mechanism of human FTE quiescent cells and its potential role in tumorigenesis.

Background: Nuclear protein in testis (NUT) carcinoma is a rare, aggressive, and poorly differentiated epithelial malignancy characterized by the rearrangement of NUTM1 (NUT midline carcinoma family member 1) on 15q14. It primarily originates along the midline structures, including the head, neck, thorax, and mediastinum. Although NUT carcinoma of the pelvic gynecological organs is exceedingly rare, reported cases have been limited to primary or metastatic ovarian tumors. Here, we present the first documented case of primary uterine NUT carcinoma. Case presentation: A 53-year-old postmenopausal woman presented with abnormal uterine bleeding and a uterine mass. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The initial postoperative histopathological evaluation suggested undifferentiated endometrial sarcoma; however, subsequent immunohistochemical (IHC) analysis and fluorescence in situ hybridization revealed NUTM1 rearrangement, confirming the diagnosis of NUT carcinoma. The patient experienced tumor recurrence six months postoperatively and succumbed to the disease nine months later. Discussion: The pathological diagnosis was challenging; the presence of abrupt squamous differentiation prompted further IHC analysis, leading to the definitive diagnosis. Primary uterine NUT carcinoma may be misdiagnosed as other undifferentiated uterine tumors due to its rarity and histological overlap. Conclusions: Given the diagnostic challenges, NUT IHC staining and molecular testing for NUTM1 rearrangement should be considered in undifferentiated uterine tumors with ambiguous histopathological features.

In the field of drug repurposing, the use of statins for treating dyslipidemia is considered promising in ovarian cancer treatment based on epidemiological studies and basic research findings. Biomarkers should be established to identify patients who will respond to statin treatment to achieve clinical application. In the present study, we demonstrated that statins have a multifaceted mode of action in ovarian cancer and involve pathways other than protein prenylation. To identify biomarkers that predict the response to statins, we subjected ovarian cancer cells to microarray analysis and calculated Pearson’s correlation coefficients between gene expression and cell survival after statin treatment. The results showed that VDAC1 and LDLRAP1 were positively and negatively correlated with the response to statins, respectively. Histoculture drug response assays revealed that statins were effective in clinical samples. We also confirmed the synergistic effects of statins with paclitaxel and panobinostat and determined that statins are hematologically safe to administer to statin-treated mice. Future clinical trials based on the expression of the biomarkers identified in this study for repurposing statins for ovarian cancer treatment are warranted.

Objectives: The initial learning curve is a barrier to introducing robotic surgery. Evidence regarding appropriate simulation programs that allow for a smooth introduction of gynecological robotic surgery remains limited. Materials and Methods: We retrospectively analyzed 149 patients who underwent robotic surgery for gynecologic diseases. Before their first procedure, the surgeons completed a robotic surgery training program. Assistant surgeons also completed simulation programs, including setup procedures and manipulation of the robotic arm. Results: The mean (± standard deviation) operative, setup, and console times were 170 ± 54 min, 22 ± 8 min, and 126 ± 51 min, respectively. No patient required blood transfusion or conversion to laparoscopy or laparotomy. Patients undergoing surgery by the same surgeon were divided into three groups (first-third, middle-third, and last-third of patients undergoing surgery) to assess chronological changes. No statistically significant differences were found between the operative and console times among these groups. The setup times for the middle and last third of patients were 20 ± 7 min and 18 ± 7 min, respectively, which were statistically significantly shorter than those for the first third of patients. No significant differences in the operative and console times done by five physicians who completed programs were observed between the first 75 and the latter 74 procedures; however, the setup times of the latter 74 procedures were significantly shorter than those of the first 74 procedures (25 ± 9 min vs. 19 ± 6 min; P < 0.001). Conclusion: The setup time was influenced by clinical experience. An appropriate simulation program allowed a safe implementation of robotic surgery.