Tohru Morisada

Associations of Lipid Metabolism Abnormalities and Obesity With Endometriosis‐Associated Ovarian Cancer

ABSTRACT Aim To investigate the differences in lipid metabolism and obesity between patients with ovarian endometrioid carcinoma (OEC) and ovarian clear cell carcinoma (OCCC), both of which are classified as endometriosis‐associated Type I ovarian cancers. Methods This retrospective study included 133 patients who underwent surgery for OEC ( n  = 50) or OCCC ( n  = 83) between 2010 and 2022. Preoperative serum lipid markers (total cholesterol [TC], low‐density lipoprotein cholesterol [LDL‐C], and high‐density lipoprotein cholesterol [HDL‐C]) and body mass index (BMI) were compared between the two groups. Associations with menopausal status and disease stage were examined, and independent predictors were evaluated by multivariate logistic regression. Results Patients with OEC had significantly higher TC (215 vs. 199.5 mg/dL, p  = 0.040), LDL‐C (139 vs. 120.6 mg/dL, p  = 0.026), and BMI (22.1 vs. 20.4 kg/m 2 , p  = 0.020) compared with those with OCCC. No significant differences were observed for HDL‐C. In premenopausal women, TC and LDL‐C were significantly higher in patients with OEC, whereas no intergroup differences were found in postmenopausal women. Among patients with OEC, those with advanced‐stage disease had higher TC and LDL‐C, whereas no stage‐related differences were observed in patients with OCCC. Multivariate analysis identified BMI and LDL‐C as independent factors associated with OEC. Conclusion Lipid metabolism abnormalities and obesity were more strongly associated with OEC than with OCCC, suggesting subtype‐specific metabolic mechanisms of carcinogenesis and progression. These findings highlight the importance of metabolic factors in OEC, warranting further prospective studies.

Maintenance therapy for platinum-sensitive recurrent ovarian cancer with a history of PARPi administration

This study explored new insights into the selection criteria for maintenance therapy for platinum-sensitive recurrent ovarian cancer by comparing the efficacy of poly(ADP-ribose) polymerase inhibitors (PARPis) and bevacizumab in patients with a history of PARPi administration. Between April 2014 and December 2024, 81 patients underwent maintenance therapy with either PARPi (52 patients) or bevacizumab (29 patients) at our institution. The primary endpoint was progression-free survival (PFS) after the end of the last chemotherapy treatment. The median PFS did not differ significantly between the PARPi and bevacizumab groups (9 vs. 12 months, p=0.942). Similarly, in the propensity score-matched cohort (15 pairs), no significant difference was observed between the PARPi and bevacizumab groups (p=0.444). In the PARPi group, a history of PARPi administration was associated with a significant difference in PFS in both univariate and multivariate analyses (PARPi-naïve vs. PARPi-experienced: 12 vs. 4 months, p=0.002; hazard ratio=3.24, 95% confidence interval=1.56-6.69). In the bevacizumab group, a history of PARPi administration was not associated with a significant difference in PFS. Among patients with a history of PARPi administration, the bevacizumab group had a significantly better PFS than the PARPi group (PARPi rechallenge vs. bevacizumab: 4 vs. 12 months, p=0.042), and the proportion of patients experiencing platinum-resistant recurrence during maintenance therapy was higher in the PARPi rechallenge group (58.8%) than in the bevacizumab group (20.0%) (p=0.049). Maintenance therapy with bevacizumab may be more beneficial for patients with platinum-sensitive recurrent ovarian cancer who have a history of PARPi administration.

Assessing the antitumor effects of metformin on ovarian clear cell carcinoma

Developing novel therapies that outperform the existing chemotherapeutic treatments is required for treatment-resistant ovarian clear cell carcinoma. We investigated the antitumor effect of metformin on ovarian clear cell carcinoma, enhancement of the antitumor effect by its combination with chemotherapy, and its molecular regulatory mechanism. First, we evaluated the viability of ovarian clear cell carcinoma lines using the water-soluble tetrazolium-1 assay and found that metformin suppressed cell viability. Cell viability was significantly suppressed by co-treatment with cisplatin and metformin. In contrast, co-treatment with paclitaxel and metformin showed no significant difference in viability compared with the group without metformin. Western blot analysis showed increased phosphorylation of AMP-activated protein kinase in some cell lines and suppressed phosphorylation of the mammalian target of rapamycin in a particular cell line. Flow cytometry analysis revealed a significant increase in the rate of apoptosis in the metformin-treated group and rate of cell cycle arrest at the G2/M phase in a particular cell line. These results indicated that metformin may be effective against cultured ovarian clear cell carcinoma cells, particularly in combination with cisplatin.

Effects of a fertility-sparing re-treatment for recurrent atypical endometrial hyperplasia and endometrial cancer: a systematic literature review

To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial cancer (EC) following initial fertility-sparing treatment. A comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Endometrial Cancer Committee. Multiple search engines, including PubMed/MEDLINE and the Cochrane Database, were searched in December 2021 using the keywords "Endometrial neoplasms," "Endometrial hyperplasia," "Endometrial intraepithelial neoplasia," "Fertility preservation," "Progestins," AND "Recurrence." Cases describing progestin re-treatment for recurrent EIN, AH and EC were compared with cases that underwent conventional hysterectomy. The primary outcomes were survival and disease recurrence, and the secondary outcome was pregnancy. After screening 238 studies, 32 with results for recurrent treatment were identified. These studies included 365 patients (270 received progestin re-treatment and 95 underwent hysterectomy). Most progestin re-treatment involved medroxyprogesterone acetate or megestrol acetate (94.5%). Complete remission (CR) following progestin re-treatment was achieved in 219 (81.1%) cases, with 3-, 6- and 9-month cumulative CR rates of 22.8%, 51.7% and 82.6%, respectively. Progestin re-treatment was associated with higher risk of disease recurrence than conventional hysterectomy was (odds ratio [OR]=6.78; 95% confidence interval [CI]=1.99-23.10), and one patient (0.4%) died of disease. Fifty-one (14.0%) women became pregnant after recurrence, and progestin re-treatment demonstrated a possibility of pregnancy (OR=2.48; 95% CI=0.94-6.58). This meta-analysis suggests that repeat progestin therapy is an effective option for women with recurrent EIN, AH and EC, who wish to retain their fertility.

Latest findings in chemotherapy

AbstractRadiotherapy and surgery are the two pivotal curative treatments for cervical cancer. Although cervical cancer is relatively sensitive to chemotherapy, chemotherapy is not included in the curative treatment of cervical cancer and has a role in limited medical conditions. Chemotherapy used to treat cervical cancer can be divided into four categories: (1) preceding chemotherapy (neoadjuvant chemotherapy) to augment the effects of radical therapy (surgery or radiation therapy), (2) chemotherapy administered concurrently with radiation therapy, and (3) adjuvant chemotherapy administered after radical therapy. In addition, (4) chemotherapy is used to prolong survival and alleviate symptoms in patients who cannot be radically cured. Recently, molecular targeted agents, angiogenesis inhibitors, and immune checkpoint inhibitors have been incorporated into existing chemotherapy regimens. This review summarizes these trends along with the history of chemotherapy for cervical cancer.

Serum CA125 level as predictors of the efficacy of olaparib maintenance therapy for platinum‐sensitive relapsed ovarian cancer

AbstractAimOvarian cancer is a gynecological malignancy with a poor prognosis. For platinum‐sensitive relapsed ovarian cancer, maintenance therapy with poly‐ADP ribose polymerase (PARP) inhibitors after chemotherapy is considered; however, olaparib treatment does not always lead to sufficient progression‐free survival (PFS). This study aimed to identify factors that predict the efficacy of maintenance therapy using olaparib in platinum‐sensitive relapsed ovarian cancer.MethodsTwenty‐seven patients with platinum‐sensitive relapsed ovarian cancer, who received initial treatment and showed complete or partial response to prior chemotherapy at our hospital, were included. The primary outcome was the time from the end of previous platinum‐based chemotherapy to disease progression (PFS). The Kaplan–Meier method was used to generate time‐to‐event curves for PFS; multivariate analysis was performed using the Cox proportional hazards regression model.ResultsThe median PFS was 12 months (95% confidence interval [CI]: 8.3–15.8). Before olaparib administration, the median PFS was 12 months in the <4.1 neutrophil‐to‐lymphocyte ratio group and 4 months in the ≥4.1 group, with PFS being significantly better in the <4.1 group (log‐rank: p = 0.023). When comparing serum cancer antigen 125 (CA125) levels, the median PFS was 13 months in the <18 U/mL group and 6 months in the >18 U/mL group (log‐rank: p = 0.022). Multivariate Cox regression analysis revealed that CA125 was the factor affecting PFS (hazard ratio: 4.85; 95% CI: 1.53–15.38).ConclusionsSerum CA125 levels at olaparib initiation in patients with platinum‐sensitive relapsed ovarian cancer may predict PFS as an effect of maintenance therapy using olaparib to treat recurrent disease.

Validation of HPV triage in cytology-based cervical cancer screening for ASC-US cases using Japanese data

In Japan, cervical cancer screening consists of a cytology examination performed once every 2 years. We verified whether the risk of cervical intraepithelial neoplasia (CIN) 3 disease or higher (CIN3+) was equivalent to that of cytology negative cases (negative for intraepithelial lesion or malignancy [NILM]) for patients with a cytological diagnosis of "atypical squamous cells of undetermined significance (ASC-US)" who tested negative for human papillomavirus (HPV). Data from a total of 22,925 cases who had undergone cervical cancer screening at least twice or who had completed follow-up examinations after cervical screening at a single facility between April 2013 and April 2018 were analyzed. The cumulative incidence of CIN3+ was calculated for each category of initial cytology finding and HPV result (NILM, > ASC-US, ASC-US/HPV (unknown), ASC-US/HPV The hazard ratio for the cumulative incidence of CIN3+ in 2 years relative to that for NILM cases was 2.7 (95% confidence interval=1.0-7.8) for > ASC-US cases, 0.5 (0.1-1.7) for ASC-US/HPV (unknown), 0.8 (0.3-2.4) for ASC-US/HPV Because the cumulative incidence of CIN3+ at 2 years for the ASC-US/HPV

Quality indicators for endometrial cancer care in Japan

The incidence and mortality rates of endometrial cancer are increasing globally, including in Japan. Quality of cancer care is promoted through guideline adherence. This study aimed to establish quality indicators (QIs) for endometrial cancer and explore the factors contributing to treatment nonadherence. QIs and pattern-of-care indicators (PCIs) were developed using the Research and Development/University of California Los Angeles modified Delphi method. QIs reflect desirable healthcare patterns, whereas PCIs address treatment areas with lacking evidence. Data from the Hospital-Based Cancer Registry and Diagnosis Procedure Combination Survey were used. Patients diagnosed or treated between January 1 and December 31, 2020 were included. The reasons for nonadherence were collected. Logistic regression was used to analyze the factors influencing adherence, including age, body mass index, comorbidities, facilities, and recurrence risk. Of the 35 proposed QI candidates, 8 QIs and 9 PCIs were selected, predominantly focusing on surgical aspects. Adherence rates varied, with peritoneal lavage cytology being the highest (93.1%), and postoperative hormone replacement therapy (HRT) for patients aged <45 years being the lowest (30.9%), when focusing on process indicators. Reasons for nonadherence included patient preference and medical comorbidities as significant factors. Multivariate analysis highlighted age, clinical stage, and Barthel index as significant contributors to nonadherence. We developed QIs to comprehensively assess endometrial cancer treatment. Adherence rates are favorable; however, HRT has a low adherence rate. Factors leading to nonadherence include advanced age and incomplete activities of daily living, particularly in advanced stages.

Japan Society of Gynecologic Oncology 2023 guidelines for treatment of uterine body neoplasm

The Japan Society of Gynecologic Oncology (JSGO) guideline for the treatment of uterine body neoplasm are revised from the 2018 guideline. This guideline aimed to provide standardized care for uterine body neoplasm, indicate appropriate current treatment methods for uterine body neoplasm, minimize variances in treatment methods among institutions, improve disease prognosis and treatment safety, reduce the economic and psychosomatic burden on patients by promoting the performance of appropriate treatment, and enhance mutual understanding between patients and healthcare professionals. The guidelines were prepared through the consensus of the JSGO guideline committee, based on a careful review of evidence from the literature searches and the medical health insurance system and actual clinical practice situations in Japan. The main features of the 2023 revision are as follows: 1) The Guidelines Formulation Committee members were asked to understand Minds' medical guideline development method in advance. 2) The clinical question (CQ) was changed to Patient, Intervention, Comparison, Outcome format as much as possible. 3) Introduced the "body of evidence," which summarizes the results of research reports collected for the CQs by outcome and study design, and the strength of evidence for each body of evidence was rated from levels A to D. 4) Introduction of systematic reviews in some CQs. 5) The strength of evidence, the balance of benefits and harms, value and hope for patients, and clinical applicability were considered while drafting recommendations. Herein, we present the English version of the JSGO guidelines 2023 for the treatment of uterine body neoplasm.

Successful Multidisciplinary Management of Uterine Carcinoma Treated With Chemotherapy Under Mechanical Ventilation

ABSTRACT We report a rare case of stage IVB endometrial carcinoma complicated by respiratory failure requiring mechanical ventilation. A 61‐year‐old woman with severe obesity developed bilateral pleural effusions and was admitted to the intensive care unit (ICU) for respiratory management. Because the organ failure was considered primarily tumor‐related and hepatic and renal functions were preserved, weekly paclitaxel–carboplatin chemotherapy was initiated under mechanical ventilation through close multidisciplinary collaboration. The treatment was effective, leading to improvement in the pleural effusions and oxygenation, and the patient was successfully extubated and discharged after 4 months of hospitalization. Although the disease eventually progressed, the chemotherapy administered in the ICU achieved temporary tumor control and functional recovery. This case suggests that ICU‐based chemotherapy for gynecologic malignancies, while nonstandard, may be feasible and beneficial in carefully selected patients with preserved organ function and potentially reversible, tumor‐related organ failure.