Yoichi Kobayashi

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.

Quality of care measurement for patients with ovarian cancer in Japan

Abstract Aim Quality of care is important to reduce disease progression, and improve both survival and quality of life. The Japan Society of Gynecologic Oncology has published treatment guidelines to promote standardized high‐quality care for ovarian cancer in Japan. We developed quality indicators based on the guideline recommendations and used them on large datasets of health service use to examine the quality of ovarian cancer care. Methods A panel of experts developed the indicators using a modified Delphi method. Adherence to each indicator was evaluated using data from a hospital‐based cancer registry of patients diagnosed in 2018. All patients receiving first‐line treatment at participating facilities were included. The adherence rates were returned to participating hospitals, and reasons for nonadherence were collected. A total of 580 hospitals participated, and the study examined the care received by 6611 patients with ovarian cancer and 1879 with borderline tumors using 11 measurable quality indicators. Results The adherence rate ranged from 22.6% for “Estrogen replacement within 6 months of operation” to 93.5% for “Bleomycin, etoposide, and cisplatin for germ cell tumor more than Stage II.” Of 580 hospitals, 184 submitted the reasons for nonadherence. Conclusions The quality of ovarian cancer care should be continuously assessed to encourage the use of best practices. These indicators may be a useful tool for this purpose.

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.

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.

Association of menopause, aging and treatment procedures with positive margins after therapeutic cervical conization for CIN 3: a retrospective study of 8,856 patients by the Japan Society of Obstetrics and Gynecology

The Japan Society of Obstetrics and Gynecology conducted a retrospective multi-institutional survey of patients who underwent cervical conization in Japan. This study aimed to determine the predictive factors for positive surgical margins in cervical intraepithelial neoplasia grade 3 (CIN 3) patients after therapeutic cervical conization and those for positive margins in patients who did not experience recurrence and did not undergo additional treatment. In 2009 and 2013, 14,832 patients underwent cervical conization at 205 institutions in Japan. Of these, 8856 patients who underwent therapeutic conization fulfilled the inclusion criteria. Their histologic findings and clinical outcomes were evaluated based on standard statistical procedures and clinical and demographic characteristics. Negative and positive margins were observed in 7,585 and 1,271 (14.4%) patients, respectively. The predictors of positive margins were menopausal status (p<0.001), loop electrosurgical excision procedure (p<0.001), and Shimodaira-Taniguchi (S-T) conization (p<0.001). Of 1,271 patients with positive margins, 1,060 underwent no additional treatment; among those 1,060 patients, 129 (12.2%) experienced recurrence. The predictors of positive margins in patients who did not undergo additional treatment and did not experience recurrence were age, parity, gravidity, S-T conization, and laser scalpel conization. Menopausal status and treatment procedures were associated with positive margins after therapeutic conization of CIN 3. It is important to understand the characteristics of treatment procedures and select an appropriate procedure for each case. For elderly or menopausal patients with positive margins, immediate additional treatment is recommended.

Comparison of treatment outcomes of surgery and radiotherapy, including concurrent chemoradiotherapy for stage Ib2-IIb cervical adenocarcinoma patients: a retrospective study

The study compared the treatment outcomes of surgery versus radiotherapy, including concurrent chemoradiotherapy, in stage Ib2-IIb cervical adenocarcinoma patients in Japan. Of 57,470 patients diagnosed with stage I-IV cervical cancer from January 2001-December 2011, 1,932 patients with stage Ib2-IIb cervical adenocarcinoma were initially treated by surgery or radiotherapy. The primary endpoint was 5-year overall survival (OS) in all and 614 propensity score-matched (PSM) patients (307 per group). We compared OS and prognosis factors based on age, primary stage, and treatment arm. In Japan, >80% (n=1,573) of stage Ib2-IIb cervical adenocarcinoma patients underwent surgery. The 5-year OS of surgery vs. radiotherapy groups were 82.1% (n=704) vs. 79.7% (n=59) (hazard ratio [HR]=1.494; 95% confidence interval [CI]=0.826-2.702; p=0.181) for stage Ib2, 76.6% (n=239) vs. 66.7% (n=54) (HR=1.679; 95% CI=0.986-2.858; p=0.053) for stage IIa, and 71.1% (n=630) vs. 58.9% (n=246) (HR=1.711; 95% CI=1.341-2.184; p65 years), treatment arm (radiotherapy), and stage IIb significantly affect OS in cervical adenocarcinoma patients. Surgery may be considered for <65-year-old patients with stage IIb adenocarcinoma.

Impact of adjuvant chemotherapy on the overall survival of patients with resectable bulky small cell neuroendocrine cervical cancer: a JSGO-JSOG joint study

The aim of this study was to review the clinicopathological characteristics of small cell neuroendocrine cervical cancer (SCNEC) and to identify the optimal treatment. The Japanese Society of Gynecologic Oncology conducted a retrospective cohort study of SCNECs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology between 2004 and 2015. All cases were modified and unified by International Federation of Gynecology and Obstetrics 2008 (Union for International Cancer Control 7th edition). There were 822 registered patients diagnosed with SCNEC from 2004 to 2015 which comprised 1.1% (822/73,698) of all uterine cervical cancer cases. Rates of lymph-node and distant metastasis were significantly higher in T1b2 (38.9% and 13.7%, respectively) than T1b1 (14.2% and 4.4%, respectively) (p4 cm in size had greater rates of lymph-node and distant metastasis when compared with tumors ≤4 cm. Adjuvant chemotherapy, rather than radiotherapy, may improve prognosis after surgery in T1bN1M0 SCNEC.

Sentinel node navigation surgery in cervical cancer: a systematic review and metaanalysis

Sentinel node navigation surgery (SNNS) is used in clinical practice for the treatment of cervical cancer. This study aimed to elucidate the appropriate sentinel lymph node (SLN) mapping method and assess the safety and benefits of SNNS. We searched the PubMed, Ichushi, and Cochrane Library databases for randomized controlled trials (RCT) and studies on SLN in cervical cancer from January 2012 to December 2020. Two authors independently assessed study quality and extracted data. We quantitatively analyzed the detection rate, sensitivity/specificity, and complications and reviewed information, including the survival data of SLN biopsy (SLNB) without pelvic lymphadenectomy (PLND). The detection rate of SLN mapping in the unilateral pelvis was median 95.7% and 100% and in the bilateral pelvis was median 80.4% and 90% for technetium-99 m (Tc) with/without blue dye (Tc w/wo BD) and indocyanine green (ICG) alone, respectively. The sensitivity and specificity of each tracer were high; the area under the curve of each tracer was 0.988 (Tc w/wo BD), 0.931 (BD w/wo Tc), 0.966 (ICG), and 0.977 (carbon nanoparticle). Morbidities including lymphedema, neurological symptoms and blood loss were associated with PLND. One RCT and five studies all showed SNNS without systematic PLND does not impair recurrence or survival in early-stage cervical cancer with a tumor size ≤ 2-4 cm. Both Tc w/wo BD and ICG are appropriate SLN tracers. SNNS can reduce the morbidities associated with PLND without affecting disease progression in early-stage cervical cancer.

Significance of histology and nodal status on the survival of women with early-stage cervical cancer: validation of the 2018 FIGO cervical cancer staging system

To assess the efficacy of the FIGO 2018 classification system for nodal-specific classifications for early-stage cervical cancer; specifically, to examine the impact of nodal metastasis on survival and the effect of postoperative treatments, according to histological subtypes. This society-based retrospective observational study in Japan examined 16,539 women with the 2009 FIGO stage IB1 cervical cancer who underwent primary surgical treatment from 2004 to 2015. Associations of cause-specific survival (CSS) with nodal metastasis and postoperative adjuvant therapy were examined according to histology type (squamous cell carcinoma [SCC], n=10,315; and non-SCC, n=6,224). The nodal metastasis rate for SCC was higher than that for non-SCC (10.7% vs. 8.3%, p<0.001). In multivariable analysis, the impact of nodal metastasis on CSS was greater for non-SCC tumors (adjusted-hazard ratio [HR], 3.11; 95% confidence interval [CI], 2.40-4.02) than for SCC tumors (adjusted-HR, 2.20; 95% CI, 1.70-2.84; p<0.001). Propensity score matching analysis showed significantly lower CSS rates for women with pelvic nodal metastasis from non-SCC tumors than from SCC tumors (5-year CSS rate, 75.4% vs. 90.3%, p<0.001). The CSS rates for women with nodal metastasis in SCC histology were similar between the postoperative concurrent chemoradiotherapy/radiotherapy and chemotherapy groups (89.2% vs. 86.1%, p=0.42), whereas those in non-SCC histology who received postoperative chemotherapy improved the CSS (74.1% vs. 67.7%, p=0.043). The node-specific staging system in the 2018 FIGO cervical cancer classification is applicable to both non-SCC tumors and SCC tumors; however, the prognostic significance of nodal metastases and efficacy of postoperative therapies vary according to histology.

Japan Society of Gynecologic Oncology 2022 guidelines for uterine cervical neoplasm treatment

The Japan Society of Gynecologic Oncology (JSGO) Guidelines 2022 for the Treatment of Uterine Cervical Cancer are revised from the 2017 guideline. This guideline aimed to provide standard care for cervical cancer, indicate appropriate current treatment methods for cervical cancer, minimize variances in treatment methods among institutions, improve disease prognosis and treatment safety, reduce the economic and psychosomatic burden of 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 gathered through the literature searches and the medical health insurance system and actual clinical practice situations in Japan. The guidelines comprise seven chapters and 5 algorithms. The main features of the 2022 revision are as follows: 1) added discussed points at the final consensus meeting; 2) revised the treatment methods based on the International Federation of Gynecology and Obstetrics 2018 staging system; 3) examined minimally invasive surgery based on Laparoscopic Approach to Cervical Cancer trial; 4) added clinical question (CQ) for treatments of rare histological types, gastric type, and small-cell neuroendocrine carcinoma; 5) added CQ for intensity-modulated radiation therapy; 6) added CQ for cancer genomic profiling test; and 7) added CQ for cancer survivorship. Each recommendation is accompanied by a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSGO Guidelines 2022 for the Treatment of Uterine Cervical Cancer.

The 2020 Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer

The fifth edition of the Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was published in 2020. The guidelines contain 6 chapters-namely, (1) overview of the guidelines; (2) epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (3) recurrent epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (4) borderline epithelial tumors of the ovary; (5) malignant germ cell tumors of the ovary; and (6) malignant sex cord-stromal tumors. Furthermore, the guidelines comprise 5 algorithms-namely, (1) initial treatment for ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (2) treatment for recurrent ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (3) initial treatment for borderline epithelial ovarian tumor; (4) treatment for malignant germ cell tumor; and (5) treatment for sex cord-stromal tumor. Major changes in the new edition include the following: (1) revision of the title to "guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer"; (2) involvement of patients and general (male/female) participants in addition to physicians, pharmacists, and nurses; (3) clinical questions (CQs) in the PICO format; (4) change in the expression of grades of recommendation and level of evidence in accordance with the GRADE system; (5) introduction of the idea of a body of evidence; (6) categorization of references according to research design; (7) performance of systematic reviews and meta-analysis for three CQs; and (8) voting for each CQ/recommendation and description of the consensus.

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.

Awareness and attitude toward cardio‐oncology among Japanese gynecologic oncologists in managing patients with endometrial cancer: The Japanese Gynecologic Oncology Group (JGOG) questionnaire surveys

AbstractAimThis study aimed to assess the awareness of the concept of “cardio‐oncology” and cardiovascular disease (CVD) in patients with endometrial cancer (EC) among the Japanese Gynecologic Oncology Group members.MethodsAn online anonymous survey, which consisted of questions about respondent attributes and cardio‐oncology, was conducted twice, in 2022 and 2024. During these surveys, guidelines for the treatment of uterine body neoplasm were published in July 2023.ResultsIn 2022, significantly numerous physicians were unaware of cardio‐oncology or the increased risk of developing CVD in patients with EC, and 25.3% of them answered that they had no idea about cardio‐oncology at all. However, in 2024, the percentage significantly dropped to 8.7%. The number of physicians who were aware that CVD is more common as the cause of death in patients with low‐grade EC than the cancer itself was significantly higher in 2024 than in 2022. Similarly, the number of physicians who were aware that the usage of platinum agents could become a risk factor for CVD was significantly higher in 2024. Furthermore, this study reported challenges in the collaboration between oncologists and primary care physicians in the region and in the provision of guidance for preventing metabolic syndrome.ConclusionJapanese Gynecologic Oncology Group members' awareness of cardio‐oncology was inadequate, but it seemed to be improving, especially after publishing the guideline for the treatment of uterine body neoplasm. Thus, raising awareness of cardio‐oncology and managing CVD risk in patients with EC are necessary to improve long‐term survival after cancer diagnosis.

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.