A 34-year-old woman with cerebral palsy was admitted to our hospital because of increased spasticity. She showed spastic quadriparesis with partially inhibited range of motion of the lower limbs. Her modified Ashworth Score (MAS) was 2 for the upper limbs and 3 for the lower limbs. Radiography showed mild scoliosis, but magnetic resonance imaging did not show any compression of the spinal cord. An abdominal computed tomography scan revealed urinary retention and a large bladder diverticulum. A urological assessment was performed, and an indwelling catheter was placed in the bladder. In addition to urological management, non-invasive spasticity management was performed, and her MAS was reduced to 1＋and 2 for the upper and lower limbs, respectively. After these treatments, the patient was able to resume self-care activities.

Cervical, endometrial, and ovarian cancers, have both high morbidity and mortality among the gynecologic malignant tumors in Japan. The present study was conducted using both the population-based cancer registry and the gynecologic cancer registry to elucidate the characteristics of gynecologic malignant tumors in Japan. Based on nationwide estimates from the population-based cancer registry in Japan, the morbidities and mortality of cervical, endometrial, and ovarian cancers were obtained and used for analysis. Clinicopathologic factors for cervical cancer, endometrial cancer, ovarian cancer, including age, clinical stage, postsurgical stage, histological type, therapeutic strategy, and prognosis were retrieved from the gynecologic cancer registry published by the Japan Society of Obstetrics and Gynecology and used for analysis. The morbidities of cervical, endometrial, and ovarian cancers were 10,908, 13,606, and 9,384 women in 2012, respectively. The prevalence of endometrial cancer has significantly and consistently been increasing and represents the most common gynecologic malignant tumor in Japan. The mortalities of cervical, endometrial, and ovarian cancers were 2.1, 1.3, and 3.2 per 100,000 in 2012, respectively. In 2014, 52.2% of cervical cancer patients were classified as stage I, 22.5% as stage II, 10.2% as stage III, and 11.2% as stage IV. In addition, 71.9% of endometrial cancer patients were classified as stage I, 6.0% as stage II, 13.3% as stage III, and 7.5% as stage IV. Finally, 43.2% of ovarian cancer patients were classified as stage I, 9.1% as stage II, 27.6% as stage III, and 7.2% as stage IV. Twelve point five percent of ovarian cancer patients received neoadjuvant chemotherapy.
Drug Therapy ; Endometrial Neoplasms ; Female ; Genital Neoplasms, Female ; Gynecology ; Humans ; Japan* ; Mortality ; Obstetrics ; Ovarian Neoplasms ; Prevalence ; Prognosis ; Registries ; Uterine Cervical Neoplasms

Objective: International Federation of Gynecology and Obstetrics (FIGO) staging for ovarian, fallopian tube, and peritoneal cancers was revised in 2014. The aim of this study is to clarify whether the revised FIGO2014 staging reflects the prognosis of patients with ovarian cancer by histological type in Japan. Methods: We extracted 9,747 patients who were diagnosed with ovarian cancer since 2004 until 2008 and who could be classified into appropriate stages from the Gynecologic Cancer Registry of Japan Society of Obstetrics and Gynecology. These cases were analyzed after revision to FIGO2014 based on the pTNM classification. Results: Among stage I, the 5-year overall survival rate (5y-OS) in FIGO2014 was 94.9% in stage IA, 92.3% in stage IC1, 86.1% in IC2, and 84.9% in IC3 with significant differences between stages IA and IC1 (p=0.012), IC1 and IC2 (p<0.001). There was a significant difference between stages IA and IC1 in clear cell and mucinous carcinoma but not in serous and endometrioid carcinoma. Among stage III, the 5y-OS was 75.6% in stage IIIA1, 68.9% in IIIA2, 58.6% in IIIB, and 44.4% in IIIC, with significant differences between stages IIIA2 and IIIB (p=0.009), IIIB and IIIC (p<0.001). Among stage IV, the 5y-OS was 43.1% in stage IVA *and 32.1% in IVB with a significant difference (p=0.002). Conclusion The results suggest that changes in classification for stage III and stage IV are appropriate, but the subclassification for stage IC might be too detailed. There was a discrepancy of prognosis by histological type between stage IA and IC1.

OBJECTIVE: Reports on the repeated administration of medroxyprogesterone acetate (MPA) for intrauterine recurrence after fertility-preserving therapy for atypical endometrial hyperplasia (AEH) and early grade 1 endometrioid carcinoma (G1) are lacking. We aimed to clarify the outcomes of repeated MPA therapy in cases of intrauterine recurrence after fertility-preserving therapy with MPA against AEH/early G1. METHODS: Patients with AEH or stage IA well-differentiated endometrioid carcinoma without myometrial invasion who underwent first-line MPA therapy for primary lesions or intrauterine recurrence were divided into initial treatment and repeated treatment groups (162 and 82 patients, respectively). Oral MPA administration (400−600 mg/day) was continued until pathological tumor disappearance. Data regarding clinicopathological factors, adverse events, and outcomes following the initial and repeated hormonal treatments were extracted from medical records and analyzed. RESULTS: Complete response rates in the initial and repeated treatment groups were 98.5% and 96.4%, respectively, among patients with AEH, and were 90.7% and 98.1%, respectively, among patients with G1. In the initial treatment group, 5-year recurrence-free survival (RFS) rates were 53.7% and 33.2% among patients with AEH and G1, respectively. In the repeated treatment group, RFS rates were 14.0% and 11.2% among patients with AEH and G1, respectively. Among patients with AEH, the pregnancy rate tended to be lower in the repeated treatment group than in the initial treatment group (11.1% vs. 29.2%; p=0.107), while no significant group difference was observed among patients with G1 (20.8% vs. 22.7%). CONCLUSION: Repeated treatment is sufficiently effective for intrauterine recurrence after hormonal therapy for AEH/early G1.
Carcinoma, Endometrioid ; Endometrial Hyperplasia* ; Endometrial Neoplasms* ; Female ; Fertility Preservation ; Fertility* ; Hormone Replacement Therapy ; Humans ; Medical Records ; Medroxyprogesterone Acetate* ; Medroxyprogesterone* ; Pregnancy Rate ; Recurrence

Carcinosarcoma ; Choriocarcinoma ; Conflict of Interest ; Endometrial Neoplasms ; Female ; Gestational Trophoblastic Disease ; Humans ; Japan ; Pharmacists ; Pregnancy ; Sarcoma ; Trophoblasts

Objective: The Japan Society of Gynecologic Oncology published the first guidelines for the treatment of cervical cancer in 2007. The aim of this research was to evaluate the influence of the introduction of the first guideline on clinical trends and outcomes of patients with earlystage cervical cancer who underwent surgery. Methods: This analysis included 9,756 patients who were diagnosed based on the pathological Tumor-Node-Metastasis (pTNM) classification (i.e., pT1b1, pT1b2, pT2b and pN0, pN1, pNX) and received surgery as a primary treatment between 2004 and 2009. Data of these patients were retrospectively reviewed, and clinicopathological trends were assessed.The influence of the introduction of the guideline on survival was determined by using a competing risk model. Results: For surgery cases, the estimated subdistribution hazard ratio (HR) by the competing risk model for the influence of the guideline adjusted for age, year of registration, pT classification, pN classification, histological type, and treatment methods was 1.024 (p=0.864). Following the introduction of the first guideline in 2007, for patients with lymph node metastasis, the use of chemotherapy (CT) as a postsurgical therapy increased, whereas that of concurrent chemoradiotherapy (CCRT)/radiotherapy (RT) decreased (p<0.010). For pN1 cases, the estimated subdistribution HR by the competing risk model for the influence of the guideline was 1.094 (p=0.634). There was no significance in the postsurgical therapy between CT and CCRT/RT (p=0.078). Conclusions Survival of surgical cases was not improved by the introduction of the guidelines. It is necessary to consider more effective postsurgical therapy for high-risk earlystage cervical cancer.

Objective: Associations between hospital treatment volume and survival outcomes for women with 3 types of gynecologic malignancies, and the trends and contributing factors for high-volume centers were examined. Methods: The Japan Society of Obstetrics and Gynecology tumor registry databased retrospective study examined 206,845 women with 80,741, 73,647, and 52,457 of endometrial, cervical, and ovarian tumor, respectively, who underwent primary treatment in Japan between 2004 and 2015. Associations between the annual treatment volume and overall survival (OS) for each tumor type were examined using a multivariable Cox proportional hazards model with restricted cubic splines. Institutions were categorized into 3 groups (low-, moderate-, and high-volume centers) based on hazard risks. Results: Hazard ratio (HR) for OS each the 3 tumors decreased with hospital treatment volume. The cut-off points of treatment volume were defined for high- (≥50, ≥51, and ≥27), moderate- (20–49, 20–50, and 17–26), and low-volume centers (≤19, ≤19, and ≤16) by cases/year for endometrial, cervical, and ovarian tumors, respectively. Multivariate analysis revealed younger age, rare tumor histology, and initial surgical management as contributing factors for women at high-volume centers (all, p<0.001). The proportion of high-volume center treatments decreased, whereas low-volume center treatments increased (all p<0.001). Treatment at high-volume centers improved OS than that at other centers (adjusted HR [aHR]=0.83, 95% confidence interval [CI]=0.78–0.88; aHR=0.78, 95% CI=0.75–0.83; and aHR=0.90, 95% CI=0.86–0.95 for endometrial, cervical, and ovarian tumors). Conclusion Hospital treatment volume impacted survival outcomes. Treatments at high-volume centers conferred survival benefits for women with gynecologic malignancies. The proportion of treatments at high-volume centers have been decreasing recently.

Objective: Regional lymph node (LN) dissection is a standard surgical procedure for endometrial cancer, but there is currently no clear consensus on its therapeutic significance. We aimed to determine the impact of regional LN dissection on the outcome of endometrial cancer. Methods: Study subjects comprised 36,813 patients who were registered in the gynecological tumor registry of the Japan Society of Obstetrics and Gynecology, had undergone initial surgery for endometrial cancer between 2004 and 2011, and whose clinicopathological factors and prognosis were appropriate for our investigation. The following clinicopathological factors were obtained from the registry: age, surgical stage classification, Union for International Cancer Control tumor, node, metastasis classification, histological type, histological differentiation, presence or absence of LN dissection, and postoperative treatment. We retrospectively analyzed the clinicopathological factors and therapeutic outcomes for patients with endometrial cancer. Results: Analysis of all subjects showed that the group that underwent LN dissection had a significantly better overall survival than the group that did not undergo dissection. Analysis based on stage showed similar results across groups, except for stage Ia. Analysis based on stage and histological type showed similar results across groups, except for stage Ia endometrial carcinoma G1 or Ia G2. Multivariate analysis of prognostic factors indicated that LN dissection is an independent prognostic factor and that it has a greater impact on prognosis than adjuvant chemotherapy. Conclusion Despite the limitations of a retrospective study with some biases, the results suggest that LN dissection in endometrial cancer has a prognostic effect.

Objective: The aim of this study was to establish criteria that would indicate whether fertility preservation therapy would likely be safe for patients aged 40 years or less with endometrioid endometrial cancer based on their DNA methylation profile. Methods: Forty-nine fresh-frozen tissue samples from patients with endometrial cancer from an initial cohort and 31 formalin-fixed paraffin-embedded tissue samples from a second cohort were subjected to genome-wide DNA methylation analysis using the Infinium MethylationEPIC BeadChip. Results: Epigenomic clustering of early-onset endometrial cancer was correlated with the widely used recurrence risk classification. Genes showing differences in DNA methylation levels between the low-recurrence-risk category and intermediate- and high-risk categories were accumulated in pathways related to fibroblast growth factor and nuclear factor-κB signaling. DNA hypomethylation and overexpression of ZBTB38 were frequently observed in the low-risk category. Eight hundred thirty-one marker CpG probes showed area under the curve values of >0.7 on the receiver operating characteristic curve for discrimination of patients belonging to the low-risk category. By combining marker CpG sites, seven panels for placing patients into the low-risk category with 91.3% or more sensitivity and specificity in both the initial and second cohorts were established. Conclusions DNA methylation diagnostics criteria using up to 6 of 8 CpG sites for LPP, FOXO1, RNF4, EXOC6B, CCPG1, RREB1 and ZBTB38 may be applicable to recurrence risk estimation for patients aged 40 years or less with endometrial cancer, regardless of tumor cell content, even if formalin-fixed paraffin-embedded biopsy or curettage materials are used.

The Fourth Edition of the Guidelines for Treatment of Uterine Body Neoplasm was published in 2018. These guidelines include 9 chapters: 1. Overview of the guidelines, 2. Initial treatment for endometrial cancer, 3. Postoperative adjuvant therapy for endometrial cancer, 4. Post-treatment surveillance for endometrial cancer, 5. Treatment for advanced or recurrent endometrial cancer, 6. Fertility-sparing therapy, 7. Treatment of uterine carcinosarcoma and uterine sarcoma, 8. Treatment of trophoblastic disease, 9. Document collection; and nine algorithms: 1-3. Initial treatment of endometrial cancer, 4. Postoperative adjuvant treatment for endometrial cancer, 5. Treatment of recurrent endometrial cancer, 6. Fertility-sparing therapy, 7. Treatment for uterine carcinosarcoma, 8. Treatment for uterine sarcoma, 9. Treatment for choriocarcinoma. Each chapter includes overviews and clinical questions, and recommendations, objectives, explanation, and references are provided for each clinical question. This revision has no major changes compared to the 3rd edition, but does have some differences: 1) an explanation of the recommendation decision process and conflict of interest considerations have been added in the overview, 2) nurses, pharmacists and patients participated in creation of the guidelines, in addition to physicians, 3) the approach to evidence collection is listed at the end of the guidelines, and 4) for clinical questions that lack evidence or clinical validation, the opinion of the Guidelines Committee is given as a “Recommendations for tomorrow”.