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We examined the expression of the steroid and xenobiotic receptor (SXR) and evaluated its clinical significance in human epithelial ovarian carcinoma. One hundred forty-one cases were examined using immunohistochemistry for SXR with archival specimens. All cases were scored using a semi-quantitative histological scoring (HSCORE) method. Specimens with an HSCORE > 60 were regarded as SXR-positive. Various clinicopathologic variables were examined. SXR showed significant differences in age, histology, grade, ERα and PR. SXR was detected in 35 of 141 (24.8%) ovarian cancer tissues. There was a statistically significant negative correlation between SXR-positive status and both disease-free survival and overall survival ( P= 0.0415 and 0.0316, respectively), independent of stage ( P= 0.0167 and 0.021, respectively). In multivariate analysis, SXR was a statistically independent risk factor for both disease-free survival and overall survival ( P= 0.049 and 0.0354). Our results support an association of SXR between ERα and PR in epithelial ovarian cancers. Our data suggest that SXR is a prognostic factor in epithelial ovarian cancer and may represent a useful marker to identify patients at risk of recurrence or death. [ABSTRACT FROM AUTHOR]

Background. In the present study, we conducted a multicenter retrospective analysis to elucidate the prognostic significance of second-look laparotomy (SLL) in early-stage epithelial ovarian cancer that was confirmed by complete surgical exploration. Methods. In July 2001, 12 Japanese institutions received questionnaires regarding patients with early-stage epithelial ovarian cancer and SLL. Eligibility criteria included patients with stage I or II epithelial ovarian cancer who were surgically diagnosed between January 1988 and December 1997. Data were collected regarding age, performance status, tumor histologic subtype, stage, preoperative carbohydrate antigen (CA) 125 level, results of SLL if performed, recurrence, disease-free survival, and overall survival. Survival analyses and comparisons were performed by univariate methods. Results. There were 87 patients who met the eligibility criteria. There were no significant differences in the back- grounds of patients who had had SLL (n = 30) and the non-SLL group (n = 57). Of the 30 SLL-group patients, 28 had negative SLL findings and 2 had positive findings. Six and 5 patients in the SLL group and the non-SLL group, respectively, had recurrence (P = 0.177), and 4 patients in the SLL group had a recurrence after ‘negative’ SLL findings. There was no significant difference between the two groups for either overall (P = 0.73) or disease-free survival (P = 0.273). On univariate analysis, only clear-cell histology was associated with a poor prognosis in early-stage epithelial ovarian cancer (P = 0.031). Conclusion. SLL is not beneficial for early-stage epithelial ovarian cancer. More favorable outcomes will be achieved for early-stage patient with the improvement of treatment for clear-cell adenocarcinoma. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the impact of nerve preservation confirmed by intraoperative electrical stimulation (IES) on subjective symptoms of urinary and sexual function in uterine cervical cancer patients who underwent radical hysterectomies. This study included 85 patients who underwent type C radical hysterectomy with IES. Pelvic splanchnic nerve preservation with IES after hysterectomy (nerve-stimulation positive group) was confirmed in 61 women and 24 women did not have nerve preservation (negative group). Urinary function was assessed with the Overactive Bladder Symptom Score (OABSS), International Prostate Symptom Score (IPSS), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaires. Sexual function was surveyed using the Female Sexual Function Index (FSFI). Longitudinal changes in those scores according to response to nerve-stimulation were evaluated using a generalized estimating equation. IPSS quality of life (QOL) scores were significantly better in the nerve-stimulation positive group compared with the scores in the negative group until 12 months after surgery, whereas OABSS, IPSS total, IPSS voiding, and ICIQ-SF scores evaluating urinary symptoms were not significantly different between the two groups. FSFI scores were better in the nerve-stimulation positive group 36 months after surgery compared with the scores in the negative group. In this study, we assessed self-reported urinary and sexual symptoms after nerve-sparing radical hysterectomy (NSRH) with IES in the long term. We demonstrated that nerve-sparing significantly reduced distress associated with QOL until 1 year, improved urinary storage symptoms at 2 years, and sexual symptoms 3 years after surgery.

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., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Advantages of lymphadenectomy for early stage endometrial cancer remain controversial. Lymphadenectomy had been routinely omitted for patients aged ≥ 70 years at our institute if lymph node metastasis was unsuspected due to an increased risk of peri- and postsurgical complications. Since 2013, with the introduction of minimally invasive surgery and considering the heterogeneous medical conditions, we started performing lymphadenectomy in patients who were considered well-tolerated. We retrospectively investigated our clinical database to assess the effect of lymphadenectomy in older patients with early stage endometrial carcinoma. Patients aged ≥ 70 years, preoperatively diagnosed with stage I endometrial carcinoma, and who underwent lymphadenectomy between 2013 and 2021 at Tohoku University Hospital were included in the lymphadenectomy group (n = 33), whereas patients who underwent surgery without lymphadenectomy before the end of 2012 were included in the no-lymphadenectomy group (n = 49). Clinical parameters and patient outcomes, such as disease-free survival (DFS) and disease-specific survival (DSS), were compared. The median age was significantly higher and fewer patients received adjuvant chemotherapy in the no-lymphadenectomy group. Neither DSS nor DFS differed significantly between the two groups. Five-year-DFS rates were 77.2% and 82.5% and 5-year-DSS rates were 89.7% and 97.8% for the lymphadenectomy and no-lymphadenectomy groups, respectively. No significant differences were observed in the subsequent survival analysis by substage, histological subtype, or risk of recurrence. Our results suggest that the indications for lymphadenectomy in older patients should be individually optimized according to the risk of recurrence and postoperative complications.

Objective: This multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers., Methods: Surgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-μm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance., Results: A total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961-0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819-0.973) and 0.989 (95% CI: 0.973-0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance., Conclusions: The OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study investigated the usefulness of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) in distinguishing metastasis of pelvic sentinel lymph nodes (SLNs) in patients with gynecological cancer. We examined 74 SLNs of patients with endometrial cancer (n = 26) and cervical cancer (n = 11). Patients underwent US and CEUS followed by SLN biopsy; US and CEUS results were evaluated visually and quantitatively and compared between pathological metastasis-negative and -positive groups. To support CEUS results, the microvessel density of SLNs was evaluated immunohistochemically. Seventeen positive and 40 negative SLNs were evaluable. Margin and enhancement patterns by visual assessment revealed significant differences (p = 0.046 and 0.022, respectively). In quantitative time-intensity curve analyses, the weakest peak intensities (PI min ), PI ratio and PI difference indicated significant differences (p = 0.045, p < 0.001 and p < 0.001, respectively). The areas under the receiver operating characteristic curves (AUCs) were 0.64, 0.82 and 0.83, respectively. The most effective PI ratio from the AUC was 1.3 (sensitivity = 82%, specificity = 70%), and the PI difference from the AUC was 20 (sensitivity = 88%, specificity = 70%). Microvessel density was significantly lower in metastatic lesions than in other areas. The quantitative analysis of CEUS seemed to be a reasonable method for distinguishing lymph node metastasis in patients with gynecological cancer., Competing Interests: Conflict of interest disclosure The authors declare that there is no conflict of interest with any financial organization, corporation or individual that can inappropriately influence this work., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Sentinel lymph node (SN) biopsy is essential for evaluating survival and minimal treatment-related morbidity associated with cervical, endometrial, and vulvar cancer in Japan. As such, our aim in this study was to evaluate the current practice pattern of using SN biopsy for cervical, endometrial, and vulvar cancer in Japan., Methods: We deployed a 47-question survey on the use of SN biopsy for gynecological cancers to 216 gynecological oncology training facilities. The survey included information on the use of SN biopsy for uterine (cervical and endometrial) and vulvar cancers; details on the type, timing, and concentration of tracers used; surgical approach used for SN biopsy; method of biopsy and pathological examination; and facilities' experience with clinical research on SN biopsy., Results: The response rate was 84% (181/216), with 40 facilities (22%) having experience in SN biopsy for gynecological cancers, 34 (85%) for uterine cancers, and 15 (37%) for vulvar cancers. Radioisotope, indocyanine green (ICG), and blue dyes were available for the detection of uterine cancers in 21 (52%), 25 (62%), and 19 (48%) facilities and for vulvar cancers in 9 (22%), 3 (7%), and 11 (27%) facilities, respectively. Thirty-four facilities (85%) used intraoperative frozen section procedure for diagnosis when possible, with 24 (71%) of these facilities using 2-mm specimen cuts. Diagnosis included pathological examination (85%), immunostaining (57%), and one-step nucleic acid amplification (5%)., Conclusion: Increasing research evidence, providing insurance coverage for radioisotope tracers, and increasing the availability of training are expected to increase the use of SN biopsy in Japan.

Background: Vulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese., Objective: The JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan., Methods: The guideline was created according to the basic principles in creating the guidelines of JSGO., Results: The guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget's disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions., Conclusion: Overall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases.

We retrospectively evaluated the clinical characteristics of a rare clinical condition of International Federation of Gynecology and Obstetrics (FIGO) stage III and IV squamous cell carcinomas arising from mature cystic teratoma of the ovary between October 1999 and September 2010 at member institutions of the Tohoku Gynecologic Cancer Unit. A total of nine cases (eight FIGO stage III and one FIGO stage IV) were included in this survey. The patients' median age was 56 years (range 46-74 years), and the median tumor diameter was 140 mm (range 95-250 mm). Five of eight patients were positive for cancer antigen (CA)-125, six of eight were positive for CA19-9, four of seven were positive for the carcinoembryonic antigen, and eight of nine were positive for squamous cell carcinoma antigen. Eight patients received postoperative therapy (five underwent chemotherapy, two underwent concurrent chemoradiotherapy, and one underwent radiation therapy alone). Two patients who received complete surgery and concurrent chemo radiotherapy achieved disease-free survival. The median overall survival was 8.9 months. Univariate analysis showed that both the patients' age (<50 years or ≥50 years) and maximum diameter of the residual tumor (<1 cm or ≥1 cm and none or persistent) did not predict the patients' prognosis. These results suggest that complete surgery should be performed because disease-free survival was observed only in patients with no residual tumor, similar to the previous findings of large number retrospective study., Competing Interests: The authors of this article declare no conflict of interest.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparative ethical standards. For this type of study formal consent in not required.Informed consent was obtained from all individual participants included in the study.

Background: This study aimed to evaluate surgical, pregnancy, and prognostic outcomes of radical abdominal trachelectomy (RAT) for Japanese patients with early-stage cervical cancer., Methods: This was a multicenter prospective cohort study conducted in member facilities of Tohoku Gynecologic Cancer Unit. Patients with FIGO 1A-1B1 squamous cell carcinoma were included., Results: A total of 42 patients were registered in this study, and all patients underwent planned RAT. The median stromal invasion and median horizontal spread of resected specimens were 4.6 (range 1.0-10.0) and 12.4 mm (range 3.0-28.0), respectively. The median surgical time and median blood loss were 304 min (range 233-611) and 848 mL (range 250-3984), respectively. Five patients (11.9 %) received blood transfusion. Five of 18 (27.8 %) patients who attempted to conceive achieved pregnancy, and 3 patients had healthy babies. However, all pregnancies required assisted reproductive technology with in-vitro fertilization and embryo transfer. Four patients (9.5 %) received postoperative adjuvant therapy, and 3 patients (7.1 %) developed disease recurrence., Conclusions: RAT may be safely performed for Japanese patients with FIGO 1A-1B1 squamous cell carcinoma of the cervix, even in educational medical facilities. However, less-invasive surgery should be considered more often to improve pregnancy outcomes.

Background: The aim of this study was to evaluate prognostic factors including efficacy of postoperative chemotherapy in Japanese patients with uterine carcinosarcoma., Methods: We conducted a retrospective survey of seven medical facilities in the Tohoku Gynecologic Cancer Unit., Results: A total of 45 patients who had undergone hysterectomy and bilateral salpingo-oophorectomy were enrolled. No significant difference was observed in overall survival according to patient age (≤ 50 years vs >50 years) or retroperitoneal lymphadenectomy (performed vs. not performed). However, the International Federation of Gynecology and Obstetrics stage (stage I/II vs stage III/IV) and postoperative chemotherapy (provided vs not provided) were significant prognostic factors in both univariate and multivariate analyses for the 25-month median follow-up period., Conclusions: Our results revealed that postoperative chemotherapy should be considered for all uterine carcinosarcoma stages in Japanese patients.

Objective: The purpose of this study was to examine the utility of the one-step nucleic acid amplification (OSNA) assay using cytokeratin (CK) 19 (KRT19) messenger RNA (mRNA) for the detection of sentinel lymph node (SLN) metastases in cervical cancer patients., Methods: To determine a cutoff value, KRT19 mRNA was assessed by OSNA assay using 239 lymph nodes (LNs) (217 histopathologically negative LNs and 22 positive LNs). A cutoff value was determined by statistical analysis of the copy numbers obtained by OSNA assay. Subsequently, performance evaluation of the OSNA assay (applying the cutoff value above) on 130 SLNs (32 patients) was used to investigate (through concordance) whether the OSNA assay exhibited diagnostic performance equivalent to the two-mm interval histopathological examination., Results: Two hundred fifty copies/μL of KRT19 mRNA in the OSNA assay appeared to be an optimal cutoff value. In performance evaluation of the OSNA assay, we identified five positive SLNs and 125 negative SLNs by OSNA assay using KRT19 mRNA, exhibiting 96.2% agreement with two-mm interval histopathological examination., Conclusions: Our results indicated that the KRT19 mRNA OSNA assay can detect LN metastases as accurately as two-mm interval histopathological examination and thus may be an effective additional or alternative method for a rapid intra-operative examination of SLNs in cervical cancer., (© 2013. Published by Elsevier Inc. All rights reserved.)

The estrogen pathway plays an important role in the etiology of human endometrial carcinoma (EC). We examined whether estrogen biosynthesis in the tumor microenvironment promotes endometrial cancer. To examine the contribution of stromal cells to estrogen signaling in EC, we used reporter cells stably transfected with the estrogen response element (ERE) fused to the destabilized green fluorescent protein (GFP) gene. In this system, the endometrial cancer stromal cells from several patients activated the ERE of cancer cells to a variable extent. The GFP expression level increased when testosterone, a substrate for aromatase, was added. The effect was variably inhibited by aromatase inhibitors (AIs), although the response to AIs varied among patients. These results suggest that GFP expression is driven by estrogen synthesized by aromatase in the endometrial cancer stromal cells. In a second experiment, we constructed an adenovirus reporter vector containing the same construct as the reporter cells described above, and visualized endogenous ERE activity in primary culture cancer cells from 15 EC specimens. The GFP expression levels varied among the cases, and in most primary tissues, ERE activities were strongly inhibited by a pure anti-estrogen, fulvestrant. Interestingly, a minority of primary tissues in endometrial cancer showed ERE activity independent of the estrogen-ER pathway. These results suggest that AI may have some therapeutic value in EC; however, the hormonal microenvironment must be assessed prior to initiating therapy.

Background: Occasionally a submucous myoma is sloughed off during the puerperium, but it is seldom that the initial location of the myoma is identified before its expulsion., Case: A 32-year-old, nulliparous woman with a cervical myoma underwent an elective cesarean section at 37 weeks. At surgery a cervical myoma was identified as not endophytic to the intrauterine cavity but exophytic to the uterine exterior and was left without any intervention. Part of the cervical myoma was sloughed off into the vagina after 16 days, and an abdominal myomectomy was performed for a refractory infection., Conclusion: Comparison with analogous cases following intervention indicates that myoma degeneration due to blood supply depletion, uterine contractions and endometrial sparseness must be important factors in this phenomenon. When these conditions are met, a shallow, intramural myoma could be sloughed off in the puerperium.

Purpose: In this study, we examined the promoter methylation status and expression of 14-3-3 sigma and evaluated its clinical significance in epithelial ovarian cancer., Experimental Design: Twelve ovarian cancer cell lines; 2 ovarian surface epithelial cell lines; and 8 normal, 8 benign, 12 borderline, and 102 ovarian cancer tissues were examined. Methylation-specific PCR, quantitative reverse transcription-PCR, and immunohistochemistry were used to evaluate methylation status and expression of 14-3-3 sigma gene and protein., Results: Among the 12 ovarian cancer cell lines, the presence of a methylated band was detected in seven cell lines. Median values of relative 14-3-3 sigma gene expression in cancers with methylation (3.27) were significantly lower than those without methylation (16.4; P < 0.001). Treatment of 5-aza-2'-deoxycitidine resulted in the demethylation of the promoter CpG islands and reexpression. All of the normal, benign, and borderline tissues were positive for 14-3-3 sigma protein, and in ovarian cancer tissues, 73.5% (75 of 102) were positive for 14-3-3 sigma protein and was almost consistent with methylation status. Negative immunoreactivity of 14-3-3 sigma was significantly correlated with high age and serous histology, high-grade, advanced-stage residual tumor of >2 cm, high serum CA125, high Ki-67 labeling index, and positive p53 immunoreactivity. 14-3-3 sigma immunoreactivity was significantly associated with overall survival (P = 0.0058)., Conclusions: Our findings suggest that 14-3-3 sigma is inactivated mainly by aberrant DNA methylation and that it may play an important role in the pathogenesis of epithelial ovarian cancer.