Published papers

Aim: The International Federation of Gynecology and Obstetrics (FIGO) revised the cervical cancer staging system in 2018. This study aims to validate the revised staging system in patients with tumors <2 cm in size who were classified as FIGO 2009 stage IB1. Methods: We evaluated 62 women with stage IB1 cervical cancer (FIGO 2009) who underwent radical hysterectomy as the initial treatment between November 2004 and August 2018 in our institution. The patients with FIGO 2009 stage IB1 and tumors <2 cm in size were enrolled. We reclassified their stage according to the FIGO 2018 staging system and analyzed their clinicopathological data retrospectively. Results: Twenty-five patients met the inclusion criteria. According to the FIGO 2018 classification, 9 (36.0%) patients were classified as stage IA, 13 (52.0%) as stage IB1, and 3 (12.0%) as stage IIIC, respectively. One (11.1%), six (46.2%), and three (100%) patients with lymphovascular space invasion were classified as stage IA, IB1, and IIIC, respectively. No significant differences were found in the 5-year overall survival or progression-free survival among the three stages. Conclusions: As many as 36.0% of patients classified as FIGO 2009 stage IB1 with a tumor <2 cm in size were classified as stage IA in the FIGO 2018 classification. For these cases, a treatment less invasive than radical hysterectomy or radiotherapy might be sufficient. Our results suggest that cervical cancer patients with tumors <2 cm should be carefully diagnosed by performing cervical conization and assessed the pathological findings before hysterectomy.

Background: Fertility preserving therapy using medroxyprogesterone acetate (MPA) is an important option for young patients with endometrial cancer or atypical endometrial hyperplasia (AEH). However, the effectiveness and feasibility of repeated MPA therapy for patients with intrauterine recurrence following initial MPA therapy is controversial. Only a few single-institution retrospective studies have been conducted on repeated MPA therapy, therefore, multicenter prospective studies for repeated MPA therapy are highly needed. The aim of this study is to assess whether repeated MPA therapy is effective and feasible for patients with intrauterine recurrence following initial MPA therapy. Methods: This is a prospective, single-arm, a multicenter phase II trial on repeated MPA therapy for intrauterine recurrence following fertility-preserving therapy for AEH or stage IA (the International Federation of Gynecology and Obstetrics [FIGO] 2008) non-myoinvasive endometrioid carcinoma grade 1. Patients are treated with oral MPA (500–600 mg/day). Pathologically assessment via dilation and curettage will be performed every 2 months until complete response. The major inclusion criteria are 1) intrauterine recurrence of AEH or stage IA (FIGO 2008) endometrioid carcinoma grade 1 without myometrial invasion or extrauterine spread confirmed by imaging tests after complete remission with the previous MPA therapy. 2) The number of recurrences should be up to twice. 3) histologically diagnosed as AEH or endometrioid carcinoma grade 1, 4) 20–42 years of age, and 5) strong desire and consent for fertility-sparing treatment. The primary endpoint is 2-year recurrence-free survival rate. A total of 115 patients will be enrolled from multiple institutions in Japan and Korea within 4 years and followed up for 2 years.

Objective: To clarify the role of radiotherapy for endometrial cancer. Methods: Data were analyzed for 39 247 patients with endometrial cancer registered with the Gynecologic Cancer Registry of the Japan Society of Obstetrics and Gynecology from 2004 to 2011. Results: The rates of 5-year overall survival (5y-OS) in the radiotherapy and surgery groups were 53.6% and 94.5% in stage I or II, and 15.5% and 67.5% in stage III or IV, respectively. The prognosis in the radiotherapy group was significantly poorer than that in the surgery group. In multivariate analysis, age, advanced stage, histological type, risk of recurrence, and initial radiotherapy were independent prognostic factors. The rates of 5y-OS with no adjuvant therapy, adjuvant chemotherapy, and adjuvant radiotherapy were 95.3%, 92.9%, and 87.1% for stage I or II, respectively, with significant differences among all groups (P < 0.001), and 60.0%, 70.4%, and 55.5% for stage III or IV, respectively, with significant differences of adjuvant chemotherapy with no adjuvant therapy (P < 0.001) and with adjuvant radiotherapy (P < 0.001). In multivariate analysis, age, advanced stage, histological type, lymphadenectomy, and adjuvant radiotherapy were independent prognostic factors. Conclusion: Patients treated with radiotherapy had a significantly poorer prognosis and the appropriate indication of radiotherapy for endometrial cancer requires further study.

Objectives: ARID1A mutation is frequently found in clear cell ovarian cancer (CCC) and endometrioid ovarian cancer (EC). Anti-PD-1 monotherapy has been found to have limited efficacy in epithelial ovarian cancer; however, anti-PD-1 therapy showed significant clinical benefit in some CCC. We sought to define the relationship of ARID1A mutation/ARID1A expression to the immunogenic profile of different histologic subtypes of ovarian cancer. Methods: We performed next-generation sequencing of 160 cancer-related genes. Also, we analyzed the immunohistochemical status of ARID1A, PD-L1, and CD8 with survival in different histologic subtypes of ovarian cancer in a total of 103 cases. Results: ARID1A mutation was found in 0% of the high-grade serous ovarian cancer (HGSC) (n = 36), 41.5% of the CCC (n = 41), 45.0% of the EC (n = 20), and 33.3% of the mucinous ovarian cancer (MC) (n = 6) cases. ARID1A loss was found in 19.4% of the HGSC, 75.6% of the CCC, 60.0% of the EC and 0% of the MC cases. ARID1A mutation was found to be associated with high PD-L1 (p < 0.001) or CD8 levels (p < 0.001) in CCC but not in other histologic subtypes. Meanwhile, ARID1A loss was associated with high PD-L1 or CD8 levels in CCC (p < 0.001) and HGSC (p < 0.001) but not in EC and MC. In addition, ARID1A mutation was associated with high tumor mutation burden in CCC (p = 0.006). Conclusions: ARID1A mutation/ARID1A expression is associated with immune microenvironmental factors in CCC but not in EC. ARID1A status can be a biomarker for selecting candidates for immune checkpoint blockade in CCC.

Aim: Tamoxifen (TAM) is widely used in adjuvant endocrine therapy for invasive breast cancer as a selective estrogen modulator, but this treatment has a risk of developing endometrial malignancy. However, hysteroscopic findings during or after TAM treatment are unclear. The aim of this study is to examine the association between hysteroscopic patterns and malignant histological findings during or after treatment with TAM. Methods: The subjects were patients who received TAM after surgery for breast cancer and underwent hysteroscopy at our institution from January 2016 to December 2019. Clinicopathological factors and hysteroscopic findings were collected from medical records and investigated retrospectively. Histologically, atypical endometrial hyperplasia, endometrial cancer, and carcinosarcoma were classified as malignant diseases. Results: A total of 26 patients were eligible for the study. Hysteroscopic findings included an irregular surface of the endometrium (n = 3, 11.5%), atypical vessels (n = 10, 38.5%), papillary structure (n = 3, 11.5%), and polypoid structure (n = 18, 69.2%). Histological examination revealed malignancy in six patients (23.0%). The percentage of atypical vessels in patients with malignancies was significantly higher than that in patients with a normal endometrium or benign lesion (100% vs. 20%, p = 0.0009). The sensitivity and specificity of atypical vessels in hysteroscopy for diagnosis of malignant diseases were 100% and 80%, respectively. Conclusions: Hysteroscopic findings of atypical vessels may be useful for prediction of malignant diseases in patients treated with TAM.

Brain metastasis from ovarian cancer is a very rare condition with a poor prognosis. However, due to its rarity, there is no established treatment strategy. We present a case series of brain metastasis with ovarian cancer, focusing on two long-term survivors treated with multimodal therapy. Among the nine cases, the median survival time after brain metastases was six months (range: 0–58 months). Eight patients had high-grade serous carcinoma (HGSC). Three of the four patients who underwent genetic testing tested positive for germline BRCA2 (gBRCA2) mutation. Two patients survived longer than 4 years after the diagnosis of brain metastases. Both of these patients received chemotherapy, radiation therapy, and olaparib, a molecularly targeted drug, as maintenance therapy. This case series suggests that patients with gBRCA2 mutation-positive HGSC may be at a high risk of developing brain metastases. A multidisciplinary approach, including PARP inhibitors, may improve the prognosis of patients with brain metastases from ovarian cancer.

Objective: Medroxyprogesterone acetate (MPA) is an effective fertility-preserving treatment for early endometrial cancer and atypical endometrial hyperplasia (AEH), and rarely leads to the development of extrauterine lesions (ELs). We aimed to clarify the characteristics of patients who developed ELs post-MPA therapy. Methods: We analyzed the clinicopathological factors and prognoses of 319 patients with endometrioid carcinoma grade 1 (EMG1) and AEH treated with MPA at our institution. All patients underwent imaging before MPA treatment to rule out ELs. Results: Seven patients (2.2%) with EMG1 showed EL after MPA treatment. Two patients developed EL during the initial treatment, 2 during repeated treatment, and 3 during follow-up. Two patients had peritoneal dissemination, 3 had regional lymph node metastasis, 1 had distant metastasis at the Virchow lymph node, and 1 had ovarian metastasis. ELs were diagnosed using imaging tests in 6 patients and elevated tumor markers in 3 (overlapping) patients. One patient was diagnosed with ELs pathologically after hysterectomy. Upon EL diagnosis, patients underwent standard treatment, including hysterectomy and chemotherapy, that was followed by a diagnosis of EMG1 for 5, EMG2 for 1, and EMG3 for 1 patient. One patient died 15 months after start of therapy and another died 119 months post-treatment initiation, while the others have been survived. Conclusion: Only 2.2% of all patients developed ELs post-MPA treatment, but some cases were fatal. It is essential to conduct imaging tests and screen for tumor markers during and after MPA treatment regularly and also when cancer progression is suspected.

Background: Japan’s health insurance covers multigene panel testing. This study aimed to determine the potential availability and utility of gene panel testing clinically in gynecologic oncology. Methods: We analyzed the characteristics of patients with gynecologic cancer who underwent gene panel testing using FoundationOne® CDx or OncoGuide™ NCC Oncopanel between November 2019 and October 2022. Results: Out of 102 patients analyzed, 32, 18, 43, 8, and 1 had cervical, endometrial, ovarian cancers, sarcoma, and vaginal cancer, respectively. Druggable gene alteration was found in 70 patients (68.6%; 21 with cervical cancer, 15 with endometrial cancer, 28 with ovarian cancer, 5 with sarcoma, and 1 with other). The most common druggable gene alteration was PIK3CA mutation (n = 21), followed by PTEN mutation (n = 12) and high tumor mutation burden (TMB-H) (n = 11). TMB-H was detected in 5 patients with cervical cancer, 5 with endometrial cancer, and 1 with endometrial stromal sarcoma. Eleven patients (10.8%) received molecularly targeted therapy according to their gene aberrations. Gene panel testing was mostly performed when the second-line treatment was ineffective. Of all 102 patients, 60 did not have recommended treatment, and 15 died or had worsened conditions before obtaining the test results. Conclusion: Through multigene panel testing, although many patients had druggable gene alterations, 10.8% of them received the recommended treatment. TMB-H was mainly observed in cervical/endometrial cancer, suggesting its potential as a therapeutic biomarker of immune checkpoint inhibitors. Furthermore, patients’ prognosis and performance status should be considered before performing the test.

Introduction: The significance of endometrial cytology in determining the therapeutic efficacy of medroxyprogesterone acetate (MPA) therapy is unclear. This study aimed to evaluate the clinical usefulness of endometrial cytology during MPA therapy. Methods: Overall, 77 patients who underwent dilatation and curettage (D&C) to evaluate the therapeutic efficacy of MPA therapy at our hospital between January 2018 and December 2019 were retrospectively analyzed. The results of D&C, cytological evaluation, and other clinicopathological factors were analyzed based on the patients' medical records. Results: The sensitivity and specificity of cytology were 61% and 92%, respectively, with D&C being the gold standard for diagnosis in 142 D&C/cytological examinations. Among patients with no residual disease on D&C, 5 (4%) had suspicious or positive cytology. Although MPA therapy was terminated in 3 of these patients, only 1 patient had early recurrence, and the frequency of recurrence was similar to that of patients who showed negative results in both D&C and cytology. Discussion/Conclusion: The sensitivity of endometrial cytology in determining the therapeutic effect of MPA therapy is low, and we confirmed that the omission of D&C is unacceptable. Our findings also suggested that the addition of cytological evaluation to D&C during MPA therapy had a low clinical significance.

Background: Olaparib maintenance therapy for platinum-sensitive relapsed ovarian cancer has been approved in Japan since April 2018. Here, we report the experience administering this therapy in our hospital, with the aim of evaluating efficacy and safety in the Japanese population. Methods: The study included 52 patients with platinum-sensitive relapsed ovarian, fallopian tube, and primary peritoneal cancer. All patients started olaparib at a dose of 300 mg twice daily. Information about treatment efficacy and adverse effects was collected retrospectively from medical records. Results: Median age was 58 years old (range: 33–80), and 82.7% of the patients were diagnosed with high-grade serous carcinoma. Sixteen patients (30.8%) possessed the BRCA1/2 pathogenic variant (15 germline and 1 tissue), 3 (5.8%) possessed variants of unknown significance (2 germline and 1 tissue), 16 (30.8%) possessed wild type, and 17 (32.7%) were not analyzed. Median progression-free survival was 15.3 months (95% CI 9.0–21.6). Patients with BRCA1/2 pathogenic variants showed significantly longer PFS than patients with wild-type BRCA1/2 (p = 0.007). Disease progression caused 34 cases to discontinue olaparib. Eighteen (34.6%) individuals exhibited ≥ grade 3 anemia, although they recovered in response to appropriate management. One patient discontinued olaparib because of prolonged renal dysfunction. Another patient presented with grade 3 fatigue, but recovered after 2 weeks of interruption and continued olaparib treatment. Conclusion: Olaparib maintenance therapy for platinum-sensitive recurrent ovarian cancer in the Japanese population is sufficiently safe and no less effective than reports from previous studies.

Purpose DNA polymerase epsilon ( POLE ) exonuclease domain-mutated endometrial cancer (EC) is associated with a favorable prognosis and significant immune cell infiltration. Cancers with significant immune cell infiltration often exhibit higher maximum standardized uptake value (SUVmax) on 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT). This study aimed to evaluate the correlation between POLE status and FDG-PET/CT imaging in patients with EC. Methods This retrospective study enrolled 102 patients (mean age, 56.2 ± 11.8 years) with EC who underwent preoperative FDG-PET/CT between July 2018 and August 2023. Patients were categorized into molecular subtypes based on molecular profiling. SUVmax of the primary tumor and lymph nodes was measured, and correlations with molecular subtypes were examined. Results The SUVmax in the primary tumor of POLE -mutated ECs was higher than that in non- POLE -mutated ECs (mean ± SD, 13.21 ± 4.78 vs 9.82 ± 3.78; p = 0.001). Multiple regression analysis showed that POLE status was associated with SUVmax in primary tumors (B = 2.30, p = 0.031). The SUVmax in non-metastatic lymph nodes of POLE -mutated ECs was higher than that in non -POLE- mutated ECs (median SUVmax, 1.31 [IQR, 1.05–2.21] vs. 1.06 [IQR, 0.91–1.20]; p = 0.003). Multiple regression analysis revealed that POLE status was the only factor associated with SUVmax in non-metastatic lymph nodes (B = 0.339, p = 0.046), while age, BMI, blood glucose level, histological type, and primary tumor size showed no significant association. Conclusion Patients with POLE -mutated EC exhibit high SUVmax in primary tumors and also tend to show elevated uptake in non-metastatic lymph nodes.

Objective: To determine the efficacy of drainage following pelvic lymph node (PLN) dissection, especially for cases involving laparoscopic surgery. Methods: In this retrospective study, 368 patients with malignant gynecological tumors who underwent systemic PLN dissection at Keio University Hospital between January 2012 and October 2018 were enrolled. Drainage tubes were placed in the retroperitoneal fossa in all patients. Medical records were used for data collection. Results: Laparoscopy was performed on 81 patients, and laparotomy was performed on 287 patients. In the laparoscopy group, tubes were removed 1 day post surgery. In the laparotomy group, tubes were removed 1 day post surgery in 167 patients and 4 days post surgery in 120 patients. Compared with the laparotomy group, we determined the laparoscopy group to have a significantly lower prevalence of lymphocyst (6.2% vs 20.2%, p = 0.002) but a similar prevalence of lymphedema (4.9% vs 5.2%), and symptomatic lymphocyst (2.5% vs 4.5%). The two laparotomy groups did not differ significantly with respect to the prevalence of lymphedema (4.8% vs 5.8%), lymphocyst (20.4% vs 20.0%), or symptomatic lymphocyst (4.2% vs 5.0%). Conclusion: Our results suggest that routine drainage should be omitted, especially in cases involving laparoscopic surgery.

Objective: To evaluate the accuracy of preoperative endometrial biopsy and magnetic resonance imaging (MRI) of endometrial cancer compared with that of intraoperative frozen section. Methods: This retrospective study included 264 patients who underwent surgery with intraoperative frozen section for endometrial cancer at our institution between 2014 and 2018. Diagnosis was determined by histologic type, grade, and myometrial invasion. Concordance rate, sensitivity, and specificity of preoperative diagnosis and intraoperative frozen diagnosis were calculated, in comparison to the final pathologic diagnosis. Results: Preoperative and intraoperative diagnoses showed no statistically significant difference in determining histologic type and grade (P = 0.152). Intraoperative diagnosis showed higher sensitivity for endometrioid carcinoma grade 3 and other types, and higher specificity for grade 1. For myometrial invasion, intraoperative diagnosis showed significantly higher concordance rate than preoperative MRI findings (P < 0.01). Intraoperative diagnosis showed higher sensitivity and specificity in patients with and without myometrial invasion, respectively. Conclusion: Higher agreement between intraoperative and final diagnoses, especially in myometrial invasion, suggests that intraoperative frozen section is a good indicator for appropriate surgical procedure decision making.

There are currently no effective treatments available for clear cell ovarian cancer (CCC). In this study, we aimed to identify effective drugs for CCC through high-throughput drug screening (HTDS) using ovarian cancer organoids and determine novel therapeutic targets based on the biological characteristics of CCC through omics analysis. An ovarian cancer organoid biobank was established, and HTDS was conducted using CCC organoids based on libraries of 361 and 4,560 compounds. The efficacy of the identified drugs was verified in in vitro and in vivo experiments using a patient-derived organoid xenograft mouse model. Transcriptome analysis was performed to identify genes related to the pathways targeted by the identified drugs in CCC and to assess their potential as therapeutic targets. Proteasome inhibitors and dinaciclib were extracted using HTDS and shown to inhibit tumorigenesis in vitro and in vivo. CCC, like multiple myeloma, exhibited activated endoplasmic reticulum (ER) stress and unfolded protein response (UPR), and treatment with proteasome inhibitors further enhanced ER stress and UPR, ultimately leading to cell death. Transcriptome analysis identified anterior gradient-2 (AGR2) as a key gene involved in UPR in CCC. CRISPR knockout of AGR2 suppressed cell proliferation, increased sensitivity to proteasome inhibitors, and reversed platinum resistance in CCC. AGR2 knockout also upregulated Schlafen 11, contributing to platinum sensitivity. ER stress and the UPR are activated in CCC, and proteasome inhibitors disrupt this balance, ultimately leading to cell death. AGR2 may serve as a potential therapeutic target in CCC.

In this study, we identified prognostic biomarkers that predict treatment outcome in patients receiving fertility-preserving high-dose medroxyprogesterone acetate (MPA) therapy through comprehensive multigene panel testing. A total of 38 patients (20 atypical endometrial hyperplasia and 18 stage IA G1 without myometrial invasion) who received first-line MPA therapy were enrolled. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples, and PleSSision-Rapid multigene panel testing was performed. Of the 38 patients, 31 (82%) achieved complete response (CR), 2 (5%) had stable disease (SD), and 5 (13%) had progressive disease (PD) following initial treatment. The median duration to achieve tumor disappearance was 7 months (range: 4–14 months). Following initial treatment, 25 of 32 patients (78%) experienced recurrence, with a median recurrence-free survival (RFS) of 21 months (range: 2–84 months). The most frequently observed actionable gene mutations were PTEN (68.4%), CTNNB1 (55.2%), and PIK3CA (33.3%). Patients harboring PTEN mutations in EMG1 required a significantly longer duration to achieve tumor disappearance (p = 0.011). In addition, the presence of PIK3CA mutations in AEH was significantly associated with shorter RFS (p = 0.048). Molecular classification identified 34 patients (89%) with no specific molecular profile (NSMP), 1 patient (3%) with POLE mutation, and 3 patients (8%) with deficient mismatch repair (d-MMR). Most patients undergoing MPA therapy were classified as having NSMP. Genetic alterations, specifically mutations in PTEN and PIK3CA, were significantly associated with treatment outcomes, highlighting their potential as prognostic biomarkers.

Objective: The prognostic value and clinical usage of peritoneal cytology in endometrial cancer are uncertain. This study aimed to determine whether positive cytology is associated with the prognosis for endometrial cancer. Methods: A Japanese nationwide retrospective registry study was conducted between 2012 and 2019. Clinicopathological data were analyzed for patients who were registered in the Japan Society of Obstetrics and Gynecology (JSOG) gynecological tumor registry and underwent initial treatment for endometrial cancer. Results: In total, 83,027 patients who met the inclusion criteria were identified. Data on peritoneal cytology status and overall survival (OS) were available for 74,984 and 36,995 patients, respectively. Positive peritoneal cytology was found in 11,536 (15.4%) patients. A higher proportion of patients who had positive peritoneal cytology were related to advanced stages, high-grade histology, deep myometrial invasion, lymph node (LN) metastasis, and poor risk of recurrence. After controlling for age, stage, myometrial invasion, LN metastasis, distant metastasis, and risk of recurrence, positive peritoneal cytology was associated with poor prognosis (p<0.001). Multivariate Cox regression analysis revealed that clinicopathological factors (i.e., age, International Federation of Gynecology and Obstetrics stage, histological type, myometrial invasion, LN metastasis, distant metastasis, and peritoneal cytology), including positive peritoneal cytology, were also significant prognostic factors for OS. Conclusion: Positive peritoneal cytology was a prognostic factor for endometrial cancer for the JSOG gynecological tumor registry.

Background: This study aimed to investigate the clinical benefit of dose-dense paclitaxel plus carboplatin (TC) with bevacizumab therapy for advanced ovarian, fallopian tube, and primary peritoneal cancer patients in the neoadjuvant setting. Methods: Ovarian, fallopian tube or primary peritoneal cancer patients with stage III–IV disease received neoadjuvant chemotherapy (NAC) every 3 weeks consisting of paclitaxel (80 mg/m2) on days 1, 8, and 15; carboplatin (AUC 6.0 mg/mL × min.) on day 1; and bevacizumab (15 mg/kg) on day 1. Interval debulking surgery (IDS) was performed after 3 cycles of dose-dense TC-bevacizumab therapy. The primary endpoint was the rate of complete resection by IDS. Secondary endpoints were treatment completion rate, treatment exposure, response rate to NAC, adverse events, and perioperative complications. Results: Twenty-four patients were included in this study. The median age was 55.5 years (37–80 years), and most patients had high-grade serous carcinoma accounted (n = 18). IDS was performed in all patients with complete resection achieved in 75% (95% confidence interval: 57.7–92.3%). The lower limit exceeded the preset threshold rate of 55%. The response rate to NAC was 79%, and serum CA125 levels were in the normal range after NAC in 57% of patients. Grade 4 hematological toxicities and grade 3/4 non-hematological toxicities occurred in 29% and 17% of patients during NAC, respectively. Grade 3/4 perioperative complications were seen in 29% of patients, but no gastrointestinal perforations or treatment-related deaths occurred. Conclusions: Neoadjuvant dose-dense TC-bevacizumab therapy was well tolerated, and a satisfactory rate of complete resection by IDS was achieved.

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.

Splenic metastases from solid tumors are rare, particularly when they occur after a long postsurgical interval. We report the case of a 69-year-old woman who developed a splenic metastasis from endometrial carcinoma, presenting as a hemorrhagic splenic cyst, 17 years after her initial surgery. Laparoscopic splenectomy achieving R0 resection was successfully performed; however, the patient subsequently developed multiple liver metastases. This case highlights the importance of periodic evaluation for recurrence, including monitoring for symptoms and elevated tumor markers, in patients with a history of endometrial carcinoma or other solid tumors.

For many years, drug therapy for endometrial cancer has centered on chemotherapy regimens such as adriamycin+cisplatin(AP)or paclitaxel+carboplatin(TC). In recent years, however, the introduction of immune checkpoint inhibitors(ICIs)has dramatically changed the treatment landscape. Multiple phase Ⅲ trials(eg, NRG-GY018, DUO-E)have demonstrated that adding ICIs to TC chemotherapy improves prognosis, and in 2024 combination therapies with pembrolizumab or durvalumab were approved in Japan for advanced or recurrent endometrial cancer. Additionally, development of antibody-drug conjugates(ADCs)is underway, and ADCs targeting HER2, TROP2, and other tumor-specific antigens are anticipated to become new therapeutic options.