Mika Mizuno

Intraoperative Evaluation of Whole Sentinel Lymph Nodes Using a One-Step Nucleic Acid Amplification Assay in Endometrial Cancer: A Prospective Study

Background and Objectives: The aim of this prospective study was to evaluate the diagnostic accuracy of the one-step nucleic acid amplification (OSNA) assay for the intraoperative assessment of sentinel lymph node (SN) metastases, including micrometastases in patients with stage IA low-grade endometrial cancer. Materials and Methods: A prospective analysis was conducted on 204 patients with low-risk endometrial cancer who underwent hysterectomy, bilateral salpingo-oophorectomy, and sentinel node navigation surgery. SNs were analyzed intraoperatively using the OSNA assay, and positive patients underwent systematic pelvic lymphadenectomy. Results: Among the 204 patients included, SN metastases were identified in 12 patients (6%), including 10 patients with micrometastases and 2 patients with macrometastases. No metastases were detected in non-SNs in any of the 12 patients. Recurrence occurred in two patients (1%), involving the vaginal stump and pelvic cavity dissemination, but no lymph node recurrence was observed. The OSNA assay identified a proportion of micrometastases in low-risk endometrial cancer. While a direct comparison with conventional pathological ultra-staging was not performed in this study, the detection rate of micrometastases appears higher than that reported in historical controls. Conclusions: This is the first prospective study to evaluate the intraoperative use of the OSNA assay for whole SNs in endometrial cancer. The results suggest that the OSNA assay enhances the detection of micrometastases, enabling a more accurate assessment of SN metastases. In low-risk endometrial cancer, systematic pelvic lymphadenectomy may be safely omitted in patients with SN-positive micrometastases. Further prospective studies are necessary to validate these findings and support the adoption of this approach in clinical practice.

Robot-assisted gynecologic surgery in elderly patients: perioperative outcomes and risk assessment in patients aged 70 years and older

Robot-assisted surgery has become widely accepted as a minimally invasive approach. However, its safety and feasibility in older women undergoing gynecologic procedures remain insufficiently explored. This retrospective study compared perioperative outcomes between two older age groups and evaluated surgical risks by using the E-PASS and POSSUM scoring systems. A total of 61 women aged ≥ 70 years who underwent robot-assisted gynecologic surgery at our institution were analyzed. Endometrial cancer cases involved hysterectomy with sentinel lymph node biopsy, while procedures for pelvic organ prolapse included sacrocolpopexy with vaginal surgery. The patients were categorized into pre-old (70-74 years) and old (75-89 years) groups. Although prior abdominal surgery was significantly more common in the old group (58.3 vs. 13.5%, p = 0.0003), no significant differences were found in comorbidities, the operative time (242 vs. 235 min), blood loss, or the duration of hospital stay. One pre-old patient developed a pelvic infection (Clavien-Dindo grade IIIa); no other serious complications occurred, and overall complication rates were similar. Two cases of postoperative delirium were not predicted preoperatively. Perioperative risk scores indicated a low risk in both groups. While midterm postoperative outcomes were generally favorable, some patients experienced new health-related events, which were unrelated to surgery. These findings suggest that robotic surgery is feasible and that age alone should not be a contraindication. However, importantly, these outcomes were achieved in a cohort that received comprehensive perioperative care; therefore, further studies with larger cohorts are needed. Moreover, perioperative planning should consider not only physical conditions but also the cognitive and mental status, the living environment, and social support.

Comparison of laparoscopic and robotic-assisted minimally invasive surgery with sentinel lymph node navigation in low-risk endometrial cancer: a retrospective analysis

To evaluate and compare the perioperative and oncologic outcomes of laparoscopic and robotic-assisted surgeries in patients with low-risk endometrial cancer who underwent minimally invasive surgery (MIS) for complete surgical staging, including sentinel lymph node mapping. A retrospective study included 190 patients diagnosed with low-risk endometrial cancer who underwent MIS combined with sentinel lymph node navigation surgery (SNNS) between December 2016 and December 2021. Among these patients, 66 underwent laparoscopic surgery, while 124 underwent robotic-assisted surgery. The analysis focused on patient characteristics, perioperative outcomes, and prognostic factors, including recurrence-free survival (RFS) and overall survival (OS). Statistical analysis was performed using Kaplan-Meier survival curves and appropriate comparative tests for outcome evaluation. The median operative time and estimated blood loss were significantly longer and greater in the robotic surgery group than in the laparoscopic group (209.5 vs. 157.5 min, 20 vs. 5 mL, respectively). The identification rates of sentinel nodes were 97% and 95.2% in the laparoscopic and robotic groups, respectively, with no significant difference between the 2. Recurrence was observed in two and three cases in the laparoscopic robotic surgery groups, respectively. The 3-year RFS rates were 97.6% (95% confidence interval [CI]=0.8482-0.9769) and 93.9% (95% CI=0.9277-0.9922) for the robotic and laparoscopic groups, respectively, while the 3-year OS rates were 99.2% (95% CI=0.8561-0.9902) and 96.1% (95% CI=0.9450-0.9989), respectively, with no statistically significant differences. MIS combined with SNNS is a highly effective approach for managing low-risk endometrial cancer, providing comparable oncologic outcomes to laparoscopy while enhancing the quality of life of patients.

Impact of obesity on the outcomes and cost of robotic surgery for Stage IA endometrial cancer: a regional perspective from Japan

Abstract Background The incidence of endometrial cancer in Japan has more than doubled over the past 2 decades because of increasing obesity rates and the unique physiological traits of Asian populations. The aim of this retrospective study was to examine the impact of obesity on surgical outcomes, prognosis, and costs. Methods A total of 197 patients with stage IA endometrial cancer who underwent robot-assisted hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy/biopsy from 2018 onward were included. Patients were divided into the BMI < 30 kg/m 2 group (n = 117) and the BMI ≥ 30 kg/m 2 group (n = 80). The clinical and pathological factors, surgical outcomes, perioperative complications, and treatment costs were compared. The median follow-up period was 34.9 months (range: 6.1–84.2). Results In the BMI ≥ 30 kg/m 2 group, significant differences in comorbidities, including diabetes mellitus (19.7% vs. 51.3%), hypertension (43.6% vs. 58.8%), and hyperlipidemia (29.9% vs. 50%), were detected. However, no significant differences were found in operative time, blood loss volume, perioperative complication rates, or 5-year cancer-specific survival rates (97.6% vs. 100%). Surgical and hospitalization costs were higher in the BMI ≥ 30 kg/m 2 group, indicating a financial burden for both patients and healthcare facilities. Additionally, a higher prevalence of newly developed lifestyle-related diseases, such as cardiovascular diseases and diabetes, was observed during the follow-up (2.5% vs. 10%). Conclusions While obesity (BMI ≥ 30) did not significantly impact surgical outcomes or cancer prognoses, it did increase treatment costs and the risk of lifestyle-related diseases. Thus, preventive strategies, including lifestyle counseling, are needed to reduce obesity-related health burdens.

Comparative analysis of surgical outcomes between the hinotori™ surgical robot system and da Vinci® Xi for simple hysterectomy with sentinel lymph node biopsy in low-risk endometrial cancer

Abstract Objectives This study aimed to compare the surgical outcomes of simple hysterectomy with sentinel lymph node biopsy for low-risk endometrial cancer performed using the hinotori™ Surgical Robot System and the da Vinci® Xi system. Materials and Methods We retrospectively analyzed the data of 234 patients who underwent simple hysterectomy with sentinel lymph node biopsy at Kagoshima University Hospital between January 2017 and June 2024. Amongst them, 20 patients underwent surgery using the hinotori™ Surgical Robot System and 214 using the da Vinci® Xi. Surgical factors, including operative time, cockpit/console time, blood loss and sentinel lymph node detection, were evaluated. Statistical analyses included chi-square and Wilcoxon tests, with significance set at P < 0.05. Results The median operative and cockpit/console times were comparable between the two systems. However, the time from roll-in to the start of cockpit/console surgery was significantly longer for the hinotori™ Surgical Robot System than for the da Vinci® Xi (P = 0.0039). No significant differences were observed for blood loss, length of hospital stay, or complication rates. The sentinel lymph node detection rates and number of sentinel lymph nodes resected were similar between the two systems, with metastatic sentinel lymph node rates of 6% in both groups. Conclusion Simple hysterectomy with sentinel lymph node biopsy performed using the hinotori™ Surgical Robot System demonstrated outcomes comparable with those using the da Vinci® Xi system, with no significant differences in key surgical factors. These results suggest that the hinotori™ Surgical Robot System is a viable alternative for minimally invasive surgery in low-risk endometrial cancer. Further studies with larger sample sizes are required to validate these findings.

Efficacy and prognosis of robotic surgery with sentinel node navigation surgery in endometrial cancer

This study aimed to validate the surgical and oncologic outcomes of robotic surgery with sentinel node navigation surgery (SNNS) in endometrial cancer. This study included 130 patients with endometrial cancer, who underwent robotic surgery, including hysterectomy, bilateral salpingo-oophorectomy, and pelvic SNNS at the Department of Obstetrics and Gynecology of Kagoshima University Hospital. Pelvic sentinel lymph nodes (SLNs) were identified using the uterine cervix 99m Technetium-labeled phytate and indocyanine green injections. Surgery-related and survival outcomes were also evaluated. The median operative and console times and volume of blood loss were 204 (range: 101-555) minutes, 152 (range: 70-453) minutes, and 20 (range: 2-620) mL, respectively. The bilateral and unilateral pelvic SLN detection rates were 90.0% (117/130) and 5.4% (7/130), respectively, and the identification rate (the rate at which at least one SLN could be identified on either side) was 95% (124/130). Lower extremity lymphedema occurred in only 1 patient (0.8%), and no pelvic lymphocele occurred. Recurrence occurred in 3 patients (2.3%), and the recurrence site was the abdominal cavity, with dissemination in 2 patients and vaginal stump in one. The 3-year recurrence-free survival and 3-year overall survival rates were 97.1% and 98.9%, respectively. Robotic surgery with SNNS for endometrial cancer showed a high SLN identification rate, low occurrence rates of lower extremity lymphedema and pelvic lymphocele, and excellent oncologic outcomes.

Cytopathological features associated with POLE mutation in endometrial cancer

AbstractObjectiveFor patients with endometrial cancer, the POLE (polymerase epsilon) mutation (POLEmut)‐subtype, one of four molecular‐analysis‐based categories in the Cancer Genome Atlas (TCGA), has the best prognosis. The following histological characteristics are typically observed in endometroid carcinoma cases with the POLEmut‐subtype: (1) the presence of tumour giant cells, (2) numerous tumour‐infiltrating lymphocytes (TILs) and/or peri‐tumoral lymphocytes, and (3) a high grade. However, in the context of cytology, the morphological characteristics of this subtype remain unknown.MethodsDNA extracted from formalin‐fixed paraffin‐embedded (FFPE) tissues was subjected to next‐generation sequencing analysis and categorised according to the TCGA classifications. Genomic mutation, tumour mutation burden (TMB), and microsatellite instability were also assessed. Cytological specimens of resected uteri obtained using the Papanicolaou method were histologically separated into three types.ResultsSeven out of 112 patients (6%) with endometrial cancer were diagnosed with the POLEmut‐subtype between January 2019 and August 2021. Tumour giant cells were observed in three cases (43%) on histology and cytology. TIL and/or peritumoral lymphocytes with inflammatory cells were detected in five cases (71%) on histology and three cases (43%) on cytology. Cases in which these three characteristics were observed on both cytology and histology may have belonged to the POLEmut‐subtype. There were no cases in which these characteristics were absent on histology but present on cytology. TMB tended to be higher in cases when the three characteristics were observed in both cytological and histological findings.ConclusionsPreoperative endometrial cytology highlighted the characteristics of the POLEmut‐subtype in the histological analysis of resected uterine specimens and has the potential to play an important role in treatment decisions.

Challenges in managing atypical glandular cells in cervical smears: Insights from real‐world data and clinicians' perspectives

AbstractObjectiveThis study evaluates clinicopathological outcomes and clinicians' awareness regarding the management of atypical glandular cells (AGC).MethodsWe analyzed 98 AGC cases, excluding known endometrial cancer, from 238 initial cases, with a median age of 42 years (range 20–82). Cytological findings, including NOS and FN subcategories, diagnostic tests, treatments, and outcomes were evaluated. A survey on AGC awareness and practices was conducted among 134 obstetrician‐gynecologists.ResultsOf 98 cases (AGC‐FN: 19.8%, AGC‐NOS: 13.2%, unspecified: 67.3%), 44.9% initially showed no neoplasia; this dropped to 38.8% following up, identifying 11 additional AIS or cervical adenocarcinomas. Overall, 28.5% had AIS or more, 18% had CIN, and 13.3% had other malignancies, indicating some over/underdiagnosis. HPV testing in 79 cases showed a 48.1% positivity rate, including 14 type‐18 and 12 type‐16 cases. Among clinicians surveyed, 25% were aware of AGC subcategories, and only 11.9% were well‐versed. Approximately 65% associated AGC with malignancy or precancerous lesions, and 52.6% used multiple diagnostic methods simultaneously. Even in the absence of neoplasia, 80% continued cytological examinations every 3–4 months.ConclusionThis study underscores the challenges in AGC management, highlighting the importance of follow‐up and collaboration between clinicians and cytopathologists to detect significant lesions. It also emphasizes the need for providing learning opportunities for clinicians to address over/undertreatment.

Veliparib with frontline chemotherapy and as maintenance in Japanese women with ovarian cancer: a subanalysis of efficacy, safety, and antiemetic use in the phase 3 VELIA trial

Abstract Background The phase 3 VELIA trial evaluated veliparib with carboplatin/paclitaxel and as maintenance in patients with high-grade serous ovarian carcinoma. Methods Patients with previously untreated stage III–IV high-grade serous ovarian carcinoma were randomized 1:1:1 to control (placebo with carboplatin/paclitaxel and placebo maintenance), veliparib-combination-only (veliparib with carboplatin/paclitaxel and placebo maintenance), or veliparib-throughout (veliparib with carboplatin/paclitaxel and veliparib maintenance). Randomization stratification factors included geographic region (Japan versus North America or rest of the world). Primary end point was investigator-assessed median progression-free survival. Efficacy, safety, and pharmacokinetics were evaluated in a subgroup of Japanese patients. Results Seventy-eight Japanese patients were randomized to control (n = 23), veliparib-combination-only (n = 30), and veliparib-throughout (n = 25) arms. In the Japanese subgroup, median progression-free survival for veliparib-throughout versus control was 27.4 and 19.1 months (hazard ratio, 0.46; 95% confidence interval, 0.18–1.16; p = 0.1 [not significant]). In the veliparib-throughout arm, grade 3/4 leukopenia, neutropenia, and thrombocytopenia rates were higher for Japanese (32%/88%/32%) versus non-Japanese (17%/56%/28%) patients. Grade 3/4 anemia rates were higher in non-Japanese (65%) versus Japanese (48%) patients. Early introduction of olanzapine during veliparib monotherapy maintenance phase may help prevent premature discontinuation of veliparib, via its potent antiemetic efficacy. Conclusions Median progression-free survival was numerically longer in Japanese patients in the veliparib-throughout versus control arm, consistent with results in the overall study population. Pharmacokinetics were comparable between Japanese and non-Japanese patients. Data for the subgroup of Japanese patients were not powered to show statistical significance but to guide further investigation.

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

PURPOSE This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.