Shintaro Yanazume

Potential prognostic predictors of treatment with immune checkpoint inhibitors for advanced endometrial cancer

Abstract Background Prognostic predictors of immunotherapy in patients with advanced endometrial cancer remain unclear. The potential role of inflammatory predictors, including pretreatment neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet scores, was investigated. Methods Between August 2018 and December 2023, 35 patients were retrospectively analyzed. Prognostic predictors were compared, and optimal cut-off values that exhibited the greatest discrimination for overall response, disease control, progression-free survival and overall survival were determined. Multivariate analysis was used to assess the prognostic significance of the predictors. Results The greatest discrimination for overall response, progression-free survival and overall survival included platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio and hemoglobin, albumin, lymphocyte and platelet; the areas under the curve were 0.638, 0.649 and 0.641, respectively. The precise cut-off values of neutrophil-to-lymphocyte ratio for progression-free survival and overall survival were 4.92 and 5.40, respectively. The lower neutrophil-to-lymphocyte ratio group had a significantly longer progression-free survival (P = 0.001, median survival; 4.0 months vs. 19 months) and longer overall survival (P = 0.002, median survival; 5.0 months vs. 21 months). Of the risk factors assessed, neutrophil-to-lymphocyte ratio (hazard ratio = 4.409; 95% CI = 1.10–17.64; P = 0.036) and regimen (hazard ratio = 5.559; 95% CI = 1.26–24.49; P = 0.023) were independently correlated with overall survival. Conclusion In patients with advanced endometrial cancer, pretreatment neutrophil-to-lymphocyte ratio may be a prognostic predictor of those who would benefit from immunotherapy.

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.

A potential inflammatory biomarker for advanced endometrial cancer treated with lenvatinib plus pembrolizumab

AbstractIntroductionTo identify prognostic biomarkers that could predict how well patients will respond to lenvatinib/pembrolizumab (LEN/PEM). The utility of certain inflammatory biomarkers in endometrial liquid‐based cytology (LBC) or peripheral blood samples, such as neutrophil counts, lymphocyte counts, and neutrophil‐to‐lymphocyte ratio (NLR) were explored.MethodsThe study included 25 patients with advanced or recurrent endometrial cancer who had received LEN/PEM between August 2018 and March 2024. Predictors for overall response (OR), disease control, and progression‐free survival, based on neutrophil/lymphocyte counts, NLR scores of the endometrial LBC prior to initial treatment, and peripheral blood prior to initial treatment and prior to LEM/PEM treatment were compared using a receiver operating characteristic curve. Significant predictors were evaluated using the log‐rank test, and multivariate analysis.ResultsAlthough neutrophil counts and NLR score in endometrial LBC prior to initial treatment were better effective predictors for OR, the most accurate predictor of a progression‐free status was NLR score in peripheral blood prior to LEM/PEM (0.722, 95% CI: 0.45–0.99, sensitivity: 57.1%, specificity: 94.4%). In peripheral blood prior to LEN/PEM, the lower NLR (NLR <5.39) group had a significantly longer PFS than the higher NLR (5.39 ≤ NLR) group (p = 0.023, median survival: 13.5 vs. 3.0 months), and tended to be independently correlated with PFS (hazard ratio = 2.571; 95% CI = 0.857–7.719; p = 0.092).ConclusionInflammatory biomarkers in endometrial LBC failed to predict the efficacy of LEN/PEM, while peripheral blood NLR score sampled prior to LEN/PEM potentially could be a significant predictor.

Pelvic Carcinosarcoma Showing a Diverse Histology and Hierarchical Gene Mutation with a Common POLE Mutation to Endometrial Endometroid Carcinoma: A Case Report

POLE mutation-type endometrial cancer is characterized by an extremely high tumor mutation burden. Most POLE mutation-type endometrial cancers are histologically endometrioid carcinomas, and POLE mutation-type carcinosarcomas are rare among endometrial cancers. We report a case of endometrial and pelvic cancer in a 53-year-old woman who was analyzed using next-generating sequencing. The endometrial lesion harbored a p.T457del POLE mutation with an elevated tumor mutation burden and low microsatellite instability. The pelvic lesion showed divergent histological features, consisting of high-grade endometrioid carcinoma, neuroendocrine carcinoma, and chondrosarcoma. In addition to the common POLE mutation detected in the endometrial lesion, the pelvic lesion in each element showed additional gene mutations in a hierarchical manner. Therefore, it is indicated that the p.T457del POLE mutation is a pathogenic mutation and may be related to POLE mutation-induced carcinogenesis and divergent morphogenesis in endometrial cancer.

One-step nucleic acid amplification (OSNA) assay for detecting lymph node metastasis in cervical and endometrial cancer: a preliminary study

To evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay for the diagnosis of lymph node (LN) metastasis in uterine cancer. A total of 116 LNs from 30 patients with cervical and endometrial cancer, enrolled in this prospective study, were used. Excised LNs were cut into 4 to 6 blocks at 2 mm intervals, and nonadjacent blocks were alternately subjected to either histological examination or the OSNA assay. The concordance rate between histological examination and the OSNA assay in cervical cancer and in endometrial cancer was 95.9% and 95.2%, respectively. The sensitivity, specificity, and negative predictive value of the OSNA assay were 80%, 97.7%, and 97.7% in cervical cancer, and 85.7%, 93.3%, and 98.2% in endometrial cancer, respectively. In cervical cancer, discordant results were observed in 2 out of 49 LNs (4.1%); 1 was OSNA assay-positive and histological examination-negative, and 1 was OSNA assay-negative and histological examination-positive. In endometrial cancer, discordant results were observed in 5 out of 67 LNs (7.5%); 4 were OSNA assay-positive and histological examination-negative, and 1 was OSNA assay-negative and histological examination-positive. The OSNA assay showed high concordance rate with histological examination, sensitivity, and specificity in uterine cancer, suggesting that it could enhance the accuracy of conventional pathological examination for the detection of LN metastasis by reducing false negative rate.

Fertility‐Sparing Trachelectomy With Sentinel Node Mapping in Early‐Stage Cervical Cancer: Oncological Safety and Obstetric Outcomes From a Single‐Institution Study

ABSTRACT Aim Trachelectomy is a fertility‐preserving surgical approach for early‐stage cervical cancer. To enhance oncological safety, intraoperative sentinel lymph node (SN) evaluation has been incorporated. This study aimed to evaluate the long‐term oncological and obstetric outcomes of trachelectomy with SN biopsy. Methods We enrolled 53 patients who underwent trachelectomy with intraoperative SN assessment at Kagoshima University Hospital between 2014 and 2022. The preoperative and intraoperative eligibility criteria were strictly applied. Surgical and obstetric outcomes were evaluated, and recurrence‐free survival (RFS) and overall survival (OS) were calculated using the Kaplan–Meier analysis. Results Among the 78 candidates, 53 met all criteria and successfully underwent trachelectomy. The 5‐year RFS and OS rates were both 98%. Bilateral SNs were detected in 98% of patients, and intraoperative SN biopsy‐guided surgical decisions were made. Postoperative complications occurred in 6% of the patients. Of the 19 patients who attempted conception, 10 (53%) became pregnant, leading to 8 live births (five preterm, three term). In vitro fertilization and embryo transfer were used in 60% of the pregnancies. Pregnancy was associated with a high risk of preterm delivery. Conclusions Trachelectomy with intraoperative SN biopsy is a feasible and safe treatment option for appropriately selected patients with early‐stage cervical cancer. It offers excellent oncological outcomes and acceptable fertility potential. However, the risk of obstetric complications, particularly preterm births, remains high. Structured postoperative and perinatal management is crucial. Further prospective multicenter studies are warranted to validate and refine this approach.

Robotic dual-docking surgery for para-aortic lymphadenectomy in endometrial cancer: a prospective feasibility study

Abstract Background The standard for robotic para-aortic lymphadenectomy has not been fully established. Para-aortic lymphadenectomy performed by sharing the same ports with pelvic procedures, a procedure known as dual-docking surgery, can be performed using the latest robotic system. We prospectively examined the ability of standardized dual-docking robotic surgery in endometrial cancer patients. Methods This study prospectively verified the feasibility and safety of dual-docking robotic surgeries performed between March 2017 and December 2021. The laterally placed ports were aligned with the umbilicus. Primary outcome was the surgical completion rate; secondary outcomes were blood loss, operative time, unexpected port placement, conversion, complications, length of hospital stay, and survival. Results Most patients (14/15, 93%) underwent surgery using our methods without additional port placements, and one patient was converted to laparotomy. Median blood loss was 162 mL (range: 20–685 mL). Median operative time was 183 and 206 min in the upper and lower abdomen. Median number of resected para-aortic lymph nodes was 19 (range: 6–29), and pelvic lymph nodes was 28 (range: 15–42). Although there was no difficulty in moving the forceps intraoperatively, major complications including vessel injury, and pelvic abscesses were observed. The lateral ports could be placed 6–10 cm apart in patients with any range of body type. Conclusion Dual-docking surgery for endometrial cancer has the potential to be a standard procedure for robotic endometrial cancer surgery, although a greater number of cases are needed to acquire proficiency.

Robotic trachelectomy with sentinel lymph node biopsy for cervical cancer: a prospective study investigating minimally invasive radicality

Abstract Objective The importance of minimally invasive fertility-sparing surgery for cervical cancer is gaining increasing interest, both to achieve a cure and for future fertility. Procedures for robotic radical trachelectomy involving uterine reconstruction are not fully established. Methods This study prospectively verified the feasibility and safety of robotic radical trachelectomy between February 2018 and May 2022. The criteria were almost identical to those for our standard abdominal radical trachelectomy. Larger tumors (> 2 cm in diameter) were acceptable for surgery, provided a secure ≥ 1 cm cancer-free space was identified between the tumor and internal os. Results Eight patients (median age, 32 y) were registered; the median body mass index was 21.8, and the median tumor size was 11.5 mm (range 0–30 mm). Robotic radical trachelectomy could be achieved in all patients with hybrid sentinel lymph node navigation surgery, confirming the precise cervical amputation line with a newer small knob ultrasonography probe, adequate cervical cerclage with non-absorbable monofilament stitches, and avoiding looseness between vaginal–uterine anastomosis with uninterrupted barbed U-shaped sutures. None of the cases were converted to laparotomy or radical hysterectomy, and there were no major complications. The median follow-up period was 49.5 mo (range 21–58 mo) and no patient had disease recurrence. Conclusion Robotic radical trachelectomy is safe and feasible using newer technologies without reducing radicality; it is also less invasive. Procedures are consistently reproducible and have the potential to be generalized to minimally invasive approaches.

Two Components of Variant Profiles in Primary Vaginal Carcinosarcoma via Next-Generation Sequencing and a Literature Review

Primary vaginal carcinosarcoma (VCS) is an extremely rare and aggressive tumor consisting of admixed malignant epithelial and mesenchymal elements. We report a case of VCS that was subjected to analysis by immunohistochemistry and next-generation sequencing (NGS). A 53-year-old woman with post-menopausal vaginal bleeding underwent surgical excision followed by concurrent chemoradiation. A well demarcated tumor was growing in a discontinuous fashion at a location some distance from both the cervix and vulva. Microscopically, the tumor consisted of adenocarcinoma components and sarcoma components consisting of a sheet-like growth of spindle-shaped cells, and we diagnosed this tumor as primary vaginal carcinosarcoma. NGS analysis of each component identified the following variants, TP53, PIK3CA, KRAS and FBXW7. A comparison of microsatellite instability (MSI) and tumor mutation burden (TMB) showed that within both tissues the sarcomatous components had a higher MSI and TMB than the carcinomatous components. This case supports “a monoclonal theory” with the genome profile being similar to other malignant mixed Müllerian tumors.

Bulky cervical tumour showing mixed unique cell clusters in cervical cytology

The cytological features of synchronous mucinous signet‐ring cell carcinoma and squamous cell carcinoma of the cervix have not been reported before. A case is described to emphasise that these two distinct carcinoma types can occur simultaneously in a high‐risk HPV infected cervix.

Segmental Renal Infarction Associated with Accessory Renal Arteries After Para-Aortic Lymphadenectomy in Gynecologic Malignancies

Background and Objectives: The causes and clinical outcomes of renal perfusion abnormalities occurring after para-aortic lymphadenectomy (PANDx) for gynecologic malignancies are unknown. We investigated the potential involvement of accessory renal artery (ARA) obstruction in their development by reassessing perioperative contrast-enhanced computed tomography (CECT). Materials and Methods: This retrospective study investigated a clinical database to identify urinary contrast defects using CECT in all patients who had undergone PANDx between January 2020 and December 2024. The perfusion defects in the kidney detected by CECT were extracted by a gynecologic oncologist and evaluated by a radiologist and urologist for suspected obstruction of ARAs. Results: Postoperative renal contrast defects were observed in 3.8% (6/157) of patients. Renal parenchymal fibrosis, cortical atrophy, and parenchymal thinning were observed as universal findings in all patients showing renal contrast defects. In five of the six cases, ARAs supplying the infarcted renal segments were identified on preoperative CECT, and arterial obstruction was confirmed on postoperative imaging. The remaining case was considered to be latent pyelonephritis. All five patients underwent laparotomy, and preoperative CECT failed to detect ARAs. The median resected para-aortic lymph node was 23 nodes (range: 15–33) in five patients, showing no statistically significant difference compared to patients without perfusion abnormalities (p = 0.19). Postoperative serum creatinine levels remained stable. Conclusions: ARA obstruction appears to be a risk factor for segmental renal infarction after para-aortic lymphadenectomy in gynecological malignancies; however, the clinical impact on urinary function may be limited. Awareness of this potential complication is essential for gynecologic oncologists performing PANDx.

Potential preoperative three‐dimensional computed tomography for para‐aortic lymphadenectomy in gynecological malignancies

Abstract Background The evaluation of anatomical abnormalities involving urinary vessel variations prior to para‐aortic lymphadenectomy in gynecological malignancies is challenging. In this context, the utility of preoperative three‐dimensional (3D) computed tomography (3DCT) angiography in improving surgical outcomes was examined. Methods This retrospective study evaluated the utility of 3DCT in patients who underwent para‐aortic lymphadenectomy between January 2023 and November 2024. 3D fusion images were constructed from the arterial phase, CT‐venography, and CT‐urography. A total of 72 patients were included and divided into two groups: non‐3DCT and 3DCT. Outcomes included detection rates of arterial, venous, or urinary tract variations and surgical outcomes, including complications, in both groups. Results The 3DCT group included 14/34 (41.2%) cases with renal vessel variations and two cases (5.9%) with double ureters; the non‐3DCT group did not detect any anatomical abnormalities. In the 3DCT group, renal vessel and urinary tract variations were clearly shown. Postoperative complications tended to be slightly higher in the non‐3DCT group, including lymphocyte infection, chylous leakage, and bowel obstruction. Postoperative CT revealed reduced contrast in the lower pole of the right kidney in the 3DCT case with the most complex urinary vessel variations. Furthermore, in the 3DCT group, 8/34 (23.5%) unilateral or bilateral renal arteries were located caudally to the lower edge of the renal vein. Conclusion In gynecological malignancies, 3DCT before para‐aortic lymphadenectomy seems superior in identifying urinary vessel variations over conventional contrast‐enhanced CT; thus, aiding realistic preoperative simulations and potentially reducing surgeons' burden and perioperative complications.

Validation of objective performance metrics via an intelligent medical network in gynecological oncology robotic surgery

Abstract Background Automated performance metrics (APMs) are potentially useful to accurately assess and improve surgeon skills and patient outcomes, while their clinical use is currently limited. We report on the use of the Medicaroid Intelligent Network System (MINS™), a network support system platform used together with the “hinotori” surgical robot system (hinotori™) for the collection of data logs from surgeries, and discuss its potential to improve surgical outcomes. Methods This study prospectively evaluated the efficacy of MINS™ for collecting data logs in gynecologic oncologic robotic surgery between December 2022 and February 2024 in nine patients. MINS™ regularly communicated with the hinotori™ via a secure network to collect and send system logs to a cloud server, quantifying various performance data for the evaluation of surgical outcomes. Results Clinical data on hinotori™ movement were successfully extracted. The number of operation arm (OA) changes was significantly higher in Patient No. 7, who underwent pelvic lymph node dissection. OA3 monopolar was used more frequently than OA1 bipolar for coagulation (mean: 6.7% vs 2.5%, P ˂0.001). The error count and percentage of inactive time associated with OA collisions decreased dramatically after Patient No. 6, following the version upgrade in July 2024. Conclusion MINS™ utilizes technology to connect the hinotori™ to various systems via the Internet, allowing objective evaluations of surgical procedures from data logs. MINS™ is a clinically applicable APM system that objectively analyzes a surgeon's individuality and has the potential to improve surgical techniques and promote standardization.