Hiroaki Komatsu

Establishment of immortalized ovarian stromal cell lines using Sendai virus vectors: a platform for studying tumor–stroma interactions and carcinogenesis

Abstract We aimed to generate immortalized stromal cell lines from the ovarian and fallopian tube tissues of a single patient using Sendai virus (SeV) vectors and identify candidate stromal genes involved in ovarian carcinogenesis. Tissues were collected from a 48-year-old woman with endometrioid borderline tumors and endometriomas. Primary cultures were established from the right ovarian endometrioma, left ovarian surface, bilateral fallopian tube, and endometrial surface. Immortalization was achieved using SeV vectors encoding human telomerase reverse transcriptase (TERT), B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1), and Simian virus 40 large T antigen (SV40T). Morphologically, the established cells exhibited spindle-shaped fibroblast-like features and expressed stromal markers (Vimentin-positive, Keratin-negative), confirming their stromal origin. Genetic and molecular changes associated with immortalization were evaluated via chromosomal analyses, transcriptome sequencing, and reverse transcription-polymerase chain reaction (RT-PCR). SeV-infected stromal cell lines retained their proliferative capacity for over 25 passages, whereas non-infected primary cells lost their epithelial characteristics and underwent senescence after five passages. Chromosomal abnormalities were more prevalent in stromal cells derived from the ovarian endometriomas, suggesting early genomic instability. Transcriptomic profiling and RT-PCR revealed upregulation of matrix metallopeptidase 1 (MMP1), pregnancy-associated plasma protein A (PAPPA), and C-X-C motif chemokine ligand 1 in cyst-derived stromal cells compared to those from the normal ovary and fallopian tube, implicating these genes in extracellular matrix remodeling and tumor–stroma crosstalk. We established immortalized ovarian and fallopian tube stromal cell lines using SeV-based vectors. The cyst-derived stromal cells exhibited early chromosomal instability and overexpression of MMP1 and PAPPA, supporting their potential role in ovarian carcinogenesis. These immortalized stromal cell lines provide a novel and stable platform for mechanistic studies and may contribute to biomarker discovery and therapeutic target development in ovarian cancer.

Questionnaire-based survey on the extent of lymph node dissection during interval debulking surgery after neoadjuvant chemotherapy for patients with advanced ovarian cancer in the Gynecologic Cancer Study Group of JCOG

The significance of lymph node dissection (LND) in primary debulking surgery (PDS) for advanced ovarian cancer was demonstrated in the LION trial. However, the role and the current practices of LND during interval debulking surgery (IDS) remains unclear. We aimed to conduct a survey of the current LND practices. A questionnaire-based survey regarding the criteria and extent of LND for advanced ovarian cancer was conducted by the Gynecologic Cancer Study Group of the Japan Clinical Oncology Group (JCOG). We defined enlarged lymph nodes as 10 mm or more in the short axis on imaging. This study included data from 51 institutions. Factors contributing to the decision regarding the extent of LND included performance status, completeness of cytoreductive surgery excluding the lymph nodes, and age. Regarding PDS cases with enlarged lymph nodes, 90% of all institutions opted for systematic LND (SyLND) or removal of only the enlarged lymph nodes (SeLND). In IDS cases with enlarged lymph nodes after neoadjuvant chemotherapy (NACT), 15 (29%) and 35 (69%) institutions opted for SyLND and SeLND, respectively. In contrast, in IDS cases in which enlarged lymph nodes were reduced after NACT, approximately half the institutions opted for no LND. This study found no established standard treatment for LND during IDS in patients with enlarged lymph nodes among the JCOG institutions. Thus, further prospective studies comparing the prognostic outcomes with or without LND are warranted.

Implementation of the Hugo Robotic System: Early Outcomes and Learning Curves in Hysterectomy by Surgeons With and Without Prior Robotic Experience

ABSTRACT Purpose To characterize early learning curves for two gynecologic oncologists and their first assistants using the Hugo robotic‐assisted surgery system for hysterectomy in benign uterine disease or FIGO stage IA endometrial cancer. Methods We retrospectively examined the first 43 Hugo hysterectomies performed at our center by two surgeons: Surgeon A (experienced with da Vinci) and Surgeon B (robotics‐naïve), assisted by three primary assistants (A, B, and C). We analyzed baseline patient characteristics, perioperative outcomes (operative time, docking time, console time, blood loss, complications, length of stay), and plotted learning curves using operative time trends and CUSUM analysis. Surgeon and assistant group comparisons used t ‐test or Kruskal–Wallis and chi‐square as appropriate, with p  < 0.05 considered significant. Complications graded ≥ Clavien–Dindo II were considered notable. Results Patient demographics were similar between groups. Surgeon A achieved significantly shorter operative times (128.6 ± 23.7 vs. 149.8 ± 19.6 min, p  = 0.003) and console times (90.9 ± 20.4 vs. 115.6 ± 18.9 min, p  < 0.001) versus Surgeon B. Docking times did not differ significantly. No conversions occurred, and complication rates were low and comparable (4% vs. 11%, p  = 0.56). CUSUM analysis revealed that Surgeon A's operative times stabilized by case 5, while Surgeon B required approximately 15 cases to reach comparable proficiency. Assistants demonstrated decreasing docking times, with no significant differences among groups. Conclusions In early Hugo RAS adoption, prior robotic experience led to a shorter learning curve, but robotics‐naïve surgeons achieved proficiency within ~15 cases without compromising safety. Assistants also rapidly mastered docking. These findings support safe and efficient implementation of new robotic platforms with structured training.

A Novel Port and Arm Placement Strategy for the Hugo Robotic‐Assisted Surgery ( RAS ) System in Gynecologic Oncology: Initial Experience and Technical Considerations

ABSTRACT Introduction The Hugo robotic‐assisted surgery (RAS) system is a novel surgical platform that expands the potential for minimally invasive procedures in gynecologic oncology. Early studies have shown promise, but the optimal configuration of ports and robotic arms requires further clarification. This study aimed to introduce a refined strategy for optimizing port placement and robotic arm arrangement with the Hugo RAS system and compare its performance to previously employed configurations. Materials and Surgical Technique Initial experiences in two cases of early‐stage endometrial cancer are presented. A new configuration was developed through iterative discussions and a review of emerging Hugo RAS literature. Port placement and arm arrangement with three arms on the patient's right side and one on the left—were designed to expand the assistant's working space. Two patients with stage IA endometrial cancer underwent surgery with this approach. Operative times, blood loss, and procedural details were evaluated. Discussion Both procedures were completed successfully with improved instrument articulation, reduced arm collisions, and enhanced workflow. Compared with previous strategies, this new configuration provided better ergonomics, minimized interference between robotic and assistant instruments, and expanded the operative field for both the first and second assistants, enabling smoother transvaginal specimen retrieval. Initial findings suggest that optimizing both port placement and arm settings enhances the surgical environment for the Hugo RAS system and may improve procedural efficiency and patient outcomes. Further studies with larger cohorts are warranted to validate these findings and potentially establish standardized guidelines.

Outcome of robot-assisted surgery for stage IA endometrial cancer compared to open and laparoscopic surgeries: a retrospective study at a single institution

Few studies have compared the efficacy of robot-assisted, laparoscopic, and open surgeries for endometrial cancer. When considering the position of robotic surgery in Japan, it was necessary to determine whether it was effective or not. We aimed to compare the efficacy and safety of these three types of surgeries for early-stage endometrial cancer. In total, 175 patients with endometrial cancer of preoperative stage IA, who had undergone laparotomic (n = 80), laparoscopic (n = 40), or robot-assisted (n = 55) modified radical hysterectomy at our hospital from 2010 to 2022, were included; surgical outcomes, perioperative complications, and prognoses were compared. Total operative and console times for robot-assisted surgery between patients who did or did not undergo pelvic lymphadenectomy were assessed. The robot-assisted group had the shortest total operative time. The estimated blood loss was lower in the laparoscopic and robot-assisted groups than in the laparotomy group. In advanced postoperative stage IA cases, there were no differences in progression-free and overall survival among the three groups. In the robot-assisted group, the operative time decreased as the number of operations increased; the learning curve was reached after 10 cases each of patients with and without pelvic lymphadenectomy. The frequency of perioperative complications of Clavien-Dindo classification Grade 1 or higher was the lowest in the robot-assisted group (p = 0.02). There were no complications of Clavien-Dindo classification Grade 2 or higher in the robot-assisted group. Robot-assisted surgery for stage IA endometrial cancer, a minimally invasive procedure, has fewer operative times and complications than those of laparoscopic and open surgeries in a single institution in Japan.

Impact of COVID‐19 on cervical cancer screening in Japan: A survey of population‐based screening in urban Japan by the Japan Society of Gynecologic Oncology

AbstractAimTo assess the impact of COVID‐19 on cervical cancer screening.MethodThe Japanese Society of Gynecologic Oncology launched COVID‐19 Task Force surveyed the municipalities in urban areas of Japan. Questionnaires were sent to 20 ordinance‐designated cities and 23 wards of Tokyo metropolitan area in Japan via telephone and mail in January 2021. An additional survey was conducted in March and April 2021, counted the monthly checkups in 2020 and, as a control data, the number of monthly checkups in 2019. “The State of Emergency” between April 7 and May 25, 2020, included 13 prefectures. The data collected in this research involved the number of screenings only. The chi‐square test was performed for statistical analysis.ResultsThe number of cancer screenings from March to August, with May being the month with the lowest number of screenings, was less than 50% of that in the previous year. In particular, the drop in the number of cancer screenings in the “Prefectures operating under special safety precautions” was remarkable and significantly lower than that in other Prefectures. However, after August, the number recovered to the usual level, despite the second wave of the pandemic occurring nationwide. The initial “the State of Emergency” caused a significant decrease in the number of people receiving population‐based screenings, but the recovery has been remarkable, and the total number is expected to be the same as in previous years.ConclusionThe initial “the State of Emergency” caused a significant decrease in the number of people receiving population‐based screenings.

A simplified procedure of nerve‐sparing radical hysterectomy

AbstractAimWe devised a simplified nerve‐sparing radical hysterectomy that is simpler than commonly used procedures.MethodsWe retrospectively examined 16 cases of classical non‐nerve‐sparing radical hysterectomy (non‐nerve‐sparing group) and 16 cases of simplified nerve‐sparing radical hysterectomy (nerve‐sparing group) performed between 2019 and 2020. We examined and compared the duration of surgery, blood loss, perioperative complications, postoperative urinary function (presence or absence of urinary sensation, number of days with residual urine measurement, and frequency and duration of oral sustained release urapidil capsules and self‐catheterization), and short‐term prognosis between the two groups.ResultsCompared to conventional non‐nerve‐sparing radical hysterectomy, the duration of surgery for nerve‐sparing radical hysterectomy was significantly shorter (407 [339–555] min vs. 212 [180–356] min; p < 0.001), and blood loss was significantly less. Compared to the nerve‐sparing group, the non‐nerve‐sparing group had more cases of oral urapidil use and a higher frequency of clean intermittent catheterization. Clean intermittent catheterization was required in two cases in the nerve‐sparing group; however, it was withdrawn at 180 and 240 days. Conversely, clean intermittent catheterization was still required in three cases in the non‐nerve‐sparing group. There were no statistically significant differences in progression‐free survival and overall survival between the two groups.ConclusionThe simple nerve‐sparing radical hysterectomy resulted in shorter duration of surgery and less blood loss as well as in a clear improvement in the postoperative urinary status and short‐term prognosis. This technique simplifies nerve‐sparing radical hysterectomy, which is commonly thought to be complicated, making it easier to understand.

A survey of carboplatin desensitization therapy in Japan: A multicenter retrospective study

AbstractIntroductionHypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs.MethodsPatients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form.ResultsThis retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre‐existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620–18,282) mg, and the mean number of doses was 14 (4–63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified.ConclusionAlthough carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider.

Current status and challenges in training the next generation of gynecologic cancer care providers in Asia

Gynecologic oncology is undergoing rapid development with continuous advances in treatment strategies, surgical techniques, and clinical research. Training programs must keep pace by providing future specialists with the necessary surgical skills and a solid understanding of evolving practices. This study aimed to examine the current state of gynecologic oncology training in Asia and to identify key challenges and opportunities for improvement. A descriptive survey was conducted in October 2023 under the leadership of the Education Committee of the Asian Society of Gynecologic Oncology (ASGO). Key stakeholders involved in clinical training and policy-making from eight countries and regions (China, Hong Kong SAR, India, Japan, the Philippines, South Korea, Taiwan, and Thailand) responded to an online questionnaire assessing the structure and quality of their national training programs. Six of the eight countries/regions have official gynecologic oncology societies. Training duration was three years or more in five regions and two years in the remaining three. Seven reported conducting formal assessments of surgical skills. While five programs offered adequate exposure to minimally invasive surgery, three noted limitations. Satisfaction with research opportunities and overall training quality also varied. The most frequently cited concern was the lack of standardized curricula. This regional overview reveals notable differences in training approaches across Asia. Standardizing educational frameworks and expanding collaborative initiatives - such as virtual tumor boards, elective rotations, and skills-based workshops - may help address current gaps and strengthen gynecologic oncology training in the region.

Characterization of immortalized ovarian epithelial cells with BRCA1/2 mutation

We aimed to elucidate the mechanism underlying carcinogenesis by comparing normal and BRCA1/2-mutated ovarian epithelial cells established via Sendai virus-based immortalization. Ovarian epithelial cells (normal epithelium: Ovn; with germline BRCA1 mutation: OvBRCA1; with germline BRCA2 mutation: OvBRCA2) were infected with Sendai virus vectors carrying three immortalization genes (Bmi-1, hTERT, and SV40T). The immunoreactivity to anti-epithelial cellular adhesion molecule (EpCAM) antibodies in each cell line and cells after 25 passages was confirmed using flow cytometry. Chromosomes were identified and karyotyped to detect numerical and structural abnormalities. Total RNA extracted from the cells was subjected to human transcriptome sequencing. Highly expressed genes in each cell line were confirmed using real-time polymerase chain reaction. Immortalization techniques allowed 25 or more passages of Ovn, OvBRCA1, and OvBRCA2 cells. No anti-EpCAM antibody reactions were observed in primary cultures or after long-term passages of each cell line. Structural abnormalities in the chromosomes were observed in each cell line; however, the abnormal chromosomes were successfully separated from the normal structures via cloning. Only normal cells from each cell line were cloned. MMP1, CCL2, and PAPPA were more predominantly expressed in OvBRCA1 and OvBRCA2 cells than in Ovn cells. Immortalized ovarian cells derived from patients with germline BRCA1 or BRCA2 mutations showed substantially higher MMP1 expression than normal ovarian cells. However, the findings need to be validated in the future.