Motoki Matsuura

Fatty Acid Metabolism Regulators Have Pivotal Roles in the Pathogenesis of Ovarian Carcinoma

To study the pathological contribution of fatty acid (FA) metabolism regulators including fatty acid binding protein 4 (FABP4), FABP5, peroxisome proliferator-activated receptor alpha (PPARα), and PPARγ in ovarian carcinoma, non-cancerous human ovarian surface epithelium (HOSE) cells and two epithelial ovarian carcinoma (EOC) cell lines, AMOC-2 and ES2 established from ovarian serous adenocarcinoma and ovarian clear cell carcinoma, respectively, were subjected to (1) an analysis of the physical properties of spheroids, (2) qPCR analysis, (3) cellular metabolic analysis, and (4) multiomic pan-cancer analysis using the Cancer Genome Atlas (TCGA). In contrast to globe-shaped spheroids of HOSE cells, AMOC-2 and ES2 cells formed non-globe-shaped spheroids and ES2 spheroids were much more fragile than AMOC-2 spheroids. Gene expression levels of FABP4 and FABP5 in AMOC-2 cells and those of PPARγ in AMOC-2 cells were significantly higher than those in HOSE cells. Metabolic phenotypes and the effectiveness against antagonists for regulators were significantly different in the two types of cancerous cells. Those regulators were identified by a multiomic pan-cancer analysis as novel factors for the prediction of the prognosis of ovarian serous adenocarcinoma. The results show that dysregulated FA metabolism in AMOC-2 and ES2 suggests that the regulation of FA metabolism may be a critical factor in the pathogenesis of EOC.

Step-by-step demonstration of “sciatic-nerve-preserved beyond-LEER” in a Thiel-embalmed cadaver: a novel salvage surgery for recurrent gynecologic malignancies

Early outcomes of three new robotic surgical systems in patients undergoing hysterectomy

New robot models, such as hinotori

Relationship between the lateral dissection lines of various radical hysterectomies and anatomical structures in the female pelvis: an educational video from the Sapporo Cadaver Surgical Workshop

Radical hysterectomy with pelvic lymph node dissection is the treatment of choice for cervical cancer. All gynecologic oncologists should master this technique. The surgical procedure requires a wide dissection of the female pelvis. Performing radical hysterectomy without a thorough knowledge of the anatomy of the female pelvis can lead to serious complications. For novice surgeons to safely perform radical hysterectomy, mastering the 3-dimensional anatomy of the pelvis and aligning the dissection lines of radical hysterectomy to the female pelvic anatomy is crucial. Educational materials that demonstrate the anatomical relationship between dissection lines in radical hysterectomy and the surrounding pelvic structures are lacking. We aimed to create educational material to overcome these problems. Laparoscopic nerve sparing, non-nerve sparing, and super-radical hysterectomies, exposing pivotal pelvic anatomical structures, were performed on a Thiel-embalmed cadaver. Nerve sparing, non-nerve sparing, and super-radical hysterectomies were laparoscopically performed in the right hemi-pelvis of the cadaver. We exposed the external and internal iliac vessels; obturator, sciatic, femoral, hypogastric, and pelvic splanchnic nerves and the pelvic nerve plexus; internal obturator, piriform, and coccygeal muscles; sacrospinous ligament; and ischial spine. Thus, we demonstrated where the dissection lines of the various radical hysterectomies are in a female pelvis. Using a Thiel-embalmed cadaver, we demonstrated the relationship between the dissection lines of various radical hysterectomies and pivotal sidewall anatomical structures in a female pelvis. The anatomical detail shown in the video captured during this procedure may assist surgeons to safely perform various radical hysterectomies.

Human papillomavirus self‐sampling and urine‐sampling tests and the management and short‐term outcomes of cervical intraepithelial neoplasia: A prospective observational study

AbstractAimThe importance of human papillomavirus (HPV) co‐testing using physician‐, self‐, and urine‐collected samples to predict cervical intraepithelial neoplasia (CIN) grade 1–2 prognoses has not been previously reported. Therefore, this study aimed to investigate outcomes of patients with CIN 1–2 who simultaneously underwent physician‐, self‐, and urine‐collection sampling tests.MethodsThis study was conducted in Japan between October 2019 and November 2022 and examined the proportion of cases with CIN 1–2 progressions, the percentage of cases with persistent CIN 1–2, and the outcome differences according to the results of physician‐, self‐, and urine‐sampling tests.ResultsThere were 105 and 59 CIN 1 and 2 cases, respectively, with progression or persistence in 27 (29.3%) and 21 (50.0%) cases, respectively. The median follow‐up was 20 and 12 months, respectively. Progression and persistence of CIN 1 were significantly associated with HPV‐positive physician‐ and self‐collected samples. No significant difference was observed between cases with CIN 2 who had HPV‐positive and HPV‐negative results using any sampling method.ConclusionsPhysician‐ and self‐testing for HPV are crucial for predicting disease progression risk in CIN 1 cases. Future research with an extended observation period and consideration of the progression risks is warranted.

Niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer: final results of a multicenter phase 2 study

To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4-78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9-26.9) and the disease control rate was 90.0% (95% CI=68.3-98.8). The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified. ClinicalTrials.gov Identifier: NCT03759600.

Niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer: final results of a multicenter phase 2 study

This study evaluated the long-term safety and efficacy of niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer. This was a follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with platinum-sensitive, relapsed ovarian cancer. Participants received niraparib (starting dose 300 mg) once daily in continuous 28-day cycles. The primary endpoint was the incidence of Grade 3 or 4 thrombocytopenia-related events (defined as the overall incidence of the MedDRA Preferred Terms "thrombocytopenia" and "platelet count decreased") occurring in the 30 days after initial administration of niraparib, and secondary endpoints included evaluation of treatment-emergent adverse events and progression-free survival. Nineteen patients (median age, 62 years; median body weight, 53.9 kg) were enrolled. As previously reported, the incidence of Grade 3 or 4 thrombocytopenia-related events during the first 30 days of treatment was 31.6%. At data cutoff, median (range) treatment exposure was 504.0 (56-1,054) days and mean ± standard deviation dose intensity was 154.4±77.5 mg/day. The most common treatment-emergent adverse events were nausea (n=14, 73.7%), decreased platelet count (n=12, 63.2%), decreased neutrophil count (n=11, 57.9%), anemia, vomiting, and decreased appetite (all n=9, 47.4%). One patient was diagnosed with treatment-related leukemia, which resulted in death. Median (95% confidence interval) progression-free survival was 18.0 (5.6-26.7) months. Overall, the safety profile of niraparib was considered manageable in this study population of Japanese patients with platinum-sensitive, relapsed ovarian cancer and was consistent with that observed in studies of non-Japanese patients. ClinicalTrials.gov Identifier: NCT03759587.