Michihide Maeda

Intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer: association for pathological factors and oncologic outcomes

To examine the association between intrauterine manipulator use and pathological factors and oncologic outcomes in patients with endometrial cancer who had laparoscopic hysterectomy in Japan. This was a nationwide retrospective cohort study of the tumor registry of the Japan Society of Obstetrics and Gynecology. Study population was 3846 patients who had laparoscopic hysterectomy for endometrial cancer from January 2015 to December 2017. An automated 1-to-1 propensity score matching with preoperative and intraoperative demographics was performed to assess postoperative pathological factors associated with the intrauterine manipulator. Survival outcomes were assessed by accounting for possible pathological mediators related to intrauterine manipulator use. Most patients had preoperative stage I disease (96.5%) and grade 1-2 endometrioid tumors (81.9%). During the study period, 1607 (41.8%) patients had intrauterine manipulator use and 2239 (58.2%) patients did not. In the matched cohort, the incidences of lymphovascular space invasion in the hysterectomy specimen were 17.8% in the intrauterine manipulator group and 13.3% in the non-manipulator group. Intrauterine manipulator use was associated with a 35% increased odds of lymphovascular space invasion (adjusted odds ratio 1.35, 95% confidence interval (CI) 1.08 to 1.69). The incidences of malignant cells identified in the pelvic peritoneal cytologic sample at hysterectomy were 10.8% for the intrauterine manipulator group and 6.4% for the non-manipulator group. Intrauterine manipulator use was associated with a 77% increased odds of malignant peritoneal cytology (adjusted odds ratio 1.77, 95% Cl 1.29 to 2.31). The 5 year overall survival rates were 94.2% for the intrauterine manipulator group and 96.6% for the non-manipulator group (hazard ratio (HR) 1.64, 95% Cl 1.12 to 2.39). Possible pathological mediators accounted HR was 1.36 (95%Cl 0.93 to 2.00). This nationwide analysis of predominantly early stage, low-grade endometrial cancer in Japan suggested that intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer may be associated with an increased risk of lymphovascular space invasion and malignant peritoneal cytology. Possible mediator effects of intrauterine manipulator use on survival warrant further investigation, especially with a prospective setting.

The activity of immune checkpoint inhibitors in patients with recurrent cervical cancer developed in previously irradiated field: clinical and immunohistochemical investigations

We aimed to 1) evaluate the efficacy of immune checkpoint inhibitors (ICIs) in cervical cancer patients according to the site of disease, 2) investigate the mechanism responsible for differential ICIs sensitivities with focuses on CD8⁺ T lymphocytes and programmed death-ligand 1 (PD-L1) expression. We retrospectively reviewed clinical data from patients with recurrent or metastatic cervical cancer treated with pembrolizumab or cemiplimab between January 2019 and January 2024 (clinical cohort). Target diseases were classified according to the site of diseases: within previously irradiated field (in-field diseases), out-of-field diseases, and both. Immunohistochemical investigations were performed using paired tumor samples (i.e. initial cervical tumor and locally-recurrent tumor developed after definitive radiotherapy: Immunohistochemical cohort). Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test. Fifty patients treated with pembrolizumab-containing chemotherapies (n=39) or cemiplimab (n=11) were assessed. Of these, six patients (12.0%) had in-field diseases alone, twenty-eight patients (56.0%) had out-of-field diseases, and the remaining sixteen (32%) patients had both types of diseases. In-field diseases demonstrated a significantly lower response rate compared to out-of-field diseases (36.3% vs. 72.7%, p=0.004). Patients with in-field diseases demonstrated significantly shorter progression-free survival (p=0.003) and overall survival (p=0.003) than those with out-of-field diseases. In-field diseases were associated with decreased tumor-infiltrating CD8⁺ T lymphocytes and PD-L1 expression. In-field cervical cancer recurrence was associated with decreased sensitivity to ICIs-containing chemotherapies when compared to out-of-field diseases. Decreased tumor-infiltrating CD8⁺ T lymphocytes and PD-L1 expression are possible reasons for this differential sensitivity to ICI-containing chemotherapies.