Kazumasa Mogi

Mesothelial cells promote peritoneal invasion and metastasis of ascites-derived ovarian cancer cells through spheroid formation

Patients with epithelial ovarian cancer (EOC) are often diagnosed with peritoneal metastasis and ascites, the accumulation of intraperitoneal fluid containing nonmalignant cells. However, the interactions between EOC and nonmalignant cells before peritoneal metastasis remain unclear. To investigate this, whole EOC spheroids were observed using a multiphoton microscope, and their invasion ability was assessed. Mesothelial cells were identified as notable components of ascites through morphological assessment, immunohistochemical/immunofluorescence staining, and single-cell RNA sequencing analyses. Almost all EOC cells were spheroids, with 60% containing mesothelial cells. EOC cells quickly generate aggregated spheroids with mesothelial cells, and these aggregated cancer-mesothelial spheroids (ACMSs) invade collagen or mesothelial layers. Mesothelial cells forming ACMSs initiated the invasion. RNA sequencing analysis revealed marked RNA expression changes in mesothelial cells, whereas the changes in EOC cells were minor. Transforming growth factor–β1–stimulated mesothelial cells showed increased invadopodium formation along with fascin-1 up-regulation. These findings suggest that EOC cells alter mesothelial cells through ACMSs, thereby elucidating the rapid spread of EOC in the abdominal cavity.

Histology-specific long-term oncologic outcomes in patients with epithelial ovarian cancer who underwent complete tumor resection: The implication of occult seeds after initial surgery

Objective Assessing the histology-specific prognosis of epithelial ovarian cancer (OvCa) is clinically challenging, especially in a patient population with a favorable prognosis. This study investigated the histology-specific long-term oncologic outcomes in OvCa patients who underwent complete tumor resection using a large-scale patient cohort form multiple institutions under a central pathological review system. Methods A regional multi-institutional study was conducted from 1986 to 2019. Of the 4,898 patients with ovarian tumors enrolled, 1,175 patients who underwent complete tumor resection were classified into three classes based on clinically important prognostic factors: stage, cytology, ascites volume. For each class category, the effect of histology types on recurrence-free survival, the site of recurrence, and post-recurrence survival was evaluated. Results Recurrence-free survival varied significantly across different histologies (P < 0.001). The risk of recurrence was higher in serous carcinoma compare to other histologies (P < 0.001). The site of tumor recurrence varied by the histology type. Multinominal logistic regression analysis revealed that mucinous histology had a significantly higher likelihood of developing recurrent tumors at distant sites from the peritoneum compared to other histologies (P = 0.002). Conversely, serous histology was associated with better post-recurrence survival (Log-rank P < 0.001). Conclusions Long-term oncologic outcomes significantly differ by histology type in OvCa patients who have undergone complete tumor resection at the initial surgery. A careful evaluation of the clinical background is necessary for these patients, and further clinical research into individualized treatment approaches is essential.

Impact of incomplete surgery and adjuvant chemotherapy for the intraoperative rupture of capsulated stage I epithelial ovarian cancer: a multi-institutional study with an in-depth subgroup analysis

The aim of the present study was to examine the effects of incomplete surgery and adjuvant chemotherapy on the prognosis of patients with intraoperative rupture of capsulated stage I epithelial ovarian cancer (OvCa). A regional retrospective study was conducted between 1986 and 2019. Among 4,730 patients with malignant ovarian tumors, 534 women with International Federation of Gynecology and Obstetrics stage IA and IC1 epithelial OvCa were eligible. Differences in survival outcomes were examined between patients with stage IA and IC1 tumors and the effects of uterine preservation, complete-staging lymphadenectomy, and adjuvant chemotherapy were investigated by an in-depth subgroup analysis. To analyze therapeutic effects, baseline imbalances were adjusted using propensity score (PS). The prognosis of patients with stage IC1 tumors was worse than those with stage IA. Surgical spill did not affect the site of recurrence. In the PS-adjusted subgroup analysis, uterine preservation (hazard ratio [HR]=1.669; 95% confidence interval [CI]=1.052-2.744), incomplete-staging lymphadenectomy (HR=1.689; 95% CI=1.211-2.355), and the omission of adjuvant chemotherapy (HR=3.729; 95% CI=2.090-6.653) significantly increased the HR of recurrence for patients with stage IC1 tumors compared to those with stage IA tumors. Adjuvant chemotherapy decreased the impact of rupture with uterine preservation (HR=0.159; 95% CI=0.230-1.168) or incomplete-staging lymphadenectomy (HR=0.987; 95% CI=0.638-1.527). The present results suggest intraoperative rupture of capsulated stage I epithelial OvCa is associated with a poor prognosis. When chemotherapy is given for patients receiving incomplete surgery, there is no longer an increased risk of recurrence observed with the rupture.

Obesity contributes to the stealth peritoneal dissemination of ovarian cancer: a multi‐institutional retrospective cohort study

AbstractObjectiveThe clinical significance of a higher BMI on the prognosis of ovarian cancer remains controversial; therefore, a more detailed analysis is demanded. This study investigated the impact of BMI on peritoneum‐specific recurrence to clarify the involvement of adipose tissue in the proliferation of cancer cells at sites of peritoneal dissemination.MethodsAmong 4,730 patients with malignant ovarian tumors, 280 diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIC epithelial ovarian cancer and who underwent complete resection in the primary surgery were included in the present study.ResultsThere were 42, 201, and 37 women in the low, normal, and high BMI groups, respectively. Peritoneum‐specific recurrence‐free survival and overall survival were both significantly shorter in patients with a high BMI than in those with a normal BMI (p = 0.028 and 0.018, respectively). No significant differences were observed in the distribution of sites of recurrence between these two groups. A multivariate analysis identified obesity as an independent prognostic factor in addition to pT3 tumor staging and positive ascites cytology.ConclusionsPatients with a high BMI had a significantly worse prognosis than those with a normal BMI, and peritoneal adipose tissue may have contributed to this difference.