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Objective The aim of this study was to investigate long-term post-recurrence survival outcomes in young women receiving fertility-sparing surgery (FSS) to verify the feasibility of the limited surgery for epithelial ovarian cancer (OvCa). Study Design We performed a regional multicenter retrospective study from January 1986 and March 2020, using clinical data corrected under the central pathological review system. Patients with recurrent tumor after surgery for stage I epithelial OvCa, aged equal or younger than 45 years were included for this study. We evaluated effect of FSS regarding long-term post-recurrence survival with statistical adjustment of propensity score-based method. Results With the Kaplan–Meier method, original and adjusted survival curves were estimated for recurrence-after survival of patients with (n = 14) and without FSS (n = 26). Median time to disease-specific death was 18.6 months. In both original and adjusted cohorts, there were no significant difference between the two groups (log rank test; P > 0.05). Hazard ratio of disease-specific death was 1.264 (95% confidence interval, 0.563–2.836; P = 0.570) in original and 1.354 (95% confidence interval, 0.702–2.611; P = 0.366) in adjusted population. This result indicated that patients with FSS was not associated with poorer prognosis for recurrence-after survival than those without. When comparing patients not receiving FSS, patients receiving FSS with recurrence at spared ovary followed not significantly different survival outcome as well as those with extra-ovarian recurrence. Conclusion There was no significant difference of long-term post-recurrence survival outcomes between patients of epithelial OvCa with and without FSS in young women of reproductive age.

Adipocyte-rich omentum offers "good soil" for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and pro-tumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt signaling inhibitor. The effects of dedifferentiated adipocytes in proliferation and migration of OvCa cells were analyzed with in vitro co-culturing experimental models and in vivo mice model, and we demonstrated that OvCa cell lines showed enhanced proliferative characteristics, as well as increased migratory abilities upon co-culturing with O-ADF. Additionally, exogenous transforming growth factor-β1 augmented desmoplastic morphological change of O-ADF, leading to higher proliferative ability. Our results suggest that OvCa cells promote dedifferentiation of peritoneal adipocytes by activating Wnt/β-catenin signaling, and generated O-ADFs exhibit pro-tumoral hallmarks. This article is protected by copyright. All rights reserved.

(1) This study investigated the prognostic impact of tumor size in patients with metastatic cervical cancer. (2) Methods: Seventy-three cervical cancer patients in our institute were stratified into two groups based on distant metastasis: para-aortic lymph node metastasis alone (IIIC2) or spread to distant visceral organs with or without para-aortic lymph node metastasis (IVB) to identify primary tumor size and concurrent chemoradiotherapy. (3) Results: The overall survival (OS) for patients with a tumor &gt, 6.9 cm in size was significantly poorer than that for patients with a tumor ≤6.9 cm in the IVB group (p = 0.0028), the corresponding five-year OS rates in patients with a tumor ≤6.9 and &gt, 6.9 cm were 53.3% and 13.4%, respectively. In the multivariate analysis, tumor size and primary treatment were significantly associated with survival in metastatic cervical cancer. (4) Conclusions: Tumor size ≤6.9 cm and concurrent chemoradiotherapy as the primary treatment were favorable prognostic factors for patients with metastatic cervical cancer.

Most advanced ovarian cancer patients experience recurrence and develop resistance to platinum-based agents. However, the diagnosis of platinum resistance based on platinum-free interval is not always accurate and timely. In this study, we employed laser ablation inductively coupled plasma mass spectrometry to visualize platinum distribution in the tissues at the time of interval debulking surgery following neoadjuvant chemotherapy. Twenty seven patients with advanced high grade serous ovarian cancer were enrolled. Two distinct patterns of platinum distribution were observed. Type A (n = 16): platinum accumulation at the adjacent stroma but little in the tumor; type B (n = 11): even distribution of platinum through tumor and adjacent stroma. Type A was significantly correlated with worse prognosis (P = 0.031). Patients classified in type A and treated with platinum-based adjuvant chemotherapy after operation were significantly shorter period of recurrence after last platinum-based chemotherapy (P = 0.020) and diagnosed with “platinum-resistant recurrence”. Treatment with non-platinum-based chemotherapy after operation could be effective for the patients who were classified in type A. Our data indicate that the platinum resistance can be predicted prior to recurrence with platinum distribution. Thus, we will be able to select more appropriate adjuvant chemotherapy, which may possibly lead to improve patient’s prognosis.

Positive ascites cytology is a strong prognostic factor in patients with early-stage ovarian cancer (OvCa). However, limited information is currently available on the impact of positive ascites cytology on patient prognoses under each clinical background. We herein investigated the comprehensive impact of positive ascites cytology on patients with epithelial OvCa and the effectiveness of additional therapeutic interventions, including complete staging surgery and chemotherapy. Among 4730 patients with malignant ovarian neoplasms, retrospectively identified in multiple institutions, 1906 with epithelial OvCa were included. In the investigation of its effects on clinical factors using a multivariate analysis, positive ascites cytology correlated with a poor prognosis. Positive ascites cytology had a significantly worse prognosis than those with negative cytology in all subgroups except for patients with stage IV tumors and a mucinous histology. Chemotherapy may be effective in reducing the negative impact of positive ascites cytology on the prognosis of patients in terms of progression-free and overall survivals, while complete staging surgery did not improve the prognosis of patients with positive ascites cytology. Collectively, our findings suggested that positive ascites cytology had a negative impact on the prognosis of patients with epithelial OvCa, but not those with stage IV tumors or a mucinous histology.

Simple Summary Ovarian cancer has a poor prognosis and tends to develop peritoneal dissemination. It is becoming increasingly clear that mesothelial cells that cover the peritoneal cavity are involved in ovarian cancer progression. Mesothelial cells are numerous in the peritoneal cavity and normally play many functions to maintain the peritoneal environment. In the tumor microenvironment, mesothelial cells that gain mesenchymal features and cooperate with ovarian cancer are called ovarian cancer-associated mesothelial cells, and they must help ovarian cancer cells to adhere to the peritoneum, invade, and disseminate. Elucidating and targeting these processes may improve the prognosis of ovarian cancer, which is difficult to cure. Abstract Ovarian cancer has one of the poorest prognoses among carcinomas. Advanced ovarian cancer often develops ascites and peritoneal dissemination, which is one of the poor prognostic factors. From the perspective of the “seed and soil” hypothesis, the intra-abdominal environment is like the soil for the growth of ovarian cancer (OvCa) and mesothelial cells (MCs) line the top layer of this soil. In recent years, various functions of MCs have been reported, including supporting cancer in the OvCa microenvironment. We refer to OvCa-associated MCs (OCAMs) as MCs that are stimulated by OvCa and contribute to its progression. OCAMs promote OvCa cell adhesion to the peritoneum, invasion, and metastasis. Elucidation of these functions may lead to the identification of novel therapeutic targets that can delay OvCa progression, which is difficult to cure.

OBJECTIVE: 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). METHODS: 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). RESULTS: 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). CONCLUSION: 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. (Less)

Key Clinical Message Portal vein thrombosis is a rare but life‐threatening complication during pregnancy and postpartum period. Color Doppler ultrasound is useful for prompt diagnosis. Although the risk of complications should be considered, successful pregnancy with comorbid portal vein thrombosis is possible with appropriate anticoagulation therapy and close monitoring.

Ovarian cancer (OvCa) is one of the leading causes of death due to its high metastasis rate to the peritoneum. Recurrent peritoneal tumors also develop despite the use of conventional platinum-based chemotherapies. Therefore, it is still important to explore the factors associated with peritoneal metastasis, as these predict the prognosis of patients with OvCa. In this study, we investigated the function of microphthalmia-associated transcription factor (MITF), which contributes to the development of melanoma, in epithelial ovarian cancer (OvCa). High MITF expression was significantly associated with a poor prognosis in OvCa. Notably, MITF contributed to the motility and invasion of OvCa cells, and specifically with their peri-mesothelial migration. In addition, MITF-positive cells expressed the melanoma cell adhesion molecule (MCAM/CD146), which was initially identified as a marker of melanoma progression and metastasis, and MCAM expression was regulated by MITF. MCAM was also identified as a significant prognostic factor for poor progression-free survival in patients with OvCa. Collectively, our results suggest that MITF is a novel therapeutic target that potentially promotes peritoneal metastasis of OvCa.