Ovarian clear cell carcinoma with uterine intramural recurrence: Case report of ovarian clear cell carcinoma with fertility sparing treatment.

OBJECTIVE: Ovarian clear cell carcinoma has a poor prognosis in comparison with other pathological types of epithelial ovarian carcinoma. It also has relative resistance to first-line platinum-based chemotherapy with a great risk of recurrence. CASE REPORT: We report a case of recurrent ovarian clear cell carcinoma status after left salpingo-oophorectomy (fertility-sparing debulking operation) and six courses of adjuvant chemotherapy (paclitaxel (175 mg/m2)/carboplatin (AUC 6)). However, two years after diagnosis, elevated CA-125 accompanied by an intrapelvic mass was noted. Uterine intramural recurrence was found during the second laparotomy. She was treated with right salpingo-oophorectomy and abdominal hysterectomy combined with systemic chemotherapy administration (paclitaxel (175 mg/m2)/carboplatin (AUC 6)) and maintenance therapy (bevacizumab (7.5 mg/kg)). There was no other recurrence until one and a half years postoperatively, and the patient was tumor free with regular follow-up. CONCLUSION: In young patients with stage I ovarian clear cell carcinoma, fertility-sparing surgery was considered. Most patients will suffer from tumor recurrence, and also intrauterine recurrence rarely happen.

Uterine leiomyoma is associated with the risk of developing endometriosis: A nationwide cohort study involving 156,195 women.

OBJECTIVE: Evidence for an association between uterine leiomyoma and increased risk of endometriosis is limited by small sample sizes and short follow-up periods. We assessed this association in a large nationwide sample with 14 years of data. DESIGN: Data were sourced from Taiwan's Longitudinal Health Insurance Database 2000 (LHID2000). MATERIALS AND METHODS: We identified 31,239 women aged ≥20 years diagnosed with uterine leiomyoma (International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] code 218) between Jan 1, 2000 and Dec 31, 2012, who were matched with 124,956 controls (1:4) by 5-year age groups and year of diagnosis. Follow-up was from the date of LHID2000 entry to the first occurrence of endometriosis, loss to follow-up, insurance termination, or until December 31, 2013, whichever was earlier. RESULTS: In Cox regression analysis, the adjusted hazard ratio (aHR) for endometriosis in women with uterine leiomyoma was 6.44 (95% CI, 6.18, 6.72) compared with controls. The risk of endometriosis was significantly increased in women with uterine leiomyoma and comorbidities of tube-ovarian infection (aHR 2.86; 95% CI, 1.28, 6.36), endometritis (1.14; 1.06, 1.24), infertility (1.26; 1.16, 1.37), or allergic diseases (1.11; 1.05, 1.17). Having both uterine leiomyoma and endometritis significantly increased the risk of endometriosis (aHR 6.73; 95% CI, 6.07, 7.45) versus having only uterine leiomyoma (6.61; 6.33, 6.91) or endometritis (1.49; 1.31, 1.69). Similarly, having both uterine leiomyoma and infertility significantly increased the risk of endometriosis (aHR 6.95; 95% CI, 6.21, 7.78) versus having only uterine leiomyoma (6.66; 6.38, 6.96) or infertility (1.78; 1.57, 2.02). CONCLUSIONS: A diagnosis of uterine leiomyoma appears to increase the risk of endometriosis. Patients presenting with uterine fibroids should be encouraged to give informed consent for possible simultaneous surgical treatment of endometriosis.

Transcriptome Analysis of Dnmt3l Knock-Out Mice Derived Multipotent Mesenchymal Stem/Stromal Cells During Osteogenic Differentiation.

Multipotent mesenchymal stem/stromal cells (MSCs) exhibit great potential for cell-based therapy. Proper epigenomic signatures in MSCs are important for the maintenance and the subsequent differentiation potential. The DNA methyltransferase 3-like (DNMT3L) that was mainly expressed in the embryonic stem (ES) cells and the developing germ cells plays an important role in shaping the epigenetic landscape. Here, we report the reduced colony forming ability and impaired in vitro osteogenesis in Dnmt3l-knockout-mice-derived MSCs (Dnmt3l KO MSCs). By comparing the transcriptome between undifferentiated Dnmt3l KO MSCs and the MSCs from the wild-type littermates, some of the differentially regulated genes (DEGs) were found to be associated with bone-morphology-related phenotypes. On the third day of osteogenic induction, differentiating Dnmt3l KO MSCs were enriched for genes associated with nucleosome structure, peptide binding and extracellular matrix modulation. Differentially expressed transposable elements in many subfamilies reflected the change of corresponding regional epigenomic signatures. Interestingly, DNMT3L protein is not expressed in cultured MSCs. Therefore, the observed defects in Dnmt3l KO MSCs are unlikely a direct effect from missing DNMT3L in this cell type; instead, we hypothesized them as an outcome of the pre-deposited epigenetic signatures from the DNMT3L-expressing progenitors. We observed that 24 out of the 107 upregulated DEGs in Dnmt3l KO MSCs were hypermethylated in their gene bodies of DNMT3L knock-down ES cells. Among these 24 genes, some were associated with skeletal development or homeostasis. However, we did not observe reduced bone development, or reduced bone density through aging in vivo. The stronger phenotype in vitro suggested the involvement of potential spreading and amplification of the pre-deposited epigenetic defects over passages, and the contribution of oxidative stress during in vitro culture. We demonstrated that transient deficiency of epigenetic co-factor in ES cells or progenitor cells caused compromised property in differentiating cells much later. In order to facilitate safer practice in cell-based therapy, we suggest more in-depth examination shall be implemented for cells before transplantation, even on the epigenetic level, to avoid long-term risk afterward.

Surgical outcomes of hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (vNOTES) compared with laparoscopic total hysterectomy (LTH) in women with non-prolapsed and benign uterine diseases.

OBJECTIVE: We aimed to compare the surgical outcomes between hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and laparoscopic total hysterectomy (LTH). MATERIALS AND METHODS: This study is a retrospective chart analysis. From January 1, 2015, to December 31, 2017, a total of 183 patients of reproductive age with an indication for hysterectomy due to non-prolapsed and benign uterine diseases were enrolled. After exclusion, 20 patients were included in the vNOTES group, and 66 patients were included in the LTH group. Various post-operative surgical outcomes such as operative time, blood loss, uterus weight, a decrease in hemoglobin level on post-operative day one, post-operative pain scale, complications, length of hospitalization, and re-admission rate were measured. RESULTS: No difference was observed between both groups regarding operative time, blood loss, uterine weight, a decrease in hemoglobin level on post-operative day one, complications, hospital stay, and re-admission rate. Patients in the vNOTES group had significantly less post-operative pain compared with those in the LTH group (p = 0.03). CONCLUSIONS: The surgical outcomes of hysterectomy by vNOTES could be similar to those of LTH. Patients undergoing hysterectomy by vNOTES may have less post-operative pain compared with those undergoing LTH. However, the sample size was small, and the results need more evidence to confirm these findings.

Patients with uterine leiomyoma exhibit a high incidence but low mortality rate for breast cancer.

The association of uterine leiomyoma with increased risk of breast cancer is controversial. Therefore, we used the National Health Insurance Research Database of Taiwan to examine breast cancer incidence and mortality among Asian patients with and without uterine leiomyoma. We compared breast cancer incidence and mortality between 22,001 newly diagnosed uterine leiomyoma patients and 85,356 individuals without uterine leiomyoma matched by age and date of diagnosis. Adjusted hazard ratios for breast cancer were estimated using the Cox model. The incidence of breast cancer was 35% higher in the uterine leiomyoma group than the leiomyoma-free group (1.65 vs. 1.22 per 1,000 individuals, p < 0.001), with an adjusted hazard ratio of 1.31 (95% confidence interval = 1.13-1.52). Interestingly, overall mortality was lower (4.12%) in the uterine leiomyoma group (mean followed time, 3.59 ± 2.70 years) than the leiomyoma-free group (8.78%; mean followed time, 3.54 ± 2.67 years) at the endpoint of the study (p <0.05). These findings indicate the incidence of breast cancer is higher in patients with uterine leiomyoma than in those without it, but overall mortality from breast cancer was lower in the patients with uterine leiomyoma.

Risk of depression in patients with uterine leiomyoma: A nationwide population-based cohort study.

BACKGROUND: Population-based cohort study investigating the depression risk for patients with uterine leiomyoma (UL) is unavailable. This study investigated the subsequent risk of depression among patients with UL in an Asian population. METHODS: Using data from the National Health Insurance Research Database of Taiwan, we established a cohort with 21,168 patients diagnosed with UL between 2000 and 2010, and a non-UL cohort of 82,108 women without UL matched by age and year of diagnosis. The occurrence of depression and Cox method measured adjusted hazard ratios (aHRs) were monitored until the end of 2011. The depression risk altered by surgery was also evaluated. RESULTS: The overall incidence of depression was 54% higher in the UL cohort than in the non-UL cohort (7.48 vs. 4.88/1000 person-years, p<0.001), with an aHR of 1.46 [95% confidence interval (CI)=1.36-1.57] for the UL cohort. The depression risk increased with age and with comorbidity in both cohorts. Surgical intervention reduced the depression incidence to 4.76/1000 person-years for women with UL, with an aHR of 0.64 (95% CI=0.51-0.81) compared with those without a surgical treatment. CONCLUSION: The risk of depression is significantly higher in patients with UL than in those without UL. Surgical intervention for UL could significantly reduce the risk of depression. Evaluation of psychiatric status in patients with UL is strongly recommended.