Transdermal estrogen gel vs oral estrogen after hysteroscopy for intrauterine adhesion separation: A prospective randomized study.

Background: This randomized controlled trial (RCT) aimed to compare two different routes of postoperative estrogen treatment on the improvements of menstruation, postoperative endometrial thickness, and fertility outcomes in patients with moderate to severe intrauterine adhesions (IUA). Methods: This study prospectively included 78 women (age: 25 to 45 years) with moderate to severe IUA who underwent hysteroscopic resection of adhesions between March 2019 and October 2020. The enrolled patients were randomized 1:1 into either the transdermal gel group (n = 39) or the estradiol valerate oral tablet group (n = 39) on the day of receiving hysteroscopy. Postoperative endometrial thickness, AFS (American Fertility Society) score, estrogen level, and the pattern and amount of menstruation were compared. Pregnancy information was actively collected during 1-year follow-up after the operation. Results: The postoperative endometrium thickness was improved in both groups, and both groups gained menstruation improvement rates of 67%. For patients who underwent second-look hysteroscopy (17 from the oral group and 19 from the transdermal group), the mean AFS score declined greater than 2 in both groups. For patients with postoperative pregnancy intention, the pregnancy rates at 1-year follow-up after the procedures were 40.5% and 28% in the transdermal group and oral group, respectively. Although no statistically significant difference was observed between the two groups, patients in the transdermal group had a tendency toward increased pregnancy rate. Conclusions: Transdermal administration of estrogen is equally efficacious as oral estrogen in postoperative treatment of IUA patients with a relatively safe profile. It is very likely to broaden its indication to the field of IUA. Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=37197, identifier ChiCTR1900022110.

Lipid reprogramming induced by the TFEB-ERRα axis enhanced membrane fluidity to promote EC progression.

BACKGROUND: Estrogen-related receptor α (ERRα) has been reported to play a critical role in endometrial cancer (EC) progression. However, the underlying mechanism of ERRα-mediated lipid reprogramming in EC remains elusive. The transcription factor EB (TFEB)-ERRα axis induces lipid reprogramming to promote progression of EC was explored in this study. METHODS: TFEB and ERRα were analyzed and validated by RNA-sequencing data from the Cancer Genome Atlas (TCGA). The TFEB-ERRα axis was assessed by dual-luciferase reporter and chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR). The mechanism was investigated using loss-of-function and gain-of-function assays in vitro. Lipidomics and proteomics were performed to identify the TFEB-ERRα-related lipid metabolism pathway. Pseudopods were observed by scanning electron microscope. Furthermore, immunohistochemistry and lipidomics were performed in clinical tissue samples to validate the ERRα-related lipids. RESULTS: TFEB and ERRα were highly expressed in EC patients and correlated to EC progression. ERRα is the direct target of TFEB to mediate EC lipid metabolism. TFEB-ERRα axis mainly affected glycerophospholipids (GPs) and significantly elevated the ratio of phosphatidylcholine (PC)/sphingomyelin (SM), which indicated the enhanced membrane fluidity. TFEB-ERRα axis induced the mitochondria specific phosphatidylglycerol (PG) (18:1/22:6) + H increasing. The lipid reprogramming was mainly related to mitochondrial function though combining lipidomics and proteomics. The maximum oxygen consumption rate (OCR), ATP and lipid-related genes acc, fasn, and acadm were found to be positively correlated with TFEB/ERRα. TFEB-ERRα axis enhanced generation of pseudopodia to increase the invasiveness. Mechanistically, our functional assays indicated that TFEB promoted EC cell migration in an ERRα-dependent manner via EMT signaling. Consistent with the in vitro, higher PC (18:1/18:2) + HCOO was found in EC patients, and those with higher TFEB/ERRα had deeper myometrial invasion and lower serum HDL levels. Importantly, PC (18:1/18:2) + HCOO was an independent risk factor positively related to ERRα for lymph node metastasis. CONCLUSION: Lipid reprogramming induced by the TFEB-ERRα axis increases unsaturated fatty acid (UFA)-containing PCs, PG, PC/SM and pseudopodia, which enhance membrane fluidity via EMT signaling to promote EC progression. PG (18:1/22:6) + H induced by TFEB-ERRα axis was involved in tumorigenesis and PC (18:1/18:2) + HCOO was the ERRα-dependent lipid to mediate EC metastasis.

Antitumor efficacy of PARP inhibitors in homologous recombination deficient carcinomas.

PARP inhibitors (PARPis) have remarkable antitumor activity in BRCA mutant ovarian carcinoma. Emerging evidence has shown that responses to PARPis are not limited to BRCA mutant tumors, but could expand to other homologous recombination deficiency (HRD) carcinomas. However, relatively little is known about the efficacy of PARPis in patients with HRD when compared to non-HRD carriers. In this systematic review, 13 clinical trials were included and analyzed for the treatment effect of PARPis on progression free survival (PFS) and overall survival (OS) for HRD (BRCA mutant HRD, n = 697; BRCA wild-type HRD, n = 478) vs. non-HRD (n = 1,417) patients. Pooled analyses of the effect of PARPis in both ovarian and nonovarian carcinoma groups showed significantly higher PFS rates at 6 months and 12 months (PFS6 and PFS12) in the HRD subgroup, as compared to the non-HRD subgroup. Within the HRD subgroup, the BRCA-mutant population achieved significantly higher PFS6 (OR: 2.29, 95% CI: 1.03-5.08) and PFS12 (OR: 1.95, 95% CI: 1.26-3.01) when compared to BRCA wild-type patients. Furthermore, within BRCA wild-type carcinomas, mutations in other HRD-related genes also led to increased PFS6 (OR: 1.72, 95% CI: 1.27-2.43) and PFS12 (OR: 1.85, 95% CI: 1.31-2.62), as compared to non-HRD counterparts. Therefore, patients with HRD carcinomas exhibited pronounced PFS advantages upon treatment with PARPis, as compared to non-HRD carcinomas. In addition to BRCA mutations, other non-BRCA HRD-related aberrations may serve as novel biomarkers for the prediction of PARPi efficacy.

Primary leiomyosarcoma of the fallopian tube: A case report and literature review.

RATIONALE: Primary leiomyosarcoma (LMS) of the fallopian tube is extremely uncommon. To the best of our knowledge, so far only 21 cases of primary fallopian tube LMS have been reported in English-language literature. No new case has been reported in the past 7 years. PATIENT CONCERNS: A 44-year-old premenopausal patient presented with a 5-day history of lower abdominal pain. DIAGNOSES: Pelvic ultrasonography detected an 8.8 × 7.8 × 6.5 cm solid and cystic mass in the left side of the pelvic cavity. The tumor was diagnosed as a primary fallopian tube LMS on paraffin section. INTERVENTIONS: The patient treated surgically followed by 4 cycles of postoperative chemotherapy with dacarbazine and DDP. OUTCOMES: The patient succumbed to the disease 27 months after the initial therapy. LESSONS: Tube LMS is a rare malignant tumor with unknown etiology, difficult early diagnosis, highly invasiveness, high local recurrence and distant metastasis rate, rapid progress, and poor prognosis. It is extremely rare so we can only summarize limited experience from limited data. Every case of tubal LMS is worth being reported.

Clinical significance of BCL11A expression in ER-negative and PR-negative endometrial carcinoma.

OBJECTIVE: To study the mechanism and clinical significance of B-cell lymphoma/leukemia 11A (BCL11A) gene in the development of endometrial carcinoma (EC). METHODS: 100 EC, 20 normal endometrium and 20 atypical hyperplasia endometrium specimens were collected from West China Second University Hospital from January 2005 to January 2015. The expression of BCL11A was detected by immunohistochemistry and its relationships with clinicopathological features and survival were analyzed. RESULTS: The expression of BCL11A in ER-/PR-EC was higher than that in normal endometrium, atypical hyperplasia endometrium, and ER+/PR+EC (P < 0.001). The expression of BCL11A in EC was associated with age, menopause, EC classification, para-aortic lymph node metastasis, tumor differentiation, histological type, ER/PR expression and p53 expression (P < 0.05). The expression of BCL11A in the deceased group was significantly higher than that in the survival group (P = 0.011). Survival analysis indicated that the high expression of BCL11A was associated with low survival rate (P < 0.001). CONCLUSIONS: BCL11A may play an important role in the development of ER-/PR-EC. It may serve as a potential target for therapy and a predict factor for prognosis. It can also provide molecular basis for new EC classification.

[The Expression of Pokemon in Endometrial Carcinoma Tissue and the Correlation with Mutant p53].

OBJECTIVE: To detect the expression of Pokemon in endometrial carcinoma (EC), to provide preliminary theoretical basis for clarifying pathogenesis and searching for effective targets. METHODS: Ninety-eight cases of endometrial tissue paraffin specimens form July 2012 to July 2014 in West China Second University Hospital, Sichuan University, were collected, including: EC group, consisting of adenocarcinoma 23 cases, adenosquamous 12 cases, serous 3 cases, mucinous 11 cases and clear cell 9 cases, and control group, consisting of atypical hyperplasia endometrium 20 cases and normal endometrium 20 cases (secretory 10 cases, hyperplasia 10 cases). Immunohistochemistry was used to detect the expression of Pokemonin each section, analyzing the correlation of Pokemon expression with clinicopathologic characteristics and p53 expression. RESULTS: The positive rate of Pokemon in normal endometrium was 25% (5/20), significantly lower than that in atypical hyperplasia endometrium (60.0%, 12/20) and EC (93.1%, 54/58) (P < 0.05); the rate in type II was 97. 12% (34/35), significantly higher than that in type I (86.96%, 20/23) (P = 0.018). The positive rate of Pokemon in III-IV stage, type II and Ki-67 ≥ 50 EC tissue was much higher (P = 0.012, 0.023, 0.029). In type II EC tissue, the correlation index between Pokemon and p53 is 0.669 (P = 0.000). CONCLUSION: The over expression of Pokemon upregulates the expression of mutant p53, which may be one of the carcinogenesis modes in type II EC.

Ewing's sarcoma/peripheral primitive neuroectodermal tumors of the uterus confirmed with fluorescence in situ hybridization in a 29-year-old Chinese female: a case report and published work review.

Ewing's sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNET) are a group of small round cell sarcomas that show varying degrees of neuroectodermal differentiation characterized by translocation involving the EWS gene. Uterine ES/pPNET is a rare entity. A 29-year-old Chinese female who presented with abdominal swelling and pain was diagnosed with a primary uterine ES/pPNET on the basis of clinicopathologic, immunohistochemical and fluorescence in situ hybridization (FISH) data. She was given a multimodal treatment, including neoadjuvant, 95% cytoreductive, chemotherapy and radiotherapy. The patient is currently alive with persistent disease after 18 months of follow-up. We emphasized the crucial role of molecular techniques in the differential diagnosis of small round cell tumors in this unusual location. Multimodal therapy may improve the outcomes of patients.

[Clinical Pathological Analysis of 29 Cases of Borderline Ovarian Tumors with Intraepithelial Carcinoma].

OBJECTIVE: To investigate the clinicopathological characteristics, prognosis and the pregnancy condition after preserving fertility function surgery of borderline ovarian tumors with intraepithelial carcinoma (OIC). METHODS: Clinical data of 29 patients with OIC at Department of Gynecology, West China Second University Hospital, Sichuan University, between January 2005 and March 2014, were collected for retrospectively analysis with 6-93 months follow-up. The recurrence rate and pregnancy rate after preserving fertility function surgery were compared. RESULTS: OIC patients accounts for 4.0% (29/719) in borderline tumors patients, including fertility preserving function requirement 51.7% (15/29). All patients underwent surgery treatment, including conservative surgery 51.7% (15/29), radical surgery 48.3% (14/29). Adjuvant chemotherapy 27.6% (8/29). Pathological types: mucinous 69.0% (20/29), serous 13.8% (4/29), endometrioid 6.9% (2/29) and mixed 10.3% (3/29). FIGO stage: I a 75.9% (22/29), I b 17.2% (5/29), I c 6.9% (2/29). The average follow-up time was 49.6 months, the recurrence rate was 10.3% (3/29), the pregnancy rate was 66.7% (10/15). The recurrence rate of higher stage and intraoperative retaining ovaries was higher (P = 0.005, P = 0.005); the pregnancy rate of younger patients was higher (P=0.017). CONCLUSION: OIC patients are young, diagnosed at an early stage. Pathological types are mainly mucinous. For patients with fertility requirements, the recurrence rate of ovarian tumor excision surgery is very high.

Laparoscopic modified sacral hysteropexy: initial experience with an original surgical approach to uterovaginal prolapse.

STUDY OBJECTIVE: To evaluate the feasibility of a modified laparoscopic approach to correct uterovaginal prolapse using cervical cerclage tape to attach the uterine isthmus to the sacral promontory. DESIGN: Retrospective study (Canadian Task Force classification III). SETTING: Tertiary referral center. PATIENTS: From January 2011 to February 2013, 33 patients underwent laparoscopic modified sacral hysteropexy with use of cervical cerclage tape at West China Second University Hospital. All patients had stage 2 to 4 uterovaginal prolapse according to the Pelvic Organ Prolapse Quantification System. MEASUREMENTS AND MAIN RESULTS: The outcome was assessed via preoperative and postoperative pelvic examinations, and the surgical results were evaluated. The mean operative time was 90.0 minutes, and blood loss was 80.5 mL. No intraoperative or postoperative complications occurred. At the minimum 6-month follow up, all patients had prolapse of stage I or lower. CONCLUSIONS: After larger trials are performed to assess the safety and efficacy of this modified laparoscopic sacral hysteropexy, this novel approach might be considered as an alternative treatment option in patients with uterovaginal prolapse.