30-Year Experience With 22 Cases of Malignant Transformation Arising From Ovarian Mature Cystic Teratoma: A Rare Disease.

Objective: To investigate the clinical characteristics and survival outcomes of patients with malignant transformation arising from ovarian mature cystic teratoma (MT-MCT). Methods: This retrospective study included patients with ovarian MCTs at Peking Union Medical College Hospital (PUMCH) during 1990.01-2020.12. When the pathologic histology was MT-MCT, detailed information was collected. Results: Overall, 7229 ovarian MCT patients and 22 patients with MT-MCT were enrolled. The rate of malignant transformation of all ovarian MCTs was 0.30%. Most patients with MT-MCT were 51 (21-75) years old, and the tumor mass size was 10 (3-30) cm. The typical clinical symptoms were mainly abdominal pain and distension. The levels of tumor markers were elevated on preoperative examination. Early diagnosis could be made by ultrasonic examination, pelvic enhanced MRI and CT. Most patients underwent debulking surgery and adjuvant chemotherapy. The most common histological type to exhibit malignant transformation was squamous cell carcinoma (59.1%), followed by adenocarcinoma (13.6%), carcinoid (9.1%), and borderline tumor (18.2%). The 5-year RFS and OS rates were 54.5% and 81.8%, respectively. Patients with FIGO stage I had the best RFS (P=0.047) and OS (P=0.018), followed by those with FIGO stage II-IV. Conclusion: MT-MCTs mainly occur in elderly females, are rare and have a poor prognosis. Advanced FIGO stage is a risk factor for survival. Although there is no standard treatment, cytoreductive debulking surgery and adjuvant chemotherapy could be considered. Perimenopausal and menopausal women with MCT should receive surgical treatment.

Case Report: Management of Recurrent Ovarian Squamous Cell Carcinoma With PD-1 Inhibitor.

Malignant transformations, such as ovarian squamous cell carcinoma (SCC) in ovarian mature cystic teratoma (OMCT), are rare tumors. The management of recurrent disease is still a challenge, and the gene mutations involved remain unclear. We herein report a recurrent case of ovarian SCC with a PIK3CA gene variation and immunohistochemical staining of programmed death-ligand 1 (PD-L1) >10%. This patient achieved clinical remission after platinum-based effective chemotherapy and programmed death 1 (PD-1) immunotherapy.

Effect and Management of Excess Weight in the Context of Fertility-Sparing Treatments in Patients With Atypical Endometrial Hyperplasia and Endometrial Cancer: Eight-Year Experience of 227 Cases.

OBJECTIVE: To investigate the oncologic and reproductive outcomes of fertility-sparing treatments (FSTs) in atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) patients with excess weight (EW). METHODS: This retrospective study comprised patients with AEH or EC who achieved a complete response (CR) after FST from 2010 to 2018. The clinical characteristics, oncological and reproductive outcomes were compared between the excess weight (EW) group (body mass index (BMI)≥25 kg/m2) and normal weight (NW) group (BMI<25 kg/m2). The risk factors associated with recurrence and unsuccessful pregnancy in patients with EW were analyzed. RESULTS: Overall, 227 patients were enrolled, including 139 (61.2%) in EW group and 88 (38.8%) in NW group. In patients with EW, the pregnancy rate, the live birth rate and the relapse rate were 29.8%, 23.4%, and 30.9%, respectively. In patients with NW, these rates were 61.1%, 47.2%, and 31.8%, respectively. No significant differences were observed in the time to remission (P=0.865) and disease-free survival (DFS) (P=0.750). Patients in NW group achieved a better pregnancy rate than patients in the EW group (P=0.034). The patients with EW using ovulation induction to increase fertility tended to have a shorter time to pregnancy (P=0.042). However, no significant risk factors associated with unsuccessful pregnancy were identified after the multivariate analysis. In terms of DFS, the combination of gonadotropin-releasing hormone agonist (GnRH-a) and LNG-IUD was better for patients with EW than GnRH-a or oral progestin therapy alone (P=0.044, adjusted hazard ratio (HR)=0.432, 95% confidence interval (CI): 0.152-1.229), especially for patients with EW diagnosed with EC (P=0.032). CONCLUSION: FSTs for overweight and obese patients should be more individualized. GnRH-a and/or LNG-IUD may be options prior to FSTs in patients with EW. Further prospective studies are needed.

Patient-Derived Xenografts Are a Reliable Preclinical Model for the Personalized Treatment of Epithelial Ovarian Cancer.

To generate robust patient-derived xenograft (PDX) models for epithelial ovarian cancer (EOC), analyze the resemblance of PDX models to the original tumors, and explore factors affecting engraftment rates, fresh cancer tissues from a consecutive cohort of 158 patients with EOC were collected to construct subcutaneous PDX models. Paired samples of original tumors and PDX tumors were compared at the genome, transcriptome, protein levels, and the platinum-based chemotherapy response was evaluated to ensure the reliability of the PDXs. Univariate and multivariate analyses were used to determine the factors affecting the engraftment rates. The engraftment success rate was 58.23% (92/158) over 3-6 months. The Ki-67 index and receiving neoadjuvant chemotherapy can affect the engraftment rate in primary patients. The PDX models generated in this study were found to retain the histomorphology, protein expression, and genetic alteration patterns of the original tumors, despite the transcriptomic differences observed. Clinically, the PDX models demonstrated a high degree of similarity with patients in terms of the chemotherapy response and could predict prognosis. Thus, the PDX model can be considered a promising and reliable preclinical tool for personalized and precise treatment.

Systematic Lymph Node Dissection May Be Abolished in Patients With Apparent Early-Stage Low-Grade Mucinous and Endometrioid Epithelial Ovarian Cancer.

OBJECTIVE: To investigate whether systematic lymph node dissection can confer clinical benefits in patients with apparent early-stage low-grade epithelial ovarian cancer. METHODS: Patients with apparent early-stage low-grade epithelial ovarian cancer seen at Peking Union Medical College Hospital from January 1, 2005, to December 31, 2015, were retrospectively enrolled. Patients with other histological types and those who did not receive necessary adjuvant chemotherapy were excluded. Data collection and long-term follow-up were performed. According to the removed lymph node number, three groups based on surgical methods were used: abnormal lymph node resection, pelvic lymphadenectomy, and systematic lymph node dissection to control surgical quality. Their effects on prognosis were analyzed in pathological subgroups. RESULTS: A total of 196 patients were enrolled; 30.1% of patients had serous, 42.3% of patients had mucinous, and 27.6% of patients had endometrioid carcinoma, of which 51 (26.0%), 96 (49.0), and 49 (25.0%) patients were treated with the above surgical methods, respectively. The occult lymph node metastasis rate was 14 (7.1%), and only five (2.6%) of apparent early-stage patients were upstaged due to lymph node metastasis alone. Systematic lymph node dissection did not benefit progression-free survival or disease-specific overall survival of apparent early-stage low-grade mucinous and endometrioid epithelial ovarian cancer but prolonged progression-free survival of apparent early-stage low-grade serous patients (OR, 0.231, 95% CI, 0.080, 0.668, p = 0.007). CONCLUSIONS: Systematic lymph node dissection may be abolished in patients with apparent early-stage low-grade mucinous and endometrioid epithelial ovarian cancer but may be considered for apparent early-stage low-grade serous patients.

A Comparison of Laparoscopies and Laparotomies for Radical Hysterectomy in Stage IA1-IB1 Cervical Cancer Patients: A Single Team With 18 Years of Experience.

OBJECTIVE: To investigate the safety and efficacy of abdominal radical hysterectomy (ARH) and laparoscopic radical hysterectomy (LRH) in managing early-stage cervical cancer. METHODS: This retrospective study comprised patients with FIGO stage IA1 with lymphovascular space invasion (LVSI), IA2, and IB1 cervical cancer who underwent radical hysterectomy performed by a single gynecologic oncology team at Peking Union Medical College Hospital from 2000-2018. The clinicopathological characteristics, surgical outcomes, and survival outcomes were compared between the two groups. RESULTS: The ARH and LRH groups consisted of 84 and 172 patients, respectively. The 5-year progression-free survival (PFS) rates were 89.3 and 95.9% in the ARH and LRH groups (P = 0.122, adjusted HR = 0.449, 95% CI: 0.162-1.239), respectively, while the 5-year overall survival (OS) rates were 95.2 and 98.8%, respectively (P = 0.578, adjusted HR = 0.650, 95% CI: 0.143-2.961). The presence of more than two comorbidities led to poor OS (P = 0.011). For patients with a BMI greater than 24 kg/m2, LRH was associated with better PFS (P = 0.039). Compared with ARH, LRH was associated with a shorter operation time (248.8 vs. 176.9 min, P < 0.001), less blood loss (670.2 vs. 200.9 ml, P < 0.001), and lower postoperative ileus rates (2.4% vs. 0%, P = 0.042). No significant differences were observed in PFS and OS between 2006-2012, 2013-2015, and 2016-2018 in the LRH group (P = 0.126 and P = 0.583). CONCLUSION: Compared with ARH, LRH yields similar survival and improved surgical outcomes in patients with early-stage cervical cancer. LRH is not inferior to ARH for select cervical cancer patients treated by a single team with adequate laparoscopy experience.

Clinical characteristics, treatment and outcomes of adnexal torsion in pregnant women: a retrospective study.

BACKGROUND: Adnexal torsion during pregnancy is a gynecological emergency. Delayed diagnosis and treatment can cause ovarian necrosis and fetal loss. This study assessed the clinical characteristics, treatment and outcomes of adnexal torsion in pregnant women. METHODS: A retrospective study was conducted at a tertiary center between January 2008 and January 2018. Eighty-two pregnant women with surgically confirmed adnexal torsion were included. The clinical characteristics, ultrasound data, surgical interventions and pregnancy outcomes were analyzed. RESULTS: The median age of the patients was 28 (range, 18-38) years. The median gestational age was 11 (range, 6-31) weeks: 53 (64.6%) were in the first trimester, 21 (25.6%) were in the second trimester, and 8 (9.8%) were in the third trimester. The most common symptoms and signs were sudden pelvic pain (100%) and adnexal or pelvic masses (97.6%), followed by nausea and vomiting (61%). The Doppler blood flow signal disappeared in 62.5% of the patients. Sixty-three (76.8%) patients underwent laparoscopy, and 29 (24.2%) underwent laparotomy. The median gestational age in patients undergoing laparotomy was higher than that in those undergoing laparoscopy (26 weeks vs 10 weeks, p < 0.001). Fifty-three (64.6%) patients underwent conservative surgery, with 48 detorsions and cystectomies, 2 detorsions and cyst fenestrations, 1 detorsion only and 2 salpingectomies only. Twenty-nine (25.4%) patients underwent unilateral salpingo-oophorectomy. There were no cases of postoperative thrombosis, spontaneous abortion or recurrence during the same pregnancy. Seven patients underwent simultaneous artificial abortion. One patient experienced intrauterine fetal death, and 74 patients had live births. CONCLUSION: Surgical intervention was required as soon as possible. Laparoscopic conservative surgery is safe and may be appropriate to preserve ovarian function.

[Niche and interspecific associations of major nekton in northern coastal waters in Yuhuan, Taizhou, China]. / 台州玉环北部沿岸海域主要游泳动物生态位和种间联结性.

Base on the data from fishery resources survey carried out in northern coastal waters in Yuhuan in November 2016 (autumn) and April 2017 (spring), we examined the niche and interspecific associations of major nekton by the methods of index of relative importance (IRI), niche breadth, niche overlap, the variance ratio (VR), X2-test, association coefficient (AC), Jaccard index (JI), point correlation coefficient (Φ) and Spearman rank correlation index. The ecological niche breadth of Portunus trituberculatus was the largest, with the absolute competitive advantage. The niche breadths of the important economic species Coilia nasus and Octopus variabilis were the smallest, which was at a weak competitive position. The niche overlap of the major nekton species in this area was uneven, possibly caused by the diversity of local environments. Overall interspecific associations indicated that insignificant negative correlation existed among major nekton species. All results of the X2-test, association coefficient (AC) and Jaccard index (JI) were consistent with that of overall interspecific associations, which indicated the independent trend among species. The correlation coefficients (Φ) and the Spearman rank correlation index revealed that the positive coupling pairs were more than the negative ones. It was due to the positive association among the other 14 species, caused by the spatial exclusion from large captured individuals of Muraenesox cinereus. According to the Spearman rank correlation and cluster analysis, 15 species could be divided into five ecological groups. The species within one ecological group had similar ecologically adaptable requirements of habitat, while the species from different ecological groups had different living habits and different ecological requirements.

Proliferation and Glia-Directed Differentiation of Neural Stem Cells in the Subventricular Zone of the Lateral Ventricle and the Migratory Pathway to the Lesions after Cortical Devascularization of Adult Rats.

We investigated the effects of cortical devascularization on the proliferation, differentiation, and migration of neural stem cells (NSCs) in the subventricular zone (SVZ) of the lateral ventricle of adult rats. 60 adult male Wistar rats were randomly divided into control group and devascularized group. At 15 and 30 days after cerebral cortices were devascularized, rats were euthanized and immunohistochemical analysis was performed. The number of PCNA-, Vimentin-, and GFAP-positive cells in the bilateral SVZ of the lateral wall and the superior wall of the lateral ventricles of 15- and 30-day devascularized groups increased significantly compared with the control group (P < 0.05 and P < 0.01). The area density of PCNA-, Vimentin-, and GFAP-positive cells in cortical lesions of 15- and 30-day devascularized groups increased significantly compared with the control group (P < 0.05 and P < 0.01). PCNA-, GFAP-, and Vimentin-positive cells in the SVZ migrated through the rostral migratory stream (RMS), and PCNA-, GFAP-, and Vimentin-positive cells from both the ipsilateral and contralateral dorsolateral SVZ (dl-SVZ) migrated into the corpus callosum (CC) and accumulated, forming a migratory pathway within the CC to the lesioned site. Our study suggested that cortical devascularization induced proliferation, glia-directed differentiation, and migration of NSCs from the SVZ through the RMS or directly to the corpus callosum and finally migrating radially to cortical lesions. This may play a significant role in neural repair.

Annexin A3 Is a Potential Predictor of Platinum Resistance in Epithelial Ovarian Cancer Patients in a Prospective Cohort.

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies and is rarely cured in the recurrent setting, mainly because of progressive chemoresistance, especially platinum resistance. In our previous studies, the platinum-resistance-related protein, annexin A3, was selected by comparative proteomics. In this study, we detected serum annexin A3 levels using a self-developed chemiluminescence immunoassay kit in a prospective EOC patient cohort. We also evaluated the capacity of serum annexin A3 levels to predict platinum resistance. Serum annexin A3 levels in healthy women exhibited a similar normal distribution (Z=0.723, P=0.673), allowing determination of a normal cutoff level of 0.11-1.45 ng/mL. Of the 89 EOC patients, 21 were platinum resistant and 68 were platinum sensitive. Residual disease after primary surgery (p=0.004) and serum annexin A3 levels (p=0.036) were both independent factors associated with platinum resistance. The AUC was 0.733 (95% confidence interval (CI), 0.627-0.823). The optimal cutoff value for serum annexin A3 levels was 2.05 ng/mL. Multivariate logistic analysis showed that expression of annexin A3 as assessed by immunohistochemistry (P=0.005) and residual tumor size (P=0.000) had a significant influence on platinum resistance. The AUC of ROC curve of annexin A3 expression by immunohistochemistry was 0.664 (95% CI, 0.554-0.763) and the cut off value was ">=moderate scores". In conclusion, we demonstrate that annexin A3 is a secreted protein that may be measured in the peripheral blood using a self-developed, chemiluminescence immunoassay kit. Serum annexin A3 levels may be a potential predictor of platinum resistance in epithelial ovarian cancer patients.

Cytotoxic ent-kaurane diterpenoids from Isodon macrophyllus.

Two new ent-kaurane diterpenoids, dayecrystals D-E (1-2), together with nine known compounds, isojaponin A (3), rabdosin A (4), lushanrubescensin J (5), wikstroemioidin B (6), maoyecrystal C (7), rabdosin B (8), isodonal (9), shikokianin (10), and effusanin A (11), were isolated from the leaves of Isodon macrophyllus. The structures of the new compounds were elucidated using 1D and 2D NMR spectroscopy. The (13)C-NMR spectral data of compound 4 are reported for the first time. All of the compounds were tested for their cytotoxicities against DU145 and LoVo human tumor cells. Compounds 4, 10, and 11 showed inhibitory effects on DU145 cells with IC(50) values 5.90, 4.24, and 3.16 microM, and LoVo cells with IC(50) values 14.20, 17.55, and 3.02 microM, respectively.

[Chemical constituents of Isodon macrophyllus (II)].

OBJECTIVE: To study the chemical constituents of Isodon macrophyllus. METHODS: Compounds were spearated and purified by silica gel column chromatography and their structures were elucidated on the basis of spectral data and chemical evidences. RESULTS: Six compounds were obtained from EtOAc extract of leaves of Isodon macroplhllus and identified as rabdophyllin H(I), lushan-ruhescensins F(II), maovecrystal J(III), Taibaijap onicain A(IV), rabdosinate(V), dancostero(VI). CONCLUSION: Co mpounds II-IV were isolated from this plant for the first time.