Hysteroscopic Curettage Followed by Megestrol Acetate Plus Metformin as a Fertility-Sparing Treatment for Women with Atypical Endometrial Hyperplasia or Well-Differentiated Endometrioid Endometrial Carcinoma.

Background: In reproductive-aged women, the incidence of atypical endometrial hyperplasia (AEH) or endometrioid endometrial carcinoma (EEC) is rising globally. The study aimed to investigate the effectiveness of hysteroscopic curettage followed by megestrol acetate (MA) plus metformin as conservative treatment in AEH and early EEC. Methods: We retrospectively studied AEH and stage IA, grade 1 EEC patients treated with hysteroscopic curettage followed by MA (160 mg/d) plus metformin (1500 mg/d) from January 2010 to December 2020 at Fudan University Shanghai Cancer Center. Treatment outcomes were assessed by complete response (CR) rate, recurrence rate, and pregnancy outcomes. Univariate and multivariate analyses were performed via the logistic regression model. Results: The study included 79 patients, 31 (39.2%) with AEH and 48 (60.8%) with EEC. The medians of age (years) and follow-up time (months) were 30 and 39.5, respectively. Seventy-six patients (96.2%) finally achieved CR. The median time to CR was 3.6 (3.0-20.6) months. The CR rate after 3 months, 6 months, and 1 year was 55 (69.6%), 67 (84.8%), and 72 (91.1%), respectively. Recurrence occurred in 26 (34.2%) patients. Treatment duration ⩾9 months was associated with a lower recurrence rate after CR (P = .012). Fourteen (93.3%) of the 15 recurrent patients who received progestin re-treatment achieved CR again. Finally, 29 patients delivered live births. Conclusions: Hysteroscopy followed by MA plus metformin can achieve CR in short time and is overall safe. Consolidation treatment should be prolonged to decrease the recurrence rate, despite a shorter time to CR.

Construction and functional analysis of an anti-human cervical carcinoma/anti-human CD3 single-chain bispecific antibody.

The aim of the present study was to construct a single-chain bispecific antibody (scBsAb) against cervical carcinoma and to investigate its biological activities. The scBsAb was constructed using a genetic cloning technique and antigen binding activities were detected by ELISA. The iodogen method was used to analyze the pharmacokinetics. The Rosette formation test was used to detect the binding ability between peripheral blood lymphocytes (PBLs) and Cs1213 cervical cancer cells. In addition, the MTT method was performed to detect the killing effect of PBLs. The molecular weight of the scBsAb was ~60 kDa. The antigen binding activities of scBsAbs were compared with the anti­human cervical carcinoma antibody single­chain Fv fragment (CSAs­1 scFv) and anti­cluster of differentiation (CD)3 scFv (P>0.05). In addition, a pharmacokinetics assay demonstrated that compared with the two corresponding scFvs, scBsAbs exhibited a significantly prolonged retention time in the body (P<0.01). In addition, the number of rosettes formed by PBLs and Cs1213 cells in the scBsAb group was markedly greater than that in the scFv groups or the RPMI­1640 group (P<0.05 and P<0.01, respectively). The killing activity of PBLs against scBsAb­mediated Cs1213 cells was significantly greater than that mediated by the other antibodies (P<0.05). When the concentration of scBsAb was 40 µg/ml, the killing rate was 64.5%. Thus, anti­human cervical carcinoma/anti­CD3 scBsAbs may possess two types of antigen binding activity, prolong the duration in vivo and improve the killing activity of PBLs against cancer cells.

A prospective study of fertility-sparing treatment with megestrol acetate following hysteroscopic curettage for well-differentiated endometrioid carcinoma and atypical hyperplasia in young women.

PURPOSE: To investigate the feasibility and efficacy of curettage with hysteroscopy followed by megestrol acetate (MA) for well-differentiated endometrioid carcinoma (EC) confined to the endometrium and for atypical hyperplasia (AH) in young women. PATIENTS AND METHODS: Fourteen patients with EC and 12 patients with AH were prospectively enrolled in this study. All of the patients received at least 12 weeks of oral MA (160 mg/day) following thorough curettage with hysteroscopy. The response was assessed histologically every 12 weeks. The primary endpoint was the complete response rate. Adverse events, pregnancy rates and recurrence rates were secondary end points. RESULTS: Twenty-one (80.8 %) patients responded to treatment. The median time to response was 12 weeks. After a median follow-up of 32 months, 6 patients had recurrences. Significantly, more patients with infertility or PCOS experienced recurrence (P = 0.040, P = 0.015). Eight patients attempted to conceive after complete response; two spontaneous conceptions and one normal delivery were achieved. No disease-related or treatment-related deaths were observed. CONCLUSIONS: Fertility-sparing treatment with MA following entirely hysteroscopic curettage is effective, demonstrating the least toxicity for rigorously selected young women with well-differentiated EC confined to the endometrium or with AH; however, close follow-up is required for the potential consequences of improper patient selection and a substantial rate of recurrence.

[Clinical implications of positive peritoneal cytology in endometrial cancer].

OBJECTIVE: To evaluate the clinical significance of positive peritoneal cytology in patients with endometrial cancer. METHODS: The records of 315 patients with endometrial cancer who were operated at Cancer Hospital, Fudan University between January 1996 and December 2008 were reviewed. Peritoneal cytology were performed and diagnosed in all patients. Factors related with peritoneal cytology were analyzed by correlation analysis. Log-rank test and Cox regression test was used for the analysis of prognosis, respectively. RESULTS: (1) Peritoneal cytology were positive in 30 (9.5%) patients. Positive peritoneal cytology was associated with pathological subtype (P = 0.013), stage (P = 0.000), myometrial invasion (P = 0.012), lymph-vascular space invasion (P = 0.012), serosal involvement (P = 0.004), cervical involvement (P = 0.016), adnexal involvement (P = 0.000), and omental involvement (P = 0.000), with no association with grade (P = 0.152) and lymph node metastasis (P = 0.066). (2) Three-year overall survival (OS) and progression-free survival (PFS) were 93.0% and 85.5%, respectively. Positive peritoneal cytology, surgical stage, pathological subtype, myometrial invasion, grade, and lymph-vascular space invasion were significantly associated with worse prognosis by univariate analysis (P < 0.05), while only surgical-pathology stage and myometrial invasion were independent prognostic factors by multivariate analysis (P < 0.05). For 30 cases with positive peritoneal cytology, the patients with no high risk factors shown significantly prognoses better than those with any risk factors. The results shown that for patients with late stage (stage III-IV) endometrial cancer with positive peritoneal cytology was significantly associated with the worse OS and PFS by multivariate analysis (P = 0.006). CONCLUSIONS: Positive peritoneal cytology was associated with serosal involvement, cervical involvement, adnexal involvement, omental involvement, and late stage. Therefore, peritoneal cytology should be performed and reported separately as a part of full surgical staging procedure.

[Clinical significance of Her-2/neu status in patients with uterine papillary serous carcinoma].

OBJECTIVE: The purpose of this study was to evaluate gene amplification by chromogenic in situ hybridization (CISH) and the protein expression of Her-2/neu gene in patients with uterine papillary serous carcinoma (UPSC) and to determine its prognostic value. METHODS: Thirty-six patients with confirmed pathologic diagnosis of UPSC in Cancer Hospital of Fudan University from Jan. 1996 to Jan. 2006, were analysed retrospectively. CISH was performed to assess Her-2/neu gene amplification, and protein expression was evaluated by immunohistochemistry (IHC). The prognostic factors were analyzed by log-rank test or Cox proportional hazard model. RESULTS: Among 36 cases with UPSC, 13 patients (36.1%) showed moderate staining (++) to strong staining (+++) for Her-2/neu protein, while amplification of the Her-2/neu gene by CISH was observed in 4 of the 36 (11.1%) cases. Her-2/neu protein over-expression was significantly associated with advanced surgical stage and worse prognosis by univariate analysis (P=0.030 and P=0.002, respectively), while the multivariate analysis shown that only Her-2/neu protein over-expression and deep myometrial invasion were associated with a poor prognosis (P<0.05). In 13 patients with Her-2/neu protein over-expression, the mean survival period with chemotherapy was shorter than those without chemotherapy (20 vs. 42 months, P=0.370). CONCLUSION: Her-2/neu protein over-expression is significantly associated with advanced surgical stage UPSC and poor survival outcome, and might reduce the chemotherapy sensitivity.