a b s t r a c tObjective. There is a need to develop and validate biomarkers for treatment response and survival in tuboovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into Gynecologic Oncology 154 (2019) 441-448 complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT.Methods. We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3-4 NACT cycles and N6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS).Results. 877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5-65) and 28 months (IQR 7-92) respectively. CRS3 was seen in 249 patients (28%). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0·55 (95% CI, 0·45-0·66; P b 0·001) and 0·65 (95% CI 0·50-0·85, P = 0·002) respectively; no heterogeneity was identified (PFS: Q = 6·42, P = 0·698, I2 = 0·0%; OS: Q = 6·89, P = 0·648, I2 = 0·0%). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0·027).Conclusions. CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design.• The Chemotherapy response score (CRS) assesses histological effect in ovarian cancer after neoadjuvant chemotherapy (NACT). • The CRS is associated with progression-free and overall survival.• CRS could provide useful information to estimate a patient's probability of early vs. late relapse.• The CRS is an appealing primary endpoint in clinical trials as a surrogate for survival as it can be measured earlier. • We recommend the CRS be incorporated as an endpoint in clinical trials of novel therapeutic agents that have a NACT arm.
Objective: To compare the efficacy of fractional CO2 laser therapy with topical estrogen therapy for the treatment of postmenopausal genitourinary syndrome of menopause. Methods: We conducted a randomized controlled clinical trial involving 25 postmenopausal women. Participants were aged between 50 and 65 years with at least 1 year of amenorrhea and follicle-stimulating hormone levels of >40 IU/L. The women were randomized into two groups: the laser therapy group (n = 13) and the vaginal topical estrogen therapy group (n = 12). Changes in the vaginal epithelium thickness, Frost index, and cell maturation were analyzed in both the groups. The female sexual quotient of each woman was also evaluated. Subjective evaluation was performed through a physical examination. Results: Histological analysis showed a significant increase in the vaginal epithelium thickness at the end of treatment in females in both the laser therapy (P < 0.001) and topical estrogen therapy (P = 0.001) groups. The topical estrogen therapy group tended to present a higher maturation index at the end of treatment when compared with that of the other group. Sexual function increased significantly over time in both the topical estrogen therapy (P < 0.001) and laser therapy (P < 0.001) groups. Subjective evaluation through physical examination showed a significant improvement in atrophy in both the groups. Conclusion: Despite the nonequivalence with topical estrogen therapy, our data suggest that laser therapy is an effective method for the treatment of vulvovaginal atrophy.
Corrigendum to "Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data" Gynecol. Oncol. 154 (2019) 441-448
VEGF and podoplanin (PDPN) have been identified as angiogenesis and/or lymphangiogenesis regulators and might be essential to restrict tumor growth, progression, and metastasis. In the present study, we evaluate the association between the expression of these markers and CIN grade. Immunohistochemistry was performed in 234 uterine cervical samples using conventional histologic sections or TMA with the monoclonal antibodies to VEGF (C-1 clone) and podoplanin (D2-40 clone). Positive-staining rates of VEGF in 191 CIN specimens were significantly associated with histological grade (P < 0.001). Negative and/or focal immunostaining for PDPN were more frequent in CIN 3 (P = 0.016). We found that patients with CIN 3 more frequently had strong and more diffuse staining for VEGF and diminished staining for PDPN (P = 0.018). Strong and more diffuse VEGF immunoexpressions in CIN 2 and CIN 3 were detected when compared to CIN 1. Negative and/or focal PDPN immunoexpression appear to be more frequent in CIN 3. Moderate to strong VEGF expression may be a tendency among patients with high-grade lesions and diminished PDPN expression.
Objetivo: Investigar os efeitos da tela sintética sobre o testículo, epidídimo e ducto deferente de cães. Métodos: Foram utilizados 10 cães, machos, adultos, pesando entre 9 e 12 kg. Os animais, após realizada anestesia, foram submetidos à laparoscopia com formação de pneumoperitônio por incisão em linha mediana. Era então fixada tela de polipropileno, de dimensões 2,5X3,5 cm² na região inguinal esquerda do cão em contato direto com o funículo espermático, com o uso de grampos metálicos, sem dissecar a região. O lado direito, sem colocação de tela, serviu de controle. O procedimento tinha duração de 15 minutos. Após observação pós-operatória de 30 dias, os animais eram novamente anestesiados e reoperados sendo o testículo e ducto deferente retirados e enviados para análise histológica. Análise estatística foi realizada com os dados obtidos desta análise. Resultados: No lado esquerdo, as secções histológicas de testículo revelaram focalmente, diminuição da espermatogênese e processo degenerativo em 20% dos animais. No epidídimo, observou-se inflamação crônica e dilatação dos túbulos seminíferos em 70%. No ducto deferente foi observado processo inflamatório crônico em 60% dos cães. Não foram verificadas alterações histológicas no lado contralateral. Conclusão: A tela de polipropileno em contato com o funículo espermático de cães provoca alterações histológicas com discreta redução da espermatogênese.
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