Helymar da Costa Machado

Implementation of a new histological grading system in ovarian mucinous carcinomas and its association with the risk of recurrence: a retrospective cohort study

ABSTRACT BACKGROUND: This retrospective cohort study evaluated the prognostic significance of the GrowthBased Grade (GBG) system compared to International Federation of Gynecology and Obstetrics (FIGO) grading in ovarian mucinous carcinoma (OMC). Although FIGO grading is commonly used, its prognostic value remains controversial. The GBG system, which classifies tumors as low-grade (G1) or high-grade (G2) based on the proportion of infiltrative growth, has emerged as a potential prognostic tool. OBJECTIVES: To assess the prognostic significance of GBG and compare it with FIGO grading in OMC. DESIGN AND SETTING: This retrospective cohort study included 37 women with OMC treated at a single institution between 2009 and 2022. METHODS: GBG was determined by a histopathological review of hematoxylin and eosin-stained slides. Clinical and demographic data, including FIGO stage, CA125 levels, surgical procedures, and follow-up information, were collected. Kaplan-Meier analysis and Cox regression were used to assess the associations between GBG grading, FIGO stage, and survival outcomes. RESULTS: GBG 2 tumors were significantly associated with elevated CA125 levels, advanced FIGO stage (III), and bilaterality. Multivariate analysis showed that GBG 2 conferred a 5.4-fold higher risk of recurrence compared with GBG 1. While FIGO stage III was predictive of overall survival, FIGO grading was not associated with recurrence risk. CONCLUSION: This study suggests a potential prognostic value of the GBG system in mucinous ovarian carcinoma. GBG 2 tumors showed a higher risk of recurrence than GBG 1 tumors, whereas FIGO grading showed no such association. These findings align with previous reports and should be interpreted in the context of additional studies to clarify the system’s clinical relevance.

Vaginal stenosis in women with cervical or endometrial cancer after pelvic radiotherapy: a cross-sectional study of vaginal measurements, risk for sexual dysfunction and quality of life

Radiotherapy (RT) for cervical (CC) and endometrial cancer (EC) is known to lead to vaginal stenosis (VS), but the comparison between vaginal anatomical measurements and the risk of sexual dysfunction presents a wide variety of results among the literature. Thus, we sought to assess the prevalence of VS, vaginal measurements, sexual dysfunction and QOL in women with CC and EC submitted to pelvic RT with or without previous surgery. Cross-sectional study that included 61 women with CC and 69 with EC. VS was classified by the Common Terminology Criteria for Adverse Effects version 5.0 (CTCAE v5.0), sexual function by the validated Female Sexual Function Index (FSFI) and QOL by the validated World Health Organization questionnaire (WHOQOL-BREF). Acrylic cylinders were used for vaginal measurements. Uni-/multivariate analyses to address factors associated with VC in both groups were performed. The prevalence of VS was 79% and 67% within patients with CC and EC, respectively. Vagina length was decreased in both groups without statistical difference (7.2 ± 1.7 vs. 6.6 ± 1.8;p = 0.072). Vaginal diameter was significantly higher (p = 0.047) in women with EC (25.4 ± 6.3) than in those with CC (23.1 ± 5.7). Sexual dysfunction was highly prevalent for both CC and EC (88% vs. 91%; p = 0.598). There was no difference in all WHOQOL-BREF domains between women with CC and EC. VS is highly prevalent in CC and EC patients, with vaginal length decreased in both groups but with a higher vaginal diameter in those with EC. Nevertheless, sexual dysfunction is highly prevalent in both groups.

The top hat procedure does not impact the management of women treated by LEEP in cervical cancer screening

To describe Top-hat results and their association with margin status and disease relapse in a referral facility in Brazil. A retrospective study of 440 women submitted to LEEP to treat HSIL, in which 80 cases were complemented immediately by the top hat procedure (Top-hat Group - TH). TH Group was compared to women not submitted to Top-hat (NTH). The sample by convenience included all women that underwent LEEP from January 2017 to July 2020. The main outcome was the histological result. Other variables were margins, age, transformation zone (TZ), depth, and relapse. The analysis used the Chi-square test and logistic regression. The TH Group was predominantly 40 and older (NTH 23.1% vs. TH 65.0%, p<0.001). No difference was found in having CIN2/CIN3 as the final diagnosis (NTH 17.0% vs. TH 21.3%, p=0.362), or in the prevalence of relapse (NTH 12.0% vs. TH 9.0%, p=0.482). Of the 80 patients submitted to top hat, the histological result was CIN2/CIN3 in eight. A negative top hat result was related to a negative endocervical margin of 83.3%. A CIN2/CIN3 Top-hat result was related to CIN2/CIN3 margin in 62.5% (p=0.009). The chance of obtaining a top hat negative result was 22.4 times higher (2.4-211.0) when the endocervical margin was negative and 14.5 times higher (1.5-140.7) when the ectocervical margin was negative. The top hat procedure did not alter the final diagnosis of LEEP. No impact on relapse was observed. The procedure should be avoided in women of reproductive age.

Association of NK6 homeobox 1 promoter methylation with HPV infection, histological sub-type, and patient outcomes in cervical lesions.

To evaluate NK6 homeobox 1 (NKX6.1) promoter methylation in cervical lesions and its association with human papillomavirus (HPV)16/18 infection, histological sub-type, and patient outcomes using clinical and bioinformatic data. A total of 207 cervical tissue samples, including cervicitis (n = 22), cervical intraepithelial neoplasia grade 3 (n = 20), adenocarcinoma in situ (n = 6), adenocarcinoma (n = 59), and squamous cell carcinoma (n = 100), were analyzed by methylation-specific polymerase chain reaction and bisulfite sequencing. HPV genotyping was performed with the INNO-LiPA assay. The Cancer Genome Atlas data (n = 309) were examined for methylation at 27 cytosine-phosphate-guanine sites and their association with overall survival. NKX6.1 promoter methylation was detected in 26.6% of cervical samples and was significantly associated with neoplastic lesions, particularly squamous sub-types (p = .002), with comparable frequencies in cervical intraepithelial neoplasia 3. Logistic regression confirmed that NKX6.1 methylation and HPV16/18 infection were independently associated with squamous cell carcinoma. The Cancer Genome Atlas analysis revealed 11 cytosine-phosphate-guanine sites within NKX6.1 significantly correlated with overall survival, with loci, such as cg12401926 and cg18297736 linked to poorer outcomes. These prognostic effects were locus-specific and not observed when global methylation was considered. NKX6.1 promoter methylation represents an early event in cervical carcinogenesis and is associated with squamous histology. Although global methylation showed no prognostic relevance, site-specific cytosine-phosphate-guanine methylation patterns demonstrated significant survival associations, supporting NKX6.1 as a potential locus-dependent prognostic biomarker in cervical cancer.