A randomized single-blind non-inferiority trial of delayed start with drospirenone-only and ethinyl estradiol-gestodene pills for ovulation inhibition.

We compared the efficacy of 4 mg drospirenone (DRSP) progestin-only pills (POPs) versus combined oral contraceptive pills (COCs) containing 0.02 mg of ethinyl estradiol (EE) and 0.075 mg of gestodene (GS) in ovulation inhibition and inducing unfavorable cervical mucus changes using a delayed-starting approach. This randomized controlled trial involved 36 participants aged 18-45 years. The major outcomes included ovulation inhibition assessed using the Hoogland and Skouby score, and cervical mucus permeability, assessed using the modified World Health Organization score. The results demonstrated ovulation inhibition rates of 77.8% for the EE/GS group and 88.9% for the DRSP group. The risk ratio and absolute risk reduction were 0.50 (95% confidence interval [CI]: 0.10, 2.40) and - 0.11 (95% CI: - 0.35, 0.13), respectively, satisfying the 20% non-inferiority margin threshold. The median time to achieve unfavorable cervical mucus changes was comparable between the DRSP (3 days, interquartile range [IQR]: 6 days) and EE/GS (3.5 days, IQR: 4 days) groups. However, the DRSP group had a higher incidence of unscheduled vaginal bleeding (55.56% vs. 11.11%; p = 0.005). DRSP-only pills, initiated on days 7-9 of the menstrual cycle, were non-inferior to EE/GS pills in ovulation inhibition. However, they exhibited delayed unfavorable cervical mucus changes compared to the standard two-day backup recommendation.Clinical trial registration: Thai Clinical Trials Registry (TCTR20220819001) https://www.thaiclinicaltrials.org/show/TCTR20220819001 .

Effect of a single dose of a combination injectable contraceptive for treatment of bothersome uterine bleeding in contraceptive implant(s) users: A randomized double-blind placebo-controlled trial.

OBJECTIVES: This study aimed to determine the proportion of participants whose uterine bleeding/spotting was interrupted for at least 7 days during the month after they received a combined hormonal injection. We also evaluated bleeding at 21 days and 12 weeks after the injection. STUDY DESIGN: We conducted a randomized, double-blind, placebo-controlled trial in 46 contraceptive implant users who presented with bothersome uterine bleeding/spotting. A single dose of a combination injectable contraceptive or placebo was administered intramuscularly at enrollment. RESULTS: The proportions of participants whose uterine bleeding/spotting was interrupted for at least 7 days the month after they received a combined hormonal injection were higher in the combination injectable contraception group than in the placebo group (87% vs 48%, p = 0.005). Participants who reported that they were bleeding free at 21 days after treatment were 52% and 35% in the combination injectable contraception group and placebo group, respectively (p = 0.24). At 12 weeks posttreatment, 17% of participants in the combination injectable contraception group and 4% in the placebo group reported cessation of bleeding with no recurrence (p = 0.34). The median days until the first bleeding interruption was shorter in the combination injectable contraception group compared with the placebo group (1 [interquartile range, 1-2] vs 8 [interquartile range, 1-28], p = 0.007). CONCLUSIONS: The combination injectable contraception interrupted bothersome uterine bleeding/spotting in contraceptive implant(s) users compared with placebo. However, this effect was limited only within the month when the treatment was administered. IMPLICATIONS: Bothersome uterine bleeding/spotting is a common side effect leading to contraceptive implant(s) discontinuation. In implant users experiencing these symptoms with no estrogen contraindications, a combined injectable contraception appears to rapidly improve bleeding for the duration of injectable exposure (1 month).

Prevalence of Tissue BRCA Gene Mutation in Ovarian, Fallopian Tube, and Primary Peritoneal Cancers: A Multi-Institutional Study.

BACKGROUND AND OBJECTIVE: Ovarian, fallopian tube, or primary peritoneal cancer patients with BRCA gene mutation have enhanced sensitivity to platinum-based regimens and PARP inhibitors. However, the knowledge regarding BRCA mutation in Thai patients is limited. This study aimed at identifying the prevalence and characteristics of somatic and germline BRCA 1 and 2 mutations in Thai patients with these cancers. MATERIALS AND METHODS: The paraffin blocks of tumors with histology of high grade serous, high grade endometrioid, or clear cell carcinoma obtained between June 2016 and December 2017 were analyzedto evaluate BRCA mutation using next-generation sequencing system. Blood or normal tissue paraffin blocks of positive patients were further tested for germline BRCA mutation. RESULTS: Tissue paraffin blocks of 178 patients were collected but only 139 were analyzed. Positive BRCA mutation was identified in 24 patients (17.3%): BRCA1 in 13 cases, BRCA2 in 10 cases, and BRCA1 and 2 in the rest one. Germline mutation study in blood or normal tissue in 23 positive patients revealed BRCA mutation in 14 cases, BRCA1 in 8 cases and BRCA 2  in 6 cases. Overall, the prevalence of somatic and germline mutation was 6.5% (9 out of 138 patients) and 8.7% (14 out of 138 patients), respectively. The most common histology associated with BRCA mutation was high grade serous cancer (27.3%). No significant difference was found between patients with or without BRCA mutation in terms of stage, outcome, platinum status, and survival outcome. CONCLUSION: BRCA mutation was demonstrated in less than 10% of Thai ovarian cancer patients. Higher rate of mutation was found in high grade serous cancer.
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BRCA immunohistochemistry for screening of BRCA mutation in epithelial ovarian cancer patients.

To evaluate BRCA1/2 immunohistochemistry (IHC) as a screening test for germline BRCA1/2 in epithelial ovarian cancer (EOC), tumor tissue from 105 EOC patients who had germline BRCA mutations, including 9 BRCA1 mutations, 6 BRCA2 mutations and 90 no BRCA mutations, were studied. Paraffin-embedded tissue blocks were stained for BRCA1 and BRCA2. Tumors were indicated as a loss of BRCA expression when neoplastic nuclear stained less than 10%. Loss of BRCA1 and/or BRCA2 expression was found in 36 patients (34.3%). BRCA1 IHC loss was found in 21 patients (20%) while 24 patients (22.9%) had BRCA2 IHC loss. There were no significant differences in patient characteristics between both groups. Loss of BRCA1 expression had 66.7% sensitivity, 84.3% specificity, 28.6% positive predictive value (PPV), and 96.4% negative predictive value (NPV) for detection of germline BRCA1 mutation. Meanwhile, loss of BRCA2 expression had 50% sensitivity, 78.8% specificity, 12.5% PPV, and 96.3% NPV for detection of germline BRCA2 mutation. There was no significant difference in survival outcomes between both groups. Based on high NPV, BRCA IHC may be useful to exclude patients without BRCA dysfunction if IHC showed intact expression. Only patients with BRCA IHC loss should be offered further genetic testing.

RAS Mutation in Mucinous Carcinoma of the Ovary

Objective: This study was designed to identify genetic mutation in mucinous carcinoma of the ovary of the patients in King Chulalongkorn Memorial hospital, Bangkok, Thailand and study the relationship between genetic mutation and patients' prognosis. Methods: Fifty cases of primary mucinous carcinoma of the ovary were selected. DNA was analyzed for genetic mutation using ColoCarta Panel v1.0 and MassArray® System. Demographic data and clinical information of the participants were reviewed from electronic medical records and government data services. Results: Median of disease-free survival is 171.33 +/- 9.04 months and the median overall survival is 171.37 +/- 9.03 months. Twelve percent of the participants had recurrence and all of recurrent cases died from disease or its complication. We found three mutations which were KRAS (27 cases, 54%), PIK3CA (4 cases, 8%) and BRAF (1 case, 2%). Among the KRAS-mutated patients, the majority of the cases (25 cases, 92.6%) were in stage I. Recurrence and disease related mortality were not observed in the KRAS mutated patients. Conclusion: The genetic mutation analysis found three mutations which were KRAS 27 cases (54%), PIK3CA 4 cases (8%) and BRAF 1 case (2%) The ovarian mucinous carcinoma patients with KRAS mutation in our study showed excellent prognosis.

Epidermodysplasia Verruciformis-like HPV Infection of the Vulva in Immunosuppressed Women.

The vast majority of vulvar human papilloma virus infections are produced by α human papilloma viruses and consist of exophytic or flat warts and classic or "usual" vulvar intraepithelial neoplasia. This report details 2 examples of epidermodysplasia verruciformis-like lesions of the vulva in women who were immunosuppressed. The most consistent morphologic feature was the presence of abnormal mature keratinocytes with large pale open nuclei with small nucleoli and eosinophilic cytoplasm, situated in the upper epithelial layers. In addition to these features, which are commonly seen in epidermodysplasia verruciformis-associated lesions, 1 case displayed in addition more extensively distributed abnormal nuclei, including involvement of both the upper epithelial strata and the epithelial/stromal interface. Both lesions were associated with ß-papilloma virus type 5. The unique aspects of epidermodysplasia verruciformis-like lesions relative to the more common human papilloma virus infections of the vulva are highlighted and these cases illustrate the range of epithelial distribution that might be encountered in lesions involving the vulvar mucosa.

Detection of human papillomavirus in male and female urine by electrochemical DNA chip and PCR sequencing.

BACKGROUND: Cervical cancer is the second most common cancer in Thai women after breast cancer. Currently, the Papanicolaou (Pap) smear is the recommended procedure for cervical cancer screening in Thailand, but only a relatively small percentage of women follow this screening program. An alternative method to detect HPV genotypes associated with cervical cancer is self-sampling of urine, which is a more widely accepted method. Our study aimed to evaluate the prevalence of HPV in Thai women using urine and cervical swabs and prevalence of HPV in Thai men using urine samples. MATERIALS AND METHODS: Tumorigenic HPV detection was accomplished by electrochemical DNA chip and PCR/direct sequencing. In addition to HPV prevalence, we report the concordance between different methods and sample types. One-hundred and sixteen women and 100 men were recruited. Histological examination revealed normal cytology in 52 women, atypical squamous cells of undetermined significance (ASCUS) in 9, low-grade squamous intraepithelial lesions (LSIL) in 24, and high-grade squamous intraepithelial lesions (HSIL) in 31. One-hundred men were classified as heterosexuals (n=45) and homosexuals (n=55). RESULTS: The most prevalent HPV genotype in our study was HPV16. The HPV detection rate was generally lower in urine samples compared with cervical samples. Overall, there was good agreement for the detection of carcinogenic HPV from female cervical samples between the DNA chip and PCR/ sequencing, with 88.8% total agreement and a kappa value of 0.76. In male urine samples, the level of agreement was higher in heterosexuals compared with homosexuals. CONCLUSIONS: Further improvement is required to increase an overall yield of HPV DNA detection in urine samples before clinical application of a urine-based HPV screening program. The electrochemical DNA chip test is a promising technique for carcinogenic HPV detection.