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Menopause (New York, N.Y.) Aug 2023Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA). (Meta-Analysis)
Meta-Analysis
Efficacy, tolerability, and endometrial safety of ospemifene compared with current therapies for the treatment of vulvovaginal atrophy: a systematic literature review and network meta-analysis.
IMPORTANCE
Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA).
OBJECTIVE
The aim of the study is to perform a systematic literature review (SLR) and network meta-analysis (NMA) to assess the efficacy and safety of ospemifene compared with other therapies used in the treatment of VVA in North America and Europe.
EVIDENCE REVIEW
Electronic database searches were conducted in November 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or nonrandomized controlled trials targeting postmenopausal women with moderate to severe dyspareunia and/or vaginal dryness and involving ospemifene or at least one VVA local treatment were considered. Efficacy data included changes from baseline in superficial and parabasal cells, vaginal pH, and the most bothersome symptom of vaginal dryness or dyspareunia, as required for regulatory approval. Endometrial outcomes were endometrial thickness and histologic classifications, including endometrial polyp, hyperplasia, and cancer. For efficacy and safety outcomes, a Bayesian NMA was performed. Endometrial outcomes were compared in descriptive analyses.
FINDINGS
A total of 44 controlled trials met the eligibility criteria ( N = 12,637 participants). Network meta-analysis results showed that ospemifene was not statistically different from other active therapies in most efficacy and safety results. For all treatments, including ospemifene, the posttreatment endometrial thickness values (up to 52 wk of treatment) were under the recognized clinical threshold value of 4 mm for significant risk of endometrial pathology. Specifically, for women treated with ospemifene, endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. No cases of endometrial carcinoma or hyperplasia were observed in ospemifene trials, nor polyps with atypical hyperplasia or cancer after up to 52 weeks of treatment.
CONCLUSIONS AND RELEVANCE
Ospemifene is an efficacious, well-tolerated, and safe therapeutic option for postmenopausal women with moderate to severe symptoms of VVA. Efficacy and safety outcomes with ospemifene are similar to other VVA therapies in North America and Europe.
Topics: Female; Humans; Dyspareunia; Vagina; Hyperplasia; Bayes Theorem; Network Meta-Analysis; Vulva; Atrophy; Tamoxifen; Selective Estrogen Receptor Modulators; Vaginal Diseases; Endometrial Neoplasms
PubMed: 37369079
DOI: 10.1097/GME.0000000000002211 -
Cancer Treatment and Research... 2022Small cell carcinoma (SCC) of vagina is extremely rare. The association between this tumor and high-risk HPV infection is unclear. To our knowledge, HPV status has been... (Review)
Review
Small cell carcinoma (SCC) of vagina is extremely rare. The association between this tumor and high-risk HPV infection is unclear. To our knowledge, HPV status has been reported in only 3 previous cases of SCC of vagina. Herein, we present a unique case of vaginal small cell carcinoma with discordant HPV testing results between vaginal and cervical samples. We also review and discuss findings from previously reported cases of small cell carcinoma of vagina.
Topics: Female; Humans; Carcinoma, Small Cell; Papillomavirus Infections; Vaginal Neoplasms; Carcinoma, Neuroendocrine
PubMed: 36274474
DOI: 10.1016/j.ctarc.2022.100645 -
The Indian Journal of Radiology &... Apr 2021Uterine cervix is the lower constricted part of uterus which is best evaluated by magnetic resonance imaging (MRI) due to its higher soft tissue and contrast resolution....
Uterine cervix is the lower constricted part of uterus which is best evaluated by magnetic resonance imaging (MRI) due to its higher soft tissue and contrast resolution. The cervical cancer is a common gynecological cancer causing much morbidity and mortality especially in developing countries. Cervical carcinomas mainly occurs in reproductive age group with prognosis mainly depending on the extent of disease at the time of diagnosis, hence it is important to identify these cancerous lesions early and stage them accurately for optimal treatment. In this article, we will review the following: (1) the normal MRI anatomy of uterine cervix; (2) MRI protocol and techniques in evaluation of cervical lesions; (3) imaging of spectrum of various congenital abnormalities and pathologies affecting uterine cervix which ranges from congenital abnormalities to various benign lesions of cervix like nabothian cysts, tunnel cysts, cervicitis, cervical fibroid, and, lastly, endometriosis which usually coexists with adenomyosis; the malignant lesions include carcinoma cervix, adenoma malignum or direct extension from carcinoma endometrium or from carcinoma of vagina; (4) Accurately stage carcinoma of cervix using FIGO classification (2018); and (5) posttreatment evaluation of cervical cancers. MRI is the most reliable imaging modality in evaluation of various cervical lesions, identification of cervical tumors, staging of the cervical malignancy, and stratifying patients for surgery and radiation therapy. It also plays an important role in detection of local disease recurrence.
PubMed: 34556931
DOI: 10.1055/s-0041-1734377 -
Medical Oncology (Northwood, London,... Mar 2017Human papilloma virus (HPV) is considered to be responsible for a large part of vaginal and vulvar carcinomas, and the p53 codon 72 polymorphism has been implicated in...
Human papilloma virus (HPV) is considered to be responsible for a large part of vaginal and vulvar carcinomas, and the p53 codon 72 polymorphism has been implicated in susceptibility to cancer induced by this virus, but with contradicting results. In this study, we have investigated the prognostic value of the codon 72 polymorphism by real-time PCR (qPCR) in two cohorts of vaginal (n = 66) and vulvar (n = 123) carcinomas. In vaginal carcinoma, arginine homozygous patients were significantly associated with a higher primary cure rate (p = 0.023) but also associated with a higher recurrence rate (p = 0.073), significant at distant locations (p = 0.009). No significant differences were found in overall survival rate (p = 0.499) or cancer-specific survival rate (p = 0.222). A higher frequency of arginine homozygosity was noted in HPV-positive tumors (p = 0.190) in comparison with HPV-negative tumors. In vulvar carcinoma, the genotype homozygous for arginine was significantly associated with a larger tumor size at diagnosis in the entire cohort (p = 0.015) and a lower cancer-specific survival rate (p = 0.024) compared with heterozygous (arginine/proline) in HPV-negative tumors. Our results indicate that the relation between HPV and the p53 codon 72 polymorphism is complex and the significance and mechanisms responsible for this relationship need to be further elucidated.
Topics: Aged; Carcinoma, Squamous Cell; Codon; Female; Genes, p53; Genetic Predisposition to Disease; Human papillomavirus 16; Humans; Papillomavirus Infections; Polymorphism, Genetic; Real-Time Polymerase Chain Reaction; Vaginal Neoplasms; Vulvar Neoplasms
PubMed: 28144815
DOI: 10.1007/s12032-017-0893-6 -
Annales de Dermatologie Et de... May 2000Precancerous and invasive carcinoma of the external genitalia and of the vagina are rare tumors and their incidence is not very well known in the Paris region. The...
OBJECTIVE
Precancerous and invasive carcinoma of the external genitalia and of the vagina are rare tumors and their incidence is not very well known in the Paris region. The objective of this study was to evaluate the frequency of precancerous and invasive lesions of the vulva, the vagina and the penis as well as their variation according to age.
METHODS
A prospective study was conducted implicating private and public pathology laboratories in Paris and the seven departments around. Four hundred and twenty three genital biopsies have been analyzed: 160 from the vulva, 151 from the vagina and 112 from the penis.
RESULTS
The mean age of the patients was 45 years. The highest frequency of genital biopsies was similar for the three anatomical sites and concerned patients of 25-34 years old. intraepithelial neoplasias represented 77p. 100 of the biopsies (32p. 100 of low grade and 45p. 100 of high grade), invasive squamous carcinoma and adenocarcinoma represented 21p. 100 and 2p. 100 of cases, respectively. The mean age of the patients with low grade vulvar intraepithelial neoplasia, low grade vaginal intraepithelial neoplasia and low grade penile intraepithelial were 34, 40 and 33 years old, respectively. An interval of three to seven years separates the mean age of low grade intraepithelial neoplasia from the mean age of high grade. High grade intraepithelial neoplasia present a peak of frequency in the same class of age for the three localizations (25-34 years) and the risk of developing a high grade intraepithelial neoplasia of the external genital was higher between 25 and 35 years and between 35-45 years of the vagina. The mean age of invasive vulvar carcinoma, vagina carcinoma and penile carcinoma was 62, 59 and 68 years old, respectively.
CONCLUSIONS
The correlation between the development of intraepithelial neoplasia of the vulva and the penis supposes a common aetiologic factor in the majority of the cases. The diagnosis of a intraepithelial neoplasia implies a clinical, colposcopic and follow-up of the entire genital area.
Topics: Adenocarcinoma; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Biopsy; Carcinoma; Carcinoma in Situ; Carcinoma, Squamous Cell; Colposcopy; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neoplasm Invasiveness; Paris; Penile Neoplasms; Precancerous Conditions; Prospective Studies; Risk Factors; Vaginal Neoplasms; Vulvar Neoplasms
PubMed: 10863176
DOI: No ID Found -
Journal of Pathology and Translational... Jul 2021A sarcomatoid variant of urothelial carcinoma in the female urethral diverticulum has not been reported previously. A 66-year-old woman suffering from dysuria presented...
A sarcomatoid variant of urothelial carcinoma in the female urethral diverticulum has not been reported previously. A 66-year-old woman suffering from dysuria presented with a huge urethral mass invading the urinary bladder and vagina. Histopathological examination of the resected specimen revealed predominantly undifferentiated pleomorphic sarcoma with sclerosis. Only a small portion of conventional urothelial carcinoma was identified around the urethral diverticulum, which contained glandular epithelium and villous adenoma. The patient showed rapid systemic recurrence and resistance to immune checkpoint inhibitor therapy despite high expression of programmed cell death ligand-1. We report the first case of urethral diverticular carcinoma with sarcomatoid features.
PubMed: 34058799
DOI: 10.4132/jptm.2021.04.23 -
Journal of Occupational Health Jan 2023The purpose of this study was to investigate the carcinogenicity of 2-bromopropane (2-BP) in rats.
OBJECTIVE
The purpose of this study was to investigate the carcinogenicity of 2-bromopropane (2-BP) in rats.
METHODS
Male and female F344 rats were exposed by whole body inhalation to 2-BP vapor at concentrations of 0, 67, 200, and 600 ppm for 6 h/day, 5 days/week for 2 years.
RESULTS
All rats of both sexes exposed to 600 ppm died or became moribund within 85 weeks. Death/moribundity was caused by 2-BP induced tumors. In males, significantly increased tumors were malignant Zymbal's gland tumors; sebaceous adenoma and basal cell carcinoma of the skin/appendage; adenocarcinoma of the small/large intestine; follicular cell adenoma of the thyroid; fibroma of the subcutis, and malignant lymphoma of the lymph node. In addition, an increased trend in tumor incidence was found in the preputial gland, lung, forestomach, pancreas islet, brain, and spleen. In females, significantly increased tumors were adenocarcinoma and fibroadenoma of the mammary gland, squamous cell papilloma of the vagina, and large granular lymphocytic leukemia of the spleen. In addition, an increased trend in tumor incidence was found in Zymbal's gland, the clitoral gland, skin, large intestine, pancreas islet, uterus, and subcutis. Particularly, malignant Zymbal's gland tumors were induced even in males exposed to the lowest concentration, 67 ppm.
CONCLUSION
Two-year inhalation exposure to 2-BP resulted in multi-organ carcinogenicity in rats. Based on sufficient evidence of carcinogenicity in this study, 2-BP has the potential to be a human carcinogen.
Topics: Humans; Mice; Rats; Animals; Male; Female; Rats, Inbred F344; Mice, Inbred Strains; Carcinogenicity Tests; Inhalation Exposure; Adenocarcinoma; Adenoma
PubMed: 36756793
DOI: 10.1002/1348-9585.12388 -
Modern Pathology : An Official Journal... Aug 2008Primary invasive squamous cell carcinoma of the vagina is rare, and the role of human papilloma virus in its pathogenesis remains unclear. The aims of our study were to...
Primary invasive squamous cell carcinoma of the vagina is rare, and the role of human papilloma virus in its pathogenesis remains unclear. The aims of our study were to determine the distribution of human papilloma virus genotypes in 21 cases of primary invasive squamous cell carcinoma of the vagina and to correlate human papilloma virus genotype with histological subtypes. Patients' clinical records were reviewed for demographic data and the stage of the disease. Tumors (n=21) were classified according to the World Health Organization criteria. Human papilloma virus genotyping (INNO-LiPA HPV Genotyping) was performed in the whole series, and statistical analysis was performed with Fisher's Exact Test and with Student's t-test. The patients' age ranged from 36 to 88 (mean 65) years. Six cases were keratinizing squamous cell carcinoma, and 15 cases were non-keratinizing squamous cell carcinoma (seven non-keratinizing not otherwise specified, three basaloid, and five warty types). The median age of patients with keratinizing squamous cell carcinoma was 73.8 years and that of non-keratinizing squamous cell carcinoma patients was 61.5 years (P=0.08). Human papilloma virus DNA was detected in 17 cases (81%): 13 non-keratinizing squamous cell carcinoma (87%) and four keratinizing squamous cell carcinoma (67%) (P=0.31). The human papilloma virus genotypes identified were: 6, 11, 16, 18, 31, 33, 35, 40, and 58, with human papilloma virus 16 DNA the most prevalent (33%). Invasive squamous cell carcinoma of the vagina is frequently associated with human papilloma virus infection, and human papilloma virus 16 is the most common genotype. Although without statistical significance, keratinizing squamous cell carcinoma is more frequent in older patients, whereas non-keratinizing squamous cell carcinoma more frequently affects younger women. All studied histological subtypes are strongly associated with human papilloma virus infection.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; DNA, Viral; Female; Genotype; Human papillomavirus 16; Humans; Keratins; Middle Aged; Neoplasm Staging; Papillomavirus Infections; Vaginal Neoplasms
PubMed: 18500261
DOI: 10.1038/modpathol.2008.91 -
Journal of Medical Cases Jan 2023Uterine inversion may be puerperal or non-puerperal. Puerperal uterine inversion is a rare obstetrics complication, with an estimated incidence of 1 in 30,000...
Uterine inversion may be puerperal or non-puerperal. Puerperal uterine inversion is a rare obstetrics complication, with an estimated incidence of 1 in 30,000 deliveries. The occurrence of non-puerperal uterine inversion is even rarer such that there is no good estimate of its incidence. It is challenging to make the diagnosis of non-puerperal uterine inversion and a high index of suspicion needs to be present. Malignancy is an uncommon cause for non-puerperal uterine inversion, but it is important to keep it in mind so as to counsel patients appropriately and prevent repeat surgery wherever possible. There are also unique complexities in the assessment of a virgo intacta patient which needs to be overcome through the use of different approaches in physical examination and imaging. In this case report, there is a unique interplay of multiple complicating factors in a virgo intacta patient presenting with abnormal uterine bleeding secondary to a malignant fibroid polyp that had prolapsed out of the vagina causing uterine inversion. She eventually required two open surgeries in the management of her condition.
PubMed: 36755999
DOI: 10.14740/jmc4023 -
La Radiologia Medica Jan 2024Vulvar carcinoma is a rather uncommon gynecological malignancy affecting elderly women and the treatment of loco-regional advanced carcinoma of the vulva (LAVC) is a...
BACKGROUND
Vulvar carcinoma is a rather uncommon gynecological malignancy affecting elderly women and the treatment of loco-regional advanced carcinoma of the vulva (LAVC) is a challenge for both gynecologic and radiation oncologists. Definitive chemoradiation (CRT) is the treatment of choice, but with disappointing results. In this multicenter study (OLDLADY-1.1), several institutions have combined their retrospective data on LAVC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of CRT.
METHODS
The primary study end-point was 2-year-local control (LC), secondary end-points were 2-year-metastasis free-survival (MFS), 2-year-overall survival (OS) and the rate and severity of acute and late toxicities. Participating centers were required to fill data sets including age, stage, histology, grading as well as technical/dosimetric details of CRT. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected. The toxicity was a posteriori documented through the Common Terminology Criteria for Adverse Events version 5 scale.
RESULTS
Retrospective analysis was performed on 65 patients with primary or recurrent LAVC treated at five different radiation oncology institutions covering 11-year time interval (February 2010-November 2021). Median age at diagnosis was 72 years (range 32-89). With a median follow-up of 19 months (range 1-114 months), 2-year actuarial LC, MFS and OS rate were 43.2%, 84.9% and 59.7%, respectively. In 29 patients (44%), CRT was temporarily stopped (median 5 days, range 1-53 days) due to toxicity. The treatment interruption was statistically significant at univariate analysis of factors predicting LC (p: 0.05) and OS rate (p: 0.011), and it was confirmed at the multivariate analysis for LC rate (p: 0.032). In terms of toxicity profile, no G4 event was recorded. Most adverse events were reported as grade 1 or 2. Only 14 acute G3 toxicities, all cutaneous, and 7 late G3 events (3 genitourinary, 3 cutaneous, and 1 vaginal stenosis) were recorded.
CONCLUSION
In the context of CRT for LAVC, the present study reports encouraging results even if there is clearly room for further improvements, in terms of both treatment outcomes, toxicity and treatment interruption management.
Topics: Humans; Female; Aged; Adult; Middle Aged; Aged, 80 and over; Vulvar Neoplasms; Retrospective Studies; Constriction, Pathologic; Vagina; Chemoradiotherapy; Carcinoma, Squamous Cell; Italy
PubMed: 37700153
DOI: 10.1007/s11547-023-01712-8