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Frontiers in Oncology 2024Vulvar cancer carries a favourable prognosis in early stages. However, therapeutic options for advanced or recurrent cases are limited despite a variety of therapeutic...
INTRODUCTION
Vulvar cancer carries a favourable prognosis in early stages. However, therapeutic options for advanced or recurrent cases are limited despite a variety of therapeutic modalities, such as extensive surgical resection, chemotherapy, and radiotherapy. The most important emerging treatment modalities are immune checkpoint inhibitors. This systematic review and meta-analysis aims to assess the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in women with advanced vulvar cancer.
MATERIALS AND METHODS
Following a comprehensive search, review, and appraisal, two relevant single-arm studies were included. Meta-analysis was conducted using R4.3.0 software and RStudio 2023.03.0, presenting the overall effect size with a 95% confidence interval. Heterogeneity was assessed using I and the Cochrane Q χ2 statistics.
RESULTS
Out of 154 studies screened for eligibility, two single-arm studies involving 119 patients receiving pembrolizumab for advanced vulvar cancer were included. The pooled objective response rate (ORR) was overall 10% (95% CI: 0.00-0.84) and 9% (95% CI: 0.00-0.89) in the PD-L1 positive subgroup. In the intention-to-treat (ITT) population, 31% (95% CI: 0.04-0.85) exhibited any clinical benefit (complete response, partial response, or stable disease). In the ITT population at six months, progression-free survival (PFS) was 19% (95% CI: 0.01-0.82), and overall survival (OS) was 48% (95% CI: 0.08-0.90). At 12 months, PFS decreased to 9% (95% CI: 0.00-0.85), and OS was 33% (95% CI: 0.04-0.85). No statistically significant heterogeneity was observed in PFS and OS analyses.
DISCUSSION AND CONCLUSION
This study suggests that one-third of women with advanced or recurrent vulvar cancer may, without the influence of PD-L1 status, benefit from pembrolizumab treatment despite a decline in both PFS and OS at 12 months. These findings provide support for considering pembrolizumab in the treatment paradigm for this specific subset of cancer patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023391888.
PubMed: 38440225
DOI: 10.3389/fonc.2024.1352975 -
Journal of Ethnopharmacology Feb 2024The genus Alchemilla L. (lady's mantle) comprises 1000 species, of which more than 300 have been characterized from Europe. Notably, as folk medicines, Alchemilla... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
The genus Alchemilla L. (lady's mantle) comprises 1000 species, of which more than 300 have been characterized from Europe. Notably, as folk medicines, Alchemilla species have long been prescribed for the treatment of dysmenorrhea, pruritus vulvae, menopausal complaints, and related diseases in women. This review summarizes the traditional uses, highlights promising plant species, and focuses on phytochemical and biological studies to highlight future areas of research.
AIM OF THE REVIEW
This literature review aims to provide a comprehensive overview of Alchemilla species, covering their botany, traditional uses, phytochemistry, and biological and pharmacological activities, and to summarize the current research status to better understand the application value of Alchemilla plants in modern phytotherapy.
MATERIALS AND METHODS
The search strategy utilized the major thematic platforms Reaxys, Web of Science, Google Scholar, Scopus, ScienceDirect, PubMed, the USDA Plant Database and Kew Science (Royal Botanic Gardens) and was performed with the term Alchemilla. These platforms were systematically searched for articles published from 1960 to 2023.
RESULTS AND DISCUSSION
Alchemilla species, as members of the Rosaceae family, produce tannins, phenolic acids, flavonoids, anthocyanins, coumarins, triterpenes and violet compounds. Effort has been made with this comprehensive review of Alchemilla plants to highlight the recent developments and milestones achieved in modern phytochemistry and phytotherapy, underlaying a broad spectrum of the activities of these plants, such as antioxidant, anti-inflammatory, neuroprotective, antimicrobial, antiobesity, cardiovascular, anticancer, and wound healing effects.
CONCLUSIONS
An increasing number of studies on the plants in the Alchemilla genus have provided data about the main constituents and their importance in modern medicine. Both in vitro and in vivo studies have indicated that Alchemilla plants possess an extensive spectrum of biological activities. Regardless of the remarkable medical potential of Alchemilla extracts, clinical studies are limited and need to be performed to produce safer and less expensive plant-based drugs.
Topics: Female; Humans; Ethnopharmacology; Plants, Medicinal; Alchemilla; Rosaceae; Anthocyanins; Phytotherapy; Plant Extracts; Phytochemicals
PubMed: 37981119
DOI: 10.1016/j.jep.2023.117439 -
Reproductive Sciences (Thousand Oaks,... Feb 2024The metastasis of a gynecological malignancy to the Bartholin gland is rare. We report the case of a 62-year-old patient who had undergone extensive treatment of...
The metastasis of a gynecological malignancy to the Bartholin gland is rare. We report the case of a 62-year-old patient who had undergone extensive treatment of metastatic ovarian cancer that involved the liver, spleen, and peritoneum. She presented with painful swelling of the left vulva. Clinical and sonographic examinations showed a solid tumor in loco typico of the Bartholin gland. Surgical excision was performed. The patient died 3 months after the diagnosis of this metastasis. We performed a systematic search of PubMed, which yielded 453 entries. We selected those with at least an abstract available in English that described metastatic lesions on the Bartholin gland (n = 5). The review showed that a variety of primary cancers (colorectal, medullary thyroid, breast cancer, and endometrial cancers) metastasize to this location. Some patients showed signs of visceral metastasis. Bartholin gland metastases appeared as initial and metachronous manifestations. Most patients were symptomatic, with painful swelling or abscess. Genetic alterations were mentioned in some cases. The main pathways of metastasis discussed were lymphatic, but the mechanism of such metastasis remains unclear. Surgical resection was the preferred treatment option. The literature review indicated that Bartholin gland metastasis of ovarian cancer is rare and associated with poor prognosis. Oncological reasons for vulvar pathologies should be taken into consideration in patients with metastases.
Topics: Humans; Female; Middle Aged; Bartholin's Glands; Ovarian Neoplasms; Breast Neoplasms; Gynecology
PubMed: 37794197
DOI: 10.1007/s43032-023-01373-y -
Archivio Italiano Di Urologia,... Oct 2023Urinary incontinence and other urinary symptoms tend to be frequent at menopause because of hormonal modifications and aging. Urinary symptoms are associated with the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Urinary incontinence and other urinary symptoms tend to be frequent at menopause because of hormonal modifications and aging. Urinary symptoms are associated with the genitourinary syndrome of menopause which is characterized by physical changes of the vulva, vagina and lower urinary tract. The treatment strategies for postmenopausal urinary incontinence are various and may include estrogens, anticholinergics, and pelvic floor muscle training. A comparison of these treatments is difficult due to the heterogeneity of adopted protocols. We systematically reviewed the evidence from randomized controlled trials (RCTs) focusing on treatment of postmenopausal women with urge incontinence.
METHODS
We conducted a systematic review and meta-analysis by searching PubMed and EMBASE databases for randomized controlled trials (RCTs) reporting results of treatments for postmenopausal urinary urge incontinence. Odds ratios for improvement of urinary incontinence were calculated using random effect Mantel-Haenszel statistics.
RESULTS
Out of 248 records retrieved, 35 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared with placebo, systemic estrogens were associated with decreased odds of improving urinary incontinence in postmenopausal women (OR = 0.74, 95% CI: 0.61-0.91, 7 series, 17132 participants, Z = 2.89, P = 0.004, I2 = 72%). In most studies, no significant improvement in urinary symptoms was observed in patients treated with local estrogens, although they showed to be helpful in improving vaginal symptoms. Vitamin D, phytoestrogens and estrogen modulators were not effective in improving symptoms of incontinence and other symptoms of genitourinary menopause syndrome or yielded contradictory results. A randomized controlled trial demonstrated that oxybutynin was significantly better than placebo at improving postmenopausal urgency and urge incontinence. The combination of anticholinergics with local estrogens has not been shown to be more effective than anticholinergics alone in improving urinary incontinence symptoms in postmenopausal women. Physical therapy showed an overall positive outcome on postmenopausal urinary incontinence symptoms, although such evidence should be further validated in the frame of quality RCTs.
CONCLUSIONS
The evidence for effective treatment of postmenopausal urinary incontinence is still lacking. Welldesigned large studies having subjective and objective improvement primary endpoints in postmenopausal urinary incontinence are needed. At present, a combination of different treatments tailored to the characteristics of the individual patient can be suggested.
Topics: Female; Humans; Urinary Incontinence, Urge; Urinary Incontinence, Stress; Postmenopause; Pelvic Floor; Urinary Incontinence; Estrogens; Cholinergic Antagonists; Randomized Controlled Trials as Topic
PubMed: 37791545
DOI: 10.4081/aiua.2023.11718 -
Cancers Jul 2023The female genital tract can be involved as a secondary manifestation of disseminated lymphomas or leukaemia but can rarely be the primary site of so-called extranodal... (Review)
Review
The female genital tract can be involved as a secondary manifestation of disseminated lymphomas or leukaemia but can rarely be the primary site of so-called extranodal lymphomas. Primary lymphomas of the female genital tract can affect the uterine corpus, uterine cervix, vulva, vagina, or adnexa. Only about 0.008% of all cervical tumours are primary malignant lymphomas. The most common clinical presentation of primary cervical lymphomas is a history of prolonged minor abnormal uterine bleeding, while unstoppable bleeding at presentation is rarely reported in the literature. "B" symptoms related to nodal lymphomas are usually absent. Since vaginal bleeding is a nonspecific symptom, the first diagnostic hypothesis is usually of one of the more common female genital conditions such as cervical or endometrial carcinoma or sarcoma, fibroids, adenomyosis, or endometriosis. Cervical cytology is usually negative. Preoperative diagnosis requires deep cervical biopsy. No guidelines regarding optimal treatment exists; radiotherapy, chemotherapy, and surgery are used in different combinations. Conservative treatment with the combination of surgery and chemotherapy or surgery and radiotherapy has been reported in a few cases with apparent success. With this review, we aim to understand what the best therapeutic approaches for this rare pathology in young and elderly women are. Moreover, we find favorable pregnancy outcome in patients treated with a fertility sparing approach.
PubMed: 37509340
DOI: 10.3390/cancers15143679 -
Journal of Clinical Medicine Jun 2023The most important causative agent of neoplasms in the anogenital area is the human papillomavirus (HPV). Due to the anatomical proximity of the genital and anus area... (Review)
Review
BACKGROUND
The most important causative agent of neoplasms in the anogenital area is the human papillomavirus (HPV). Due to the anatomical proximity of the genital and anus area and the ease with which HPV infection is transmitted, it seems that patients after the treatment of HPV-related gynecological diseases may have an increased risk of developing a second HPV-related neoplasm anal cancer. The aim of this study was to determine the risk of anal intraepithelial neoplasia (AIN) and anal cancer (AC) among patients after the treatment of HPV-related gynecological diseases.
METHODS
We conducted a comprehensive review of the available literature from multiple databases. The study was performed following and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. Moreover, we assessed the quality of each study using QUADAS-2.
RESULTS
Twenty-five studies were included in the final analysis. Patients after the treatment of HPV-related gynecological diseases have a significantly higher risk of AC (mean standardized incidence ratio (SIR) = 5.387, mean incidence risk (IR) = 0.096%, mean IR per 100,000 person-years = 10.37) and AIN (mean IR = 23.683%) compared to the population risk.
CONCLUSIONS
patients with HPV-related gynecological diseases should constitute a group for which an appropriate primary and secondary screening for AC should be introduced.
PubMed: 37445251
DOI: 10.3390/jcm12134216 -
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 -
Cancers Apr 2023Medical use of (non-)thermal plasmas is an emerging field in gynaecology. However, data on plasma energy dispersion remain limited. This systematic review presents an... (Review)
Review
Medical use of (non-)thermal plasmas is an emerging field in gynaecology. However, data on plasma energy dispersion remain limited. This systematic review presents an overview of plasma devices, fields of effective application, and impact of use factors and device settings on tissues in the female pelvis, including the uterus, ovaries, cervix, vagina, vulva, colon, omentum, mesenterium, and peritoneum. A search of the literature was performed on 4 January 2023 in the Medline Ovid, Embase, Cochrane, Web of Science, and Google Scholar databases. Devices were classified as plasma-assisted electrosurgery (ES) using electrothermal energy, neutral argon plasma (NAP) using kinetic particle energy, or cold atmospheric plasma (CAP) using non-thermal biochemical reactions. In total, 8958 articles were identified, of which 310 were scanned, and 14 were included due to containing quantitative data on depths or volumes of tissues reached. Plasma-assisted ES devices produce a thermal effects depth of <2.4 mm. In turn, NAP effects remained superficial, <1.0 mm. So far, the depth and uniformity of CAP effects are insufficiently understood. These data are crucial to achieve complete treatment, reduce recurrence, and limit damage to healthy tissues (e.g., prevent perforations or preserve parenchyma). Upcoming and potentially high-gain applications are discussed, and deficits in current evidence are identified.
PubMed: 37190314
DOI: 10.3390/cancers15082386 -
Journal of Clinical Virology : the... Jul 2023Human papillomavirus associated anogenital cancers are a significant global burden. The detection of biomarkers (circulating tumour DNA; ctDNA or circulating HPV DNA;... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Human papillomavirus associated anogenital cancers are a significant global burden. The detection of biomarkers (circulating tumour DNA; ctDNA or circulating HPV DNA; cHPV DNA) in blood referred to as "liquid biopsy" may support the early diagnosis and monitoring of affected individuals.
METHODS
A systematic review, including meta-analysis of studies available in the literature on the utilization of ctDNA and cHPV DNA as diagnostic, predictive, and monitoring biomarker tests of HPV associated anogenital cancers was performed following the criteria of PRISMA.
RESULTS
A total of 31 studies were eligible for systematic review; 20 used cHPV DNA in cervical cancers; 7 used ctDNA in cervical cancer; 5 used cHPV DNA in anal cancer; no eligible studies on vulva, vaginal or penile cancer were available. The meta-analysis identified low sensitivity (0.36) and high specificity (0.96) of cHPV DNA as diagnostic for cervical cancer. Comparatively, there was high sensitivity (0.95) and specificity (1.0) of cHPV DNA for the diagnosis of anal cancer. cHPV DNA and/or ctDNA in cervical cancer were prognostic markers associated with poor clinical outcomes. Additionally, in anal cancer the post treatment detection of cHPV DNA was informative in the prediction of treatment response or progression-free survival.
CONCLUSION
ctDNA and cHPV DNA are promising diagnostic and prognostic biomarkers for the detection of anogenital disease. Evolution and refinement of molecular tools is likely to improve performance further. Additionally the comparative absence of studies in the vulval, vaginal and penile context warrants further exploration and research.
Topics: Female; Humans; Uterine Cervical Neoplasms; Papillomavirus Infections; Human Papillomavirus Viruses; Anus Neoplasms; DNA
PubMed: 37163963
DOI: 10.1016/j.jcv.2023.105469 -
Skin Health and Disease Apr 2023Lichen sclerosus (LSc) is a chronic, inflammatory, destructive skin disease with a predilection for the genitalia (GLSc). An association with vulval (Vu) and penile (Pe)... (Review)
Review
BACKGROUND
Lichen sclerosus (LSc) is a chronic, inflammatory, destructive skin disease with a predilection for the genitalia (GLSc). An association with vulval (Vu) and penile (Pe) squamous carcinoma (SCC) is now well established but melanoma (MM) has only rarely been reported complicating GLSc.
METHODS
We have performed a systematic literature review of GLSc in patients with genital melanoma (GMM). Only articles that mentioned both GMM and LSc affecting either the penis or vulva were included.
RESULTS
Twelve studies with a total of 20 patients were included. Our review shows that an association of GLSc with GMM has been more frequently reported in women and female children than men viz, 17 cases compared with three. It is notable that five of the cases (27.8%) concerned female children aged under twelve.
DISCUSSION
These data suggest a rare association between GLSc and GMM. If proven, there arise intriguing questions about pathogenesis and consequences for counselling of patients and follow-up.
PubMed: 37013116
DOI: 10.1002/ski2.198