The landscape of diagnosing and treating endometrial cancer is undergoing a profound transformation due to the integration of molecular analysis and innovative therapeutic approaches. For several decades, the cornerstone treatments for endometrial cancer have included surgical resection, cytotoxic chemotherapy, hormonal therapy, and radiation therapy. However, in recent years, the concept of personalised medicine has gained momentum, reshaping the way clinicians approach cancer treatment. Tailoring treatments based on specific biomarkers has evolved into a standard practice in both initial and recurrent therapy protocols. This review aims to provide an in-depth exploration of the current state of molecular analysis and treatment strategies in the context of endometrial cancer, focusing on the immunological aspect of the PD-1/PD-L1 axis. Furthermore, it seeks to shed light on emerging and innovative approaches that hold promise for the future modulation of endometrial cancer treatments. In essence, as researchers delve into the complex molecular landscape of endometrial cancer and harness the understanding of the PD-1/PD-L1 axis, we are paving the way for more targeted, effective, and personalised therapies that have the potential to significantly improve the outcomes and quality of life for patients with this challenging disease.
The discovery that ameloblastoma has a high mutation incidence of BRAF V600E may enable a better investigation of pathophysiology. However, there is inconsistent evidence regarding this mutation occurrence and its association with clinical information. This systematic review and meta-analysis aim to pool the overall mutation prevalence of BRAF V600E in reported ameloblastoma cases and to determine its association with patient demographic and clinicopathological features. Following the PRISMA guidelines, a comprehensive article search was conducted through four databases (Scopus, Google Scholar, PubMed, and Web of Science). Seventeen articles between 2014 and 2022 met the inclusion criteria with 833 ameloblastoma cases. For each included study, the significance of BRAF V600E on the outcome parameters was determined using odd ratios and 95% confidence intervals. Meta-analysis prevalence of BRAF V600E in ameloblastoma was 70.49%, and a significant meta-analysis association was reported for those younger than 54 years old and in the mandible. On the contrary, other factors, such as sex, histological variants, and recurrence, were insignificant. As a result of the significant outcome of BRAF V600E mutation in ameloblastoma pathogenesis, targeted therapy formulation can be developed with this handful of evidence.
Endometriosis affects the sexual functioning and marital satisfaction of couples in a complex manner due to its clinical presentation of the disease. This study aimed to evaluate the prevalence of sexual dysfunction and marital disharmony among women with endometriosis beyond their diagnosis and treatment. A cross-sectional online survey was conducted among women with endometriosis in an endometriosis society at a Malaysian university hospital. Sociodemographic and clinical data were collected. Sexual function was measured using the Malay Version Female Sexual Function Index (MVFSFI), while marital satisfaction was evaluated with the Malay Version Golombok Rust Inventory for Marital Satisfaction (MVGRIMS). A total of 166 patients participated in this survey. The median age was 35 years (Interquartile range, IQR:32.00-39.25 years); 91.6% of participants were Malay. The median score of MVFSFI was 56.00 (IQR: 34.75-68.00). Most of the study subjects (n = 96) reported poor to very severe marital satisfaction problems, equivalent to MVGRIMS transformed score of more than 5. High levels of MVGRIMS scores have a moderately strong negative correlation with lower scores for most domains of the MVFSFI. In the stepwise multiple logistic regression, only MVFSFI total scores (p = 0.029), MVFSFI lubrication scores (p = 0.009), and MVFSFI satisfaction (p = 0.010) scores were significantly associated with poor marital satisfaction. Both sexual dysfunction and marital satisfactions commonly affect women with endometriosis and are closely interlinked. Targeted efforts should be made in multiple aspects to improve the quality of sexual functioning and marital satisfaction among endometriosis patients.
Endometrial cancer (EC) is one of the most common malignancies of the female genital tract and its current treatment mainly relies on surgical removal of the tumour bulk, followed by adjuvant radiotherapy with or without chemotherapy/hormonal therapy. However, the outcomes of these approaches are often unsatisfactory and are associated with severe toxicity and a higher recurrence rate of the disease. Thus, more clinical research exploring novel medical intervention is needed. Involvement of the immune pathway in cancer has become important and the finding of a high positive expression of programmed cell death-ligand 1 (PD-L1) in EC may offer a better targeted therapeutic approach. Numerous studies on the PD-L1 role in EC have been conducted, but the results remained inconclusive. Hence, this systematic review was conducted to provide an update and robust analysis in order to determine the pooled prevalence of PD-L1 expression in EC and evaluate its association with clinicopathological features in different focuses of tumour cells (TC) and immune cells (IC). A comprehensive literature search was conducted using the PubMed, Web of Science, and Scopus databases. Twelve articles between 2016 and 2021 with 3023 EC cases met the inclusion criteria. The effect of PD-L1 expression on the outcome parameters was estimated by the odds ratios (ORs) with 95% confidence intervals (CIs) for each study. The pooled prevalence of PD-L1 was 34.26% and 51.39% in the tumour cell and immune cell, respectively, among women with EC. The PD-L1 expression was significantly associated with Stage III/IV disease (in both TC and IC) and correlated to the presence of lympho-vascular invasion in IC. However, the PD-L1 expression in TC was not associated with the age groups, histology types, myometrial invasion, and lympho-vascular invasion. In IC, PD-L1 expression was not associated with age group, histology type, and myometrial invasion. The meta-analysis survival outcomes of PD-L1 high expression had a significant association with worse OS in IC but not in TC.
The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway plays a crucial role in the immune escape mechanism and growth of cancer cells in endometrial cancer (EC). Clinical trials investigating PD-1/PD-L1 inhibitor have shown promising results in other cancers, but their efficacy in EC still remains uncertain. Therefore, this meta-analysis aims to provide an updated and robust analysis of the effectiveness and safety of PD-1/PDL1 inhibitor as single-agent immunotherapy in EC, focusing on the objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). This meta-analysis utilized STATA version 17 and RevMan version 5.4 software to pool the results of relevant studies. Five studies conducted between 2017 and 2022, comprising a total of 480 EC patients enrolled for PD-1/PD-L1 inhibitor immunotherapy met the inclusion criteria. The pooled proportion of EC patients who achieved ORR through PD-1/PD-L1 inhibitor treatment was 26.0% (95% CI: 16.0-36.0%; p < 0.05). Subgroup analysis based on mismatch repair (MMR) status showed an ORR of 44.0% (95% CI: 38.0-50.0%; p = 0.32) for the deficient mismatch repair (dMMR) group and 8.0% (95% CI: 0.0-16.0%; p = 0.07) for the proficient mismatch repair (pMMR) group. Pooled proportion analysis by DCR demonstrated an odds ratio (OR) of 41.0% (95% CI: 36.0-46.0%, p = 0.83) for patients undergoing PD-1/PD-L1 inhibitor treatment. Subgroup analysis based on MMR status revealed DCR of 54.0% (95% CI: 47.0-62.0%; p = 0.83) for the dMMR group, and 31.0% (95% CI: 25.0-39.0%; p = 0.14) for the pMMR group. The efficacy of PD-1/PD-L1 inhibitors was significantly higher in the dMMR group compared to the pMMR group, in terms of both ORR (OR = 6.30; 95% CI = 3.60-11.03; p < 0.05) and DCR (OR = 2.57; 95% CI = 1.66-3.99; p < 0.05). In terms of safety issues, the pooled proportion of patients experiencing at least one adverse event was 69.0% (95% CI: 65.0-73.0%; p > 0.05), with grade three or higher AEs occurring in 16.0% of cases (95% CI: 12.0-19.0%; p > 0.05). Based on the subgroup analysis of MMR status, PD-1/PD-L1 inhibitor immunotherapy showed significantly better efficacy among dMMR patients. These findings suggest that patients with dMMR status may be more suitable for this treatment approach. However, further research on PD-1/PD-L1 inhibitor immunotherapy strategies is needed to fully explore their potential and improve treatment outcomes in EC.