Status of the sentinel lymph node in patients with endometrial cancer stage I-II

Endometrial cancer (EC) is the most common gynecological cancer in developed countries. In literature, there are discordant data regarding the therapeutic value of systematic lymphadenectomy whereas the importance of lymph node status for determining prognosis and the need for adjuvant treatment is undoubted. Given the low risk of lymph node metastases in stage I-II of EC and the significant surgical and postoperative risks when performing a complete pelvic lymphadenectomy, the surgical approach in these patients is controversial, ranging from no nodal evaluation to comprehensive pelvic and aortic lymphadenectomy. The recent introduction of sentinel node detection represents the mid-way between the execution and omission of node dissection in EC patients. Indeed, the sentinel node mapping has rapidly emerged as an alternative to complete lymphadenectomy to reduce morbidity. In the present research, we discuss the role of sentinel node mapping in the surgical management of EC in early stage. Results of study on SLN in EC in early stages seem to be promising, but only a small series have been published so far.peer-reviewe

Rapid systematic review of clinical trials on pharmacological therapies for rare gynecological cancers

The purpose of this study is to systematically review clinical trials on pharmacological therapies for rare gynecological cancers and analyze their characteristics. The PRISMA guidelines for systematic reviews were followed and two databases were searched (WHO´s International Clinical Trials Registry Platform and clinicaltrials.gov). The Jadad score was used to assess the methodological quality of completed clinical trials. A total of 212 records, covering trials from 1993 to 2022, were included in the final review. More than half were phase II trials (110; 51.89%) and the status of recruiting was mainly completed (80; 37.74%). There were 26 (12.26%) terminated or withdrawn clinical trials. Just 42.45% of the trials were specific only for rare types of gynecological cancers. The most common type of investigated therapy was chemotherapy (89; 41.98%), followed by targeted therapy (64; 30.19%) and a combination of therapies (23.11%). However, in the last five years there was an increase in trials investigating targeted therapies such as immunotherapy, overgrowth-related and angiogenesis-related therapies. All completed trials except one, had a Jadad score 0-2, indicating low-quality. Thirty-six (45.00%) completed clinical trials had neither posted results, nor publications. Higher quality clinical trials with better reporting of results are needed for rare gynecological cancers.peer-reviewe

Epigenetic silencing of MLH1 as a prognostic factor for endometrial cancer recurrence

Introduction/Background Aberrant DNA methylation is a common phenomenon in different types of cancer, but its patterns, causes, and consequences are poorly defined. Promoter hypermethylation of the DNA mismatch repair (MLH1) has been implicated in prognosis of endometrial cancer (EC). Methodology Fifty women diagnosed with endometrioid-type endometrial adenocarcinoma from 2018–2021 at the Institute of Oncology of Moldova were included in this study. DNA was isolated from plasma, formalin-fixed, paraffin-embedded tumor. The methylation status of the MLH1 gene was determined using the Methylation specific Polymerase Chain Reaction (MS-PCR) method and specific primers for both unmethylated and methylated fragments. (figure 1). Results Clinical and pathological characteristics for the 50 endometrial cancer patients are summarized in table 1. The mean age of the cohort was 59,9 ± 0,64 years (range, 39–87), and most of the patients had early stage (Stage I or II), grade 2 tumors with less than 50% myometrial invasion. The mean tumor size was 4,2 cm and the mean depth of invasion 0,5cm. Myometrial lymphatic/vascular space and perineural invasion was present in nearly half the tumors and was much more common in stage II cases. Overall, 80% of the patients with EC had intact tumors, while 20% had hypermethylation of MLH1 (table 2). The presence of MLH1 epimutation was observed in 22.0% of EC patients in stage I and only in 2 patients in stage II. Conclusion Recent developments in the field of epigenetics, especially studies of DNA methylation, have provided valuable insights for understanding the role of epigenetic alterations in normal cellular processes and abnormal changes leading to endometrial carcinogenesis. Promoter hypermethylation of MLH1 displayed a direct correlation with increasing age, poor differentiation of tumor, presence of myometral and limphovascular invasion. These phenotypes may underlie the different developmental pathways that are known to occur in endometrial cancer.peer-reviewe

Analysis of the molecular profile of endometrial cancer depending on microsatelite instability

Introduction/Background MLH1 is the MMR gene most frequently mutated or epimutated in endometrial cancer and its hypermethylation is found in the vast majority of MMR-deficient EC cases. The high rate of raw data accumulation with reference to cancer genomics as well as the development of bioinformatics algorithms necessary for the re-analysis of cohorts are key elements for obtaining new smart data. Methodology In the present study we aimed to re-analyze a set of genomic data obtained by sequencing 197 EC samples and downloaded from the public database cBioPortal for Cancer Genomics - Endometrial Cancer (MSK, 2018). The aim of the research was to separate the genomic data into two cohorts based on the presence or absence of microsatellite instability and analyze the molecular profile of these cohorts. Results As a result, two sets of data were obtained: SM (Microsatellite Stability) – 153 samples IM (Microsatellite Instability) – 25 samples In the MS cohort, an almost 2-fold higher frequency of changes in the tumor suppressor TP53 is observed, while in IM – a considerably increased rate of PTEN, ARID1A, MLL2, JAK1, POLE, MLH1, MSH6, MSH2 and PMS1 mutations (figure 1). SNV (Single Nucleotide Variation) classes in the IM group compared to SM have higher rates of T>C transitions that are associated with mutational signature no. 5 and lower C>G transversions - markers of signature 13 (figure 2). TMB in the two study groups revealed an index of less than 10 mut/Mb in MS and more than 10 mut/Mb in MI (figure 3). Conclusion Comparative analysis of molecular data in the two subtypes of CE reveals major differences in the mutational profile. A higher frequency of deletions with the displacement of the reading frame is observed in the SI cohort. TMB index in IM reveals tumors with MI have a better response to treatment with immune checkpoint inhibitors.peer-reviewe

Potentially inappropriate prescription of drugs in hospitalized older patients

Tesis Univ. Granada. Departamento de Medicina Preventiva y Salud Públic

Prevalence of potentially inappropriate prescriptions in primary care and correlates with mild cognitive impairment

Background: Potentially inappropriate prescribing is clearly associated with adverse health consequences among older people. Nevertheless, scarce evidence exists regarding the prevalence of potentially inappropriate prescriptions (PIP) in Albania, a Western Balkans country. Objective: The aim of this study was to assess the prevalence of PIP among older Albanian patients in primary care and to determine the associated sociodemographic and medical factors, including the presence of mild cognitive impairment (MCI). Methods: Cross-sectional study in two primary healthcare centers located in two different cities of Albania, a middle-income country in the Western Balkans. The Montreal Cognitive Assessment (MoCA) tool was applied to evaluate MCI. PIPs were assessed by two trained pharmacists using the Beers criteria 2019 update. Multivariate logistic regression analysis was conducted for possible risk factors predicting PIP in the study population. Results: At least one PIP was identified among 40.23 % of the participants (174 older patients) and 10.35 % had more than one PIP. MCI was detected among 79.31 % of the patients. The most commonly represented drug groups in PIP were diuretics (24.71 %), benzodiazepines in the presence of MCI and antidepressants (both 8.62 %). The lack of electrolytes monitoring was the most common reason for PIP. According to the multivariate analysis, the only statistically significant association observed was between PIP and number of drugs prescribed [three to four drugs (OR 3.34; 95% CI 1.65:6.76), five or more than five drugs (OR 4.08; 95% CI 1.42:11.69)]. Conclusions: About four out of 10 older Albanian patients experience PIP in primary care. Further studies are needed for a comprehensive estimation of the prevalence and factors associated with PIP, particularly among elderly with mild cognitive impairment

PDIA in the Balkans: The Western Balkans Alumni Association (WBAA) as Positive Deviance: EU Enlargement and Regional Cohesion

This chapter aims to portray why and how WBAA, as an organism, organization, entity, agent, actor, network, … produces emergent effects as a regional entity is a Positive Deviance, as recognized in theory, and more specifically within the Problem Driven Iterative Adaptation by Harvard’s Center for International Development. Positive Deviance is one of the core principles in the PDIA strategy—by “creating (and protecting) environments within and across organizations that encourage experimentation and positive deviance.” First we will briefly elaborate on PDIA and its concepts and describe and encode the distinctiveness of WBAA arguing why and how it is a positive deviance for our Balkans. The expected outcome: to inspire leaders, institutions, CSOs, citizens, academia, … to take the regional approach, moves beyond the silos of a country/domain, has functional bridges with developed countries (for knowhow, funding, coopetition, alignment), and shows “how” coopetition within Western Balkans is to be done. If volunteers can do it, others can surely follow. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG

Pharmacist's Perspectives on Administering a COVID-19 Vaccine in Community Pharmacies in Four Balkan Countries

Community pharmacists expanded their roles and engaged in vaccination services in many countries around the world, but not in Balkan countries. This research aimed to assess the perceptions of pharmacists on involvement in the coronavirus disease (COVID-19) vaccine administration in four Balkan countries (Albania, Bulgaria, Romania, and Serbia). A cross-sectional survey was conducted using an online questionnaire that was distributed to community pharmacists across these countries between February and March 2021. A total of 636 community pharmacists were included in the analysis of the survey. The willingness to administer vaccines for COVID-19 (or other vaccines well established in the practice, like a flu vaccine) in community pharmacies is significantly different among the countries: the pharmacists from Albania were more willing to administer vaccines. The factors associated with the eagerness to vaccinate are almost the same among the countries: the lack of training in the faculty classes and the lack of a special place where to administer vaccines. Additional significant factors were found in Bulgaria (pharmacists from independent pharmacies wanted more than the pharmacists working in chain pharmacies to administer vaccines) and in Serbia (male pharmacists agreed more with administering vaccines than female pharmacists). Further national reforms are needed for adopting the expanding role of community pharmacists