Faculty of Medicine
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Item type:Publication, RELATIONSHIP OF IMMUNOHISTOCHEMICAL EXPRESSION OF MISMATCH REPAIR GENE PRODUCTS AND CLINICOPATHOLOGICAL FEATURES IN PATIENTS WITH LOW-GRADE ENDOMETRIAL CANCER(Macedonian Association of Anatomists and Morphologists, 2024); ; ; ;Ognenoska Jankovska, BiljanaBackground: This study examines the relationship between mismatch repair (MMR) gene expression and clinicopathological features in patients with low-grade endometrial cancer (EC). Methods: A prospective cohort of 40 patients with histologically confirmed low-grade EC underwent immunohistochemical analysis to determine MMR status. Clinical data, including age, body mass index (BMI), menopausal status, parity, and comorbidities, were collected. Histopathological evaluations assessed myometrial invasion,lymphovascular invasion and disease stage. Results: MMR deficiency (MMRd) was identified in 35% of patients, predominantly associated with MLH1/PMS2 loss. No significant associations were found between MMR status and clinical characteristics such as age, BMI, or comorbidities. However, MMRd tumors exhibited a significantly higher prevalence of myometrial invasion over 50% (85.71% vs. 38.46%, p=0.0042) and lymphovascular invasion (71.43% vs. 19.23%, p=0.00114). Additionally, MMRd cases were more frequently associated with advanced disease stages, particularly in stage IIIC (28.57% vs. 7.69%, p=0.078). Conclusion: The importance of MMR status in the biological behavior of low-grade endometrial cancer is highlighted in this study. The strong correlation between MMR deficiency and aggressive histopathological features such as increased myometrial and lymphovascular invasion, highlights the need to integrate MMR testing into clinical practice, even if clinical parameters showed no significant association with MMR expression. These results suggest that MMRd may be a useful prognostic indicator that requires more research to improve patient outcomes and treatment approaches for low-grade endometrial cancer. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, DETECTION OF LYNCH SYNDROME IN ENDOMETRIAL CANCER PATIENTS(Faculty of Medicine, University Ss. Cyril and Methodius in Skopje, 2023-12-27) ;Kubelka Sabit, Katerina ;Petrova, Deva; ;Jashar, DzangisFilipovski, VanjaLynch syndrome (LS) is an autosomal dominant inherited disease defined by germline mutations in mismatch repair (MMR) genes, leading to a defective DNA MMR system. Patients with LS havepredisposition to a spectrum of cancers, primarily colorectal cancer, but LS-associated endometrial cancer (LS-EC) is the most common extraintestinal cancer and occurs in 2% of LS patients. The most frequently mutated MMR genes are MLH1, MSH2, MSH6 and PMS2. Clinico-pathologic features of LS-EC are: early age of onset, lower body mass index, endometrioid type of carcinoma and lower uterine segment involvement. Recent studies support LS screening in every EC patient since MMR status is also part of the molecular subclassification of endometrial cancers.Screening methods include traditional clinical criteria and molecular techniques, such as MMR-immunohistochemistry(MMR-IHC), microsatellite instability (MSI) testing, MLH1promoter methylation testing and gene sequencing. MSI can also be detected in sporadic tumors, through epigenetic events inactivating the MMR system. Patients with diagnosed LS and their affectedrelatives should be closely monitored in order to prevent the development of other types of cancer. Patients with advanced recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) endometrial cancer can also benefit from immunotherapy.We describe our 3-year experience in screening of Lynch syndrome in EC patients. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Small intestine metastasis from endometrial carcinoma initially presented as enterocutaneous fistula: a case report and literature review(Oxford University Press (OUP), 2024-05); ;Limani, Nimetula ;Ristova Tancheva, Aleksandra ;Manasievska Bogoevska, AntonelaAlthough endometrial cancer is the fourth most common malignancy among women, it rarely metastasizes to the small intestine. Cases of endometrial recurrence to the intestine clinically present with secondary anemia, melena, abdominal cramps, and epigastric pain. Only a dozen cases are reported in the literature, but none presented with an enterocutaneous fistula. In this report, we present a case of an 88-year-old female patient previously treated for endometrial adenocarcinoma with surgery and adjuvant radiotherapy. Fourteen months after the surgery, the patient presented with an enterocutaneous fistula on the anterior abdominal wall, which was confirmed to be a metastasis from the primary tumor. To our knowledge, this is the first case of endometrial cancer metastasizing to the small intestine with involvement of the anterior abdominal wall and the occurrence of an enterocutaneous fistula, which was treated with radical surgery. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Dopler ultasound scoring system for identification of endometrial cancer in postmenopausal patients(Department of Anaesthesia and Reanimation, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, R.N. Macedonia, 2023-10-09); ; ; ; Spasoski, SIntroduction: Endometrial cancer (EC) is the most common malignancy of the female genital tract in the developed world. Nowadays, preoperative evaluations using advanced imaging techniques have become more common, but little has been done on the best imaging technique for routine use and preoperative evaluations of endometrial carcinoma. The aim of this study was to evaluate the predictive value of Doppler ultrasound scoring system in detection of endometrial malignancy in postmenopausal patients with vaginal bleeding. Material and Methods: This cross-sectional study, was conducted at the University Clinic of Obstetrics and Gynecology, Skopje and included 164 postmenopausal patients admitted to the Gynecology Department of the clinic. They were divided into two main groups based on their clinical presentation and further subdivided according to histopathological results. All patients underwent a standard transvaginal ultrasound examination followed by power Doppler endometrial vascularity assessment, as well as histopathological analyses of endometrial sampling for each of them was performed. Univariate and multivariate logistic regression were utilized to determine the predictive values of Doppler parameters and the scoring system. Results: Significant associations were found between endometrial malignancy and various factors, including number of blood vessels, presence of densely packed bundles, the values of pulsatility index, resistance index, time averaged maximum velocity and peak systolic velocity. Among these, pulsatility index had the greatest influence (Wald=11.32/ p<0.01 (p=0.001)) and time averaged maximum velocity had the weakest influence (Wald=0.10/ p>0.05 (p=0.73)). Clinical scoring system exhibited a sensitivity of 79.60%, the specificity is 97.30%, and overall model accuracy is 91.50%. Conclusion: The results of our study have proved that all Doppler parameters are significant predictive factors in determining endometrial cancer in postmenopausal patients with vaginal bleeding. Their combination could obtain a non-invasive scoring system that could reduce invasive procedure in diagnosis of the endometrial malignancy in patients with ultrasound characteristic of thickened endometrium more than 5mm. For this scoring system, there is a need of modern ultrasound device and clinician with greater experience. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, THE IMPACT OF OBESITY AND FAT DISTRIBUTION ON ENDOMETRIAL CANCER RISK IN POSTMENOPAUSAL PATIENTS(Macedonian Association of Anatomists, 2023); ; ; ; Endometrial cancer (EC) is the fourth most common cancer in women worldwide, with rising incidence partly due to changing reproductive trends and ever increasing obesity. Obesity, especially central adiposity, is linked with endometrial adenocarcinoma, possibly due to elevated estrogen and decreased sex hormone-binding globulin levels. The study aims to evaluate the impact of obesity on endometrial malignancy and to determine whether central adiposity (measured by the waist-to-hip circumference ratio) serves as a better indicator of endometrial cancer risk than BMI. In this cross-sectional study, we studied 164 postmenopausal patients from the University Clinic of Obstetrics and Gynaecology in Skopje. Patients were admitted to the hospital for histopathological examination of endometrial layer because of vaginal bleeding with endometrial thickness >4mm, or other sonographic endometrial abnormalities. Histopathological findings subdivided them into two categories: with malignancy (group I) or benign abnormality (group II). Standard examinations and measurements, including BMI and waist-to-hip ratio, were performed. A significant association was observed between endometrial malignancy and obesity as measured by waist-to-hip ratio. In the distribution of data related to BMI and histopathological findings from the endometrial biopsy for Pearson Chi-square=8.35 and p<0.01(p=0.004) there is a significant difference. For Odds Ratio=2.71 (95.%CI:1.36-5.38), patients who had a BMI ≥ 30 kg/m2 were 2.71 times more likely to have endometrial malignancy than patients who had a BMI <30 kg/m2, (p<0.01). There is a significant difference in the shown distribution of data related to waist circumference/hip circumference and histopathological findings of endometrial sampling Pearson Chi-square=79.22 and p<0.001(p=0.000). For Odds Ratio=40.89 (95.% CI:15.23-109.78), patients who had waist circumference/hip circumference ≥ 0.85 were 40.89 times more likely to have endometrial malignancy than patients who had waist circumference/hip circumference <0.85, (p<0.001). Upon analysing the contribution of central obesity determined by waist-to-hip ratio, it was found to have a more substantial impact (Wald = 37.76, p < 0.001) compared to BMI (Wald = 0.97, p= 0,32). Our study confirms that obesity is a risk factor for endometrial malignancy. Furthermore, fat distribution proves to be a more crucial and accurate indicator of endometrial cancer risk than overall obesity. The statistical significance of the waist circumference to hip circumference ratio exceeded that of BMI. Therefore, even if a patient has a normal BMI, but a waist-to-hip circumference ratio greater than 0,80, she should be considered at increased risk for endometrial malignancy and should be closely monitored in the future in order to detect any malignant changes. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Adjuvant chemotherapy in patients with stage IIIA endometrial carcinoma with solitary adnexal involvement(Macedonian Association of Pathology, 2016-09); ;Veljanoska, Slavica; ; Objective: The optimal adjuvant therapy in endometrial cancer patients with solitary adnexal involvement is still controversial. The purpose of this study was to evaluate, retrospectively, the outcome and efficacy of adjuvant chemotherapy in these patients. Material and Methods: The medical records of the patients with stage IIIA endometrial cancer with solitary adnexal involvement who were treated with surgical resection and adjuvant chemotherapy between 2005 and 2010, were retrospectively analyzed. A total of 40 patients treated with platinum-based adjuvant chemotherapy were included. Following surgery, all patients received 4 cycles of Carboplatin 300 mg/m2 and Paclitaxel 175 mg/m2 by intravenous injection every 3 weeks. The survival and recurrence rates were evaluated. Results: The median follow-up period was 5 years (60 months). Recurrences occurred in 12.5 % (n=5) of the patients. One local recurrence (1/5, 20%) and 4 distant metastases (4/5, 80%) in liver (n=2, 40%), lung (n=1, 20%) and paraaortal lymph nodes (n=1, 20%) were observed. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 87.5% and 92.3%, respectively. Conclusions: In conclusion, platinum-based adjuvant chemotherapy may improve prognosis and survival in stage IIIA endometrial cancer patients with solitary adnexal involvement and could be considered as a potential adjuvant treatment. Although adjuvant chemotherapy has demonstrated improved both disease-fee and overall survival compared to radiotherapy (DFS 87.5% vs 69%; OS 92.3% vs 78%), further studies are needed to define the optimal treatment strategy. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Adjuvant chemotherapy and radiotherapy for Stage III endometrial cancer: Impact on Survival(RAD Association, 2018-06); ;Veljanoska, Slavica; ; Introduction. Adjuvant treatment options for advanced-stage endometrial cancer include chemotherapy (CT) and radiation therapy (RT), but the optimal treatment strategy is currently under debate. The aim of this study is to investigate the utilization of adjuvant RT and CT in patients with stage III endometrial cancer and their impact on overall survival (OS) and disease-free survival (DFS). Materials and Methods. A retrospective review was performed of 40 patients with Stage III endometrial cancer who received adjuvant treatment at University Clinic of Radiotherapy and Oncology (UCRO) in Skopje between 2012 and 2015. Postoperative treatment was administered based on performance status and medical comorbidities. Chemotherapy regimens comprised of Carboplatin (AUC 5) and Paclitaxel (175 mg/m2), a 3-week interval for 6 cycles (chemotherapy alone) and 4 cycles (sequential arm). RT was delivered using 3-D CRT with a total dose of 50 Gy in 25 fractions prescribed in PTV for 5 weeks with/without an additional 7 Gy prescribed at a depth of 0.5 cm from the vaginal surface. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Combined radiotherapy and chemotherapy were compared with radiotherapy alone and chemotherapy alone. Results. The distribution of surgical stages is as follows: IIIA accounted for 60% (n=24), stage IIIB accounted for 9.8% (n=4) and stage IIIC accounted for 30% (n=12). The median age was 65 years and median follow-up was 35.5 months. There were 40 patients who received adjuvant treatment, 10% (n=4) received CT alone, 27.5% (n=11) received RT alone, and 62.5% (n=25) received sequential combined CT followed by 3D CRT with/without vaginal vault brachytherapy. Relapse occurred in 55% (n=22) of the patients. High grade and lymphovascular space invasion (LVSI) are risk factors for recurrence and poor prognosis. Overall survival (OS) and Disease-free survival (DFS) at 3 years for patients receiving combined CT and RT, adjuvant RT alone and adjuvant CT alone were 68.8%, 41.26%, and 37.57% for OS and 58.03%, 33.08%, and 24.96% for DFS, respectively. DFS and OS were significantly longer in patients treated with combined RT and CT than in those treated with CT alone (DFS: p= 0.0005; hazard ratio [HR], 5.677; OS: p= 0.0143; HR, 4.289) or RT alone (DFS: p = 0.0137; HR, 2.482; OS: p = 0.0151; HR, 3.036). Conclusion. Combined modality treatment with chemotherapy and radiotherapy can improve both overall and disease-free survival in patients with Stage III endometrial cancer compared with single modality alone. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Preoperative detection of sentinel lymph node in patients with endometrial cancer - comparison of planar lymphoscintigraphy, spect and SPECT/CT(2022); ;Stoilovska Rizova, Bojana; ; Sentinel lymph node (SLN) mapping allows minimal invasive assessment of lymph node status in patients with early-stage endometrial cancer (EC). Intraoperative detection of SLNs is based on the results obtained from preoperative nuclear medical images. The purpose of this study was to compare the data obtained from planar lymphoscintigraphy (PL), single-photon emission computed tomography (SPECT), and SPECT with computed tomography (SPECT/CT) for preoperative SLN detection in patients with EC. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Endometrioid Adenocarcinoma Arising in Adenomyoma in a Woman with a Genital Prolapse - Case Report(Scientific Foundation SPIROSKI, 2018-06-14); ;Krstevska, Iskra ;Trajanova, Milka ;Chelebieva, JasminaGosheva, IrenaBACKGROUND: Endometrial cancer is the third-ranked genital malignancy in women and includes 3% of cancer deaths. There is a 2.8% chance of a woman developing endometrial cancer during her lifetime. Low-grade endometrioid adenocarcinomas are often seen along with endometrial hyperplasia, but high-grade endometrioid adenocarcinomas have more solid sheets of less-differentiated tumour cells, which are no longer organised into glands, often associated with surrounded atrophic endometrium.CASE REPORT: We present an unusual case of endometrial adenocarcinoma arising in adenomyoma in 74-year old woman presented with genital prolapse, without other clinical symptoms. Ultrasound evaluation revealed endometrium with 4 mm-thickness and atrophic ovaries. The cervical smear was normal. The patient underwent a total vaginal hysterectomy. The histopathology of the anterior uterine wall revealed an intramural adenomyoma of 4 mm in which some endometrial glands with malignant transformation of well-differentiated endometrioid adenocarcinoma without infiltration in surrounding myometrium and lymphovascular invasion were present. The endometrium lining the uterine cavity was predominantly atrophic, and only one focus of simplex and complex hyperplasia was found, with cell-atypia. According to AJCC/FIGO 2010, the tumour was classified: pTNM = pT1B pNX pMX G1 R0 L0 V0 NG1, Stage I. On dismiss, the near-future oncological consultation was recommended.CONCLUSION: We would like to point out the rare occurrence of such type of malignancy and the importance of meticulous histopathology evaluation, even after reconstructive surgery for genital prolapse. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Brachytherapy alone in the postoperative treatment of stage I endometrial carcinoma(Institut za onkologiju Vojvodine, 2018-11-17); ; ;Stojmenovska V; Dimoski IIntroduction: This study evaluate the local control efficacy and toxicity of postoperative intravaginal brachytherapy (IVBT) alone among patients with endometrial cancer stage I. Material and methods: Between January-2004 and December-2011, 60 stage I endometrial adenocarcinoma patients were treated with IVBT alone, 47 in stage IA, 13 patients in stage IB. The surgical approaches were total abdominal hysterectomy (HTA) and bilateral salpingoopforectomy (BSO) in 45 patients, plus bilateral pelvic, paraaortic lymph node dissection in 15 patients. The mean interval between the surgery and the brachytherapy was 30-37 days. <½ miometrial invasion was found in 48 patients, and >½ in 12 patients. The brachytherapy was applied in 3 weekly fractions of 7Gy per fraction, prescribed at depth of 0,5cm from the applicator surface with HDR, Iridium-192. The mean diameter of the vaginal applicator was 3 (2-3,5) cm. Results: With a mean follow up time of 38 months (12-84), all 60 patients are alive. Reccurence was observed in 5 patients (8,3%): 3 patients experienced local recidiv and 2 patients developed a pelvic mass. The mean rectal dose was estimated 14,1Gy and the mean bladder dose was 13Gy. Acute genitourinary toxicity was observed in 31 patients during the therapy. Vaginal stenosis as late complication occurred in 3 patients. Conclusion: Intravaginal brachytherapy alone in the postoperative treatment of stage I endometrial carcinoma achieves local control associated with acceptable toxicity and minimal morbidity.
