Faculty of Medicine
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Item type:Publication, Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival(Research Square Platform LLC, 2023-02-13) ;Morra, Anna ;Schreurs, Maartje A C ;Andrulis, Irene L ;Anton-Culver, HodaAugustinsson, AnnelieBreast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. We aimed to assess the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations of treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR(95%CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR(95%CI) :1.30 (1.09-1.56)]. In conclusion, systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk. (Main MS: 3201 words). - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Immunohistochemical expression of CD44 in patients with hepatocellular carcinoma(Macedonian Association of Anatomists and Morphologists, 2020); ; ; ; Nikolovska Trpchevska, EmilijaIntroduction: CD44, a transmembrane glycoprotein with a role in cell-cell and cell-matrix interactions and one of the stem cell markers, is considered to participate in progression and prognosis of hepatocellular carcinoma (HCC), which makes it a potential prognostic marker and therapeutic target. We aimed to evaluate immunoexpression of CD44 in tumor and surrounding non-tumor liver tissue and to correlate it to multiple clinicopathological data in order to determine its prognostic value in patients from the Republic of North Macedonia. Material and Methods: Presence of the immunosignal and the percentage of CD44+ tumor cells at the whole tumor tissue sample and adjacent cirrhotic liver tissue were semi-quantitatively determined. The immunohistochemistry results were correlated to B and C hepatitis, tumor dimensions, enlarged lymph nodes, T status, differentiation (G), microvascular invasion, and survival. Results: We found a significant difference in CD44 expression between tumor and non-tumor liver tissue (p < 0.000) and significantly higher CD44 expression was also found in T4 tumors in comparison with T1 tumors (p < 0.01). Conclusion: Expression of CD44 was significantly higher in tumor in comparison to non-tumor tissue and was significantly associated to T4 local tumor growth, making it a potential prognostic marker and therapeutic target. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, The Incidence of Lymphovascular and Perineural Invasion and their Impact on Survival in Patients with Rectal Cancer(Walter de Gruyter GmbH, 2023-12) ;Misimi, Shqipe ;Cako, Dajana ;Demirel, Ali İlbey; Ulusoy, CemalAim: Lymphovascular Invasion (LVI) and Perineural Invasion (PNI) represent undesirable but still realistic pathological features of rectal cancer, associated with poor prognosis and worse survival. The aim of this study is to assess the incidence of LVI and PNI in patients treated for rectal cancer and the impact of LVI and PNI on patient survival. Material and Methods: This retrospective single center observational study, conducted in the period of 2016-2019, includes patients with rectal cancer treated with/without long-course neoadjuvant chemoradiotherapy (nCRT). Data collection encompassed demographics, tumor characteristics, type of surgery (abdominal perineal rectal resection - APR and low anterior rectal resection - LAR), and LVI/PNI presence. Survival during follow-up was estimated and compared for patients with/without LVI and PNI involvement. Results: A total number of 234 patients (77 females and 157 males) with mean age of 61.3 enrolled in the study. Neoadjuvant CRT was conducted in 170 patients. APR procedure was performed in 67 of them and LAR in 167. LVI presence was noted in 55 (24.4%) and PNI in 77 (34.2%) patients. Mean survival during follow-up was 42.07 months. The use of nCRT influenced on survival (p < 0.033). Patients treated with LAR had better survival outcomes (p = 0.001). Presence of LVI and PNI was associated with a worse prognosis (p < 0.001). Conclusion: PNI was more frequent than the LVI in this study. Patients with nCRT conduction had better overall survival. LVI and PNI presence was associated with poor prognosis in terms of overall survival in patients with rectal cancer. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Survival in Patients with Liver Cirrhosis: A Prospective Study(Walter de Gruyter GmbH, 2023-12); ; The differences in the survival time of cirrhotic patients reported by different studies are probably caused by the influence of many contributing factors. The aim of the study was to evaluate the survival over a one-year period, to register the occurrence of acute decompensation (AD) and to determine the most frequent causes of death. Material and methods: Out of 71 patients enrolled in the study, 63 completed the prospective one-year follow-up. During the follow-up, we evaluated the occurrence of AD, the causes of death, and we registered three-month, six-month and one-year survival regarding the AD status at presentation. Results: Of the 63 patients, 24 (38.09%) died before the end of the study (14 patients before the end of three months, 6 before the end of six months and 4 patients before the end of one year). The overall survival was 38.09% and the mean survival time was 108 ± 98.53 days. The most prevalent cause of death was bleeding from esophageal varices (5 patients, 20.83%). AD patients had a significantly shorter survival than patients without AD (97±90.54 vs. 229±138.59) and 78.57% of them died during the follow-up. The estimated six-month and one-year median survival time were 272.8 [95% CI (238.4-307.2)] and 267.1 [95% CI (232.9-301.2)] days, respectively. The six-month and one-year survival were significantly shorter in AD patients (p<0.0001). Conclusion: The etiology, stage of liver disease and the presence of AD are important factors that influence on the survival in cirrhotic patients. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Prognostic factors in the survival in patients with medulloblastoma in adult population(2013); ;Shumkovski, R; ;Micunovic, M - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Tumour budding – an additional prognostic facto r in colorectal cancer survival(Termedia, 2023-03) ;Gülçİn Harman Kamall ;Cemal Ulusoy; Sedat KamallTumour budding (TB) in cancer is a phenomenon of tumour cells forming clusters, and it is associated with an epithelial-mesenchymal transition into the extracellular matrix of the tumour. It has been shown that the presence of TB in colorectal cancer (CRC) is associated with worse overall survival, higher possibility for vessel invasion, lymph node involvement, and distant metastases appearance. In this retrospective study TB presence in operated patients for CRC is analysed. In the data from 81 patients, 26 presented with TB. Analysis revealed high statistical significance of the effect of TB presence on the number of metastatic lymph nodes, and the lymphovascular and perineural invasion. A statistically meaningful correlation was found between the presence of TB and CRC survival (p = 0.016). Patients with right-sided colon cancer presented with worse overall survival (p = 0.011). The patients who presented lymph node metastases and TB presence had worse overall survival (p = 0.026 and p = 0.021, respectively). Tumour budding, tumour location, and age over 64 years are found to be the independent prognostic factors in CRC patients. Tumour budding is an important prognostic factor in CRC patients that will contribute to treatment. Pathological examination must consider TB in detail. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Epidermal Growth Factor Receptor immunohistochemical expression in hepatocellular carcinoma without Epidermal Growth Factor Receptor exons 18-21 mutations(Walter de Gruyter GmbH, 2022-09-01); ; ; ; Introduction: EGFR targeted therapies, have been proved beneficial for patients with HCC, nevertheless additional research on EGFR immunoexpresion and EGFR mutations is still needed, especially in population in which it has not been done yet. The aim of this study is to evaluate EGFR immunoexpression in HCC without EGFR exons 18-21 mutations and to evaluate its influence on survival in HCC patients in North Macedonia. Methods: We studied 31 cases of HCC for EGFR immunohistochemical expression and EGFR exons 18-21 mutations. The following clinical parameters were analyzed: Hepatitis B and C virus infection, presence of cirrhosis, tumor size, enlarged lymph nodes, metastases, alpha fetoprotein level and overall survival. Presence of the EGFR immunosignal (membranous and cytoplasmic) and the percentage of positive tumor cells in the entire tumor tissue specimen were semi-quantitatively determined. Results: Hepatitis B and C virus infection, tumor size, metastatic disease and EGFR immunoexpression have influence on patient's survival. No EGFR exons 18-21 mutations were detected in this group of HCCs. EGFR expression of 61%-80% in tumor tissue significantly influenced survival of the patients (p < 0.01). Multiple Cox regression confirmed tumor size of 5-10 cm (p < 0.05), tumor size > 10 cm (p < 0.01) and EGFR expression in range of 61% to 80% (p < 0.05) as independent survival predictors in patients with HCC. Conclusion: EGFR overexpression in range of 61% to 80% was an independent survival predictor in patients with HCC, implying that these patients could benefit from EGFR inhibition. However, the absence of EGFR mutations in exons 18-21 in any of the cases of this study suggest that single drug EGFR targeted therapy in patients with HCC may be insufficient. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Immunohistochemical Expression of Epidermal Growth Factor Receptor in Hepatocellular Carcinoma(Macedonian Academy of Sciences and Arts/Sciendo, 2018-12-01); ; ;Genadieva Ivanova, Magdalena?; Epidermal growth factor receptor (EGFR) signaling plays an important role in various cancers, including hepatocellular carcinoma (HCC). We aimed to evaluate immunoexpression of EGFR in HCC and surrounding non-tumor liver tissue and to correlate it to multiple clinicopathologic data. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Current treatment options and considerations for patients with relapsed/refractory diffuse large B cell lymphoma in North Macedonia(Macedonian Pharmaceutical Association, Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy, 2021-12); ; ; ; Kocoski, BozidarAutologous stem cell transplantation (ASCT) is considered standard therapeutic approach for patients with relapsed and refractory (R/R) diffuse large B cell lymphoma (DLBCL) that are transplant eligible. For transplant ineligible patients there are few therapeutic options and novel targeted therapies and immunotherapy that are still in development. Treatment of such patients with poor prognosis is considered to be a challenge and there is constant need for new salvage treatment regimens. The aim of this study was to evaluate patients’ characteristics and treatment strategies and considerations for diffuse large B cell lymphoma in our department, and to promote new therapeutic possibilities for R/R patients with NHL DLBCL. A total of 308 patients with NHL were treated at University Clinic for hematology from 2008 until 2020 and 49% (151) of patients with NHL DLBCL were included in this study. Survival analysis of all analyzed relapsed/refractory NHL patients revealed statistically significant better survival in patients with low risk IPI score, disease stage I/II and patients with age <60 years. R CHOP was superior treatment as first line regimen and in the R/R patients, ASCT was statistically superior to other available second line treatment options. Overall survival in patients with DLBCL that achieved complete response after initial treatment was 80%. The incidence of disease relapse after initial treatment in the first 12 months was 18%. Overall survival in all treatment groups was 60% in the evaluated period of 2.5 years follow up. A total of 60% of patients with relapsed forms of NHL DLBCL were candidates for treatment with high-dose chemotherapy and ASCT. Other 40% patients were not candidates for ASCT. In conclusion we confirm the need for new treatment options for patients that relapse after ASCT and that are transplant ineligible. Patients and disease characteristics can be used to identify high-risk patients, classify once relapsed patients and define decision on further treatment - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Effect of bladder cancer variant histology on survival outcome in patients treated with radical cystectomy: A single-centre experience(Wolters Kluwer - Medknow, 2021-07); ; ; ; Context: Bladder cancer (BC) is the sixth most common malignant neoplasm in men. Recently, great effort has been devoted to the study of BC variant histology (VH). Yet, the results from these studies have shown conflicting data and remain unclear whether their presence alters recurrence and survival rates after radical cystectomy (RC). Aims: We undertook this study aiming to test the effect on VH on recurrence-free survival (RFS) and overall survival (OS) in single-center RC patients. Settings and Design: We have retrospectively analyzed medical records and pathology reports from 331 patients who underwent RC with or without pelvic lymphadenectomy at University Urology Clinic-Skopje, North Macedonia, in the period between 2010 and 2018. Subjects and Methods: Microscopic analysis of the specimens involved the evaluation of histological tumor type, tumor grade, pathological tumor node metastasis stage, presence of lymphovascular invasion, and resection margin status. Statistical Analysis Used: Univariable and multivariable Cox regression models were applied to test the effect of VH on RFS and OS. Results: We found 185 patients who matched our inclusion criteria. At multivariable analyses, lymphovascular invasion and positive resection margins were associated with shorter RFS. Similarly, patients diagnosed with lymphovascular invasion, positive resection margins, and a pelvic lymph node metastasis had poorer OS. VH was not found to be an independent predictor of both RFS and OS (P > 0.05). Conclusions: The present study did not reveal prognostic effect of VH on RFS and OS. In our series, histomorphologic parameters including lymphovascular invasion, resection margins, and pelvic lymph node metastasis were the most relevant predictors on survival outcome after RC.
