Faculty of Medicine
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Item type:Publication, Influence of MSI and 18q LOH markers on capecitabine adjuvant monotherapy in colon cancer patients(Dove Press Ltd., 2018) ;Matevska Geshkovska, Nadica ;Staninova Stojovska, Marija; ;Petrushevska Angelovska, NatalijaPanovski, MilchoPurpose: The aim of this study was to evaluate whether pretreatment analysis of selected molecular markers can be used for the prediction of disease-free survival (DFS)/overall survival (OS) of capecitabine adjuvant monotherapy in colon cancer patients. Patients and methods: A total of 126 patients enrolled in a capecitabine Phase IV clinical trial were analyzed for microsatellite instability (MSI), 18q loss of heterozygosity (LOH), thymidylate synthase (TYMS) 5' variable number of tandem repeat (VNTR), and methylene tetrahydrofolate reductase (MTHFR) C677T variants. The significance in predicting 5-year DFS/OS was assessed by Kaplan-Meier and Cox regression analyses. Results: The MSI-high (MSI-H) genotype was significantly associated with DFS (HR 0.205, 95% CI 0.05-0.88, P=0.033) and OS (HR 0.208, 95% CI 0.05-0.89, P=0.035) compared to the microsatellite stable genotype. In models stratified according to clinicopathologic characteristics, the MSI-H genotype remained a positive predictive factor for DFS/OS only in patients with stage III (P=0.023) and patients with tumors localized proximally to the splenic flexure (P=0.004). Distal colon cancers with 18q LOH have a greater survival rate when treated with capecitabine than patients with stable tumors (81.3% vs 50.0%, HR for relapse 0.348, 95% CI 0.13-0.97, P=0.043). TYMS 5'VNTR and MTHFR C677T variants were not associated with DFS or OS. Conclusion: MSI and 18q LOH markers have the potential to be utilized in the selection of colon cancer patients eligible for capecitabine adjuvant monotherapy. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Molecular Basis of Inherited Colorectal Carcinomas in the Macedonian Population: An Update(Macedonian Academy of Sciences and Arts / De Gruyter, 2019) ;Staninova Stojovska, Marija ;Matevska Geskovska, Nadica ;Panovski, Milcho ;Angelovska, BiljanaHereditary factors are assumed to play a role in ~35.0-45.0% of all colorectal cancers (CRCs) with about 5.0-10.0% associated with high penetrant disease-causing mutations in genes correlated to hereditary polyposis (HP) or hereditary non polyposis syndromes (HNPCC). Although inherited germline mutations in mismatch repair (MMR) and the APC genes contribute significantly to CRC, genetic diagnosis cannot yet be obtained in more than 50.0% of familial cases. We present updated data of 107 probands from the Macedonian population with clinically diagnosed HP (n = 41) or HNPCC (n = 66) obtained by next generation sequencing (NGS) with three different gene panels covering the coding, flanking and promoter regions of 114 cancer predisposition genes. Using this approach, we were able to detect deleterious mutations in 65/107 (60.7%) patients, 50.4% of which were in known well-established CRC susceptibility genes and 10.2% in DNA repair genes (DRG). As expected, the highest frequencies of deleterious variants were detected in familial adenomatous polyposis (FAP) and in HNPCC patients with microsatellite instability (MSI) tumors (93.8 and 87.1%, respectively). Variants of unknown significance (VUS) were detected in 24/107 (22.4%) patients, mainly in HNPCC patients with microsatellite stable (MSS) tumors or patients with oligopolyposis. The majority of VUS were also found in DRG genes, indicating the potential role of a doble-strand brake DNA repair pathway deficiency in colorectal cancerogenesis. We could not detect any variant in 18/107 (16.8%) patients, which supports the genetic heterogeneity of hereditary CRC, particularly in HNPCC families with MSS tumors and in families with oligopolyposis. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Efficacy of Intraperitoneal Bupivacaine on Pain Relief After Laparoscopic Cholecystectomy(Macedonian Academy of Sciences and Arts /Walter de Gruyter GmbH, 2018-07-01) ;Toleska, Marija; ; ;Panovski, MilchoPatients undergoing laparoscopic cholecystectomy do experience postoperative pain, especially in the abdomen. Postoperative pain management remains a major challenge after laparoscopic procedures. Administration of intraperitoneal local anesthetic (IPLA) after surgery is used as a method of reducing postoperative pain. In this study, we evaluated the effect of intraperitoneal infiltration of local anesthetic (bupivacaine) for pain relief after laparoscopic cholecystectomy.</jats:p> <jats:p><jats:bold>Material and methods:</jats:bold> In this prospective, controlled, and randomized study were included 50 patients aged 25-60 years (35 female and 15 male), scheduled to laparoscopic cholecystectomy with ASA classification 1 and 2. Patients were classified randomly into two groups: group A, which included 25 patients who received intraperitoneal instillation of bupivacaine 0.5% 20 ml; and group B, which included 25 patients who didn’t receive any intraperitoneal instillation. Postoperative pain was recorded using the visual analogue scale (VAS) for 24 hours after laparoscopic cholecystectomy.</jats:p> <jats:p><jats:bold>Results:</jats:bold> There was no significant difference with respect to age, weight, and sex; duration of surgery; and anesthesia time. VAS scores at different time intervals were statistically significantly lower at all times in group A compared to group B. There were statistically significant differences in VAS scores between group A and group B at all postoperative time points - 1hr,4 hr,8 hr,12hr and 24hr (p < 0.00001).</jats:p> <jats:p><jats:bold>Conclusion:</jats:bold> Intraperitoneal instillation of bupivacaine provides good analgesia in the postoperative period after laparoscopic cholecystectomy.</jats:p>
