Popova jovanovska, Rozalinda
Preferred name
Popova jovanovska, Rozalinda
Official Name
Popova jovanovska, Rozalinda
Main Affiliation
Email
rozalinda.popova@medf.ukim.edu.mk
28 results
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Item type:Publication, FOUR YEAR RESULTS OF CONSERVATIVE TREATMENT OF BENIGN STRICTURES OF THE ESOPHAGUS WITH SVARY GILLIARD TECHNIQUE OF BOUGIENAGE: CROSS-SECTIONAL STUDY REPRESENTING FIRST EXPERIENCES IN REPUBLIC OF MACEDONIA(Macedonian Academy of Sciences and Arts, 2018-01); ; ; - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Polymorphism IL 28B and response to therapy in chronic hepatitis C(2016); ; ; ; INTRODUCTION: Chronic hepatitis C is still a majgor cause for developing cirrhosis and hepatocellular carcinoma which often results in liver failure and thus in liver transplantation. According to the World Health Organisation 180 million people are infected worldwide and 3-4 million new infections per year were estimated (1). The current standard of care (SOC) for chronic HCV infection is a combination of pegylated interferon (PegINF -2a or PegINF -2b) plus body-weighted ribavirin (RBV) for the duration of 24 weeks or 48 weeks depending on the HCV viral genotypes (2). The primary goal of the treatment is HCV eradication, which is actally sustained viral response (SVR). The SVR is defined as undetectable HCV RNA in serum, 24 weeks after the completion of the antiviral treatment (3). However, only about 40-50% genotype 1 or 4 patients treated and 80% genotype 2 or 3 patients treated could respond completely and achive sustained virological response (4,5). Moreover, side effects from the therapy such as influenza-like symptoms, psychiatric symptoms and hematological abnormalities, could result in the dose reduction or even the premature discontinuation of the treatment (6). To avoid these potential adverse events in patients who do not benefit from the treatment and to reduce the cost of therapy, it is necessary to predict an individual’s response before at the early stage of the treatment. Virus-specific characteristic (viral load, genotype, viral variants as mutations of interferon sensitivity determining region- ISDR) may be responsible for virologic response but also clinical parametars (age, gender, BMI, fibrosis stage, liver enzymes) (7,8). Investigations on genetic determinants of chronic hepatis C established that a single nucleotide polymorphism (SNP) in the interleukin (IL)-28B gene promoter region affected the spontaneous and induced clearance of hepatitis C virus (9). Among 500 000 genetic variants which were analyzed genome-wide, a few associated with virologic response were identified, and showed variable frequency and importance across human ethnic groups (10). The mechanism by which SNPs influence the outcome of HCV infection and its treatment is not clear. It is suggested that regulation of the promoter region of IL28B in antiviral activity may also affect two other genes belonging to interferon (INF)- family encoded in this region (10, 11). INF- possess antiviral activities agains hepatitis C virus (12). The genome-wide associated studies (GWAS) showed that SNPs near IL28B gene (CC for rs12979860, TT for rs8099917 and AA for rs12980275) were associated significantly with treatment outcome in patient with chronic hepatitis C. However, about 50% of patients with a sustained virological response do not carry favorable IL28B alleles (13). The factors which increase the chance of a therapeutic response in these patient are not yet known. A detailed analysis if the course of therapy of chronic hepatitis C with pegylated INF and ribavirin in the presence of a hazardous IL28B allele might better delineate the clinical characteristics of the difficult-to-treat group of patients. The aim of the study was to evaluate the effects of IL28B polymorphism on response to treatment with peginterferon and ribavirin in patients with chronic hepatitis C. MATERIAL AND METHODS: Twenty-five adult Caucasians previous assessed with chronic hepatitis C due to HCV genotupe 1 and 3 were included in the study. The study protocol was approved by the institutional ethics committee and written informed consent was obtained from each study participant. Patients were treated with standard antiviral therapy with pegylated INF alfa and ribavirin. Pegylated interferon alfa 2a 180 μg was administered subcutaneously once a week. Body-weighted ribavirin was administered daily. The treatment duration was 48 weeks for patients with HCV genotype 1 and 24 weeks for patients infected with HCV genotype 3. SVR was used for the assessment of the antiviral treatment effectiveness. SVR is defined by undetectable viral RNA 24 weeks after the end of treatment. Finaly eighteen patients were analysed, because two premature discontinuated the treatment and for five there are no available data for SVR. Sample od peripheral blood were collected from each patient enrolled in the study for HCV quatntification and IL28B polymorphism genotyping. Reverse transcriptase-polymerase chain reaction assay for HCV quantification was done with One-tube real time PCR HCV amplification with lower detection limit 70 IU/ml. Polymorphisms rs12979860 (C>T) and rs8099917 (T>G) in gene IL28B were genotyed by PCR. Each polymorphism assay contained one pair of primers and one pair of probes, and each allele of the polymorphisms was labeled. For statistical analysis mean and standard deviation were used for parametric variables. Considering the small sample difference test (percentage of structure) was used to determinate the genetic predictors of the SVR. A p<0.05 was consideded statistically significant. RESULTS: The study population included 9 genotype 1 and 9 genotype 3 HCV infected patients. Their median age was 31.4±4.4 years and 88.88% were males. SVR were achived in 83.3% patients. The distribution of the frequencies od rs12979860 genotypes in the analyzed sample was: 10 (55.55%) patients with CC genotype and 8 (44.44%) patients with CT genotype. The distribution of the frequencies od rs8099917 genotypes was: 15 (83.33%) patients with TT genotype and 3 (16.66%) patients with TG genotype. The difference test showed that difference in persentage which is registered between SVR in CC and CT is not statistically significant (p=0,6714). There is no association in achievement SVR in CC and non-CC genotypes of rs12979860. There also no significance in achieving SVR in patients with TT genotype of rs8099917 and in patients with TG genotypes (p=0.3961). Futhermore there was no association with the achivment od SVR as compared with genotype (p=0.0579). DISCUSION: In this study, no significant difference was found in the response to treatment and allele proportions of SNPs rs12979860 and rs8099917 possibly due to the small size of the sample. The study of Silva Conde et al. confirmed similar effect of IL28B polymorphism on SVR in infected HCV patients (14). In another study from Norway and Denmark involving genotype 3 HCV-infected patients, RVR was achived by a significantly greater number of patients who had CC and TT genotypes at rs 12979860 and rs8099917, respectively, but these genotypes showed no association with SVR (15). Consistent to our findings were results of the study of Sarrazin et al.which present no significant association of SNPa rs8099917 with virologic treatment response (16). Investigation of a comparable number of genotype 2/3 infected patients in study by Rauch et al. also showed no correlation between the rs8099917 genotype and virologic response to pegylated interferon/ribavirin combination therapy (17). In contrast, the GWAS identified that homozygosis for C allele of rs12979860 and homozygosis for the T allele of rs8099917 were favorable genotypes of the IL28B gene polymorphisms which predicted the SVR in patients with chronic hepatitis C treated with peginterferon and ribavirin (18,19). The distribution of frequencies of rs12979860 genotypes in our study group was : CC 55.55% and CT in 44.44% . The distribution of frequencies of rs8099917 genotypes in our study sample was TT 83.33% and TG 16.66%. Sticchi et al. reported distribution of rs8099917 genotypes TT in 55%, TG in 40% and GG in 5% of the study participants (20). Results of other studies reported bigger percentage of CT than CC for distribution of the frequencies of rs12979860 (21.22). However, about 50% of patients with a sustained virological response do not carry favorable IL28B alleles (13). The factors which increase the chance of a therapeutic response in these patient are not yet known. Other factors, such as HCV genotype, viral-load, ethnicity should be used together with IL28B genotype as predictors of response on antiviral therapy. CONCLUSION: We did not find a significant association of SNPs rs12979860 and rs8099917 with SVR thus disagreeing with studies that found an association between genotype CC (rs12979860) and SVR in individuals with genotype 1, 2 and 3 as well as between genotype TT (rs 8099917) and SVR in individuals with genotype 3. Our study is limited by its sample size. And possibly results due to this fact. Nevertheless genotyping of this polymorphism on a large HCV population will aid clinical decision making for both current standard care and potentially for the integration of other agents in future, providing an opportunity for clinicians to individualize treatment regimens for hepatitis C patients. - Some of the metrics are blocked by yourconsent settings
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Item type:Publication, KRAS MUTATIONS IN PANCREATIC ADENOCARCINOMA IN CORRELATION WITH CLINICAL AND PATHOLOGICAL CHARACTERISTICS(Macedonian Association of Anatomists and Morphologists, 2020); ; ; Pancreatic adenocarcinoma is the seventh cause of death of all malignant tumors worldwide and has the worst prognosis of all solid tumors. In Europe, it is the sixth most common cause of cancer related death and in United States it is the fifth cause of death after lung cancer, prostate cancer, breast and colorectal cancer. Numerous molecular studies have analyzed genetic and epigenetic changes as responsible for the histological variants of this cancer, their correlation with family predisposition, and opportunities for better treatment and survival. This study included 42 patients with pancreatic adenocarcinoma. Tumor tissue samples obtained from surgical specimen were histopathologicaly examined and genetic mutations were determinate. Prior to surgery, patients were diagnosed by imaging modalities (abdominal ultrasound and/or CT), clinical and laboratory examinations. Histopathological analyses included: T category, grade of tumor differentiation, vascular invasion, lymph node involvement and metastasis. We obtained the KRAS and EGFR gene mutations on the Randox investigator diagnostic platform. The aim of the study was to determine the frequency of KRAS and EGFR mutations in pancreatic adenocarcinoma and their correlation with multiple tumor characteristics. No one patient had EGFR mutation. The results showed that more of the patients with KRAS genetic mutations are frequently associated with advanced disease stage and worse prognosis, although the difference was not statistically significant in comparison to patients without KRAS mutations. - Some of the metrics are blocked by yourconsent settings
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Item type:Publication, Rare case presentation of dermoid cyst of pancreas(Department of Anaesthesia and Reanimation, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, R.N. Macedonia, 2021); ; ; Teratomas are classified as either mature or immature, and according to tissue density can be classified to solid or cystic, also known as “dermoid cyst.” Immature teratomas are generally solid, histologically undifferentiated malignant tumors. Mature cystic teratomas (MCTs) in the pancreas are extremely rare with small number of cases reported in the literature. The most common location of the mass is in the head/ body of the pancreas. Diagnosis of teratomas is challenging, since there are no peculiar imaging findings, or characteristic serum markers. We present a case of a 42-years-old woman with a mature cystic teratoma in the head of the pancreas incidentally found at ultrasound imaging, who after surgical treatment remained asymptomatic. This case emphasizes the necessity of specific diagnostic tools and increased awareness about MCT, when a pancreatic cystic lesion is disclosed. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Portal vein thrombosis – etiology, clinical features, complications.(2012); ; ; ; SUMMARY: Portal vein thrombosis as a condition is more frequently discovered in recent years, due to the routine use of imaging procedures, especially Duplex and color Doppler ultrasound, in everyday clinical practice. Portal vein thrombosis either acute or chronic, is usually presented with non-specific clinical features. Etiology can be different, systemic and local factors are involved, among them prothrombotic disorders, cancer and cirrhosis, are the most frequent. Our study included 16 patients (pts), admitted to our hospital between 2010 and 2012, with varying clinical symptoms, starting from abdominal pain, up to abundant variceal bleeding. Duplex and color Doppler ultrasound examination revealed portal vein thrombosis in all of the them, the diagnosis was confirmed by the means of contrast enhanced Computed Tomography, Magnetic Resonance Imaging or during surgery. In patients presented with variceal bleeding, endoscopic measures for bleeding management were undertaken immediately, whereas patients presented with non-bleeding episodes required anticoagulant treatment (i.v. Heparin, s.c. Clexane, maintened by oral Syntrom). The treatment outcome was different in different patients, mostly depending on etiology and clinical features, furthermore the final assessment of the treatment was difficult to achieve, due to the retrospective nature of the study and the limited period of time. INTRODUCTION: When we speak about portal vein thrombosis, we mean exactly: thrombosis of the main portal vein and it’s tributaries, superior and inferior mesenteric vein and splenic vein. Thrombosis occurs in different segments of the main portal vein, just in extrahepatic part, or in whole portal trunk and it’s intrahepatic branches. Occlusion by the clot may be complete, or occurring in a part of the vessel, with a present blood flow around the clot. Thrombosis of the splenic vein can be isolated from the rest of the portal venous system, whereas occlusion of the superior and inferior mesenteric vein, usually occurs together with main portal vein thrombosis. The diagnosis of portal vein thrombosis may be established in the “acute phase”, or in advanced “chronic phase” with already developed complications as a result of portal hypertension. The diagnosis of portal vein thrombosis is much more frequently established recently, due to the routine use of Doppler ultrasonography during abdominal examinations. It has been shown that overall risk of getting portal vein thrombosis in general population during lifetime is 1% , whereas in cirrhotic patients is much more higher, from 10% to 20%. Etiology of portal vein thrombosis can be different, and systemic and local risk factors are involved. The most frequent are prothrombotic disorders, established cirrhosis, cancer, abdominal infection/inflammation and intra-abdominal surgery. Risk factors remain unknown in only small percent of cases. The cause of portal vein thrombosis in cirrhotic patients differs from non-cirrhotics, it is mainly because the reduced and extremely slow blood flow, which sometimes becomes retrograde in patients with portal hypertension. These two conditions can lead to blood clot formation in portal vein, despite the decreased production of prothrombin complex factors in the diseased liver. Depending on etiology, and weather portal vein thrombosis is in acute or chronic phase, clinical presentation will vary. Patients refer to the hospital with abdominal pain, nausea and vomiting due to the bowel ischemia from congestion, or with variceal bleeding as a result of portal hypertension and developed collateral circulation. Patients with portal vein thrombosis without cirrhosis will develop varices but no ascites, because the liver is not involved. When ascites is present it implies presence of underlying liver disease. Bleeding can be presented either as upper (haemathemesis and/or melaena) or lower gastrointestinal bleeding (enteral/rectal). Treatment strategies of portal vein thrombosis are still not completely defined, mainly because of the different etiologies, and absence of sufficient prospective studies. When thrombotic disorder is the main risk factor, anticoagulation treatment should be introduced immediately. We may use this treatment even in cirrhotic patients , with no recent evidence of variceal bleeding, in order to resolve the clot and achieve revascularization, which is important for decreasing portal hypertension and avoiding potential bowel ischaemia and infarction. Anticoagulation therapy is not an issue if patient is referring with variceal bleeding and portal vein thrombosis. THE AIM OF THE STUDY which is retrospective is on establishing etiology, diagnosis, complications and treatment of 16 patients admitted to the hospital with portal vein thrombosis, detected by duplex/color Doppler ultrasound. MATERIAL AND METHODS Study includes 16 patients, 9 male and 7 female (age range 41 to 74) referred to the hospital between 2010 to 2012y. Patients were admitted to the hospital with variety of clinical presentations: from abdominal pain followed by nausea, vomiting and fever; through weight loss, malaise and yellowing of the skin; or with different forms of acute gastrointestinal bleeding. On admission all patients underwent routine blood testing, coagulation screen, liver and renal functional biochemistry. Portal vein thrombosis was diagnosed by duplex/color Doppler ultrasound, and was confirmed in three patients by contrast enhanced Computed Tomography, in two patients by Magnetic Resonance Imaging, and in one patient during surgery procedure. There was no need of second imaging procedure in rest of the cases. In determining the etiology of thrombosis, fine needle aspiration biopsy under ultrasound control, as well as endoscopic biopsy were used. Endoscopic procedures were used for detecting and treating complications such as gastric and esophageal varices. RESULTS Duplex and color Doppler ultrasound revealed isolated thrombosis of splenic vein in 2 (12,5%) pts; thrombosis of the main portal trunk without involvement of intrahepatic branches in 6 (37,5%) pts; thrombosis of the whole portal vein (extra and intrahepatic) in 3 (18,7%) pts; thrombosis of the whole portal system (portal, superior mesenteric and splenic vein) in 3 (18,7%) pts and cavernous transformation of the portal vein in 2 (12,5%) pts. Regarding etiology, malignancy was discovered in 4 (25%) cases ( hepatocellular carcinoma in 2 pts, gastric carcinoma in one, and retroperitoneal malignancy in one); 5 (31%) of the cases had proven liver cirrhosis; in 2 (12,5%) cases thrombosis was a sequel of previous abdominal inflammation (acute pancreatitis) and in 1(6,25%) case sequel of previous abdominal surgery; 3 (18,7%) pts had prothrombotic disorder and in one case the cause of thrombosis remained unknown (duodenal malignancy suspected, but without histological evidence). Main complications of portal vein thrombosis, sequel of developed portal hypertension, in a form of esophageal and gastric varices were detected just in 8 (50%) pts. Esophageal varices were detected in 6 (37,5%) pts; gastric (subcardial ) varices in 5 (31%) pts and in 1 (6,25%) pt varices were detected in the antral region of the stomach. Same number of patients 8 (50%) ,were admitted to the hospital with bleeding as a leading symptom, but not all of them had variceal bleeding. One case (6,25%) suffered from intestinal bleeding (difficult general condition did not allowed any further investigations); one patient (6,25%) had bleeding gastric carcinoma; onether one (6,25%) had bleeding duodenal tumor (not confirmed as malignancy); bleeding from gastric ulcer (in presence of gastric varices) was confirmed in one case(6,25%); 3 pts (18,7%) had bleeding from esophageal varices and one patient (6,25%) had gastric-variceal bleeding. Bleeding from esophageal varices was urgently managed with band-ligation in 2 cases, and with endoscopic sclerotherapy in 1 case; patient with ulcer bleeding was treated by adrenalin infiltration; while bleeding from gastric varices was temporarily stopped by applying histoacryl glue, unfortunately emergency surgery was needed due to heavy bleeding reccurence. Patients presented with bleeding due to malignancy of stomach and duodenum, and a patient with intestinal bleeding were medically treated, with PPI , transfusions of fresh frozen plasma and red-blood cells. Patients presented without bleeding : 3 pts with prothrombotic disorder and acute portal thrombosis; 1 pt with thrombosis of whole portal system as a sequel of previous abdominal surgery; 2 pts with cirrhosis, portal thrombosis and non-bleeding varices, and one patient with liver carcinoma on underlying cirrhosis without bleeding but with symptoms of bowel ischaemia, underwent anticoagulation treatment. Anticoagulation treatment was started by i.v. Heparin for 3 days, followed by 7 days s.c. Clexane (2x40mg) and finally maintained on oral anticoagulant therapy (Syntrom). Patients with cirrhosis and chronic portal vein thrombosis, as well as the patients with cavernous transformation of portal vein , without signs of active bleeding, were medically treated with PPI, β-blockers, transfusions of fresh frozen plasma and red-blood cells. DISCUSSION Portal vein thrombosis in clinical practice is usually presented as a sequel of decreased hepatopatal blood flow in cirrhotic patients (10-20%), or as a complication of abdominal malignancy (hepatocellular, pancreatic, gastric carcinoma), although in a few cases prothrombotic tendency and abdominal inflammation (acute pancreatitis, diverticulitis) may be the underlying causes. Recent years, portal vein thrombosis is more frequently detected in clinical practice, due to the routine use of duplex/color Doppler ultrasound, a non-invasive, safe, easily reproducible, and cost-effective method, comparing with other imaging procedures. In case of non-conclusive finding, diagnosis confirmation can be made with contrast-enhanced CT or MRI. Most frequent, and at the same time, life-threatening presentation of portal vein thrombosis is esophageal and/or gastric varices bleeding. This presentation is a medical emergency , and requires immediate haemostatic procedures , usually endoscopic ligation/sclerotherapy, but sometimes there is also need of urgent surgical treatment. The treatment of portal vein thrombosis depends on etiology and whether it is discovered in acute, or in chronic phase. Patients who suffer from thrombosis due to a prothrombotic disorder should be immediately anticoagulated. When thrombosis is discovered in cirrhotic patients with decreased blood flow, anticoagulation treatment may be used in hope of recanalization of portal vein, in order to postpone portal hypertension, only in patients with non-bleeding varices. In case of variceal bleeding, anticoagulant treatment is not advisible. In such cases literature review is recommending clot removal during TIPS or surgical procedure. However, such a risk should be undertaken only after managing the variceal bleeding endoscopically.
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