Kalina Gjorgjievska, Maja Slaninka-Miceska and Gordana Petrusevska
Protective Effects of Aliskiren, Enalapril and Valsartan on Hypertension Target Organs in Spontaneously Hypertensive Rats
Aim: Aliskiren is the first orally active renin inhibitor approved for treatment of essential hypertension. There are as yet no clinical data regarding the ability of aliskiren to prevent clinical end-points or reduce end-organ damage over and above the presumed effects of blood pressure reduction. The aim of this study was to find out if aliskiren has a potential to improve renal function and if it has a protective effect on hypertension target organs (kidney, heart and aorta).
Materials and Methods: The study was conducted on 64 SHR rats (male and female), 20 weeks old, weighing from 250-300 g. Animals were divided into 4 groups and treated with aliskiren (100 mg/kg bw/24 h), enalapril (10 mg/kg bw/24 h) and valsartan (10 mg/kg bw/24 h). Effects of investigated drugs were evaluated by urinalysis and histopathological analysis.
Results: Diuresis was significantly increased in the group of animals treated with enalapril and valsartan. Effect on diuresis with aliskiren was mild and statistically insignificant. No significant difference in urine pH between treated and control group of SHR rats was noted. Albuminuria was decreased in animals treated with enalapril and valsartan. Aliskiren after 28 days of treatment had a statistically insignificant effect on albuminuria in SHR rats. Only certain changes of wall thickness of arteries and arterioles were noted that led to improved perfusion and function of the kidneys more pronounced in rats treated with valsartan and enalapril. Effects of aliskiren on target organs were inferior compared to valsartan and enalapril.
Conclusion: In SHR experimental model aliskiren has minor effects on hypertension target organs when compared to enalapril and valsaratan.
Igor Aluloski, Mile Tanturovski, Gordana Petrusevska, Rubens Jovanovic and Slavica Kostadinova-Kunovska
Aim: To evaluate the factors that influence the surgical margin state in patients undergoing cold knife conization at the University Clinic of Gynecology and Obstetrics in Skopje, Republic of Macedonia
Materials and methods: We have retrospectively analyzed the medical records of all patients that underwent a cold knife conization at our Clinic in 2015. We cross-referenced the surgical margin state with the histopathological diagnosis (LSIL, HSIL or micro-invasive/invasive cancer), menopausal status of the patients, number of pregnancies, surgeon experience, operating time and cone depth. The data was analyzed with the Chi square test, Fisher’s exact test for categorical data and Student’s T test for continuous data and univariate and multivariate logistical regressions were performed.
Results: A total of 246 medical records have neen analyzed, out of which 29 (11.79%) patients had LSIL, 194 (78.86%) had HSIL and 23 (9.34%) patients suffered micro-invasive/invasive cervical cancer. The surgical margins were positive in 78 (31.7%) of the patients. The average age of the patients was 41.13 and 35 (14.23%) of the patients were menopausal. The multivariate logistic regression identified preoperative forceps biopsy of micro-invasive SCC, HSIL or higher cone specimen histology and shorter cone depth as independent predictors of surgical margin involvement in patients undergoing cold knife conization.
Conclusion: In the current study, we have found no association between the inherent characteristics of the patient and the surgeon and the surgical margin state after a CKC. The most important predictors for positive margins were the severity of the lesion and the cone depth.
Sinisa Stojanoski, Nevena Ristevska, Daniela Pop Gjorceva, Borce Antevski and Gordana Petrusevska
Introduction: Breast cancer accouns for 22.9% of all cancers in women and 13.7% of cancer deaths. Positive axillary lymphnodes (ALN) predict the development of distant metastases. The status of the sentinel lymphnode (SLN) is crutial for the treatment selection.
Aim: To determine the benefits of SLN detection in patients with breast cancer. Material and methodology: 38 female patients (pts), age 44 ± 12 years, with T1-2 N0 M0 breast cancer, without enlarged ALN on ultrasound (US), were included. SLN detection was performed using gamma camera and gamma detection probe after periareolar subcutaneous and/or peritumoral injection of (99m-Technetium-SENTISCINT). Blue dye was administered 20 min before the operation. SLN was extirpated and ex tempore histopathology was performed.
Results: Ex tempore SLN evaluation was negative and the lymphatic pathways preserved in 28/38 (74%) pts. In 10/38 (26%) pts SLN was positive, followed by radical surgery. In 3/28 ex tempore negative patients, histopathological analysis showed metastatic involvement (false negative). In 3/10 ex tempore positive patients micro metastases 0,2-2 mm were detected. 12 pts had 2 SLN, 8/12 (66%) had negative and 4/12 (34%) had positive SLN. 3 pts had a rare double drainage to axilla and a. mammaria int.
Conclusion: Our results confirm that SLN detection technique is non-invasive, safe and reliable and should be incorporated into the guidelines for breast cancer pts (T1-2 N0 M0). The most reliable option for colloid application is the combined technique of periareolar and peritumoral injection. Patients with drainage to a. mammaria interna should be selected for adjuvant protocols.
Biljana Poposka, Snezana Smickova, Simonida Crvenkovska, Beti Ivanovska, Tome Stefanovski and Gordana Petrusevska
Prognostic value of immunohistochemical expression of HER-2/neu in patients with lung carcinoma
Background. The amplification and the overexpression of the Her-2/neu gene have been shown in certain human tumours and are postulated to be important in human carcinogenesis. In this study we evaluated the expression of HER-2/neu gene in patients with lung carcinoma (LC) and assessed its prognostic significance.
Patients and methods. HER-2/neu expression was determined in 127 LC patients using immunohistochemistry (IHC) performed on paraffin-embedded section - Hercep Test™ (DAKO).
Results. The overall HER-2/neu expression was seen in 36 (28.35%) of 127 LC patients. According to the histological type, HER-2/neu overexpression was detected in 12 patients with adenocarcinomas (60%), in 19 patients with squamous cell carcinomas (31.14%), in 4 patients with small cell-lung carcinomas (10%) and in 1 patient with other carcinomas (16.66%). Only in patients with small cell-lung carcinomas HER-2/neu overexpression was in correlation with the stage of the disease (p<0.001). The patients with HER-2/neu positive expression were associated with a significantly shorter survival compared with those who were HER-2/neu negative (log rank, p<0.002).
Conclusions. These observations suggest that HER-2/neu positivity may serve as a prognostic indicator in patients with LC. HER-2/neu plays a role in identifying patients at risk for the shortened survival, who may benefit from a more aggressive therapy.
Biljana Poposka, Snezhana Smickova, Simonida Crvenkovska, Beti Ivanovska, Tome Stefanovski, Marija Metodieva and Gordana Petrusevska
Prognostic Value of the Expression of p53 in Patients with Non-small Cell Lung Cancer
Background. The p53 gene is frequently mutated in non-small-cell lung cancer (NSCLC). However, the effect of p53 gene mutations on patient prognosis remains unclear.
Aim. The aim of this study is to determine the association of p53 abnormalities with clinical data and prognosis in patients with NSCLC.
Material and Methods. Tumor tissues from 80 patients with NSCLC were assessed by immunohistochemistry for expression of p53. The immunohistochemical study was performed on formalin-fixed, paraffin-embedded sections using LCAB immunoperoxidase method with mouse anti-p53 monoclonal antibody (clone DO-7; DAKO).
Results. Forty-three (53,75%) of 80 patients revealed aberrant immunostaining for p53. Except to the histological type of tumors, there was no correlation of p53 expression with the clinicopathologic features. The Kaplan-Meier survival analysis demonstrated that patients with p53 positive status had poor survival rate (p=0,005 by the Log Rank test= 7,914). In Cox, regression analysis p53 and performance status emerged as independent prognostic factors (p<0,009 and p<0,000 respectively).
Conclusion. The results from this study indicated that the aberrant expression of p53 is significant and independent predictable prognostic factor for patients with NSCLC.
Marija Petrusevska, Irina Panovska Stavridis, Kristina Mladenovska and Gordana Petrushevska
Herein synchronous occurrence of Hodgkin lymphoma and secondary myelodysplastic syndrome in a 60 year old male patient with small cell lung cancer treated with combined chemotherapy (carboplatin and paclitaxel) and radiotherapy is presented. The objective of this report is to stress the importance of documenting and monitoring adverse drug reactions that arise from chemotherapy.
After four years of treatment with the combined chemotherapy, the patient presented inguinal lymphadenopathy and enlarged lymph nodes and histopathology rapport was suggestive for plasmacytoid variant of Castleman disease. Three years later, biopsy of lymph node was performed and diagnosis of Hodgkin lymphoma – mixed cellularity has been established. Molecular analyses revealed presence of dominant monoclonal population of the immunoglobulin genes in the oligo/monoclonal background. Bone marrow biopsy findings suggested secondary myelodysplasia and revealed signs of hematopoietic cells dismaturation with signs of megaloblastic maturation of the erytropoetic lineage, appearance of ALIP (abnormal localization of immature precursors) in the myeloid lineage and dysplastic megakaryocytes. In addition, an increased level of polyclonal plasmacytes (lambda vs kappa was 60%:40%) was found.
Hodgkin lymphoma and MDS occurring after 4 years of carboplatin/paclitaxel therapy might be contributed to the accumulation of alkylator-related DNA damage. This emphasize the need of outlining a monitoring plan regarding development of secondary leukemia and other malignant hematological proliferations should be outlined in the protocols.
Borislav Kondov, Goran Kondov, Zoran Spirovski, Zvonko Milenkovikj, Risto Colanceski, Gordana Petrusevska and Meri Pesevska
Aim: The aim of the study was to identify the impact of T stage, the presence of estrogen, progesterone, HER2neu receptors and the values of the Ki67 on the positivity for metastases of the axillary lymph nodes, from primary breast cancer.
Material and methods: 290 surgically treated patients for breast cancer were included in the study. All cases have been analyzed by standard histological analysis including microscopic analysis on standard H&E staining. For determining the molecular receptors - HER2neu, ER, PR, p53 and Ki67, immunostaining by PT LINK immunoperoxidase has been done.
Results: Patients age was ranged between 18-90 years, average of 57.6+11.9. The mean size of the primary tumor in the surgically treated patient was 30.27 + 18.3 mm. On dissection from the axillary pits 8 to 39 lymph nodes were taken out, an average of 13.81+5.56. Metastases have been found in 1 to 23 lymph nodes, an average 3.14+4.71. In 59% of the patients there have been found metastases in the axillary lymph nodes. The univariate regression analysis showed that the location, size of tumor, differentiation of the tumor, stage, the value of the Ki67 and presence of lymphovascular invasion influence on the positivity of the axillary lymph nodes. The presence of the estrogen receptors, progesterone receptors and HER2neu receptors showed that they do not have influence on the positivity for metastatic deposits in axillary lymph nodes. The multivariate model and the logistic regression analysis as independent significant factors or predictors of positivity of the axillary lymph nodes are influenced by the tumor size and the positive lymphovascular invasion.
Conclusion: Our study showed that the involving of the axillary lymph nodes is mainly influenced by the size of the tumor and the presence of lymphovascular invasion in the tumor. Ki67 determined proliferative index in the univariate analysis points the important influence of positivity in the axillary lymph nodes, but not in the multivariate regressive analysis.
Medullary thyroid carcinomas (MTCs) are rare neoplasms comprising 2-10% of all thyroid malignnancies. More than 75% are sporadic tumors and the remainder is familial and MEN2 related. Both sporadic and syndromic MTCs frequently show mutations in the RET proto-oncogene. It has been noted that some MTC cases present an indolent, and some an aggressive clinical course. Ki-67 expression is generally low, with documented exceptions, whereas high expression of Bcl-2 has been reported in majority of the cases. Some studies have shown that Ki-67 and Bcl-2 expressions have prognostic value, as well as RET mutational status. We analyzed 20 unrelated MTC cases for Ki-67, Bcl-2 expression and RET mutations and tested their intercorrelations, correlations to the morphologic features and stage of the tumors, as well as their influence on survival. In 13 of the 20 analyzed cases we found 23 sequence changes distributed in exons 8, 10-13 and 16. There were 11 different missense mutations, single nucleotide deletion with frameshift, and 8 different synonymous mutations. Only 4 of the sequence changes have been previously published. Twelve patients (60%) had tumors expressing one or more missense mutations or single nucleotide deletion and 7 of them (35%) had at least one damaging or possibly damaging RET mutation. Most of the tumors had low Ki-67 expression (mean 6.48% of cells) and high Bcl-2 expression (mean 68.3%). Significantly better survival was observed in cases with low Ki-67 (< 6.5%; p < 0.05), high Bcl-2 expression (> 68.3%; p < 0.01) and younger age at diagnosis (< 51 years; p < 0.05).