Ljiljana Bogdanovic

Survivin gene promoter -31 G/C polymorphism is associated with Wilms tumor susceptibility in Serbian children.

Survivin, an apoptotic inhibitor, is overexpressed in various types of cancer. Mechanisms of survivin upregulation are still poorly understood, but single nucleotide polymorphisms in the survivin gene promoter have been shown to modulate survivin expression and consequently the risk for some types of cancer. The aim of the present study was to investigate whether survivin promoter −31 G/C and −241 C/T polymorphisms could represent susceptibility factors for Wilms tumor (WT) development in Serbian population. Genotype and allele frequencies for the 2 polymorphisms in survivin promoter have been analyzed by polymerase chain reaction/restriction fragment length polymorphism in 59 WT patients and 82 controls. The frequencies of alleles and genotypes were significantly different between patients and controls for the −31 G/C polymorphism. Individuals with CC and CG genotypes had significantly decreased risk of WT compared with GG individuals (odds ratio 0.26, 95% confidence interval, 0.07-0.96; odds ratio 0.30, 95% confidence interval, 0.15-0.60). There was also a statistically significant difference in genotype frequencies between intermediate and high-risk prognostic groups (P=0.015). The −241 C/T polymorphism did not show association with WT susceptibility. Our findings suggest that the G allele at −31 survivin gene promoter position is associated with a significantly higher cancer risk in Serbian children, with a gene dosage effect.

Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma

The aim of this study was to evaluate specific glutathione S-transferase (GST) gene variants as determinants of risk in patients with clear cell renal cell carcinoma (cRCC), independently or simultaneously with established RCC risk factors, as well as to discern whether phenotype changes reflect genotype-associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 cRCC patients and 274 matched controls. Benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were determined in DNA samples obtained from cRCC patients by ELISA method. Significant association between GST genotype and risk of cRCC development was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and p<0.001, respectively). Furthermore, 22% of all recruited cRCC patients were carriers of combined GSTM1-null, GSTT1-active, GSTA1-low activity and GSTP1-variant genotype, exhibiting 9.32-fold elevated cRCC risk compared to the reference genotype combination (p = 0.04). Significant association between GST genotype and cRCC risk in smokers was found only for the GSTP1 genotype, while GSTM1-null/GSTP1-variant/GSTA1 low-activity genotype combination was present in 94% of smokers with cRCC, increasing the risk of cRCC up to 7.57 (p = 0.02). Furthermore, cRCC smokers with GSTM1-null genotype had significantly higher concentration of BPDE-DNA adducts in comparison with GSTM1-active cRCC smokers (p = 0.05). GSTM1, GSTT1, GSTA1 and GSTP1 polymorphisms might be associated with the risk of cRCC, with special emphasis on GSTM1-null and GSTP1-variant genotypes. Combined GSTM1-null, GSTT1-active, GSTA1 low activity and GSTP1-variant genotypes might be considered as “risk-carrying genotype combination” in cRCC.

Malignant diseases as suicidal motives

INTRODUCTION Suicide is a conscious and intentional destruction of ones own life, which occurs as a result of mutual influence of a persons disposition and motives (facts inspiring the commitment of suicide). It is well known that various diseases, including malignancies, could be important and in some cases the only motive for committing suicide. OBJECTIVE The purpose of the study was to analyze in detail suicides of persons whose only motive was an established malignant disease. METHOD The analysis was performed using the autopsy material of the Institute of Forensic Medicine, School of Medicine, University of Belgrade, during the period from 1990 to 2004. The reports on performed medico-legal autopsies were used, as well as history data obtained from the family members of suicidal persons, investigation reports and the available medical documents. RESULTS In 1931 cases there was established suicidal nature of a violent death. Neoplasms were the suicidal motive in 37 persons (1.9%). The basic characteristics of the analyzed sample were predominance of males (26:11, ratio 2.4:1), the age of over 70 years and the highest incidence of malignant lung and breast tumours. Almost all cases were the persons who underwent treatment for malignant neoplasms over a longer period of time. During 19 autopsies (51.3% out of 37), a progressive phase of malignancy was established, i.e. metastases. The data on prior oral announcement of suicide intention were obtained for 70.3% (26 cases), and on previous suicidal attempts only for 13.5% (5) cases. In the majority of cases (78.4%) the place of committed suicide was the persons home. In 16 cases (43.2%) the suicide was committed with a firearm. Hanging as a manner of destroying ones own life was chosen by 12 persons (32.4%), while other ways were less frequently used. CONCLUSION Although malignancies were not present with high incidence as a suicidal motive in our analyzed sample, such cases require particular care of health workers in order to enable the application of adequate measures in the prevention of suicides in persons with malignant diseases. The suicide analyses performed so far indicated that a malignant disease was the motive. Doctors have to show maximal interest for the patient. Prevention is crucial, so the patient should be provided with such surroundings in which the person will not feel alone and abandoned.

Knowledge and attitudes on medical waste management among Belgrade medical and dental students

Online first: October 16, 2018 SUMMARY Introduction/Objective Knowledge and practical skills in medical waste (MW) management are of equal importance for medical and dental doctors. The first comparative study on the knowledge and skills in the field of MW management among Belgrade students was conducted with the goal of examining whether students of medicine and dentistry are equally familiar with this extremely important field. Methods A cross-sectional study included 558 students of the sixth year of studies (430 medical and 128 dental students) who completed an anonymous semi-structured questionnaire to determine attitudes and knowledge on MW management. Results The majority of medical and dental students had no training in MW management (79.5% and 74.6%, respectively). Dental students use protective equipment more frequently than medical students (94.5% vs. 42%, p < 0.001). However, full vaccinal protection against hepatitis B is better among medical students compared to dental students (57.7% vs. 39.1%, p < 0.001). Complete knowledge on postexposal prophylaxis is better among medical students compared to dental students (44.5% vs. 13.3%, p < 0.001). However, dental students are more disciplined in reporting injuries (63.1% vs. 52.4%, p = 0.038). The students’ knowledge on primary separation of infectious waste (93% vs. 77.8%, p < 0.001) and used needles (80.3% vs. 70.4%, p = 0.007) is better among dental students compared to medical students’ correct answers. Conclusion Dental students show better knowledge on MW management and are more disciplined in using personal infection protection compared to medical students. The students support continued training on MW management and investigations on this topic.

Acute Renal Failure in Different Malignant Tumors

Acute renal failure (ARF) represents a severe complication of malignancies, that causes significant morbidity and mortality. ARF is a common part of multiple organ dysfunction in critically ill patients with cancer with reported mortality rates from 72% to 85% in patients who need renal replacement therapy. The pathways leading to ARF in cancer patients are common to the development of ARF in other conditions. However, certain factors leading to the development of ARF may be associated to the tumor or to the tumor therapy. The purpose of this review is to give specific aspects of renal disease in critically ill cancer patients (CICPs), to overview the causes of ARF in CICPs and to describe recent progress in the management of these complications, including treatment toxicity and bone marrow transplantation (BMT). The prevention of ARF is obligatory and therefore the possible treatments of ARF in CICPs are also discussed.

Malignant diseases in medicolegal practice

INTRODUCTION In many cases of natural death (so-called obscure natural death), medicolegal assessment and elucidation are required. Although malignant tumors may be the cause of obscure natural death, their forensic significance has not been particularly studied in our population. OBJECTIVE The objective of the study was to provide a general report on medicolegal importance of malignant diseases. METHOD Autopsy material of the Institute of Forensic Medicine, Belgrade, from 1990 to 2000, was analyzed. The data were obtained from autopsy records, investigation reports, family members of the deceased and available medical documentation. RESULTS The malignant tumor was the cause of death in 81 cases (0.69% out of a total of 11771 autopsies), in 52 males and 29 females, respectively. The incidence of malignant diseases increased with age. The most frequent cause of death was the lung cancer--diagnosed in 33 cases (40.7% out of 81), with somewhat higher percentage in females (41.4%) than in males (40.4%), but this difference was not statistically significant (chi2 = 0.13; p > 0.05). Other locations of malignancies were less frequently found: brain (7 cases), colon (6), stomach (5) and pancreas (4). In 67 cases, widespread tumor with metastases was identified as an immediate cause of death, in 8 cases there was a hemorrhage from eroded blood vessels, and in 6 cases peritonitis due to gastric or intestinal leakage into the abdominal cavity at the site of wall perforation. In 61.7% cases, fatal tumor was not diagnosed during the life, and was recorded more frequently in female group (75.9%) than in males (53.8%), but this difference was not statistically significant (chi2 = 2.71; p > 0.05). In most cases of lung cancer (22 or 66.7% out of 33), which was predominant type in the analyzed sample, malignancy remained unrecognized during the life. CONCLUSION The most important medicolegal problems regarding fatal malignant diseases are associated with exclusion of violent death in cases that are characterized as obscure (suspicious) natural death, as well as assessment of possible legal responsibility of medical staff in cases in which malignant tumor has not been diagnosed during the life.