Zemun hospital, the present-day Clinical Hospital Zemun-Belgrade, was founded in 1784, is the oldest hospital in the Serbia. For over two centuries, it blazed the trial and still pioneers in the application of numerous advanced medical achievements and knowledge in this region.

The aim of this case report was to review the therapeutic effect of therapeutic plasma exchange in the treatment of retrobulbar neuritis in relation to its side effects, in the absence of the desired therapeutic response to previously applied immunomodulatory therapy, as a justification of therapeutic plasma exchange in the treatment of patients suffering from central nervous system demyelinating diseases. Optic neuritis is an inflammatory optic nerve lesion that may lead to partial or complete loss of vision. Therapeutic plasma exchange was performed on the SPECTRA OPTIA apheresis apparatus, according to a predefined disease diagnosis (RN), which according to the 2016 AFSA criteria belongs to the III category of disease in which apheresis is accepted as the second line of treatment. Three procedures were analyzed and an average of 5050ml of blood was processed. In conclusion, this therapeutic method is absolutely justified, with the appropriate prior preparation of the patient.

Adult intussusception caused by inverted Meckel diverticulum is infrequent but important clinical entity, presenting with nonspecific symptoms. It may be observed in any age. We report a 26-year-old male patient with intussusception, who was examined several times for abdominal pain accompanied with nausea and vomiting. Basic diagnostics were inconclusive, so the patient was discharged each time with conservative therapy. After the last episode, CT scan showed suspicious intussusception, so the patient was admitted to general surgery ward. The next day there was a complete regression of all difficulties, and he was free of them in the month ahead. Finally, NMR enterography verified the presence of intussusception, and the operative procedure was performed. At laparotomy, ileo-ileal double intussusception was observed and the affected segment was resected with T-T anastomosis. Histopathological examination demonstrated an inverted Meckel diverticulum, measuring 8cm, with ectopic gastric antral type mucosa and ectopic pancreatic tissue. Postoperatively, the patient made an uneventful recovery.

The effect of hyperbaric oxygenation on the treatment of ischemic ulcers on patients with diabetic angiopathy is known, but the effect of HBO t (hyperbaric oxygen therapy) on diabetic claudicates is less known, i.e. to those that havethe second stage of peripheral vascular disease (without ulceration). In this study, we tried to point out the impact of hyperbaric oxygen (HBO) on the development of collateral arteries, i.e. the process of arteriogenesis, and consequently the symptom of claudication. 30 subjects in total were included in the case-control study. Inclusion criteria were: diagnosis of diabetes mellitus for at least five years, as well as Doppler-verified distal angiopathy. The respondents were randomly divided into two groups. The control group (n = 15) was treated by standard methods only.The respondents in the experimental group received 20 HBOTs each in a single-chamber hyperbaric chamber for 70 minutes at a pressure of 2.0 ATA. In this regard the assumptions of the arteriogenic effect of hyperbaric oxygenation, the eventual development of new arterial collaterals it was monitored by Doppler. after 20 HBO treatments and at the follow-up, 3 months after HBO therapy. It was observed that there was a statistically highly significant difference before treatment, in the number of registered functional small blood vessels of the lower leg and three months later, and after 20 HBO sessions, both on the left and the right leg, within the experimental group. There was observed also a highly statistically significant difference in the number of newly formed blood vessels on experimental patients in comparison with the patients from the control group. Our study shows that HBO therapy has a positive effect on the development of collateral blood vessels of the legs and that it may find application in the treatment of patients with diabetes mellitus with angiopathy and claudication disorders. Our study shows that HBO therapy has a positive effect on the development of collateral blood vessels of the legs and that it may find application in the treatment of patients with diabetes mellitus with angiopathy and claudication disorders.

The liver is an organ with many indispensable functions in the body. Liver diseases can be caused by numerous ethiological factors, and are divided into two basic groups, according to an anatomical substrate which is primarily affected – on hepatocellular (parenchymal) and billiard diseases. Approximately 10% of patients with liver disease require a surgical procedure (not including a liver transplant) in the last 2 years of life. Because of its reserves and regenerative abilities, the liver can suffer a great deal of damage before the clinical manifestations of its own dysfunction, which is a challenge for the pre-operative assessment of its condition. The goal of preoperative screening is to determine the presence of preexisting liver disease without the need for extensive or invasive testing. Routine testing of liver function has a low prediction value. The post-operative outcome depends on the nature and severity of the existing liver disease, as well as the type of the operation. It is often necessary to treat complications of severe liver damage, such as coagulopathy, thrombocytopenia, ascites, kidney failure, encephalopathy and malnutrition. Predisposition for infections of patients with cirrhosis requires prophilactic use of antibiotics. Induction of anesthesia, bleeding during surgery, hypoxia, hypotension, the use of vasoactive drugs, and even positioning of patients and surgical techniques can reduce intraoperative and perioperative delivery of oxygen in liver and increase the risk of hepatic dysfunction. Pharmacokinetic parameters of anesthetic agents, muscle relaxants, painkillers and sedatives may be altered in connection with plasma proteins, detoxification in liver etc.. The postoperative liver dysfunction depends on surgical trauma, ischemia during surgery or loss of hepatocite mass, and it can be divided into three groups – hepatocelulcular, cholesterol and mixed liver dysfunction. Posthepatectomy liver failure is one of the most serious complications after the liver resection and is a post-operative deterioration of liver capability to maintain its main functions. In recent years, liver function support systems have been developed. Molecular recirculation system with absorption (MARS), modified fractional plasma separations and adsorption (Prometheus) and bioartifical liver and extracorporal device for assistence of liver activity. Extensive clinical studies are needed to prove the effectiveness of these artefical systems for temporary replacement of the edible functions to its recovery or to transplantation.

Colorectal cancer, as one of the leading oncological causes of disease worldwide, is a major challenge in terms of treatment and patient access. Technological advances have made it possible to apply a minimally invasive laparoscopic surgical technique that has proven superior to open surgery. In order to optimize treatment, reduce mortality and morbidity, a perioperative strategy has been developed summarized in the principles of ERAS protocol (Enhanced Recovery After Surgery). The basic postulates of the ERAS protocol include prehabilitation, comorbidity control, prevention of postoperative nausea and vomiting, minimally invasive surgical method, multimodal analgesia, achieving euvolemia, prevention of hypothermia and early mobilization of the patient. The principles of the ERAS protocol are based on evidence to support safety, applicability and effectiveness, however, there are not yet enough studies to examine the long-term benefits of their implementation. The implementation of the ERAS protocol at KBC “Dr Dragisa Misovic -Dedinje” is not complete, but there is significant compliance with the guidelines of the 2018 ERAS Association, which has reduced inpatient stays and the number of postoperative complications. Although there is ample evidence to support the safety and effectiveness of this treatment approach, a multimodal strategy poses a major challenge to traditional surgical doctrine, making its implementation slow and incomplete in practice.

Aim: The aim of the study is to investigate the effect of prenatal treatment of metronidazole on the process of cerebellar foliation in the guinea pig. Introduction: The use of metronidazole in pregnancy still occupies very different attitudes among doctors who prescribe them. Neurotoxicity is a common side effect in the use of metronidazole, but there is still no clear animal study. Materials and Method: We studied 42 guinea pig fetuses obtain from 12 pregnant guinea pig dams.  Dams were separated in experimental (6) and control6) group(K). Experimental group(E) received from 42-49 day of gestation at every PLENARY ORAL PRESENTATION 22 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. 12 hour (at 8 a.m. and 8 p.m.) subcutaneous injection od saline solution of metronidazole in concentration of 28 mg/kg.  Control group received using same time protocol just saline solution. At 50th day of gestation all dams were sacrified and fetuses were used for further analysis. In each  fetuses (22 in E, and 20 K group). Firstly we make gross picture of the brain and secondary we separated vermis region for further histological and immunohistochemical analysis. Results: An analysis of macroscopic images of the dorsal side of the cerebellum in the experimental group of individuals revealed malformations in 15 out of 22 fetuses (68.2%). The most affected folia was VII and characterized with aberrant diagonal positioning along the entire dorsal side of the vermis. Other folia were partial presence, with micro, and agyria changes. Conclusion: Prenatal use of metronidazole in guinea pigs during the 42-49th day of gestation cause disturbance in cerebellar foliation.

Aim: To determine the degree of correlation between TTF-1 (+) expression and EGFR mutation status in lung adenocarcinoma. Introduction: Adenocarcinoma of the lung is mainly diagnosed based on standard morphological criteria. The thyroid gland transcription factor (TTF-1) is currently the most commonly used immunohistochemical marker in the differentiation of invasive adenocarcinoma of the lung from another primary and metastatic carcinoma, has a prognostic significance and is a predictor of the EGFR mutation status. Material and Methods: This retrospective study enrolled 60 patients with histologically confirmed primary lung adenocarcinoma who underwent lung cancer surgery at Institute for lung disease Vojvodina between 2010 and 2015. Tumor specimens of these patients were investigated for TTF-1 expression and mutations in EGFR using immunohistochemistry and PCR analysis. Statistical analysis is in statistic software Statistica 12. Results: The study included 35 men and 25 women, with an average age of 61.8 ą 8.08 years. Of the 60 cases, TTF-1 ( ) expression was recorded in 52 (87%) (p <0.001), the statistical difference is not significant when comparing smoking habitsby gender, and tumor size among them. EGFR ( ) mutation status was found in 3/60 (5%) cases [egzon 21 (2) and exon 20 (1)], of which TTF-1 (+) expression was in two cases. Conclusion: There is a statistically significant difference between the TTF-1 (-) and TTF-1 (+) adenocarcinoma and a high degree of correlation between EGFR mutation status and TTF-1 (+) expression.

Aim: Reporting of autopsy case of fatal accidental poisoning by colchicine from meadow saffron. Introduction: Meadow saffron (Colchicum autumnale) is a perennial herbaceous plant similar to the edible wild garlic (Allium ursinum). Toxic substance in meadow saffron is alcaloid colchicine. Colchicine poisoning is a very dangerous condition, which can lead to fatal outcome. Case report: A 50-years-old male was admitted to the hospital complaining of weakness, abdominal pain, nausea, vomiting and diarrhea without blood. Day before he ate two plants thinking they’re wild garlic and seven hours after ingestion he felt first symptoms. During the course of the hospital stay, he had gastroenterocolitis, acute renal failure, hepatic lesion and cardiorespiratory insufficiency with fatal outcome. Post-mortem examination reveled:brain oedema, lung oedema and congestion, heart weighing 700 grams, ventricular hypertrophy, myocardial fibrosis, liver congestion and steatosis, spleen congestion, pancreatic fibrosis. Organs sections were taken for pathohistological analysis. Body fluids and parts of organs were toxicologically analyzed. Pathohistological findings:brain oedema, diffuse perivascular and interstitial myocardial fibrosis, myocardial haemorrhage, lungs congestion and edema, micro- and macrovesicular liver steatosis, centrilobular liver necrosis, lymphocytic inflammatory infiltrate in liver portions, spleen’s red pulp congestion, kidney congestion and interstitial bleeding, coagulation necrosis of the proximal tubules of the kidney. Toxicological analysis showed colchicine in blood-0.011 mg/L, urine-0.051 mg/L, liver with gallbladder-0.007 mg/ kg, kidney-0.008 mg/kg. Conclusion: Ingestion of the meadow saffron can lead to poisoning with fatal outcome due to colchicine. Colchicine intoxication should be suspected in patients with gastrointestinal symptoms after consuming wild plants.

Sarcomatoid differentiation in renal cell carcinoma (sarcomatoid renal cell carcinoma – sRCC) represents a dedifferentiated high grade neoplasm of the kidney that contains carcinomatous and sarcomatous component. sRCC is an uncommon tumor, with the incidence of 5-8% of renal carcinoma. Sarcomatoid differentiation is a result of divergent differentiation of malignant epithelial cells. During this process tumor cells lose their epithelial features, and acquire mesenchymal characteristics, which provides them higher APSTRAKTI 79 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. capacity for migration and metastasis.This phenotype can be encountered in all RCC subtypes, including clear cell, papillary, chromophobe RCC, and carcinomaof collecting duct. Sarcomatoid component may resemble fibrosarcoma or undifferentiated pleomorphic sarcoma. Less often heterologous differentiation can be found, with histologic patterns resembling rhabdomyosarcoma, chondrosarcoma, or osteosarcoma. Rhabdoid phenotype is an aggressive form of divergent differentiation which has been described in clear cell RCC, papillary RCC, as well as in chromophobe RCC (CRRCC). CRRCC comprise about 6% of RCC, and has better prognosis compared to other RCC subtypes. Sarcomatoid differentiation is found in 8% of these tumors, and is an indicator of poor prognosis, as it is in other RCC types. Sarcomatoid component may represent terminally dedifferentiated clone which can arise from any RCC subtype, or can develop from a special clone. Although sRCC is most frequently found in high grade tumors, the occurrence of sarcomatoid differentiation in RCC, Fuhrman 1/2, detected in 30% of the cases, denies the claim that sarcomatoid differentiation is a continual process of classic RCC dedifferentiation, but a consequence of sarcomatoid stem cell activation within the tumor. In a case of sarcomatoid differentiation in renal carcinoma it is necessary to detect focuses of any morphological type of renal cell carcinoma, and to verify the immunohistochemical positivity of sarcomatoid component to epithelial and mesenchymal markers. Their epithelial origin is confirmed by the expression of cytokeratins, and EMA. PAX8, CAIX, and CD10 can be used to confirm the renal origin, which is of particular importance in finding of sarcomatoid cells in needle biopsy, as well as in metastatic RCC. CAIX, p53, and Bcl-2 can play a major role in transformation of RCC to highly malignant neoplasm with sarcomatoid differentiation. The expression of CAIX, p53, and Bcl-2 is indicator of poor prognosis and worse survival of the patients with sRCC. Significant micromorphological parameters that may influence the clinical course of the disease comprise percentage of sarcomatoid differentiation (>50%), presence of vascular invasion, extent of necrosis, and advanced TNM stage. Type and grade of sarcomatoid component, as well as RCC subtype do not influence the clinical outcome. The prognosis of patients with sRCC is worse compared to prognosis of other histologic forms of RCC. Sarcomatoid differentiation in RCC is a significant cause of mortality, with average survival of 4-9 months after diagnosis. The majority of unclassified RCCs contains variable percent of tumor cells with sarcomatoid morphology, without recognizable epithelial component. About 3% of RCC are exclusively sarcomatoid. These tumors are larger, more often invade adrenal glands and other adjacent organs, metastasize more frequently into regional lymph nodes and bones, and have significantly shorter survival (average is 4.3 months). Differential diagnosis of sRCC should exclude primary renal sarcoma, sarcomatoid urothelial carcinoma, and angiomyolipoma. Micromorphologically sRCC may resemble classic sarcoma, however it should be taken into account that primary renal sarcomas are extremely rare in adults, and comprise less than 1% of renal malignancies. The half of primary renal sarcomas are leiomyosarcomas, consisting of smooth muscle component, which is extremely rare in sRCC. In sarcomatoid urothelial carcinoma, the location of tumor is of significance, also the presence of carcinoma in situ, recurrence of urothelial carcinoma, and immunohistochemical positivity to CKhmw and p63. In angiomyolipoma, immunoreactivity to HMB45, as well as the presence of focuses with classic morphology, excludes sarcomatoid RCC. Conclusion: Sarcomatoid differentiation in renal cell carcinoma is a result of divergent differentiation of malignant epithelial cell, and can be found in all renal cell carcinoma subtypes. During this process tumor cells lose their epithelial features, and acquire mesenchymal characteristics, which provides them higher capacity for migration and metastasis. It is very important to recognize the presence of sarcomatoid differentiation in renal cell carcinoma, since it is an indicator of poor prognosis irrespective of RCC subtype.