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Background/Aim. Immune checkpoint therapy is a well-established therapeutic approach in the treatment of malignant diseases and is thought to be mostly based on facilitating the adaptive immune response. However, the cells of the innate immune response, such as natural killer T (NKT) cells, might also be important for a successful anti-programmed cell death protein-1 (anti-PD-1) therapy, as they initiate the antitumor immune response. The aim of this study was to investigate the influence of anti-PD-1 therapy on the immune response against tumors. Methods. For tumor induction, 4T1 cells synergic to BALB/c back-ground were used, after which mice underwent anti-PD-1 treatment. After the mice were sacrificed, NKT cells, dendritic cells (DCs), and macrophages derived from spleen and primary tumor tissue were analyzed using flow cytometry. Results. Anti-PD-1 therapy enhanced the expression of activating molecules CD69, NKp46, and NKG2D in NKT cells of the tumor and spleen. This therapy activated NKT cells directly and indirectly via DCs. Activated NKT cells acquired tumoricidic properties directly, by secreting perforin, and indirectly by stimulating M1 macrophages polarization. Conclusion. Anti-PD-1 therapy activates changes in DCs and macrophages of primary tumor tissue towards protumoricidic activity. Since anti-PD-1 therapy induces significant changes in NKT cells, DCs, and macrophages, the efficacy of the overall antitumor response is increased and has significantly decelerated tumor growth.

Background/Aim. Myocardial bridges (MB) are narrower or wider fascicles of the atrial or ventricular muscle fibres which form a “bridge” either across the main trunks of coronary arteries or their major subepicardial branches. The aim of this research was to determine and present the exact frequency, morphological, morphometric and histological characteristics of the MB in the level of anterior interventricular branch (AIB) in human fetal hearts. Methods. The study was performed on 63 human fetal hearts. Images of the analyzed hearts were captured with a digital camera and afterwards morphometrically evaluated with ImageJ. Characteristic cases of the MB were dissected, sampled and further routinely processed for the subsequent histological analysis. Finally, the obtained morphometric data were statistically analyzed. Results. The presence of the MB on the AIB was proven histologically and under the magnifying glass. Myocardial bridges were found in 53.97% of the hearts. The percentage of the hearts with only one MB detected on AIB 88.24% was significantly higher than the percentage of the hearts with two MBs on the AIB (11.76%) (p < 0.001). Conclusion. We suggest that the MBs are just one anatomical variation of the fetal period as well as of adulthood. [Projects of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175092 and Grnat no. III 41017]

Bacground/Aim. Upper urinary tract urothelial carcinoma (UUT-UC) constitutes 5% of malignant neoplasms arising from transitional epithelium, but is more invasive than bladder cancer. Lzmphovascular invasion (LVI) is associated with biologically aggressive carcinoma and with occult metastases. The aim of this study was to investigate the correlation between LVI and immunohistochemical expression of two frequently routinely applied immunohistochemical biomarkers, Ki-67 and E-cadherin, in UUT-UC. Methods. The specimens from 106 patients with UUT-UC who had undergone nephroureterectomy were analyzed for pathologic parameters and LVI, while Ki-67 and E-cadherin expression were assessed by immunohistochemistry. Results. Ki-67 was overexpressed in 38% of the cases, while 45% of tumors demonstrated aberrant E-cadherin staining. The presence of LVI was significantly associated with tumor stage, grade, non-papillary growth, nodular invasion pattern, high Ki-67 labeling index and altered E-cadherin expression. Analyzing logistic regression models, we have shown that tumor properties such as stage, grade, growth and invasion pattern (p < 0.001), as well as the expression of Ki-67 and E-cadherin (p < 0.001) significantly predicted the presence of LVI. In the first model, only solid tumor architecture (p < 0.05) and nodular invasion pattern (p < 0.05) were significant predictors of LVI. In the second model, Ki-67 expression was found to improve the prediction of LVI (p < 0.05). Conslusion. Our results suggest that Ki-67 overexpression is an independent predictor of LVI in UUTUC, indicating the progression of the disease. E-cadherin staining adds no valuable information to LVI probability assessment. This emphasizes the importance of Ki-67 staining of UUT-UC sections in routine pathological practice. Patients with Ki-67 overexpression, especially in solid tumors with nodular invasion, should be monitored more closely after surgery. [Projekat Ministarstva nauke Republike Srbije, br. 175092: Etiology, diagnosis, prevention and therapy of endemic nephropathy and associated tumors of the urothelium - the significance of genome and proteome study]

Introduction. Watermelon stomach (WS) or gastric antral vascular ectasia (GAVE) is a rare cause of upper gastrointestinal bleeding described in a variety of autoimmune disorders. Association of watermelon stomach with Sj?gren's syndrome is extremely rare. Case report. We presented a 67-year old female with primary Sj?gren's syndrome (SS) who had developed a persistent severe iron-deficiency anemia. An upper gastric endoscopy revealed the presence of gastric antral vascular ectasia (GAVE) as a cause of occult gastrointestinal bleeding. The treatment with argon-plasma coagulation was postponed as the conservative therapy with iron substitution and proton pump inhibitor led to improvement of anemia and hemoglobin levels normalization. Conclusion. This is the first report of WS in a patient with primary SS without the presence of coexisting autoimmune disorder. Recognition of this rare, but clinically important, cause of gastrointestinal bleeding may decrease comorbidity in patients with autoimmune disorders including primary Sj?gren's syndrome.

Introduction. Whipple's disease is a chronic, multisystem, infectious disease caused by Tropheryma whipplei. It most commonly affects Caucasian males, middle-aged. Morbus Whipple is primarily gastrointestinal disease, manifested as malabsorption syndrome, and diagnosed by endoscopy and intestinal biopsy. Extraintestinal manifestations are not rare. Case report. A 48-year-old male was admitted due to diarrhea, weight loss and weakness in the extremities. Physical examination findings pointed out diffuse hyperpigmentation, pleural effusion and leg edema. Anemia, inflammatory syndrome and malabsorption signs were discovered through laboratory tests. The diagnosis was confirmed by intestinal biopsy. The patient was treated with antibiotic and symptomatic therapy. After 9 months, the patient had no symptoms, and clinical and laboratory findings were regular. Conclusion. Whipple's disease is a rare disease. A high degree of clinical suspicion for the disease (malabsorption, arthritis, fever, neurological symptoms) is the most important for diagnosis. Timely diagnosis and appropriate therapy prevent the disease progression and fatal outcome.

Background/Aim. Most studies of esophageal and gastric adenocarcinomas have shown a very high rate of p53 gene mutation and/or protein overexpression, but the influence of the tumour site upon the frequency of p53 protein expression has not been evaluated (gastroesophageal junction, Barret's esophagus, and antrum). The aim of our study was to analyze the correlation between the selected clinico-pthological parameters, and p53 protein overexpression in regards to the particular tumour location. Methods. The material comprised 66 sugical specimens; 10 were Barrett’s carcinomas, 25 adenocarcinomas of the gastric cardia (type II adenocarcinoma of the esophagogastric junction – EGJ), and 31 adenocarcinomas of the antrum. Immunostaining for p53 protein was performed on formalin-fixed, paraffin-embedded tissue sections, using the alkaline phosphatase – antialkaline phosphatase (APAAP) method. The cases were considered positive for p53 if at least 5% of the tumour cells expressed this protein by immunostaining. Results. There was no significant difference observed between the studied groups in regards to age, sex, Lauren’s classification and tumour differentiation. There was, however, a significant difference observed in the depth of tumour invasion between Barrrett’s adenocarcinoma and adenocarcinoma of the cardia compared with the adenocarcinoma of the antrum. Namely, at the time of surgery, both Barrett’s adenocarcinomas and adenocarcinomas of the cardia, were significantly more advanced comparing with the adenocarcinomas of the antrum. Overexpression of p53 was found in 40% (4/10) of Barrett’s adenocarcinomas, 72% (18/25) of adenocarcinoma of the cardia and 65% (20/31) of adenocarcinoma of the antrum. No significant differences in p53 expression in relation to sex, type (Lauren) of tumour, depth of invasion, lymph node involvement, or tumour differentiation were observed in any of the analyzed groups of tumours. Patients with more advanced Barrett’s adenocarcinoma and in the cases of lymph node invasion revealed tendency for the greater p53 positivity compared with the early forms and lymph node-negative cases; however, this difference was not significant according to the statistical analysis. With regard to adenocarcinoma of the cardia, higher rates of p53 positivity were recorded in poorly differentiated, more advanced cases with lymph node invasion. Nevertheless, none of these differences was statistically significant. On the contrary, in the patients with adenocarcinoma of the antrum, greater p53 positivity was revealed in early forms without lymph node involvement, but the observed difference was not statistically significant. Conclusion. No significant differences in p53 protein expression in terms of sex, type (Lauren) of tumour, depth of invasion, lymph node involvement, or tumour differentiation were observed in any of the analyzed groups of tumours (Barrett’s adenocarcinoma, adenocarcinoma of the cardia and adenocarcinoma of the antrum). K e y w o r d s : adenocarcinoma; barrett esophagus cardia; pyloric