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Background/Aim. Lung cancer is one of the most com-mon cancer types worldwide. More than 70% of patients are diagnosed with lung cancer in the advanced stages of the disease, with limited therapeutic options based on cytological and histopathological material. The value of cytology in diagnosing and subtyping non-small cell lung cancer (NSCLC) is very important for modern personalized therapies. The aim of this study was to find out the concordance between cytological and histopathological diagnosis of NSCLC and the accuracy, sensitivity, specificity, and the positive and negative predictive value of cytology in diagnosing lung cancer. Methods. A two-year retrospective study included 169 patients with cytological diagnosis of NSCLC, who, at the same time, had small biopsy and surgical specimens for histopathological diagnoses confirmation that were compared with cytological one. Histopathological diagnosis on surgical specimens was the golden standard for evaluation concordance to the cytological diagnosis of NSCLC and evaluation accuracy, specificity, sensitivity, and the positive and negative prognostic value of cytology as a diagnostic method for detecting lung cancer. Results. This study included 129 (76.3%) male and 40 (23.7%) female patients, aged between 39 and 83, with the average of 62.53 ± 7.6. There was no statistically significant difference between the ages of different genders (p = 0.207). The most frequent diagnosis among cytological diagnoses was NSCLC in 99 (58.58%) patients. Concordance between cytological and histopathological diagnoses of surgical specimens was 61.48%. There was no statistically significant difference between cytological diagnoses and histopathological diagnoses of small biopsies specimens (p = 0.856). The sensitivity, specificity, positive and negative prognostic value, and accuracy of cytology as a diagnostic method of lung cancer were 94.98%, 98.60%, 95.72%, 98.35%, and 97.71%, respectively. Conclusion. Cytological diagnosis of NSCLC is accurate, with high sensitivity, specificity, and benefits for patients. Most patients are diagnosed with advanced cancer when there is no surgical therapy option, and the only available diagnostic material is a small biopsy sampled during bronchoscopy.

Background/Aim. Permanent proliferation and periodical infection are the main clinical characteristics of acquired middle ear cholesteatoma. The aim of this study was to research immunohistochemical characteristics of the skin along with the cholesteatoma process in the nearby tissue. This research should influence further studying of etiology and development of acquired middle ear cholesteatoma. Methods. We investigated clinical, histological and immunohistochemical characteristics of cholesteatoma in 50 samples from operated patients with acquired middle ear cholesteatomas. We classified all samples according to their clinical characteristics of cholesteatoma such as bone destruction, presence of infection or cholesteatoma extension and histological characteristics of cholesteatoma such as keratinisation, inflammatory process and extracellular matrix proliferation. We used mouse monoclonal antibodies for proliferating cell nuclear antigen (MAbs for PCNA), Ki-67, COX-2, CD 4 and CD 8 lymphocytes to investigate the expression of those characteristics in the cholesteatoma and in the control skin tissue. Statistical analyses were performed using SPSS for Windows version 16.0 (SPSS, Chicago, IL, USA). We used the independent group t-test, Spearman’s correlation analysis and Mann-Whitney U test to analyze statistical analysis. Results. Expression of PCNA, Ki-67, COX-2 and CD 8 lymphocytes in more serious clinical picture of cholesteatoma was almost equal as in less serious clinical picture of cholesteatoma. There was statistically significantly higher concentration of inflammation marker CD 4 lymphocytes, both in the acquired cholesteatoma and in the skin of bony portion of the external auditory canal near fibrocartilaginous annulus in more serious clinical picture of cholesteatoma than in less serious clinical picture of cholesteatoma (p < 0.01). There was statistically significant difference of expression of PCNA, Ki- 67, COX-2, CD 4 and CD 8 lymphocytes between all cholesteatoma samples and the skin of bony portion of the external auditory canal (p < 0.05) and statistically significant difference of expression of those markers between the skin of bony portion of the external auditory canal and retroauricular skin (p < 0.05). Conclusion. Inflammation of the skin of bony portion of the external auditory canal is a milestone in pathogenesis of acquired middle ear cholesteatoma. Expression of CD 4 lymphocytes can be the prognostic factor for acquired cholesteatoma clinical picture development. We found so much diversity in biological behavior through very different levels of cholesteatoma development. Expression of Ki-67 in acquired middle ear cholesteatoma is a reliable and stable marker of proliferation for acquired middle ear cholesteatoma.

Introduction/Objective. Association of Graves’ disease (GD) and thyroid cancer is reported in a wide range from 0% to 33.7%. Papillary thyroid carcinoma (PTC) is the most commonly diagnosed malignancy in GD, namely its variant – papillary thyroid microcarcinoma (PTMC). The increasingly frequent PTMC disclose favorable biological behavior with low mortality and recurrence rates. The aim of this work is to report our experience on the frequency and morphological features of PTMC in surgically treated patients with GD. Methods. Over a period of three years, total or near-total thyroidectomy was performed in 129 patients with GD. Results. Incidental PTMC was diagnosed in 24 (18.7%) patients with GD. The mean tumor diameter was 3.03 ± 2.17 mm. The average age of patients in the GD with PTMC group was 48.50 ± 13.07 years, while in the GD without PTMC group it was 41 ± 13.12 years, and it proved to be statistically significant ( p = 0.045). Most of the PTMC were unifocal (83%), and the most common morphological features of PTMC were intraparenchymal localization (62.5%), follicular morphology (66.7%), and infiltrative growth pattern (62.5%). Extrathyroidal extension, lymphatic invasion and multifocality of PTMC were more commonly related with subcapsular localized PTMC. The presence of at least one nodule in the GD with PTMC group was 58.3%, while in the GD without PTMC group it was 26.7%, and it was statistically significant (p = 0.003). Conclusion. Our results showed a high incidence of PTMC (18.7%) in patients with GD. Clinically, the most important morphological characteristics of PTMC were related with its subcapsular localization.

Introduction/Objective. Radical prostatectomy (RP) is the best form of treatment of patients with locally confined prostate cancer (PC). Biochemical progression (BP) of the disease occurs in 27–53% of patients after RP. The aim of our analysis was to assess the significance of the correlation of preoperative prostate-specific antigen (PSA) values and the percentage volume of PC in biochemical progression in patients with RP and the biopsy Gleason score of 6 and 7. Methods. The analysis included the results of treatment of 228 patients with the committed radical retropubic prostatectomy for localized PC in the 2007–2011 period. According to the Gleason grade system values, three groups were identified – 6 (3 + 3), 7 (3 + 4) and 7 (4 + 3). According to the preoperative PSA values the following three groups were determined and monitored: ≤ 4 ng/ml, 4.1–10 ng/ml, and ≥ 10.1 ng/ml. Biochemical progression was defined as two consecutive increases of PSA values ≥ 0.2 ng/ml after RP. The percentage of tumor volume (PTV) is determined by a visual assessment of the percentage of PC in each microscopic sample. Four PTV groups were determined: 0–5%, 6–25%, 26–50%, and 51–100%. Results. Biochemical progression was registered in 19 patients. Most frequent PTV in the group of patients with BP and from biopsy and RP was 6–50%, an average of 30%. Conclusion. Our study showed predictive significant connections between preoperative PSA values and the values of PTV after operational treatment and that these are independent parameters in the assessment of treatment results.

Background/Aim. Sarcoidosis is a multisystem infmammatory disease of unknown etiology, with the lungs and intrathoracic lymph nodes the most commonly involved. The aim of this study was to assess the contribution of conventional transbronchial needle aspiration (TBNA) cytology in the diagnosis of sarcoidosis presenting as mediastinal/hilar lymphadenopathy. Methods. In this retrospective study, 58 patients with suspicion of stage I and II sarcoidosis underwent first flexibile, and then, a rigid bronhoscopy, during which TBNA of mediastinal or hilar lumph node with a 19 gauge (G) needle was done. Material from the needle was put on glass slide and prepared for the cytological and histopathological examination. Results. Out of 58 patients submitted to TBNA of mediastinal or hilar lymph nodes, adequate material for cytological diagnostics was obtained in 53 (91.37%). Out of 53 adequate cytological samples, in 38 (71.69%) noncaseous granulomatous inflammation (NGI) was found, while in corresponding histopathological samples, NGI was found in 48 (90.56%), which was significantly higher (p < 0.05). Of cytological smears, out of the cell types typical for granulomatous inflammation, in 26 (63.15%) patients the clusters of the epitheloid cells were found, in 8 (21.05%) there were both, clusters of epitheloid cells and giant multinuclear hystiocytes, and in 6 (15.76%) only single scattered epitheloid cells or small clusters of several epitheloid cells were found. The sensitivity of TBNA cytology in our group of patients with sarcoidosis was 76%, specificity 100% and accuracy 77.34%. Conclusion. TBNA is an efficient and safe procedure in the diagnosis of sarcoidosis, minimally invasive and with a little risk of complications. Using 19 G needle enables obtaining material for histological and cytological analyses, as well which contribute to the sensitivity of diagnosting sarcoidosis. The value of this type of diagnostics depends on qualification and experience both of bronchoscopist and cytologist/pathologist, as well, of the interpreter of such a material.

Background/Aim. Attic cholesteatoma is an epithelial cystic pseudotumor which arises in the top compartment of the middle ear. Surgery is the only therapeutic treatment for attic cholesteatoma. The aim of this study was to analyze the surgical and audiological results in tympanoplasties that use a logical application of several techniques for the management of attic cholesteatoma. Our hypothesis was that the tympanoplasty technique with cartilage/bone reconstruction of the achieve better outcome than the tympanoplasty technique with only temporal fascia reconstruction of the lateral attic wall. Methods. This retrospective clinical study included 80 patients, aged 16–65 years, with attic cholesteatoma undergoing canal “wall up” tympanoplasty with lateral attic wall reconstruction, under general anesthesia in the Eear, Nose and Throat Clinic, Military Medical Academy in Belgrade between 2006 and 2010. The patients were divided into two groups according to the type of lateral attic wall reconstruction: the group I of 60 patients with cartilage/bone plus temporalis fascia lateral attic wall reconstruction and the group II of 20 patients with only temporal fascia lateral attic wall reconstruction. Postoperative follow-up examinations were done at least 5 years after the surgery. The χ2 test was used to compare postoperative sequelae for two groups of operated patients with lateral attic wall reconstruction. The independent and paired samples t-test of air conduction and air-bone gap were used to compare the results of preoperative and postoperative hearing tests. Results. The differences between hearing measurements of the two groups according to preoperative and postoperative auditory thresholds of the air conduction and the air-bone gap were considered no statistically significant. The difference between the two groups recarding to recurrent attic retraction pocket appearance and recurrence of cholesteatoma was considered statistically significant and the results were much better in the group I of the operated patients with cartilage/ bone lateral attic wall reconstruction. Conclusion. “Wall up” tympanoplasty for attic cholesteatoma with lateral attic wall reconstruction leads to good anatomical and audiological results. A significant hearing improvement was obtained in both the types of lateral attic wall reconstructions in this study. Reconstruction with cartilage or mastoid cortex bone showed favorably long-term functional and anatomical results compared to primary tympanoplasty using only temporal fascia for lateral attic wall reconstruction in cases of attic cholesteatoma.

Background/Aim. Renal cell carcinoma (RCC) is the third most frequent urological carcinoma. Radical nephrectomy (RN) is considered as the gold standard in the treatment of localized RCC, but recently the use of minimally invasive techniques are more frequently used. The aim of this study is to determine is there a difference in the incidence of complications in the group of patients treated by RN and partial nephrectomy (PN) for renal cell carcinoma up to 7 cm. Methods. The retrospective study included the analysis of the medical history of patients surgically treated in the six years period. The inclusion criteria were RCC size up to 7 cm and no detectable metastasis. The exclusion criterion was the presence of a bilateral tumor. Intraoperative and early postoperative complications were followed-up. The Clavien- Dindo grade system was used for classification of surgical complications. Results. In six years period 481 (76.35%) radical transperitoneal nephrectomies and 149 (23.65%) partial nephrectomies were performed. Bilateral RCCs were verified in 2.06% (13/630), an initial metastatic disease in 15.8% (100/630) and lymph node involvement in 7.14% (45/630) of the patients and their data were not included in analysis. Therefore, data from 120 patients with RN and 97 patients with PN who fulfill inclusion criteria were analyzed. Complications were recorded in 29.5% (64/217) of patients. Significantly less patients had complications in the RN group [22.5 % (27/120)] compared to the PN group [38.1% (37/97)] (p = 0.006). These complications were mostly grade I and II. Complications grade III and IV were only present in the group of patients treated by PN. Conclusion. Based on our data in selected patients with renal cell carcinoma in stage T1, PN is a proper and safe choice. The patient must be involved in making the definitive decision of modalities of surgical treatment.

Introduction. Pheochromocytoma of the urinary bladder is a rare tumor and presents less than 0.06% of all urinary bladder tumors. Case report. We presented a 49-year-old female patient with a history of daily paroxysmal hypertension accompanied with flushing of the face and upper chest, palpitations and excessive sweating prior to micturition. Ultrasonography reported a 3 cm bladder wall tumor. The 131I-metaiodobenzylguanidine (131I-MIBG) scan showed a pathological isotope accumulation in the projection of the bladder. The patient underwent a partial cystectomy. One year following the operation the patient was normotensive and without recurrence. Conclusion. The most efficient treatment option for bladder pheochromocytoma is surgical resection. The most important fact in the diagnostics is suspicion on this rare condition.

Bacground/Aim. The ileal neobladder should be a lowpressure reservoir with acceptable volume and relatively small resorptive surface. A larger inner surface of the ileal pouch is associated with the high resorption of urine metabolites through intestinal mucosa and systemic metabolic disturbances, while a too small pouch results in a higher frequency of voiding and incontinency. The aim of this study was to investigate it is possible to create a neobladder from a shorter ileal segment compared to standard surgical techniques, and reduce metabolic complications. Methods. This prospective study included 77 male patients, scheduled for radical cystectomy and orthotopic neobladder derivation. The patients were divided into two groups: the standard pouch (SP) group of 37 patients scheduled for standard orthotopic neobladder, using a 50−70 cm long terminal ileum segment; the “Belgrade pouch” (BP) group of 40 patients scheduled for original, orthotopic urinary reservoir, using a 25−35 cm long terminal ileum segment. We measured neobladder capacity, acidosis, base excess and bicarbonate concentration in the postoperative month 3rd, 6th, 12th and 15th. Results. At the end of the study, the patients from the SP group had much higher neobladder capacity than the natural bladder − 750 mL (range 514−2,050 mL); in contrast, the patients from the BP group had average capacity of 438 mL (range 205−653 mL) (p < 0.001). At the end of the study, there were more patients with acidosis (37.8% : 2.5%), base excess (35.1% : 7.5%) and low bicarbonate level (40.5% : 20.0%) in the SP group, than in the BP group, respectively (p < 0.001). Conclusion. “Belgrade pouch”, make from 25−35 cm long terminal ileum segment may obtain adequate capacity and lower rate of metabolic disturbances than standard, high capacity orthotopic neobladders.

Background/Aim. Survivin is a multifunctional protein abundantly expressed in tumors of various types, including melanoma. There are still sparse data regarding relationship of melanoma cell survivin expression with accepted histopathological characteristics as well as serum concentration. The aim of this study was to investigate the association of local tumor survivin expression (primary tumor and metastatic lesions) and serum concentration with clinical and histopathological parameters in melanoma patients. Methods. The level of survivin expression was determined immunocytochemically in tumor tissue and with ELISA test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the Institute for Pathology and Forensic Medicine and Institute for Medical Research at Military Medical Academy, Belgrade, Serbia. Results. The intensity of survivin expression was significantly higher in the patients whose tumor had ulceration, higher mitotic index, higher Clark and Breslow stage, that made vascular invasion or spread through lymphatic vessels in primary tumor, and was significantly higher in the patients with metastatic disease. Survivin expression and the number of survivin positive cells in metastatic lesions were significantly associated with the duration of disease free interval (DFI). The patients with high expression score had almost double shorter DFI comparing to those with weak local survivin expression and a small number of survivin+cells (9 ± 7 vs 19 ± 13 months, respectively). The degree of tumor infiltrating lymphocytes presence in tumor tissue was significantly associated with serum survivin concentration, with lowest average level detected in samples of patients with the highest degree of infiltration. Serum survivin concentrations were highest in samples of melanoma patients with IA American Joint Commission on Cancer (AJCC) clinical stage, pT1a histological stage, patients whose tumors were still in horizontal growth phase, without signs of lympho-hematological disease spreading, with the highest number of mitoses and the smallest Clark index. Conclusion. Survivin expression in tumor tissue and its serum concetration significantly correlate with clinical and histopathological parameters. Serum levels could be important in initial follow-up as indicators of those patients that would have aggressive local tumor growth and spreading. Survivin determination in tumor tissue is of great significance in estimation of DFI.

Introduction. Pseudomesotheliomatous lung carcinoma is a special, rare entity characterized by large pleural growth and minor invasion of lung tissue. Clinically, radiologically, macroscopically and even histologically this tumor can be misdiagnosed as malignant pleural carcinoma. Case report. We represent a 64-year-old male patient, former smoker. Due to difficulties in the form of dry cough, feeling of dis-comfort and pain in the right hemithorax, fatigue, heavy breathing, sweating, fever up to 39.6°C the patient was treated as with combined antibiotic therapy (macrolides, cephalosporins and penicillin), but without improving of his condition. Chest radiography showed a shadow of pleural effusion by the height of the front end of the third right rib. Chest MSCT showed the extremely thickened pleura apically and to the posterior along the upper right lobe in addition to existence of massive pleural effusion. Subpleural condensation of parenchyma ranging about 30 mm was described in the upper right lobe. Cytological analysis of the pleural effusion showed the presence of malignant cells impossible to differentiate whether they were metastasis of adenocarcinoma or malignant pleural mesothelioma. By histochemical and immunohistohemical analyses of a pleural sample, pseudomesotheliomataus lung adenocarcinoma was diagnosed. Conclusion. Pseudomesotheliomataus carcinoma of the lungs can be a diagnostic problem. Its diagnosis is based on recognition of histopathological characteristics which enable its discernment from the epithelial variant of malignant pleural mesothelioma.

Background/Aim. Kidney injury molecule-1 (KIM-1) and aquaporin-1 (AQP-1) are potential early urinary biomarkers of clear renal cell carcinoma (cRCC). The aim of this study was to ascertain relationship between the urine concentrations KIM-1 and AQP-1 with tumor size, grade, pT stage and type of operation (radical or partial nephrectomy) in patients with cRCC. Methods. Urinary concentrations of urinary KIM-1 (uKIM-1) and urinary AQP-1 (uAQP-1) were determined by commercially available ELISA kits. The analysis included 40 patients undergoing partial or radical nephrectomy for cRCC and 40 age- and sex-matched healthy adult volunteers. Results. The median preoperative concentrations of KIM-1 in the cRCC group [0.724 ± 1.120 ng/mg urinary creatinine (Ucr)] were significantly greater compared with controls (healthy volunteers) (0.210 ± 0.082 ng/mgUcr) (p = 0.0227). Postoperatively, uKIM-1 concentration decreased significantly to control values (0.177 ± 0.099 ng/mgUcr vs 0.210 ± 0.082 ng/mgUcr, respectively). The size, grade and stage of tumor were correlated positively with preoperative uKIM-1 concentrations. Contrary to these results, concentrations of uAQP-1 in the cRCC group were significantly lower (0.111 ± 0.092 ng/mgUcr) compared with the control group (0.202 ± 0.078 ng/mgUcr) (p = 0.0014). Postoperatively, the concentrations of uAQP-1 increased progressively up to control values, approximately. We find no significant correlation between preoperative uAQP-1 concentrations and tumor size, grade and stage. Conclusion. uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy. [Projekat Ministarstva nauke Republike Srbije, br. III41018]

Introduction. The extramedullary plasmacytomas (EMPs) are rare tumors of plasma cell disorders which are rarely found in the duodenum. We presented a case of solitary EMPs involving the duodenum and pancreas successfully treated by surgical resection after failure of chemotherapy. Case report. A 55-year-old female with previously diagnosed solitary EMP of the duodenum was admitted to our institution after failure of three cycles of vincristine, adriablastine, dexamethasone (VAD) chemotherapy regimen with an upper gastrointestinal obstruction. On admission computed tomography of the abdomen showed tumor in the region of the second part of duodenum and uncinate process of the pancreas with a complete duodenal obstruction. Intraoperatively a tumor formation was in the region of the second duodenal part, originated from the wall of duodenum with the total diameter of 7 x 5 cm, covering the entire circumference of duodenal wall leaded to a narrowing of duodenal lumen to the thigh gap with an upper gastrointestinal obstruction. Infiltration in the head of the pancreas and uncinate process were also found. The Whipple’s procedure was performed but postoperative course was complicated by rapidly refilling chylous ascites which was resolved 4 days after the surgery. Conclusion. Each patient with gastrointestinal EMPs should be considered separately and in timely manner, thus adequate treatment could provide local disease control.

Introduction. Renal cell carcinoma (RCC) is derived from renal tubular epithelial cells and represents approximately 3.8% of all malignancies in adults. The incidence of renal cell carcinoma has been growing steadily and ranging from 0.6 to 14.7 for every 100,000 inhabitants. Patients with end-stage renal disease and acquired cystic kidney disease are at increased risk of developing RCC while undergoing dialysis treatment or after renal transplantation. Case report. We presented 3 patients undergoing hemodialysis, with acquired cystic kidney disease accompanied by the development of RCC. In all the patients tumor was asymptomatic and discovered through ultrasound screening in 2 patients and in 1 of the patients by post-surgery pathohistological analysis of the tissue of the kidney excised using nephrectomy. All the three patients had organ-limited disease at the time of the diagnosis and they did not require additional therapy after surgical treatment. During the follow- up after nephrectomy from 6 months to 7 years, local recurrence or metastasis of RCC were not diagnosed. Conclusion. Acquired cystic kidney disease represents a predisposing factor for the development of renal cell carcinoma in dialysis patients and requires regular ultrasound examinations of the abdomen aimed at early diagnosis of malignancies. Prognosis for patients with endstage renal disease and RCC is mostly good because these tumors are usually of indolent course.

Bacground/Aim. The therapy with intravesical instillation of bacillus Calmette-Guérin (BCG) after transurethral resection (TUR) of tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC). The role and importance of BCG intravesical therapy in various shape of tumors, were confirmed by our previous investigation. The aim of this study was to examine whether incidence of recurrence and tumor regression differs depending on sex and age of patients. Methods. This study included a total of 899 patients suffering from NIMBC, treated at our institution from January 1, 2007 to March 1, 2013. Two groups of patients were formed: patients underwent TUR + BCG therapy (the group I) and the group II with patients in whom TUR was performed as only therapy. These two groups of patients were divided into subgroups of respondents male and female, age 60 years or younger and older than 60 years. Statistical analysis was performed using χ2 test and the Kolmogorov-Smirnov test. Results. This research suggests that if the frequency of recurrence is seen as the only parameter, considering all the subjects, the lowest recurrence rate was determined in the male subjects, aged 60 years and younger who had received BCG after TUR. A high statistical significance was found in the incidence of recurrence in patients younger than 60 years, depending on the response to the therapy, while in those older than 60 years, the difference was at the level of statistical significance. This can be attributed to a certain degree of infravesical obstruction in older men. Conclusions. Sex and age of patients may have a significant influence on the course and outcome of NMIBC. The disease has the most malignant and most aggressive behavior when present in males older than 60 years.

Background/Aim. The therapy with intravesical instillation of bacillus Calmette-Guérin (BCG) after transurethral resection (TUR) of the tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC). The aim of this study was to compare the frequencies of reccurence between a group of patients submitted to TUR + BCG therapy (group I) and a group of patients submitted only to TUR (group II). Methods. The patients with NMIBC, a total of 899, treated in our Institution from January 1, 2007 to March, 2013, were included in this study and divided into two groups: group I and group II. These two groups were divided into three subgroups: solitary first diagnosed tumor ≤ 3 cm (SFDGT), solitary first diagnosed tumor > 3 cm and multiple first diagnosed tumors (MFDGT), and recedive tumors (RCT). Statistical analysis was performed by using χ2-test and Kolmogorov-Smirnov test. Results: In the group I a total of 133 cases had reccurence contrary to 75 in the group II, making a statistically highly significant difference. Analysis of recurrences through the subgroups revealed: in the group I SFDGT recurrence occured in 27 of the cases vs 9 cases in the group II; in the group I MFDGT recurrence occured in 49 of the cases vs 31 in the group II (p < 0.001), and finally, in the group I RCT recurrence occured in 57 cases vs 35 cases in the group II (p < 0.001). Conclusion. The obtained results indicate no difference in the frequency of reccurence between the group I and group II regarding SFDGT, but a very high significant difference regarding those with MFDGT and RCT. These results should be taken into consideration in everyday clinical practise.

Background/Aim. Radical cystectomy is the method of choice for the treatment of muscle invasive bladder cancer. This major surgery is associated with many complications, especially in older patients. The aim of this study was to analyze preoperative comorbidity, and intraoperative and postoperative complicatons in patients older than 75 years. Methods. This clinical, retrospective study included 46 patients over 75 years, who underwent radical cystectomy. Indications for surgery, and complications during and after the surgery were followed up. Results. Preoperatively, anemia caused by hematuria was registered in 76% of the patients. In 52% of the patients urine derivation was performed by ileal conduit, in 35% by ureterocutaneostomy and in 13% orthotopic ileal neobladder was created. The average duration of surgery was 190 (120-300) min. A total of 76% of the patients were treated by blood supstitution intraoperatively, average 630 (310-1230) mL. Concerning pathological stage of transitional cell carcinoma of urinary bladder, 26% of the patients had T2, 4% T3a, 52% T3b, and 14% T4a stage. In one case, planocellular carcinoma was diagnosed by patohistological examination, and in 2 cases prostate carcinoma was incidentally found. The average duration of hospitalization was 16 (8-35) days. Conclusion. The main reason for cystectomy in patients over 70 and 80 years was gross hematuria caused by bladder cancer, with consecutive anemia which could not be solved using endoscopic treatment or blood supstitution. As expected, a prolonged stay in hospital after cystectomy, and a higher rate of complications were recorded in this population.

Introduction. Sclerosing mesenteritis is a rare pathological entity characterized by non-specific tumor-like expansion in mesentery. Accurate diagnosis of this disease is rarely made preoperatively. Surgery takes place in diagnosis, as well in treatment of the disease. We presented a case of sclerosing mesenteritis that affected the final portions of duodenum and initial part of jejunum with clinical picture of upper gastrointestinal obstruction. Case report. A 46-year-old man without previous medical history was presented with vomiting and loss of weight in the last 6 months. Due to suspicion of parapancreatic tumor by CT examination and clinical presentation of the disease, the patient underwent laparotomy. A mass infiltrated mesenteric root, initial part of superior mesenteric artery, the fourth duodenum portion and the ligament of Treitz, while the stomach and duodenum were dilatated. The intraoperative biopsy indicated a benign process. The mass was reduced with desobstruction of the duodenum. Definitively, histopathological finding showed fibromatosis in different phases of activity. Postoperative course passed without complications. The patient continued to receive an immunosuppressive drug therapy. After a 6-month treatment the patient showed no gastrointestinal problems. Conclusion. Sclerosing mesenteritis that affects the duodenum and the proximal part of the jejunum with subacute upper gastrointestinal obstruction is an extremely rare condition. In the presented case a surgical procedure was necessary for marking the diagnosis and treatment as well.

Prostate cancer (PCa) is the second most commonly diagnosed cancer among men worldwide. Despite its high incidence rate, the molecular basis of PCa onset and its progression remains little understood. Genome-wide association studies (GWAS) have greatly contributed to the identification of single nucleotide polymorphisms (SNP) associated with PCa risk. Several GWAS identified 8q24 as one of the most significant PCa-associated regions. The aim of this study was to evaluate the association of SNP rs378854 at 8q24 with PCa risk in the Serbian population. The study population included 261 individuals diagnosed with PCa, 257 individuals diagnosed with benign prostatic hyperplasia (BPH) and 106 healthy controls. Data quality analysis yielded results showing deviations from Hardy-Weinberg equilibrium in groups of PCa patients and BPH patients as well as in the control group. There was no significant association between alleles and genotypes of the genetic variant rs378854 and PCa risk in the Serbian population. [Projekat Ministarstva nauke Republike Srbije, br. 173016]

Introduction. Keratocystic odontogenic tumor (KCOT) is defined as a benign cystic neoplasm of the jaws of odontogenic origin with a high rate of recurrence. The most lesions occur in the posterior part of the mandible. Treatment of KCOT remains controversial, but the goals of treatment should involve eliminating the potential for recurrence while minimizing surgical morbidity. However, another significant therapeutic problem related to the management of KCOT is an adequate and early reconstruction of the existing jaw defect, as well as appropriate aesthetic and functional rehabilitation of a patient, especially in cases of a very large destruction of the jaws bone. Case report. We presented a 65-year-old female patient with very large KCOT of the mandible. Orthopantomographic radiography showed a very large elliptical multilocular radiolucency, located on the right side of the mandible body and the ascending ramus of the mandible, with radiographic evidence of cortical perforation at the anterior border of the mandibular ramus and the superior border of the alveolar part of the mandible. The surgical treatment included two phases. In the first phase, the tumor was removed by enucleation and additional use of Carnoy solution, performing peripheral ostectomy and excision of the affected overlying mucosa, while in the second phase, restorative surgery of the existing mandibular defect was performed 6 months later. Postoperatively, we did not register any of postoperative complications, nor recurrence within 2 years of the follow-up. Conclusion. Adequate and early reconstruction of the existing jaw defect and appropriate aesthetic and functional rehabilitation of the patient should be the primary goal in the treatment of KCOT, having in mind the need for a long-term post-surgical follow-up.

Introduction. Bronchial carcinoids belong to a rare type of lung tumors. If they do not expose outstanding neuroendocrine activity, they develop without clearly visible symptoms. They are often detected during a routine examination. According to their clinical pathological features, they are divided into typical and atypical tumors. Typical bronchial carcinoids metastasize to distant organs very rarely. Localized forms are effectively treated by surgery. The methods of conservative treatment should be applied in other cases. Case report. We presented a 65-year-old patient with carcinoid lung tumor detected by a routine examination. Additional analysis (chest X-ray, computed tomography of the chest, ultrasound of the abdomen, skeletal scintigraphy, bronhoscopy, histopathological analysis of the bioptate of bronchial tumor, as well as bronchial brushing cytology and immunohistochemical staining performed with markers specific for neuroendocrine tumor) proved a morphologically typical lung carcinoid with dissemination to the liver and skeletal system, which is very rarely found in typical carcinoids. Conclusion. The presented case with carcinoid used to be showed morphological and pathohistological characteristics of typical bronchial carcinoid. With its metastasis to the liver and skeletal system it demonstrated unusual clinical course that used to be considered as rare phenomenon. Due to its frequent asymptomatic course and varied manifestation, bronchial carcinoid could be considered as a diagnostic challenge requiring a multidisciplinary approach.

Background/Aim. Parathyroid hyperplasia (PHP) is defined as an absolute increase in the mass of parenchymal cells of the parathyroid gland. PHP is classified as primary, secondary and tertiary. The enlargement of parathyroid glands (PG) is usually asymmetric, resulting in a “dominant“ gland. In order to confirm the diagnosis, at least two glands should be examined histologically. Subtotal parathyroidectomy, i.e. removal of the three PG and leaving a small remnant of the forth, is the treatment of choice. High percent of PHP recurrence imposes the need for preoperative high sensitivity localizing procedures. Parathyroid scintigraphy localizes about 60% of hyperplastic glands. The aim of this study was to correlate findings of subtraction parathyroid scintigraphy (SPS) with weight, pathohistologic finding and oxyphil cell (OC) content of PG in patients with primary, secondary and tertiary parathyroid hyperplasia. Methods. Twenty-seven patients with primary/secondary PHP underwent SPS before surgery. Scintigraphic results were graded from 1-5, in relation to the degree of uptake. SPS graded 3, 4 and 5 were considered positive. The number and weight of operated PG were evaluated macroscopically. Pathohistologic and cellular types were defined on standard stained hematoxylin-eosin slides. OC content was defined as a percent of OC and graded from 1 to 3: grade 1 < 10%, grade 2 ≥ 10% and grade 3 ≥ 20% of OC. Results. SPS localized dominant gland in all patients with sensitivity 100%, and 51 from 73 hyperplastic PG, with sensitivity per gland of 70%. PG weighed 0.1 g to 6.7 g (median 1 g). A significant positive correlation (p < 0.0001) was found between the SPS results and PG weight. A significant positive correlation was found between PG weight and OC content (p = 0.0002). An insignificant correlation was found between SPS and OC content. Thirty-eight PG had < 10% of OC, 32 PG had < 10% and 3 PG had ≥ 20% of OC. Four patients had diffuse PHP and 23 patients nodular PHP. There was no statistically significant difference in SPS results compared to hyperplasia type, and between OC content and hyperplasia type. A significant positive correlation (p = 0.05) was found between PG weight and hyperplasia type. Conclusion. A high positive correlation was found between SPS results and PG weight, PG weight and OC content and PG weight and hyperplasia type. Between SPS results and OC content, and between SPS results and hyperplasia type, an insignificant correlation was found. Our results showed that SPS is a reliable and very sensitive diagnostic tool in detecting abnormal PG in parathyroid hyperplasia, reaching 100% sensitivity in detecting a “dominant gland” and sensitivity per localized gland of 70%. Causes that affect increased uptake of liposolubile Tc99m radiopharmaceuticals (RF) in the hyperfunctional PG tissue and conditions which prevent RF admission into the PG cells still remain to be accurately and precisely determined.

Backgraund/Aim. Conventional cytomorphology of thyroid cell aspirates is limited in preoperative differential diagnosis of follicular adenomas (FA) and hyperplastic adenomatoid nodular goiters from well differentiated thyroid follicular carcinoma (FTC) and follicular variant of thyroid papillary carcinoma (PTC). This is the reason of inaccurate presurgical differential diagnosis and in the same cases of inadequate operative managament. The aim of the study was to evaluate the role of quantitative estimation of thyreocite nuclear features (cariomorphometry) in thyroid aspirated smears in preoperative differential diagnosis of benign from malignant thyroid lesions. Methods. A total of 48 patients with thyroid nodular disease underwent fine needle aspiration biopsy for cytomorphology, cariomorphometric analysis of the aspirates, and histopathologic explorations conducted fully postoperatively. On the basis of cytomorphology classification the patients were divided into three groups: benign (B), n = 8; malignant (M), n = 15, and suspicious for malignancy (S), n = 25. Using a microscope connected to a computerized video system, mean nuclear area, the nuclear area coefficient of variation (NACV) and anisocariosis ratio were measured and calculated. Results. In all the 15 patients with cytologically malignant results the diagnosis of PTC was confirmed histopathologically. All cytologically benign lesions were confirmed histopathologically. Thyroid carcinoma was found in 15 out of 25 patients with suspicious lesions. The highest mean values of nuclear area were in the PCT (90.74 ± 26.71 μm2), and were significantly different from all other groups (p < 0.001). The mean nuclear area in FTC was 69.20 ± 27.31 μm2 and was significantly higher than in the benign adenomatous group (p < 0.01). There was no significant difference in mean nuclear area between FTC and FA, but there was a significant difference in NACV between these two groups (FTC: 39.46 % vs FA: 23.42%, p < 0.001). In 27 out of 30 patients with thyroid carcinoma higher values of NACV than 18% were found. Conclusion. Preoperatively cariomorphometry is a useful method in differential diagnosis of thyroid carcinoma from benign lesions, as a complementary method to convencional cytodiagnostics. The NACV showed highest sensitivity as a parameter of malignant thyroid cell transformation.

Apoptosis or programmed cell death is a genetically regulated process of cellular suicide. Apoptosis has been implicated in a wide range of pathological conditions, and mutations in apoptotic genes play important roles in the process of malignant transformation. Chronic leukemia represents a neoplastic disorder caused primarily by defective programmed cell death, as opposed to increased cell proliferation. This paper presents the main results of our ten-year research on the apoptosis of leukemia cells. The research included the morphological aspects of the process, the effect of antineoplastic agents on the induction of apoptosis in leukemia cells and expression analysis of the proteins involved in programmed cell death. Special attention was paid to the expression and interaction of the Bcl-2 family of proteins in leukemia cells. The ultimate aim of the study of apoptosis of leukemic cells is the discovery of new biological agents that might be used in the treatment of chronic leukemia.

Background. Angiofibromas are histologically benign vascular tumors, originating from the nasopharynx, near by the area of sphenopalatine foramen. These neoplasms occur typically in male adolescents. Reports of primary extranasopharyngeal angiofibromas have appeared sporadically in the literature in English. We present the first case of an elderly woman with tumor arising from the middle turbinate, diagnosed as angiofibroma. Case report. A 63-year-old female presented with left-sided nasal obstruction and epistaxis. Endoscopic evaluation revealed a polypoid mass arising from the anteroinferior portion of the left middle turbinate. Computed tomography (CT) scan showed a soft-tissue opacity that filled the anterior part of the left nasal cavity. After the endoscopic excision of the mass, postoperative pathohistological and immunohistochemical analysis confirmed the diagnosis of an angiofibroma. Two years later, the patient was free of symptoms and without endoscopic evidence of recurrence. Conclusion. Extranasopharyngeal angiofibromas arising from the nasal cavity are extremely rare tumors. Immunohistochemical analysis is very important in all doubtful cases, especially in those with atypical location.

Background/Aim. Primary hyperparathyroidism (pHPT) is an endocrine disease with the third highest incidence of all endocrine disorders after diabetes mellitus and hyperthyroidism. pHPT is typically caused by a solitary parathyroid adenoma, less frequently by multiple parathyroid gland disease (MGD) and rarely by parathyroid carcinoma. Secondary hyperparatyroidism (sHPT) is a common complication in patients with chronic renal failure. The aim of this study was to estimate sensitivity of dual tracer 99mTctetrofosmin and 99mTc-pertechnetate subtraction scintigraphy in detection of abnormal parathyroid glands in patients with pHPT and sHPT confirmed by histopathology. Methods. In 46 patients, (77 abnormal parathyroid glands), 30 with pHPT and 16 with sHPT parathyroid scintigraphy was done preoperatively. All the patients had histopathological confirmation of diagnosis. Abnormal parathyroid glands weighted from 0.1 to 7 g. After iv injection dynamic scintigraphy during 25 minutes (one frame-one minute) using 555 MBq of 99mTc-tetrofosmin, and three hours latter using 111 MBq of 99mTc /pertechnetate was performed. 99mTc-tetrofosmin dynamic study was followed by static scintigraphy of the neck and chest 30 minutes, 1, 2 and 3 hours after iv injection. Results. An abnormal scintigraphic finding was found in 44 of 46 patients with sensitivity of 96%. In pHPT sensitivity was 93% (28 of 30 patients, and 28 of 30 glands). In sHPT scintigraphy was abnormal in all the patients (sensitivity 100%). In the patients with sHPT scintigraphy detected 30 of 47 abnormal parathyroid glands (sensitivity 64%). An overall sensitivity of scintigraphy per gland, for pHPT and sHPT in detecting 58 of 77 abnormal parathyroid glands was 75%. Conclusion. An abnormal scintigrafic result per patient was found in 44 patients (sensitivity 96%) and 58 of 77 abnormal parathyroid glands were detected (sensitivity 75%). A high sensitivity of dual tracer subtraction 99mTc-tetrofosmin/99mTc-pertechnetate parathyroid scintigraphy in detecting abnormal parathyroid glands in primary and secondary hyperparathyroidism was achieved.

Background/Aim. Although there are several types of malignant oral cancers, more than 90% of all diagnosed oral cancers are squamous cell carcinoma (OSCC). Angiogenesis is a cascade-like mechanism which is essential for tumor growth and metastasis. Therefore, vascular endothelial growth factor (VEGF) expression in OSCC and its effect on clinicopathological characteristics and prognosis is of major interest. So far researches have shown that increased expression of this gene, in other words enhanced synthesis of this protein (VEGF), independently on other factors, increases a chance for local relapse, and distant metastasis. Consequently, patients with OSCC have poor disease-free survival, as well as poor overall survival. The aim of the study was to determine clinical significance of VEGF expression in patients with stage II and III OSCC. Methods. This retrospective study analyzed 40 patients who had been operated for OSCC of their tongue and the mouth floor. Of these patients, some had stage II and III OSCC with histological grade, G1-G3 and nuclear grade Ng1-Ng3. Two high quality tissue samples were obtained and immunohistochemical expression of VEGF was quantitatively determined by using high microscope amplification. The value of VEGF expression of 20% was rated as significant expression, whereas tumor cells reactivation less than 20% was considered very low or no expression at all. The patients were followed up for a 3-year period. Results. The obtained results showed that 11 (17.5%) patients had VEGF expression less than 20% and 29 (82.5%) above 20%. A statistical significance was immanent with positive nodal status (p < 0.05) and disease stage (p < 0.05). No statistical correlation was found between the level of VEGF expression and histological and nuclear grade, tumor size, disease relapse or patients overall survival. Conclusion. In spite the controversy about the prognostic relevance of VEGF our results as well as the results of previous studies, suggest that the expression of VEGF is not reliable as a clinical parameter for the prognosis and disease outcome but it is one of the important factors for the disease progression.

Background/Aim. Feasibility of radical prostatectomy (RP) in patients with locally invasive prostate cancer (PC) is assessed by the standard parameters such as the stage of the disease, serum prostate-specific antigen (PSA) and bioptic Gleason grade (GG). Intermediate values of PSA are important in predicting the local confines of the tumor, but can also be detected in more than 30% of patients with locally advanced PC. The aim of this study was to find out the incidence of locally advanced PC in the patients with intermediate serum PSA in whom RP had been performed. Methods. We used the biopsy cores and the tissue obtained after RP from 46 patients who had intermidiate PSA values which were defined as PSA from 2.6-10 ng/ml. In all the patients classical regional lymphadenectomy was performed. In all the patients, preoperative stage was determined according to the Partin tables (PT) from 2001. Results. In 52,17% of the patients biopsy GG was ≤6, while it was 7 in 47.83% of the patients. Clinically localized disease (cT2b) was found in 86.96% of patients; other 13.04% of the patients had locally advanced PC. After RP, the incidence of localized PC was 47.83%, while the advanced disease was found in 52.17%. Metastasis in one or two regional lymph nodes (N1) was found in 10.87% of the patients with the advanced PC. According to PT, the expected incidence of positive lymph nodes should have been 8% for pT3 stage. Positive correlation between the assumed N1 stage according to PT and N1 stage in our radical prostatectomies was statistically significant (p = 0.012). Conclusion. In more than 50% of patients with intermediate values of PSA locally advanced disease can be expected after RP. The use of the Partin tables have an important predictive value in assessing the local confines of the cancer and metastasis in regional lymph nodes. .

Background. Simultaneous presence of Hashimoto's thyroiditis and papillary thyroidal carcinoma in thyroidal gland with papillary carcinoma association in thyroglossal duct is quite rare. The questions like where the original site of primary process, is where metastasis is, what the cause of coexisting of these diseasesis present a diagnostic dilemma. Case report. We presented a case of a 53-year old female patient, with the diagnosis of Hashimoto's thyroiditis and symptoms of subclinical hypothyreosis and nodal changes in the right lobe of thyroidal gland, according to clinical investigation. Morphological examination of thyroidal gland, ultrasound examination and scintigraphy with technetium (Tc) confirmed the existence of nonhomogenic tissue with parenchyma nodular changes in the right lobe of thyroidal gland that weakly bonded Tc. Fine needle biopsy in nodal changes, with cytological analyses showed no evidence of atypical thyreocites. Hashimoto's thyroiditis was confirmed on the basis of the increased values of anti-microsomal antibodies, the high levels of thyreogobulin 117 ng/ml and TSH 6.29 μIU/ml. The operation near by the nodular change in the right lobe of thyroidal gland revealed pyramidal lobe spread in the thyroglossal duct. Total thyroidectomia was done with the elimination of thyroglossal duct. Final patohystological findings showed papillary carcinoma in the nodal changes pT2, N0 and in the thyroglossal duct with the presence of Hashimoto's thyroiditis in the residual parenchyme of the thyroid gland. After the surgery the whole body scintigraphy with iodine 131 (131I) did not reveal accumulation of 131I in the body, while the fixation in the neck was 1%. After that, the patient was treated with thyroxin with suppressionsubstitution doses. Conclusion. Abnormality in embrional development of thyroidal tissue might be the source of thyroidal carcinoma or the way of spreading of metastasis of primary thyroidal carcinoma from thyroid gland. The cause of this process is most probably a hereditary mutation in RET oncogenes.

Background. Multiple myeloma is a plasmaproliferative disease characterized by the uncontrolled proliferation of a pathogenic plasma cell clone engaged in the production of monoclonal immunoglobulin. This condition affects the bone marrow, but it can be manifested in any other organ or tissue. The urinary bladder involvement is extremely rare. Case report. We reported a 70-year-old male with the history of multiple myeloma, receiving chemotherapy containing melphalan and prednisone (MP). Two years after the treatment, there was a renal failure associated with oligoanuria, hematuria and bilateral hydronephrosis. The urine cytology tests revealed the atypical cells, so was suspected obstructive uropathy to be caused by urothelium cancer. However, only upon the cystoscopy and biopsy performed on the urinary bladder mass, plasmacytoid infiltration diagnosis was confirmed. This extremely rare variant was presented throughout the illness period and proved to be resistant to the administered chemotherapy. Conclusion. When renal failure associated with hematuria and bilateral hydronephrosis is presented in a patient with multiple myeloma, this unusual and rare extramedular localization should be also considered.

Background/Aim. Radical prostatectomy (RP) provides the best cancer control in patients with clinically prostate gland confined cancer. Multiple models and nomograms combining preoperative prostate-specific antigen (PSA) serum level, clinical stage and Gleason score have been developed to predict the probability of metastatic disease. In prostate cancer (PC) the presence of metastases to the pelvic lymph nodes (PLNs) is recognized widely as an unfavorable prognostic factor. Currently, PLNs dissection is not done in a low-risk group of prostate cancer patients. The aim of this study was to analyze PLN metastases in PC patients, in clinically localized stages of PC. Methods. Radical prostatectomy specimens with pelvic lymphadenectomy specimens from 82 PC patients were reviewed. In this group of patients, serum preoperative PSA values ranged from 2 to 23 ng/ml. Results. We diagnosed 11/82 (13.4%) patients with PLN metastases. There were 8 (72%) patients with pT3c pathological stage, and 3 (28%) patients with pT4a stage. PSA below 4 ng/ml was detected in 2/5 (40%) patients with PLN metastases. There was no statistically significant difference between preoperative PSA values and postoperative T stage, and PLN metastases. A statistically significant correlation between PLN metastases and the stage was found in the patients with pT4 and the patients with pT3c PC stages (p < 0.05). Conclusion. Recent RP series indicate PLN metastases to be less than 10%. We demonstrated higher detection of PLN metastases (13.4%) in our RP series. Our results suggest that PLNs dissection should be performed even in patients with low-risk PC.

Background. Chronic lymphocytic leukemia (CLL) is a neoplastic disease characterized by the accumulation of morphologically mature monoclonal CD5+ B cells in the early phase (G0/G1) of the cell cycle. The accumulation of neoplastically transformed B-lymphocytes (CLL cells) is primarily the consequence of apoptosis blocking in these cells. Bcl-2 proteins are well-known modulators of this process. Some of these proteins are anti-apoptotic while the others are pro-apoptotic. All contain at least one of the four conserved regions called the Bcl-2 homologous domains (BH1-BH4). Evidence indicates that Bcl-2 and Bax form homo- and heterodimers. The anti-apoptotic effect of Bcl-2 protein is based on its ability to bind Bax protein in the heterodimer form, and thus to block the forming of Bax/Bax proapoptotic homodimers. The ratio of Bcl-2/Bax represents the cell autonomous rheostat which determinates the type of the cell reaction to an apoptotic stimulus. Methods. The aim of this study was to determine the level of interaction between these two proteins in CLL cells using the co-immunoprecipition method. The study included the analysis of 20 peripheral blood specimens from 20 patients with CLL, and 20 peripheral blood specimens from healthy persons, who were in the control group. Specimens were precipitated with the monoclonal antibody for Bcl-2 protein, and immunoblotted with the palyclonal antibody for Bax protein (IP: Bcl-2/WB:Bax). At the same time, specimens were precipitated with the polyclonal antibody for Bax protein, and immunoblotted with the monoclonal antibody for Bcl-2 protein (IP: Bax/WB:Bcl-2). The intensity of Bcl-2 and Bax protein's binding compared to the control samples of the peripheral blood from healthy persons, was increased in CLL cells. Results. IP: Bax/WB: Bcl-2 showed a high level of “free“ Bcl-2 protein which was not bound in the heterodimer form to Bax protein. Simultaneously IP: Bcl- 2/WB: Bax showed that a higher quantity of Bax protein was bound in the heterodimer form to Bcl-2 protein as opposed to the quantity of pro-apoptotic Bax protein potentially bound in the homodimer form. Conclusion. Further studies involving larger groups of patients are necessary to explore the potential significance of the Bcl-2/Bax protein ratio as a prognostic parameter in the CLL treatment.

Background. High-dose chemotherapy followed by hematopoietic stem cell support can be used as a first-line treatment in patients with germ-cell tumor (GCT) with poor prognosis. Long-term survival rate is attained in 50% of these patients. The aim of this paper was to present the experience at the Department of Hematology, Military Medical Academy, with high-dose cytostatic therapy as first-line chemotherapy in GCT patients with poor prognosis. Methods. Between 1997 and 2003, five patients with high-risk germ-cell tumors were treated with high-dosage chemotherapy followed by an autologous stem cell transplantation. All the patients were with non-seminomatous germ-cell tumors with mixed histology, and one was with extragonadal retroperitoneal germ-cell tumor. Results. The follow-up period ranged from 8 to 33 months. Three patients achieved complete remision, two patients only partial remision, and one was not followed-up. One patient was with residual tumor resection, using retroperitoneal lymphadenectomy, after autologous stem cell transplantation. All the patients were treated according to standard protocols. Conclusion. Early high-dose chemotherapy associated with hematopoietic stem cell support as a first-line treatment in the patients with germ-cell tumor with a poor prognosis, represented an efficient treatment modality.

Background. In numerous recent studies attention has been focused to neuroendocrine differentiation (NED) in prostate cancer (PC). Focal NED is present in almost all PCs, but it is prominent in only 5-10% of the carcinomas. The prognostic significance of focal NED in PC is controversial, but current evidence suggests its influence on the onset and/or conversion of hormon resistant tumor phenotype. The aim of this study was to evaluate the relationship between NED status, based only on immunohistochemical use of neuroendocrine (NE) markers, with PC grade and stage, and preoperative serum levels of prostate-specific antigen (PSA). Methods. The study included the biopsy material of 73 untreated PC patients (pts.) obtained by transurethral resection (TUR) (37 pts.), and radical retropubic prostatectomy (RRP) (36 pts.). Two representative tissue samples (tipically the block containing the largest amount of neoplasm) were selected for immunohistochemical (IMM) staining. NE cells were identified using a panel of IMM markers: chromogranin A, neuron-specific enolase, and serotonin. The level of PC exocrine differentiation was detected by monoclonal antibodies against PSA. Results. Significant expression of NE cells was demonstrated in 26 (70.2%) pts. with PC after TUR. In this group, serum preoperative PSA values ranged from 0.1 to 9.6 ng/ml. The majority of pts. with NED had low differentiated PC with Gleason grade score (GGS) >7, and normal PSA values below 4 ng/ml (77%), in clinical stage D (54%). Statistically significant correlation (p

Chronic lymphocytic leukemia (CLL) is a neoplastic disease characterized by the accumulation of morphologically mature monoclonal CD 5+ B cells in the early phase (G0/G1) of the cell cycle. It is considered that the accumulation of neoplastically transformed lymphocytes B (CLL cells) is primarily the consequence of the disturbance, i.e., blockade of these cells' apoptosis process. Apoptosis is the specific process of programmed cell death regulated by numerous extracellular and intracellular mechanisms. The Bcl-2 proteins are well-known modulators of this process. Some of these proteins (such as Bcl-2, and Bcl-Xl) are anti-apoptotic, while others (such as Bad or Bax) are pro-apoptotic. Our study included the analysis of 20 peripheral blood specimens from 20 patients with CLL, and 20 peripheral blood specimens of healthy persons who represented the control group. Using Western blotting analysis, we quantitatively examined the protein expression of Bcl-2 family (Bcl-2, Bax, Bad, and Bcl-Xl). The level of Bcl-2 (p=3,68´10-10), Bax (p=0,019), and Bad (p=0,073) proteins expression was significantly increased in all the analyzed peripheral blood samples of patients, while the level of Bcl-Xl protein (p=0,75) did not significantly differ in peripheral blood samples of patients, compared to the controls. The results of this study showed that the increased level of expression of Bcl-2, Bax, and Bad protein represented the most striking feature of CLL cells. Moreover, the variations in the expression of only one protein of the Bcl-2 family could not represent the prognostic parameter in the treatment of this disease.

The serum levels of prostate-specific antigen (PSA) represent a significant diagnostic and monitoring parameter of prostatic carcinoma (PC). The aim of the study was to establish correlation of serum PSA level in addition to grade, histological type, and clinical stage of PC in patients with normal or intermediary PSA serum level. In 37 untreated PC patients with preoperative serum PSA levels ranging between 0.1 and 9.6 ng/ml, paraffin-embedded tissue and serum samples were immunohistological studied and immunoassay for PSA was done. The most representative was poorly differentiated PC with D stage In serum samples from PC patients 27 (73.7%) normal (≤ 4.0 ng/ml), and 10 (27.3%) intermediate (4.1-10 ng/ml) PSA levels were found Immunohistochemistry, in 36 PC (97.3%) had demonstrated the expression of PSA. Our study results had shown low serum PSA levels in some patients with advanced poorly differentiated PC.

BACKGROUND: B-chronic lymphocytic leukemia (B-CLL) is an example of human malignancy caused by alternations in the pathways of apoptosis. Mitochondria play a critical role in the regulation of this process. The B-CLL cells dying in apoptosis showed typical morphological characteristics: the reduction of the nuclear volume is accompanied with the reduction of the cytoplasmatic volume, while many of organelles remain intact. The aim of our study was ultrastructural investigation of mitochondrial morphology in apoptotic B- CLL cells. METHODS: Our study included peripheral blood samples from 32 B-CLL patients. The samples were fixed in 4% glutar-aldehyde buffered in 0.1 cacodylate buffer and postfixed in 1% osmium tetroxide in the same buffer. The specimens were dehydrated in a graded series of alcohol and embedded in EPON 812. The ultra-thin sections were stained with uranyl acetate and lead citrate. Ultrastructural analysis of sections was performed on Philips electron microscope 208S at 80 kV. RESULTS: The most frequent mitochondrial abnormalities in apoptotic B-CLL cells were a reduction of size with a hyperdensity of their matrix (mitochondrial pyknosis), or markedly swollen mitochondria with peripherally placed, disorientated, and disintegrated cristae. In some apoptotic cells, we also detected close association of mitochondria with loops of rough endoplasmatic reticulum. CONCLUSION: The results of our study showed the numerous of mitochondria damages in B-CLL cells during apoptotic process. The correlation between ultrastructural damage and functional activity of mitochondria in apoptotic B-CLL cells is still not clear and requires further investigation.