Comparison of Demographic, Epidemiological, Immunological, and Clinical Characteristics of Patients with HIV Mono-infection Versus Patients Co-infected with HCV or/and HBV: A Serbian Cohort Study.

OBJECTIVE: The study aimed to correlate the status of hepatitis C (HCV) and hepatitis B virus (HBV) co-infection in patients with human immunodeficiency virus (HIV) infection with clinical and demographic data prior to starting highly active antiretroviral therapy (HAART) and assess the impact of HCV and HBV co-infection on the natural history of HIV infection. PATIENTS AND METHODS: The study involved a total of 836 treatment-naive patients with available serological status for HBV and HCV at the point of therapy initiation. Patients were stratified into four groups: HIV mono-infection, HIV/HCV, HIV/HBV, and HIV/HCV/HBV co-infection. Demographic, epidemiological, immunological and clinical characteristics were analyzed in order to assess the possible impact of HCV and HBV co-infection on HIV - related immunodeficiency and progression to AIDS. RESULTS: The prevalence of HCV and HBV co-infection in our cohort was 25.7% and 6.3%, respectively. Triple HIV/HCV/HBV infection was recorded in 1.7% of the patients. In comparison with those co-infected with HCV, patients with HIV mono-infection had lower levels of serum liver enzymes activity and higher CD4 cell counts, and were less likely to have CD4 cell counts below100 cells/µL and clinical AIDS, with OR 0.556 and 0.561, respectively. No difference in the development of advanced immunodeficiency and/or AIDS was recorded between patients with HIV monoinfection and those co-infected with HBV, or both HCV/HBV. CONCLUSION: HIV/HCV co-infection was found to be more prevalent than HIV/HBV co-infection in a Serbian cohort. Co-infection with HCV was related to more profound immunodeficiency prior to therapy initiation, reflecting a possible unfavorable impact of HCV on the natural history of HIV infection.

Prognostic significance of clinical parameters and Epstein-Barr virus infection in non-endemic undifferentiated carcinoma of nasopharyngeal type: a Serbian report.

Undifferentiated carcinoma of nasopharyngeal type (UCNT) is very rare tumour in Serbia, like in most of the countries of Europe, with incidence less than 0.5 per 100,000 people per year. The aim of this study was to assess the presence of Epstein-Barr virus (EBV) in the UCNT of a non-endemic population in Serbia and identify the main clinical parameters that interfere with patients' survival rate. This study included 102 patients with UCNT who were diagnosed between 1996 and 2003. Biopsies were analysed for EBV-encoded RNA (EBER) by in situ hybridization of tumour tissue microarray. Of 102 patients, 76 were men and 26 were women with ages ranging between 18 and 82 years (median 52.5, mean 53.0±14.1). Survival rates were 80, 39 and 31% for one, three and five years, respectively. Ninety-three of 102 cases were EBER positive (92%). Factors with unfavourable prognostic values were age over 50 years at the time of diagnosis, advanced clinical stage, therapy other than chemoradiotherapy and EBER negative status. In regard to the clinical data, EBER expression in UCNT was shown to be a strong independent predictor of overall and progression-free survival. To our knowledge, the current report constitutes the largest European non-endemic series of UCNT samples from a single institution with correlation between survival and clinical parameters/EBER status.

Major salivary gland sonography in Sjögren's syndrome: diagnostic value of a novel ultrasonography score (0-12) for parenchymal inhomogeneity.

OBJECTIVE: To validate ultrasonographic criteria for examination of the major salivary glands in the diagnosis of primary Sjögren's syndrome (SS). METHOD: A total of 209 consecutive patients with rheumatic diseases were selected according to the American-European Consensus Group (AECG) classification criteria for SS. One hundred and fifteen patients had primary SS, 44 had secondary SS, and 50 had sicca symptoms, and 36 subjects served as asymptomatic controls. This cohort was analysed for size, echogenicity, parenchymal inhomogeneity, focal changes, and posterior borders of the major salivary glands by ultrasonography (US). A novel US score for parenchymal inhomogeneity (0-12) was assigned and its diagnostic accuracy evaluated. RESULTS: Ultrasonographic abnormalities of salivary glands were detected in 107/115 (93.0%) patients with primary SS, in 12/44 (27.3%) with secondary SS, in 25/50 (50.0%) with sicca symptoms, and in 4/36 (11.1%) asymptomatic controls. Area under the receiver operating characteristic curve (AUC-ROC) for US inhomogeneity score was highly significant [0.96 +/- 0.01; 95% confidence interval (CI) 0.94-0.99, p < 0.000] for primary SS, with a sensitivity to specificity ratio of 91/83 for parotid and 93/90 for submandibular glands. Setting the cut-off US inhomogeneity score at 6 resulted in the best ratio of specificity (90.0%) to sensitivity (95.1%), with a positive predictive value of 72% and a negative predictive value of 96%. A US inhomogeneity score >or= 6 was closely correlated with positive biopsy (p < 0.000) and scintigraphy findings (p < 0.000). CONCLUSIONS: We demonstrate the high diagnostic value of a novel US score for parenchymal inhomogeneity (0-12) that could serve as a useful single US criterion in the evaluation of salivary gland involvement in primary SS.

Large-cell neuroendocrine carcinoma of the ampulla of Vater.

Large-cell neuroendocrine carcinoma is a high-grade neuroendocrine carcinoma, originally described in the lung. The tumor rarely occurs in extrapulmonary sites like the gastrointestinal tract, and only few examples have been described in the ampulla of Vater. A new case of large-cell neuroendocrine carcinoma of the ampulla of Vater in a 60-year-old man is reported. After pancreatoduodenectomy, macroscopic examination revealed ulcerated tumor in the region of the ampulla of Vater. Microscopically, the tumor exhibited organoid, predominantly nested growth pattern, consisting of large, polygonal cells with pleomorphic nuclei. Average number of mitoses was 36 per 10 high-power fields. Small and large areas of necrosis were identified. Immunohistochemically, the tumor cells were positive for synaptophysin, chromogranin A, PGP 9.5, neuron-specific enolase, pancytokeratin, CK8 and somatostatin and negative for CK7, CK20, S-100, TTF-1, HMB-45, CD117, E-cadherin and regulatory peptides. Ki-67 proliferative index was 41%. Histone deacetylase (HDAC) analysis showed almost identical results for HDAC1, HDAC2 and HDAC3--60, 60.3 and 61%, respectively. Two months after surgery, liver metastases occurred, confirming highly aggressive behavior of large-cell neuroendocrine carcinoma.

Human Dirofilaria repens infection in Serbia.

Human infection by Dirofilaria repens in Serbia has been increasing steadily. The first case was reported in 1971, presented in the form of a single subcutaneous nodule on the back of a young boy. As established by a literature search, eight additional cases were reported until mid-2001. The most frequent site of infection was subcutaneous tissue, with the exception of two cases, in which parasites were found in subconjunctiva and epididymis. Our study, conducted from 2001 to 2008, encompasses 19 new cases. Most of them (63.1%) presented as ocular or periocular infections, in which the parasite was typically found under the conjunctiva. In other cases a parasitic nodule was localized in the temporal region of the head, epididymis, testicle, abdomen, breast or arm. The diagnosis was made by morphological and histological analysis of the extracted intact worms and parasite sections from the tissue. Morphology of the filarial worms was well preserved in more than half of the cases (12/19) and there was never more than one parasite found inside the lesions. Adult worms and immature nematodes were observed in nine and seven cases, respectively. Furthermore, in two cases microfilariae were discovered inside the pseudocoelom, sections of the female reproductive tubes filled with clearly visible larval stages. Dirofilaria repens infection was diagnosed by its morphological features (17/19) or by performing polymerase chain reactions (PCR) using paraffin-embedded tissues (2/19) in the cases where the morphology was insufficient for identification and the parasites had been determined initially as Dirofilaria spp. The amplified 246 bp PCR product showed that the worms were D. repens.

[Postoperative histopathologic findings in sino-nasal polyposis].

INTRODUCTION: Sino-nasal polyposis is a frequent condition in clinical practice and various pathohistological features that they exhibit can be significant for clinical picture and prognosis of the illness. Aim of this research was to examine pathohistological characteristics of sino-nasal polyposis and according to references from literature to make a pathohistological classification. MATERIALAND METHOD: In the period from May to October 2009. we have analyzed pathohistological characteristics of sino-nasal polyposis in 25 patients. All patients were operated with funcional endoscopic surgery at the Institute of Otorhinolaryngology and Maxillofacial Surgery and pathohistologycal researches were done at the Institute of Pathology, University Medical School of Belgrade. RESULTS: Pathohistological findings in all operated patients confirmed sino-nasal polyposis and classification was establish in following pattern: 16 patients with edematous or eosinophilic polyps (64%), 6 patients with fibro-inflamatory polyps (24%) and 3 patients with hyperplasia of sero-mucous glands (12%). In 3 cases (12%) we have found atypical stromal cells but because of the rest of predominant pathohistological characteristics we did not separate these patients in additional group. CONCLUSION: Edematous or eosinophilic polyps represents predominant pathohistological type which is according to data from literature.

[Fungal sinusitis diagnostic management and classification].

The aim of this paper is to present the current classification of fungal sinusitis and share our experiences in diagnostic procedures and treatment outcomes. The study includes 31 patients operated since 2000-2009 in whom some form of fungal infection had been dignosed. There were 10 patients with mycetoma, and 16 patients with chronic non-invasive fungal sinusitis, while in five patients allergic fungal sinusitis was proven. All patients were treated postoperatively with topical steroids and irrigation with saline solution, without use of fungicides. Characteristics of chronic non-invasive fungal sinusitis and mycetoma are CT with specific opacification and calcification with involement of maxillary sinus unilaterally or bilateral together with pathohistological finding of positive staining by Grocott with the identification of fungi from secret or tissue. Allergic fungal Sinusitis is characterized by eosinophilia, positive skin test to fungal allergens, elevated serum level of both specific IgE antibodies to causal fungus and total IgE, as well as, pathohistological finding of allergic mucus which include non-invasive hifa. Fungal sinusitis in immunocompetent patients is classified into the following categories: mycetoma, chronic non-invasive fungal sinusitis, chronic indolent sinusitis (which does not occur in our population) and allergic fungal sinusitis.

Granular cell tumor of the common hepatic duct presenting as cholangiocarcinoma and acute acalculous cholecystitis.

Granular cell tumors (GCT) are rare benign tumors. Less than 1% of GCTs involve the extrahepatic biliary tree. Most researches favour a Schwann cell origin. Patient, caucasion, female, 31-year-old presented with 4 month history of painless jaundice and pruritus. US and CT revealed dilatation of intrahepatic biliary tree and surgery was performed. Firm tumor mass was found above the conjunction of cystic duct and common hepatic duct (CHD) that caused obstruction and gallblader empyema. The patient underwent radical surgical procedure because Klatskin tumor was clinically suspected. Patohystology and immunohistochemistry confirmed granular cell tumor. Eight years after surgery the patient is wellbeing without symptoms. To our knowledge 69 cases of GCT of the extrahepatic biliary tree have been reported and none of the acute acalculous cholecystitis case acompanied by GCT of CHD. Granular cell tumors are rarely diagnosed preoperatively. Wide resection offers the best chance for cure.

[Retrohepatic veins of the posterior section of the right hepatic lobe--terminology and surgical significance].

Three main hepatic veins: right, middle and left are constant, but there is a variable number of retrohepatic vessels called accessory or minor hepatic veins. The most important of them are veins reffered to as middle right hepatic vein (MRHV) draining segment VII and inferior right hepatic vein (IRHV) draining segment VI. The incidence of large MRHV and IRHV reaching or exceeding a caliber of 5mm, their arrangement in the liver and drainage territories were investigated in our collection of 142 injection-corrosion specimens of the liver. In 1/5 of the cases with large IRHV this vein drains small part of segment VI, sometimes its insignificant marginal part so it couldn't be used for segment VI preservation when it is necessary. A precise knowledge of the vein anatomy of right posterior sector of the liver and its vein drainage territories is very important during complex dissections of the retrohepatic areas, resections and preservation liver parenchima.

Cyclin A and beta-catenin expression in actinic keratosis, Bowen's disease and invasive squamous cell carcinoma of the skin.

BACKGROUND: Actinic keratosis (AK) has been defined as a precancerous lesion or an early phase in the evolution of squamous cell carcinoma (SCC) and histological changes seen in the individual cells of an AK are indistinguishable from those seen in SCC, which invade the dermis. Cyclin A is an increasingly utilized proliferation marker that has functions in both S phase (DNA replication) and initiation of mitosis, whereas alterations of beta-catenin, the molecule involved in cell-cell adhesion and in signalling transduction, could promote invasive and proliferative capacities of malignant tumours. OBJECTIVES: To determine cyclin A and beta-catenin expression pattern in cutaneous SCC and in in situ lesions classified as keratinocytic intraepidermal neoplasia (KIN) and, using traditional terms, as AK and Bowen's disease (BD), and to analyse it in relation to SCC differentiation, diameter and thickness. METHODS: Immunohistochemical staining was performed on 110 formalin-fixed paraffin-embedded tissue samples with the streptavidin-biotin technique using antibodies to cyclin A and beta-catenin. On histological examination, 53 lesions were diagnosed as AK, 16 as BD and 41 as SCC-11 well differentiated (WD), 16 moderately differentiated (MD) and 14 poorly differentiated (PD). Using KIN classification, 22 lesions were KIN1, 23 were KIN2 and 24 were KIN3. For cyclin A, distribution and labelling index (LI), and for beta-catenin, level of membranous staining and presence of aberrant (nuclear/cytoplasmic) localization were examined. RESULTS: Diffuse cyclin A presence was observed more frequently in BD than in AK (P < 0.0001) or SCC (P = 0.0002), and in SCC-PD compared with SCC-WD (P < 0.0001) or SCC-MD (P = 0.0003). Differences between KIN3 and KIN2, as well as KIN3 and KIN1 lesions, were statistically significant (P < 0.0001), and the same result appeared when KIN1 and KIN2 cases were grouped and compared with those of KIN3 (P < 0.0001). Cyclin A LI was significantly lower (P < 0.05) in AK than in BD or SCC, but no difference between BD and SCC was found, and LI in BD was even higher than in SCC-WD or SCC-MD, while analysis regarding SCC differentiation and KIN classification revealed the same correlation as for the cyclin A distribution. Reduced or absent beta-catenin membranous staining was found in 90 cases (81.8%), more often in SCC than in AK (P = 0.03) or in AK and BD grouped together (P = 0.02). There was no statistical difference between SCCs of various level of differentiation, or between different KIN grades. Diffuse loss of membranous beta-catenin staining showed 36 lesions (32.7%), more frequently SCC than AK (P = 0.003) or AK and BD grouped (P = 0.006), as well as SCC-PD compared with SCC-WD (P = 0.01) and SCC-MD (P = 0.03), whereas all KIN comparisons remained nonsignificant. Aberrant beta-catenin cellular localization demonstrated 28 lesions (25.5%), most often in the basal or peripheral parts and in the lesions with diffuse beta-catenin loss (P = 0.009), but revealed no correlation with the histological type, SCC level of differentiation or KIN grades. Diffuse loss of membranous beta-catenin staining was found to be significantly more frequent in SCC thicker than 4 mm (P = 0.03), while all other comparisons between cyclin A or beta-catenin with the tumour size remained nonsignificant. Cyclin A LI was higher in cases with diffuse loss of membranous staining (P = 0.001) or with aberrant cellular localization of beta-catenin (P = 0.002). CONCLUSIONS: Cyclin A LI showed greater difference between AK and BD than between BD and SCC, suggesting that increased proliferation (measured by cyclin A LI) characterizes progression of in situ lesions from AK to BD, whereas reduced beta-catenin expression separates more clearly SCC from the in situ lesions. Diffuse pattern of loss of membranous beta-catenin staining correlated better with the type of lesion, SCC differentiation and tumour size than reduced expression in general or aberrant cellular localization of beta-catenin. KIN classification does not seem to be supported by our findings, except when KIN1 and KIN2 lesions (in situ, partial thickness) are grouped.

Umbilical metastasis (Sister Joseph's nodule) as a first sign of a disseminated ovarian carcinoma: comparative immunohistochemical analysis of primary tumor and its metastases.

The case of a 46-year-old female with umbilical metastasis as a first sign of an ovarian carcinoma is reported with the results of immunohistochemical analysis of primary tumor and lymph node and umbilical metastases. All specimens were positive for cytokeratin 7, CA 125, E-cadherin, alpha-, beta-, and gamma-catenin, as well as for MSH2. Staining with cytokeratin 20 and MLH1 was negative, and Ki-67 labeled from 5% (in the center of the lesions) to over 25% (at the periphery of the lesions) of the nuclei. Beta-catenin showed membranous positivity in the central parts and absence of staining at the periphery of ovarian tumor and umbilical metastasis, whereas lymph node metastasis presented with uniform reaction throughout. The results of immunohistochemical staining could point to the mechanisms employed by malignant tumors during invasion and growth of metastasis and suggest the possible role of the microenvironment in the expression of some adhesion molecules on tumor cells.

Giant nevus lipomatosus superficialis with multiple folliculosebaceous cystic hamartomas and dermoid cysts.

Nevus lipomatosus superficialis (NLS) is a rare benign condition characterized by papules and nodules usually in the pelvic and sacral areas, with ectopic mature adipose tissue reaching the superficial dermis. We report the case of a 47-year-old female with large NLS in the sacral region that had been present since birth and, after an asymptomatic course for most of the time, became associated with episodes of mild pain that prompted the patient to look for medical help. After a complete resection of the cerebriform plaque, measuring 23 cm in diameter, histopathological examination revealed typical NLS architecture in as yet undescribed association with multiple folliculosebaceous cystic hamartomas (FCHs) and dermoid cysts.

Patient with double cancer--successfully treated.

INTRODUCTION: Etiology of thrombosis in malignant diseases is multifactorial, and mechanisms that lead to thrombosis include release of the procoagulants from tumor cells (PC), factor related to bed rest, infections, as well as oncological therapy --chemotherapy, hormones, radiotherapy and surgical treatment. Thrombocytosis has frequently been found to be associated with various malignancies. CASE REPORT: 53 years old female patient hospitalised because of hypopharingeal cancer with metastasis in the left neck. Her state was complicated with deep leg vein trombosis and pseudomonas infection. Persistent thrombocitosis in laboratory monitoring indicated more adequate diagnostic procedures, which led to discovering of Chorioidal Malignant Mellanoma as a second cancer. She was treated: surgically, with antibiotics, with anticoagulants and radiotherapy. Patient was discharged from the hospital in good health condition, free of any other symptom of the malignant disease. CONCLUSION: Presense of thrombocytosis and idiopatic thrombosis can suggest occult malignancy. It would be prudent to further evaluate the relationship of trombotic events, trombocitosis and head and neck tumors. We suggest anticoagulants to prevent thromboembolic complications, affect the angiogenesis and prevent development of metastatic disease. It may lead to lower mortality rate.

[Primary liver cancer mortality in Belgrade population]. / Mortalitet od primarnih malignih tumora jetre u populaciji Beograda.

The aim of this analysis was to estimate death rates for primary liver cancer (PLC) and their secular trends in the population of Belgrade during the period 1982-2001. Mortality data (number of deaths caused by PLC) in Belgrade were obtained from the Belgrade Municipal Institute of Statistics (unpublished data). Death rates per 100,000 population were adjusted by direct method using world population as a standard. Regression coefficient was assessed by Fisher's test., Average annual age-adjusted mortality rate for PLC in Belgrade was 5.7/100,000 (95%CI-confidence interval 5.3-6.0), for males 7.5/100,000 (95%CI 7.0-7.9), and for females 4.2/100,000 (95%CI 3.8-4.7). The lowest mortality for PLC was in the age up to 45 (bellow 1/100,000) for both sexes, and the highest values were registered in the age group over 75, 71.1/100,000 (95%CI 62.2-84.0) for males, and 52.9/100,000 (95%CI 45.6-60.3) for females. Mortality trends for PLC in Belgrade in the period 1982-2001 showed increasing tendency in males (y=7.079+0.039x, p=0.331) and decreasing tendency in females (y=4.747-0.048x, p=0.199).

Comparative ultrastructural studies on mitochondrial pathology in the liver of AIDS patients: clusters of mitochondria, protuberances, "minimitochondria," vacuoles, and virus-like particles.

The present comparative conventional electron microscopic studies of the liver biopsy in 20 AIDS patients revealed numerous disintegrated mitochondria in hepatocytes, Kupffer cells lymphocytes, and eosinophile leukocytes. It was observed that (1) AIDS mitochondria are clustered, disorganized, and with protuberances; (2) the number of cristae is reduced and they are branched dichotomously; (3) vacuoles are located both within the mitochondria and, in their vicinity, (4) " minimitochondria" are within the ordinary mitochondria; (5) virus-like particles are at the periphery of electron-dense mitochondrial remains.

[Liver damage caused by sensitivity to anti-inflammatory agents]. / Ostecenja jetre izazvana senzibilizacijom na antiinflamacione lekove.

Nonsteroidal antiinflammatory drugs may cause hepatic sensibilization and impairment. The incidence of these changes is low and referential data are scarce and related mainly to reaction which clinically corresponds to hepatic or cholestatic reaction. We present a patient who is sensitive to Diclofenac and has hepatic granuloma which developed after the use of the drug. History, clinical presentation, laboratory results, US examination of the liver and pathohistologic analysis of the hepatic biopsy sample enabled us to diagnose hepatitis with granulomatous impairment. Improvement of symptoms and signs of the disease was spontaneous and without administration of glucocorticoid drugs.

Focal tuberculosis of the liver with local hemorrhage in a patient with acquired immunodeficiency syndrome.

Tuberculosis of the liver is common in patients with acquired immunodeficiency syndrome (AIDS). Tuberculous liver granulomas in such patients are usually atypical. The liver granulomas may be even totally absent, but liver tissue usually reveals numerous acid-fast bacilli. Focal tuberculosis of the liver is a less common form of liver tuberculous infection. We present a 33-year old white homosexual man infected with the human immunodeficiency virus. He had three tumour-like lesions in the left liver lobe, which were subsequently diagnosed as focal hepatic tuberculosis with local hemorrhage. This unusual presentation of liver tuberculosis indicates the necessity of an aggressive diagnostic approach for the evaluation of focal liver lesions in patients with AIDS.

The role of membrane water permeability in characterization of pathologically altered human stomach tissues: NMR studies.

Comparative NMR studies of normal and pathologically altered human stomach tissues were performed on the basis of proton T1 relaxation time measurements in the presence of high external concentrations of relaxation (contrast) agents manganese ethylenediaminetetraacetic acid (Mn-EDTA) and gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Diffusion permeability of the cell membrane to water, Pd, was determined by measuring the longest proton T1 component sensitive to the exchange of water molecules through the cell membrane. Pathologically altered tissues showed substantially higher (2 to 10 times) average cell membrane permeabilities to water.