Clinical Hospital Center Sestre milosrdnice

Zagreb, Croatia

Clinical Hospital Center Sestre milosrdnice

Zagreb, Croatia
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Dzombeta T.,University of Zagreb | Dzombeta T.,Clinical Hospital Center Sestre milosrdnice | Kruslin B.,University of Zagreb | Kruslin B.,Clinical Hospital Center Sestre milosrdnice
Pathology and Oncology Research | Year: 2017

Differentiation of noninvasive from invasive papillary urothelial carcinoma can be challenging due to inability of proper orientation and thermal damage of transurethrally obtained material. The aim of this study was to analyze the presence and extent of peritumoral retractions in pT1 compared to pTa papillary urothelial carcinoma. Since peritumoral retractions may result from altered expression profiles of extracellular matrix proteins, we additionally analyzed the expression of matrix metalloproteinase 2 (MMP-2) and interleukin 8 (IL-8) in these tumors. The study comprised 50 noninvasive (pTa) and 50 invasive (pT1) cases of transurethrally obtained primary papillary urothelial carcinomas. The invasive nature of nests showing peritumoral retractions was confirmed immunohistochemically using antibody against collagen IV. Staining for MMP-2 and IL-8 was evaluated semiquantitatively using immunohistochemical staining index, calculated by multiplying the percentage of positive cells and staining intensity. Peritumoral retractions were found in 32% of pT1 carcinomas but in none of the pTa carcinomas. All tumors showing peritumoral retraction were high grade tumors. There was no statistically significant correlation between the expression of MMP-2 or IL-8 and the presence of peritumoral retractions or stage of the tumor (pTa vs. pT1). A statistically significant but weak correlation was found between MMP-2 and IL-8 expression (χ2-test, p=0,015). There was no statistically significant correlation between the presence of peritumoral retractions or MMP-2 expression and tumor recurrence and progression. Our study shows that, in doubtful cases, when differentiating between pTa and pT1 stages of papillary urothelial carcinoma, the presence of peritumoral retractions could favor the diagnosis of invasive neoplasm. © 2017 Arányi Lajos Foundation

Van Der Horst M.P.J.,University of Edinburgh | Marusic Z.,Clinical Hospital Center Sestre Milosrdnice | Hornick J.L.,Harvard University | Luzar B.,University of Ljubljana | Brenn T.,University of Edinburgh
Modern Pathology | Year: 2015

Spiradenocarcinoma is a rare skin adnexal neoplasm with potential for aggressive behavior, classified histologically into low-and high-grade tumors. Morphologically, low-grade tumors are thought to behave more favorably. Limited information is available, however, with only 18 published cases. To study their clinical behavior, histological features, and the diagnostic value of immunohistochemistry, 19 morphologically low-grade spiradenocarcinomas were retrieved and compared with 21 spiradenomas and cylindromas. H&E-stained sections were reviewed, follow-up was obtained, and immunohistochemistry for Ki-67, p53 and, MYB was performed. The tumors were solitary, measuring 0.8-7 cm (median: 2.7 cm), with a predilection for the head and neck of elderly patients (median age: 72 years; range 53-92) without gender bias. Histologically, the tumors were multinodular and located in deep dermis and subcutis. A pre-existing spiradenoma was present in all cases. The malignant component was characterized by expansile growth with loss of the dual cell population, up to moderate cytological atypia and increased mitotic activity (median: 10/10 HPF; range 1-28). Additional findings included squamoid differentiation (n=9), necrosis (n=7), and ulceration (n=5). P53 expression was variable and no significant differences were noted in the benign compared with the malignant parts of the tumors. In contrast, in the malignant components the Ki-67 proliferative index was slightly increased, and MYB expression was lost. Follow-up (median: 67 months; range: 13-132) available for 16 patients (84%) revealed a local recurrence rate of 19% but no metastases or disease-related mortality. In this large study with long-term follow-up, we demonstrate that spiradenocarcinomas with low-grade morphology pursue an indolent course, characterized by local recurrence only. Metastases and disease-related mortality appear to be exceptional. Lack of MYB expression may be useful as an additional aid in the diagnosis of these challenging tumors. © 2015 USCAP, Inc. All rights reserved.

PubMed | Clinical Hospital Center Sestre milosrdnice, University of British Columbia, Biopticka Laborator, Herzegovina University and 2 more.
Type: | Journal: Annals of diagnostic pathology | Year: 2016

Conflicting data have been published on the prognostic significance of tumor necrosis in papillary renal cell carcinoma (PRCC). Although the presence of necrosis is generally considered an adverse prognostic feature in PRCC, we report a cohort of 10 morphologically distinct cystic and extensively necrotic PRCC with favorable biological behavior. Ten cases of type 1 PRCC with a uniform morphologic pattern were selected from the 19 500 renal tumors, of which 1311 were PRCCs in our registry. We focused on precise morphologic diagnosis supported by immunohistochemical and molecular-genetic analysis. Patients included 8 men and 2 women with an age range of 32-85 years (mean, 62.6 years). Tumor size ranged from 6 to 14 cm (mean, 9.4 cm). Follow-up data were available in 7 patients, ranging from 0.5 to 14 years (mean, 4 years). All tumors were spherical, cystic, and circumscribed by a thick fibrous capsule, filled with hemorrhagic/necrotic contents. Limited viable neoplastic tissue was present only as a thin rim in the inner surface of the cyst wall, consistent with type 1 PRCC. All cases were positive for AMACR, OSCAR, CAM 5.2, HIF-2, and vimentin. Chromosome 7 and 17 polysomy was found in 5 of 9 analyzable cases, 2 cases demonstrated chromosome 7 and 17 disomy, and 1 case showed only chromosome 17 polysomy. Loss of chromosome Y was found in 5 cases, including 1 case with disomic chromosomes 7 and 17. No VHL gene abnormalities were found. Papillary renal cell carcinoma type 1 can present as a large hemorrhagic/necrotic unicystic lesion with a thick fibroleiomyomatous capsule. Most cases showed a chromosomal numerical aberration pattern characteristic of PRCC. All tumors followed a nonaggressive clinical course. Large liquefactive necrosis should not necessarily be considered an adverse prognostic feature, particularly in a subset of type 1 PRCC with unilocular cysts filled with necrotic/hemorrhagic material.

PubMed | University of Tirana, County Emergency Hospital, Clinical Hospital Center Sestre Milosrdnice, Multiprofile Hospital for Active Treatment and 7 more.
Type: | Journal: Scientific reports | Year: 2016

Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary real-world AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.110.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the truly low-risk patients (CHA2DS2-VASc=0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5%22.3%). Age80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region.

Augustin G.,University of Zagreb | Zigman T.,University of Zagreb | Davila S.,University of Zagreb | Udilljak T.,University of Zagreb | And 3 more authors.
Clinical Biomechanics | Year: 2012

Background: Bone drilling is a common step in operative fracture treatment and reconstructive surgery. During drilling elevated bone temperature is generated. Temperatures above 47 °C cause thermal osteonecrosis which contributes to screw loosening and subsequently implant failures and refractures. Methods: The current literature on bone drilling and thermal osteonecrosis is reviewed. The methodologies involved in the experimental and clinical studies are described and compared. Findings: Areas which require further investigation are highlighted and the potential use of more precise experimental setup and future technologies are addressed. Interpretation: Important drill and drilling parameters that could cause increase in bone temperature and hence thermal osteonecrosis are reviewed and discussed: drilling speed, drill feed rate, cooling, drill diameter, drill point angle, drill material and wearing, drilling depth, pre-drilling, drill geometry and bone cortical thickness. Experimental methods of temperature measurement during bone drilling are defined and thermal osteonecrosis is discussed with its pathophysiology, significance in bone surgery and methods for its minimization. © 2011 Elsevier Ltd. All rights reserved.

Zaja O.,Clinical Hospital Center Sestre Milosrdnice | Tiljak M.K.,University of Zagreb | Stefanovic M.,Clinical Hospital Center Sestre Milosrdnice | Tumbri J.,Clinical Hospital Center Sestre Milosrdnice | Jurcic Z.,Clinical Hospital Center Sestre Milosrdnice
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2014

Objective: The etiology of jaundice in otherwise healthy breastfed newborns that can present as early-onset exaggerated physiologic jaundice, or late breast milk jaundice (BMJ), is not yet entirely understood. This study tested the hypothesis that molecular marker for Gilbert's syndrome (GS), UGT1A1 TATA-box polymorphism, is associated with this disorders. Methods: We have investigated the UGT1A1 polymorphism frequency and its relation to severity of hyperbilirubinemia and jaundice duration among 220 exclusively breastfed term newborns; 57 of them with non-physiologic hyperbilirubinemia (NH), and 163 with BMJ, and in 187 healthy controls. Results: Significant differences in TA7/7 genotype frequency were established. The highest frequency was observed among the newborns with BMJ (42.0%), intermediate in the NH group (24.6%), while the controls had the lowest TA7/7 frequency (12.8%). Linear increase in TA7/7 frequency was observed depending on the duration of jaundice, peaking at 42.4% in newborns with the longest jaundice duration. Positive correlation between the serum bilirubin levels and the TATA-box length was established in all groups. Conclusion: This study provides evidence that UGT1A1 TATA-box polymorphism is an important risk factor for developing jaundice in term breastfed newborns, presented as either early non-physiologic hyperbilirubinemia or breast milk jaundice. These results further support the original Odell's idea of neonatal jaundice as an early presentation of GS. © 2014 Informa UK Ltd.

Augustin G.,University of Zagreb | Davila S.,University of Zagreb | Udilljak T.,University of Zagreb | Staroveski T.,University of Zagreb | And 2 more authors.
International Orthopaedics | Year: 2012

Purpose: Bone drilling causes an increase in bone temperature, and a temperature above 47°C is critical because it causes thermal bone necrosis. Thermal osteonecrosis is common with the drill diameter of ≥4.5 mm without cooling. The aim of this study was to determine the increase of bone temperature during drilling using newly contructed two-step and internally cooled drills. Methods: An experiment was set up according to a central composite design. An internally cooled drill (3.4 mm and 4.5 mm) and a two-step drill (2.5/3.4 and 3.4/4.5 mm) were used in combination with feed rates of (0.02, 0.04, 0.10, 0.16 and 0.18 mm/rev) and cutting speeds (1.18, 10.68, 33.61, 56.55 and 66.05 m/min) with and without cooling with water of 24°C. Bone temperatures were measured with thermocouples. Drilling was performed on pig diaphyses with a three-axis mini milling machine. Results: Bone temperatures in all combinations of parameters with internal cooling were below the critical 47°C (p00.05). The highest temperatures were detected using a 4.5-mm drill (40.5°C). A statistically significant effect other than cooling was found with the drill diameter and feed. A drill diameter of 3.4 mm with internal cooling developed a maximum temperature of 38.5°C and without cooling 46.3°C. For the same conditions a drill with diameter of 4.5 mm reached temperatures of 40.5°C and 55.7°C, respectively. The effect of feed rate is inversely proportional to the increase in bone temperature. With the feed rate 0.16 mm/rev, temperature was below critical even using the 4.5-mm drill (46.4°C, p00.05). Using the 3.4-mm drill all temperatures were below critical (46.2°C, p00.05). The two-step drill compared to a standard drill with the same diameter did not show statistical differences in maximum bone temperatures for all combinations of parameters (p00.05). Conclusions: A two-step drill does not have any advantages over a standard twist drill of the same diameter. An internally cooled drill causes a significantly smaller increase of bone temperature during drilling with water of 24°C. An internally cooled drill is currently the 'ideal' drill for traumatology/orthopaedics because it produces the smallest increase in bone drilling temperature. If internal cooling is used the regulation of other drilling parameters is of no importance. © Springer-Verlag 2012.

Savic Pavicin I.,University of Zagreb | Dumancic J.,University of Zagreb | Jukic T.,Clinical Hospital Center Sestre Milosrdnice | Badel T.,University of Zagreb | Badanjak A.,University of Zagreb
Dentomaxillofacial Radiology | Year: 2014

Objectives: To determine the correlation of skeletal bone mineral density (BMD) with mandibular density and mandibular radiographic indices estimated on digital panoramic radiographs.Methods: Study comprised 112 female subjects older than 45 years. Digital panoramic radiographs were taken, and patients were referred to densitometric measuring (dual energy X-ray absorptiometry) of BMD in the hip bones and lumbar spine regions (L1-L4). On the radiographs, mandibular bone density was estimated and the following indices were measured by the DIGORA® software (Soredex, Tuusula, Finland): mental index (MI), gonial index (GI), antegonial index (AI), panoramic mandibular index (PMI) and alveolar crest resorption degree (M/M). Mandibular cortical index (MCI) was visually estimated.Results: Mandibular density and visual index MCI are significant predictors of hip and spine BMD. Mandibular density was marked by a significant square trend: it decreased until the age of 54 years and remained constant until the age of 64 years when it started to increase. Significant correlations were found between MI, AI and PMI values and BMD in the hip but not in the lumbar spine region. The GI and M/M values did not show statistically significant correlations with BMD of either region.Conclusions: Mandibular bone density and mandibular radiographic indices are useful in detecting patients with decreased BMD. The applicability of orthopantomograms in diagnosing osteoporosis/osteopenia should be recognized as the potential greatest benefit of this everyday diagnostic method in dental practice. © 2014 The Authors.

Zivkovic M.V.,Clinical Hospital Center Sestre Milosrdnice | Dediol I.,Clinical Hospital Center Sestre Milosrdnice | Ljubicic I.,Clinical Hospital Center Sestre Milosrdnice | Situm M.,Clinical Hospital Center Sestre Milosrdnice
Journal of the European Academy of Dermatology and Venereology | Year: 2012

Background Melanoma is one of the most aggressive skin tumours for which the major risk factor is ultraviolet radiation. Sun protection is extremely important, especially for melanoma patients who, once diagnosed with melanoma, have 500 times greater chance of developing another melanoma than the general population. Objective In this study, we examined the perception of melanoma and attitudes towards sun protection among melanoma patients and compared their results with the patients suffering from other dermatological disorders. Methods In total, 240 participants were included in the study: 120 patients suffering from melanoma and 120 participants in the control group. The Sun Behaviour Patterns Questionnaire and the Brief Illness Perceptions Questionnaire were used in this study to assess sun behaviours and perception of melanoma. Results Melanoma patients have negative attitude towards sunbathing: 57% avoid sunbathing and 27% spend time in the sun only during swimming, otherwise seeking shade, whereas participants in the control group have more positive attitude towards sunbathing. Results indicate very short time of using sunscreen protection during the year and very small number of people using adequate SPF value, in both melanoma and control group. Conclusion Participants in control group perceive melanoma as a more serious illness than patients who think that melanoma has mild symptoms, is easy to cure and control, has moderate consequences and lasts relatively long. Both melanoma patients and participants in the control group show relatively good sun behaviour patterns and slightly negative attitudes towards sun protection. © 2011 European Academy of Dermatology and Venereology.

Marusic Z.,Clinical Hospital Center Sestre Milosrdnice | Buljan M.,Clinical Hospital Center Sestre Milosrdnice | Busam K.J.,Sloan Kettering Cancer Center
Journal of Cutaneous Pathology | Year: 2015

Background Multiple BAP1 negative melanocytic neoplasms are a hallmark of familial cancer susceptibility syndrome caused by BAP1 germline mutation. The syndrome is characterized by increased incidence of renal cell carcinoma, mesothelioma, cholangiocarcinoma, cutaneous and uveal melanoma and some other neoplasms. Methods We report histomorphologic characteristics of six cutaneous melanocytic neoplasms with loss of BAP1 expression in two members of a family with BAP1-associated cancer susceptibility syndrome. Results The neoplasms were dermal melanocytic nevi characterized by a proliferation of large epithelioid (spitzoid) melanocytes, and adipocytic metaplasia. Nuclear pseudoinclusions and multinucleated melanocytes were present in most neoplasms. In two of the cases, a nodular melanoma was found associated with a dermal nevus. None of the melanomas recurred or metastasized after 6 and 3 years of follow up. Conclusions We report two new cases of melanoma arising in a BAP1-deficient melanocytic nevus in the setting of familial tumor predisposition syndrome. Adipocytic metaplasia and nuclear pseudoinclusions may be additional morphologic clues to a BAP1-deficient nevus. It remains to be seen whether these features are more common in familial than sporadic lesions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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