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Cancer of unknown primary (CUP) site comprises very heterogeneous group of various malignant tumors presented in metastatic phase of the disease. Diagnosis is set when primary site remains unidentified after a thorough diagnostic evaluation in patients with histologically proven malignant metastatic disease. Despite poor prognosis in most patients, favorable prognostic clinical entities have been recognized constituting the most important group of patients for oncological treatment. The following text presents the clinical guidelines in order to standardize the diagnosis, treatment and follow-up of patients with cancer of unknown primary site in the Republic of Croatia.

Ultrazvučni rezač rabi mehaničke vibracije za istodobnu koagulaciju i rezanje. Cilj rada je prikazati naše iskustvo sa 161 bolesnikom operiranim s pomoću ovog instrumenta. Ultrazvučni rezač je korišten u razdoblju od 5 mjeseci za 123 operacije štitnjače, 13 parotidektomija te 25 tonzilektomija. U kontrolnoj skupini bolesnika učinjeno je 106 tiroidektomija, 9 parotidektomija te 30 tonzilektomija uz upotrebu elektrokoagulacije i ligatura kao primarnih hemostatskih postupaka. Upotrebom ultrazvučnog rezača trajanje operacija na štitnoj i parotidnoj žlijezdi skraćeno je za 20– 30% u usporedbi s konvencionalnim zahvatima. Kožna incizija kod zahvata na štitnjači u prosjeku je bila kraća 1, 5 cm. Prosječno trajanje tonzilektomije izvedene s pomoću ultrazvučnog rezača bilo je 5, 5 minuta kraće u odnosu na kontrolnu skupinu. Intenzitet boli, kao i postoperativne komplikacije, bile su komparabilne u obje skupine. Upotreba ultrazvučnog rezača skraćuje operativno vrijeme i smanjuje intraoperativni gubitak krvi te omogućuje manji kožni rez u kirurgiji štitnjače.

Although for inverted papillomas (IP) local aggressiveness and marked tendency to recur have been known for decades, association with squamous cell carcinoma (SCC) is still a subject of investigation since neither histologic feature nor local aggressiveness can be used as prognostic marker. According to our previous results and to results of other p53 and Ki67 immunohistochemistry have some diagnostic but little prognostic potential. We analyzed 50 cases of IP including 6 cases of synchronous SCC. The patients had diagnosed IP in the period from 1982 to 2005 at the Departments of Pathology, University in Zagreb, University of Osijek and the National Medical Center Budapest, Hungary. Immunohistochemistry for VEGF was performed according to manufacturers’ specification (Santa Cruz, USA). A PC based image analysis system (ISSA/SFORM, Vamstec, Zagreb) was used to determine the rate and intensity of nuclear staining. The histological pattern and intratumoral distribution of immunoreactivity was accessed together with the immunoreactivity of neighboring normal epithelium. Although the normal sinonasal epithelium shows VEGF immunoreactivity, the epithelium of both benign and malignant inverted papillomas demonstrated stronger reactivity following the histological pattern.

Thyroid nodules are today very common, because of widespread use of now diagnostic methods, specially ultrasonography. The prevalence of thyroid nodules by means of ultrasound is from 10-76 %. The goal of diagnostic procedure is to reduce unnecessary surgery of benign thyroid disese, and earlier treatment malignant nodules. to reduce morbidity and mortality. Diagnosis of thyroid nodules is now easy. After clinical examination and compiling a family history of thyroid disases, the diagnosis can be improved with sensitive TSH determination for evaluation of funcional status, use of high resolution ultrasound and on the basis of ultrasound findings application of fine needle aspiration biopsy. To be able to recognize typical echografhic features suspected of malignancy and to select the nodule for FNAB, an experienced physician is needed. FNAB is the most important method for differentiating benign from malignant thyroid nodules. It is generally accepted that FNAB must be done under US guidance. After the recommended diagnostic procedure, a decision can be made on appropriate therapy. Conclusion: US is the most important method for detection of thyroid nodules. Decision on which nodule must be submitted to FNAB made a physician with experience in utrasound. If echographic criteria suggest malignancy, the size of nodule is not important.

Prikazali smo dio molekularno genetičkih istraživanja malignog švanoma u obitelji sa više oboljelih članova. Željeli smo vidjeti da li novootkriveni signalni put Hedgehog/Patched je uključen u patogenezu ovog oboljenja. Desert Hedgehog i Sonic Hedgehog su ligandi za transmembranski receptor Ptch, koji sa koreceptorom Smo prenosi signal u stanicu. Tijekom razvoja Švan stanice izlučuju ligand Desert Hedgehog, koji se veže na receptor i može se odrediti u mezenhimu. Prema podacima u literaturi Desert hedgehog uključen je u prijenos signala između neurona i Švan stanica. Izolirali smo DNK iz tkiva švanoma jednog od oboljelih članova jedne obitelji sa malignim švanomom te umnožili lančanom reakcijom polimeraze koristeći polimorfne biljege iz regije 9q22.3 : D9S180, D9S287 i PTCH intra. Dva biljega su u blizini PTCH a jedan je unutar introna samog gena PTCH. Nastojali smo pokazati da gubitak funkcije PTCH utječe na maligni tok bolesti.

Retrosternalno smještene štitnjače traže zahtijvniji dijagnostički i terapijski pristup. Zbog svog nepovoljnog smještaja u medijastinumu ultrazvučna, citološka i scintigrafska obrada nije uvijek pouzdana zbog otežanog ili nemogućeg prikaza dijela štitnjače iza prsne kosti.Zbog mogućeg pomaka anatomskih struktura, teže idetifikacije povratnog živca i doštitnih žlijezda, veće mogućnosti intraoperativnog krvarenja, kiruški zahvat je složeniji i zahtijevniji. Iako se većina retrosternalnih struma može odstraniti kroz cervikalnu inciziju, operater mora biti svjestan ograničenosti tog pristupa i biti spreman na eventualnu strenotomiju i produljeni poslijeoperacijski oporavak. Prikazat ćemo naša iskustva i rezultete u liječenju retrosternalne strume..

Invertni papilom je epitelna neoplazma lateralnog zida nosa i susjednih sinusa karakteriziran sklonosti ponovnog javljanja i značajno povezan s karcinomom. Do sada nije bilo pouzdanih indikacijskih kriterija sklonosti ponovnog javljanja tumora niti maligne alteracije. Ispitivali smo moguću prognostičku važnost p53 i Ki67 u ovim tumorima. U studiju su bili uključeni 41 pacijent sa 49 biopsija (15 od rekurirajuće bolesti) iz tri bolnice. 8 pacijenata je imalo ili istovremeni ili metakroni karcinom. p53 imunoreakcija je dokazana u većini karcinoma, no u samo dva papiloma, dok je jača imunoreakcija Ki67dokazana u karcinomima i okolnom promijenjenom epitelu. Zaključili smo da imunohistokemijsko bojanje invertnih papiloma sinusa na p53 i Ki67 mogu pružiti korisne informacije glede prisutnosti istovremenog karcinoma.

Inverted papilloma is an epithelial neoplasm of the lateral nasal wall and adjacent sinuses characterized by a marked propensity for recurrence and a significant association with carcinoma In this retrospective study we present 31 cases treated by our departments between 1982 and 1999. The aim was to compare our results to those of other authors especially regarding surgical management. The male to female ratio of these patients was 2:1 and most patients were in the 6th and 7th decades of life. Conservative surgery was used in most cases as the initial treatment. The overall recurrence rate was low and there were 3 cases associated with carcinoma. We conclude that the results of conservative surgery in selected cases are comparable to those using radical methods. A review of the literature is presented and particular attention is dedicated to the literature concerning analysis of p53 expression, HPV and Epstein-Barr infection and apo-ptosis in inverted papilloma.

U kirurgiji diferenciranog karcinoma štitnjače postoje mnogi pokušaji da se preko različitih prognostičkih činitelja odredi optimalno kirurško liječenje (GAMES, AGES, MACIS, AMES, DAMES). Noviji pristup ovoj problematici, obzirom na preživljenje, dijeli bolesnike u tri grupe: grupa niskog rizika, grupa srednjeg rizika, grupa visokog rizika, uzimajući u obzir dob bolesnika, veličinu tumora, njegovu proširenost, te stupanj malignosti i udaljene metastaze. U ovom selektivnom pristupu kirurško liječenje ovisi o rizičnoj grupi u koju bolesnik pripada: grupa niskog rizika - lobektomija, grupa srednjeg rizika - strogo individualni pristup, grupa visokog rizika - terapija istovjetna u nas uobičajenoj totalnoj kirurškoj ablaciji štitnjače.

P53 je tumor supresorski gen koji ima značajnu ulogu u patogenezi mnogih vrsta karcinoma u ljudi uključujući glavu i vrat. Mutirani p53 protein može se otkriti rutinskim imunohistokemijskim tehnikama. Invertni papilom nosa i sinusa rijedak je benigni tumor koji čini 0, 5-4% svih primarnih tumora nosa. Uočeno je da ima izrazitu sklonost recidiviranju koja se u literaturi kreće između 13-70%, te značajnu povezanost s karcinomom. Učestalost karcinoma udruženog s invertnim papilomom je 10-20% i može se očitovati kao sinhroni karcinom koji je prisutan u trenutku inicijalne dijagnoze invertnog papiloma ili se karcinom razvija naknadno na mjestu gdje je prethodno odstranjen invertni papilom (metakroni karcinom). Cilj ovoga rada bio je analizirati prisutnost p53 mutacije u invertnom papilomu i udruženost s malignitetom. Analizirali smo 39 uzoraka invertnog papiloma od 31 bolesnika s inverinim papilornom. Klinički podaci pokazuju da je invertni papilom bio češći u muškaraca i to najčešće u 6. i 7. desetljeću života. Kod većine ispitivanih bolesnika inicijalno je učinjena konzervativna resekcija tumora. Učestalost recidiva bila je niska, 16%. Tri bolesnika su imala sinhroni karcinom, nije bilo bolesnika s metakronim karcinomom. Za obradu rezultata imunohistokernije upotrijebljena je semiautomatska kompjutorska analiza. Osam uzoraka invertnog papiloma bilo je p53 pozitivno, 5 invertnih papiloma s malignitetom i 3 benigna invertna papiloma. U statističkoj obradi Fisherov exact test je pokazao značajnu povezanost prekomjerne ekspresije p53 proteina i maligniteta. Zbog malog broja uzoraka nije se mogla statistički utvrditi povezanost recidiviranja i p53 pozitivnosti. Možemo zaključiti da gen p53 igra značajnu ulogu u patogenezi planocelularnog karcinoma povezanog s invertnim papilomom.

Eozinofilni granulom, rijedak oblik granulomatoze glave i vrata, poremećaj nepoznate etiologije, karakteriziran je abnormalnom proliferacijom histiocita koji infiltriraju kosti, sluznicu, epidermis i/ili unutarnje organe. U radu je prikazan iznimno rijedak slučaj izoliranog eozinofilnog granuloma štitnjače te njegova dijagnostika i liječenje.

Tritonov tumor, sarkom ovojnica perifernih živaca tj. maligni švanom s rabdomioblastičnom komponentom je rijetki, visoko maligni tumor glave i vrata s vrlo visokom stopom recidiva i niskim petogodišnjim preživljenjem. U radu je prikazan slučaj Tritonovog tumora desne orbite i etmoida te njegova dijagnostika i liječenje

Our previous investigations demonstrated prognostic significance for cathepsin D immunoreactivity in laryngeal SCC. We also demonstrated heterogeneity for AgNOR and DNA content in different areas of LSCC showing prognostic potential for DNA content of invasive tumor border. As this heterogeneity is a potential source of highly variable results we decided to investigate cathepsin D parameters in different microscopically defined tumor areas of LSCC. Patients and methods: 100 total laryngectomy specimen have been immunostained with anti-cathepsin D antibody (DAKO). Three distinct regions were analyzed: transformation zone, invasive tumor margin and tumor center. Immunoreactivity in tumor and stromal cells was accessed by scoring (0 - 4) in at least 200 cells respectively. Tumor and stromal cell positivity was accessed in the most positive area of tumor staining of the respective tumor region. Results and conclusion. Significant difference of immunostaining was observed between tumor invasive margin and the other regions. In most cases the invasive margin was the most prominently stained region for tumor as well as for stromal cells. Most patients showed stronger staining of stromal than tumoral cells. Only patients with survival less than 30 months showed stronger tumor than stromal cell staining in invasive margin. From this we can conclude that the basis for cathepsin D prognostic value in laryngeal SCC lies in the tumor/stromal cell correlation of cathepsin D immunoreactivity of the invasive tumor margin.

Invertni papilom, rijedak je benigni, lokalno agresivni epitelni tumor nosa i paranazalnih sinusa sa značajnom sklonošću recidiviranju i malignoj transformaciji. U radu je prikazan 31 slučaj invertnog papiloma liječenih od 1982. do 1999. godine. Komparirali smo naše rezultate s rezultatima drugih autora i to obzirom na kirurško liječenje (konzervativna kirurgija u većini slučajeva kao inicijalni tretman i funkcionalna endoskopska kirurgija sinusa kao novija metoda liječenja). U pregledu literature naročita je pozornost posvećena analizi recidiva s obzirom na kirurško liječenje, zatim malignoj transformaciji, p53 ekspresiji, HPV i Epstein-Barr virus infekcijama, te apoptozi povezanoj s invertnim papilomom.

The use of hyperthermia in cancer treatment has been more studied in last two decades. Heat is frequently used with irradiation and/or cytostatcs. The aim of this study was to investigate the antitumour effect of heat, drugs and radiation on the growth of mouse mammary carcinoma and melanoma implanted into mouse footpad. When tumour volume was cca 200 mm3 in size animals were treated with heat, heat+drug and/or radiation. Drugs (cisplatin, etoposide, ifosfamide and cyclophosphamide) were dissolved in saline and given i.p. Heat was applied by immersing footpad of tumour bearing leg into water bath at 43.5°C/60 min. The end point was the time needed for treated tumour to increase its volume fivefold. The obtained data have shown that heat increases tumour growth time three times while drugs increase tumour growth time from twice to thrice. However, when heat and drugs were applied simultaneously antitumour effect was synergistic for cisplatin, ifosfamide and cyclophosphamide while etoposide gives the best antitumour effect when given 72 h before heat. If radiation and heat were combined the best antitumour effect was achieved when radiation was given 4 h before heat. When all three treatments were applied together antitumour effect was only additive.

Competitiveness of tourist destinations is a complex process, which primarily follow some basic starting points contained in the definition of tourism, health tourism, environmental sustainability and competitiveness in gneral. Tourism compromises of the activities of persons traveling to and staying in place outside their usual environment for leisure, business and other purposes(UNWTO). Health tourism is any kind of travel to make yourself or a member of your family healthier (Tabacchi, Cornell University's) Medical tourism is a direct result of globalization of healthcare. The medical tourism is the set of activities in which a person travels often long distance or across the border, to avail medical services with direct or indirect engagement in leisure, business or other purposes. Emergency or critical care travels should not be considered as medical tourism. (Jagyasi. Travel medicine is a multidisciplinary and complex approach to the tourists in the protection and improvement of his health while traveling and staying at the destination (before, during and after), which is based on almost all branches of medicine (Croatian National Institute of Public Health). Environmentally responsible tourism involves travel and visitation to relatively undisturbed natural areas with the object of enjoying, admiring, and studying the nature (the scenery, wild plants and animals), as well as any cultural aspect (both past and present) found in these areas, through a process which promotes conservation, has a low impact on the environment and on culture and favors the active and socio-economically beneficial involvement of local communities (Ceballos-Lascuráin). This paper is based on the main sources of Kvarner tourim offerim assessing: "Towards quality coastal tourism, IQM–Integrated Quality Management of coastal tourism destinations", EU level research, Enterprise Directorate General Tourism Unit, EU, Brussels – methodological approach (1999 - 2003, "Research of tourists’ satisfaction at the County Primorsko-Goranska //tourist destination KVARNER, Republic of Croatia", a I part of the research results on the project “Tourism Regionalization in Global Processes” , supported by Ministry of science, education and sport, No 0116003 (2004), "Master plan of tourism development in County Primorsko-Goranska//tourist destination KVARNER"(2005), "Research of tourists’ satisfaction at the County Primorsko-Goranska//tourist destination KVARNER, Republic of Croatia", a II part of research results on the project “Tourism Regionalization in Global Processes”, supported by Ministry of science, education and sport, No 0116003 (2007), Projekt "Assessment of environment care, in the Croatian tourism and hospitality industry"(2010), and "The results of the monitoring process of the Master plan of tourism development in County Primorsko-goranska//tourist destination KVARNER"(2011). The conclusion of this researche was, as follow: (1) urgently issue the missing legislation and strategic documents for all areas of health tourism (2) introduce the classification and standardization in health tourism offer, based on internationally accepted standards, best world practices and the historical experiences of the achieved level of development of health tourism in Croatia (3) install the system of certification and licensing of health tourism offer and health-eco tourism destination in Croatia (4) converted achieved comparative advantage into competitive advantage, to be successfully economic evaluate on the tourism market.

Papillary thyroid carcinoma and diffuse lung infiltrates....

The introduction of aspiration cytology into the preoperative diagnosis of thyroid disease in the 1970s has reduced the rate of thyroid surgery by 50% while increasing the rate of patients with neoplastic nodules undergoing surgery by 10-15% (according to some authors even up to 20-50%). Ultrasonography enables the detection of nonpalpable nodules, identification of suspicious nodules for performing fine-needle aspiration (FNA) biopsy and targeted cytological biopsy in order to obtain adequate material. Reduction of the number of unnecessary surgical procedures with an increase in the required surgery rate essentially depends on the specificity and sensitivity of the cytological diagnosis of benign and malignant thyroid tumors. Cytologic features of papillary carcinoma (~80% of malignancies) are clearly defined and include nuclear inclusions, irregular and overlapping nuclei, psammoma bodies and papillary formations with fibrovascular stroma. This form of thyroid neoplasm is rarely primarily diagnosed as a metastatic process in the cervical lymph nodes and even more rarely as metastasis to distant organs (lungs, etc.) when the size of the primary tumor in the thyroid is

Objectives: Salivary gland tumours are uncommon and unique in their morphologic complexity, variability and overlapping, thus making it more difficult to acquire diagnostic expertise in fine needle aspiration cytology (FNAC). Very few reports have focused solely on intraoral minor salivary gland tumour especially in cytology. The purpose of this study was to asses the value of FNAC in lesions' differentiation. Methods: Within five years 66 FNAC of minor salivary gland lesions have been performed by a cytologist. We acquired adequate material from 58 (87.9 %) patients. FNAC was performed using 23G needle attached to 20ml syringe. The smears were stained with MGG, Papanicoalou and cytochemical staining. The cytological diagnoses were compared with histopathological ones. Results: A total of 41 patients underwent surgery: 21 with benign and 20 with malignant tumours. The two most common tumours were pleomorphic adenoma (16 patients) and adenoid cystic carcinoma (12 patients). The most commonly affected site was the palate (34 patients). The team work of cytologist and surgeon enables specificity of 95.2%, sensitivity of 95% and diagnostic accuracy of 95.1%. Conclusions: It is very important to know whether the lesion is malignant or benign for planning surgery and may prompt or postpone decision for surgical intervention. Close co-operation of surgeon and cytologist performing FNAC enables more accurate preoperative cytological diagnoses of minor salivary gland tumours