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Objective Desmoplastic small round cell tumor (DSRCT) is a rare intraabdominal neoplasm that grows along serosal surfaces and is primarily found in young men. To date, only 16 cases of ovarian DSRCT have been previously reported in women in the English literature, and no large population-based studies on this topic exist. Case Report We report the case of a 19-year-old virgo with unremarkable past medical history, initially presented with abdominal fullness. After being treated with the optimal treatment modality (primary and secondary surgical debulking, unique chemotherapy, protocol and adjuvant radiotherapy), the patient has remained without tumor disease for 40 months. Conclusion Although the best therapy for patients with DSRCT has yet to be determined, combining complete surgical resection, adjuvant chemotherapy, and radiotherapy is required to prolong survival and to achieve proper quality of life.

Introduction Bevacizumab is a recombinant humanized monoclonal antibody to vascular endothelial growth factor. It is an effective treatment for epithelial ovarian cancer, both in primary and recurrent disease. The incidence of ovarian cancer increases with advancing age. Despite the high prevalence of the ovarian cancer in elderly, the management of these patients is often less aggressive than that in younger patients. Our aim was to investigate the safety of bevacizumab administration in patients older than 65 years. Methodology Retrospectively, we have analysed the medical data of 65 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer who started treatment with bevacizumab in primary advanced and in first relapse of the disease at the Department of Gynaecologic Oncology in the University Hospital Centre Zagreb in the period from April 2017 to December 2018. Patients are divided in two categories according to age: group 1 (>65 years) and group 2 (≤65 years). Results Our analysis included 65 patients:18 (27,7%) patients in group 1 compared with 47 (72.3%) in group 2. Bevacizumab have been administered to 38 (58.5%) patients as first-line treatment and to 27 (41.5%) patients as second-line treatment. The median age was 70 (range 66–76) years in group 1 and 55 (range 35–65) in group 2. ECOG performance status 0 had 44.7% of patients in group 2 compared with only 33.3% in group 1. At the time of diagnosis, elderly patients had presented with at least one comorbidity in 66.6% of the cases, compared with 40.4% in group 2. The median number of cycles of bevacizumab was 9 in elderly patients and 17 cycles in group 2. Among those patients receiving bevacizumab in the first-line setting, median progression free interval (PFI) was 12 months in younger patients versus 7 months in elderly patients. Similarly, among those receiving bevacizumab in the second-line setting PFI was 9 months in younger patients versus 1 months in elderly patients. The occurrence of adverse events did not increase in elderly patients; 51.1% of patients in group 2 reported some adverse events versus only 27.8% in elderly patients. Conclusion In Croatia, from February 2017 we have opportunity to treat patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer with bevacizumab in the first-line and second-line settings. Our experience in treating patients with bevacizumab shows good results with acceptable toxicity and our findings suggest that its use in the elderly population should be considered as safe and manageable. Disclosures The authors have declared no conflicts of interest.

Introduction: Cervical cancer is one of the most common malignant tumors of the female reproductive system in women between 15-35 years of age. It takes third place in the frequency of all reproductive system cancers in Croatia. The aim of the present study was to analyze prognostic factors influencing on reccurence to improve therapeutic management. Materials and Methods: We reviewed medical records and pathological materials obtained from 61 patients with stage IA2-IB2 between 2003 and 2013. The comparison of women with and without recurrence showed statistical significance in certain factors; age when diagnosed, size of tumor, depth of stromal invasion, lymph vascular space invasion, infiltration of the uterine isthmus and lymph node metastases. Results: Median age at diagnosis was 46 years. Lymph-vascular space invasion (LVSI) was present in 22 (36.1%) with cervical isthmus involvement in 18 (29.5%) patients. Tumor recurrence within observation interval was present in 6 (9.8%) patients. Median time of reccurrence was 24 (range 14-48) months. In univariate statistical analysis lymph-vascular space invasion (P=0.011), cervical isthmus involvement (P=0.002) and positive lymph nodes (P=0.005) were significant parameters for occurrence of recidive while in multivariate statistical analysis cervical isthmus involvement (P=0.036) remained as only independent risk factor for recidive occurrence. Conclusion: Cervical isthmus involvement could be of prognostic importance especially in the early stage of cervical cancer when we might decide in adding radiotherapy and concomitant chemotherapy to improve overall survival and lower recurrence rate.

Objectives The aim of this study was to determine RHESUS D GENE (RHD) allelic variants among Croatian D-negative blood donors and compare our results with respective data from other European countries. Background Altered or reduced D antigen expression can result in D variants, which can be mistyped and can lead to the alloimmunisation of the blood recipient. RHD genotyping can distinguish D variants: weak D, partial D and DEL, thus preventing alloimmunisation. Material/methods A total of 6523 samples obtained from D-negative Croatian donors were screened for the presence of RHD using the real-time polymerase chain reaction (PCR) method. PCR-SSP was performed for D variant genotyping by using commercial genotyping kits (Inno-Train, Kronberg, Germany). Genomic DNA sequencing for all 10 exons of the RHD was performed when the genotyping kits failed to assign a D variant. Results RHD molecular screening revealed 23 (0.35%) RHD-PCR positive samples, all C/E positive, in decreasing frequency: 11 hybrid RHD-CE (2-9) D-CE variants, 4 weak partial D type 11 and 2 weak D type 2. Six samples remained unresolved and were sequenced. For 12 of 23 samples (excluding large hybrids), an adsorption/elution of anti-D serum was performed, confirming that all 12 were RhD+. The calculated frequency of clinically significant D alleles in RhD-negative blood donors was 1:543 (0.18%) or 1:53 (1.89%) in C/E blood donors. Conclusion Data on the significant frequency of D variants among serologically D-negative blood donors in the north-eastern region of Croatia could help in introducing RHD molecular screening of blood donors in a routine workflow.

Manuscript describing initial experience with novel robotic platform the Senhance. We describe the technical aspects of surgery and the operative technique.

Epithelial ovarian cancer is the seventh most common cancer among women and the leading cause of gynecological cancer related deaths in Croatia. Approximately 70% of patients are diagnosed at an advanced stage of the disease (FIGO III and IV). The usual approach to treatment involves complete surgical cytoreduction (R0), followed by combined platinumbased chemotherapy. Bevacizumab is recommended to add to paclitaxel/carboplatin chemotherapy in patients diagnosed at FIGO IIIB and IIIC stage with residual disease after surgery and all patients FIGO IV stage of disease, which can extend the time to progression of the disease in these patients. In this retrospective study, we analyzed the medical data of 98 patients with newly diagnosed advanced FIGO IIIB-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer treated at the Department of Gynecology and Obstetrics in the University Hospital Centre Zagreb in the period from January 2017 to December 2018. We have analyzed the followingdata: age, ECOG status, FIGO stage of disease, principle of surgery, pathohistological type of the tumor, number and type of adjuvant chemotherapy, application of bevacizumab, number of bevacizumab cycles, side effects related to bevacizumab therapy. Data from 98 patients were obtained. The median age was 60 years. The most patients were ECOG status 0-1 (78 %). According to the pathohistological findings, 89 % of patients had serous carcinoma, 5% endometrioid carcinoma, 3% mucinous carcinoma, 1% clear cell carcinoma, 1% borderline tumors and 1% poorly differentiated epithelial carcinoma. Most of the patients (68.5%) were underwent to primary cytoreduction, 12% “interval debulking” operation, whereas biopsy was performed in only 19.5% patients. HIPEC during surgery had 6% of patients. Resection without residual disease was achieved in only 25.5% of patients underwent surgery, while in others were reported macroscopic residual disease after surgery. 87% of patients were treated with chemotherapy with paclitaxel and carboplatin in three weeks schedule. 38 patients received antiangiogenetic drug bevacizumab. After exclusion of patients with a poor general condition (ECOG 2-4) and patients with FIGO stage IIIB and IIIC without residual disease after surgery, the percentage of patients receiving bevacizumab was 56% in 2017 and 75% in 2018. The average number of received cycles was 13 (range 1-22), and 8 patients continued the therapy in May 2019. Sixty-eight percent of the patients which received bevacizumab did not have any side effects associated with the bevacizumab therapy. The most common side effects associated with the bevacizumab were hypertension, development of deep vein thrombosis, ileus and proteinuria. In Croatia, since February 2017, we have the possibility of using bevacizumab for the treatment of newly diagnosed ovarian cancer patients stage IV or incompletely resected patients stages III B and III C. Our results are in concordance with the literature data and show that we can safely add bevacizumab to the first line chemotherapy of advanced ovarian cancer., Epitelni rak jajnika je sedmi najčešći maligni tumor u ženskoj populaciji i najčešći uzrok smrti od malignih ginekoloških tumora u Hrvatskoj. U vrijeme dijagnoze, oko 70% bolesnica nalazi se u uznapredovalom stadiju bolesti (stadiji FIGO III i IV). Uobičajeni pristup liječenju uključuje pokušaj kompletne kirurške citoredukcije (R0), nakon koje slijedi kombinirana kemoterapija na bazi platine. Kod bolesnica stadija bolesti FIGO IIIB i IIIC kod kojih postoji ostatna bolest nakon operativnog zahvata ili pak kod stadija FIGO IV, preporučuje se kemoterapiji dodati inhibitor angiogeneze (bevacizumab), kojim se može produžiti vrijeme do progresije bolesti u tih bolesnica. Ovom retrospektivnom analizom obuhvatili smo medicinske podatke 98 bolesnica s novodijagnosticiranim uznapredovalim (FIGO IIIB-IV) epitelnim rakom jajnika, jajovoda ili primarnog peritonealnog raka liječenih u Klinici za ginekologiju i porodništvo, Kliničkog bolničkog centra Zagreb u razdoblju od 01.01.2017. do 31.12.2018. Ispitivali smo slijedeće parametre: dob, ECOG status, stadij bolesti, princip kirurškog liječenja, patohistološki tip tumora, tip i broj kemoterapijskih ciklusa, aplikacija bevacizumaba, broj ciklusa bevacizumaba, te nuspojave povezane sa terapijom bevacizumabom. Obrađeni su podaci 98 bolesnica. Prosječna dob bolesnica bila je 60 godina. Većina bolesnica bila je ECOG status 0-1 (78 %). Prema patohistološkom nalazu, serozni karcinom utvrđen je u 89% bolesnica, u 5% endometrioidni, 3% mucinozni, a po 1% su bili zastupljeni klarocelularni, bordeline tumori i slabo diferencirani epitelni karcinom. Većina bolesnica (68.5%) je podvrgnuta primarnoj citoredukciji, 12% “interval debulking” operaciji, dok je u 19.5% učinjena samo biopsija tumora. U 6% bolesnica je tijekom operacije proveden HIPEC. Resekcija bez rezidualne bolesti postignuta je u 25.5% bolesnica podvrgnutih operativnom zahvatu, dok je u drugih bolesnica zabilježena ostatna makroskopska bolest nakon operativnog zahvata. Trotjednom kemoterapijom paklitaksel/karboplatin liječeno je 87% bolesnica. Terapiju inhibitorom angiogeneze (bevacizumab) primilo je 38 bolesnica. Kada isključimo bolesnice lošeg općeg stanja (ECOG 2-4) te bolesnice bez ostatne makroskopske bolesti nakon operativnog zahvata stadija FIGO IIIB i IIIC, postotak bolesnica koje su primile bevacizumab bio je 56 % u 2017. godini i 75% u 2018.g. Prosječni broj primljenih ciklusa je 13 (raspon 1-22), a 8 bolesnica nastavilo je navedenu terapiju i u svibnju 2019. 68% bolesnica koje su liječene bevacizumabom nisu imale nikakvih nuspojava povezanih sa navedenom terapijom. Najčešće zabilježene nuspojave povezane s terapijom bevacizumabom bile su hipertenzija, razvoj duboke venske tromboze, ileus i proteinurija. U Hrvatskoj, od veljače 2017. godine imamo mogućnost primjene bevacizumaba u liječenju bolesnica s novodijagnosticiranim rakom jajnika stadija IV ili stadija IIIB i IIIC kod kojih postoji ostatna bolest nakon operativnog zahvata. Naši rezultati su u skladu s literaturnim podacima i pokazuju da sigurno možemo dodati bevacizumab prvolinijskom liječenju u bolesnica s uznapredovalim rakom jajnika.

BACKGROUND: Making a diagnosis of vulvar intraepithelial neoplasia in a young woman that mainly presents skin manifestations of lupus and with no other risk factors is a big challenge. CASE: The case of a 27-year-old woman with systemic lupus erythematosus and vulvar intraepithelial neoplasia is described. CONCLUSION: Even though progression of vulvar intraepithelial neoplasia to invasive planocellular carcinoma is rare, prompt and adequate diagnosis and treatment will lead to the best possible quality of life.

Change in the host and/or human papillomavirus (HPV) DNA methylation profile is probably one of the main factors responsible for the malignant progression of cervical lesions to cancer. To investigate those changes we studied 173 cervical samples with different grades of cervical lesion, from normal to cervical cancer. The methylation status of nine cellular gene promoters, CCNA1, CDH1, C13ORF18, DAPK1, HIC1, RARβ2, hTERT1, hTERT2 and TWIST1 was investigated by Methylation Specific Polymerase Chain Reaction (MSP). The methylation of HPV18 L1-gene was also investigated by MSP, while the methylated cytosines within four regions, L1, 5’LCR, enhancer, and promoter of the HPV16 genome covering 19 CpG sites were evaluated by bisulfite sequencing. Statistically significant methylation biomarkers distinguishing between cervical precursor lesions from normal cervix were primarily C13ORF18 and secondly CCNA1, and those distinguishing between cervical cancer from normal or cervical precursor lesions were CCNA1, C13ORF18, hTERT1, hTERT2 and TWIST1. In addition, the methylation analysis of individual CpG sites of the HPV16 genome in different sample groups, notably 7455 and 7694 sites, proved to be more important than the overall methylation frequency. The majority of HPV18 positive samples contained both methylated and unmethylated L1 gene, and samples with L1-gene methylated forms alone had better prognosis when correlated with the host cell gene promoters’ methylation profiles. In conclusion, both cellular and viral methylation biomarkers should be used for monitoring cervical lesion progression to prevent invasive cervical cancer.

We report on a patient who presented with symptoms of acute abdomen and sudden abdominal pain that had started 4 h before hospitalization. Emergent laparoscopy was immediately done. A perforated peptic ulcer in the anterior prepyloric region was detected and laparoscopically sutured. The patient’s postoperative course was uneventful. The risks and advantages of laparoscopic treatment of peptic ulcer perforation are further discussed.

Rak vrata maternice, u odnosu na malignome drugih ginekoloških sijela, jest bolest mlađih žena koja se može redovitim kontrolama i zdravstvenim odgojem prevenirati, a u slučaju pojave bolesti učinkovito liječiti. Metode liječenja uključuju kirurgiju, radioterapiju i kemoterapiju, ovisno o stadiju bolesti i općem stanju bolesnica. Odluku o liječenju donosi multidisciplinarni tim. S obzirom na važnost ove bolesti, potrebno je definirati i provoditi standardizirani pristup u dijagnostici, liječenju i praćenju ovih bolesnica. U tekstu koji slijedi iznesene su kliničke smjernice s ciljem implementacije standardiziranih postupaka u radu s bolesnicama s rakom vrata maternice u Republici Hrvatskoj., Cervical cancer, in comparison with other gynecological malignancies, mainly affects younger women. It can be prevented trough educational programs, screening and early detection. It also can be efficiently treated when it appears. Treatment modalities include surgery, chemotherapy and radiotherapy, according to the stage of the disease and patient condition. Treatment decisions should be made after multidisciplinary team discussion. Due to the significance of this disease it is important to define and implement standardized approach for diagnostic, treatment and monitoring algorithm as well. The following text presents the clinical guidelines in order to standardize the procedures and criteria for the diagnosis, management, treatment and monitoring of patients with uterine cervical cancer in the Republic of Croatia.

Genital human papillomavirus (HPV) infection is a most common sexually transmitted infection among women (Munoz et al., 2003). The immune system effectively repels most HPV infections, and is associated with strong localized cell mediated immune responses. However, approximately ten percent of individuals develop a persistent infection, with risk of development of high-grade precursor lesions and eventually invasive carcinoma (Stanley, 2006). The causal role of HPV in all cancers of the uterine cervix has been firmly established (zur Hausen, 1999; Walboomers et al., 1999; Bosch et al., 2008). Most cancers of the vulva and vagina are also induced by oncogenic HPV types. In precancerous lesions, most HPV genomes persist in an episomal state whereas, in many high-grade lesions and carcinomas, genomes are found integrated into the host chromosome. Two viral genes, E6 and E7, are invariably expressed in HPV-positive cancer cells. Their gene products are known to inactivate the major tumour suppressors, p53 and retinoblastoma protein (pRB), respectively. In addition, E6 oncoprotein is also capable to up regulate the expression of inhibitors of apoptosis, and E6 and E7 cooperate to effectively immortalise primary epithelial cells. Tumour formation is not an inevitable consequence of viral infection; it rather reflects the multi-step nature of oncogenesis where each step constitutes an independent (reversible or irreversible) genetic change that cumulatively contributes to deregulation of cell cycle, cell growth and survival.

Karcinom vrata maternice u svijetu je drugi po učestalosti u žena. U Hrvatskoj je na osmome mjestu zastupljenosti. Ova vrsta karcinoma je bolest mlađih žena. Cervikalne intraepitelijalne neoplazije i karcinom vrata maternice su povezani su s trajnom infekcijom visoko onkogenim sojevima HPV-a. Cijena liječenja bolesti ovisi o njenom stadiju. Cjepivo Cervarix, primijenjeno u još spolno neaktivnih djevojčica i djevojaka, je u multinacionalnim dvostruko slijepim randomiziranim studijama pokazalo svoju visoku učinkovitost u stvaranju cirkulirajućih protutijela u serumu te smanjenju prevalencije HPV infekcije, preinvazivnih lezija i karcinoma vrata maternice. Cjepivo Cervarix također smanjuje prevalenciju trajne infekcije HPV-om u spolno aktivnih žena. Korištenjem matematičkih modela, uz visoku učinkovitost cjepiva od 100%, predviđa se 60–75% smanjenje morbiditeta i mortaliteta od karcinoma vrata maternice. Analizom izravnih troškova liječenja karcinoma vrata maternice i neizravnih troškova te kvalitetom života i usporedbom s cijenom cijepljenja u Hrvatskoj bi se godišnje moglo uštedjeti oko 50 milijuna kuna., Cervical carcinoma is the second most fequent female carcinoma in the world. In Croatia it took the 8th place. Cervical intraepithelial neoplasms and cervical carcinoma are related to permanent infection caused by high oncogenic type of HPV. The cost of treatment and therapy depends on grade of disease. In multinational double blinded randomised studies Cervarix vaccine has demonstrated its high efficiency in production of circulating serum antibodies, and the decrement of prevalence of HPV infection, preinvasive lesions and cervical carcinoma when applied in sexually not active adolescents. Cervarix vaccine also decreases the prevalence of permanent infections caused by HPV in sexually active women. Using mathematical models and considering high vaccine efficiency, it is predicted decrease of morbidity and mortality due to cervical carcinoma by 60–75%. When direct and indirect costs of therapy of cervical carcinoma and life quality were compared to cost of vaccination by Cervarix, it could be saved more than 50 milions of kunas in Croatia annually.

We report the case of an acquired large arteriovenous malformation due to invasive gestational trophoblastic tumor that was treated successfully with laparoscopic surgery. After 4 cycles of methotrexate chemotherapy, a vascular tangle (volume, 28 cm(3)) was noted that emerged from the right uterine horn, invading the broad ligament adjacent to the uterine artery. Doppler ultrasonography along with magnetic resonance arteriography confirmed the diagnosis. The location, size and relation of this arteriovenous malformation to the uterine vasculature demanded urgent intervention. Laparoscopy was performed, and bipolar coagulation of the ovarian and uterine artery feeding branches was achieved after surgical resection of the tumor. The defect in the uterine wall with an intact uterine cavity was reconstructed using sutures. There were no intraoperative or postoperative complications. The patient underwent chemotherapy, and at 2- month follow-up was cured and has since had regular menstrual cycles.

Humani papilomavirus (HPV) glavni je etiološki čimbenik zloćudne preobrazbe vrata maternice. Najvećim dijelom zloćudna preobrazba stidnice i rodnice također je inducirana ovim virusom. Humani papilomavirusi odlično su prilagođeni svom prirodnom domaćinu, epitelnim stanicama kože i sluznica, koristeći se njihovim staničnim mehanizmima za svoje potrebe. U prvom koraku nastaje mikrotrauma i infekcija bazalnog sloja višeslojnoga pločastog epitela genitalnog trakta. Virus se veže za staničnu membranu, ulazi u stanicu i razmnožava se u jezgri. Ključnu ulogu u replikaciji virusa imaju virusni proteini E6 i E7. Vezanje onkoproteina E7 za protein Rb aktivira transkripcijski faktor E2F, koji je odgovoran za ekspresiju proteina potrebnih za replikaciju DNK. Nepravilnosti u tijeku S-faze staničnog ciklusa u fi ziološkim uvjetima dovode do apoptoze posredovane proteinom p53. Međutim, u stanicama inficiranim HPV-om taj je proces onemogućen djelovanjem proteina E6, koji dovodi do proteolitičke razgradnje p53. Stalna aktivnost virusnih proteina E6 i E7 dovodi do nestabilnosti genoma, nakupljanja mutacija, gubitka kontrole staničnog rasta i na kraju do razvoja karcinoma. Putem prirođenog i stečenog imunosnog odgovora organizam prepoznaje i suzbija strane agense, ali u slučaju HPV-infekcije taj je odgovor ponekad nedovoljan. Nadalje, HPV-infekcija dovodi do gubitka ekspresije citokina djelovanjem E6 i E7- onkoproteina, posebice suprimiranjem ekspresije gena interferona. U oko 10% zaraženih nastaje perzistentna infekcija HPV-om što donosi značajan rizik od nastanka prekursorskih ("premalignih") lezija, kao i od nastanka invazivnog karcinoma., The causal role of human papilloma virus (HPV) in all cancers of the uterine cervix has been fi rmly established biologically and epidemiologically. Most cancers of the vulva and vagina are also induced by HPV. Papillomaviruses are perfectly adapted to their natural host tissue, the differentiating epithelial cell of skin or mucosae, and exploit the cellular machinery for their own purposes. The infectious cycle is initiated when infectious particles reach the basal layer of the epithelium, where they bind to and enter into cells. The critical molecules in the process of virus replication are the viral proteins E6 and E7, which interact with a number of cellular proteins. In experimental system these interactions have been shown to induce proliferation and eventually immortalization and malignant transformation of cells. Binding of E7 to pRb activates the E2F transcription factor, which triggers the expression of proteins necessary for DNA replication. Unscheduled S-phase would normally lead to apoptosis by the action of p53. However, in HPV-infected cells, this process is counteracted by the viral E6 protein, which targets p53 for proteolytic degradation. As an aberration of virus infection, constant activity of the viral proteins E6 and E7 leads to increasing genomic instability, accumulation of oncogene mutations, further loss of cell-growth control and ultimately cancer. The immune system uses innate and adaptive immunity to recognize and combat foreign agents that invade the body, but these methods are sometimes ineffective against human papillomavirus. HPV has several mechanisms for avoiding the immune system. Furthermore, HPV infections disrupt cytokine expression with the E6 and E7 oncoproteins, particularly targeting the expression of interferon genes. Approximately 10% of individuals develop a persistent infection, and it is this cohort who are at risk of cancer progression, with the development of high-grade precursor lesions and eventually invasive carcinoma.

With correct staging a large number of patients with cervical cancer FIGO stages IA2 and IB can be spared of unnecessary radiation therapy by laparoscopic assisted vaginal radical hysterectomy (LAVRH) as an option of radical surgical treatment in such patients. The development of laparovaginal surgery, indication and contraindication were presented. Also, the surgical technique was described in detail. Fifty-two patients were followed up in 2003 after LAVRH or open surgery, performed in our single center. Only 5 (14%) patients died from cervical cancer within 3 years following the treatment. They were all clinical stage IB treated with open surgery. There were 4 (11%) complications following treatment and they were all in patients with clinical stage IB, also treated with open surgery. There was no complication in LAVRH treated patients. The results and complications of the sole Croatian center performing LAVRH or open surgery in patients with cervical cancer FIGO stages IA and IB were similar to those in centers across the world.

Karcinom vrata maternice drugi je najčešći karcinom u žena u svijetu. Najveća incidencija ove bolesti u nerazvijenim je zemljama jugozapadne Afrike, Južne Amerike i jugoistočne Azije. U Europi najveća incidencija ove bolesti je u zemljama istočne Europe. Hrvatska ima nižu incidenciju ove bolesti od mnogih država srednje i jugoistočne Europe. Karcinom vrata maternice bolest je mlađih žena. Veliko istraživanje International Agency for Research on Cancer (IARC) iz 1995. godine otkrilo je u 99,7% svih karcinoma vrata maternice genom humanog papilomavirusa (HPV). Genitalni sojevi HPV-a podijeljeni su u tri skupine: sojevi visokog onkogenog rizika, mogući karcinogeni sojevi i sojevi niskog onkogenog rizika. Sojevi 16 i 18 odgovorni su za oko 70% karcinoma cerviksa podrijetla pločastih stanica i oko 86% adenokarcinoma vrata maternice. Infekcija HPV-om danas je najčešća spolno prenosiva bolest. 90–95% slučajeva infekcija HPV-om prolazi spontano. Za razvoj preinvazivnih lezija vrata maternice (CIN – cervikalna intraepitelna neoplazija) i potom karcinoma potrebna je trajna infekcija visokoonkogenim sojevima HPV-a. Pretpostavka je da od trajne infekcije HPV-om do invazivnog karcinoma vrata maternice treba proći 7–10 godina, što ostavlja dovoljno vremena za prevenciju. Teoretski karcinom vrata maternice bolest je od koje ni jedna žena ne bi smjela oboljeti, a kamoli umrijeti. Ipak incidencija ove bolesti “stabilna” je. Razlog tomu je oportunistički program probira u Hrvatskoj. Na PAPA-obrisak uglavnom dolaze uvijek iste žene individualnom inicijativom. Stoga se nameće potreba organiziranog programa probira. Prošle godine u mnogim zemljama registrirano je cjepivo protiv HPV-a. Organizaciju nacionalnih imunizacijskih programa moguće je aplicirati samo u zemljama s dobro organiziranim programima sekundarne prevencije i u zemljama koje to mogu platiti., Cervical carcinoma is the second most frequent carcinoma in women worldwide. The highest incidence is recorded in developing countries of southwest Africa, South America and Southeast Asia. In Europe, the highest incidence is recorded in eastern European countries. In Croatia, its incidence is lower than in many CEE countries. Cervical carcinoma is the disease of young women. The major study conducted by the International Agency for Research on Cancer (IARC) in 1995 revealed that 99.7% of all cervical carcinoma cases could be attributed to human papillomavirus (HPV). Genital HPV strains are divided into three groups: high oncogenic risk strains, potentially carcinogenic strains, and low oncogenic risk strains. Strains 16 and 18 are responsible for about 70% of cervical epithelial cancers, and about 86% of cervical adenocarcinomas. Nowadays the HPV infection is the most frequent sexually transmitted disease. Remission can be spontaneous in 90-95% of HPV cases. Pre-invasive cervical lesions (CIN - cervical intraepithelial neoplasia) and subsequent carcinoma develop after a persistent infection with highly oncogenic HPV strains. The presumed interval between a persistent HPV infection and invasive cervical carcinoma is seven to ten years, which leaves suffi cient time for prevention. Theoretically, no woman should develop cervical carcinoma, or let alone die. However, the incidence of cervical carcinoma is stable. The reason is opportunistic screening in Croatia. These are mostly the same women who have Pap smears, and it is on their own initiative. Therefore, there is a need for organized screening program. Last year, HPV vaccine was registered in many countries. National immunization programs can be realized only in countries with well-organized secondary prevention and fi nancial prerequisites.

Duboka venska tromboza je drugi najčešći uzrok smrti bolesnika oboljelih od raka. Bolesnici oboljeli od zloćudne bolesti imaju veću sklonost zgrušavanju krvi i time veći rizik od tromboembolijskih komplikacija. Operacija, kemoterapija, radioterapija i imobilizacija tih bolesnika dodatno doprinose nastanku duboke venske tromboze. Imajući u vidu preoperativne i intraoperativne prognostičke čimbenike za nastanak duboke venske tromboze, u mogućnosti smo pravovremeno intervenirati i smanjiti moguće komplikacije. Niskomolekularni heparin se pokazao uspješnim u prevenciji i liječenju tromboembolijskih komplikacija, a nekoliko studija izvještava o duljem očekivanom preživljenju bolesnika oboljelih od zloćudne bolesti liječenih antikoagulantnom terapijom., Deep venous thrombosis is the second most common cause of death in cancer patients. Patients with cancer are at heightened risk of venous and arterial thromboembolism due to the hypercoagulable state. Surgery, chemotherapy, radiotherapy and immobilization of the cancer patients heighten this risk even more. Having in mind all the pre- and intraoperative prognostic factors, we are capable to prevent and reduce possible complications. Low-molecular-weight heparin is proven to be beneficial in the prevention and treatment of the thrombotic complications. There are numerous studies reporting on improved survival of cancer patients treated with LMW heparin.

Cilj istraživanja. Standardna kemoterapija u bolesnica s lokalno uznapredovalim rakom jajnika stadija II do IVa je kombinacija paklitaksela s cisplatinom/karboplatinom. Više od 75% bolesnica javlja se upravo u tim stadijima bolesti. Početkom 90-tih godina prošlog stoljeća ova kombinacija lijekova koristila se u recidivima nakon incijalne kemo-terapije s cisplatinom/karboplatinom, u kombinaciji s ciklofosfamidom i/ili adriamicinom, da bi se nakon zadovoljavajućih rezultata nakon 1995. godine počela koristiti i u »prvoj« liniji liječenja. Metode. U Zavodu za ginekološku onkologiju Klinike za ženske bolesti i porode KBC-a Zagreb započeli smo primjenom paklitaksela 1994. godine. Od 1994.–1996. godine davali smo ga isključivo u slučaju recidiva da bismo 1996. godine prvi puta započeli liječenje spomenutom kombi-nacijom kao prvom linijom. Od 1994. do 2002. godine ukupno je liječeno 65 bolesnica; paklitaksel je ušao na listu lijekova Hrvatskog Zavoda za zdravstveno osiguranje (HZZO) za recidiv bolesti 1997. godine, a tek 1998. godine za prvu liniju uz posebne zamolbe HZZO-u. Svaka je bolesnica primila između 4–10 ciklusa kemoterapije te je ukupno primijenjeno preko 650 ciklusa kemoterapije. Rezultati. Tijekom primjene ni u jedne bolesnice nismo imali smrtni ishod, a samo kod dvije (3%) ozbiljnije alergijske reakcije koje su uspješno zbrinute, pa je nastavljeno s kemoterapijom. Zaključak. Na temelju našega iskustva možemo reći da je paklitaksel u kombinaciji s cisplatinom/karboplatinom vrlo učinkovit citostatik te da se naši rezultati liječenja ne razlikuju od rezultata objavljenih u svjetskoj literaturi., The aim of investigation. Standard chemotherapy in patients with locally advanced ovarian cancer stage II to stage IV is the combination of paclitaxel with cisplatin/carboplatin. More than 75% of patients are diagnosed at these stage of disease. At the begining of the 90’s of last century this combination of agents was used in recurrencies after initial chemotherapy with cisplatin/carboplatin with cyclophosphamide and/or adriamycin and has, proving to have satisfactory results, since 1995 been used in the first-line therapy. Methods. At Gynecologic Cancer Center, University Hospital Zagreb the use of paclitaxel started in 1994; from 1994 to 1996 paclitaxel was exclusively used for patients with recurrent disease. The use of paclitaxel plus cisplatin/carboplatin combination began as the first-line therapy in 1996. From 1994 to 2002 a total of 65 patients were treated with this combination. In 1997 paclitaxel was listed by the Croatian Health Insurance Agency (HZZO) as therapy for recurrent disease; in 1998 was the special request to HZZO for the first-line therapy and in 2002 separate funds were allocated for the treatment of patients with ovarian cancer stage II to IV with paclitaxel. From 1994 to 2001 paclitaxel was used in 23 patients, of which 5 in the first-line therapy and 18 after recurrencies as second-line therapy. In 2002, 42 patients were treated with paclitaxel – 32 in the first-line and 10 in the second-line therapy. Considering the fact that each patient was treated with between 4 to 10 cycles of chemoterapy, it has amounted to a total of more than 650 cycles of chemotherapy. Results. No treatment had a death outcome, only two patients (3%) experienced a serious allergic reaction but were successfully managed and chemotherapy was continued. Conclusion. Our experience confirms that paclitaxel in combination with cisplatin/carboplatin is a very effective drug and our results of chemotherapy do not differ from the results published in the world literature.

Tamoksifen i ostali selektivni regulatori estrogenskih receptora nova su terapijska sredstva koja imaju visoki afinitet za estrogenske receptore. U određenim tkivima imaju učinak sličan estrogenima, a u drugima se ponašaju kao antagonisti estrogenske akcije. U ovom pregledu prikazana je njihova primjena i rezultati u liječenju karcinoma dojke i endometrija te je dan osvrt na njihov potencijalni učinak kod karcinoma vrata maternice i jajnika. Prema rezultatima velikog broja istraživanja tamoksifen se pokazao učinkovitim u liječenju karcinoma dojke u premenopauzalnih i u postmenopauzalnih žena. Izneseni su i rizici ove terapije poput razvoja sekundarnog karcinoma endometrija. Također je obrađena primjena gestagena u liječenju karcinoma endometrija. Ovaj rad daje i pregled utjecaja hormonske nadomjesne terapije na pojavnost raka dojke i endometrija te sigurnost njegove primjene u bolesnica liječenih zbog karcinoma dojke, endometrija, jajnika i vrata maternice., Tamoxifen and other selective estrogen receptor modulators are new medications characterised by high estrogen receptor affinity. In certain tissues they express estrogen-like activity and in the others they act as estrogen antagonists. This review discussess their use in breast and endometrial carcinoma as well as their treatment results. It also reviews their potential effects on ovarial and cervical carcinoma. According to numerous clinical trials tamoxifen has proved effective in breast cancer treatment of premenopausal and postmenopausal women. The risks of this therapy, such as development of secondary endometrial carcinoma, have also been presented. The use of gestagenes in endometrial carcinoma treatment has been discussed too. This paper reviews the influence of hormone replacement therapy on the development of breast and endometrial carcinoma as well as the safety of its application in patients diseased of breast, endometrial, ovarian or cervical carcinoma.