Expression of Vascular Endothelial Growth Factor-A (VEGF-A) in Adenocarcinoma and Squamous Cell Cervical Cancer and Its Impact on Disease Progression: Single Institution Experience.

Background and Objectives: The aim of this retrospective study was to determine the difference in VEGF-A expression in adenocarcinoma and squamous cell cervical cancer and to show the influence of VEGF-A expression on clinical, pathological, and therapeutic prognostic factors on the outcome of treatment and the survival of patients. Materials and Methods: The study included patients with cervical cancer who were treated in the period from 1 January 2010 to 31 December 2021 at the Clinic for Gynecology and Obstetrics, University Hospital Centre, Osijek. The researchers conducted a retrospective analysis of data from patients' medical history, along with the pathohistological findings and oncologist findings. The study included 66 patients with cervical cancer (divided into two subgroups of 33 with adenocarcinoma or squamous cell cervical cancer). Diagnosis was based on the pathohistological status and FIGO staging. VEGF-A expression was significantly higher in adenocarcinoma. Subjects with a higher expression of VEGF-A had a significantly higher rate of disease progression and a higher possibility for lethal outcome. Results: Statistically significant prognostic factors in bivariate analysis in predicting a negative treatment outcome were: older age, greater depth of stromal invasion, FIGO IIB stage, chemotherapy, and positive lymph nodes. In the multivariate analysis, age and positive lymph nodes were shown to be significant predictors for a negative treatment outcome. Conclusions: VEGF-A has shown to be statistically more expressed in adenocarcinoma, which correlates with disease progression, but not statistically significant in multivariate regression analysis as an independent prognostic factor for poor survival of the subjects.

ARSENIC IN DRINKING WATER AND URINE AND ITS RELATIONSHIP WITH MALIGNANT TUMORS OF URINARY TRACT IN OSIJEK-BARANJA COUNTY, CROATIA.

Increased values of arsenic in potable water in eastern Croatia has been a matter of scientific interest for the past two decades due to numerous health effects, including carcinogenic ones. This study investigated whether prolonged exposure to increased arsenic from water could be detectable through increased arsenic in urine, and whether it influenced the incidence of kidney and bladder cancer in Osijek-Baranja County. Inductively coupled plasma mass spectrometry (ICP-MS) was used for analysis of water samples from available water sources (wells, aqueducts). In addition, examinees from Osijek, Nasice, Vladislavci, Cepin and Dalj gave their urine samples for analysis. Data on cancer incidence were obtained from the Institute for Public Health Registry and cumulative incidence of kidney and bladder cancer was calculated for the period between January 1, 2000 and December 31, 2018. Elevated arsenic concentration in drinking water was recorded in Vladislavci, Cepin and Osijek area with values above the allowed maximum according to the EU standards (10 µg L-1) and as a result, arsenic levels in urine of the inhabitants were also elevated. Cumulative incidence for bladder cancer showed correlation between increased arsenic in water and urine in the areas affected by increased arsenic in water. Epidemiologic data suggest a conclusion that elevated arsenic could be considered at least as a cofounding factor for urinary tract cancer.

PROGNOSTIC FACTORS FOR VULVAR CANCER.

The aim of this retrospective study was to show the effect of clinical, pathologic, cytologic and therapeutic prognostic factors on treatment outcome and survival of patients suffering from vulvar cancer and to determine prognostic significance of each of the individual factors, their mutual significance and impact on survival. The study included patients treated for vulvar cancer at Department of Gynecology and Obstetrics, Osijek University Hospital Centre during the 2000-2011 period. Retrospective analysis included data from patient medical files, along with their pathologic and cytologic findings, and oncologist findings. The study included 59 patients aged 45 to 88 years. Diagnosis was based on pathologic and cytologic status and staging. Univariate analysis showed the lymph node status, adjuvant radiotherapy, chemotherapy and clinical staging of the disease to be statistically significant prognostic factors for overall survival and prognosis of vulvar cancer patients. Multivariate analysis of independent prognostic factors for survival of vulvar cancer patients yielded lymph node status, adjuvant radiotherapy and chemotherapy as positive prognostic factors.

Prognostic SIGNIFICANCE of Cytoreductive Therapy of Ovarian Cancer - eastern Croatia experience.

The aim of this retrospective study was to present the impact of successful optimal cytoreductive therapy on the overall prognosis of ovarian cancer treatment. Several factors were analyzed, including clinical (stage, age and parity), histopathologic/cytological (histologic type and grade of tumors, cytological findings of ascites or peritoneal washout), and therapeutic (surgery performed with the degree of cytoreduction, adjuvant chemotherapy and response to therapy). The study included 126 patients treated during a 5-year period at the Department of Gynecology and Obstetrics, Osijek University Hospital Centre in Osijek. Patient age ranged from 29 to 82, total 5-year survival was 55.5% and median survival was 76.2 months. Optimal cytoreduction (residual tumor <1 cm) was performed in 49.2% of patients. On data analysis, the life chart method, χ2-test and Cox regression analysis were used. The level of significance was set at p<0.05. Parity, histologic tumor grade, presence of malignant cells in ascites and peritoneal washout, as well as clinical stage yielded statistical significance on univariate analysis. Cytoreductive ovarian cancer therapy turned out to be a significant prognostic factor and on multivariate analysis proven to be an independent prognostic factor. Optimal cytoreduction, besides direct effect on survival, improved the quality of therapeutic response of the tumor to chemotherapy.

Climatic Factors and Epidemiologic Characteristics of Head and Neck Skin Malignancies in Osijek Baranja County, Croatia.

AIM: The aim of this study was to investigate and compare the incidence and epidemiological characteristics of head and/or neck skin malignancies in Osijek-Baranja County, Croatia, and to connect them with relative climatic indicators such as the number and intensity of sunny and cloudy days over a longer period of time. METHODS: The study included patients from Osijek Baranja County with confirmed pathohistological diagnosis of the head and/or neck malignancies from January 1, 2004 to December 31, 2012. The patients were analyzed according to gender, age, residence, occupation, type and location of the neoplasm, and hair and eye colour. The analysis of climatic elements (mean monthly and annual cloudiness values, mean monthly and annual sum values of sunny days) for a period of 50 years (1961-2011) based on the data of the Croatian Meteorological and Hydrological Service for the investigated area was performed. RESULTS: The study included a total of 2,952 patients: 1,487 (50.4%) males and 1,465 (49.6%) females, representing the estimated annual incidence of 104/100,000. The mean age was 72 years. The patients were mostly from rural areas, 1,952 (66.2%); 2,137 (72.4%) worked outdoors: 907 farmers (42.4%) and 889 construction workers (41.6%). Given the type of neoplasm, the most common was a basal cell cancer (BCC) in 2,160 patients (73.2%). Malignant melanoma was found in 93 patients (3.1%). The most common localizations were face (839 cases, 28.7%) and nose (643 cases, 22.0%). Males had a significantly higher number of planocellular malignancies--341 (56.6%) than females--262 (43.4%) (p=0.005). The median age of the patients was 67 years. There were no significant differences in types of malignancies, place of residence, workplace, or occupation (with respect to working outdoors or indoors). It has been shown that the ears and lips are significantly more affected by squamous cell malignancies (p=0.039 and p<0.001) compared to the neck, eye and head with malignant melanoma (p=0.004, p<0.001, and p=0.026) and the nose where basal cell neoplasms (p=0.002) prevail. There were no significant differences in the type and frequency of malignant neoplasms in relation to hair and eye colour of the patients. The last 50 years in Osijek-Baranja County have seen a declining trend in the number of cloudy days and upward trend in the mean annual sum of sunny days. When compared, the increase in sunny days results in a higher number of patients suffering from malignant melanoma (ρ=0.695, p=0.038). CONCLUSION: It is obvious that malignant neoplasms of the skin, head and neck occur after decades of exposure, and as a cumulative effect of exposure to risk factors. A direct exposure to sun seems to play an important role, especially with regard to melanoma. Nevertheless, further research is needed.

[CHARACTERISTICS AND INCIDENCE OF HEAD AND NECK SKIN MALIGNANT NEOPLASMS IN THE POPULATION OF THE OSIJEK-BARANYA COUNTY 2004-2012]. / UCESTALOST I KARAKTERISTIKE POJAVNOSTI MALIGNIH NEOPLAZMI KOZE GLAVE I VRATA STANOVNIKA OSJECKO-BARANJSKE ZUPANIJE U RAZDOBLJU OD 2004. DO 2012. GODINE.

UNLABELLED: The aim of this study was to investigate the incidence and characteristics of malignant neoplasms of the skin of the head and neck region in the Osijek-Baranya County during the 2004-2012 period according to gender, age, place of residence, place of work, occupation, type and location of the neoplasm, and phenotypic characteristics of patients. SUBJECTS: The study included all subjects with the diagnosis confirmed by histopathology finding and residents of the Osijek-Baranya County. The study included a total of 2952 persons, 1487 (50.4%) male and 1465 (49.6%) female, yielding an approximate annual incidence of 104/100,000. Mean age was 72 years. Respondents were mostly from rural areas (n = 1952, 66.2%). There were 2137 (72.4%) of respondents mostly working outdoors, mainly farmers (n = 907, 42.4%) and construction workers (n = 889, 41.6%). RESULTS: According to the type of neoplasm, the basal cell type was most common with 2160 (73.2%) patients. Ninety-three (3.1 %) patients had malignant melanoma. According to localization, face was the most common site of malignant neoplasms with 839 (28.7%) and nose with 643 (22.0%) patients. Squamous cell carcinoma was significantly more common in men (n = 341, 56.6%) as compared with women (n = 262, (43.4%; p = 0.005). Subjects with malignant melanoma were significantly younger, with median age of 67 years. There were no significant differences according to the type of malignant neoplasms and place of residence, place of business, and occupation with regard to working outdoors or indoors. According to localization, significantly more squamous cell malignancies were found on the ears and lips (p = 0.039 and p < 0.001, respectively), malignant melanomas on the neck, head and eyes (p = 0.004, p < 0.001 and p = 0.026, respectively), and basal cell neoplasms on the nose (p = 0.002). There were no significant differences in the type and frequency of malignant neoplasms according to hair and eye color. CONCLUSION: It is obvious that the disease occurs after a decades-long incubation period and the cumulative effect of exposure to risk factors, with direct sun exposure, seems to have a significant role. Additional research is needed.

Trace metals in the environment and population as possible long term consequence of war in Osijek-Baranja County, Croatia.

War in Croatia resulted with a significant release of contaminants into the environment as a result of the use of combat assets, mainly conventional, mostly aimed at civilian targets. The aim of the study was to investigate the concentration of metals and metalloids in the soils, water, plants (Taraxacum officinale), serum, urine and hair of the inhabitants in eastern Croatia. Overall results show minor abnormalities in presence of some trace metals in soil (As, Hg, Pb, Sb), water (As, Fe) and dandelion leaves (As) in some locations. Compared with soil samples from areas exposed to low intensity combat activity soil samples from areas exposed to heavy fighting had higher concentrations of As, Hg and Pb than allowed by national legislation for ecologic farming. Drinking water with the exceptions of the concentrations of Fe, As and Mn was in accordance with national legislation. Examinees from Dalj had mean hair Sb level 10-19x higher then examinees from any other location. However, when these data are correlated through methods of principal component analysis, presence of trace metals in some war affected areas can be followed from soil, through plants up to population proving that intense combat activities over small area leave metal presence that can be followed even 15 years after the war.

Heavy metals and metalloid content in vegetables and soil collected from the gardens of Zagreb, Croatia.

Aim of this study was to determine concentration of Pb, Cd, As and Hg in green leafy vegetables and soil in the urban area of Zagreb, Croatia and to determine if there is a connection between the contamination of soil and vegetables. Green leafy vegetables and soil samples were taken from the gardens located in the outskirts of the city. Concentrations of Pb, Cd, As and Hg were determined by atomic absorption spectrometry; showing that average concentrations of metals and metalloids in vegetables and in soil, regardless of the location of sampling were below the maximum allowed concentration (MAC). The analysis determined that metal concentrations in only nine vegetable samples (9%) were above maximum allowed values prescribed by national and European legislation (three with higher concentrations of Pb, one with a higher concentration of Cd and five with higher concentrations of Hg). Concentrations of contaminants present in the analysed samples, in general, are lower than the ones published in similar studies. The final distribution and concentration of contaminants in vegetables of Zagreb, besides industry and traffic, is affected by the dominant wind direction.

Methotrexate in local treatment of cervical heterotopic pregnancy with successful perinatal outcome: case report.

This case report describes a case of heterotopic cervical ectopic pregnancy in a nulliparous woman that was successfully treated with single-dose local, intra-amniotic methotrexate injection in the gestational sac. Pregnancy was achieved spontaneously. The patient had previously undergone hysteroscopic myomectomy. By using local, single-dose treatment we avoided the continued effects of the drug on the intrauterine pregnancy and the possible adverse effect of systemically applied methotrexate. The treatment resulted in the term vaginal delivery of a healthy child and preserved the patient's fertility for future pregnancies.

An analysis of the pollution problem in Slavonski Brod (eastern Croatia).

H2S, PM2.5, O3, NO2, SO2 and meteorological parameters such as temperature, relative humidity, precipitation, wind speed and wind direction were measured simultaneously in an eastern Croatian town called Slavonski Brod during the season winter/spring 2010. Emissions from the nearby cross-border (Bosnia and Herzegovina) oil refinery were identified as sources of temporary elevated concentrations of H2S. The maximum daily averages of PM2.5 concentrations during the winter period were as high as 240 microg m(-3) which is a value 10 times greater than the threshold prescribed by the World Health Organization. It is considered that the heating season, dense traffic, intense industrial activities and temperature inversion during stable weather conditions are prevailing contributors to higher winter concentrations of PM2.5. The results of the principal component analysis technique (PCA) have shown that lower air temperature, lower wind speed and higher relative humidity play a significant role in the winter pollution episodes. From a public health point of view, implementation of measures aimed at reducing the levels of H2S and PM2.5 should be considered.

Peritoneal and upper genital tract tuberculosis.

Aim To present diagnostic and therapeutic possibilities for genital and peritoneal tuberculosis, mimicking to other pathological conditions, mainly, ovarian cancer. Methods Transabdominal and transvaginal ultrasound, computerized tomography, Ca125 and HE 4, ROMA- index (Risk of Ovarian Maligancy Algorithm index) and diagnostic laparoscopy were performed in order to diagnose genital tuberculosis in a female patient. Results: A 23-year-old woman from Morocco presented with intermitting abdominal pain, unintentional weight loss and primary infertility. There was no positive family history for breast or ovarian cancer and no history of previous tuberculosis (TB). Elevated CA-125 level, HE 4 normal, ROMA-Index of 13.2 % suggested high risk for epithelial ovarian cancer (EOC). Ultrasound revealed free fluid, dilated fallopian tubes and a cystic mass near the right ovary. Suspecting fallopian tube or ovarian cancer, we performed exploratory laparoscopy, revealing adhesions, multiple miliary nodes and dilated fallopian tubes. Histological investigation revealed granulomatous abscessing salpingitis with suspicion of genital TB, so antituberculous therapy was administered with success. Conclusion Female genital tuberculosis is very rare but important in differential diagnosis and should be kept in mind regarding suspected fallopian tube or ovarian carcinoma to prevent women from extensive surgery. An algorithm for possible differentiation between peritoneal/female genital TB and EOC may be helpful in clinical setting.

The soluble fms-like tyrosin kinase-1 (sFLT-1) to placental growth factor (PIGF) ratio as a possible indicator for the severity of preeclampsia - single institution experience.

Aim To investigate a potential of the clinical use of the soluble fms-like tyrosine kinase 1 (sFLT-1) to placental growth factor (PlGF) ratio from the perspective of a small hospital centre. Methods Maternal serum samples were analysed at 241/7-28 0/7, and 281/7-320/7 weeks of gestation. The level of sFLT-1 and PIGF was determined by immunoassay platform and used to calculate the sFLT-1/PIGF ratio in 35 pregnant women, and divided into subgroups according to preeclampsia occurrence at the time of delivery: preterm (≤37 weeks) or term (37-42 weeks'), and matched a control group. Results Patients in the preterm delivery group had a significantly higher incidence of intrauterine growth restriction, lower gestational age at the time of delivery, and lower infant birth weight compared to the other two groups. There was a negative correlation between the sFLT-1/PlGF ratio and GA and between the sFLT-1/ PlGF ratio and birth weight at the time of delivery. The value of the sFLT-1/PlGF ratio was significantly higher in the preterm delivery PE group. All the PE group pregnancies ended with caesarean delivery compared to 25% in the control group. However, none of the patients from the PE group had any of the possible complications of preeclampsia nor did they require additional therapy such as blood transfusion or additional non-standard hypertensive therapy. Conclusion The sFLT-1/PlGF ratio could be used as an indicator for the development and estimation of the severity of PE to provide objective evidence for the management of preeclampsia patients, and as a predictive marker of preeclampsia at low cost.

Determinations of uranium concentrations in soil, water, vegetables and biological samples from inhabitants of war affected areas in eastern Croatia (ICP-MS method).

The occurrence of elevated uranium levels in post-war areas raise concerns among populations, especially in areas affected by heavy bombardment and potential use of depleted uranium weapons. The aim of this study was to assess public exposure to the uranium Water, soil, vegetables, urine, serum and hair samples were collected for the first time in eastern Croatia and analysed using an inductively coupled plasma mass spectrometry (ICP-MS) method, in order to try to explain the possible origins of uranium in the population and environment. Urine, serum and hair samples were collected from 389 inhabitants. A large variation of uranium concentrations in urine, serum and hair samples was found in this study. The majority of urine, serum and hair samples from our study had uranium concentrations below the reference literature values. A higher uranium concentration in the hair of 4% of inhabitants, mostly from rural areas, could not be explained at this stage of research. A further, extended epidemiological study should be made of uranium in the region.

Management of cervical ectopic pregnancy after unsuccesful methotrexate treatment.

BACKGROUND: Cervical pregnancy is rare and dangerous form of ectopic pregnancy which can be treated surgically or conservatively. Methotrexate is reasonable conservative option with high efficiency and acceptable level of side effects. Aim of this paper is to present possible treatment option in case of methotrexate failure, still keeping the postulates of minimal invasive surgery. CASE: We describe a case of cervical ectopic pregnancy in nulliparous female that was unsuccessfully treated with single dose, local, ultrasound guided intraamniotic methotrexate. Due to vaginal bleeding caused by remaining products of conception a hysteroscopic resection was performed. CONCLUSION: Despite the problems that can occur in methotrexate treatment, it is still by far, cheapest and most effective treatment of cervical pregnancies. If necessary, procedure can be combined with other minimal invasive surgical procedures leading to satisfactory results. Hysteroscopic resection has enabled us to remove the product of conception from cervix making the minimal damage to the local tissue, thus preserving fertility.

Primary serous papillary adenocarcinoma of the fallopian tube.

Fallopian tube cancer is least common of all gynecologic tumors, with the mean age at onset between 54 and 63 years. This case report presents a 67-year-old female, gravida 1, para 1, with primary adenocarcinoma of the fallopian tube, detected and diagnosed preoperatively in clinical stage IIIc. The patient was asymptomatic, with only mild vaginal discharge of amber color and normal measured value of CA 125. The diagnosis was based on routine clinical and ultrasound examination, followed by surgery, surgical-pathological staging of the disease, and finally paclitaxel and platinum based chemotherapy. The patient has been in remission for nine years now.

Secondary abdominal appendicular pregnancy: case report.

INTRODUCTION: The case report describes a 29-year-old nulliparous woman that was admitted at the Department of Gynecology and Obstetrics of the Clinical Hospital Osijek complaining of mild abdominal pain without vaginal discharge. CASE OUTLINE: The patient's menstrual cycle was irregular, from 30-45 days. An ultrasound examination showed suspicion of an ectopic pregnancy with a betaHCG level of 1358 IU/L. Due to the presence of liquid in the pouch of Douglas the patient underwent emergency laparoscopy, which showed the presence of tumor mass between the right Fallopian tube and the appendix. These two structures associated with adhesions corresponded to secondary implantation after spontaneous tubal abortion which was confirmed by histopathologic analysis. CONCLUSION: Laparoscopy has emerged as the"gold standard"in the diagnosis and treatment of ectopic pregnancy, in this case the secondary abdominal pregnancy. From the diagnostic point of view, all women of reproductive age should be considered pregnant until proven otherwise, also keeping in mind that ectopic pregnancies can have different locations and many clinical features.

Role of laparoscopic surgery in treatment of infertility.

The role of laparoscopy in assisted reproduction is disputed by many. A rising problem of infertility is battled by an increasing number of centres for reproductive medicine in the region. Nevertheless, there is a large number of indications and conditions where laparoscopic surgery should not be avoided as a therapeutic choice or an aid in assisted reproductive techniques (ART). The number of centres where laparoscopic surgery is performed is significantly higher than the number of reproductive centres; a number of gynaecologists educated in laparoscopic gynaecology is growing, making it more available for patients.

Chemometric analysis of groundwater quality data around municipal landfill and paper factory and their potential influence on population's health.

AIM: To assess the level of 15 groundwater quality parameters in groundwater samples collected around municipal landfill and paper factory in order to evaluate usefulness of the groundwater and its possible implication on the human health. METHODS: Obtained data have been analyzed by principal component analysis (PCA) technique, in order to differentiate the groundwater samples on the basis of their compositional differences and origin. RESULTS: Wastes and effluents from municipal landfill did not contribute significantly to the pollution of the aquatic medium. Groundwater degradation caused by high contents of nitrate, mineral oils, organic and inorganic matters was particularly expressed in the narrow area of the city centre, near the paper factory and most likely it has occurred over a long period of time. The results have shown that the concentrations of the most measured parameters (NO3-N, NH4-N, oils, organic matter, Fe, Pb, Ni and Cr) were above allowed limits for drinking and domestic purposes. CONCLUSIONS: This study has provided important information on ecological status of the groundwater systems and for identification of groundwater quality parameters with concentrations above allowable limits for human consumption. The results generally revealed that groundwater assessed in this study mainly does not satisfy safe limits for drinking water and domestic use. As a consequence, contaminated groundwater becomes a large hygienic and toxicological problem, since it considerably impedes groundwater utilization. Even though, all of these contaminants have not yet reached toxic levels, they still represent long term risk for health of the population.

Intermittent hepatic porphyria in pregnancy with good perinatal outcome.

Porphyrias are rare metabolic diseases caused by enzymatic defects of the haeme biosynthesis. Association of pregnancy and acute porphyria is rare, but mortality rate among pregnant women from acute attack has been reported up to 42%. This paper presents a patient with pregnancy complicated by intermittent hepatic porphyria with good perinatal outcome. The pattern of the attack in pregnancy varies individually and it makes porphyric pregnancies a challenge. Previously diagnosed porphyria patients should be closely monitored during pregnancy and diagnosis of acute porphyria must be also considered in all pregnant women with unexplained abdominal pain.

Surgical treatment of large smooth muscle tumor of uncertain malignant potential during pregnancy.

This paper presents a case of a 37-year old pregnant woman with a large tumor extending from pelvis to xyphoid, diagnosed at 14 weeks of pregnancy. At 18 weeks myomectomy was performed and the tumor weighing 4250 g was removed. Hystopathological findings showed a uterine smooth muscle tumour of uncertain malignant potential. Due to preeclampsia an urgent caesarean section was performed at 34 weeks of gestational age. A live and healthy female neonate was delivered. According to hystopathological findings and in agreement with the patient hysterectomy without adnexectomy was performed in the same act.