[Clinical recommendations for diagnosing, treatment and monitoring of patients with endometrial cancer -- Croatian Oncology Society and Croatian Society for Gynecology and Obstetrics as Croatian Medical Association units and Croatian Society of Gynecological Oncology]. / Klinicke upute za dijagnostiku, lijecienje i pracenje bolesnica oboljelih od raka maternice hrvatskoga onkoloskog drustva i hrvatskog drustva za ginekologiju i opstetriciju hrvatskoga lijecni(ckog zbora te hrvatskoga ginekoloskoonkoloskog drustva.

Uterine cancer occurs mainly in postmenopausal women, usually as vaginal bleeding. Following ovarian and cervical cancer it is the third most common cause of female reproductive system cancer death. Diagnosis is set by analyzing samples obtained via hysterectomy with salpingo-oophorectomy and pelvic / paraaortal lymphadenectomy. The following text presents the clinical guidelines in order to standardize the procedures and criteria for the diagnosis, treatment and monitoring of patients with uterine cancer in the Republic of Croatia.

[Clinical recommendations for diagnosing, treatment and monitoring of patients with ovarian cancer -- Croatian Oncology Society and Croatian Society for Gynecology and Obstetrics as Croatian Medical Association units and Croatian Society of Gynecological Oncology]. / Klinicke upute za dijagnostiku, lijecenje i pracenje bolesnica oboljelih od raka jajnika hrvatskoga onkoloskog drustva i hrvatskog drustva za ginekologiju i opstetriciju hrvatskoga lijetnickog zbora te hrvatskoga ginekoloskoonkoloskog drustva.

Ovarian cancer together with fallopian tube represents the fifth most common female cancer in the Republic of Croatia. Epithelial ovarian cancer, serous subtype, encompasses most of malignant ovarian neoplasms. Less common are various non-epithelial ovarian malignancies. A special group consists of epithelial carcinomas of low malignant potential with clinically indolent flow, good prognosis and no invasion, and primary cancer of the peritoneum and fallopian tube cancer. Clinically, these malignant tumors are generally asymptomatic in early stages, and usually diagnosed in advanced stages. The diagnosis is confirmed by pathological examination, and occasionally, cytological findings after completing diagnostic procedures. Multidisciplinary team makes treatment decisions, taking into account age, general condition and comorbidities of the patient and characteristics of the tumor itself, including disease stage, histological type and grade of the tumor. The principles of treatment of primary peritoneal and fallopian tube cancer are based on the principles of treatment of epithelial ovarian cancer involving surgery, chemotherapy, immune and hormone therapy, and symptomatic-supportive care throughout the treatment. Less common histological types have a different treatment approach being more frequently diagnosed in the early stages of the disease, have more indolent flow, so in these patients conservative surgeries with the goal of preserving fertility are more often employed. 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 ovarian carcinoma, fallopian tube and primary peritoneal cancer in the Republic of Croatia.

[Clinical recommendations for diagnosing, treatment and monitoring of patients with uterine cervical cancer -- Croatian Oncology Society and Croatian Society for Gynecology and Obstetrics as Croatian Medical Association units and Croatian Society of Gynecological Oncology]. / Klinicke upute za dijagnostiku, lijecenje i pracenje bolesnica oboljelih od raka vrata maternice hrvatskoga onkoloskog drustva i hrvatskog drustva za ginekologiju i opstetriciju hrvatskoga lije nickog zbora te hrvatskoga ginekoloskoonkoloskog drustva.

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.

Is there difference in perinatal outcome of singleton and twin pregnancies after assisted conception: two-year experience.

The aim of the study was to compare perinatal outcome of singleton and twin pregnancies conceived after assisted reproductive technologies (ART). This retrospective study included singleton and twin pregnancies conceived after ART in the period from January 1, 2007 until December 31, 2008. The study variables were maternal age (years), parity, body mass index (BMI; kg/m2), week (< or =36 (6/7) and > or = 37) and mode of delivery (vaginal and cesarean section), birth weight (grams) and APGAR score (< or = 7; 8-10). During the study period, there were 195 pregnancies after ART that fulfilled inclusion criteria. We found no between-group difference in parity (chi2 = 0.0133; P = 0.9081), but such difference was found in mean age (t = 2.0486; P = 0.0419) and BMI (chi2 = 31.038; P = 0.001). A statistically significant difference was recorded in preterm delivery rate (chi2 = 25.539; P = 0.001), average duration of pregnancy (t = 12.8591; P = 0.001), average birth weight (t = 10.5446; P = 0.001) and mode of delivery (chi2 = 13,691; P = 0.001). A statistically significant difference was found in low birth weight babies (chi2 = 102.02; P = 0.001) and APGAR score (chi2 = 19.96; P = 0.001), but there was no difference in the prevalence of small for gestational age babies (chi2 = 0.90629; P = 0.635). In conclusion, this study indicated the perinatal outcome after ART to be considerably poorer in twins than in singletons.

Maternal pre-pregnancy underweight and fetal growth in relation to institute of medicine recommendations for gestational weight gain.

PURPOSE: Maternal nutritional status is one of the most important factors of fetal growth and development. Consequently, the currently increasing prevalence of underweight women worldwide has come in the focus of interest of perinatal medicine. The aim of the study was to assess the effect of low pre-pregnancy body mass index (BMI) on fetal growth. MATERIALS AND METHODS: Data on 4678 pregnant women and their neonates were retrospectively analyzed. Pre-pregnancy BMI of study women was categorized according to the WHO standards. Fetal growth was assessed by birth weight and birth length, birth weight for gestational age, and ponderal index. RESULTS: Study group included 351 (7.6%) women with pregestational BMI<18.5kg/m(2), while all women with pregestational BMI 18.5-25kg/m(2) (n=3688; 78.8%) served as a control group. The mean birth weight and birth length of neonates born to underweight mothers were by 167g and 0.8cm lower in comparison with the neonates born to mothers of normal nutritional status, respectively (P<0.001 both). The prevalence of small for gestational age (SGA) births was twofold that found in the control group of mothers of normal nutritional status (9.7% vs. 4.9%; P<0.001). The inappropriately low gestational weight gain additionally increased the rate of SGA infants in the group of mothers with low pre-pregnancy BMI (21.4% vs. 10.4%; P=0.02). Pre-pregnancy BMI category did not influence neonatal growth symmetry. CONCLUSION: Low maternal pregestational BMI is associated with fetal growth assessment. Improvement of the maternal nutritional status before pregnancy can increase the likelihood of perinatal outcome.

Estrogen replacement therapy improves pulmonary function in postmenopausal women with genital prolapse.

OBJECTIVE: This study examined the impact of estrogen replacement therapy with spirometry on pulmonary function in surgically castrated (salpingo-oophorectomy) postmenopausal women with genital prolapse. METHODS: The study included 60 postmenopausal women with pelvic organ prolapse. The study received institutional Ethics Committee approval, and all subjects signed an informed consent. Women were randomly divided into two groups of 30 subjects: Group 1 (n=30) was administered estrogen replacement with 1 mg of stradiol hemihydrate (1 mg/day) orally for 6 months, and group 2 (n=30) was not taking estrogen. Both groups were matched by age, height, body mass index, parity, and duration of postmenopause. All subjects were evaluated with spirometry initially and after 6 months. For statistical analysis, descriptive and analytical methods were used, based on data type and distribution. The mean and standard deviations were used as measures of central tendency and variability. Categorical data were expressed as absolute and relative numbers (percentage). The t-test for independent samples (for comparison of groups) and t-test for dependent samples (for comparison of serial measurements in the same patients) were used. The analysis was performed using R software ( www.r-project.org ), with the level of significance set at p<0.05. RESULTS: Analysis of spirometry parameters showed statistically significant differences between the estrogen users and the nonusers groups. CONCLUSION: The most important study result was the significantly improved lung respiratory function in postmenopausal women with genital prolapse after 6 months of taking estrogen, confirming that hormone replacement therapy should be recommended to postmenopausal women. The findings of our study suggest the need for further research into the effect of estrogen on pulmonary function.

First Croatian transvaginal laparoscopically assisted cholecystectomies.

BACKGROUND/AIMS: The aim of this study was to determine the feasibility and technical aspects of a new endoluminal surgical procedure: transvaginal laparoscopically assisted endoscopic cholecystectomy. METHODOLOGY: Three female patients underwent transvaginal laparoscopically assisted endoscopic cholecystectomy (aged 40, 61 and 33 years). Pneumoperitoneum was created through a 5mm supraumbilical incision. Through the posterior fornix of the vagina the second 10mm trocar, laparoscope and 5mm laparoscopic grasper were introduced. The gallbladder was dissected using standard 5mm laparoscopic grasper, hook, electrocoagulation and harmonic shears introduced supraumbilically. The dissected gallbladder was removed in a specimen retrieval bag. RESULTS: Transvaginal laparoscopically assisted endoscopic cholecystectomy was feasible in all patients. No intraoperative or postoperative complications were observed and there was no need for extra-umbilical skin incisions. Total operative time ranged between 60 and 75 minutes. Median length of hospital stay was 1 day. CONCLUSIONS: This was the first clinical application of transvaginal laparoscopically assisted cholecystectomy in Croatia. The initial clinical application of this technique in 3 female patients was feasible, effective and safe when performed by experienced laparoscopic surgeons using standard laparoscopic instruments.

Difference in expression of collagen type I and matrix metalloproteinase-1 in uterosacral ligaments of women with and without pelvic organ prolapse.

OBJECTIVE: To compare the expression of collagen type I and matrix metalloproteinase-1 (MMP-1) in uterosacral ligament biopsies from women with and without pelvic organ prolapse (POP). STUDY DESIGN: Uterosacral ligament biopsies were obtained from women with POP (n=46) and control subjects (n=49). Immunohistochemistry for collagen type I and MMP-1 was performed on formalin-fixed and paraffin-embedded sections. The two groups were matched for age, body mass index, parity and postmenopausal status. Statistical Package for the Social Sciences Version 13.0 was used for statistical analysis. RESULTS: The expression of collagen type I (p=0.034) and MMP-1 (p=0.038) differed between women with POP and control subjects. There was increased expression of MMP-1 and decreased expression of collagen type 1 in uterosacral ligaments of women with POP compared with control subjects. CONCLUSIONS: This difference indicates a possible relationship between POP and the immunohistochemical expression of collagen type I and MMP-1 in uterosacral ligaments.

Respiratory infections in children hospitalized at the University Hospital Mostar during war and post-war period.

Our aim was to investigate the incidence of respiratory infections in children treated at the Pediatric Department of the University Hospital Mostar during war (1993 and 1994) and after the war (2003 and 2004). In order to collect data we used medical histories of children with respiratory infections. Incidence of respiratory infections in children in war period was 230/1000, while in post-war period it was 190/1000. There was no significant difference in the incidence of respiratory infections in children during war and after the war (p = 0.051). We have not found increase in respiratory infections prevalence in children treated during war period at the Pediatric department of University Hospital Mostar, compared to the period after the war. However, we did report certain differences related to age, clinical parameters, seasonal pattern, diagnosis, therapy and mean hospitalization time.

Increased expression of matrix metalloproteinase-1 in uterosacral ligament tissue from women with pelvic organ prolapse.

Mechanical stability of the urogenital tract depends on intact collagen fibers. Because of difficulties in quantitating collagen, some authors have investigated collagen breakdown by measuring matrix metalloproteinases expression. We biopsied 68 post-menopausal women during operation to evaluate matrix metalloproteinase-1 (MMP-1) expression in uterosacral ligament biopsies from women with pelvic organ prolapse (POP) (n = 34) and controls with normal pelvic support (n = 34). The controls were matched to the POP group by age, body mass index, parity and duration of postmenopausal state. Immunohistochemistry for MMP-1 was performed on formalin fixed and paraffin embedded sections. Women with POP had a significantly higher MMP-1 expression (p = 0.047) which confirms an association, although not a causal relation, between POP and increased MMP-1 expression.

Expression of matrix metalloproteinase-1 in uterosacral ligaments tissue of women with genital prolapse.

Collagen metabolism is altered in the pelvic organ tissues of women with genital prolapse. The aim of this study was to compare collagen metabolism by measuring matrix metalloproteinase-1 (MMP-1) expression in uterosacral ligament tissues of postmenopausal women with and without genital prolapse. Uterosacral ligament tissues were obtained at the time of abdominal or vaginal surgery from twenty-four patients with pelvic organ prolapse (POP) and 21 women who underwent gynecologic surgery for benign indications. The tissue samples were analyzed by immunohistochemistry. There were no differences in age, BMI and parity between two groups. The patients with genital prolapse demonstrated significantly higher occurences of MMP-1 expression compared to controls. These findings indicate that increased MMP-1 expression in uterosacral ligaments is associated with genital prolapse. Our data are consistent with the theory that increased collagen breakdown may play an important role in the onset and development of pelvic organ prolapse (POP).

Matrix metalloproteinases-1, -2 expression in uterosacral ligaments from women with pelvic organ prolapse.

OBJECTIVE: This study investigated matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-2 (MMP-2) immunohistochemical expression in uterosacral ligament biopsies from women with pelvic organ prolapse (POP), and controls with normal pelvic support. DESIGN: Prospective observational experimental study. SETTING: A tertiary Urogynecology Unit and Institute of Pathology, University Hospital Split, Croatia. POPULATION: Women referred for hysterectomy for prolapse or benign gynecological disease. METHODS: Eighty postmenopausal women were included in the study after Ethical Committee approval and informed consent. During surgery, uterosacral ligament biopsies were obtained from patients with POP (n=40) and women without evidence of pelvic floor weakening (n=40). Immunohistochemistry for MMP-1 and MMP-2 was performed on formaline fixed and paraffin embedded sections. Statistical evaluations were made by Student t-test or chi(2) test. MAIN OUTCOME MEASURES: Immunohistochemical expression of MMP-1 and MMP-2 in the uterosacral ligaments of women with and without genital prolapse. RESULTS: Forty women with POP and 40 controls without POP were included. The controls were matched to the women with POP in age, body mass index, parity and duration of postmenopausis. A significant increase in MMP-1 immunohistochemical expression was seen in uterosacral ligament tissue from women with POP (P=0.029). In contrast, there was no difference in immunohistochemical expression of MMP-2 between women with POP and those without (P=0.899). CONCLUSION: These data suggest that MMP-1 may be marker of collagen degradation. Increased MMP-1 immunohistochemical expression in uterosacral ligaments is associated with urogenital prolapse.

Epidemiology of pelvic floor disorders between urban and rural female inhabitants.

The aim of this study was to investigate the prevalence of pelvic organ prolapse in urban and rural women and to identify possible related factors. They were 1749 participants; one thousand four hundred seventeen (81%) urban women and 332 rural residents (19%). The urban and rural women were congruently regarding to age, parity, using oral contraceptives and postmenopausal status. The urban women were more often obese (p < 0.01), estrogen replacement users (p < 0.001), smokers (p < 0.001), with mild (p < 0.001) and high (p < 0.001) education, and they were often divorced (p < 0.05) than rural women. Rural women were more often alcohol consumers (p < 0.001), with low level of education (p < 0.001) and more often married (p < 0.05) than rural examinees. There were no association between the presence of prolapse and: weight, menopausal status, oral contraceptives and estrogen replacement using, smoking, alcohol consuming and marital status. There were not observed differences in prevalence of prior hysterectomy, urinary incontinence, uroinfectio, sexual and bowel dysfunction between both groups. The prevalence of cystocele, rectocele and uterine prolapse were similar among urban and rural participants. In conclusion, a more complete picture of factors associated with genital prolapse would include in investigation, such as molecular and genetic ones.

Cord blood cortisol level is lower in growth-restricted newborns.

AIM: To establish the difference in plasma cortisol concentrations between newborns with intrauterine growth-restricted (IUGR) and appropriate for gestational age (AGA) birthweights. SUBJECTS AND METHODS: We measured plasma cortisol concentrations in the umbilical venous cord blood of 68 IUGR newborns and 71 AGA birthweight newborns. All newborns were delivered in term, vaginally, in the morning, within 8 hours and had APGAR scores greater or equal to eight. RESULTS: There was no significant difference between compared groups according to maternal age, parity, gestational age and neonatal gender. Neonatal plasma cortisol levels were significantly lower in the IUGR (median: 312.3 mmol/L, min-max: 158.9-588.1 mmol/L) compared to the AGA group (median: 458.7 mmol/L, min-max: 314.5-718.5 mmol/L) (Mann-Whitney U-test; P<0000). The probability of having a cortisol plasma level greater than or equal to 458.7 mmol/L for IUGR newborns was only 1:12, and to have cortisol plasma level less than or equal to 312.3 mmol/L for AGA newborns was much lower (0:34). In the range of plasma cortisol level between 312.3 mmol/L and 458.7 mmol/L, no statistically significant difference in the plasma cortisol level between IUGR and AGA newborns was found. CONCLUSIONS: Neonatal plasma cortisol level is lower in the IUGR compared to the AGA group. Our results suggest that endocrine relationships seem to be lost in a specific group of the IUGR newborns. Although we usually tend to simplify the problem and declare only one cause, this time it is impossible. It is probable that the cause is hidden in small and insufficient placenta with deranged auto-regulation of placental 11beta-HSD-2 mechanism.

Socio-demographic characteristics and lifestyle habits of pregnant women smokers.

The aim of this study was to describe anthropometric, clinical, socio-demographic characteristics and lifestyle habits of pregnant smokers in comparison to pregnant nonsmokers. During years 1999-2003, 1,435 pregnant smokers and 4,772 pregnant nonsmokers were interviewed after delivery with a questionnaire. They were recorded clinical, anthropometric and socio-demographic data, smoking status, labor outcome, maternal and fetal hemoglobin concentrations for each patient. The two groups were comparable in anthropometric and clinical characteristics, duration of pregnancy and mode of delivery, except for birth weights, which were significantly lower in newborns of smokers. Maternal hemoglobin concentrations were significantly lower in smokers, but fetal hemoglobin concentrations were significantly higher in babies of smokers. The proportion of pregnant women who smoked during pregnancy was higher among urban women, among women with lower educational level and among unemployed subjects in comparison with nonsmokers. The pregnant women who smoked during pregnancy were more often caffeine and alcohol consumers. To further reduce smoking during pregnancy it is important to continue to promote smoking cessation among teenagers.

Comparison of fetal plasma cortisol level between eutrophic and hypotrophic newborns.

We tested two groups of singletons born at term: fifty-six eutrophic newborns and 56 hypotrophic subjects. They were selected randomly from all newborns delivered by vaginal route between 8 and 14 hours. Excluded were preeclampsia, diabetes, labours longer than 12 hours and newborns with malformations. Written informed consent was obtained from all women and data were collected before and after labour. Umbilical cord blood samples were obtained immediately following the delivery and plasma cortisol concentrations were measured by radioimmunoassay. The groups did not differ significantly regarding maternal age, parity, gestational age and Apgar score, but birth weight was significant differed (p < 0.001). In addition, eutrophic newborns had significantly elevated cortisol levels (457.7 nmol/L, 321.8-696.6 nmol/L) compared with hypotrophic newborns (320.5 nmol/L, 215.1-578.7 nmol/L, p < 0.001). The role of fetal cortisol in intrauterine growth restriction (IUGR) pregnancy and labour is uncertain, but fetal plasma cortisol levels may be lower in IUGR newborns.

Differences in sexual functioning between patients with benign and malignant breast tumors.

The aim of this study was to compare differences in sexual behavior between patients with benign and malignant breast tumors. A total of 187 patients treated for breast tumors (benign or malignant) at the General Hospital >>Pozega<<, Croatia, filled in the questionnaire between January 2001 and May 2003. Patients were asked to fill in the questionnaire one to ten years after treatment of breast tumor, while they were on their regular control visit. Deterioration in sexual life experienced 36.27% of patients with benign tumors and 51.76% of patients with malignant tumor (p<0.01). The main reason of sex life impairment in both groups was distortion of body image perception. Most of partners did not change their behavior toward women with breast tumors (48.72% for benign group and 41.82% or malignant group, p>0.05). A great amount of women in both groups felt certain change in her >>body image<<, but in greater extent in malignant group (41.18% vs. 25.49%), (p<0.05). From our results we can see that patients in this study do not recognize need for consultation with their physician regarding sex life after treatment of tumor (41.18% for benign and 35.29% in malignant group). It can be concluded that considerable amount of attention should be given to psychological aspects of recovery which can improve prognosis and quality of life in general.

Uterine artery embolization for the treatment of uterine fibroids.

Uterine artery embolization can be regarded as a less invasive procedure for the treatment of fibroids compared with myomectomy, hysterectomy, and laparoscopic myolysis. The aim of this study was the evaluation of safety and efficacy of uterine artery embolization and of womens' opinion about this treatment. After gynecological examination sixty-nine premenopausal women underwent uterine artery embolization. All procedures but four were technically successful; three women underwent unilateral embolization because of vascular malformation and one of them had an allergic reaction to contrast medium. Of the 69 patients: 58 went home the day after embolization, and 11 within first week. The follow-up examinations after 3, 6 and 12 month showed a significant reduction of uterine and fibroid volume with significant improvement of bleeding. Therefore, according to this report, uterine artery embolization is a successful, minimal invasive treatment of myoma that preserves the uterus and requires shorter hospitalization and recovery times than surgery.