Otopalatodigital Syndrome Type I: Novel Characteristics and Prenatal Manifestations in two Siblings.

Otopalatodigital spectrum disorder (OPDSD) is rare group of X-linked disorders caused by mutations in the filamin A (FLNA) gene. It is characterized by skeletal dysplasia of variable severity and different extra skeletal manifestations. Its presentation in the fetal period is quite unspecific, so diagnosis is usually made after birth. We present prenatal ultrasonography and postmortem findings that led us to a diagnosis of the mildest form of OPDSD (OPD type I) in two consecutive pregnancies. This is the first report on prenatal diagnosis (PND) of OPD type I. Affected fetuses showed facial dysmorphy (hypertelorism, micrognathia, cleft palate) and digital anomalies, features typical of OPD type I. In addition, microphtalmia and early neonatal death due to severe respiratory distress syndrome are described as a novel characteristics of the disorder. Clinical exome sequencing revealed a hemizygous missense pathogenic variant in the FLNA gene (NM_ 001110556.1: c.620C>T). We suggest that the presence of hypertelorism, micrognathia, digital anomalies on prenatal ultrasound examination should alert suspicion to OPDSD. Detailed clinical examination of mother and other female relatives is of great importance in establishing definitive diagnosis of OPD type I.

Laparoscopic management of ovarian benign masses.

PURPOSE: To determine whether the presence of normal ovarian tissue could assist in the diagnosis of large benign ovarian neoplasms in young females and in choosing the laparoscopic treatment. MATERIALS AND METHODS: A prospective study of 25 patients treated surgically for a cystic ovarian neoplasm measuring diameter more than ten cm or volume more than 500 ml and having normal ovarian tissue or ovarian crescent sign (OCS). Ultrasonography was performed at six weeks, then at three, six, nine, and 12 months postoperatively. RESULTS: The mean age of patients was 15.3 +/- 3.6 years, ranging between 6.5 and 19 years. The mean preoperative volume of the ovarian neoplasm was 1,686 +/- 1,380 cm3, ranging between 550 and 6,000 cm3. The presence of OCS was visualized by ultrasonography in all 25 patients and serum tumor markers were negative in 22. No borderline tumors or malignancies were identified. There was a statistically significant difference between the volume of the affected ovary and the contralateral ovary during the first six weeks follow-up, but without significant difference after three months. CONCLUSIONS: Postoperative ultrasound revealed that the affected ovary resumed its normal volume within three months after surgery, despite the thinned appearance of the ovarian cortex present on ultrasound as the OCS. Laparoscopic ovarian preservation should be the preferred surgical approach for adolescents to ensure the conservation of the entire ovarian tissue.

Giant Gartner duct cyst and elevated CA-125.

BACKGROUND: Gartner duct cysts represent vestigial remnants of the caudal end of the mesonephric (Wolffian) ducts. They are often associated with ureteral and renal abnormalities. In most cases they are solitary, less than 2 cm in diameter. Giant Gartner duct cysts are extremely rare. CASE: We present a girl with a giant Gartner duct cyst, without notable associated abnormalities or pathology, successfully treated by surgical excision. Preoperative aspiration revealed elevated level of CA-125 in the cyst fluid, with normal serum level of the same marker. CONCLUSION: Analyzing the aspirated fluid for CA-125 may be a useful tool for evaluation of cystic lesions in this region.

Ovary-preserving tumorectomy for immature teratoma in an adolescent--case report.

The authors present a case of a 14-year-old premenarchal girl with a large solid tumor of the left ovary. The rim of normal ovarian tissue was visible around the tumor on ultrasonography scan. Although the levels of two tumor markers, LDH and CA125, were elevated, the authors performed an organ-sparing tumorectomy. The final pathology report revealed foci of immature neural tissue, with a final diagnosis immature teratoma Stage Ia.

Prognostic value of survivin expression in Wilms tumor.

PURPOSE: To determine survivin expression patterns in Wilms tumor (WT) and compare it with the expression in normal renal tissue. Also, to analyse cytoplasmic and nuclear survivin expression in relation to histological type, prognostic group and tumor stage. METHODS: Immunohistochemical expression of survivin was analysed in 59 cases of primary WT and in 10 normal kidney specimens, taken from the same patients, but distant from the tumor. RESULTS: 51 out of 59 cases of WT (86.44%) showed decreased cytoplasmic survivin expression and 4 out of 59 cases of WT (6.78%) showed nuclear overexpression of survivin. There was statistically significant difference in the frequency of decreased cytoplasmic expression of survivin in individual components of WT (p=0.005). Decreased cytoplasmic expression of survivin in epithelial, blastemal and stromal component was found significantly more often in low stage WT compared to high stage WT (Fisher exact test, p=0.0002, p=0.002, p=0.002, respectively). There was no statistically significant difference in the frequency of survivin nuclear overexpression between different stages of WT (Fisher exact test, p=0.564), histological types (Fisher exact test, p=0.915), or between different prognostic groups (Fisher exact test, p=1). CONCLUSION: Decreased survivin cytoplasmic expression or nuclear overexpression may be related to favorable prognosis of WT.

Minimal invasive treatment of cervical rhabdomyosarcoma in an adolescent girl.

Rhabdomyosarcomas are the most common soft tissue sarcomas in childhood and adolescence. In cases of minimal cervical invasion, less invasive local excision in combination with adjuvant chemotherapy has resulted in excellent survival rates with complete preservation of the bladder, rectum, uterus and vagina. Herein we present the case of an adolescent girl with a large rhabdomyosarcoma of the uterine cervix treated with minimal invasive therapy.

Epithelial ovarian tumors and CA125 in premenarchal girls.

PURPOSE: This is a review of our 18-year experience with premenarchal girls with epithelial ovarian tumors. Special attention was focused on the predictive value of CA125 serum levels. METHODS: Analysis of premenarchal patients with resected or biopsied ovarian masses from 1988 to 2005 was performed. Patient age, clinical presentation, operative procedures, histologic type of tumor, treatment and outcome were obtained. RESULTS: Six premenarchal girls (aged from 6 to 14 years) were surgically treated for epithelial tumors, representing 13% of all ovarian tumors at this age. Histological findings revealed cystadenoma in four girls, one with a mucinous borderline tumor and one with undifferentiated carcinoma. Tumor volume was higher than 400 cm3 in four girls. Sensitivity, specificity and positive predictive value of CA125 level for ovarian malignant epithelial tumors were 0.50, 0.50, and 0.33, respectively. The premenarchal girl with undifferentiated carcinoma in Stage III died after six months in spite of chemotherapy. CONCLUSION: Ovarian epithelial tumors in premenarchal girls show important growth potential and a relatively high malignancy rate with great influence of borderline neoplasms. CA125 is a tumor marker with low sensitivity and specificity for detection of epithelial ovarian malignancy in this age group.

[Mathematical modeling in preooperative planning for reconstructive and plastic surgery].

Social importance of skin emphasizes an importance of quality of methods of planning for reconstructive and plastic surgery. With modern technical improvement the usage of complex mathematical model based on biomechanical characteristics of tissue is possible. Two- and three-dimensional model, expert systems and mechanical analysis are used. In this work we tested the system for mechanical analysis in preoperative planning of a simple procedure of the Z-plastic, named the finite-element method. Computer model simulates tissue coverages. With geometrical data some physical characteristics are added. Complex surface of skin is marked by the grid divided in quadrangular elements. Mechanical consequences and definitive results of surgical procedure are analysed during the computer simulation of the action of tension of skin and suture material. In our analysis we found the finite-element method of great usefulness and noticed that "surgery simulators" might be an efficient way to speed-up learning curve in reconstructive surgery.

Sputum cytopathological findings in pig farmers.

The purpose of this study is to compare the cytological changes in the respiratory tracts of pig farmers exposed to an environment of swine confinement buildings with control, non-exposed subjects living in the same geographical area. Spontaneously produced sputum specimens were obtained from 133 pig farmers and 120 control subjects, all clinically healthy, and grouped according to smoking habits and sex. The findings of siderophages, eosinophils, abnormal columnar cells and respiratory spirals were significantly more frequent in the pig farmers. Siderophages were noted in 25.6% of pig farmers and in 5% of control subjects. By logistic regression analysis, pig farming is the single predictive factor for siderophages and eosinophils. For other cytological abnormalities, except Creola bodies and granular debris, smoking is the most significant predictive variable, but pig farming, age and male sex also correlate with smoking. Atypical squamous metaplasia was observed in 11.3% of pig farmers and in 5.8% of control subjects. These findings are in concordance with previous epidemiological and clinical studies and also reveal a new aspect of the harmful effect of pig farming exposure to the vascular and epithelial structures of the respiratory tract. It also demonstrates the usefulness of the simple method of sputum cytological analysis.

[Sertoli-Leydig cell tumour (arrhenoblastoma) in a patient with polycystic ovary syndrome: clinical, ultrasonographic, hormonal and histopathological evaluation]. / Tumor Sertoli-Lajdigovih celija (arenoblastom) kod bolesnice sa sindromom policisticnih jajnika: klinicka, ultrasonografska, hormonska i histopatoloska evaluacija.

UNLABELLED: Nowadays, the polycystic ovary syndrome is considered the most common endocrinopathy in women. A patient referred for oligomenorrhea or amenorrhea, will probably be classified as suffering from this syndrome if at least one of the three characteristics of the syndrome is present: 1. polycystic ovaries (ultrasonographic finding); 2. hirsutism, and 3. hyperandrogenism. However, differential diagnosis of PCOS must also include patients with menstrual disorders and hirsutism, suffering from disorders of the pituitary gland (hyperprolactinaemia or acromegaly), disorders of adrenal glands (congenital classical or non-classical adrenal hyperplasia) or androgen secreting ovarian tumours. CASE REPORT: A PCOS patient with a very high serum testosterone level -8.2 nmol/L (normal concentrations 0.7-3.47 nmol/L), and clinical signs of hyperandrogenism, which had been deteriorating during the monitoring period of approximately two years, is presented. The first ultrasound examination diagnosed polycystic ovaries, having a volume at the upper limit of normal range (7.9 cml). After one year ultrasound showed an asymmetrical enlargement of the right ovary (volume 25.34 cm3). Three months later a tumour of the right ovary was diagnosed (Figure 1). Salpingo-oophorectomy was performed. Microscopic analysis indicated without doubt the presence of a Sertoli-Leydig cell tumour of intermediate differentiation (Figure 2). DISCUSSION: In adolescence, congenital adrenal hyperplasia and adrenal tumours may be a source of elevated androgen concentrations. Adrenal tumours usually also cause excess secretion of dehidroepiandrosteron-sulfate (DHEAS). However, rare cases of adrenal tumours with excess testosterone secretion, but with normal or even low DHEAS levels, have also been reported. Adrenal carcinoma can cause virilization, however, in this case excess cortizole secretion is also frequently present. In young patients, the most common state accompanied by hyperandrogenism is PCOS. Hyperthecosis is also accompanied by high testosterone levels, but an ultrasound finding of cystic ovaries is not typical for this condition. Androgen-secreting ovarian tumours are a more common cause of hyperandrogenism than hyperthecosis. Sertoli-Leydig cell tumours are tumours of sexual cords and ovarian stroma. They present as unilateral, solid tumours (bilateral in < 3% of cases). In all cases when they are histologically well or intermediately differentiated, as in our patient, they are limited to the ovary. The percentage of Sertoli-Leydig cell tumours, manifesting endocrine activity has not been established, but it most probably amounts to about 50%, while virilization develops in about 1/3 of patients. In tumours showing hormonal activity the testosterone level is elevated, while the DHEAS level is within the normal range. Analysis of our patient confirmed the immense importance of detailed anamnesis, physical examination and regular control check-ups. Asymmetrical ovarian volume, especially if accompanied by unusually high testosterone concentrations, very probably points to an ovarian tumour, and when dealing with a patient with progressive hirsutism and/or virilization, even with a negative ultrasound finding, the clinician should remain suspicious and careful and request control examinations.

[The effect of sex factors on cytologic changes in the sputum of young adults exposed to urban air pollution]. / Uticaj pola na citoloske promene u sputumu kod mladih odraslih ljudi islozenih gradskom aerozagadjenju.

UNLABELLED: The harmful effect of occupational and urban air pollution on the function and structure of the respiratory tract has been proved. The severity and incidence of epithelial changes are in direct relation to duration of exposure and age of the examined population groups [1]. Squamous metaplasia of bronchial epithelium is an indicator of predisposition to chronic obstructive pulmonary disease and lung cancer [1-5]. Due to its topography and the development of industry and traffic, Sarajevo used to be the city with an extremely high level of air pollution [10-12]. Some studies in adults showed that the respiratory tract exposed to air pollution responded with more severe changes in men than in women [7-9]. The aim of this study was to compare cytological changes in sputa, depending on the sex of young adults exposed to a high level of urban air pollution, and to examine whether a big difference in duration of exposure has an effect on these relations. MATERIALS AND METHODS: The subjects in the study were young adults, university students (21 to 25 years of age), all non-smokers. At the time of sputa collection (March-April 1991) they were clinically healthy with no history of chronic and serious acute respiratory diseases. They were divided into two groups according to the duration of air pollution exposure. The first group included those who had been living in Sarajevo since birth. The second group included those who used to live in pollution-free areas, but for the last two to three years had been living in Sarajevo where they came to attend the University (Table 1). Specimens were early morning spontaneously produced sputa, expectorated directly into Saccomanno's fixative and after centrifugation immersed in paraffin. Nine sections from each block were cut and stained with haematoxylin and eosin. The differences between cytological findings were tested with Hi2 test and Fisher's exact test, regarding sex and duration of exposure to air pollution. RESULTS: The findings are summarized in Table 1. As many as 63% and 64% of the subjects from the first and the second group, respectively, were able to produce sputum, while the others produced saliva only. All sputa contained abnormal bronchial columnar cells and half of them contained respiratory spirals (Figures 1 and 2). Squamous metaplastic cells were found in 7% and 9% of subjects in the first and second group, respectively. These cells showed no evidence of atypia. Statistical tests failed to identify significant differences in the incidence of cytological findings between the groups regarding both the sex of the subjects and duration of their exposure to air pollution (Table 2). DISCUSSION: The ability to produce sputum with the frequent presence of respiratory spirals in both groups of our subjects indicate an extremely harmful effect of smog. However, the incidence of squamous metaplastic cell findings was less severe comparing to adults and the elderly urban population. In the elderly (65 to 105 years of age) severe epithelial changes developed spontaneously in the absence of any other known aetiological factor [8, 9]. The increase in severity of changes in the course of aging, in our opinion, due to a gradual decline in efficiency of the defence mechanisms and regenerative potential of the respiratory system. The experimental study showed a decline of the efficiency of mucociliary clearance [14] as well as the damage of the function and decrease in number of alveolar macrophages in lung parenchyma and bronchoalveolar lavage [15, 16]. Trying to answer the question why the sex-related differences in the severity and incidence of epithelial changes appear in the groups of adults and the elderly, it is presumed that in aging the defence and regenerative potentials decline more rapidly in men than in women. (ABSTRACT TRUNCATED)

Cytological changes of the respiratory tract in young adults related to high levels of air pollution exposure.

Several histopathological and cytological studies have shown that lesions of the respiratory tract epithelium become increasingly severe with duration of exposure to high levels of urban air pollution as well as with ageing of studied population groups. In this study we investigated and compared findings of cytological abnormalities in sputa of young adults (21-25 years of age) exposed to high levels of air pollution since birth with those who were exposed in the last 2-3 years only. All subjects were non-smokers and were clinically healthy at the time of sampling. No significant differences in the incidence or severity of any of the cytological findings were found. The fact that even 10 times longer exposure to air pollution resulted in no major respiratory tract epithelial changes is, in our opinion, a result of the extremely efficient defence mechanisms and enormous regenerative potential of the respiratory tract of younger people.