Stress urinary incontinent women, the influence of age and hormonal status on estrogen receptor alpha and beta gene expression and protein immunoexpression in paraurethral tissues.

The underlying cause of stress urinary incontinence (SUI) is an anatomical abnormality associated with paraurethral connective tissue dysfunction. The question as to whether estrogens affect the quality of that tissue remains unexplained. Samples of paraurethral connective tissue from 81 women were examined (the SUI's n = 49; the control's n = 32). In both groups, the patients were subdivided into pre- and postmenopausals. Primary study outcome was comparison of the estrogen receptor alpha (ERα) and the estrogen receptor beta (ERß) gene and protein in paraurethral tissue between SUI and control group. Secondary study outcome was comparison of these receptors according to hormonal status of the patients and their age. In both examined groups, we found both ER proteins. The ERα gene expression was detected in-19/32 (SUI) samples and in 24/31 (control), and ERß gene expression 31/32 and 30/31 samples, respectively. The SUI's had significantly lower ERa gene expression premenopausally than the control's. The analysis found considerably lower ERß and reduced ERα gene expression in postmenopausals, approaches the significance level. There was also significant decrease in both receptors' genes expression in post-53 women, compared to younger patients. Spearman's correlation test revealed a statistically significant decrease in ERß gene with age. Both estrogen receptors are found in women's paraurethral tissue, so this tissue is an estrogen target. No correlation between ERß gene expression and immunoexpression and SUI was found. The ERα gene seems to play a key role in SUI in the premenopausal period, but ERß gene expression in the paraurethral connective tissue decreases with age.

Influence of ovarian cancer type I and type II microenvironment on the phenotype and function of monocyte-derived dendritic cells

PURPOSE. The aim of this study was to evaluate the influence of ovarian cancer cell lysates isolated from type I or type II ovarian cancer (OC) on the phenotype of monocyte-derived dendritic cells (Mo-DCs) and the cytokine profile. We also determined whether the Mo-DCs and tumor microenvironment, reflected by peritoneal fluid (PF) from type I or II ovarian cancer, could promote regulatory T cell (Tregs) differentiation from naive CD4+ lymphocytes in vitro. RESULTS. Our results show a significant role of the ovarian cancer microenvironment reflected by PF from type I or II OC in the inhibition of the DC differentiation process. Interestingly, the percentage of cells co-expressing CD45 and CD14 antigens in the cultures stimulated with PF from both type I and type II OC was higher than in the control. Furthermore, the percentage of cells expressing CD1a, i.e., a marker of immature DCs, was significantly reduced in the cultures stimulated with PF from type I and type II OC. The results obtained show that ovarian cancer type II lysates induce differentiation of monocytes into macrophage-like cells with a CD1a+/HLA-DR+/CD83− phenotype and significantly higher CD86/HLA-DR expression. We show that ovarian cancer type II Mo-DCs are able to prevent an immune response by release of IL-10, whereas OC type I Mo-DCs can promote the generation of Tregs. CONCLUSIONS. We demonstrate that each type of ovarian cancer can induce a unique phenotype of DCs and differentiation of Tregs, both associated with immune-suppressive function, which may be an obstacle while developing effective anticancer dendritic cell vaccination (AU)

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Influence of ovarian cancer type I and type II microenvironment on the phenotype and function of monocyte-derived dendritic cells.

PURPOSE: The aim of this study was to evaluate the influence of ovarian cancer cell lysates isolated from type I or type II ovarian cancer (OC) on the phenotype of monocyte-derived dendritic cells (Mo-DCs) and the cytokine profile. We also determined whether the Mo-DCs and tumor microenvironment, reflected by peritoneal fluid (PF) from type I or II ovarian cancer, could promote regulatory T cell (Tregs) differentiation from naive CD4+ lymphocytes in vitro. RESULTS: Our results show a significant role of the ovarian cancer microenvironment reflected by PF from type I or II OC in the inhibition of the DC differentiation process. Interestingly, the percentage of cells co-expressing CD45 and CD14 antigens in the cultures stimulated with PF from both type I and type II OC was higher than in the control. Furthermore, the percentage of cells expressing CD1a, i.e., a marker of immature DCs, was significantly reduced in the cultures stimulated with PF from type I and type II OC. The results obtained show that ovarian cancer type II lysates induce differentiation of monocytes into macrophage-like cells with a CD1a+/HLA-DR+/CD83- phenotype and significantly higher CD86/HLA-DR expression. We show that ovarian cancer type II Mo-DCs are able to prevent an immune response by release of IL-10, whereas OC type I Mo-DCs can promote the generation of Tregs. CONCLUSIONS: We demonstrate that each type of ovarian cancer can induce a unique phenotype of DCs and differentiation of Tregs, both associated with immune-suppressive function, which may be an obstacle while developing effective anticancer dendritic cell vaccination.

Patient's Education Before Mastectomy Influences the Rate of Reconstructive Surgery.

Breast reconstruction (BR) should be offered and discussed to each woman with breast cancer who planned for mastectomy, except the cases with severe comorbidities. However, the majority of these patients do not undergo reconstructive surgery. A 20-question survey was administered to a group of 50 women (age 29-83 years, median 53) treated with mastectomy. 22.4 % underwent reconstruction of the breast, 24.5 % declared an interest in BR in the future, 53.1 % were not interested in reconstructive surgery. 51.2 % obtained information concerning BR before surgery, 58.1 % after and 44.2 % both before and after mastectomy. 59.2 % were informed about reimbursement. Information given before surgery had a statistically significant impact on performing reconstruction or a declared interest in BR (X 2 = 4.950, df = 1, p < 0.05), as well as information about reimbursement (X 2 = 8.875, df = 1, p < 0.05). Age <55 years was another significant factor (X 2 = 13.522, df = 1, p < 0.05, C Pearson = 0.525). Level of education did not impact upon the choice (p > 0.05). The main reasons for the refusal were fear of complications (47.4 %), priority to recovery over aesthetic (36.8 %), age, defined by the patient as "advanced" (31.6 %), high level of acceptance of the body after amputation (31.6 %), fear of cancer recurrence (26.3 %) and fear of the pain and discomfort (15.8 %). Each patient who planned for mastectomy should obtain sufficient information regarding breast reconstruction. Exact information is of special benefit to women discouraged by imagined disadvantages of surgery. Patients' education impacts the quality of life-not only before surgery but also lifelong after finishing the treatment.

Upper Extremity Lymphedema After Axillary Lymph Node Dissection: Prospective Lymphoscintigraphic Evaluation.

This prospective study was designed to evaluate changes in upper extremity lymphatic drainage after ALND in comparison to the preoperative status using lymphoscintigraphy. The study enrolled 44 women (mean age: 57.95; range: 35-80) with a new diagnosis of unilateral invasive breast carcinoma who had been scheduled to undergo ALND. This was a substudy of the physiotherapeutic project, in which subjects after ALND were randomized into 4 groups treated with: 1) rehabilitation exercises; 2) manual lymphatic drainage; 3) pneumatic compression pump; and 4) education only. Clinical evaluation which included arm measurements and lymphoscintigraphy was performed in every subject before surgery and 3 times after surgery (1-6 weeks, 1 and 2 years after ALND). Follow-up was completed in 44 subjects at 1 year and in 32 subjects at 2 years. Lymphedema diagnosis was made in 4 subjects 1 year after ALND (9%) and in 8 subjects 2 years after ALND (25%). Among them, respectively, only 50% and 62% noticed and reported lymphedema. Quantitative analysis of lymphoscintigrams and photoplethysmography results did not reveal upper extremities lymphatic transport and/or venous function impairment after the ALND procedure. Qualitative analysis of lymphoscintigrams revealed most commonly disappearance of previously functional lymph nodes and appearance of dermal backflow in subjects who developed lymphedema. Conversely, appearance of functional lymph nodes in different locations after ALND may indicate protection from development of upper extremity lymphedema.

Paget's disease of the nipple treated successfully with cryosurgery: a series of cases report.

INTRODUCTION: Paget's disease of the nipple is a rare form of breast malignancy. Underlying breast cancer, either in situ or invasive accompanies lesions of the nipple in most of the cases. The connection between both entities and their exact origin remains unclear. Nevertheless, underlying ductal breast cancer is often confined to the central, subareolar part of the breast. Radical mastectomy, although successful, seems to be too mutilating treatment in the era of breast sparing surgery. Studies describing breast conserving surgery performed without adjuvant treatment are rare and the patients not numerous. Due to low incidence of the disease, there are no randomised trials conducted which could show the optimal method of treatment. MATERIALS AND METHODS: We performed cryosurgery of the affected nipple-areola complex (NAC) in treatment of six patients with Paget's disease of the nipple who presented general contraindications or lack of consent for surgery. RESULTS: With a follow up ranging from 60 to 121 months (average 94) we obtained very good results in terms of disease specific survival: there were two cases of recurrent disease, confined to the scar and treated successfully with cryosurgery again; four patients are alive without disease. Death was not related to cancer in the remained two cases. CONCLUSIONS: Cryotherapy is successful form of treatment of localised Paget's disease of the nipple--especially in face of contraindications for surgery or lack of patient's agreement for operational treatment.

Axillary lymph nodes and arm lymphatic drainage pathways are spared during routine complete axillary clearance in majority of women undergoing breast cancer surgery.

Alterations in axillary lymph nodes (ALNs) after complete axillary lymph node dissection (ALND) in comparison to the preoperative status were evaluated using lymphoscintigraphy performed preoperatively and 1-6 weeks after surgery in 30 women with a new diagnosis of unilateral, invasive breast carcinoma. Analysis of lymphoscintigrams revealed that ALNs after surgery were present in 26 of 30 examined women. In comparison to preoperative status, they were visualized in the same location (12 women), in the same and additionally in different locations (9 women), or only in different locations (4 women). No lymph nodes were visualized in one woman and lymphocoele were in 4 women. Thus, after ALND, a variable number of axillary lymph nodes remain and were visualized on lymphoscintigraphy in the majority of women. The classical ALND, therefore, does not allow complete dissection and removal of axillary nodes with total disruption of axillary lymphatic pathways, accounting in part for the variable incidence and severity of lymphedema after the procedure.

Leptin gene expression in subcutaneous adipose tissue in girls before and during puberty.

OBJECTIVES: Leptin functions as a neuroendocrine hormone and it is related to the onset of puberty in animal models. Its role in normal human sexual maturation is still incompletely defined. The aim of the study was to assess the relationships between leptin mRNA (gene) expression, thickness of subcutaneous fat tissue and the serum concentration of leptin in girls before and during puberty. STUDY DESIGN: Twenty-nine lean girls were studied (mean age 10.8+/-1.9 years). The subjects were divided into two groups according to pubertal status. The first group consisted of 14 prepubertal girls and second group of 15 girls who were in puberty. Body height, weight, arm circumference, skin fold thickness at abdominal, triceps and subscapular sites were measured. Serum leptin was assessed by RIA method. Leptin mRNA was measured in subcutaneous abdominal adipose tissue by semi-quantitative assays based on reverse transcription (RT) of the mRNA and polymerase chain reaction (PCR) amplification of the cDNA. RESULTS: Girls in pubertal stages had higher serum leptin concentration than prepubertal girls. The mean values of leptin mRNA level in subcutaneous abdominal adipose tissue were not statistically different between groups. There was also no difference between the thickness of skin folds in investigated girls. A positive correlation between leptin mRNA expression and skin fold thickness, BMI and arm circumference as well as between the leptin concentration and skin fold thickness, BMI and arm circumference were observed. CONCLUSIONS: The level of leptin gene expression and serum leptin concentrations depend on the amount of fat tissue. We can propose that initiation of pubertal events does not result from increased of leptin mRNA expression in subcutaneous abdominal fat cells or from its increased concentration in blood.

Therapeutic results in low-rectal cancer patients treated with abdominosacral resection are similar to those obtained by means of anterior resection in mid- and upper-rectal cancer cases.

AIMS: To present the experiences of the Regional Comprehensive Cancer Center in Wroclaw with abdominosacral resection (ASR) carried out in low-rectal cancer patients. METHODS: Rectal cancer patients (n=294) were operated on by the same surgical team using the standardized TME technique between May 5, 1998 and February 23, 2001. Depending on the distance from the anal verge, the primary tumor was removed by means of standard abdominal resection (AR-mid- and upper-rectal cancers) or abdominosacral resection (ASR-low-rectal cancers). The patients who underwent the different operative procedures were comparable in terms of distributions of age, gender, tumor infiltration depth and regional lymph node involvement with no significant statistical difference between the groups. RESULTS: Ninety-seven cases were excluded from the analysis of survival based on exclusion criteria defined. Consequently, 197 cases were left for further analysis, including 154 patients operated on by AR and 43 who underwent ASR. AR and ASR patients did not differ significantly in terms of postoperative morbidity (11% and 14%, respectively), observed (57.1% vs. 60.4%) and relative 5-year survivals (74.3% vs. 73.2%) and the cumulative 5-year local recurrence rate (5.8% vs. 4.7%). CONCLUSION: The combined use of the modern TME technique and the "historical" abdominosacral excision of the rectum seems to give new, potentially attractive perspectives for successful surgical treatment of low-rectal cancers.

Leptin messenger ribonucleic acid (mRNA) content in the human placenta at term: relationship to levels of leptin in cord blood and placental weight.

During fetal life, placental tissue represents an additional source of leptin for the mother and conceptus. It has been suggested that feto-placental production of leptin may be involved in placental and fetal growth regulation. The aim of this study was to examine the correlation between leptin mRNA expression in the placenta and the concentrations of leptin in cord blood. A total of 30 healthy, pregnant women who gave birth to healthy neonates were included in the study. Maternal blood (obtained from the cubital vein) and umbilical cord blood were drawn immediately after birth. Serum leptin concentration was determined by enzyme-linked immunosorbent assay and serum insulin concentration was measured by radioimmunoassay. Leptin mRNA was measured in placental tissue by a reverse transcriptase-polymerase chain reaction. The estimated mean leptin mRNA expression in placenta was 4.65 +/- 1.83 pg mRNA/microg DNA. Leptin mRNA correlated with cord serum leptin concentrations (r = 0.3691, p = 0.045). Placental weight correlated with placental leptin mRNA (r = 0.3686, p = 0.045). The mean leptin concentration in cord serum at birth was slightly lower (3.1 +/- 1.9 ng/ml) than that found in maternal serum (3.9 +/- 1.2 ng/ml). A positive correlation was observed between cord and maternal serum leptin levels (r = 0.58, p = 0.001). The mean insulin concentration in maternal serum was not significantly higher than that in umbilical serum: 22.2 +/- 17.8 microIU/ml vs. 6.9 +/- 3.6 microIU/ml; r = 0.069, p = 0.71). Neither maternal nor umbilical insulin concentrations correlated with leptin concentration in cord or maternal peripheral serum.

[Lipid peroxides, tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in peritoneal fluid from infertile women with minimal and mild endometriosis]. / Produkty peroksydacji lipidów, czynnik martwicy nowotworów alpha (TNF-alpha) oraz interferon gamma (IFN-gamma) w plynie otrzewnowym nieplodnych kobiet z lagodna postacia endometriozy.

OBJECTIVES: To assess the concentrations of tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and lipid peroxides (the marker of free radicals activity) in peritoneal fluid (PF) of infertile women with minimal and mild endometriosis. MATERIALS AND METHODS: 19 women were studied, including 9 infertile women with minimal or mild endometriosis and 10 patients with tubal occlusion (the reference group). Lipid peroxides (malonyldialdehyde and 4-hydroxynonenal), TNF-alpha and IFN-gamma concentrations were measured in the PF using commercially available kits. RESULTS: Concentration of IFN-gamma was detectable in PF of 7 (77.8%) women with endometriosis and in PF from 3 (30%) patients with tubal occlusion. Neither TNF-alpha or lipid peroxides PF concentration differed significantly (p < 0.05) between the groups. In the group with endometriosis we have found a positive correlation (R = 0.77, p = 0.04) between the concentrations of TNF-alpha and IFN-gamma. CONCLUSIONS: Our results suggest that oxidative stress in the PF doesn't appear to play a role in endometriosis-associated infertility.

[Peritoneal fluid and plasma 4-hydroxynonenal and malonyldialdehyde concentrations in infertile women]. / Stezenie 4-hydroksynonenalu i dialdehydu malonowego w plynie otrzewnowym i osoczu krwi nieplodnych kobiet.

OBJECTIVES: To investigate the possible role of oxidative stress in the pathogenesis of female infertility, we examined the peritoneal fluid (PF) and plasma lipid peroxides levels in infertile women. MATERIALS AND METHODS: 4-hydroxynonenal (4-HNE) and malonyldialdehyde (MDA) concentrations were measured in peritoneal fluid and plasma samples obtained from: 10 infertile women with minimal and mild endometriosis, 24 patients with unexplained infertility, 11 women with PCOS and 14 patients with tubal infertility. RESULTS: PF lipid peroxides level was significantly higher in women with idiopathic infertility compared to other groups. Plasma 4-HNE and MDA concentrations did not differ significantly between the infertile groups. No significant difference or relationship was observed between peritoneal fluid and plasma lipid peroxides levels. CONCLUSIONS: Increased free radicals activity in the peritoneal fluid environment may be the factor responsible for some cases of "unexplained infertility".

[Luteal and follicular phase inhibin A and B in regularly cycling women]. / Inhibina A oraz inhibina B fazy follikularnej oraz lutealnej cyklu u kobiet w piatej dekadzie zycia.

OBJECTIVE: To investigate the level of inhibin A nad B in luteal and follicular phase in women of reproductive age. PATIENTS: Seventy women 39-52 years of age with regular menstrual cycle. INTERVENTIONS: Blood samples obtained on days 3-8 and on days 22-25 of menstrual cycle were assayed for FSH, estradiol, inhibin A, inhibin B. RESULTS: Luteal and follicular phase inhibin B was correlated inversely with age. Luteal phase inhibin A was correlated inversely with follicular phase FSH. CONCLUSION: Main form of inhibin in follicular phase of the cycle is inhibin B and in luteal phase inhibin A. Inhibin B can be potential marker of ovarian aging.

[Expression of the survivin gene in the scar endometriosis and in normal human endometrium]. / Ekspresja genu surviviny w tkance endometriozy w bliznie oraz w prawidlowym endometrium.

UNLABELLED: The survivin gene encoding a novel inhibitor of apoptosis protein (IAP) is located on chromosome (17q25). It is expressed during development and in human cancer in vivo. Endometriosis in cicatrix after cesarean section represents the only localization of endometriotic implant which etiology is known. It is believed that during the surgical procedure when the uterine cavity is open there is a high risk of decidualized endometrium implantation. The aim of the study was to estimate the expression of the survivin mRNA in the scar endometriosis after cesarean section (n = 6) and perineum endometriosis (n = 2) and in normal human endometrium (n = 12, reference group) using reverse transcribed-polymerase chain reaction (RT-PCR). METHODS: Total cellular RNA was isolated from the tissues using TriReagent according to the manufacturer's protocol. Total cellular mRNA was transcribed into cDNA with reverse transcriptase (RT) then the survivin gene fragment (430 bp) was amplified with PCR using specific primers. The products of the PCR reaction were separated on 2% agarose gel. The survivin gene was expressed in 4 of 6 cases of scar endometriosis after cesarean section and in 2/2 cases of perineum endometriosis. In all cases of normal endometrium we found the expression of survivin with a peak in the late proliferative phase. The antiapoptosis function of this gene product may play an important role in the endometriotic implant growth promotion.

[Glutathione peroxidase concentration in the peritoneal fluid from infertile women]. / Stezenie peroksydazy glutationowej w plynie otrzewnowym nieplodnych kobiet.

OBJECTIVES: To assess the concentration of Plasma Glutathione Peroxidase (plGPx) in the peritoneal fluid (PF) of patients with unexplained infertility and infertile women with minimal and mild endometriosis. MATERIALS AND METHODS: 33 women were studied, including 8 infertile women with minimal or mild endometriosis, 15 patients with unexplained infertility and 10 patients with tubal occlusion (a reference group). Concentration of plGPx was measured in the PF using a commercially available ELISA kit (Oxis Inc.). RESULTS: The plGPx concentration was significantly (p = 0.04) lower in PF from women with unexplained infertility (846 +/- 177 ng/ml) compared to the reference group (1023 +/- 238 ng/ml), but did not differ significantly (p = 0.25) between women with endometriosis (918 +/- 81 ng/ml) and patients with tubal infertility. CONCLUSIONS: Our results suggest that low peritoneal plGPx concentration may play a role in the pathogenesis of infertility.

[Expression of the survivin gene in normal and hyperplastic endometrium]. / Ekspresja genu surviviny w prawidlowym i rozrostowym endometrium.

OBJECTIVE: Surviving a novel anti-apoptotic gene is expressed during fetal development and in numerous human cancers. MATERIAL AND METHODS: We analyzed the expression of surviving in human normal endometrium: proliferative n = 8, secretive n = 4 cases and hyperplastic endometrium 6 cases. RESULTS: RT-PCR revealed surviving expression in all cases of normal and hyperplastic endometrium. The highest expression of surviving gene was observed in hyperplastic endometrium and in the late proliferative phase.

[Aromatase (P450AROM) mRNA expression in normal, hyperplastic and malignant endometrium and aromatase activity in endometrial cancer tissue culture]. / Ekspresja genu P450AROM w prawidlowym, rozrostowym i nowotworowym endometrium oraz aktywnosc aromatazy w hodowli skrawków raka endometrium.

Aromatase (P450AROM) is the enzyme complex with converts testosterone to estradiol and androstendione to estrone. This enzyme was detected in various normal tissues and uterine pathology such as uterine myoma, endometrial cancer and endometriosis. The aim of the study was to estimate expression of P450AROM messenger ribonucleic acid (mRNA) in normal, hyperplastic and malignant endometrium, and the ability to convert androstenedione to estrone by endometrial cancer tissue. Normal endometrium was obtained from 16 (12 proliferative phase, 4 secretory phase) regularly cycling women after hysterectomy for myomas, hyperplastic endometrium (n = 5) and endometrial cancer (n = 5) from postmenopausal women. The ability to convert androstenedione to estrone was estimated in 16 cases of endometrial cancer in postmenopausal women. P450AROM mRNA was measured by a quantitative assay based on reverse transcribing the mRNA into cDNA with reverse transcriptase (RT) then amplification of the cDNA using the polymerase chain reaction (PCR). The mean (+/- SEM) expression of aromatase gene in proliferative endometrium was 84.4 +/- 14.0 pg mRNA/microgram DNA and in secretory endometrium 200.3 +/- 87.8 pg mRNA/microgram DNA. The mean (+/- SEM) P450AROM mRNA expression in endometrial hyperplasia was 92.9 +/- 17.8 pg mRNA/microgram DNA, in endometrial cancer was 14.3 +/- 7.7 pg mRNA/microgram DNA. Androstenedione to estrone conversion in endometrial cancer tissue culture was 252.5 +/- 91 fmol/g tissue/h. Our data confirm that human normal, hyperplastic and malignant endometrium do express P450AROM mRNA and that aromatase activity is present in endometrial cancer tissue.

[Laparoscopic modification of Vecchietti operation in the treatment of congenital vaginal aplasia]. / Laparoskopowa modyfikacja metody Vecchietiego u dziewczat z aplazja pochwy.

Four young women aged 16-18 years were treated by laparoscopic modification of Vecchietti operation because of congenital vaginal aplasia. In all cases the postoperative period was uneventful and in every case functional vagina with the length 12 cm was achieved within 4 to 14 days of treatment. No pain killers were used during the olive traction in order to create a vagina. Our own instrumentarium necessary to perform such kind of operation was presented. Technical aspects of laparoscopic modification of Vecchietti operation were discussed.