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PURPOSE To generate and present survey results on important issues relevant to treatment and follow-up of localized and locally advanced, high-risk prostate cancer (PCa) focusing on developing countries. METHODS A panel of 99 PCa experts developed more than 300 survey questions of which 67 questions concern the main areas of interest of this article: treatment and follow-up of localized and locally advanced, high-risk PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up of localized and locally advanced, high-risk PCa in areas of limited resources discussed in this article. RESULTS The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion and not on a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations considered cost-effectiveness as well as the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. Results were tabulated in real time. CONCLUSION The voting results and recommendations presented in this article can guide physicians managing localized and locally advanced, high-risk PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment of localized and locally advanced, high-risk PCa in developing countries have not been defined, this article will serve as a point of reference when confronted with this disease.

PURPOSE To present a summary of the treatment and follow-up recommendations for the biochemical recurrence in castration-sensitive prostate cancer (PCa) acquired through a questionnaire administered to 99 PCa experts from developing countries during the Prostate Cancer Consensus Conference for Developing Countries. METHODS A total of 27 questions were identified as related to this topic from more than 300 questions. The clinician's responses were tallied and presented in a percentage format. Topics included the use of imaging for staging biochemical recurrence, treatment recommendations for three different clinical scenarios, the field of radiation recommended, and follow-up. Each question had 5-7 relevant response options, including “abstain” and/or “unqualified to answer,” and investigated not only recommendations but also if a limitation in resources would change the recommendation. RESULTS For most questions, a clear majority (> 50%) of clinicians agreed on a recommended treatment for imaging, treatment scenarios, and follow-up, although only a few topics reached a consensus > 75%. Limited resources did affect several areas of treatment, although in many cases, they reinforced more stringent criteria for treatment such as prostate-specific antigen values > 0.2 ng/mL and STAMPEDE inclusion criteria as a basis for recommending treatment. CONCLUSION A majority of clinicians working in developing countries with limited resources use similar cutoff points and selection criteria to manage patients treated for biochemically recurrent castration-sensitive PCa.

Background Exercise is recommended for all patients with COPD. Evidence for its benefit is considerably weaker in the more severe stages of the disease. The aim of this study was to investigate whether high-intensity interval training could improve exercise capacity, pulmonary hemodynamics and cardiac function in patients with severe COPD and hypoxemia. Methods Stable patients with COPD GOLD stage III or IV and hypoxemia were included. They underwent extensive cardiopulmonary testing including right heart catheterization, lung function tests, echocardiography and 6-minute walk test before and after completion of 10 weeks of high-intensity interval training performed with supplemental oxygen. Primary endpoint was change in pulmonary artery pressure measured by right heart catheterization. Results Ten patients with very severe airflow obstruction, mean FEV1 28.7% predicted and mean FEV1/VC 0.39 completed the exercise programme. Pulmonary artery pressure remained unchanged following the intervention (26,3 mmHg vs. 25,8 mmHg at baseline, p 0.673). Six-minute walk distance improved by a mean of44.8 m (p 0.010), which is also clinically significant. We found marginally improved left ventricular ejection fraction on echocardiography (54.6% vs 59.5%, p 0.046). Conclusion High-intensity interval training significantly improved exercise capacity while pulmonary hemodynamics remained unchanged. The improvement may therefore be due to mechanisms other than altered pulmonary artery pressure. The increase in ejection fraction is of uncertain clinical significance. The low number of patients precludes firm conclusions.

Background The Expanded Prostate Index Composite for Clinical Practice (EPIC-CP) is a short version of the original EPIC, developed to facilitate the instrument’s use in routine care. This study aimed to validate the EPIC-CP Portuguese version, and evaluate its role in presenting early functional outcomes of surgically treated prostate cancer patients at a Latin American referral center. Methods The EPIC-CP was self-administered prospectively and individually by all localized prostate cancer patients, before and after robotic-assisted radical prostatectomy, from March 2017 to June 2018 at a single institution. For validation, we used the Cronbach’s alpha coefficient to evaluate internal consistency. The EPIC-CP domains were compared before surgery, and 6 months and 12 months after surgery. Statistical analyses were performed using the student’s t test, and Wilcoxon and Friedman tests, with p values Results One hundred and fifty two patients answered the EPIC-CP. The patients had a median age of 62.7 (± 8.5) years and prostate specific antigen level of 6.3 (± 4.6) ng/ml. The Cronbach’s alpha varied from 0.75 to 0.77 for all domains with good internal consistency, except for the “vitality/hormonal” domain, which had a score of 0.35. The domain evolution for the preoperative and 6-month postoperative groups revealed that the domains related to urinary continence and bowel worsened, and were increased during the first 6 months; however, this variation had no obvious clinical implications, and the irritative symptoms improved. Regarding the sexual domain, the scores worsened, and also increased over the first 6 months. The results of the confirmatory factor analysis were robust, with an explained variance of 0.951 and covariance of 0.929. Conclusions The Portuguese version of the EPIC-CP is a reliable and valid questionnaire for postoperative patients, and very useful to improve the knowledge of the early functional outcomes of men treated for prostate cancer.

Background Use of transrectal ultrasound (US)-guided biopsies improved diagnosis and treatment for patients with high prostate-specific antigen (PSA) or abnormal digital rectal exam (DRE). Purpose To investigate whether taking two transition zone (TZ) biopsies in addition to routine prostate double-sextant biopsies (12-cores) would improve detection rates of prostate cancer (PCa). Material and Methods A retrospective analysis of 1107 in a single institution database after Institutional Review Board approval, which underwent US-guided prostate biopsies from January 2014 to June 2016. All patients with suspected PCa based on positive DRE or high PSA submitted to US-guided prostate biopsy (double-sextant 12-cores alone and 12-cores with two TZ extra cores) were included. Results A total of 1107 patients were included; 120 patients underwent double-sextant 12-cores alone and 987 underwent 12-cores with two TZ extra cores. Among patients submitted to two TZ extra cores, TZs of 755 (76.5%) patients were negative to neoplasia and 232 (23.5%) were positive to neoplasia. Among these patients, 26 (2.6%) had their final Gleason score increased with TZ core; TZ fragments of 20 (2.0%) patients led to a treatment change (re biopsy, active surveillance or from active surveillance to radiation therapy or radical prostatectomy). When the complication rate is analyzed (with or without hospital admission), among the patients submitted to TZ cores, 259 (26.2%) complications were observed; between those submitted to double-sextant 12-cores, 26 (21.7%) complications were observed ( P=0.279). Conclusion Extended core biopsy protocol with two TZ extra fragments improves detection rates of cancer when compared to double-sextant biopsy protocol without increasing complication rates. TZ routine cores should be considered.

Insomnia and Hypersomnia among Children and Adolescents with Psychiatric Disorders The common symptom of sleep disorders is non-restorative sleep, which results in daytime sleepiness. Therefore in clinical practice simultaneous complaints of "not enough" and "too much" sleep are very frequent. For the investigation and treatment of organic sleep disorders, available instruments, guidelines and specialised institutions (sleep centres or sleep laboratories) are more advanced than for non-organic sleep disorders. Especially in the child and adolescent psychiatric and psychotherapeutic field this complicates an appropriate treatment. In addition multiple psychiatric, neurological and other somatic diseases can disrupt nighttime sleep and cause impairments during the day too. There are various instruments and methods to cover disturbed nocturnal sleep, some of which have already found widespread use in clinical practice (e. g. sleep diaries or specific questionnaires and interviews). For the examination of daytime sleepiness instruments and methods are available too, which by now seem to be less widely used. Against this background an overview of definitions, distinctive features and clinical instruments as well as guidelines for dealing with "too much and too little sleep" during the day or at night shall be presented.

This study aims to evaluate safety and efficacy of different endoscopic enucleation of the prostate (EEP) techniques, by comparing laser (L-EEP) and non-laser (NL-EEP) procedures; and EEP versus other endoscopic non-enucleation (ENE) surgeries for benign prostatic enlargement (BPE). A systematic literature review was performed for randomized clinical trials (RCT) that compared different endoscopic treatments for BPE, between 1982 and 2018. Two analyses were performed: (1) EEP versus ENE; and (2) L-EEP versus NL-EEP. Efficacy was assessed using perioperative data (removed tissue volume, operation time (OT), catheterization time, length of hospital stay); and functional outcomes [IPSS, IIEF-5, maximum flow rate (Qmax), postvoid residual volume (PVR), quality of life (QoL)]. Safety was assessed through complications (Hb and sodium decrease, transfusion rate). Meta-analyses were performed using RevMan® 5.3. Out of 35 RCTs (4066 patients), 31 (3909 patients) evaluated EEP versus ENE, and 4 (327 patients) evaluated L-EEP versus NL-EEP. EEP presented greater Qmax. Also, EEP presented less catheterization time, length of hospital stay, Hb decrease, transfusion rate. OT and bladder injury were greater with EEP. There were no significant differences between other items. L-EEP removed more tissue volume, with a smaller drop in serum Hb. There were no significant differences in other perioperative data, functional outcomes, complications. EEP and ENE are effective and safe for treating BPE. Perioperative data favors EEP. Statistical differences, with questionable clinical significance in functional outcomes and complication rates were encountered. L-EEP provides greater tissue removal and smaller Hb decrease then NL-EEP, with similar functional profiles.

INTRODUCTION AND OBJECTIVES:A great variety of surgical treatments are available for benign prostatic enlargement (BPE). This study aims to evaluate the safety and efficacy profile of different met...

BACKGROUND Although greater than 40% of breast cancers occur in patients aged ≥65 years, these individuals are frequently undertreated. Taxane-based adjuvant chemotherapy is considered the treatment of choice but to the authors' knowledge has only limited evidence in elderly patients. METHODS Patients aged ≥65 years with a Charlson comorbidity index ≤2 and pT1/2 pN0/1 disease and either human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor-negative, grade 3 (according to Common Terminology Criteria for Adverse Events [version 3.0]), high uPA/PAI-1 or any stage pT3/4 pN2/3 breast cancer were randomized to receive 4 cycles of adjuvant epirubicin and cyclophosphamide (EC) (epirubicin at a dose of 90 mg/m2 and cyclophosphamide at a dose of 600 mg/m2 intravenously [iv] on day 1 every 3 22 days) or 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (cyclophosphamide at a dose of 500 mg/m2, methotrexate at a dose of 40 mg/m2, and 5-fluorouracil at a dose of 600 mg/m2 iv on days 1 plus 8 every 29 days) versus 6 cycles of nab-paclitaxel and capecitabine (nPX) (nab-paclitaxel at a dose of 100 mg/m2 iv on days 1, 8, and 15 every 21 days with 1 week of rest every 6 weeks plus capecitabine at a dose of 2000 mg/m2 orally on days 1-14 every 21 days). Primary endpoints were treatment discontinuations and overall frequency of adverse events. RESULTS Thirteen of 198 patients (6.6%) discontinued EC/CMF and 69 of 193 patients (35.8%) discontinued nPX (P

Situs inversus, a very rare congenital anomaly of reversal site of thoracic and abdominal organs, can be very problematic to surgeon while dealing with a case of trauma in emergency. Surgical procedures are considered difficult, complex and more challenging in patients with this condition due to the anatomical difference and position of organs. We came across an interesting and very rare case of isolated blunt traumatic diaphragmatic injury in a case of situs inversus. Traumatic injuries of the diaphragm are uncommon and isolated blunt traumatic injuries of diaphragm are very rare. Our case is very unique of its kind of situs inversus with isolated right sided diaphragmatic rupture in a 60-year-old male patient presenting 4 hours after blunt trauma to chest and abdomen.

Background: Gallstones are generally uncommon in infants and children. Formation of gallstone is a very poorly understood phenomenon. In general, the risk factors for cholithiasis in infants include patients who are ill, are receiving hyperalimentation, are premature, have congenital anomalies and have necrotizing enterocolitis. Children aged 1 - 5 years most frequently have hemolysis as the underlying condition [1]. Materials and Methods: From Jan 2012 to Feb 2014, a study entitled “A Prospective Study of Cholelithiasis in Children” was conducted in Postgraduate Department of General Surgery Govt. Medical College Srinagar. The patients selected for the study were in the age group of 1 to 14 years of either sex. There were a total of 141 cases, out of which only 38 had ultrasound documented gallstones. All the patients included in the study were evaluated for prevalence, clinical presentation, and pathological features of gallstones, and were analysed for metabolic causes of gallstones. Results: The prevalence of chliothiasis in symptomatic patients was found to be 26.95% higher than the prevalence of gallstones in children in other parts of world, also the mean age of presentation was 9.3 years ranging from 6 - 14 years. Male to female ratio was 3:2 and male predominance was found in all age groups contrary to female predominance in adults. Most common presenting symptom was right upper quadrant pain followed by vomiting and nausea similar to presentation of symptomatic gallstones in adults. 4 patients had a positive family history of cholithiasis in the first degree relatives; 25 (65.7%) patients had no underlying risk factor for gallstones contrary to presumption that gallstones in children are mostly secondary to some hematological disorder or other predisposing factors. Chronic cholecystities was found in 81% of patients with gallstones and composition of gallstones retrieved was different from those of adult gallstones with calcium carbonate gallstones relatively common in children but composition of black and brown stones was almost similar to adult stones. Conclusion: Gallstone disease was increasingly gaining recognition in peadiatic practice due to significant documented increase in non-heamolytic cases over the last two decades. The observed gallstones prevalence, clinical presentation, pathological features of gallstones, and analysed metabolic causes of gallstones in children are different from those stones found in adults. The results of our study demonstrated that gallstones and gallstone related complications in peadiatic populations were different from the adult gallstone disease and there was an increase in prevalence of gallstones in children with no under lying risk factor for gallstones, and surgery remained the corne stone of treatment for peadiatric cholithiasis as in adults.

Background: The experience of short term results of laparoscopic inguinal hernia repair using 3D mesh in a developing country is reviewed. Methods: From January 2012 to February 2014, 53 patients underwent laparoscopic inguinal hernioplasty. A retrospective case series of 53 consecutive patients undergoing TEP/TAPP by a single surgical team was followed prospectively with a focused physical examination and interview. 4 out of 53 patients had recurrent hernia following open repairs and 49 had primary hernias. Data collected included operative time, intraoperative bleeding, intraoperative difficulties, immediate postoperative pain, chronic groin pain, recurrence, sensory disturbance, activity or occupational limitation and personal satisfaction. Results: All the patients were male aged 32 to 75 years with a mean age of 53.5 years. Mean operative time was 37.4 minutes; intraoperative dissection, blood loss were less; and immediate postoperative pain was negligible as assessed by VAS. There was no mortality or major morbidity. Mean follow-up was 12 months (2 to 18 months). Follow-up was completed by interview and physical examination. Hernia was not found to recur during the follow up period. Chronic pain occurred in 2 patients (3.7%), which was mild in nature. Ninety-seven percent of patients were satisfied with their repair and would or had recommended TEP/TAPP to others using 3D Mesh. Conclusions: Short-term results of TEP/TAPP hernia repair using 3D mesh demonstrated to be an effective and safe procedure with low prevalence of chronic pain that is generally of a mild, infrequent nature. It was also concurred that there is decrease in operative time. Manipulation of mesh was significantly reduced. Intraoperative bleeding and use of post operative analgesia was reduced considerably. There was no recurrence, however the cost of the mesh increased the overall cost of the procedure acting as a limiting factor in a developing country.

Geburtshilfe und Frauenheilkunde 77(07), 756-764 (2017). doi:10.1055/s-0043-111899, Published by Thieme, Stuttgart [u.a.]

Aim: To assess behavioral and sleep disturbances in childhood, it is necessary to implement standardized brief questionnaires for children and their parents. Especially complaints of insomnia often are underdiagnosed in pediatric medicine. Methods: We developed a sleep questionnaire (K?SI-KJ) and used it together with German versions of the SDQ (parent and child reports) for epidemiologic studies in Cologne. The sleep questionnaire obtains 33 items for parents and 28 items for children. Ratings were dichotomized for this analysis in “sometimes/ often present” versus “not present”. The German versions of SDQ contain 5 subscales each with 5 items. Data from a sample of 1490 children of fourth grade in elementary schools inCologne(age ranged from 8 to 11 years) are shown. Results: Children indicate signs of sleep disturbances in higher frequency than their parents do. Concerning gender and ethnical group, there no significant differences can be shown. Children with signs of insomnia, dyssomnia, daytime sleepiness or restless sleep showed significantly higher scores for all relevant SDQ subscales in parental and children's reports. Children with signs of parasomnia showed higher scores concerning emotional problems and the SDQ total score. Children with enuresis showed higher scores for all SDQ subscales and the total score.

Classen-Linke I, Moss S, Groting K, Beier H M, Alfer J & Krusche C A (2012) Histopathology 61, 955–965 Mammaglobin 1: not only a breast-specific and tumour-specific marker, but also a hormone-responsive endometrial protein Aims: The secretoglobin mammaglobin 1 (MGB1) is strongly expressed in breast tumours, and is therefore used to detect breast cancer metastases, although it has also been detected in other tissues. The aim of this study was to examine MGB1 expression and its hormonal regulation in human endometrium to further investigate the use of MGB1 as a marker molecule. Methods and results: Mammaglobin 1 expression was assessed immunohistochemically in endometrial samples from 60 normal fertile patients throughout the menstrual cycle, in 49 endometriotic tissue samples, in 15 endometrial adenocarcinomas, and in 36 breast carcinomas. In addition, 25 endometrial samples were analysed by western blot and quantitative real-time reverse transcription polymerase chain reaction. To prove hormonal regulation, primary endometrial epithelial cells were cultured with 17β-oestradiol and promegestone. MGB1 was detected in human endometrial tissue, with peak expression during the luteal phase, in 31% of endometriotic samples, in 53% of endometrial adenocarcinomas, and in 64% of breast carcinomas. MGB1 mRNA expression was increased in vitro by hormonal treatment. Conclusions: Our data show that MGB1 expression is not restricted to normal and malignant breast tissue. Besides its documented occurrence in endometriotic and malignant endometrial tissues, MGB1 is also expressed in normal human endometrium, and such expression is controlled by steroid hormones.

Oncology reports 33(5), 2129-2134 (2015). doi:10.3892/or.2015.3851, Published by Spandidos Publ., Athens

The etiology and the pathogenesis of congenital pseudarthrosis of the tibia (CPT) are still unknown. The affected tibia exhibits insufficient mechanical strength and osteogenetic capability. CPT is frequently associated with neurofibromatosis type 1 (NF1; von Recklinghausen's disease); however, both diseases have not yet been linked pathogenetically. This study presents the pathomorphologic findings of CPT under special consideration of NF1. Therefore, samples from patients operated on for CPT (n = 4) with (n = 3) and without (n = 1) neurofibromatosis were investigated by light microscopy, immunohistochemistry, and electron microscopy. The most striking finding in all patients was thickened periosteum with accumulation of nerval cells surrounding small arteries, causing subtotal or complete obliteration. In conclusion, impaired vascularization can result in decreased osteogenic capabilities. The similarity of ultrastructural findings in the abnormal periosteum and in skin neurofibromas of neurofibromatosis patients may indicate a pathogenetic association of both diseases.

The most frequent complications of total hip arthroplasty are septic and aseptic wear-induced loosening. A reliable differentiation between septic and aseptic loosening with current diagnostic tools is not possible. Therefore, we examined the diagnostic valency of positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) in cases of septic or aseptic hip arthroplasty loosening compared with conventional triple-phase bone scan (TPBS).Fifty patients with 70 total hip replacements (symptomatic n=50, asymptomatic n=20) were examined by means of FDG-PET and TPBS to detect septic and aseptic loosening and differentiate between the two. A differentiated algorithm subdivided into categories I-V was developed for FDG-PET. Additionally, standardized uptake values (SUV) were calculated from the lesion with the highest FDG uptake. Interpretations of the TPBS were done according to the criteria described by Wilson. The final diagnosis was based on operative findings including microbiological and histological examinations (n=50), while the remaining asymptomatic arthroplasties (n=20) were integrated into a clinical follow-up (or =9 months).Sensitivity/specificity of FDG-PET was 91%/92% (accuracy 91%) compared with 78%/70% (accuracy 74%) for TPBS. A high correlation could be proved between FDG-PET investigation and operative histopathological findings (r(Spear)or =0.9). No significant differences were found regarding cemented and uncemented implanted hip arthroplasties (por =0.05). Calculation of the SUV turned out to be inappropriate as a sole criterion for image interpretation.FDG-PET is a promising, highly accurate examination method to detect polyethylene and metal wear-induced chronic inflammation followed by periprosthetic osteolysis. In addition, FDG-PET has a significantly higher sensitivity and specificity than TPBS for differentiating between aseptic loosening and infection.

The human endometrium prepares for implantation of the blastocyst by reorganization of its whole cellular network. Endometrial stroma cells change their phenotype starting around the 23rd day of the menstrual cycle. These predecidual stroma cells first appear next to spiral arteries, and after implantation these cells further differentiate into decidual stroma cells. The phenotypical changes in these cells during decidualization are characterized by distinct changes in the actin filaments and filament-related proteins such as α-actinin. The carboxy-terminal LIM domain protein with a molecular weight of 36 kDa (CLP36) is a cytoskeletal component that has been shown to associate with contractile actin filaments and to bind to α-actinin supporting a role for CLP36 in cytoskeletal reorganization and signal transduction by binding to signaling proteins. The expression patterns of CLP36, α-actinin and actin were studied in endometrial stroma cells from different stages of the menstrual cycle and in decidual stroma cells from the 6th week of gestation until the end of pregnancy. During the menstrual cycle, CLP36 is only expressed in the luminal and glandular epithelium but not in endometrial stroma cells. During decidualization and throughout pregnancy, a parallel upregulation of CLP36 and smooth muscle actin, an early marker of decidualization in the baboon, was observed in endometrial decidual cells. Since both proteins maintain a high expression level throughout pregnancy, a role of both proteins is suggested in the stabilization of the cytoskeleton of these cells that come into close contact with invading trophoblast cells.

Embryo implantation and subsequent decidualization, trophoblast invasion and formation of a functional placenta are crucial for establishment and maintenance of pregnancy. Interleukin-11 signalling has been shown to be obligatory for adequate decidualization and trophoblast invasion in mice. Defects in IL-11 signalling in mice result in trophoblast over-invasion and fetal loss. The pathological situation of human tubal pregnancy resembles that of IL-11Ralpha(-/-) mice concerning these symptoms. As our interest is focused on the human early pregnancy, we compared IL-11 expression at the implantation site of ectopic tubal pregnancy (EP) to 1st and 2nd trimester of normal intrauterine pregnancies (IP), and to the normal cycling endometrium. The mRNA expression of IL-11 and IL-11Ralpha was analysed by semiquantitative RT-PCR. Protein expression was detected by western blotting and immunohistochemistry. IL-11Ralpha is expressed constitutively in all tissue specimens analysed. IL-11 is expressed predominantly during follicular and early luteal phase of the menstrual cycle. In IP, IL-11 expression peaks during the 1st trimester and declines from the beginning of the 2nd trimester onwards. In tubal abortions, IL-11 expression is reduced in comparison to vital EP and IP. Cultured primary endometrial and decidual epithelial cells were analysed for hormonal regulation of IL-11 by enzyme-linked immunosorbent assay and RT-PCR. IL-11 is up-regulated by estrogen and down-regulated by progesterone. Overall, our results indicate that in humans, IL-11 signalling is significantly involved in regulation of trophoblast invasion. In the case of tubal abortion, inadequate IL-11 signalling may therefore result in dysregulation of trophoblast invasion.

Die diagnostische Typisierung zystischer Nierenerkrankungen kann im Einzelfall Schwierigkeiten bereiten, da die nach Potter benannten pathologisch-anatomisch definierten Typen oft keine eindeutige Klassifikation erlauben. Die molekulargenetischen Erkenntnisse haben neue Einsichten geschaffen, tragen in der Praxis jedoch nur wenig zur Einteilung bei. Da eine prazise Klassifikation vor allem kindlicher, aber auch fetaler Zystennieren fur die humangenetische Beratung betroffener Familien von groser Bedeutung ist, sollte neben einer prazisen pathoanatomischen Beschreibung von Veranderungen der Nieren und der Leber, sowie eventuell weiterer Fehlbildungen, immer auch die Familienanamnese berucksichtigt werden. In der klinischen Praxis werden fur die erblichen polyzystischen Nierenerkrankungen die genetischen Begriffe (autosomal-dominant und autosomal-rezessiv) bevorzugt.

Compared to other members of the fibroblast growth factor receptor (FGFR) family, only few studies investigate FGFR3 in tumour angiogenesis. We investigated the connection between angiogenesis and FGF/FGFR expression including FGFR3 mutation status in urothelial carcinomas. Immunohistochemistry was performed in invasive and non-invasive urothelial cancers of 61 patients. Protein expression of CD31, factor VIII (FVIII), FGF-1/2, FGFR1, FGFR3 and FGFR4 and FGFR3 mutation status were evaluated. Morphometric assessment of angiogenesis including microvessel count (MVC) and vascular surface area (VSA) was analysed. Correlation and survival analyses (overall survival (OS) and disease-free survival (DFS)) with univariate and multivariate analyses were performed. CD31 values (MVC and VSA) significantly correlated with OS and DFS. OS and DFS were significantly better in patients with FGFR3 overexpression. Multivariate analysis revealed FGFR3 protein expression and tumour grading (WHO classification 2004) as independent prognostic factors of OS and VSA of CD31 and FGFR3 protein expression of DFS. FGFR3 mutation status was correlated with VSA measured by FVIII. FGFR3 may be able to induce a pro-angiogenic phenotype in urothelial carcinomas and significantly influence prognosis. Consequently, FGFR3 is a potential therapeutic target also from the angiogenesis perspective.

Biologisch ist die Reifung des Endometriums in jedem Zyklus darauf gerichtet, einer Blastozyste gunstige Bedingungen fur die Implantation zu bieten. Infertilitat und fruhes Ende einer Schwangerschaft beruhen nicht selten auf einer unvollkommenen Reifung des Endometriums. Bereits eine mangelhafte Rezeptivitat des Endometriums fuhrt zum Scheitern der Implantation. Um die endometriale Ursache einer Infertilitat zu erkennen, werden die normalen zyklischen Veranderungen des Endometriums studiert. Morphologische Veranderungen bilden bis heute in diesem Bemuhen der Gynakologen noch die Grundlage der klassischen histologischen Diagnostik nach Noyes et al. (1950). Da jedoch evident ist, dass molekulare Defizite des Endometriums sich nicht unmittelbar histologisch erfassen lassen, werden neue Methoden und signifikante Parameter gesucht, die diese Art funktioneller Defekte diagnostisch erfassen lassen. Histochemische Lokalisierungen von definierten Proteinen, von Adhasionsmolekulen und Zytokinen, erlauben bereits eine detailliertere und aussagekraftigere molekulare Analyse als es die klassische Morphologie ermoglicht. Uberzeugende Argumente sprechen inzwischen dafur, mit einfachen biochemischen Analysen die Proteine des Uterussekrets als weitergehende signifikante Parameter zu nutzen. Die elektrophoretische Auftrennung des Uterussekrets ergibt typische Proteinmuster, welche die zyklischen Funktionsphasen des Endometriums darstellen. Das adaquate Proteinmuster der Lutealphase ist als das Produkt eines rezeptiven Endometriums zu betrachten und reprasentiert das fur diese molekulare Analytik charakteristische „Implantationsfenster“. Es wird bereits 2 Tage post ovulationem exprimiert und bei ungestortem Zyklusverlauf 8 Tage aufrechterhalten (15.–24. Zyklustag).

The influences of the synthetic progestin, medroxyprogesterone acetate (MPA), the progesterone receptor modulator J867, and the antagonist ZK137316 were studied in vitro on isolated endometrial epithelial cells, as well as endometrial fibroblasts. We evaluated the expression of estrogen receptor alpha (ER) and the progesterone receptor (PR) by RT-PCR. ER and PR were strongly expressed in the fibroblasts and epithelial cells under treatment with 10(-8) M 17beta-estradiol (E(2)). Treatment with 10(-6) M J867 or ZK137316 upregulated the PR expression as did E(2), in contrast to treatment with 10(-6) M MPA, which caused a downregulation of PR in epithelial cells, but not in fibroblasts. In addition, the vascular endothelial growth factor (VEGF) release into the cell culture medium was analyzed by a VEGF-ELISA. VEGF which plays an important role in angiogenesis, is regulated by steroid hormones as well as hypoxia. E(2) stimulates VEGF release into the medium in both cell types. MPA reduces VEGF release significantly in the fibroblast cell culture, but increases it in the epithelial cell culture. ZK137316, in the presence or absence of E(2), reduces VEGF release in fibroblast cell culture. J867 increases the VEGF production in fibroblasts only in the presence of E(2). Both compounds show no significant effects, compared to E(2), in epithelial cell culture. The different results for the epithelial cells and fibroblasts indicate that the pharmacological effects of PR modulators (PRMs) and progesterone antagonists (PAs) may be cell specific and depend on the presence or absence of partial progestagenic agonistic activities. This observation opens up new perspectives for various clinical applications.

Leptin and its receptor are involved in endocrine and paracrine regulation of metabolism, obesity and reproduction. Here, we describe the detection of the functional long isoform receptor of leptin in human endometrium. The leptin receptor protein was shown to be expressed in glandular and luminal epithelium and is periodically regulated throughout the menstrual cycle, demonstrating main expression in follicular and mid-luteal phase. In contrast, leptin receptor mRNA is detectable by reverse transcription-polymerase chain reaction (RT-PCR) as a constitutive component. Since RT-PCR analyses showed that leptin is not expressed in this tissue, the present study suggests that the human endometrium is a novel target for leptin. Therefore, we investigated 11 subfertile patients who underwent two biopsies in one menstrual cycle. The patients presented with a repetitive endometrial maturation defect, but showed adequate serum hormone concentrations and normal steroid hormone receptor expression and down-regulation in the endometrium. These patients were, however, deficient for expression of the functional leptin receptor. These analyses provide evidence that the lack of the leptin receptor in an ovulatory cycle may contribute to subfertility by a yet undefined 'endometrial factor'.

Uteroglobin is a progesterone binding protein, a member of the antiflammin gene family and possibly a novel cytokine. Initially, uteroglobin was identified as the major protein of rabbit uterine secretion during the phase of preimplantation. Counterparts of the rabbit uteroglobin or its gene are described in rat, mouse, hamster, hare, pig, horse and human. While uteroglobin appears as one of the most extensively studied proteins, particularly its physico-chemical properties, including its crystal structure and its gene, the true physiological role of this protein still remains to be unravelled. Essential to understanding the significance of human uteroglobin in reproductive organs, particularly in the endometrium, is a knowledge of the spatial and chronological expression of this secretory protein. Our studies on 115 volunteers combined reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry and quantitative assessment by an enzyme-linked immunosorbent assay for uteroglobin. The expression, localization and release of uteroglobulin in the human endometrium are presented. Secretory uteroglobin is found in endometrial tissue homogenates in highest levels of expression during the early luteal phase (days 15-19, 340 pg/mg total protein). In turn, uteroglobin is released into the uterine lumen in peak amounts during the receptive phase of the menstrual cycle (mid-luteal phase, days 20-23, secretion level 833.4 pg/mg total protein). Our immunohistochemical studies match with these results, as uteroglobin is located during the early and mid-luteal phase in the apical compartments of endometrial gland cells. These observations strongly suggest an involvement of uteroglobin in endometrial preparations for implantation.

An established cell culture system of isolated human endometrial stromal and epithelial cells has been used to study the effects of oestrogen and progesterone, as well as their antagonists, upon endometrial cells. Normal hormonal regulation in vivo was investigated simultaneously in endometrial tissue samples taken at different phases of the menstrual cycle. Several marker molecules analysed by immunohistochemistry appeared to depend strongly on endocrine regulation and could be traced in culture. Immunohistochemically, basic parameters of cell biology were identified in vitro, e.g. cell proliferation (Ki-67), adhesion molecules (beta3 integrin) and paracrine factors (leukaemia inhibitory factor). The most reliable parameters to assess hormonal influences were oestrogen and progesterone receptor molecules. Immunohistochemical localization could be improved by molecular biological analysis using RT-PCR. In the presence of oestrogen, a significant expression of hormone receptors was also shown by RT-PCR, and withdrawal of oestrogens and addition of gestagen, i.e. medroxyprogesterone acetate, caused receptor downregulation. Addition of the anti-oestrogen ICI 182.780 to cell-culture medium significantly decreased the synthesis of progesterone receptors.

Introduction Primary infertility, miscarriage, and preeclampsia have been correlated with reduced numbers of regulatory T-cells (T reg ) suggesting that decreased extravillous trophoblast (EVT) invasion originates from inadequate EVT tolerance. In contrast increased numbers of T reg -cells may be responsible for over-invasion of EVT. As the maturation status of dendritic cells (DC) influences T-cell behavior (tolerance or immune activation), altered relation between immature and mature DCs may also influence EVT invasion. Method Paraffin-embedded specimens of placenta accreta/increta (Pc; n = 11) and healthy intrauterine pregnancy (IUG; n = 18) were double-stained for cytokeratin and CD45, CD68, CD56, CD20, CD3, or CD8 as well as FoxP3/CD4 and FoxP3/CD8 and single-stained for CD4, CD25, FoxP3, CD209, Dec205 and CD83. Quantification of the leukocyte subpopulations was performed for decidua parietalis and basalis as characterized by cytokeratin-positive EVT. Statistical analysis was performed by using the Mann–Whitney test. Result There were significantly fewer CD4 + cells in Pc than in IUG. Concerning the T reg -markers, FoxP3 + cells are significantly increased. CD25 + cells showed a small non-significant increase in Pc in comparison to IUG. Concerning dendritic cells, immature non-activated CD209 + DCs were significantly decreased in Pc while immature activated CD205 + DCs were slightly but non-significantly increased. Mature activated CD83 + DC were non-significantly decreased in IUG vs Pc. Discussion and conclusion The increased number of T reg -cells in Pc suggests significance for these cells in the regulation of trophoblast invasion. Their adequate interaction with other lymphocyte populations (e.g. adequately maturated dendritic cells) may be one mechanism to assure controlled EVT invasion.

The Brazilian Wilms Tumor Study Group has registered 16 cases of synchronous bilateral Wilms tumor since 1986, of which 14 were available for analysis. Most patients were treated according to a prospective trial in which bilateral renal preservation was emphasized. Overall survival was 79% (11 of 14 cases), and both kidneys were preserved in 57% (8 of 14) of the patients with synchronous disease. Of the 14 patients 5 had undergone at least 3 surgical procedures. In 10 cases in which pathological reports were available for review residual disease was documented in 5 but none had relapse.

BACKGROUND: Class I histone deacetylases (HDACs) and acetylases (HATs) are members of transcriptional pre-initiation complexes assembled by steroid hormone receptors. Recently, HDAC inhibitors were shown to enhance differentiation of endometrial fibroblasts and endometrial adenocarcinomas. However, there is only rare information on HDAC and HAT expression in the human endometrium. METHODS: HDAC-1, -2, -3 and HAT (PCAF and GCN5) mRNA expression was studied in tissue from premenopausal women undergoing hysterectomy by real-time or semiquantitative RT‐PCR. HDAC protein expression was assessed by Western Blot and immunohistochemistry. In endometrial adenocarcinomas (n 5 17), HDAC-1 expression was studied by immunohistochemistry. RESULTS: In the human endometrium, HDAC-1, -2, -3 and PCAF mRNA are expressed without cyclical changes. Western blot analysis demonstrated that HDAC-2 protein expression was slightly, but significantly elevated in the secretory phase ( P< 0.01 versus day 5‐8), whereas HDAC-1 and -3 protein expression was constitutive throughout the menstrual cycle. By immunohistochemistry, nuclear expression of HDAC proteins was detected in all endometrial cell types. In the case of HDAC-3, immunostaining was significantly reduced in the endometrial surface epithelium on day 6‐10 ( P< 0.01 versus days 15‐18 and 24‐28). Compared to normal endometrium, a high proportion of endometrial adenocarcinomas showed impaired HDAC-1 protein expression in the epithelial and stromal compartment. CONCLUSIONS: Class I HDACs and HATs are expressed in the human endometrium throughout the menstrual cycle, suggesting the cyclic endometrium as a potential target for HDAC inhibitors. We hypothesis that alterations of HDAC and/or HAT expression are potentially involved in impaired endometrial differentiation.

Background There is controversy about the consequences of physical exercise on human sleeping behaviors. Evidence suggests that voluntary physical exercise affects brain structures and functions. However, there are inconsistent data regarding the effects of exercise on sleep architecture and sleep continuity, especially the amounts of slow wave sleep (SWS) and rapid eye movement (REM) sleep. Objective The aim of the present study was to investigate the effects of moderate and high intense physical exercise on vigilance state and sleep patterns in school-aged children. Methods Eleven healthy children (12.6 ± 0.8 years old) were recruited for this polysomnographic study and underwent two exercise sessions. The two exercise sessions on a bicycle ergometer were performed 3–4 h prior to bedtime, lasted 30 min and varied in intensity. The moderate-intensity exercise was at 65–70% of maximal heart rate (HRmax) while the high-intensity exercise was at 85–90% HRmax to exhaustion. Polysomnographic and physiological measurements, including oximetry, were made on three nights in random order and separated by 1 week. Vigilance tests were carried out before and after the three sleep periods. Results Only high-intensity exercise resulted in a significantly elevated SWS proportion and less sleep in stage 2 as well as a higher sleep efficiency and shorter sleep onset latency. No significant effects on REM sleep were found. Conclusion The results suggest that exercise intensity is responsible for the effects on stage 2 sleep and SWS in children and support the hypothesis of homeostatic sleep regulation.

PURPOSE: To evaluate percutaneous cryotherapy as a primary treatment option for high-risk prostate cancer patients. PATIENTS AND METHODS: From October 2000 to February 2005, 21 high-risk (Gleason e•8 and/or PSA >; 10 and/or stage >; T2a) prostate cancer patients underwent 24 percutaneous prostate cryoablation procedures. Patients' median age was 70.9, and the average pretreatment PSA was 19.5 ng/dL. The follow-up period ranged from 6 to 60 months (median, 41 months). RESULTS: The PSA failure rate was 39%, 52.9%, and 42.8% at 12, 24, and 60 months of follow-up, respectively. Overall complication rates were low, with 8% of urinary incontinence and no cases of rectal injury; however, 96% of erectile dysfunction occurred. The cryoablation procedure failed in 12 patients (57.2%); 7 (58.3%) of these were local failures (positive prostate biopsies). CONCLUSION: Percutaneous cryoablation of the prostate is a safe minimally invasive treatment, but it has poor PSA-free survival outcomes in high-risk prostate cancer patients. OBJETIVO: Avaliar a crioterapia percutânea como tratamento primário para o câncer de próstata de alto risco. PACIENTES E MÉTODOS: De outubro de 2000 a fevereiro de 2005, 21 pacientes com câncer de próstata de alto risco foram submetidos a 24 crioablações de próstata como tratamento primário. A mediana de idade dos pacientes foi de 70,9, e a média do PSA pré-tratamento de 19,5 ng/dl. O tempo de seguimento variou de 6 a 60 meses (mediana de 41 meses). RESULTADOS: Os índices de falha do PSA foram de 39% e 52,9% respectivamente aos 12 e 24 meses de seguimento. A sobrevida livre de doença em 5 anos foi de 42,8%. De maneira geral os índices de complicações foram baixos, com 8% de incontinência urinária e nenhum caso de lesão retal. Os índices de impotência foram de 96%. Em doze pacientes (57,2%) onde houve falha da crioablação, 7 (58,3%) apresentaram recidivas locais (biópsia positiva) e os demais recidiva a distância. CONCLUSÃO: A crioablação percutânea da próstata é um tratamento minimamente invasivo da próstata, seguro, porém ainda com resultados modestos em pacientes com câncer de próstata de alto risco, quando se considera a sobrevida livre de doença em 5 anos, havendo portanto necessidade de associação de outras modalidades terapêuticas no tratamento deste grupo específico de doentes.

Aim: To evaluate percutaneous cryotherapy as a primary treatment option for prostate cancer, comparing different risk groups. Patients and Methods: Forty-seven prostate cryoablation procedures were performed on 44 patients. Patients median age was 70.9, and average pretreatment PSA of 13.8 ng/dl. Patients were divided into low-risk (13 patients), high-risk (24 patients) and radiation failure patients (7 patients). The follow-up period ranged from 18 to 60 months (median 41 months). Results: In the low-risk group, we found after 12 and 24 months of follow-up, 92 and 86% of patients free of PSA relapse (PSA Conclusion: Prostate cryoablation is a viable and promising minimally invasive alternative for localized or locally advanced prostate cancer patients.

BACKGROUND The clinical outcome of treatment of odontogenic cysts differs depending on separate entities. Particular clinical relevance must be attached to the distinction between odontogenic keratocysts, which have an evident tendency to recur, and other odontogenic cysts. The aim of this study was to evaluate cytokeratin (CK) expression patterns as an additional tool for characterization of different cysts as the histomorphologic appearance often is not decisive. METHODS Thirty cases of dentigerous and radicular cysts respectively as well as 15 cases of odontogenic keratocysts were considered. Expression of CK 5/6, 7, 10, 13, 17, 19 and 20 was determined in addition to Ki-67 immunohistochemically. RESULTS Expression of CK 17 was discernible in 93.3% of the odontogenic keratocysts, but only in 35.0% of dentigerous and radicular cysts under study (P < 0.001). CK 19 could be detected in 48.3% of dentigerous and radicular cysts, whereas odontogenic keratocysts were completely negative (P < 0.002). CONCLUSION Immunohistochemical detection of CK 17 and 19 seems to be a valuable additional parameter distinguishing between odontogenic keratocysts and other odontogenic--especially dentigerous--cysts which clinically are likely the most significant differential diagnoses in this context. J Oral Pathol Med (2005) 34: 558-64.

e15537 Background: PC-RPLND plays an important role in the management of residual masses of advanced NSGCT of the testis. Teratomatous elements in the primary tumor is a risk factor for teratoma in...

Endogenous nitric oxide (NO) can be synthesized by endothelial cells and can act as a potent vasodilator. We investigated endothelial nitric oxide synthase (eNOS), one of the three different enzymes responsible for the synthesis of NO by immunohistochemical methods throughout the menstrual cycle on 34 endometrial samples and compared its detection with the von Willebrand Factor (vWF) as a reliable marker molecule of the endothelium on serial sections. Immunoreactivity for eNOS was clearly localized in various types of arterial and venous endothelial cells as well as in capillaries. In addition, in some samples there was a positive staining in endometrial glandular epithelium. There was no staining in endometrial fibroblasts or in myometrial smooth muscle cells. Whereas the endothelium was constantly stained by the monoclonal antibody against vWF, eNOS was not always expressed in the endothelial lining of the vessels during the menstrual cycle. The number of vessels positively stained for eNOS increased gradually during the proliferation phase and most of the vessels were positive in the early secretory phase. These results suggest that its markedly increased expression during the early secretory phase of the menstrual cycle indicates a physiological significance.

e15043 Background: Evidence suggests that obesity is biologically associated with the development of prostate cancer (PCa) and may increase the risk of a more aggressive cancer. We investigated if ...

A twenty-nine-year-old patient with a Wilms tumor on the right side was treated with surgery, radiotherapy, and chemotherapy. Since no study of treatment of adult Wilms tumor is yet available, the combined therapy was instituted in accordance with the one existing for children. The results of the 5 adult cases previously reported which were treated with triple therapy, and the relevant literature, are reviewed.