Primary pulmonary glomangioma: a coin lesion negative on PET study. Case report and literature review.

Glomus tumor is an uncommon perivascular lesion usually located in the dermis of the extremities. It rarely involves the respiratory tract or the lungs. We present the clinical and pathological features of a 39-year-old man who was evaluated for an incidental radiological finding of a pulmonary nodule. A chest computed tomography (CT) confirmed the presence of an upper left lobe coin lesion. Bronchoscopy and 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) were negative. An intraoperative frozen section examination was interpreted as a neuroendocrine tumor; therefore a left upper lobectomy with lymphadenectomy was performed. An immunohistochemical examination supported the diagnosis of a primary pulmonary glomangioma. The patient was free of disease at the 51-month follow-up. Due to its uncertain behavior we stress the usefulness of typical lung resection, lymph node dissection, and accurate follow-up.

ESX1 gene expression as a robust marker of residual spermatogenesis in azoospermic men.

BACKGROUND: It would be of value to identify ongoing spermatogenesis molecular markers which can predict successful sperm recovery in patients with non-obstructive azoospermia undergoing conventional or microsurgical testicular sperm extraction (TESE/microTESE). ESX1 is an X-linked homeobox gene expressed in testis, placenta, brain and lung in humans and specifically in pre- and post-meiotic germ cells of the testis in mice. METHODS: We investigated the sequence, expression (by RT-PCR) and epigenetic status (by promoter pyrosequencing) of ESX1 in testicular tissue samples, obtained from 81 azoospermic subjects in the context of surgical sperm extraction, to check a possible association between ESX1 alterations and impaired spermatogenesis, as determined by histological analysis. RESULTS: The ESX1 transcript was detected in 100% of cases diagnosed as obstructive azoospermia (33), hypospermatogenesis (18) and incomplete maturation arrest (MA) (2), and sperm recovery was also successful in 100% of these cases. ESX1 mRNA was also detected in 5 of 6 patients with incomplete Sertoli cell-only syndrome, in 4 of 6 subjects with complete MA but in only 3 of 16 cases of complete Sertoli cell-only syndrome (cSCOS), whereas sperm recovery was successful in 4 of 6, 2 of 6 and 5 of 16 of these patients, respectively. In cases of focal spermatogenesis, ESX1 expression and sperm retrieval were concordant in 14 of 19 (74%) cases subjected to TESE, but in only 3 of 11 (27%) men who underwent microTESE. With TESE, but not with microTESE, both samples originated from adjacent testicular areas. The pyrosequencing of the ESX1 CpG island revealed methylation levels that were significantly lower in ESX1 expressors when compared with non-expressors. CONCLUSIONS: ESX1 emerges as a potentially reliable spermatogenesis molecular marker, whose clinical value as a predictor of successful sperm retrieval warrants further studies.

The seminiferous tubule caliber pattern as evaluated at high magnification during microdissection testicular sperm extraction predicts sperm retrieval in patients with non-obstructive azoospermia.

BACKGROUND: microTESE proved to be the gold standard surgical approach for patients with non-obstructive azoospermia (NOA), but sperm retrieval rates (SRRs) vary considerably among centers. Some authors compared their SRRs with the pattern of seminiferous tubule caliber found at high magnification, but none provided diagnostic accuracy measures. OBJECTIVE: The present retrospective study sought to verify the diagnostic accuracy of the pattern of seminiferous tubule caliber in predicting the sperm retrieval in NOA patients. MATERIALS AND METHODS: Data from 143 infertile NOA men undergoing unilateral (64) or bilateral (79) microTESE (222 testes) were retrospectively evaluated. During microTESE, if present, dilated tubules (DTs) were retrieved, otherwise tubules with slightly larger caliber (SDT) (×24) than that of the surroundings were removed. When no DT or SDT were found, not dilated tubules (NDTs) were excised. RESULTS: Spermatozoa were retrieved in 95 of 222 testes (42.8%); sperm retrieval was successful in 90% of testes with DTs, in 47% of those with SDTs, and only in 7% of those with NDTs (p < 0.0001). Stepwise binary logistic regression revealed that the combination of seminiferous tubule pattern and testis histology was significantly predictive of SSR, being able to classify 86.8% of testes, with an excellent diagnostic accuracy (AUC 0.93). The median number of spermatozoa retrieved was significantly higher in DTs compared with SDTs and NDTs. DISCUSSION: The results of the present study provide reliable accuracy measures in support of the relationship between seminiferous tubule caliber pattern and SSR in patients with non-obstructive azoospermia. We are proposing for the first time that spermatozoa may be retrieved even from slightly dilated tubules in about half of cases. The pattern of tubules retrieved, together with histology, may represent an additional outcome measure of microTESE. CONCLUSION: The pattern of seminiferous tubules together with testis histology predicts sperm retrieval with an excellent diagnostic accuracy.

Histopathological findings after radiofrequency (RITA) treatment for prostate cancer.

Radiofrequency interstitial tumor ablation (RITA) is a thermal ablation method that uses needles and low radiofrequency (RF) energy. The aim of our study was to evaluate the histopathology of thermal lesions induced by RF energy delivered interstitially in prostate cancer patients who subsequently underwent prostatectomy, and to determine the feasibility, effectiveness and safety of this new method in a pilot study.

Immunoradiometric versus enzymatic renin assay: results of the Italian Multicenter Comparative Study. Italian Multicenter Study for Standardization of Renin Measurement.

OBJECTIVES: The measurement of plasma renin activity (PRA) is very convenient for estimating the action of the renin system, but its interlaboratory reproducibility is notoriously poor. This multicentre study aimed to examine whether an immunoradiometric assay which quantifies renin directly with monoclonal antibodies can reduce this limitation of the enzymatic assay. The study also aimed to establish the reference values of immunoreactive renin (IrR) in a large sample of normotensive subjects and patients with various pathophysiological conditions. DESIGN AND METHODS: PRA and IrR were measured once in each of the eight participant centres in eight pool plasma samples with a wide range of renin content; in seven centres these measurements were repeated twice more in order to compare the intralaboratory interassay reproducibility of both methods. Finally, PRA and IrR were measured in the supine and standing positions in 503 subjects including normal controls, patients with various forms of hypertension, patients with Cushing's and Bartter's syndromes, patients with hepatic cirrhosis and pregnant women. RESULTS: We found that both the inter- and intralaboratory coefficients of variation for PRA measurements were higher than those for IrR. In plasma samples from normal subjects and from patients, mean +/- SEM supine PRA and IrR ranged, respectively, from 0.08 +/- 0.03 ng/ml per h and 2.6 +/- 0.5 pg/ml in patients with Conn's syndrome to 7.2 +/- 2.5 ng/ml per h and 138 +/- 51 pg/ml in patients with hepatic cirrhosis. PRA and IrR were found to be significantly correlated in all laboratories (mean +/- SEM of correlation coefficients 0.84 +/- 0.03) and for all of the conditions (correlation coefficient ranging from 0.98 in patients with Cushing's syndrome to 0.50 in pregnant women). However, for the pregnant women the slope of the regression line depicting the PRA-IrR relationship was significantly steeper than for all of the other conditions. CONCLUSIONS: In our experience the inter- and intralaboratory reproducibilities of the immunoradiometric assay appear to be greater than can be achieved with the enzymatic assay, the difference being probably due to the greater complexity of the latter. The two methods provide superimposable information on the renin-angiotensin system activity, except in pregnancy, during which the PRA:IrR ratio is much higher than in the other conditions. Therefore, in this and other pathophysiological situations associated with marked angiotensinogen concentration alterations, the enzymatic assay may be still preferable for assessing the activity of the system accurately.

Superiority of acceleration and acceleration time over pulsatility and resistance indices as screening tests for renal artery stenosis.

OBJECTIVE: To compare the accuracy of four echo-Doppler-derived velocimetric indices (pulsatility and resistance indices, acceleration and acceleration time) in detecting renal artery stenosis in hypertensive patients. PATIENTS AND METHODS: In 73 hospitalized patients with moderate-to-severe hypertension, 18 of whom had normal renal arteries and 55 renal artery stenosis (50-95%) either atherosclerotic (30 cases, five bilateral) or fibromuscular dysplasia (25 cases, two bilateral), we measured the four velocimetric indices using the lateral abdominal approach and sampling Doppler waveforms distally to the stenosis. The diagnostic accuracy of each index was calculated using as cut-off limit the ideal threshold determined with the receiver-operating characteristic curves. RESULTS: On average all of the indices were altered significantly in arteries with stenosis of both aetiologies with respect to normal arteries, the alterations of pulsatility and resistance indices being, however, less pronounced than those of acceleration and acceleration time, particularly in atherosclerotic stenosis. With the cut-off limits of 0.93, 0.59 and 7.4 m/s2 and 60 ms, respectively, for pulsatility and resistance indices, acceleration and acceleration time, their diagnostic accuracies were 80, 73, 93 and 92%. In stenotic arteries, only the acceleration time was correlated with the degree of arterial narrowing, whereas, in normal arteries, only pulsatility and resistance indices were directly correlated with the age of patients. CONCLUSIONS: Acceleration and acceleration time are more accurate indices than pulsatility and resistance to screen for renal artery stenosis, probably because their alterations are less attenuated by the counterbalancing effects of age and of atherosclerosis.

Effects of exposure to high altitude on plasma endothelin-1 levels in normal subjects.

OBJECTIVE: To assess whether the hypoxia associated with exposure to high altitude affects plasma endothelin-1 levels, and whether changes in endothelin-1 are related to those in systemic and pulmonary blood pressure. DESIGN: Eight normal subjects ascended Mount Everest to an altitude of 5050 m within a period of 8 days (study 1) and 10 ascended Mount Rosa in the Italian Alps to an altitude of 4559 m within 2 days (study 2). In study 1 systemic blood pressure, heart rate, haematocrit, haemoglobin oxygen saturation (evaluated by percutaneous oximetry) and venous plasma endothelin-1 were measured several times during the ascent, and twice more during the time spent at high altitude. In study 2 the same parameters as well as systolic pulmonary pressure by echocardiography were evaluated on the second day of resting at 4559 m. In both studies, data obtained during the expeditions were compared with those collected from the same subjects at sea level. RESULTS: In study 1 plasma endothelin-1 increased progressively up to 4240 m (from 1.8 +/- 0.1 pg/ml at sea level to 2.7 +/- 0.2 pg/ml) and decreased slightly thereafter; these increments were directly related to the decrements in percutaneous oxygen saturation, which, at that altitude, fell from 98.6 +/- 0.2% at sea level to 80.8 +/- 0.4%. Blood pressure and haematocrit also rose in response to exposure to high altitude but these changes were not related to changes in endothelin-1. In study 2 the increments in plasma endothelin-1 were similar to those observed in study 1 and the changes again correlated with changes in oxygen saturation as well as with those in systolic pulmonary pressure. On average, systolic pulmonary pressure increased from 19 +/- 1 to 26 +/- 1.9 mmHg, whereas systemic blood pressure and haematocrit were unchanged. CONCLUSION: Exposure to high altitude is associated with consistent increases in plasma endothelin-1. This is probably the result of augmented secretion of the peptide in response to hypoxia and may contribute to the physiological adaptation of the pulmonary circulation to this condition.

Macrocryosectioning of the prostate: a simple technique.

Whole mount sections of the prostate are widely used in many laboratories. Macrocryosections of the gland; that is, whole mount frozen sections of the prostate from radical prostatectomies represent a useful new research protocol. The technique is very simple and does not require expensive equipment.

[A case of arterial hypertension after use of oral contraceptives]. / Un caso di ipertensione arteriosa dopo uso di contraccettivo orale.

It is known that oral contraceptives may induce high blood pressure that usually returns to normal values a few weeks after interruption of the drugs, and without any specific treatment. The precise mechanism by which oral contraceptives cause hypertension is not clear. A severe hypertension and mild heart failure in a young woman using oral contraceptives has been observed in the case described. The patient needed a careful and prolonged therapy to maintain a normal blood pressure.

Topographic and quantitative relationship between prostate inflammation, proliferative inflammatory atrophy and low-grade prostate intraepithelial neoplasia: a biopsy study in chronic prostatitis patients.

Inflammatory processes are important components in the pathogenesis of many human cancers. According to the 'injury and regeneration' model for prostate carcinogenesis, injury caused by pathogens or pro-inflammatory cytotoxic agents would trigger proliferation of prostatic glandular cells, leading to the appearance of epithelial lesions named 'Proliferative Inflammatory Atrophy' (PIA). Inflammatory cells infiltrating the prostate would release genotoxic reactive oxygen species, leading atrophic cells to neoplastic progression. The hypothesis pointing to PIA as risk-lesion for prostate cancer has been extensively investigated at the cellular and molecular levels, but few morphological data are available linking PIA or prostatic intraepithelial neoplasia (PIN) to inflammation or clinical prostatitis. We investigated at the morphological level 1367 prostate biopsies from 98 patients with a recent history of chronic prostatitis, and 32 patients with biopsies positive for carcinoma. Our results show that i) PIA is found more frequently in biopsy cores containing a severe or moderate inflammatory focus, compared to NON-PIA lesions (partial or cystic atrophy); ii) the PIA lesion post-atrophic hyperplasia is more frequently found in tissues showing mild or no inflammation; iii) the extent of PIA per patient correlates with the burden of moderate or severe inflammation, whereas NON-PIA lesions do not; iv) low-grade PIN is in over 90% of cases emerging from normal, non-atrophic glands and is more frequently found in biopsy cores with absent or mild inflammatory burden; v) the inverse relationship between the prevalence of low-grade PIN and the extent of PIA lesions per patient is described by a power law function, suggesting the low likelihood of the concomitant presence of these lesions in the same tissue; vi) NON-PIA lesions correlate inversely with neoplasia in patients with prostate cancer; vii) the total scores of the NIH-CPSI questionnaire correlate with both PIA and inflammation burdens at diagnosis of prostatitis but not after pharmacological intervention. These results point to a positive association between tissue inflammation, clinical prostatitis and the putative cancer risk-lesion PIA, but do not support a model whereby low-grade PIN would arise from PIA.

High prevalence of testicular cancer in azoospermic men without spermatogenesis.

BACKGROUND: An increased risk of testicular cancer in men with infertility and poor semen quality has been reported. Our aim was to investigate the prevalence of testicular nodules and cancer in azoospermic subjects with different spermatogenetic patterns. METHODS: A total of 1443 consecutive infertile men were investigated, out of which 145 (10.0%) were found to be azoospermic. By using clinical examination and testicular ultrasound, 11 out of the 145 patients showed testicular nodules (2.8-26 mm). To obtain spermatozoa for assisted reproduction, 97 subjects required testicular sperm extraction (TESE) and biopsy, including the 11 patients with nodules. They were divided into two groups according to biopsy results: Group A (n = 38) with complete Sertoli cell-only syndrome (SCOS) and Group B (n = 59) with varying spermatogenetic patterns. Ten nodules were found in Group A and one in Group B. RESULTS: In azoospermic men, the overall prevalence of nodules was 7.5%. In complete SCOS, the prevalence of nodules and cancer was 10/38 (26.3%) and 4/38 (10.5%), respectively. Amongst the cancers, one embryonal carcinoma, one seminoma and two in-situ carcinomas were found. CONCLUSION: The prevalence of testicular nodules and cancer in azoospermic men with complete SCOS is very high. In these subjects, the role of clinical evaluation, ultrasound and biopsy should be emphasized.

Restoration of posterior aspect of rhabdosphincter shortens continence time after radical retropubic prostatectomy.

PURPOSE: Prolonged postoperative incontinence is a major drawback of RRP. Age, scars in the rhabdosphincter, nonnerve sparing surgery and postoperative sphincter insufficiency can cause temporary or definitive urinary incontinence. We believe that sphincter deficiency is the main cause of early incontinence. Urinary leakage results from the shortening of anatomical and functional sphincter length due to caudal retraction of the urethral sphincteric complex and disruption of the median posterior fibrous raphe. We describe a modification of the Walsh RRP that overcomes caudal retraction, reconstructs the posterior fibrous raphe and decreases time to continence. The primary study end point was early continence rate assessment. Long-term continence (1 year) and erectile function assessment were secondary end points. MATERIALS AND METHODS: To avoid caudal retraction of the urethrosphincteric complex, before completing the vesicourethral anastomosis the posterior semicircumference of the sphincter is joined to the residuum of Denonvilliers' fascia and fixed to the posterior bladder wall 1 to 2 cm cranial and dorsal to the new bladder neck. Vesicourethral anastomosis is subsequently performed with care taken not to involve the neurovascular bundles. A total of 161 patients with clinically confined disease underwent modified RRP (group 1). They were compared with a historical series of 50 patients who underwent standard RRP (group 2). Early continence was defined as no pad use but patients using 1 diaper were also considered continent. Continence, assessed prospectively as the number of pads daily, was evaluated 3, 30 and 90 days, and 1 year after catheter removal. The continence state was assessed by a multivariate logistic model. Erectile function was evaluated using the International Index of Erectile Function questionnaire preoperatively and after 18 months in patients younger than 65 years who underwent nerve sparing surgery. RESULTS: In group 1, 116 (72%), 127 (78.8%) and 139 patients (86.3%) were continent 3, 30 and 90 days after catheter removal compared with 7 (14%), 15 (30%) and 23 (46%), respectively, in group 2. One-year continence rates were 96% and 90%, respectively. Erectile function was similar in groups 1 and 2 (46% and 42%, respectively). Multivariate analysis showed that continence was significantly influenced by operation type, stage and patient age. CONCLUSIONS: Careful reconstruction of the posterior aspect of the rhabdosphincter markedly shortens time to continence.

[Male breast cancer. Histochemical and flow cytometry analysis of 6 cases]. / Carcinoma mammario maschile. Analisi immunoistochimica e citofluorimetrica di 6 casi.

The authors studied immunohistochemical and flow cytometric parameters of 6 male breast carcinomas. All patients were ER positive and frequency of aneuplody was 66%. Diploid tumors showed low proliferative activity and S-phase fraction < 3%.

Validation study of thoracic fluid bioimpedance for assessing the haemodialysis-induced changes in total body fluids.

Thoracic fluid bioimpedance (TFB) has been proposed as a noninvasive technique for monitoring both haemodynamics and fluid homeostasis in patients on regular dialysis. To validate the reliability of TFB in assessing the haemodialysis (HD)-induced changes in plasma volume (PV) in these patients, we examined the changes of TFB during and after HD in relation to those in total plasma protein (TP) concentration, haematocrit (Ht), heart rate (HR), total body water (TBW) and plasma angiotensin II (A-II) concentration. Data were recorded in 13 HD patients with a wide range of interdialytic weight gains before, at the end, and 4, 8, 24, 48 h after the HD session. We found that the percent TFB changes were closely and inversely related with those of TP, Ht and TBW (r = -0.54, r = -0.45 and -0.68, respectively, p < 0.001 for all). Similar relations were found between the percent changes in TFB and those in absolute TP and Ht. In addition, a direct relation was found between the percent changes of TFB and those of HR and of A-II (r = 0.33 and r = 0.31, respectively, p < 0.01 for both). These data indicate that TFB is a reliable method for evaluating the HD-induced changes of intra- and extravascular fluids and, with respect to the conventional techniques, has the advantage of providing this information dynamically, and in conjunction with the haemodynamic data of patients.

Effect of atrial natriuretic factor infusion on basal and CRH-stimulated ACTH, cortisol and aldosterone levels in patients with Cushing's or Addison's disease.

OBJECTIVE: While it has been shown that atrial natriuretic factor (ANF) is able to inhibit CRH-stimulated ACTH secretion in vitro, in normal men conflicting results on its effect on ACTH/cortisol responses to insulin and CRH have been reported. Since no data are available concerning the possible influence of ANF on the hypothalamic-pituitary-adrenal axis in states of ACTH hypersecretion, the effect of ANF on pituitary-adrenal function in basal conditions and after CRH stimulation has been investigated in patients with Cushing's (n = 4) and Addison's disease (n = 4). DESIGN: On two different days all patients underwent the following procedures: (a) alpha-human ANF was infused, after a priming dose of 100 ng i.v., at a rate of 0.01 microgram/kg/min over 5 hours. After 120 minutes of ANF infusion, oCRH (1 microgram/kg) was i.v. injected as a bolus; (b) vehicle infusion was given over 5 hours and at 120 minutes oCRH was injected. Plasma ANF, ACTH, cortisol, aldosterone, renin activity and K+ were measured; heart rate and blood pressure were monitored. RESULTS: In Cushing's disease plasma ANF rapidly increased within 30 minutes of the exogenous peptide infusion (from 27 +/- 5 to 73 +/- 14 pmol/l; mean +/- SE), whereas in the vehicle study its concentration was unchanged. During the first 2 hours of both tests no significant modifications in ACTH levels were observed. After CRH the plasma ACTH peak was unchanged. Serum cortisol levels progressively declined during the first 2 hours of ANF infusion (from 778 +/- 150 to 461 +/- 48 nmol/l; P < 0.05), whereas no changes were observed during vehicle. After CRH serum cortisol rose to similar peaks. Plasma aldosterone levels were significantly reduced during the first 2 hours of ANF infusion (from 81 +/- 20 to 35 +/- 7 pmol/l P < 0.05), whereas no changes were found during vehicle. A similar aldosterone rise was induced by CRH during either vehicle or ANF. Mean plasma renin activity slightly declined and the changes were similar on both occasions. In Addison's disease ANF levels rose within 30 minutes of the peptide infusion (from 12 +/- 1 to 49 +/- 8 pmol/l), while they were unchanged during vehicle. A slight decline in ACTH levels in the first 2 hours was observed during either vehicle or ANF infusion. After CRH the plasma ACTH peaks were similar. Mean plasma renin activity was unaffected by vehicle, while ANF caused a decline during the first 2 hours (from 13.4 +/- 0.8 to 7.7 +/- 0.3 ng/ml/h). In all patients, heart rate, blood pressure and K+ were only slightly affected on both occasions. CONCLUSIONS: (1) In patients with corticotrophin hypersecretion ANF does not influence basal and CRH-stimulated ACTH secretion; (2) in Cushing's disease ANF inhibits cortisol and aldosterone basal secretion; this effect is not mediated by ACTH and is over-ridden by CRH stimulation.

Plasma active and inactive renin and fetal complications in women with high risk pregnancies.

To examine whether the activation of the renin system, which occurs during pregnancy, may be relevant for the development and the outcome of the fetus, we measured active and inactive renin throughout gestation in 29 women having a pregnancy defined as "high risk" because of a clinical history of hypertension, nephropathy, and unexplained abortions. In 23 of these women who delivered full-term infants with normal weight and status, we found that active renin increased progressively from early pregnancy until the end of the second trimester and then declined slightly thereafter. In contrast, in the remaining six women who had fetal complications consisting of either signs of distress requiring cesarean section or growth retardation, the increase in active renin failed to occur. In all women the levels of inactive renin were more elevated throughout gestation than those observed in nonpregnant women, and were higher, although not significantly, in women without fetal complications than in those with fetal complications. Thus, a blunted activation of the renin system during pregnancy is associated with alteration in fetal development and may possibly contribute to it.

Abnormal hemodynamics and elevated angiotensin II plasma levels in polydipsic patients on regular hemodialysis treatment.

To investigate the cause and the mechanisms responsible of the compulsive thirst and excessive fluid intake observed in many patients on chronic dialysis treatment, we measured plasma antidiuretic hormone (ADH), angiotensin II (Ang II) and some hemodynamic parameters in seven polydipsic and in six normodipsic patients before hemodialysis, at the end of it and several times during the interdialytic interval. Before dialysis we found that ADH was elevated in both groups (6.9 +/- 1.9 vs. 6.9 +/- 1.3 pg/ml, respectively in polydipsics and controls), whereas Ang II was abnormally high only in polydipsics (51 +/- 12 vs. 11 +/- 3 pg/ml, P < 0.01); these patients also had significantly higher heart rate and cardiac indices and lower total peripheral resistances than control patients. Overall these hemodynamic indices were related with Ang II but not with ADH. Ang II rose markedly in polydipsics after dialysis, reaching a peak at the fourth hour after its termination (136 +/- 12 pg/ml) and remained consistently elevated throughout the interdialytic period, whereas in controls Ang II was practically unchanged with respect to baseline. In contrast, ADH had minor and similar modifications in both groups, in whom also the hemodynamic changes were superimposable. Significant correlations were found between the absolute and percent changes of Ang II and those of plasma volume during the interdialytic interval (P < 0.001 for both), and between the individual values of Ang II measured during the whole study and the interdialytic weight gain (P < 0.05). These results demonstrate that polydipsic patients have abnormally high levels of Ang II before and after the hemodialysis-induced volume depletion.(ABSTRACT TRUNCATED AT 250 WORDS)