[Which non pharmacological interventions should be offered to patients treated with androgen deprivation therapy for prostate cancer? A systematic review]. / Quelles interventions non médicamenteuses proposer aux patients traités par hormono-suppression pour un cancer de la prostate ? Revue systématique de la littérature.

AIM: Prostate cancer is a frequent disease and one of the main treatments used is androgen deprivation therapy, which is a therapy with disabling side effects. Non-pharmacological interventions (NPIs) are evidenced based, non-invasive interventions on human health. They are classified into five categories (physical, psychological, nutritional, digital, elemental). The NPIs sphere is booming and still remains underused in this context. METHODS: A systematic review concerning randomized controlled trials was executed according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We used the "Medline" and "Kalya Research" databases. After searching and selecting eligible publications, we included 37 randomized controlled trials. RESULTS: The majority of articles concerned physical NPIs with 30 clinical studies, 3 publications dealt with nutritional NPIs, 2 with psychological NPIs and 2 articles concerned elemental NPIs. No publication about digital NPI was found. All of the studies aimed to manage and improve the side effects of treatment. No elemental NPI has demonstrated benefit. Only one psychological NPI and one nutritional NPI were effective. Five types of physical NPI protocols have shown efficacy. The main benefits related to physical abilities, body composition, osteoporosis, quality of life, fatigue, reduced cardiovascular risk and finally anxiety and depression. CONCLUSION: Non-pharmacological interventions, especially physical ones, are effective in managing and reducing the side effects associated with androgen deprivation therapy and should be offered to patients in this context.

[Laparoscopic robot-assisted artificial urinary sphincter in women: First approach]. / Sphincter urinaire artificiel robot chez la femme : début d'expérience.

OBJECTIVE OF THE STUDY: To analyze the medium-term results and complications of the artificial urinary sphincter (AUS) AMS 800 implanted using laparoscopic robot surgery in women with stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD). DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective cohort study, which included all procedures done in the CHU of Nîmes from July 2015 to January 2017. Patients with SUI by ISD needing an AUS or patients with a malfunctioning AUS needing to be changed were included. We collected data on intraoperative complications, length of hospitalization, postoperative complications, continence rate at twelve months and satisfaction of patients. RESULTS: Nineteen patients were included, 10 for primo-implantation and 9 for AUS revision. There were 4 postoperative bladder injuries, of which 2 led to laparoconversions. The mean length of hospitalization was 4.1days. Three patients had postoperative complications, which needed an intervention without AUS removal. One patient with persisting SUI due to bladder weakness preferred AUS ablation rather than having a cuff change. There was a median follow-up of 22months (12 to 33months). Sixteen patients out of 19 were completely continent and were satisfied of their intervention and the improvement of their quality of life. CONCLUSION: The laparoscopic robot surgery for AUS implantation is safe and reproducible with good medium-term results. LEVEL OF EVIDENCE: 4.

Validation of a suite of ERP and QEEG biomarkers in a pre-competitive, industry-led study in subjects with schizophrenia and healthy volunteers.

OBJECTIVE: Complexity and lack of standardization have mostly limited the use of event-related potentials (ERPs) and quantitative EEG (QEEG) biomarkers in drug development to small early phase trials. We present results from a clinical study on healthy volunteers (HV) and patients with schizophrenia (SZ) that assessed test-retest, group differences, variance, and correlation with functional assessments for ERP and QEEG measures collected at clinical and commercial trial sites with standardized instrumentation and methods, and analyzed through an automated data analysis pipeline. METHODS: 81 HV and 80 SZ were tested at one of four study sites. Subjects were administered two ERP/EEG testing sessions on separate visits. Sessions included a mismatch negativity paradigm, a 40 Hz auditory steady-state response paradigm, an eyes-closed resting state EEG, and an active auditory oddball paradigm. SZ subjects were also tested on the Brief Assessment of Cognition (BAC), Positive and Negative Syndrome Scale (PANSS), and Virtual Reality Functional Capacity Assessment Tool (VRFCAT). RESULTS: Standardized ERP/EEG instrumentation and methods ensured few test failures. The automated data analysis pipeline allowed for near real-time analysis with no human intervention. Test-retest reliability was fair-to-excellent for most of the outcome measures. SZ subjects showed significant deficits in ERP and QEEG measures consistent with published academic literature. A subset of ERP and QEEG measures correlated with functional assessments administered to the SZ subjects. CONCLUSIONS: With standardized instrumentation and methods, complex ERP/EEG testing sessions can be reliably performed at clinical and commercial trial sites to produce high-quality data in near real-time.

Inter-individual differences in novelty-seeking behavior in rats predict differential responses to desipramine in the forced swim test.

RATIONALE: Antidepressant medications are effective only in a subpopulation of patients with depression, and some patients respond to certain drugs, but not others. The biological bases for these clinical observations remain unexplained. OBJECTIVE: To investigate individual differences in response to antidepressants, we have examined the effects of the norepinephrine reuptake inhibitor desipramine (DMI) and the selective serotonin reutake inhibitor fluoxetine (FLU) in the forced swim test (FST) in rats that differ in their emotional behavior. METHODS: As response to novelty correlates with numerous other measures of emotionality and substance abuse, we contrasted animals that are high responders (HR) in a novel environment with animals that are low responders (LR) and asked whether the two groups exhibit differential responses to DMI (10mg/kg) and FLU (20mg/kg). RESULTS: At the behavioral level, DMI caused a significant decrease in immobility in LR animals only, while FLU caused a significant reduction in immobility in both groups. Moreover, at the neural level, DMI treatment led to a decrease in FST-induced c-fos messenger RNA levels in medial prefrontal cortex (PFC) and paraventricular nucleus of the hypothalamus (PVN) in LR but not HR animals. CONCLUSIONS: Taken together, our results suggest that the HR-LR model is a useful tool to investigate individual differences in responses to norepinephrine reuptake inhibitors (NRIs) and that a differential activation of PFC and/or PVN could underlie some of the inter-individual differences in the efficacy of NRIs.

Differential responses to morphine-induced analgesia in the tail-flick test.

We compared acute and chronic antinociceptive effects of morphine in animals with high reactivity (HR) vs. low reactivity (LR) to novelty. Antinociception was assessed by tail-flick test. Rats were i.p. injected with either saline or morphine (1.5 or 3mg/kg) every 12h for 7 days according to the treatment group. On day 1 of the experiment, LR animals in the 1.5mg/kg morphine group showed significantly higher tail-flick latency than HR. Moreover, significant tolerance to the antinociceptive effects of morphine at the used doses was observed in LR but not HR animals. However, effects of chronic morphine treatment on tail-flick latency in rat groups with similar morphine-induced acute antinociception were undistinguishable. The difference in tail-flick latency between HR and LR rats observed after acute 1.5mg/kg morphine injection was eliminated if beta-funaltrexamine (3mg/kg, i.p.) was administered 24h before the test, an indication that mu opioid receptors are responsible for the difference observed. Studies to anatomically characterize the difference in the acute analgesic effect of morphine in HR vs. LR animals did not however yield any significant difference in mu opioid receptor mRNA levels in locus coeruleus (LC), ventral periaqueductal gray (vPAG), nucleus raphe magnus (NRM) and nucleus reticularis paragigantocellularis (NRPG) between these two groups of animals. In conclusion, our results show that differences in novelty-seeking behavior can predict inter-individual variability in morphine-induced antinociception in rats. Such variability is dependent upon activation of mu opioid receptors, but does not correlate with mu opioid receptor expression in LC, vPAG or ventral medulla.

ePTFE soft tissue patch reconstruction of hemidiaphragmatic agenesis with late clinical presentation.

In this paper we describe a case of a 71-year-old man affected by left hemidiaphragm agenesis who presented an extensive enterothorax after an asymptomatic history for many years. The patient had late development of severe constipation and occasional episodes of bowel obstruction and vomiting. The surgical correction of this congenital anomaly consisted of restoring the continuity of the diaphragmatic barrier with a 2-mm-thick expanded polytetrafluoroethylene soft tissue patch(Gore-Tex) after the herniated viscera have been replaced into the abdominal cavity. At 26 months' follow-up no recurrence has been observed. We would suggest that this is the first known elderly patient surgically treated and the eighth case reported in the literature. The use of a single-layer ePTFE mesh allows a good anatomical and functional repair. An overview of the literature is also reported.

Anti-C1q antibodies in pregnant patients with systemic lupus erythematosus.

OBJECTIVE: To study anti-C1q antibodies in pregnant patients with systemic lupus erythematosus (SLE) and to evaluate their prognostic significance for the occurrence of disease flares or pregnancy complications. METHODS: Twenty-one pregnancies in 19 SLE patients prospectively followed were analyzed. Disease activity was evaluated on the basis of the physician's intention to treat and a modified version of the ECLAM index. Anti-C1q and anti-dsDNA antibodies were detected in the sera by an ELISA assay. Antinuclear antibodies, anti-ENA antibodies, anticardiolipin antibodies and lupus anticoagulant were also performed. RESULTS: In all the patients the disease was inactive at the beginning of the pregnancy. Four flares of disease activity were observed in 4 pregnancies (19%) and obstetric complications were encountered in 7 pregnancies (43%). Anti-C1q antibodies were positive in 4 (19%) pregnancies and anti-dsDNA antibodies in 8 (38%). The presence of anti-phospholipid antibodies at the first assessment was correlated with the occurrence of obstetric complications (p<0.05). The presence of anti-C1q and anti-dsDNA antibodies at the first assessment had no prognostic significance for the occurrence of flares or obstetric complications during the course of pregnancy. Although the small number of patients studied did not allow for statistically significant analysis, flares appeared to be more likely to occur in patients presenting with anti-dsDNA or anti-C1q antibodies during pregnancy compared to patients with no changes in these antibody titers (43% vs 8% respectively). CONCLUSIONS: The presence of anti-C1q and anti-dsDNA antibodies does not seem to be prognostic for the occurrence of flares during pregnancy. Further studies are warranted to explore this possibility.

A Novel Eigenvector-based Method to Detect Mild Alzheimer's Disease Using Event-Related Potentials.

Event-related potentials (ERPs) are a physiological measure of cognitive function that have shown diagnostic and prognostic utility in Alzheimer's disease (AD). In this study, we used a novel eigenvector-based technique to better understand brain electrophysiological differences between subjects with mild AD and healthy controls (HC). Using ERPs from 75 subjects with mild AD and 95 HC, we first calculated cognitive task eigenvectors within each subject from three conditions and then calculated second-order eigenvector components to compare the AD group to the HC group. A MANOVA of the three second-level components discriminated between AD and HC multivariately (Wilks' lambda=.4297, p<0.0001, R2 = .5703), and also on each of the three components univariately (all 3 p-values<0.0001). The eigenvector-based technique used in this study accurately discriminated between the mild AD group and HC. As such, this analysis method adds to our understanding of the differences in ERP signal between AD and HC, and could provide a sensitive biomarker for diagnosis and monitoring of AD progression.

New devices for inguinal hernia repair in elderly patients.

A recent meta-analysis concluded that there was a lower incidence of recurrences after mesh hernioplasty, as opposed to non-mesh open methods. Inguinal mesh and plug hernioplasties have been performed using prostheses of different sizes and shapes, either sutured or not to the tissues. However, hernia repair using mesh is sometimes associated with postoperative pain, more or less severe and/or persistent. As a consequence it may interfere with the time required to return to work and to normal daily activities. Finally, concerning the postoperative complications and recurrences, the data presented in our study confirm the very low rate for both aspects; then, as regards the time to return to work, our good results are similar to those of other studies available in literature. In conclusion the tension-free hernia repair described, based upon the use of Prolene 3D patch, is a safe operation, simple to be acquired, it can be performed on an outpatient basis, with a low complication rate, a low level of pain, and an excellent quality of life thereafter. The new device seems to satisfy all requisites of a feasible, reliable and effective system for repairing primary inguinal hernia, at low cost, high patient comfort, and with low risk of recurrences.

Estrogen receptor beta in the paraventricular nucleus of hypothalamus regulates the neuroendocrine response to stress and is regulated by corticosterone.

The function of the second nuclear estrogen receptor, estrogen receptor beta (ERbeta), in the brain is largely unknown. The present study tested whether 1) ERbeta in the paraventricular nucleus (PVN) of the hypothalamus has a direct role in the hypothalamic-pituitary-adrenal (HPA) axis-mediated stress function, and 2) whether corticosterone (CORT) can regulate ERbeta gene expression in the PVN in the intact, cycling female rat. To test the first hypothesis a pure estrogen receptor antagonist, ICI182, 780, was microinjected into the PVN bilaterally and stress-induced CORT response to an acute stressor (15 min restraint) was measured at 0, 15, 30, 60 and 90 min time points. Estrogen antagonist-injected rats showed inhibited CORT levels at the peak (15 min) of the stress response compared with vehicle-injected animals. To test the second hypothesis, ERbeta mRNA levels were measured in the PVN using in situ hybridization histochemistry following sham surgery, adrenalectomy, and adrenalectomy with low or high CORT replacement. Adrenalectomy reduced ERbeta mRNA expression in the PVN, whereas CORT replacement fully reversed this effect in a dose-dependent fashion. Both antagonist inhibition of CORT response and CORT-mediated regulation of ERbeta mRNA were found to be estrus cycle-dependent in the intact, cycling female. These data suggest that ERbeta in the PVN may critically modulate the HPA axis response to stress and is, in turn, regulated by circulating CORT.

Modulatory effects of norepinephrine in the lateral bed nucleus of the stria terminalis on behavioral and neuroendocrine responses to acute stress.

The brain noradrenergic system is activated by stress, and modulates the activity of forebrain regions involved in behavioral and neuroendocrine responses to stress, such as the lateral bed nucleus of the stria terminalis (BSTL). This region of the limbic forebrain receives dense noradrenergic innervation, and has been implicated in both anxiety and regulation of the hypothalamic-pituitary-adrenal axis. We hypothesized that stress-induced release of norepinephrine in the BSTL modulates anxiety-like behavioral responses to stress and activation of the hypothalamic-pituitary-adrenal stress axis. Using microdialysis, we showed that release of norepinephrine was increased in the BSTL of male Sprague-Dawley rats during immobilization stress. In the next experiment, we then microinjected noradrenergic antagonists into the BSTL immediately prior to acute immobilization stress to examine noradrenergic modulation of behavioral stress reactivity. Either the alpha(1)-receptor antagonist benoxathian, or a cocktail of beta(1)- and beta(2)-receptor antagonists (betaxolol+ICI 118,551) blocked the anxiety-like reduction in open-arm exploration on the elevated plus-maze, but not the reduction in social behavior induced in the social interaction test. In a third experiment, benoxathian reduced plasma levels of adrenocorticotropic hormone following stress, but beta-receptor antagonists had no effect. From these results we suggest that stress-induced norepinephrine release acts on both alpha(1)- and beta-receptors in the BSTL to facilitate anxiety-like behavioral responses on the plus-maze but not the social interaction test, and modulates hypothalamic-pituitary-adrenal axis activation via alpha(1)-receptors only. Together with previous results in which adrenergic antagonists in central amygdala attenuated behavioral responses on the social interaction test but not the plus-maze, these observations suggest the two behavioral tests measure different dimensions of stress reactivity, and that norepinephrine facilitates different components of the stress response by region- and receptor-specific mechanisms.

Inhibition of cortical acetylcholine release and cognitive performance by histamine H3 receptor activation in rats.

1. The effects of histamine and agents at histamine receptors on spontaneous and 100 mM K(+)-evoked release of acetylcholine, measured by microdialysis from the cortex of freely moving, rats, and on cognitive tests are described. 2. Local administration of histamine (0.1-100 microM) failed to affect spontaneous but inhibited 100 mM K(+)-stimulated release of acetylcholine up to about 50%. The H3 receptor agonists (R)-alpha-methylhistamine (RAMH) (0.1-10 microM), imetit (0.01-10 microM) and immepip (0.01-10 microM) mimicked the effect of histamine. 3. Neither 2-thiazolylethylamine (TEA), an agonist showing some selectivity for H1 receptors, nor the H2 receptor agonist, dimaprit, modified 100 mM K(+)-evoked release of acetylcholine. 4. The inhibitory effect of 100 microM histamine was completely prevented by the highly selective histamine H3 receptor antagonist, clobenpropit but was resistant to antagonism by triprolidine and cimetidine, antagonists at histamine H1 and H2 but not H3 receptors. 5. The H3 receptor-induced inhibition of K(+)-evoked release of acetylcholine was fully sensitive to tetrodotoxin (TTX). 6. The effects of intraperitoneal (i.p.) injection of imetit (5 mg kg-1) and RAMH (5 mg kg-1) were tested on acetylcholine release and short term memory paradigms. Both drugs reduced 100 mM K(+)-evoked release of cortical acetylcholine, and impaired object recognition and a passive avoidance response. 7. These observations provide the first evidence of a regulatory role of histamine H3 receptors on cortical acetylcholine release in vivo. Moreover, they suggest a role for histamine in learning and memory and may have implications for the treatment of degenerative disorders associated with impaired cholinergic function.

Symptomatic adrenal myelolipoma: therapeutic considerations.

Four cases of symptomatic myelolipoma of the adrenal gland are presented. Three were treated at laparotomy and one with a laparoscopic approach. On the basis of these four cases we discuss the aetiology, pathogenesis, clinical manifestations, diagnosis and treatment of this rare disease. We also report the follow-up of a patient with bilateral myelolipoma, who underwent monolateral excision. We conclude that myelolipoma, if correctly diagnosed, can be treated conservatively with careful follow-up, limiting surgery to symptomatic cases.

Bilateral synchronous testicular involvement in multiple myeloma. Case report and review of the literature.

The authors describe a case of synchronous bilateral involvement of the testes in a 70-year-old patient seven years after the onset of an IgG k IIIA multiple myeloma. Ultrasonographic and postoperative immunohistochemical studies were performed. A complete review of the literature shows the rarity of testicular plasmacytoma. The present one is the second reported case of syncronous involvement of the testes.

[Liposarcoma of the spermatic cord. Clinical case]. / Liposarcoma del funicolo spermatico. Caso clinico.

Sarcomas are neoplasms originating from connective tissues of any anatomical region; the sarcoma of spermatic cord is a rare neoplasm with only little more than two hundred cases described in the literature. Rhabdomyosarcomas in childhood and leiomyosarcomas in adults are the most frequent histological types. Liposarcomas, fibrosarcomas and osteosarcomas are less frequent. The spermatic cord liposarcoma originates from the spermatic cord fatty tissue and therefore it consist of adipose cells, fibroblasts and myxomatosus cells; such neoplasms are usually very well differentiated. Diagnosis is suggested by the appearance of a progressively enlarging mass and by echotomography which shows a solid or liquid mass of the spermatic cord. Therapy consists of surgical intervention (orchifunicolectomy) which also allows a correct histological diagnosis. The case of a 56 year-old male who underwent left orchifunicolectomy for a sarcoma of spermatic cord occasionally discovered during surgical repair of a left groin hernia is reported. Six months after the intervention the patient is in good condition and there is no evidence of relapse.

[Fibrous pseudotumors of the tunica vaginalis testis. A clinical case]. / Pseudotumore fibroso della tunica vaginale del testicolo. Caso clinico.

A case of multiple fibrous pseudotumors of the tunica vaginalis is reported. Ultrasonography led to diagnosis 10 years previously and the patient underwent surgical exploration when the lesions were up to 6 cm in diameter.

[Unusual development of urothelioma of the upper urinary tract]. / Insolita evoluzione di urotelioma delle vie urinarie superiori.

A case of extrarenal spreading of transitional cell carcinoma caused by rupture of ureterohydronephrosis by ureteral transitional cell carcinoma is reported. Ultrasonography and CT revealed the presence of a severe right ureterohydronephrosis with large septa and a 2 cm diameter exophytic neoplasia of the middle ureter. Nephroureterectomy was performed with excision of a perirenal mass. Histologic examination revealed the presence of transitional cell carcinoma in the perirenal mass, caused by dissemination after renal rupture. CT and ultrasonography were not able to differentiate hydronephrosis from pericapsular spreading because of the extreme disruption of the renal parenchyma.

[Adenoid cystic carcinoma of the prostate. Clinical case]. / Carcinoma adenoido-cistico della prostata. Caso clinico.

The authors report an extremely rare case of adenoid cystic carcinoma of the prostate. No satisfactory clinical and pathological classification exists for this tumour, creating particular difficulties for therapeutic decisions and prognosis. Descriptions of cases with excellent survival rates are reported in the literature, to the extent that this is sometimes regarded as a low-malignancy tumour, but other reports also exist of massive diffusion of the pathology with fatal consequences. Advances in the knowledge of this tumour have enabled a number of earlier pathogenetic hypotheses to be ruled out, namely its possible derivation from ectopic salivary cells, ectopic periurethral glands or metaplastic urethral mucosa, but the origin of this carcinoma is still not certain. It is also difficult to differentiate this form from the typical adenocarcinoma and to make a prognosis for survival. In the case reported here, the final diagnosis was made on the lymph node biopsy obtained during surgery, given that a preoperative biopsy was not feasible owing to the scarcity of material available. The patient received standard hormonal therapy for prostate carcinoma.

Polymerase chain reaction in the early diagnosis of HIV-1 infection in high risk subjects.

We investigated the presence of the HIV-1 infection using the polymerase chain reaction (PCR) test in seronegative sexual partners of HIV-infected subjects and in children born to seropositive mothers. By using PCR assay, no HIV-1 DNA was detected in 32 female partners of HIV positive patients including three pregnant women who were also studied during pregnancy and after delivery. HIV-1 DNA was found in 12 out of 38 children born to seropositive mothers; five of them also had detectable serum HIV-1 p24 Ag levels. On the whole, our data stress the importance of using a very sensitive technique, i.e. PCR, for the early diagnosis of HIV-1 infection.