cAMP-EPAC-PKCε-RIM1α signaling regulates presynaptic long-term potentiation and motor learning.

The cerebellum is involved in learning of fine motor skills, yet whether presynaptic plasticity contributes to such learning remains elusive. Here, we report that the EPAC-PKCε module has a critical role in a presynaptic form of long-term potentiation in the cerebellum and motor behavior in mice. Presynaptic cAMP-EPAC-PKCε signaling cascade induces a previously unidentified threonine phosphorylation of RIM1α, and thereby initiates the assembly of the Rab3A-RIM1α-Munc13-1 tripartite complex that facilitates docking and release of synaptic vesicles. Granule cell-specific blocking of EPAC-PKCε signaling abolishes presynaptic long-term potentiation at the parallel fiber to Purkinje cell synapses and impairs basic performance and learning of cerebellar motor behavior. These results unveil a functional relevance of presynaptic plasticity that is regulated through a novel signaling cascade, thereby enriching the spectrum of cerebellar learning mechanisms.

Targeted Next-Generation Sequencing for the Diagnosis of Gene Variants in Patients with 46,XY Disorder of Sex Development.

INTRODUCTION: Disorders of sex development (DSDs) are congenital abnormalities in which chromosomal, gonadal, and anatomical sex development are atypical. One of these disorders, 46,XY DSD, is particularly difficult to diagnose and manage because its etiology and clinical phenotypes are highly heterogeneous. METHODS: We used a gene panel containing 141 genes implicated in DSDs to perform targeted next-generation sequencing (NGS) in 50 patients with 46,XY DSD. RESULTS: Gene variants were detected in 23 patients (46%). Among them, 13 patients had previously reported pathogenic or likely pathogenic variants, 9 patients had novel variants, and 1 patient had a previously reported variant of uncertain significance. Three of the novel variants were pathogenic, and the remaining were variants of uncertain significance; therefore, 16 patients had pathogenic or likely pathogenic variants according to ACMG guidelines, and the overall diagnostic rate of 46,XY DSD was 32%. The most common gene variants were SRD5A2 variants, followed by the AR variant. In addition, we analyzed the association between gene variants and clinical phenotypes. Most patients presented with multiple DSD phenotypes (i.e., two or more DSD phenotypes were observed, such as micropenis, hypospadias, and cryptorchidism), but the phenotype with the highest diagnostic rate was micropenis. CONCLUSION: Our results indicate that targeted NGS can effectively detect pathogenic gene variants in patients with 46,XY DSD.

LAMP-2A ablation in hippocampal CA1 astrocytes confers cerebroprotection and ameliorates neuronal injury after global brain ischemia.

Reactive astrogliosis and neuronal death are major features of brain tissue damage after transient global cerebral ischemia/reperfusion (I/R). The CA1 subfield in the hippocampus is particularly susceptible to cell death after I/R. Recently, attention has focused on the relationship between the autophagy-lysosomal pathway and cerebral ischemia. Lysosomal-associated membrane protein type-2A (LAMP-2A) is a key protein in chaperone-mediated autophagy (CMA). However, LAMP-2A expression in astrocytes of the hippocampus and its influence on brain injury following I/R remain unknown. Here, we show that LAMP-2A is elevated in astrocytes of the CA1 hippocampal subfield after I/R and in primary cultured astrocytes after transient oxygen-glucose deprivation (OGD). Conditional LAMP-2A knockdown in CA1 astrocytes inhibited astrocyte activation and prevented neuronal death by inhibiting the mitochondrial pathway of apoptosis after I/R, suggesting that elevated astrocytic LAMP-2A contributes to regional ischemic vulnerability. Furthermore, astrocytic LAMP-2A ablation ameliorated the spatial learning and memory deficits caused by I/R. Conditional astrocytic LAMP-2A knockdown also prevented the loss of hippocampal synapses and dendritic spines, improved the synaptic ultrastructure, and inhibited the reduced expression of synaptic proteins after ischemia. Thus, our findings demonstrate that astrocytic LAMP-2A expression increases upon I/R and that LAMP-2A ablation specifically in hippocampal astrocytes contributes to cerebroprotection, suggesting a novel neuroprotective strategy for patients with global ischemia.

Grim-19 plays a key role in mitochondrial steroidogenic acute regulatory protein stability and ligand-binding properties in Leydig cells.

Grim-19 (gene associated with retinoid-IFN-induced mortality 19), the essential component of complex I of mitochondrial respiratory chain, functions as a noncanonical tumor suppressor by controlling apoptosis and energy metabolism. However, additional biological actions of Grim-19 have been recently suggested in male reproduction. We investigated here the expression and functional role of Grim-19 in murine testis. Testicular Grim-19 expression was detected from mouse puberty and increased progressively thereafter, and GRIM-19 protein was observed to be expressed exclusively in interstitial Leydig cells (LCs), with a prominent mitochondrial localization. In vivo lentiviral vector-mediated knockdown of Grim-19 resulted in a significant decrease in testosterone production and triggered aberrant oxidative stress in testis, thus impairing male fertility by inducing germ cell apoptosis and oligozoospermia. The control of testicular steroidogenesis by GRIM-19 was validated using the in vivo knockdown model with isolated primary LCs and in vitro experiments with MA-10 mouse Leydig tumor cells. Mechanistically, we suggest that the negative regulation exerted by GRIM-19 deficiency-induced oxidative stress on steroidogenesis may be the result of two phenomena: a direct effect through inhibition of phosphorylation of steroidogenic acute regulatory protein (StAR) and subsequent impediment to StAR localization in mitochondria and an indirect pathway that is to facilitate the inhibiting role exerted by the extracellular matrix on the steroidogenic capacity of LCs via promotion of integrin activation. Altogether, our observations suggest that Grim-19 plays a potent role in testicular steroidogenesis and that its alterations may contribute to testosterone deficiency-related disorders linked to metabolic stress and male infertility.

Whole-exome sequencing for high-risk primary prostatic extra-gastrointestinal stromal tumor: A case report.

The low incidence rates of prostatic extra-gastrointestinal stromal tumors (EGIST), combined with the lack of published guidelines on its treatment, often results in its misdiagnosis and challenges in the treatment of patients, even in cases with high-risk factors. The present case study reported a 65-years-old Chinese male patient, who presented with intermittent hematuria and lower urinary tract symptoms for three months. The colonoscopy results revealed no gastrointestinal lesions; however, a core biopsy diagnosed an EGIST, which subsequently underwent radical prostatocystotomy, standard pelvic lymph node resection, and bricker ileal conduit diversion. The postoperative pathological results suggested a high-risk primary prostatic EGIST, according to the aggressive behavior of the GIST. The immunohistochemistry results revealed the positive expression of CD117, DOG1, CD34, androgen receptor AR, prostate-specific antigen (PSA), a 2% Ki-67 index and a positive surgical margin. The whole exome sequencing (WES) results revealed that the patient harbored a single nucleotide mutation in 121 genes and copy number variations in 601 genes, including a defect in c-Kit (in-frame deletion in p.Q556-V560; fold, 17.5%). By compiling the data obtained from the ConsensusPathDB and the drug-gene interaction databases and expert opinions, the patient was prescribed with the personalized drugs (400 mg per day imatinib mesylate and 50 mg per day bicalutamide, which were stopped when the PSA levels remained stable below 0.01 ng/ml) for 18 months follow-up and there were no signs of recurrence. In conclusion, WES identified multiple genomic alterations and the underlying genetic defect in the rare case enabled the evaluation of the prognosis and the decision of potential drug candidates. The underlying mechanism of the substantial genetic variations in the primary prostatic EGIST, as well as the malignant behaviors of the tumor, remain to be investigated.

Intravenous injections of the oncolytic virus M1 as a novel therapy for muscle-invasive bladder cancer.

Muscle-invasive bladder cancer (MIBC) is associated with low survival and high recurrence rates even in cases in which patients receive systemic treatments, such as surgery and chemotherapy. Here, we found that a naturally existing alphavirus, namely, M1, selectively kills bladder cancer cells but not normal cells, findings supported by our observations of changes in viral replication and MIBC and patient-derived MIBC cell apoptosis. Transcriptome analysis revealed that interferon-stimulated genes (ISGs) are expressed at low levels in sensitive bladder cancer cells and high levels in resistant cells. Knocking down ZC3HAV1 (ZAP), an antiviral factor in ISGs, restores M1 virus reactivity in resistant cells, and overexpressing ZAP partially reverses M1 virus-induced decreases in cell viability in sensitive cells. In orthotopic MIBC mice, tail vein injections of M1 significant inhibit tumor growth and prolong survival period, antitumor effects of M1 are stronger than those of the first-line chemotherapy agent cisplatin (CDDP). Treated tumors display enhanced cleaved-caspase-3 signals, which are representative of cell apoptosis, and decreased Ki-67 signals, which are representative of cell proliferation. Moreover, tissue microarray (TMA) analyses of clinical tumor specimens revealed that up to 45.6% of cases of MIBC presented with low ZAP expression, a finding that is prevalent in advanced MIBC. Our results indicate that the oncolytic virus M1 is a novel agent capable of functioning as a precise and effective therapy for MIBC.

Downregulation of Glutamate Transporter EAAT4 by Conditional Knockout of Rheb1 in Cerebellar Purkinje Cells.

Excitatory amino acid transporter 4 (EAAT4) is believed to be critical to the synaptic activity of cerebellar Purkinje cells by limiting extracellular glutamate concentrations and facilitating the induction of long-term depression. However, the modulation of EAAT4 expression has not been elucidated. It has been shown that Ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) signaling plays essential roles in the regulation of protein translation, cell size, and cell growth. In addition, we previously found that a cascade including mTOR suppression and Akt activation induces increased expression of EAAT2 in astrocytes. In the present work, we explored whether Rheb/mTOR signaling is involved in the regulation of EAAT4 expression using conditional Rheb1 knockout mice. Our results demonstrated that Rheb1 deficiency resulted in the downregulation of EAAT4 expression, as well as decreased activity of mTOR and increased activity of Akt. The downregulation of EAAT4 was also confirmed by reduced EAAT4 currents and slowed kinetics of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor-mediated currents. On the other hand, conditional knockout of Rheb1 did not alter the morphology of Purkinje cell layer and the number of Purkinje cells. Overall, our findings suggest that small GTPase Rheb1 is a modulator in the expression of EAAT4 in Purkinje cells.

Numb deficiency in cerebellar Purkinje cells impairs synaptic expression of metabotropic glutamate receptor and motor coordination.

Protein Numb, first identified as a cell-fate determinant in Drosophila, has been shown to promote the development of neurites in mammals and to be cotransported with endocytic receptors in clathrin-coated vesicles in vitro. Nevertheless, its function in mature neurons has not yet been elucidated. Here we show that cerebellar Purkinje cells (PCs) express high levels of Numb during adulthood and that conditional deletion of Numb in PCs is sufficient to impair motor coordination despite maintenance of a normal cerebellar cyto-architecture. Numb proved to be critical for internalization and recycling of metabotropic glutamate 1 receptor (mGlu1) in PCs. A significant decrease of mGlu1 and an inhibition of long-term depression at the parallel fiber-PC synapse were observed in conditional Numb knockout mice. Indeed, the trafficking of mGlu1 induced by agonists was inhibited significantly in these mutants, but the expression of ionotropic glutamate receptor subunits and of mGlu1-associated proteins was not affected by the loss of Numb. Moreover, transient and persistent forms of mGlu1 plasticity were robustly induced in mutant PCs, suggesting that they do not require mGlu1 trafficking. Together, our data demonstrate that Numb is a regulator for constitutive expression and dynamic transport of mGlu1.

Repair of urethral defects with polylactid acid fibrous membrane seeded with adipose-derived stem cells in a rabbit model.

AIM: The aim of this study is to evaluate the capacity of polylactid acid (PLA) fibrous membrane seeded with allogeneic rabbit adipose tissue-derived stem cells (ADSCs) to repair urethral defects in a rabbit model. MATERIALS AND METHODS: Rabbit ADSCs were harvested and phenotypically characterized. Twenty-four New Zealand male rabbits with 5-mm urethral mucosal defects were randomly divided into two groups. They underwent urethroplasty either with PLA fibrous membrane seeded with ADSCs (group A) or blank PLA fibrous membrane (group B). At 4 and 6 weeks after urethroplasty, the urethral grafts were collected and analyzed grossly and histologically. The incidence rate of urethrostenosis was measured. RESULTS: The adipose tissue-derived cells in monolayer culture showed a typical morphology of mesenchymal stem cells (MSCs). They were positive for the MSC marker CD44 but negative for lineage markers CD45 and CD105. Six weeks after surgery, the incidence rate of urethrostenosis in group A was significantly lower than that in group B (p < 0.05). In group A, the ADSC-seeded grafts showed a normal urethral architecture with a thickened muscle layer. In contrast, the newly developed urethra in group B demonstrated a fewer number of urothelial layers and scarce or no smooth muscle cells. CONCLUSION: The PLA scaffold seeded with ADSCs is effective in urethral regeneration in a rabbit model. ADSCs may represent a promising source of seed cells for urethral tissue engineering.

Long-term potentiation at cerebellar parallel fiber-Purkinje cell synapses requires presynaptic and postsynaptic signaling cascades.

Long-term depression (LTD) and long-term potentiation (LTP) at cerebellar parallel fiber-Purkinje cell (PF-PC) synapses play critical roles in motor learning. The 1 Hz stimulation at PF-PC synapses induces a postsynaptically expressed LTP that requires a postsynaptic Ca(2+) transient, phosphatases, and nitric oxide (NO). However, the mechanism underlying 1 Hz PF-LTP remains unclear because none of the known events is related to each other. Here, we demonstrated that 1 Hz PF-LTP requires postsynaptic cytosolic phospholipase A2 α (cPLA2α)/arachidonic acid (AA) signaling and presynaptic endocannabinoid receptors. Using patch-clamp recording in cerebellar slices, we found that 1 Hz PF-LTP was abolished in cPLA2α-knock-out mice. This deficit was effectively rescued by the conjunction of 1 Hz PF stimulation and the local application of AA. 2-Arachidonoylglycerol and the retrograde activation of cannabinoid receptor 1 (CB1R) were also involved in 1 Hz LTP because it was blocked by the hydrolysis of 2-AG or by inhibiting CB1Rs. The amount of NO released was detected using an NO electrode in cultured granule cells and PF terminals. Our results showed that the activation of CB1Rs at PF terminals activated NO synthetase and promoted NO production. The 1 Hz PF-stimuli evoked limited NO, but 100 Hz PF stimulation generated a large amount. Therefore, 1 Hz PF-LTP, distinct from classical postsynaptically expressed plasticity, requires concurrent presynaptic and postsynaptic activity. In addition, NO of sufficient amplitude decides between the weakening and strengthening of PF-PC synapses.

Retrograde cPLA2α/arachidonic acid/2-AG signaling is essential for cerebellar depolarization-induced suppression of excitation and long-term potentiation.

Cytosolic phospholipase A2 alpha (cPLA2α) responds to micromolar intracellular Ca(2+) and produces arachidonic acid, which regulates cellular homeostasis, neurotoxicity, and inflammation. Endocannabinoids are the derivates of arachidonic acid and widely distributed in the cerebellum. However, the role of cPLA2α/arachidonic acid pathway in cerebellar synaptic transmission and plasticity is unknown. We utilized cPLA2α knockout mice and slice whole-cell patch clamp to study the action of cPLA2α/arachidonic acid signaling on the depolarization-induced suppression of excitation (DSE) and long-term potentiation at parallel fiber-Purkinje cell synapses. Our data showed that DSE was significantly inhibited but rescued by arachidonic acid in cPLA2α knockout mice. The degradation enzyme of 2-arachidonoylglycerol (2-AG), monoacylglycerol lipase, blocked DSE, while another catabolism enzyme for N-arachidonoylethanolamine, fatty acid amide hydrolase, did not, suggesting that 2-AG is responsible for DSE in Purkinje cells. Co-application of paxilline reversed the blockade of DSE by internal K(+), indicating that large-conductance Ca(2+)-activated potassium channel is sufficient to inhibit cPLA2α/arachidonic acid-mediated DSE. On the other hand, we found that 1 Hz parallel fiber stimuli-triggered long-term potentiation (LTP) was deficient in cPLA2α knockout mice. LTP was also inhibited when AACOCF3, an inhibitor of cPLA2α, was given. Arachidonic acid was necessary for the LTP induction. Therefore, these data showed that cPLA2α/arachidonic acid/2-AG signaling pathway mediates DSE and LTP at parallel fiber-Purkinje cell synapse.

Cytosolic phospholipase A2 alpha/arachidonic acid signaling mediates depolarization-induced suppression of excitation in the cerebellum.

BACKGROUND: Depolarization-induced suppression of excitation (DSE) at parallel fiber-Purkinje cell synapse is an endocannabinoid-mediated short-term retrograde plasticity. Intracellular Ca(2+) elevation is critical for the endocannabinoid production and DSE. Nevertheless, how elevated Ca(2+) leads to DSE is unclear. METHODOLOGY/PRINCIPAL FINDINGS: We utilized cytosolic phospholipase A(2) alpha (cPLA(2)α) knock-out mice and whole-cell patch clamp in cerebellar slices to observed the action of cPLA(2)α/arachidonic acid signaling on DSE at parallel fiber-Purkinje cell synapse. Our data showed that DSE was significantly inhibited in cPLA(2)α knock-out mice, which was rescued by arachidonic acid. The degradation enzyme of 2-arachidonoylglycerol (2-AG), monoacylglycerol lipase (MAGL), blocked DSE, while another catabolism enzyme for N-arachidonoylethanolamine (AEA), fatty acid amide hydrolase (FAAH), did not affect DSE. These results suggested that 2-AG is responsible for DSE in Purkinje cells. Co-application of paxilline reversed the blockade of DSE by internal K(+), indicating that large conductance Ca(2+)-activated potassium channel (BK) is sufficient to inhibit cPLA(2)α/arachidonic acid-mediated DSE. In addition, we showed that the release of 2-AG was independent of soluble NSF attachment protein receptor (SNARE), protein kinase C and protein kinase A. CONCLUSIONS/SIGNIFICANCE: Our data first showed that cPLA(2)α/arachidonic acid/2-AG signaling pathway mediates DSE at parallel fiber-Purkinje cell synapse.

Presence of tumour-infiltrating FOXP3+ lymphocytes correlates with immature tumour angiogenesis in renal cell carcinomas.

BACKGROUND: FOXP3+ regulatory T cells (Tregs) inhibit effector T cell functions and are implicated in tumour progression. However, together with microvessel density (MVD) they remain controversial prognostic predictors for renal cell carcinoma (RCC), and potential associations have yet to be determined. The objective of this study was to determine the prognostic significance of Tregs and MVD and their potential relationship in RCCs. DESIGN: Paraffin-embedded tissues from 62 RCC patients were analysed using immunohistochemistry to detect FOXP3+ lymphocytes, and double immunohistochemistry to detect different microvessel types in the tumour interior, rim and normal kidney tissue, and their correlation with clinicopathological characteristics. Survival analysis was also performed. RESULTS: The presence of FOXP3+ cells in the tumour interior or the rim showed no correlation with death from RCC and other pathological characteristics. Negative correlations were noted between the immature MVD in the tumour interior or the rim and tumour size, tumour stage and overall survival; however, there was no correlation with the nuclear grade or pathological type. A positive correlation between FOXP3+ Tregs and immature MVD (r=0.363, P=0.014) and mature MVD (r=0.383, P=0.009) was confirmed in the tumour interior. However, there was no correlation between FOXP3+ Tregs and mature MVD (r=0.281, P=0.076) or immature MVD (r=0.064, P=0.692) in the tumour rim. CONCLUSIONS: In this study, a positive correlation between the presence of FOXP3+ Tregs and immature and mature MVD in RCC was confirmed, which suggests a link between suppression of immunity, tumour angiogenesis and poor prognosis.

Comparative study on ureteroscopic lithotripsy and laparoscopic ureterolithotomy for treatment of unilateral upper ureteral stones.

PURPOSE: To compare the curative effects of ureteroscopic lithotripsy and laparoscopic ureterolithotomy for unilateral upper ureteral stones, and to explore optimal surgical indications and skills. METHODS: Fifty cases of unilateral upper ureteral stones were randomly divided into two groups: one group underwent ureteroscopic holmium laser lithotripsy under epidural or lumbar anesthesia (n=25), and another group underwent laparoscopic ureterolithotomy under general anesthesia (n=25). Double-J stent was routinely indwelled in both groups. Operating time, postoperative hospitalization time, stone clearance rate and perioperative complications were compared. RESULTS: Operation was successfully performed in all 50 cases, and no open surgery was converted in any case. In the ureteroscopy and laparoscopy groups, the mean operating time was 49.0 ± 10.7 min and 41.8 ± 8.0 min (t=2.68, P=0.00999), respectively, their hospitalization time was 2.8 ± 1.3 days vs. 2.9 ± 0.8 days (t =-0.40, P=0.69413), and stone clearance rate was 88.0% (22/25) vs. 100% (25/25). Stone moved to the renal pelvis in three cases in the ureteroscopy group, and residual stones were removed by extracorporeal shock-wave lithotripsy (ESWL). All patients were followed up for more than three months, and no serious complications such as ureterostenosis occurred. CONCLUSIONS: Laparoscopic ureterolithotomy has a higher stone clearance rate and shorter operation time compared with ureteroscopic lithotripsy. Laparoscopic ureterolithotomy is one safe and effective treatment on unilateral upper ureteral stones.

Comparative study on ureteroscopic lithotripsy and laparoscopic ureterolithotomy for treatment of unilateral upper ureteral stones / Estudo comparativo entre litotripsia e ureterolitotomia laparoscópica no tratamento de cálculos unilaterais altos

PURPOSE: To compare the curative effects of ureteroscopic lithotripsy and laparoscopic ureterolithotomy for unilateral upper ureteral stones, and to explore optimal surgical indications and skills. METHODS: Fifty cases of unilateral upper ureteral stones were randomly divided into two groups: one group underwent ureteroscopic holmium laser lithotripsy under epidural or lumbar anesthesia (n=25), and another group underwent laparoscopic ureterolithotomy under general anesthesia (n=25). Double-J stent was routinely indwelled in both groups. Operating time, postoperative hospitalization time, stone clearance rate and perioperative complications were compared. RESULTS: Operation was successfully performed in all 50 cases, and no open surgery was converted in any case. In the ureteroscopy and laparoscopy groups, the mean operating time was 49.0±10.7 min and 41.8±8.0 min (t=2.68, P=0.00999), respectively, their hospitalization time was 2.8±1.3 days vs. 2.9±0.8 days (t =-0.40, P=0.69413), and stone clearance rate was 88.0 percent (22/25) vs. 100 percent (25/25). Stone moved to the renal pelvis in three cases in the ureteroscopy group, and residual stones were removed by extracorporeal shock-wave lithotripsy (ESWL). All patients were followed up for more than three months, and no serious complications such as ureterostenosis occurred. CONCLUSIONS: Laparoscopic ureterolithotomy has a higher stone clearance rate and shorter operation time compared with ureteroscopic lithotripsy. Laparoscopic ureterolithotomy is one safe and effective treatment on unilateral upper ureteral stones.

OBJETIVO: Comparar os efeitos curativos da litotripsia ureteroscópica e a ureterolitotomia laparoscópica para cálculos unilaterais altos e pesquisar as indicações e resultados. MÉTODOS: Cinquenta casos de cálculos unilaterais altos foram distribuídos aleatoriamente em dois grupos: um grupo submetido a litotripsia ureteroscópica com laser holmium sob anestesia epidural ou lombar (n=25) e outro grupo submetido a ureterolitotomia laparoscópica sob anestesia geral (n=25). Duplo-J stent foi rotineiramente instalado em ambos os grupos. Comparou-se o tempo operatório, tempo de hospitalização pós-operatória, nível de desaparecimento dos cálculos e complicações pós-operatórias. RESULTADOS: Atos operatórios nos 50 casos sem ocorrências e nenhum ato convertido. Nos grupos por ureteroscopia e laparoscopia, o tempo operatório médio foi 49,0±10,7 minutos e 41,8±8,0 minutos (t=2,68, P=0,00999) respectivamente, tempo de hospitalização foi 2,8±1,3 dias vs. 2,9±0,8 dias (t=0,40, P=0,69413) e o nível de desaparecimento dos cálculos foi 88.0 por cento (22/25) vs. 100 por cento (25/25). Cálculo deslocado para pelve renal em três casos no grupo ureteroscópico e cálculos residuais foram removidos por litotripsia por onda de choque extracorpóreo (ESWL). Todos pacientes foram seguidos por mais de três meses e não ocorreram complicações sérias como estenoses ureterais. CONCLUSÕES: A ureterolitotomia laparoscópica teve maior nível desaparecimento dos cálculos e tempo operatório menor comparado à litotripsia ureteroscópica A ureterolitotomia laparoscópica é um tratamento seguro e efetivo para cálculos ureterais unilaterais altos.

Laparoscopic extraperitoneal repair of symptomatic hydrocele in children: a single-center experience with 73 surgeries.

PURPOSE: To introduce a novel, two-port laparoscopic technique for treatment of hydrocele in children, which allows completely extraperitoneal closure of the patent processus vaginalis (PPV) and does not necessitate laparoscopic suturing skills. PATIENTS AND METHODS: We describe a consecutive series of 56 boys with a median age of 36 months (range 12-144 mos) who presented with a presumably communicating hydrocele. Laparoscopic repair of these hydroceles was performed between July 2009 and June 2010. During surgery, a 5-mm laparoscope and a 3-mm grasping forceps were inserted through an identical umbilical incision (10 mm). The hydrocele sac orifice was closed extraperitoneally by circuit suturing around the internal inguinal ring. RESULTS: All cases were preoperatively diagnosed to be unilaterally based on physical examination and ultrasonography. During surgery, 17 of the 56 (30%) patients presented a contralateral PPV. A total of 73 laparoscopic procedures were achieved, with a success rate of 100%. The mean operative time was 25±6 and 36±5 minutes for unilateral and bilateral operations, respectively. During a median follow-up period of 6 months (range 1-12 mos), neither recurrence nor other postoperative complication was encountered. CONCLUSIONS: Our limited experiences suggest that the two-port, totally extraperitoneal laparoscopic technique could be a safe, effective, and reliable alternative for management of pediatric hydrocele.

Endourologic treatments of distal ureteral obstruction in patients with history of pelvic malignancies: efficacy and safety evaluation.

BACKGROUND & OBJECTIVE: Postoperative tissue adherence, scarring and radiotherapy often lead to extrinsic compression and stricture in the distal ureter of the patients who had history of pelvic malignancies. Our aim was to evaluate the efficacy and safety of endourologic techniques in treating this kind of ureteral obstruction. METHODS: From Jan. 1998 to Mar. 2007, 46 patients with obstruction in the distal ureter and had history of pelvic malignancies underwent endoscopic treatments at the Third Affiliated Hospital of Sun Yat-sen University for relief of the obstruction. Perioperative and follow-up data were analyzed. RESULTS: Of the 46 patients, 25 underwent laparoscopic ureterolysis and uretero-neocystostomy, 18 underwent placement of ureter stent under ureteroscope, 3 underwent percutaneous nephrostomy. No severe complication was recorded. The mean operating time was 82.5 min (range, 30-140 min). The mean blood loss was 45.5 ml (range, 5-180 ml). No blood transfusion was needed. The median follow-up time was 18.2 months (range, 3 months to 6.5 years). Three months after operation, B-ultrasonography and intravenous urography (IVU) showed that 39 (84.8%) patients had recovered normal renal function, the other 7 (15.2%) had hydronephrosis relief and renal function improvement. Nuclear renal scanning showed that the mean postoperative glomerular filtration rate (GFR) in the obstructive kidney was higher than the preoperative level (37.6 ml/min vs. 21.3 ml/min, P<0.05). No stricture in the uretero-bladder anastomotic stoma was recorded. CONCLUSION: Endoscopic operation is an effective and feasible option for managing some selected kinds of distal ureteral obstruction caused by postoperative tissue adherence and radiotherapy in the patients with history of pelvic malignancies.