S. Droupy

Supra and infralevator neurovascular pathways to the penile corpora cavernosa

The aim of this study was to provide a comprehensive description of both penile innervation and vascularisation. Eighty‐five male cadavers were examined through gross and microscopic anatomical analysis. The pelvic nerve plexus had both parasympathetic and sympathetic roots. It was distributed to the external urethral sphincter giving rise to cavernous nerves which anastomosed in 70% of the cases with the pudendal nerve in the penile root. Accessory pudendal arteries were present in the pelvis in 70% of the cases, anastomosing in 70% of the cases with the cavernous arteries that originated from the pudendal arteries. Transalbugineal anastomoses were always seen between the cavernous artery and the spongiosal arterial network. There were 2 venous pathways, 1 in the pelvis and 1 in the perineum with a common origin from the deep dorsal penile vein. It is concluded that there are 2 neurovascular pathways destined for the penis that are topographically distinct. One is located in the pelvis and the other in the perineum. We were unable to determine the functional balance between these 2 anastomosing pathways but experimental data have shown that they are both involved in penile erection. These 2 neurovascular pathways, above and below the levator ani, together with their anastomoses, form a neurovascular loop around the levator ani.

Prevalence of renal cell carcinoma in patients with autosomal dominant polycystic kidney disease and chronic renal failure.

OBJECTIVES To study the prevalence and the characteristics of renal cell carcinoma (RCC) in patients with autosomal dominant polycystic kidney disease (ADPKD) in our series. METHODS We reviewed retrospectively all the nephrectomies performed in our department between 1982 and 2003 in patients with ADPKD and chronic renal failure. RESULTS Seventy-nine patients (42 males and 37 females) with ADPKD and chronic renal failure underwent 89 nephrectomies; in 10 of 79, both kidneys were removed but not simultaneously. Mean age was 50.4 years (range, 32-69 years). Of 79 patients, 50 had end-stage renal disease (ESRD) and were on hemodialysis or had received a transplant for >1 year. On histologic examination, 11 of 89 kidneys were diagnosed with carcinomas. There was 1 patient with bilateral tumor (tubulopapillary Ca) and 3 kidneys (27.3%) with multifocal tumors. Regarding the histologic type, there were 7 of 12 (58.3%) clear cell carcinomas and the remaining 5 (41.7%) were tubulopapillary carcinomas. CONCLUSIONS The prevalence of RCC was higher in patients with ADPKD and ESRD, with >1 year on dialysis or renal transplantation undergoing nephrectomy according the protocol. It would be 2 to 3 times more frequent than RCC in patients with ESRD alone. The clinician should maintain a high alert of suspicion for RCC in such patients.

Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma

BackgroundChromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC.MethodsGene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors.ResultsA novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities.ConclusionsGene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.

The structure and innervation of the male urethra: histological and immunohistochemical studies with three-dimensional reconstruction.

The structure of the striated urethral sphincter, the so‐called rhabdosphincter, remains the subject of controversy. There are two main concepts regarding its structure: either it is a part of the urogenital diaphragm, or it extends from the base of the bladder up to the urogenital diaphragm and is an integral part of the urethra. It is also uncertain whether it possesses a somatic innervation or a mixed innervation (i.e. autonomic and somatic). The purpose of this study was to show the precise location of the nerves running to the urethra, and to try to determine their exact nature. Histology and immunohistochemistry were performed in the external urethral sphincter of ten male fetuses (114–342 mm crown–rump length, or between 14 and 40 weeks of gestation). A three‐dimensional (3D) reconstruction of the urethral structure and its innervation was made from serial sections. The 3D reconstruction of the same section levels with different strains allowed us to identify the precise structure of the muscle layers (smooth and striated muscle fibres) and the nature of the nerve elements (myelinated and unmyelinated), their distributions and their relationship to the urethral wall, the prostate and the seminal vesicles. Histological and immunohistochemical 3D reconstruction of the anatomical elements of the urethral sphincter helps us to understand the 3D arrangement of the sphincter muscle layers. It also provides a better understanding of the origin and nature of the nerve elements that play a role in urinary continence.

Autonomic-somatic communications in the human pelvis: computer-assisted anatomic dissection in male and female fetuses

Sphincter continence and sexual function require co‐ordinated activity of autonomic and somatic neural pathways, which communicate at several levels in the human pelvis. However, classical dissection approaches are only of limited value for the determination and examination of thin nerve fibres belonging to autonomic supralevator and somatic infralevator pathways. In this study, we aimed to identify the location and nature of communications between these two pathways by combining specific neuronal immunohistochemical staining and three‐dimensional reconstruction imaging. We studied 14 normal human fetal pelvic specimens (seven male and seven female, 15–31 weeks’ gestation) by three‐dimensional computer‐assisted anatomic dissection (CAAD) with neural, nitrergic and myelin sheath markers. We determined the precise location and distribution of both the supra‐ and infralevator neural pathways, for which we provide a three‐dimensional presentation. We found that the two pathways crossed each other distally in an X‐shaped area in two spatial planes. They yielded dual innervation to five targets: the anal sphincter, levator ani muscles, urethral sphincter, corpus spongiosum and perineal muscles, and corpora cavernosa. The two pathways communicated at three levels: proximal supralevator, intermediary intralevator and distal infralevator. The dorsal penis/clitoris nerve (DN) had segmental nitrergic activity. The proximal DN was nNOS‐negative, whereas the distal DN was nNOS‐positive. Distal communication was found to involve interaction of the autonomic nitrergic cavernous nerves with somatic nitrergic branches of the DN, with nitrergic activity carried in the distal part of the nerve. In conclusion, the pelvic structures responsible for sphincter continence and sexual function receive dual innervation from the autonomic supralevator and the somatic infralevator pathways. These two pathways displayed proximal, intermediate and distal communication. The distal communication between the CN and branches of the DN extended nitrergic activity to the distal part of the cavernous bodies in fetuses of both sexes. These structures are important for erectile function, and care should therefore be taken to conserve this communication during reconstructive surgery.

A Histopathologic Investigation of PGE2 Pathways as Predictors of Proliferation and Invasion in Urothelial Carcinomas of the Bladder

INTRODUCTION AND OBJECTIVES The pattern of arachidonate acid (AA) transformation in tumor cells has been shown to play a role in determining tumor cell invasiveness. AA is released from membrane phospholipids by cPLA(2). Then it is metabolized into prostaglandins and PGE(2) especially via cyclooxygenase pathways. PGE(2) production seems to be necessary for rendering the cells invasive. We aimed to characterize cPLA(2), cyclooxygenase 2 (COX2) and prostaglandine E synthase (PGES) expression in human transitional carcinoma (TCC) of the urinary bladder and correlate with the Ki-67 proliferating marker. METHODS Formalin-fixed human TCC tissues (n=54) obtained from TURB or cystectomies were evaluated for cPLA(2), COX2, PGES and Ki-67 expression using specific antibodies. There were 6 CIS, 9 pTaG1, 9 pTaG3, 10 pT1G3 and 10 pT2G3. 10 normal bladder tissues were also evaluated. Control slides were incubated without primary antibodies and treated in a similar way. RESULTS cPLA(2), COX2 and PGES were not expressed in the 10 normal tissues. In the same normal tissues, Ki-67 expression was observed only in 1% of the cells. However, cPLA(2) was expressed in 1/6 CIS, 1/9 pTaG1, 3/9 pTaG3, 6/10 pT1G3 and 2/10 pT2G3. COX2 was expressed in 0/6 CIS, 0/10 pTaG1, 2/9 pTaG3, 3/10 pT1G3 and 1/10 pT2G3. PGES was expressed in 4/6 CIS, 0/9 pTaG1, 4/9 pTaG3, 2/10 pT1G3 and 5/10 pT2G3. Ki-67 expression was 39.5% for CIS, 6.5% in pTaG1, 37% in pTaG3, 34.5% in pT1G3 and 55% in pT2G3. If we consider it a positive result when at least one enzyme was expressed, there were 5/6 CIS positive, 1/9 pTaG1 positive, 9/9 pTaG3 positive, 10/10 pT1G3 positive and 10/10 pT2G3 positive. Also the Ki-67 is more often expressed in cells with high grade tumor. CONCLUSIONS These results suggest that (i). not only COX2 is involved in the tumorogenesis of the TCC but also cPLA(2) and PGES, (ii). there is relationship between the AA metabolic PGE(2) pathway expression and the aggressiveness of the TCC of the urinary bladder.

Surgical injuries occurring during kidney procurement performed by a renal transplantation team

ENAL surgery injuries, which sometimes occur during organ procurement, may contribute to morbidity and renal function impairment as well as increased hospital stay and cost. 1 In France, renal procurements are customarily performed by urologists directly involved in renal transplantation, who also have to deal with transplant complications. Prevention is the best way to manage renal surgery injuries, but this requires identifying the manner in which they may occur. The purpose of the present study was to clarify the causes of renal injuries during organ harvests over the past 15 years at our institution. PATIENTS AND METHODS Between 1985 and 2000 we performed 627 renal procurements (191 female and 436 male donors) including 558 from heart-beating and 69 from non– heart-beating donors. We noted the surgical injuries to the kidneys and the causes cited by physicians for not using organs. Statistical analysis was performed according to initial injury assignments based on our database. The chi-square test was used as appropriate; differences were considered statistically significantly if P .05. RESULTS A total of 1239 kidneys were harvested. Fifteen kidneys were not harvested. There were 106 kidneys not transplanted. The presence of surgical lesions was the reason for transplant refusal in four cases (1 renal decapsulation, 1 arterial injury, and 2 venous injuries, which could not be repaired properly). Twenty kidneys were refused for transplantation because they were macroscopically abnormal, namely a renal tumor or renal rupture, or because they displayed microscopic abnormalities, namely nephroangiosclerosis, glomerulosclerosis, or arteriolar injuries. Macroscopic surgical arterial injuries were observed in 2.3% (29 of 1254) of cases (26 polar artery transections and 3 hilar artery transsections). Venous lesions were observed in 0.5% (7 of 1254) of cases. Surgical injuries were more frequently observed during single-organ procurements than during multiorgan procurements: 8.2% vs 3.7%, respectively (P .05). Similarly, injuries were more frequent during non– heart-beating donor procurement: 9.3% vs 4.6% (P .01), or when the surgeon had less training (30 organ vs 30 procurements): 12% vs 3%, respectively (P .01).

Benign cortisol-secreting adrenocortical adenomas produce small amounts of androgens

Background  Serum androgen levels are below normal in patients with benign cortisol‐secreting adrenocortical adenomas, owing to ACTH suppression. Associated androgen secretion is usually considered as indicative of malignancy. The objective of the study was to analyse the androgen‐producing ability of cortisol‐secreting adrenocortical adenomas.

Successful treatment of encrusted pyelitis in a renal transplant with local acidification and surgical ileocaliceal anastomosis.

Encrusted pyelitis was initially described in 1993. The incidence has increased with the increasing number of patients with immunodeficiency, particularly those with a renal transplant. This condition is secondary to urinary tract infection due to ureolytic microorganisms. More than 45 microorganisms have been implicated as etiological factors of encrusted cystitis and pyelitis. The treatment of encrusted cystitis or pyelitis includes specific antibiotics, urinary acidification and endoscopic excision of the calcified lesions. When treatment is not rapidly instituted, excision of the transplant is necessary. Nevertheless, in some cases the renal transplant may be surgically and medically treated. Such therapy may be beneficial to the renal transplant, which may be functional after infection. We report a case of renal transplant salvage after the development of encrusted pyelitis.

Renoprotective potency of amifostine in rat renal ischaemia–reperfusion

PURPOSE Kidneys from haemodynamically unstable donors may suffer from renal ischaemia-reperfusion (RIR) injury. RIR is associated with reactive oxygen species production that induces inflammation and activates the arachidonic acid (AA) pathway which converts AA into prostaglandin E(2). Amifostine was investigated for its renoprotective potential in RIR. MATERIALS AND METHODS The effect of amifostine (25 mg/kg  =  910 mg/m(2)) on the COX pathway, enzymatic antioxidant activity, the lipid peroxidation marker MDA, serum creatinine and apoptosis was determined in rats. Kidneys were subjected to 45 min of ischaemia and 1 or 24 h of reperfusion. Control groups (sham: coeliotomy, no ischaemia; r1: 45 min ischaemia/1 h reperfusion; r2: 45 min ischaemia/24 h reperfusion) were administered physiological saline intraperitoneally, and treated groups (E1: 45 min ischaemia/1 h reperfusion; E2: 45 min ischaemia/24 h reperfusion) received amifostine 30 min before reperfusion. RESULTS Serum creatinine increased in non-treated control rats: r1 vs sham (1.6-fold; P <0.007), r2 vs sham (2-fold; P <0.007). Amifostine decreased serum creatinine levels in treated rats: E1 vs r1 (8%; P <0.0025), E2 vs r2 (44%; P <0.0025). Amifostine reduced acute tubular necrosis (25%) 24 h after reperfusion: E1 vs r1 (P <0.004), E2 vs r2 (P <0.03) and reduced COX-2 and microsomal prostaglandin E synthase expression: E1 vs r1 (P <0.03), E2 vs r2 (P <0.02). Amifostine decreased MDA (P <0.04) and reduced caspase-3 expression but did not alter enzymatic antioxidant activity after RIR. CONCLUSIONS Amifostine decreased the degree and severity of tubular damage after reperfusion, probably by scavenging oxygen free radicals and attenuating the cytotoxic effects of inflammatory infiltrates and apoptosis.