Thomas Bessede

Division of Autonomic Nerves Within the Neurovascular Bundles Distally into Corpora Cavernosa and Corpus Spongiosum Components: Immunohistochemical Confirmation with Three-Dimensional Reconstruction

BACKGROUND Detailed knowledge of the distribution and distal course of periprostatic nerves is essential to improve functional outcomes (erection and continence) after radical prostatectomy (RP). OBJECTIVE To describe the location of nerve fibres within neurovascular bundles (NVBs) and around the prostate by three-dimensional (3D) computer-assisted anatomic dissection (CAAD) in human foetuses and adult cadavers. DESIGN, SETTING, AND PARTICIPANTS Serial transverse sections of the pelvic portion were performed in seven human male foetuses and four male adult cadavers. Sections were treated by histologic coloration and neuronal immunolabelling of S100 protein. 3D pelvic reconstruction was achieved with digitised serial sections and WinSurf software. MEASUREMENTS We evaluated the distribution of nerve fibres within the NVB qualitatively. The distribution of periprostatic nerves was also evaluated quantitatively in the adult specimens. RESULTS AND LIMITATIONS Periprostatic nerve fibres were dispersed around the prostate on all sides with a significant percentage of these fibres present in the anterior and anterolateral sectors. At the prostate apex and the urethral levels, the NVBs have two divisions: cavernous nerves (CNs) and corpus spongiosum nerves (CSNs). The CNs were a continuation of the anterior and anterolateral fibres around the apex of the prostate, travelling towards the corpora cavernosa. The CSNs were a continuation of the posterolateral NVBs, and they eventually reached the corpus spongiosum. The limitations of this study were the small number of specimens available and the lack of functional information. CONCLUSIONS The anterolateral position of CNs at the apex of the prostate and the autonomic innervation towards the corpus spongiosum via CSNs indicate possible ways to minimise the effect of prostate surgery on sexual function. The ideal dissection plane should probably include the preservation of the anterolateral tissues and fascias to avoid CN lesions. Anatomic knowledge gained from CAAD pertains directly to proper surgical technique and subsequent recovery of erectile function after RP.

Coexistence of adrenergic and cholinergic nerves in the inferior hypogastric plexus: anatomical and immunohistochemical study with 3D reconstruction in human male fetus

Classic anatomical methods have failed to determine the precise location, origin and nature of nerve fibres in the inferior hypogastric plexus (IHP). The purpose of this study was to identify the location and nature (adrenergic and/or cholinergic) of IHP nerve fibres and to provide a three‐dimensional (3D) representation of pelvic nerves and their relationship to other anatomical structures. Serial transverse sections of the pelvic portion of two human male fetuses (16 and 17 weeks’ gestation) were studied histologically and immunohistochemically, digitized and reconstructed three‐dimensionally. 3D reconstruction allowed a ‘computer‐assisted dissection’, identifying the precise location and distribution of the pelvic nerve elements. Proximal (supra‐levator) and distal (infra‐levator) communications between the pudendal nerve and IHP were observed. By determining the nature of the nerve fibres using immunostaining, we were able to demonstrate that the hypogastric nerves and pelvic splanchnic nerves, which are classically considered purely sympathetic and parasympathetic, respectively, contain both adrenergic and cholinergic nerve fibres. The pelvic autonomic nervous system is more complex than previously thought, as adrenergic and cholinergic fibres were found to co‐exist in both ‘sympathetic’ and ‘parasympathetic’ nerves. This study is the first step to a 3D cartography of neurotransmitter distribution which could help in the selection of molecules to be used in the treatment of incontinence, erectile dysfunction and ejaculatory disorders.

Tridimensional Computer-Assisted Anatomic Dissection of Posterolateral Prostatic Neurovascular Bundles

BACKGROUND Detailed knowledge of nerve distribution in the neurovascular bundle (NVB) is essential to preserve sexual function after prostatic surgery. OBJECTIVE To identify the location as well as the type (adrenergic, cholinergic, and sensory) of nerve fibres within the NVB and to provide a three-dimensional (3D) representation of their structural relationship in the human male foetus. DESIGN, SETTING, AND PARTICIPANTS Serial transverse sections were performed every 150-200 microm in the pelvic portion of six human male foetuses (15-20 wk of gestation). Sections were treated with histologic and immunohistochemical methods (hematin-eosin-safran, Luxol Fast Blue, immunolabelling of protein S100, vesicular acetylcholine transporter, tyrosine hydroxylase, calcitonin gene-related peptide, and substance P). The 3D pelvic reconstruction was obtained from digitised serial sections using WinSurf software. MEASUREMENTS NVB nerve location and type were evaluated qualitatively. RESULTS AND LIMITATIONS The 3D reconstruction allowed precise identification of pelvic organ innervation. Nerve fibres derived from the inferior hypogastric plexus followed two courses: posterior and lateral, providing cholinergic, adrenergic, and sensory innervation to seminal vesicles, vas deferens, prostate, and urethral sphincter. Cavernous nerve fibres did not strictly follow the NVB course; they were distributed at several levels, in a fanlike formation. The main limitations of this study were the limited number of specimens available due to legal restriction and the time-consuming nature of the manually performed stages in the method. CONCLUSIONS The distribution of nerve fibres within the posterolateral prostatic NVB and the existence of mixed innervation in the posterior and lateral fibre courses at the level of the prostate and seminal vesicles give us an insight into how to minimise effects on sexual function during prostatic surgery. The 3D computer-assisted anatomic dissection represents an original method of applying anatomic knowledge to surgical technique to improve nerve preservation and decrease postoperative sexual complications.

Internal anal sphincter parasympathetic-nitrergic and sympathetic-adrenergic innervation: a 3-dimensional morphological and functional analysis.

BACKGROUND: Little detailed information is available concerning morphological and functional autonomic nerve supply to the internal anal sphincter. However, denervation of the sphincter potentially affects anal function after rectal surgery for cancer. OBJECTIVE: The aim of this study was to identify the location and type (nitrergic, adrenergic, and cholinergic) of nerve fibers in the internal anal sphincter and to provide a 3-dimensional representation of their structural relationship in the human fetus. MATERIALS AND METHODS: serial transverse sections were obtained from 14 human fetuses (7 male, 7 female, 15–31 weeks of gestation) and were studied histologically and immunohistochemically; digitized serial sections were used to construct a 3-dimensional representation of the pelvis. MAIN OUTCOMES MEASURES: The location and type of internal anal sphincter nerves were assessed qualitatively. RESULTS: Posteroinferior fibers originating from the inferior hypogastric plexus posteroinferior angle projected to the posterolateral and posterior rectal wall and internal anal sphincter, forming the inferior rectal plexus. The inferior rectal plexus contained vesicular acetylcholine transporter-positive (cholinergic), tyrosine hydroxylase-positive (adrenergic/sympathetic), and neural nitric oxide synthase-positive (nitrergic) fibers. The intrasphincteric vesicular acetylcholine transporter-positive fibers included both neural nitric oxide synthase-negative fibers and neural nitric oxide synthase-positive fibers (nitrergic-parasympathetic). LIMITATIONS: The study focused on topographic and functional anatomy, so that quantitative data were not obtained. A small number of fetal specimens were available. CONCLUSIONS: We report the precise location and distribution of the autonomic neural supply to the internal anal sphincter. This description contributes to the understanding of neurogenic postoperative sphincteric dysfunction. Three-dimensional cartography of pelvic-perineal neurotransmitters provides an anatomical and physiological basis for the selection and development of pharmacological agents to be used in the treatment of primary or postoperative continence and evacuation disorders.

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.

Surgical prevention and management of vascular complications of kidney transplantation

The main surgical changes in kidney procurement, preparation, and transplantation procedures occurred 20 years ago and were undertaken despite the inability to design randomized studies. The objective was to assess the evolution of vascular complications after kidney transplantation in a setting of surgical preventive measures in a historical series. A monocentric series of 3129 consecutive kidney transplantations performed over 3 decades was reviewed. The occurrence of arterial or venous thromboses, stenoses, and aneurysms was analyzed in relation with kidney procurement, preparation, and transplantation techniques. Vascular complications occurred in 13.5% of the recipients with a mean 3‐year decrease in kidney graft function. The transplantation of a right kidney without renal vein extension, multiple renal arteries, ex vivo vascular repairs, and end‐to‐end arterial anastomoses were the unfavorable surgical vascular factors. It was possible to manage Transplant Renal Artery Stenosis (TRAS) nonsurgically in 80% of the cases. The prevention of vascular complications begins from the time of organ procurement by skilled surgeons. The aims of organ preparation are to evaluate the vascular risk, select the organs, and to simplify the anatomical constraints of vascular implantations. The three surgical steps of kidney transplantation are determinant in postoperative vascular complications and the duration of graft function.

Evolution in the concept of erection anatomy

PurposeTo review and to summarize the literature on anatomy and physiology of erection in the past three decades, especially the work done in our institution.MethodsA search of the PubMed database was performed using keywords erection, anatomy and erectile dysfunction (ED). Relevant articles were reviewed, analyzed and summarized.ResultsPenile vascularisation and innervation vary substantially. Internal pudendal artery is the major source of penile blood supply, but a supralevator accessory pudendal artery that may originate from inferior vesical or obturator or external iliac arteries is not uncommon. Section of this artery during radical prostatectomy (RP) may adversely affect postoperative potency. Anastomoses between the supra and the infralevator arterial pathways are frequent. The cavernous nerves (CNs) contain parasympathetic and sympathetic nerve fibers and these nerves lie within leaves of the lateral endopelvic fascia. Anastomoses between the CNs and the dorsal nerve of the penis are common. Nitric oxide released from noradrenergic, noncholinergic neurotransmission of the CN and from the endothelium is the principal neurotransmitter-mediating penile erection. Interactions between pro-erectile and anti-erectile neurotransmitters are not completely defined. Finally, medial preoptic area and paraventricular nucleus are the key structures in the central control of sexual function and penile erection.ConclusionsThe surgical and functional anatomy of erection is complex. Precise knowledge of penile vascularisation and innervation facilitates treatment of ED especially after RP.

Computer-assisted anatomic dissection (CAAD): evolution, methodology and application in intra-pelvic innervation study

ObjectiveClassic anatomical methods have limitations in micro determination of nerve fibre location. Furthermore, the precise detection of the nerve fibres nature is not possible by means of dissection. The combination of immunohistochemistry and three-dimensional reconstruction could be used to resolve these limitations of morphological sciences. Our aim is to describe the evolution of computer-assisted anatomic dissection (CAAD), which is an original method applied to study the distribution of intra-pelvic nerves in anatomic research.Materials and methodsSerial transverse sectioning of the pelvic region in rabbit, human fetus, infant and adult cadaver was performed. Sections were immuno-histochemically stained and digitized with a high optical resolution scanner. Photoshop 7 software was used in regrouping of the adult cadaver sections then a tri-dimensional reconstruction was achieved using WinSurf software.ResultsThe 3D reconstruction of the immuno-histochemically stained histologic sections of the pelvis allowed for precise structural identification of the prostate and its innervations (in fetus, infant and adult). In addition, we reconstructed the entire intra-pelvic organs with accurate demonstration of the location of both adrenergic and cholinergic pathways. Moreover, we performed a virtual dissection of each of the pelvic structures with description of the exact location of the inferior hypogastric plexus, as well as the nature and the distribution of its fibres.ConclusionThe CAAD is an original method in anatomic research, which illustrates the fact that descriptive anatomy is still a dynamic science. This method allows for a 3D presentation of the intra-organic innervation, the nature of the nerve fibres, and the distribution of receptors and their neurotransmitters. This technique improves the understanding of the complex anatomic regions such as the pelvis from both surgical and educational point of view.

Nephron-sparing surgery is superior to radical nephrectomy in preserving renal function benefit even when expanding indications beyond the traditional 4-cm cutoff

OBJECTIVES To analyze to what extent partial nephrectomy (PN) is superior to radical nephrectomy (RN) in preserving renal function outcome in relation to tumor size indication. METHODS AND MATERIALS Clinical data from 973 patients operated at 9 academic institutions were retrospectively analyzed. Glomerular filtration rate (GFR) before and after surgery was calculated with the abbreviated Modification of the Diet in Renal Disease equation. For a fair comparison between the 2 techniques, all imperative indications for PN were excluded. A shift to a less favorable GFR group following surgery was considered clinically significant. RESULTS Median age at diagnosis was 60 years (19-91). Tumor size was smaller than 4 cm in 665 (68.3%) cases and larger than 4 cm in 308 (31.7%) cases. PN and RN were performed in 663 (68.1%) and 310 (31.9%) patients, respectively. In univariate analysis, patients undergoing PN had a smaller risk for developing significant GFR change following surgery than those undergoing RN did. This was true for tumors≤4 cm (P = 0.0001) and for tumors>4 cm (P = 0.0001). In multivariate analysis, the following criteria were independent predictive factors for developing significant postoperative GFR loss: the use of RN (P = 0.0001), preoperative GFR<60 ml/min (P = 0.0001), tumor size≥4 cm (P = 0.0001), and older age at diagnosis (P = 0.0001). CONCLUSIONS The renal function benefit carried out by elective PN over RN persists even when expanding nephron-sparing surgery indications beyond the traditional 4-cm cutoff.

Tissue Engineering for Penile Surgery: Comparative Study of Noncellular and Cell‐Seeded Synthetic Grafts for Tunica Albuginea Replacement

INTRODUCTION Surgical treatment outcomes in Peyronies disease remain controversial because of high rates of recurrence. AIM The aim of this study was to engineer in vitro a new type of tunica albuginea (TA) autologous graft obtained by culture of autologous fibroblast on a polyglycolic acid (PGA) scaffold. This engineering graft was compared with PGA with morphological and functional outcomes for TA replacement, 4 months after graft upon corpus cavernosum in a rat model. METHODS Thirty-nine Sprague Dawley adult male rats were divided into four groups: (i) control group (C) with resection and resuture of a 5 mm long and 2 mm large piece of original TA; (ii) PGA scaffold group (P) with the same resection of TA and suture of PGA scaffold; (iii) autologous fibroblast-seeded on PGA scaffold graft after resection of the same piece of TA (F + P); and (iv) sham group for functional and histological comparison. MAIN OUTCOME MEASURE The main outcome measure was assessment of graft size variation at 4 months and comparison between the three test groups. The secondary objective is assessment of erectile function by measuring erectile response to cavernous nerve electrical stimulation in each group. RESULTS At 4 months, there was a significant difference in graft area retraction between the groups (P = 0.0081) with higher retraction in P group vs. in C or F + P groups. Erectile response to cavernous nerve stimulation significantly differed between the groups and was sham equivalent to C equivalent to F + P superior to P group. CONCLUSIONS This study provides experimental evidence for the feasibility and the functionality of fibroblast-seeded scaffold compared with acellular graft for TA replacement.