[Research progress on urogenital function preservation in extralevator abdominoperineal resection].

Extralevator abdominoperineal excision (ELAPE) has been suggested to potentially improve oncological outcomes in advanced low rectal cancer patients. However, the urogenital function impairment as one of the main complications deteriorates the quality of life in these patients. The key point to prevent urogenital function impairment is to avoid autonomic nerve injury, including the superior and inferior hypogastric nerve plexus and neurovascular bundle. Three areas should be especially focused during surgery, including the posterolateral aspect of the prostate during the separation of the rectum from prostate, the lateral wall of ischioanal fossa and the area in front of anal canal. Previous presumption supposed that extended resection, though promoting oncologic outcomes, might lead to enlarged injury to surrounding vessels and nerves that deteriorated patients' urogenital function. But recent studies show that postoperative urogenital function outcomes of rectal cancer patients who underwent ELAPE are not inferior to conventional APE after the induction of minimal invasive approaches including laparoscopic and robotic surgery. Their quality of life can be comparable with patients who underwent conventional APE, and are even better in some particular area. Moreover, as further improvement of ELAPE procedure has been made, the concept of individualized ELAPE addressed the importance of personalized surgical procedure based on tumor stage and location, dedicating to avoid injury to vessels and nerves through preserving more surrounding tissues. Urogenital function outcomes, as part of postoperative outcomes, get more and more attention in recent years. We review current studies on urogenital function after ELAPE from anatomy to clinical research, in order to raise surgeons' attention of nerve preservation technique and to improve their understanding of ELAPE procedure.

Migration pathways of sacral neural crest during development of lower urogenital tract innervation.

The migration and fate of cranial and vagal neural crest-derived progenitor cells (NCPCs) have been extensively studied; however, much less is known about sacral NCPCs particularly in regard to their distribution in the urogenital system. To construct a spatiotemporal map of NCPC migration pathways into the developing lower urinary tract, we utilized the Sox10-H2BVenus transgene to visualize NCPCs expressing Sox10. Our aim was to define the relationship of Sox10-expressing NCPCs relative to bladder innervation, smooth muscle differentiation, and vascularization through fetal development into adulthood. Sacral NCPC migration is a highly regimented, specifically timed process, with several potential regulatory mileposts. Neuronal differentiation occurs concomitantly with sacral NCPC migration, and neuronal cell bodies are present even before the pelvic ganglia coalesce. Sacral NCPCs reside within the pelvic ganglia anlagen through 13.5 days post coitum (dpc), after which they begin streaming into the bladder body in progressive waves. Smooth muscle differentiation and vascularization of the bladder initiate prior to innervation and appear to be independent processes. In adult bladder, the majority of Sox10+ cells express the glial marker S100ß, consistent with Sox10 being a glial marker in other tissues. However, rare Sox10+ NCPCs are seen in close proximity to blood vessels and not all are S100ß+, suggesting either glial heterogeneity or a potential nonglial role for Sox10+ cells along vasculature. Taken together, the developmental atlas of Sox10+ NCPC migration and distribution profile of these cells in adult bladder provided here will serve as a roadmap for future investigation in mouse models of lower urinary tract dysfunction.

[Anatomic application of the genitofemoral nerve in uroandrological surgery].

The genitofemoral nerve (GFN) has its unique anatomic characteristics of location, run and function in the male urinary system and its relationship with the ureter, deferens and inguinal region is apt to be ignored in clinical anatomic application. Clinical studies show that GFN is closely correlated with postoperative ureteral complications and pain in the inguinal region after spermatic cord or hernia repair. GFN transplantation can be used in the management of erectile dysfunction caused by cavernous nerve injury. Therefore, GFN played an important role in the clinical application of uroandrology. This review summarizes the advances in the studies of GFN in relation to different diseases in uroandrology.

Effect of intra-operative autonomic nerve stimulation on pelvic nerve preservation during radical laparoscopic proctectomy.

AIM: This study assessed the effect of intra-operative electrical nerve stimulation (INS) on pelvic autonomic nerve preservation (PANP) during laparoscopic resection for rectal cancer. METHOD: A total of 189 consecutive cases of radical laparoscopic proctectomy were included. PANP was assessed visually or with INS. Urinary function was evaluated by residual urine volume (RUV), International Prostatic Symptom Score (IPSS) and recatheterization rate. Erectile function was evaluated using the International Index of Erectile Function (IIEF-5) scale. RESULTS: INS successfully confirmed PANP in 65 (91.5%) patients, while direct vision confirmed PANP in only 72 (61.0%) patients. Compared with the successfully confirmed patients, failed patients in the INS group exhibited higher postoperative RUV (100.0 ± 34.6 vs 25.2 ± 13.6 ml, P = 0.003), higher IPSS (7 days, 20.0 ± 8.6 vs 6.5 ± 2.4, P = 0.012; 1 month, 13.5 ± 6.0 vs 5.3 ± 1.9, P = 0.020; 6 months, 11.7 ± 5.1 vs 4.5 ± 1.7, P = 0.018), a greater number of incidences of a micturition disorder (66.7% vs 1.5%, P = 0.000), higher recatheterization rates (33.3% vs 1.5%, P = 0.017) and a lower IIEF score at 3 months (8.25 ± 0.96 vs 10.93 ± 1.99, P = 0.012) and 6 months (12.50 ± 1.29 vs 15.63 ± 1.65, P = 0.001) postoperatively. Compared with the vision group, the INS group had less deterioration in postoperative RUV (31.5 ± 26.4 vs 54.0 ± 46.7 ml, P = 0.000), lower IPSS (7 days, 7.7 ± 5.0 vs 11.0 ± 6.6, P = 0.000; 1 month, 6.0 ± 3.3 vs 7.6 ± 5.4, P = 0.012) and higher IIEF score (3 months, 10.69 ± 2.07 vs 9.42 ± 2.05, P = 0.001; 6 months, 15.36 ± 1.85 vs 13.64 ± 2.00, P = 0.000) as well as a lower incidence of urination disorders (7.0% vs 17.8%, P = 0.038). CONCLUSION: INS is effective for the accurate evaluation of PANP during radical laparoscopic proctectomy. Combined with INS, laparoscopic proctectomy is more effective in urogenital function protection.

Gross anatomical study of the nerve supply of genitourinary structures in female mongrel hound dogs.

Anatomical variations in lumbosacral plexus or nerves to genitourinary structures in dogs are under described, despite their importance during surgery and potential contributions to neuromuscular syndromes. Gross dissection of 16 female mongrel hound dogs showed frequent variations in lumbosacral plexus classification, sympathetic ganglia, ventral rami input to nerves innervating genitourinary structures and pudendal nerve (PdN) branching. Lumbosacral plexus classification types were mixed, rather than pure, in 13 (82%) of dogs. The genitofemoral nerve (GFN) originated from ventral ramus of L4 in 67% of nerves, differing from the expected L3. Considerable variability was seen in ventral rami origins of pelvic (PN) and Pd nerves, with new findings of L7 contributions to PN, joining S1 and S2 input (23% of sides in 11 dogs) or S1-S3 input (5%), and to PdN, joining S1-S2, unilaterally, in one dog. L7 input was confirmed using retrograde dye tracing methods. The PN also received CG1 contributions, bilaterally, in one dog. The PdN branched unusually in two dogs. Lumbosacral sympathetic ganglia had variant intra-, inter- and multisegmental connectivity in 6 (38%). Thus, the anatomy of mongrel dogs had higher variability than previously described for purebred dogs. Knowledge of this variant innervation during surgery could aid in the preservation of nerves and reduce risk of urinary and sexual dysfunctions.

Female-biased dimorphism underlies a female-specific role for post-embryonic Ilp7 neurons in Drosophila fertility.

In Drosophila melanogaster, much of our understanding of sexually dimorphic neuronal development and function comes from the study of male behavior, leaving female behavior less well understood. Here, we identify a post-embryonic population of Insulin-like peptide 7 (Ilp7)-expressing neurons in the posterior ventral nerve cord that innervate the reproductive tracts and exhibit a female bias in their function. They form two distinct dorsal and ventral subsets in females, but only a single dorsal subset in males, signifying a rare example of a female-specific neuronal subset. Female post-embryonic Ilp7 neurons are glutamatergic motoneurons innervating the oviduct and are required for female fertility. In males, they are serotonergic/glutamatergic neuromodulatory neurons innervating the seminal vesicle but are not required for male fertility. In both sexes, these neurons express the sex-differentially spliced fruitless-P1 transcript but not doublesex. The male fruitless-P1 isoform (fruM) was necessary and sufficient for serotonin expression in the shared dorsal Ilp7 subset, but although it was necessary for eliminating female-specific Ilp7 neurons in males, it was not sufficient for their elimination in females. By contrast, sex-specific RNA-splicing by female-specific transformer is necessary for female-type Ilp7 neurons in females and is sufficient for their induction in males. Thus, the emergence of female-biased post-embryonic Ilp7 neurons is mediated in a subset-specific manner by a tra- and fru-dependent mechanism in the shared dorsal subset, and a tra-dependent, fru-independent mechanism in the female-specific subset. These studies provide an important counterpoint to studies of the development and function of male-biased neuronal dimorphism in Drosophila.

Autonomic control of the urogenital tract.

The urogenital tract houses many of the organs that play a major role in homeostasis, in particular those that control water and salt balance, and reproductive function. This review focuses on the anatomical and functional innervation of the kidneys, urinary ducts and bladders of the urinary system, and the gonads, gonadal ducts, and intromittent organs of the reproductive tract. The literature, especially in recent years, is overwhelmingly skewed toward the situation in mammals. Nevertheless, where specific neurochemical markers have been investigated, common patterns of innervation can be found in representatives from most vertebrate classes. Not surprisingly the vasculature, epithelia and smooth muscle of all urogenital organs receives adrenergic innervation. These nerves may contain non-adrenergic non-cholinergic (NANC) neurotransmitters such as ATP and NPY. Cholinergic nerves increase motility in most urogenital organs with the exception of the kidney. The major NANC nerves found to influence urogenital organs include those containing VIP/PACAP, galanin and neuronal nitric oxide synthase. These can be found associated with both smooth muscle and epithelia. The role these nerves play, and the circumstances where they are activated are for the most part unknown.

[Prostatitis syndromes and sporting activities]. / Sindromi prostatiche e sport.

INTRODUCTION: Prostatitis-like syndromes are high prevalent health problems and frequently considered by patients and physicians as strictly correlated to sports causing perineal compression. These syndromes and their relationships with sporting activities have been discussed in this report. METHODS: We reviewed peer-reviewed scientific articles published by May 2009 and searched according to the following term selection: prostatitis, pudendal nerve, sport, cycling. RESULTS: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a major healthcare burden heavily affecting patients' Quality of Life. No clear evidence of any direct etiologic relationship has been found in literature between prostatitis, either bacterial or non-bacterial, and sports activities. On the other hand, some types of sport causing perineal compression, such as cycling, can exacerbate symptoms of acute and chronic prostatitis; a temporary sport discontinuation is justified in these patients. CP/CPPS may be often caused by pudendal nerve entrapment (PNE). Prostatitis-like urogenital neuropathic pain together with voiding and sexual dysfunctions are the hallmark of PNE. A common feature is that flexion activities of the hip, such as climbing, squatting, cycling provoke or worsen urogenital pain or pelvic pain. Many of the patients with PNE are cyclists, played American football, lifted weights, or wrestled as teenagers and young adults. PNE represents the most common bicycling associated urogenital problems. CONCLUSIONS: Overall, studies show that no causal relationship has been demonstrated between prostatitis and sporting activities. Conversely, urologists should be aware that sports involving vigorous hip flexion activities or prolonged perineal compression are a potential and not an infrequent cause of uroandrological symptoms caused by pudendal nerve entrapment.

Nerve-preserving sacrocolpopexy: anatomical study and surgical approach.

OBJECTIVE: The aim of our study is to describe the course of the autonomic nerves in the presacral space and to find the best nerve-preserving approach for sacrocolpopexy. STUDY DESIGN: The autonomic nerves of the presacral space were dissected on six specially preserved female cadavers. RESULTS: The superior hypogastric plexus is located in front of the abdominal aorta and its bifurcation and deviates to the left of the midsagittal plane. At the level of the promontory, or just below, the superior hypogastric plexus branches into two hypogastric nerves that run in front of the sacrum. In the presacral space the parasympathetic pelvic splanchnic nerves from the ventral rami of the sacral spinal nerves (S2-S3) join the hypogastric nerves, forming the inferior hypogastric plexus on both sides. From the inferior hypogastric plexus, nerve fibres spread out bilaterally to the pelvic organs. In two of the six cadavers sacral splanchnic nerves could be identified leading from the sacral sympathetic ganglion S1 of the sympathetic trunk to the inferior hypogastric plexus. CONCLUSION: Longitudinal incision of the peritoneum along the right common iliac artery and above the promontory allows for a safe approach for sacrocolpopexy. After exposing the vascular structure (e.g. medial sacral vessels) above the promontory, the anterior longitudinal ligament becomes visible and can be prepared for the fixation of the mesh for vaginal suspension. By protecting the superior hypogastric plexus and the part of the presacral area below the promontory we can preserve the hypogastric nerves, the sacral and pelvic splanchnic nerves and thus the autonomic innervation of the pelvic organs. Awareness of the course of the autonomic nerves in the presacral space will significantly improve the functional outcome of sacrocolpopexy and reduce bowel, urinary and sexual dysfunctions.

Afferent neurourology: A novel paradigm.

The term "afferent neurourology" is introduced to describe the study of sensory processing related to the genitourinary tract. Urologic disorders that are characterized by abnormal sensory processing are reviewed, and unique challenges to our understanding of these disorders are described. A paradigm which separates afferent urologic disorders from efferent disorders and structural abnormalities is presented.

Experimental models of visceral pain.

Visceral pain models are used to study afferent nerve traffic during noxious stimulation at the level of the visceral organ. This chapter provides details on several in vitro and in vivo models of organs in the gastrointestinal and genitourinary tract that use electrophysiological recordings of afferent nerve fibres in order to directly characterize stimulus-response relationships. These models can also be used to investigate stimulus-response patterns during physiological (nonpainful) stimulation of the visceral organs or during exposure to pathological stimuli, such as inflammatory mediators during inflammation of the visceral organ.

Diagnosis and treatment of pudendal nerve entrapment syndrome subtypes: imaging, injections, and minimal access surgery.

OBJECT: To improve diagnostic accuracy and achieve high levels of treatment success in patients with pudendal nerve entrapment (PNE) syndromes, the author of this study applied advanced technology diagnostics in distinguishing the various syndrome types according to the different entrapment locations and evaluated new minimal access surgical techniques to treat each subtype. METHODS: Two hundred cases were prospectively evaluated using a standardized set of patient-completed functional and symptom assessments, a collection of new physical examination maneuvers, MR neurography, open MR image-guided injections, intraoperative neurophysiology, minimal access surgery, and formal outcome assessment with the Oswestry Disability Index, pain diagrams, and analog pain scales. RESULTS: Four primary types of PNE syndromes were identified based on the different locations of entrapment: Type I, entrapment at the exit of the greater sciatic notch in concert with piriformis muscle spasm; Type II, entrapment at the level of the ischial spine, sacrotuberous ligament, and lesser sciatic notch entrance; Type III, entrapment in association with obturator internus muscle spasm at the entrance of the Alcock canal; and Type IV, distal entrapment of terminal branches. The application of new, targeted minimal access surgical techniques led to sustained good to excellent outcomes (50-100% improvement in the pain score or functional score) in 87% of patients. Most of these patients obtained most of their improvement within 4 weeks of surgery, although some continued to experience progressive improvements up to 12 months after surgery. CONCLUSIONS: The application of advanced diagnostics to categorize PNE syndrome origins into 4 major subtypes and the subsequent treatment of each subtype with a tailored strategy greatly improved therapeutic outcomes as compared with those reported when only a single treatment paradigm was applied to all patients.

The neurourological examination in women.

The review provides a description of a physical examination protocol to rule out significant neurologic disease as a cause for a woman's sexual complaints, or to confirm a neurologic cause for the sexual dysfunction, particularly in women with known neurologic disease.

Nerve-sparing open radical retropubic prostatectomy.

INTRODUCTION: In recent years, the surgical technique for open radical prostatectomy has evolved and increasing attention is paid to preserving anatomic structures and the impact on outcome and quality of life. METHODS: Technical aspects of nerve-sparing open radical retropubic prostatectomy (RRP) are described. Patient selection criteria and functional results are discussed, focusing on postoperative urinary continence. RESULTS: The video demonstrates the nerve-sparing open RRP and important steps are elucidated with schematic drawings. The value of nerve sparing, not only for preserving erectile function, but also for preserving urinary continence is discussed and results from our institution are presented. In our series, urinary incontinence was present in 1 of 71 patients (1%) with attempted bilateral nerve-sparing, 11 of 322 (3%) with attempted unilateral nerve-sparing, or 19 of 139 (14%) without attempted nerve-sparing surgery. In multiple logistic regression analysis, the only statistically significant factor influencing urinary continence after open RRP was attempted nerve sparing (odds ratio, 4.77; 95% confidence interval, 2.18-10.44; p=0.0001). CONCLUSIONS: Nerve-sparing surgery has a significant impact on erectile function and urinary continence and should be performed in all patients provided radical tumour resection is not compromised. For successful nerve preservation we advocate a lateral approach to the prostate to improve visualisation and simplify separation of the neurovascular bundles from the dorsolateral prostatic capsule. Bunching, ligating, and incising Santorini's plexus over the prostate and not over the sphincter ensures a bloodless surgical field. Mucosa-to-mucosa adaptation of the reconstructed bladder neck and the urethra is another important factor to be observed.

Plasticity of pelvic autonomic ganglia and urogenital innervation.

Pelvic ganglia contain a mixture of sympathetic and parasympathetic neurons and provide most of the motor innervation of the urogenital organs. They show a remarkable sensitivity to androgens and estrogens, which impacts on their development into sexually dimorphic structures and provide an array of mechanisms by which plasticity of these neurons can occur during puberty and adulthood. The structure of pelvic ganglia varies widely among species, ranging from rodents, which have a pair of large ganglia, to humans, in whom pelvic ganglion neurons are distributed in a large, complex plexus. This plexus is frequently injured during pelvic surgical procedures, yet strategies for its repair have yet to be developed. Advances in this area will come from a better understanding of the effects of injury on the cellular signaling process in pelvic neurons and also the role of neurotrophic factors during development, maintenance, and repair of these axons.

Expression profiles of high voltage-activated calcium channels in sympathetic and parasympathetic pelvic ganglion neurons innervating the urogenital system.

Among the autonomic ganglia, major pelvic ganglia (MPG) innervating the urogenital system are unique because both sympathetic and parasympathetic neurons are colocalized within one ganglion capsule. Sympathetic MPG neurons are discriminated from parasympathetic ones by expression of low voltage-activated Ca2+ channels that primarily arise from T-type alpha1H isoform and contribute to the generation of low-threshold spikes. Until now, however, expression profiles of high voltage-activated (HVA) Ca2+ channels in these two populations of MPG neurons remain unknown. Thus, in the present study, we dissected out HVA Ca2+ channels using pharmacological and molecular biological tools. Reverse transcription-polymerase chain reaction analysis showed that MPG neurons contained transcripts encoding all of the known HVA Ca2+ channel isoforms (alpha1B, alpha1C, alpha1D and alpha1E), with the exception of alpha1A. Western blot analysis and pharmacology with omega-agatoxin IVA (1 microM) confirmed that MPG neurons lack the alpha1A Ca2+ channels. Unexpectedly, the expression profile of HVA Ca2+ channel isoforms was identical in the sympathetic and parasympathetic neurons of the MPG. Of the total Ca2+ currents, omega-conotoxin GVIA-sensitive N-type (alpha1B) currents constituted 57 +/- 5% (n = 9) and 60 +/- 3% (n = 6), respectively; nimodipine-sensitive L-type (alpha1C and alpha1D) currents made up 17 +/- 4% and 14 +/- 2%, respectively; and nimodipine-resistant and omega-conotoxin GVIA-resistant R-type currents were 25 +/- 3% and 22 +/- 2%, respectively. The R-type Ca2+ currents were sensitive to NiCl2 (IC50 = 22 +/- 0.1 microM) but not to SNX-482, which was able to potently (IC50 = 76 +/- 0.4 nM) block the recombinant alpha1E/beta2a/alpha2delta Ca2+ currents expressed in human embryonic kidney 293 cells. Taken together, our data suggest that sympathetic and parasympathetic MPG neurons share a similar but unique profile of HVA Ca2+ channel isoforms.

Functional imaging of stress urinary incontinence.

Stress urinary incontinence (SUI) is defined as an involuntary loss of urine during increases in intraabdominal pressure such as coughing or laughing. It is often a consequence of weakness of the pelvic floor. Treatment of SUI consists of pelvic floor muscle training with EMG-biofeedback (PFMT) or contraction-exercises, with voluntary pelvic contractions in order to strengthen the pelvic floor. We investigated neuroplastic changes comparing PFMT with EMG-biofeedback before and after training in ten female patients with SUI using event-related functional Magnetic Resonance Imaging (fMRI). After a 12-week training a more focused activation in the primary motor and somatosensory cortical representation sites of the lower urogenital tract was found. In addition, reductions in brain activation in the insula, right frontal operculum and the anterior cingulate cortex suggest changes in emotional arousal in micturition after treatment. These changes are related to clinical improvement documented by decreased number of incontinence episodes and increased EMG-activity of the pelvic floor muscles after training. The changes in EMG-activity were correlated with heightened BOLD responses in the primary motor and primary sensory cortical representation sites of the lower urogenital tract.

Anatomy of pudendal nerve at urogenital diaphragm--new critical site for nerve entrapment.

OBJECTIVES: To investigate the relations of the pudendal nerve in this complex anatomic region and determine possible entrapment sites that are accessible for surgical decompression. Entrapment neuropathies of the pudendal nerve are an uncommon and, therefore, often overlooked or misdiagnosed clinical entity. The detailed relations of this nerve as it exits the pelvis through the urogenital diaphragm and enters the mobile part of the penis have not yet been studied. METHODS: Detailed anatomic dissections were performed in 10 formalin preserved hemipelves under 3.5x loupe magnification. The pudendal nerve was dissected from the entrance into the Alcock canal to the dorsum of the penis. The branching pattern of the nerve and its topographic relationship were recorded and photographs taken. RESULTS: The anatomic dissections revealed that the pudendal nerve passes through a tight osteofibrotic canal just distal to the urogenital diaphragm at the entrance to the base of the penis. This canal is, in part, formed by the inferior ramus of the pubic bone, the suspensory ligament of the penis, and the ischiocavernous body. In two specimens, a fusiform pseudoneuromatous thickening was found. CONCLUSIONS: The pudendal nerve is susceptible to compression at the passage from the Alcock canal to the dorsum of the penis. Individuals exposed to repetitive mechanical irritation in this region are especially endangered. Diabetic patients with peripheral neuropathy can have additional compression neuropathy with decreased penile sensibility and will benefit from decompression of the pudendal nerve.

The long-term voiding function and sexual function after pelvic nerve-sparing radical surgery for rectal cancer.

BACKGROUND: The aim of the present study is to symptomatically analyze the extent to which pelvic nerve-sparing radical surgery for rectal cancer impacts on long-term voiding and male sexual function. METHODS: A self-administered questionnaire was mailed to 68 patients who underwent pelvic nerve-sparing radical surgery for invasive rectal cancer with 52 responses (28 men and 24 women; 27 complete and 25 incomplete preservation; response rate 76.5%). Each patient was asked to record if there had been any changes in lower urinary tract symptoms after surgery. Sexual function was also investigated in men. RESULTS: Of the 52 patients, 48 (92%) maintained voluntary voiding without catheterization in the long term. Clean intermittent self-catheterization was performed in only four patients with incomplete preservation because of persistent voiding dysfunction. Subjectively, approximately 60% of the patients remained unchanged in lower urinary tract symptoms after surgery. The satisfaction rate regarding the current voiding status was significantly higher in women than in men (83% versus 61%, P = 0.0294), but was not significantly different between those with complete (76%) and incomplete preservation (64%). Despite the acceptable urinary status, 88% of men had some deterioration in the erectile function, regardless of the types of surgical procedures. Overall, 64% of men were unsatisfied with the current sexual function. CONCLUSIONS: Pelvic nerve-sparing radical surgery for rectal cancer preserved the long-term voiding function in the majority of patients. In completely preserved patients and in women, symptomatic outcomes were more satisfactory. Postoperative erectile dysfunction was found to be a serious problem, even in complete nerve-sparing procedure.