Nerve-Sparing Technique during Laparoscopic Radical Hysterectomy: Critical Steps.

STUDY OBJECTIVE: To show the feasibility and safety of nerve-preserving laparoscopic radical hysterectomy (type C1 Querleu-Morrow Classification [1]) for the treatment of early cervical cancer. DESIGN: A surgical video article (Canadian Task Force classification III). SETTING: A university hospital (University Hospital of Barcelona, Barcelona, Spain). PATIENTS: Nerve-preserving radical hysterectomy is performed in a patient with Fédération Internationale de Gynécologie et d'Obstétrique stage 1B1 cervical cancer with deep stromal invasion. INTERVENTIONS: Three steps are fundamental for the removal of the cérvix with a safe oncologic margin and preservation of the pelvic autonomic nerves [2]. 1. Step 1: for the correct preservation of the pelvic splanchnic nerves (ventral roots from spinal nerves S2-S4) and the inferior hypogastric plexus during the section of the paracervix, it is essential to identify the deep uterine vein. This vein will correspond with the inferior limit of the dissection. 2. Step 2: during the dissection of the uterosacral ligament and after dissecting the Okabayashi space, the inferior hypogastric nerve is isolated. This nerve runs 2 cm parallel below the uterosacral ligament in the peritoneal leaf of the broad ligament. 3. Step 3: during the section of the vesicouterine ligament, the lateral side must be preserved because it includes the medial and inferior vesical veins that drain to the deep uterine vein. CONCLUSION: Nerve-sparing laparoscopic radical hysterectomy is an attractive surgical approach for early-stage cervical cancer. Direct visualization of the pelvic autonomic nervous system (sympathetic and parasympathetic branches) innervating the bladder and rectum makes the nerve-sparing approach a safe and feasible procedure.

Resection rectopexy--laparoscopic neuromapping reveals neurogenic pathways to the lower segment of the rectum: preliminary results.

PURPOSE: Nerve sparing in functional pelvic floor surgery is strongly recommended as intraoperative damage to the autonomic nerves may predispose to persistent or worsened anorectal and urogenital function. The aim of this study was to investigate the intraoperative neural topography above the pelvic floor in patients undergoing laparoscopic resection rectopexy in combination with electrophysiologic neuromapping. METHODS: Ten consecutive female patients underwent laparoscopic resection rectopexy for rectal prolapse. Intraoperative identification of pelvic autonomic nerves was carried out with a novel intraoperative neuromonitoring system based on electric stimulation under simultaneous electromyography of the internal anal sphincter and manometry of the bladder. Neuromonitoring results were compared to patients' preoperative anorectal and urogenital function and their functional results at the 3-month follow-up. RESULTS: Laparoscopy in combination with electrophysiologic neuromapping revealed neurogenic pathways to the lower segment of the rectum during surgical mobilization. In all procedures, intraoperative neuromonitoring finally confirmed functional nerve integrity to the internal anal sphincter and the bladder. Patients with preoperatively diagnosed fecal incontinence were continent at the 3-month follow-up. The Wexner score improved in median from preoperative 4 (range 1-18) to 1 (range 0-3) at follow-up (p = 0.012). Cleveland Clinical Constipation Score improved in median from 10 (range 5-17) to 3 (range 1-7; p = 0.005). In none of the investigated patients a new onset of urinary dysfunction did occur. No change in sexual function was observed. CONCLUSIONS: Laparoscopy in combination with electrophysiologic neuromapping during nerve-sparing resection rectopexy identified and preserved neurogenic pathways heading to the lower segment of the rectum above the level of the pelvic floor.

Nerve-sparing class III-IV radical hysterectomy: urodynamic study and surgical technique.

OBJECTIVE: The aim of this study was to demonstrate the impact of the nerve-sparing radical hysterectomy on the bladder function. METHODS: Patients with cervical cancer stage 1B1 to IIB, who underwent type 3 to 4 nerve-sparing radical hysterectomy, were evaluated with urodynamic test before and within 6 months from surgery. Stage IB2 to IIB patients were treated with platinum-based neoadjuvant chemotherapy. Bladder catheter was removed in postoperative day 4, and patients were educated to clean intermittent self-catheterization. Urinary symptoms were evaluated with a questionnaire administered before and 3, 6, and 12 months after surgery. Patients treated with adjuvant chemoradiotherapy were excluded from the study. RESULTS: Fifteen patients (stage IB1, 7; IB2, 3; and IIB, 5) completed the study. Eight (53%) patients were treated with neoadjuvant chemotherapy. Bilateral nerve sparing was feasible in 13 (87%) patients, unilateral in 2 (13%). At postoperative day 10, only 3 (20%) patients continued intermittent self-catheterization. Before surgery, 1 (6.2%) patient had urodynamic symptoms of incontinence, and 3 (20%) had overactive bladder detrusor. Postoperative urodynamic study (median, 4 months; range, 3-6) showed reduced detrusor activity in 8 (53%), overactive detrusor in 4 (27%), and normal profile in 3 (20%) patients. Reduced bladder sensation was observed in 2 (12.5%), and residual urine more than 30% of bladder capacity in 2 (12.5%) patients, respectively. No patient showed de novo incontinence. Bladder compliance was unchanged. CONCLUSIONS: The separation of the hypogastric nerve from the parametrium is a feasible surgical step, which can be implemented in the radical hysterectomy technique in different clinical settings. The comparative urodynamic study showed a mild functional impairment in the early postoperative period. The most frequent finding was the reduced detrusor activity observed during the voiding phase, consistent with the straining needed to void reported in the questionnaire. These data suggest that a mild bladder impairment occurs despite the conservation of the hypogastric nerve.

Effects of vagotomy, splanchnic nerve lesion, and fluorocitrate on the transmission of acute hyperosmotic stress signals to the supraoptic nucleus.

The response to hyperosmotic stresses in the abdominal cavity is regulated, in part, by vasopressin (VP)-secreting neurons in the supraoptic nucleus (SON). How osmotic stress signals are transmitted to the brain is incompletely understood, and whether the transmission routes for osmotic stress signals differ between acute and chronic stresses is unknown. Here we investigated the role of the vagus, splanchnic nerves, and astrocytes in the SON in transducing acute hyperosmotic-stress signals from the abdominal cavity. We found that acute administration of hyperosmotic saline triggered the activation of neurons as well as astrocytes in the SON and the adjoining ventral glia limitans (SON-VGL). Severing the subdiaphragmatic vagal nerve (SDV) prevented the normal response of cells in the SON to HS treatment and attenuated the release of VP into the bloodstream. Lesioning the splanchnic nerves (SNL) diminished HS-induced release of VP, but to a much lesser extent than SDV. Furthermore, SNL did not significantly affect the up-regulation of Fos in SON neurons or the up-regulation of Fos and GFAP in SON and SON-VGL astrocytes that normally occurred in response to HS and did not affect HS-induced expansion of the SON-VGL. Inhibiting astrocytes with fluorocitrate (FCA) prevented the response of the SON to HS and attenuated the release of VP, similarly to SDV surgery. These results suggest that the vagus is the principle route for the transmission of hyperosmotic signals to the brain and that astrocytes in the SON region are necessary for the activation of SON neurons and the release of VP into the bloodstream.

Nerve sparing in radical surgery for early-stage cervical cancer: yes we should!

Radical hysterectomy with pelvic lymphadenectomy is considered to be the cornerstone in the treatment of early-stage cervical cancer. Although survival in early-stage cervical cancer is up to 95%, long-term morbidity with regard to bladder, bowel, and sexual function is considerable. Damage to the pelvic autonomic nerves may be the cause of these long-term complications following radical hysterectomy. Some authors have presented surgical techniques to preserve the autonomic nerves (ie, the hypogastric nerves and the splanchnic nerves) without compromising radicality. Safety, efficacy, and the surgical techniques of nerve-sparing radical hysterectomy are presented, and data confirm that whenever the decision is made to perform a radical hysterectomy, nerve-sparing techniques should be considered.

[Anatomical consideration for the technique of nerve-sparing during radical hysterectomy for cervical cancer]. / Bases anatomiques et principe du nerve-sparing au cours de l'hystérectomie radicale pour cancer du col utérin.

Radical hysterectomy (RH) is an effective treatment for early-stage cervical cancer IA2 to IIA1 but RH is often associated with several significant complications such as urinary, anorectal and sexual dysfunction due to pelvic nerve injuries. Pelvic autonomic nerves including the superior hypogastric plexus (SHP), hypogastric nerves (HN), pelvic splanchnic nerves (PSN), sacral splanchnic nerves (SSN), inferior hypogastric plexus (IHP) and efferent branches of the IHP. We aimed to precise the neuroanatomy of the female pelvis in order to provide key-points of surgical anatomy to improve NSRH for cervical cancer. The SHP could be injured during periaortic lymph node dissection and its preservation necessitates an approach on the right side of the aorta and a blunt dissection of the promontory before lomboaortic lymphadenectomy. Injuries to HN can occur during the resection of USL at the posterior pelvic wall and of rectovaginal ligaments and to preserve HN only the medial fibrous part of the uterosacral ligament should be resected. The middle rectal artery, the deep uterine vein and the ureter should be identified to preserve PSN and IHP during resection of paracervix. Vesical branches can be preserved by blunt dissection of the posterior layer of the vesicouterine ligament after identifying the inferior vesical vein. In most of cases, NSRH for cervical cancer can be performed. Anatomical landmarks as middle rectal artery, deep uterine vein, inferior vesical vein and ureter and the respect of nervous part of uterine ligament and of parametrium provide to surgeon a safe preservation of pelvic innervation without compromising oncological outcomes.

Current concepts and practical techniques of nerve-sparing laparoscopic radical hysterectomy.

Laparoscopic radical hysterectomy has been widely performed for patients with early-stage cervical cancer. The operative techniques for nerve-sparing to avoid bladder dysfunction have been established during the past three decades in abdominal radical hysterectomy, but how these techniques can be applied to laparoscopic surgery has not been fully discussed. Prolonged operation time or decreased radicality due to less accessibility via a limited number of trocars may be a disadvantage of the laparoscopic approach, but the magnified visual field in laparoscopy may enable fine manipulation, especially for preserving autonomic nerve tracts. The present review article introduces the practical techniques for sparing bladder branches of pelvic nerves in laparoscopic radical hysterectomy based on understanding of the pelvic anatomy, clearly focusing on the differences from the techniques in abdominal hysterectomy.

Reinnervation of renal afferent and efferent nerves at 5.5 and 11 months after catheter-based radiofrequency renal denervation in sheep.

Previous studies indicate that catheter-based renal denervation reduces blood pressure and renal norepinephrine spillover in human resistant hypertension. The effects of this procedure on afferent sensory and efferent sympathetic renal nerves, and the subsequent degree of reinnervation, have not been investigated. We therefore examined the level of functional and anatomic reinnervation at 5.5 and 11 months after renal denervation using the Symplicity Flex catheter. In normotensive anesthetized sheep (n=6), electric stimulation of intact renal nerves increased arterial pressure from 99±3 to 107±3 mm Hg (afferent response) and reduced renal blood flow from 198±16 to 85±20 mL/min (efferent response). In a further group (n=6), immediately after denervation, renal sympathetic nerve activity was absent and the responses to electric stimulation were abolished. At 11 months after denervation (n=5), renal sympathetic nerve activity and the responses to electric stimulation were at normal levels. Immunohistochemical staining for renal efferent (tyrosine hydroxylase) and renal afferent nerves (calcitonin gene-related peptide), as well as renal norepinephrine levels, was normal 11 months after denervation. Findings at 5.5 months after denervation were similar (n=5). In summary, catheter-based renal denervation effectively ablated the renal afferent and efferent nerves in normotensive sheep. By 11 months after denervation the functional afferent and efferent responses to electric stimulation were normal. Reinnervation at 11 months after denervation was supported by normal anatomic distribution of afferent and efferent renal nerves. In view of this evidence, the mechanisms underlying the prolonged hypotensive effect of catheter-based renal denervation in human resistant hypertension need to be reassessed.

Nicotinic and muscarinic acetylcholine receptors are essential for the long-term response of tyrosine hydroxylase gene expression to chronic nicotine treatment in rat adrenal medulla.

Nicotine induces tyrosine hydroxylase (TH) mRNA by interacting with nicotinic acetylcholine receptors (nAChRs) in cultured adrenal medullary cell systems; however, the mechanisms responsible for the induction of adrenal TH in response to systemically administered nicotine under in vivo conditions are more complex. In the present study, we tested whether nAChRs and muscarinic acetylcholine receptors (mAChRs) participate in the induction of adrenal TH observed after long-term treatment with nicotine. Chronic nicotine treatment (1.6 mg/kg, two daily injections spaced 12 h apart for 7 days) induced TH mRNA, TH protein and TH activity in rat adrenal medulla. This induction of TH gene expression was totally blocked when an antagonist of either nAChRs or mAChRs was administered prior to each nicotine injection. Repeated injections of the mAChR agonist bethanechol (5 mg/kg injected twice per day for 7 days) also produced increases in TH mRNA levels; however, TH protein levels and TH activity did not increase in response to bethanechol. In denervated adrenal glands chronic nicotine treatment did not lead to induction of either TH mRNA, TH protein or TH activity, whereas chronic bethanechol treatment led to induction of TH mRNA, but not TH protein or activity. These results suggest that agonist occupation of both nAChRs and mAChRs are essential for the complete response of TH gene expression to chronic nicotine treatment in rat adrenal medulla, but that stimulation of either cholinergic receptor by itself is not sufficient to elicit a full response. The results also suggest that both transcriptional and post-transcriptional mechanisms may potentially need to be regulated to induce TH protein in response to some stimuli.

Urinary incontinence and vesicourethral dysfunction in pediatric surgical conditions.

The most common cause for urinary incontinence in children with pediatric surgical conditions of the pelvic region and perineum is lower urinary tract dysfunction caused by concomitant sacral agenesis, especially in children with anorectal malformations. Another common cause is iatrogenic pelvic nerve damage secondary to reconstructive surgery. Moreover, an intrinsically altered pelvic floor anatomy as seen in some cases of complex cloacas, or disruption of pelvic floor muscles with consecutive loss of supportive structures, as in sacrococcygeal teratoma, should also be taken into consideration. It is important to understand that the causes of urinary incontinence in these children are not isolated problems concerning only the urinary tract. They may have the same negative impact on anorectal function as they have on the bladder and urethral sphincter. Therefore, children with pediatric surgical conditions of the pelvic and perineal region often will present with a combination of both fecal incontinence caused by anorectal dysfunction and urinary incontinence caused by vesicourethral dysfunction. The additional morbidity caused by urinary incontinence may have an enormous impact on the patient's life and well being, not only with regard to physical disability, but also in terms of emotional problems, social handicap, and socioeconomic burden. It is obvious that a patient's quality of life will be significantly reduced if he or she suffers from both fecal and urinary incontinence. Therefore, an integrated approach to the management of both vesicourethral and anorectal dysfunction should be developed to achieve the optimum care for these children.

Laparoscopic identification of pelvic nerves in patients with deep infiltrating endometriosis.

BACKGROUND: Nerve sparing is suggested for cancer surgery, but no experience is available for deep endometriosis. The aim of this study was to laparoscopically identify the pelvic nerves in the posterior pelvis. METHODS: A total of 24 patients operated for deep endometriosis were considered. During surgery and on videotapes of the procedures, we evaluated single- or double-sided resection of the uterosacral ligaments and other structure's visualization of the inferior hypogastric and the splanchnic nerves. The most important objective criteria for resection of the nerves was urinary retention after surgery, which was compared to surgical resection on the videotapes. RESULTS: Visualization of the inferior hypogastric nerves was possible in 20 of 22 patients (90.1%). Eight of the 24 patients had at least one inferior hypogastric nerve resected (33.3%). In seven patients (29.2%) resection of the uterosacral ligaments was bilateral, and in three of these the nerves were resected. Postoperatively, the median residual urine volume after the first spontaneous voiding was 40 ml (range, 20-400). Seven of eight patients (29.2%) with resection of the nerves had urinary retention and self-catheterization at discharge. The difference in urinary residuum after first voiding between patients undergoing self-catheterization and patients released without the catheter was significant ( p < 0.01). The median time to resume the voiding function in patients with self-catheterization was 18 days (range, 9-45). CONCLUSIONS: Nerve visualization is possible by means of laparoscopic surgery for deep endometriosis in a high rate of patients. Careful technique is necessary, but the laparoscopic approach may help. Even single-sided radical dissection can induce important urinary retention.

Antro-pancreatic reflexes: long- and short-route reflexes in exocrine and endocrine pancreatic secretion in dogs.

Pancreatic exocrine secretion is known to be facilitated by gastric antral distension via long- and short-route reflexes. In this study, we studied the effects of gastric distension on intra-pancreatic nerve discharges and blood insulin level as well as pancreatic exocrine secretion. Mongrel dogs were anesthetized with ketamine and thiopental, and immediately decerebrated. This study consisted of two series of experiments. In the first series, efferent discharges in an intra-pancreatic nerve branch were recorded, and its responses to antral distension were analyzed. In the second series, effects of antral distension on pancreatic exocrine secretion and blood insulin level were observed before and after vagotomy in splanchnicectomized dogs. Efferent discharges in a pancreatic nerve branch were increased by antral distension. Neither vagotomy nor splanchnicectomy produced obvious changes in the neural response. In splanchnicectomized dogs, antral distension elevated blood insulin level and increased pancreatic exocrine secretion. After subsequent vagotomy, these effects were reduced, but the increases were still greater than 50%. These results indicate that the antro-pancreatic short-route reflex plays a significant role in exocrine secretion, and also suggest that insulin release is increased by antral distension independent of blood glucose level.

Causes of fecal and urinary incontinence after total mesorectal excision for rectal cancer based on cadaveric surgery: a study from the Cooperative Clinical Investigators of the Dutch total mesorectal excision trial.

PURPOSE: Total mesorectal excision (TME) for rectal cancer may result in anorectal and urogenital dysfunction. We aimed to study possible nerve disruption during TME and its consequences for functional outcome. Because the levator ani muscle plays an important role in both urinary and fecal continence, an explanation could be peroperative damage of the nerve supply to the levator ani muscle. METHODS: TME was performed on cadaver pelves. Subsequently, the anatomy of the pelvic floor innervation and its relation to the pelvic autonomic innervation and the mesorectum were studied. Additionally, data from the Dutch TME trial were analyzed to relate anorectal and urinary dysfunction to possible nerve damage during TME procedure. RESULTS: Cadaver TME surgery demonstrated that, especially in low tumors, the pelvic floor innervation can be damaged. Furthermore, the origin of the levator ani nerve was located in close proximity of the origin of the pelvic splanchnic nerves. Analysis of the TME trial data showed that newly developed urinary and fecal incontinence was present in 33.7% and 38.8% of patients, respectively. Both types of incontinence were significantly associated with each other (P = .027). Low anastomosis was significantly associated with urinary incontinence (P = .049). One third of the patients with newly developed urinary and fecal incontinence also reported difficulty in bladder emptying, for which excessive perioperative blood loss was a significant risk factor. CONCLUSION: Perioperative damage to the pelvic floor innervation could contribute to fecal and urinary incontinence after TME, especially in case of a low anastomosis or damage to the pelvic splanchnic nerves.

A systematic nerve-sparing radical hysterectomy technique in invasive cervical cancer for preserving postsurgical bladder function.

The objective of this study is to describe a technique for preserving the autonomic nerve systematically, including the hypogastric nerves, pelvic splanchnic nerves, and pelvic plexus and its vesical branches, based on anatomic considerations for the autonomic nerves innervating the urinary bladder, in radical hysterectomies and to assess postsurgical bladder function. A nerve-sparing radical hysterectomy was carried out on 27 consecutive patients with uterine cervical cancer treated between 2000 and 2002. The FIGO stages of the disease consisted of 10 stage Ib1, 6 stage Ib2, 3 stage IIa, and 8 stage IIb. The nerve-sparing procedure was successfully completed in 22 of the 27 patients (81.5%) in the study. At 1 year after the operation, bladder symptoms were significantly improved in the nerve-sparing group compared to the non-nerve-sparing group. Urinary incontinence and abnormal (diminished) bladder sensation were observed in three of the five patients (two patients had both symptoms), for whom the nerve-sparing procedure could not be performed, but none of the 22 patients for whom the nerve-sparing procedure was performed had incontinence, and only two patients had abnormal (increased) bladder sensation (P= 0.0034 for incontinence and P= 0.030 for abnormal bladder sensation). The patients' survival was not adversely affected by the nerve-sparing procedure. Although it is still preliminary, the surgical technique described in this report is thought to be effective for preserving bladder function, and thus, the quality of life could be improved for patients with cervical cancer who are treated with a radical hysterectomy. For further evaluation of the efficacy of nerve-sparing radical hysterectomy, a prospective randomized trial needs to be performed.

Repeated, non-habituating stress suppresses inflammatory plasma extravasation by a novel, sympathoadrenal dependent mechanism.

The mechanism by which chronic stress affects the course of inflammatory diseases is still not well understood. We have evaluated the effect of two types of nonhabituating stress on a major component of the inflammatory response, synovial plasma extravasation, induced by perfusion of the potent inflammatory mediator, bradykinin and evaluated the underlying neuroendocrine mechanism in the rat. Chronic intermittent noise or ether stress induced profound inhibition of bradykinin-induced plasma extravasation, which is associated with increased adjuvant-arthritis severity. This inhibition, however, took 24 h to fully develop after the last exposure to stress and persisted for at least 48 h. The inhibition could be reversed by an additional exposure to the stressor, just prior to measuring the inflammatory response, suggesting that the delay is due to stress-induced release of a factor that acutely masks the inhibition of the inflammatory response. This novel, unexpected feature of the effect of nonhabituating stress on inflammation may help explain variability in effects of stress in patients with inflammatory disease. The effect of nonhabituating stress on inflammation was dependent on the sympathoadrenal axis with no detectable contribution by the hypothalamic-pituitary-adrenal axis.

Hypothalamus-brain stem circuitry responsible for vagal efferent signaling to the pancreas evoked by hypoglycemia in rat.

Circulating glucose levels significantly affect vagal neural activity, which is important in the regulation of pancreatic functions. Little is known about the mechanisms involved. This study investigates the neural pathways responsible for hypoglycemia-induced vagal efferent signaling to the pancreas and identifies the neurotransmitters involved. Vagal pancreatic efferent nerve activities were recorded in anesthetized rats. Insulin-induced hypoglycemia, a decrease of blood glucose levels from 114 +/- 5 to 74 +/- 6 mg dl(-1), stimulated an increase in pancreatic efferent nerve firing from a basal rate of 1.1 +/- 0.3 to 19 +/- 3 impulses 30 s(-1). In contrast, vagal primary afferent neuronal discharges recorded in the nodose ganglia were unaltered by systemic hypoglycemia. Vagal afferent rootlet section plus splanchnicotomy had no effect on hypoglycemia-induced vagal efferent firing, suggesting a central site of action. Decerebration reduced the increase in nerve firing stimulated by hypoglycemia from 21 +/- 4 to 9.6 +/- 2 impulses 30 s(-1). Chemical ablation of the lateral hypothalamic area, but not the arcuate nucleus, inhibited pancreatic nerve firing evoked by hypoglycemia. Microinjection of the orexin-A receptor antagonist SB-334867 into the dorsal motor nucleus of the vagus (DMV) inhibited pancreatic nerve firing evoked by insulin-induced hypoglycemia by 56%. In contrast, injection of orexin-A (20 pmol) into the DMV elicited a 30-fold increase in pancreatic nerve firing. We concluded that systemic hypoglycemia stimulates pancreatic efferent nerve firing through a central mechanism. Full expression of pancreatic nerve activities during hypoglycemia requires both the forebrain and the brain stem. In addition to activating neurons in the brain stem, central neuroglucopenia activates subpopulations of neurons in the lateral hypothalamic area that contain orexin. The released orexin acts on DMV neurons to stimulate pancreatic efferent nerve activities and thus regulate pancreatic functions.