Retroperitoneal adipose tissue denervation improves cardiometabolic and autonomic dysfunction in a high fat diet model.

Sympathetic vasomotor overactivity is a major feature leading to the cardiovascular dysfunction related to obesity. Considering that the retroperitoneal white adipose tissue (rWAT) is an important fat visceral depot and receives intense sympathetic and afferent innervations, the present study aimed to evaluate the effects evoked by bilateral rWAT denervation in obese rats. Male Wistar rats were fed with HFD for 8 consecutive weeks and rWAT denervation was performed at the 6th week. Arterial pressure, splanchnic and renal sympathetic vasomotor nerve activities were assessed and inflammation and the components of the renin -angiotensin system were evaluated in different white adipose tissue depots. HFD animals presented higher serum levels of leptin and glucose, an increase in arterial pressure and splanchnic sympathetic nerve activity; rWAT denervation, normalized these parameters. Pro-inflammatory cytokines levels were significantly increased, as well as RAAS gene expression in WAT of HFD animals; rWAT denervation significantly attenuated these changes. In conclusion, HFD promotes vasomotor sympathetic overactivation and inflammation with repercussions on the cardiovascular system. In conclusion, the neural communication between WAT and the brain is fundamental to trigger sympathetic vasomotor activation and this pathway is a possible new therapeutic target to treat obesity-associated cardiovascular dysfunction.

Pelvic Neuroanatomy: An Overview of Commonly Encountered Pelvic Nerves in Gynecologic Surgery.

OBJECTIVE: This video tutorial identifies key anatomic landmarks useful in identifying the path of the most commonly encountered pelvic nerves in benign gynecologic surgery. DESIGN: This is a narrated overview of commonly encountered pelvic nerves during benign gynecology, their origin, sensory, and motor function, as well as sequelae related to injury. SETTING: The unintended injury of pelvic neural connections can be a complication of any pelvic surgery, however, surgery for malignancy or endometriosis may increase the likelihood of encountering these nerves. The majority of focus surrounding surgical nerve injury, however, relates to patient positioning [1]. Injury to the pelvic nerves can lead to lifelong sexual, bladder, and defecatory dysfunction [2]. INTERVENTIONS: We review the Genitofemoral, Lateral Femoral Cutaneous, Ilioinguinal, Obturator, Superior and Inferior Hypogastric nerves, Pelvic Splanchnic nerves, and the Sacral nerves. Surgical illustrations are used (Fig. 1) alongside real-time narrated video to help viewers recognize the normal course of commonly encountered pelvic nerves at the time of gynecologic surgery (Figs2-3). CONCLUSION: The surgical management of complex pelvic disease can unfortunately carry significant patient morbidity [3]. The neural pathways traveling through the pelvis via the hypogastric nerves are responsible for proprioception, vaginal lubrication, and proper functioning or the urethral and anal sphincters [4]. Sparing these nerves during pelvic surgery, and especially when anatomic planes are distorted by pelvic disease, requires surgical expertise and an immense understanding of pelvic neuroanatomy [4,5]. Preservation of the pelvic neural pathways is necessary to deliver the best patient outcomes while minimizing unwanted surgical complications. This video tutorial also highlights the origin of these nerves, their anatomic location, procedures in which these nerves may be encountered, and what sequelae occur from their unintended injury.

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.

Clinical history and antithrombotic treatment of incidentally detected splanchnic vein thrombosis: a multicentre, international prospective registry.

BACKGROUND: Little information is available about the clinical history of patients with incidentally detected splanchnic vein thrombosis and its therapeutic management remains controversial. The aim of this study was to assess the risk factors, therapeutic strategies, and long-term outcomes of incidentally detected splanchnic vein thrombosis. METHODS: We analysed data from patients with incidentally detected splanchnic vein thrombosis who were enrolled in an international, multicentre, prospective cohort study of splanchnic vein thrombosis between 2008 and 2012. The study was done at 31 centres in 11 countries (Italy, South Korea, Germany, Canada, Belgium, the Netherlands, Brazil, USA, France, Israel, UK). Information about demographic characteristics, risk factors, and treatment was collected. The study outcomes during the 2-year follow-up were major bleeding (International Society on Thrombosis and Haemostasis definition plus the need for hospital admission), thrombotic events (venous or arterial thromboses), and mortality. The primary analysis period was from the diagnosis of incidentally detected splanchnic vein thrombosis until the first adjudicated clinical outcome or the end of follow-up. FINDINGS: Between May 2, 2008, and Jan 30, 2012, we enrolled 177 patients with incidentally detected splanchnic vein thrombosis (median age 57 years [IQR 49-66], 118 [67%] men, 138 [78%] patients with portal vein thrombosis). The most common underlying diseases were liver cirrhosis (82 [46%] patients) and solid cancer (62 [35%] patients). Anticoagulant treatment was prescribed to 109 (62%) patients. Median duration of anticoagulation was 6 months (IQR 5-12) for patients who received parenteral anticoagulants alone and 24 months (IQR 12-24) for patients treated with vitamin K antagonists. During a median follow-up of 2 years (IQR 1-2), the incidence of major bleeding was 3·3 events (95% CI 1·7-6·3) per 100 patient-years and the incidence of thrombotic events was 8·0 events (95% CI 5·2-12·1) per 100 patient-years. On-treatment incidence was 3·2 events (95% CI 1·2-8·4) per 100 patient-years for major bleeding and 3·9 events (95% CI 1·6-9·5) per 100 patient-years for thrombotic events. In multivariate analysis, anticoagulant treatment as a time-dependent variable reduced the incidence of thrombotic events (hazard ratio 0·85, 95% CI 0·76-0·96) without increasing the risk of major bleeding (p>0·05). In patients with clinically suspected splanchnic vein thrombosis, the incidence of major bleeding was 3·9 events (95% CI 2·6-5·7) per 100 patient-years and the incidence of thrombotic events was 7·0 events (95% CI 5·2-9·3) per 100 patient-years. INTERPRETATION: Our results show that the prognosis of incidentally detected splanchnic vein thrombosis is similar to that of clinically suspected splanchnic vein thrombosis and suggest that similar treatment strategies should be applied. FUNDING: Pfizer Canada research grant.

GABA(A) receptor overexpression in the lateral hypothalamic area attenuates gastric ischemia­reperfusion injury in rats.

Excessive activation of the greater splanchnic nerve (GSN) has previously been determined to contribute to the progression of gastric ischemia­reperfusion (GI­R) injury. The present study was designed to estimate the protective effects of GABAA receptor (GABA(A)R) overexpression in the lateral hypothalamic area (LHA) against GI­R injury. The GI­R injury model was induced in rats by clamping the celiac artery for 30 min and then reperfusing for 1 h. Microinjection of recombinant adenoviral vectors overexpressing GABA(A)R (Ad­GABA(A)R) or control adenoviral vectors (Ad­Con) into the LHA was conducted in GI­R and normal control rats. Significant protective effects were observed on day 2 after Ad­GABA(A)R treatment in the GI­R injury rats. Ad­GABA(A)R treatment reduced plasma norepinephrine levels, plasma angiotensin II levels and peripheral GSN activity, but increased the gastric mucosal blood flow, as compared with Ad­Con treatment. These results indicate that adenoviral vector­induced GABA(A)R overexpression in the LHA blunts GSN activity and subsequently alleviates the effects of gastric injury in GI­R rats.

Inherent variations in CO-H2S-mediated carotid body O2 sensing mediate hypertension and pulmonary edema.

Oxygen (O2) sensing by the carotid body and its chemosensory reflex is critical for homeostatic regulation of breathing and blood pressure. Humans and animals exhibit substantial interindividual variation in this chemosensory reflex response, with profound effects on cardiorespiratory functions. However, the underlying mechanisms are not known. Here, we report that inherent variations in carotid body O2 sensing by carbon monoxide (CO)-sensitive hydrogen sulfide (H2S) signaling contribute to reflex variation in three genetically distinct rat strains. Compared with Sprague-Dawley (SD) rats, Brown-Norway (BN) rats exhibit impaired carotid body O2 sensing and develop pulmonary edema as a consequence of poor ventilatory adaptation to hypobaric hypoxia. Spontaneous Hypertensive (SH) rat carotid bodies display inherent hypersensitivity to hypoxia and develop hypertension. BN rat carotid bodies have naturally higher CO and lower H2S levels than SD rat, whereas SH carotid bodies have reduced CO and greater H2S generation. Higher CO levels in BN rats were associated with higher substrate affinity of the enzyme heme oxygenase 2, whereas SH rats present lower substrate affinity and, thus, reduced CO generation. Reducing CO levels in BN rat carotid bodies increased H2S generation, restoring O2 sensing and preventing hypoxia-induced pulmonary edema. Increasing CO levels in SH carotid bodies reduced H2S generation, preventing hypersensitivity to hypoxia and controlling hypertension in SH rats.

Laparoscopic nerve-sparing transperitoneal approach for endometriosis infiltrating the pelvic wall and somatic nerves: anatomical considerations and surgical technique.

PURPOSE: Endometriotic or fibrotic involvement of sacral plexus and pudendal and sciatic nerves may be quite frequently the endopelvic cause of ano-genital and pelvic pain. Feasibility of a laparoscopic transperitoneal approach to the somatic nerves of the pelvis was determined and showed by Possover et al. for diagnosis and treatment of ano-genital pain caused by pudendal and/or sacral nerve roots lesions and adopted at our institution. In this paper we report our experience and anatomo-surgical consideration regarding this technique. METHODS: Confidence with this technique was obtained after several laparoscopic and laparotomic dissections on fresh, embalmed and formalin-fixed female cadavers and is now routinely performed at our institution in all cases of extensive endometriosis of the pelvic wall, involving the somatic nerves. RESULTS: We describe two different laparoscopic transperitoneal approaches to the lateral pelvic wall in case of: (A) deep pelvic endometriosis with rectal and/or parametrial involvement extending to pelvic wall and somatic nerves; (B) isolated endometriosis of pelvic wall and somatic nerves. CONCLUSIONS: Laparoscopic transperitoneal retroperitoneal nerve-sparing approach to the pelvic wall proved to be a feasible and useful procedure even if limited to referred laparoscopic centers and anatomically experienced and skilled surgeons.

Morphometric evaluation of the aging process in various human nerve fibers.

We carried out a morphometric comparison of tissue sections from the human spinal cord, medulla oblongata, cranial nerves, autonomic nerves and spinal nerves with the help of a very accurate method that includes two-step fixation, nitrocellulose embedding and discriminative staining. We conducted morphometric evaluations to compare various axonal areas between different individuals using a combination of an image analyzer and a high power microscope. Our study showed a negative correlation between age and axonal area in all nerves except the greater splanchnic nerve. We believe that such data would not have been discovered without the use of our sophisticated electronic equipment together with the special preparation method we employed. Recourse to such methodology will allow more precise study of neurohistology and lead to better understanding of the aging process in human beings.

Laparoscopic nerve-sparing complete excision of deep endometriosis: is it feasible?

BACKGROUND: Little is known about the morbidity associated with laparoscopic complete excision of endometriosis in terms of urinary, digestive and sexual function. METHODS: We performed a prospective non-randomized study in 45 patients with laparoscopic complete excision of all detectable foci of endometriosis with segmental bowel resection using a non nerve-sparing technique (control group-group A n=20) and a nerve-sparing technique (case group-group B n=25). At initial gynaecological evaluation, and at follow-up details on dysmenorrhoea, pelvic pain, dyspareunia and dyschezia were evaluated using an interview-based questionnaire (10-point analogue rating scale: 0=absent, 10=unbearable). RESULTS: The mean (+/-SD) follow-up period was 15.3+/-10 months (range, 8.8-23 months) for group A and 3.5+/-2.1 months (range, 0.3-5.2 months) for group B. In the immediate postoperative course, in group A three women required blood transfusion vs seven women in group B (P=0.003). The median time to resume the voiding function was significantly shorter in group B (12.5 vs 3.0 days; P<0.01). At the time of follow-up a higher proportion of patients in group B were 'very satisfied' than those in group A (87.7% vs 59.0%, P=0.013). CONCLUSIONS: Laparoscopic nerve-sparing complete excision of endometriosis seems to be feasible and offers good results in terms of bladder morbidity reduction with apparently higher satisfaction than classical technique. Larger series with longer follow-up are needed to confirm our results.

[Cutaneous-splanchnic neurofibromatosis]. / Neurofibromatose segmentaire cutanéo-splanchnique.

BACKGROUND: Segmental neurofibromatosis (NF V) is ten times less frequent than Recklinghausen disease. Would the risk of visceral involvement in this uncommon form of neurofibromatosis warrant systematic imaging procedures? CASE REPORT: A 31-year-old man consulted for a voluminous plexiform neurofibroma in the left lumbar area. More ventrally, on the left side, there was also a café au lait spot. There were no Lisch nodules. The chest and abdominopelvic computed tomography and magnetic resonance imaging showed intramuscular tumoral extension, two neurofibromas in the 9th intercostal space and a voluminous 5-cm tumor situated in the left adrenal area. After resection pathology examination of the surgical specimen confirmed the diagnosis of ganglioneuroma. DISCUSSION: In this patient, all the neurofibromas and the café of lait spot developed in the territories of the left T10 and adjacent spinal roots. This was also true for the ganglioneuroma which developed on the deep sympathetic ramus to the adrenal gland which originates essentially from roots T8 to T11. This would place this case in the second subgroup of NF V in Roth's classification. Only six other cases have been reported in the literature. Such deep localizations are very likely to be underestimated, raising the problem of their detection and the correct protocol to follow asymptomatic forms, especially to detect disease progression to malignant degeneration which has a poor prognosis. Patients with a NF V should receive genetic counselling with a search for a family history, other signs of neurofibromatosis and Lisch nodules. In young patients, the risk of deep asymptomatic spread underlines the importance of regional computed tomographic or magnetic resonance explorations.

Bilateral endoscopic splanchnicectomy through a posterior thoracoscopic approach.

The technique of bilateral total splanchnicectomy performed through a posterior thoracoscopic approach is described. The advantages of this route include excellent visual exposure of the neural anatomy of the sympathetic and avoidance of single lung anaesthesia. The procedure was performed for the relief of intractable pain in patients with advanced pancreatic cancer (n = 3) and patients suffering from chronic pancreatitis (n = 5). Persistent relief of pain until death was obtained in the patients with pancreatic cancer (2, 4, 6 months). In patients with chronic pancreatitis, the benefit to date has varied with the severity of the disease. In two patients with severe advanced disease and previous percutaneous blocks, the relief of pain lasted only 3 and 5 weeks and both patients required resection for renewed intractable pain. In three patients with minimal change disease, relief of pain has been good in the short term (maximum follow-up of 8 months). Bilateral thoracoscopic total splanchnicectomy merits further evaluation in patients with pancreatic pain. No complications including hypotension have been encountered.

[The surgical anatomy of the genital nerves of the male and their preservation in excision of the rectum]. / Die chirurgische Anatomie der Genitalnerven des Mannes und ihre Schonung bei der Excision des Rectums.

Studies of the fetus and new-born were undertaken to determine the exact localization of the nn. erigentes in the lower pelvis. The particular topography was visualized using histological slides and a special digital imaging technique. The nn. erigentes were found to be bundled along the diaphragmatic part of the urethra before entering the two cavernous bodies of the penis. These findings suggest that a small anterior patch of rectal muscle covering the diaphragmatic part of the urethra should be left behind in male patients undergoing total proctocolectomy in order to preserve potency. This operative technique cannot be employed for carcinomas extending to the anterior rectal wall. Since 1980, the new technique has been used in 18 male patients with rectal carcinoma and sexual function was preserved in all cases.

Osteophytes of the spine compressing the sympathetic trunk and splanchnic nerves in the thorax.

The presence of osteophytes compressing the sympathetic structures in the thorax was found in 655 (65.5%) of 1,000 cadavers. In 60.4% of the affected cases, the compression was on the right side, and in 36.9% it was bilateral, although the right side was more severely affected. In 2%, the compression was on the left only. The highest frequency of compression was at the T8-10 level, the right greater splanchnic nerve being the structure most frequently involved. The sympathetic trunk itself (ganglia and cord) was affected only by osteophytes of vertebrae at the lowest thoracic levels; however, bony excrescences due to costovertebral joint arthritis were frequently found impinging on the sympathetic trunk and its rami communicantes at similar frequencies on both sides. The factors governing the characteristic compression of the sympathetic structures in the thorax are the typical development of the osteophytes and the special relations of the sympathetic structures to the vertebral column at the various levels. It is proposed that these observations are useful in understanding certain observed clinical conditions and act an anatomic baseline for research in the future.

Autonomic neuropathy in the trembler mouse.

There is little detailed histological information concerning the autonomic nervous system in hereditary demyelinating neuropathies in man. An opportunity was therefore taken to study the autonomic nervous system of the trembler mouse which suffers from a dominantly inherited peripheral neuropathy. Schwann cell myelination in trembler vagus and splanchnic nerves was abnormal. Morphometric analysis of myelinated and unmyelinated fibres in these nerves showed a marked reduction in myelinated fibre density distribution, whilst unmyelinated fibre densities were within the control range. The trembler vagus contained increased numbers of large diameter unmyelinated fibres probably as a result of trembler Schwann cell failure to form myelin around axons of the appropriate diameter for myelination. The trembler splanchnic nerve, however, contained increased numbers of small diameter unmyelinated fibres, possibly postganglionic fibres which fail to achieve their expected diameters.

Autonomic neuropathy in experimental allergic neuritis: an electrophysiological and histological study.

Electrophysiological and histological studies have been performed on the vagus and splanchnic nerves of guinea pigs with experimental allergic neuritis. Slowing of conduction and dispersion of the compound action potential were consistent with the pathological changes of demyelination. In teased single fibre preparations, axonal degeneration was found more frequently than was expected and in the splanchnic nerves, the unmyelinated fibres appeared to have been indirectly involved. These findings in experimental allergic neuritis are relevant to the pathogenesis of autonomic dysfunction in the Landry-Guillain-Barré syndrome.

The splanchnic autonomic outflow in Shy-Drager syndrome and idiopathic orthostatic hypotension.

Since splanchnic outflow is important in the maintenance of postural normotension in man, we performed a quantitative analysis of preganglionic autonomic neuron cell bodies of the seventh thoracic spinal cord segment and their corresponding axons in 2 patients with Shy-Drager syndrome (SDS) and 1 with idiopathic orthostatic hypotension (IOH) and compared these values to control data. The intermediolateral column (ILC) neuron cell body counts were reduced to 17% of control levels in SDS and 52% of control levels in IOH. The B fiber counts in the corresponding ventral spinal root were reduced to 21% and 41% in SDS and IOH, respectively. From the present study and our previous results of ILC counts with age, we infer that orthostatic hypotension does not develop until half or more of the preganglionic autonomic neurons have degenerated. An additional finding in SDS is that there is involvement beyond autonomic neurons.

Abnormalities in pelvic visceral nerves. A basis for neurogenic bladder in the diabetic Chinese hamster.

In order to determine whether bladder dysfunction and hydronephrosis in diabetic Chinese hamsters are associated with nerve pathology, the pelvic visceral nerves of diabetic and normal hamsters were examined with histochemical and electron microscopic techniques. Acetylcholinesterase activity was reduced in the nerves and on smooth muscle fibers in the urinary bladder of diabetic hamsters when compared to controls. Depression of enzyme staining was most marked in those hamsters with the most severe hydronephrosis. Frequent examples of aberrant myelination were found in the pelvic plexus and urinary bladder of diabetics. Many of these myelinated fibers exhibited wide periaxonal spaces lined by unusual processes of Schwann cells. An increase in the number of microtubules in axons and circular profiles of Schwann cells, which failed to enclose axons, gave evidence of axonal degeneration or Schwann cell injury in diabetic nerves. These findings suggest that pathologic changes in pelvic visceral nerves may underlie urinary bladder dysfunction in the diabetic Chinese hamster.

Acrylamide autonomic neuropathy in the cat. Part 1. Neurophysiological and histological studies.

Neurophysiological and histological studies have been performed on the sympathetic nervous system of cats poisoned with acrylamide. The neurophysiological studies indicate that the large and small diameter myelinated fibres are damaged in the sympathetic nervous system in association with damage to the fibres of the peripheral nervous system. Quantative histological studies confirmed and extended the neurophysiological findings; there was a loss of myelinated fibres of all diameters from the sympathetic, parasympathetic and peripheral nervous system.