Exploring the safety and efficacy of stomach-partitioning gastrojejunostomy with distal selective vagotomy versus conventional gastrojejunostomy with highly selective vagotomy for treating benign gastric outlet obstruction: study protocol for a randomised controlled trial.

INTRODUCTION: Benign gastric outlet obstruction (BGOO) severely impacts the quality of life of patients. The main treatment methods for BGOO include surgery and endoscopy, but both have significant drawbacks. Therefore, this study aims to explore the safety and efficacy of a new technique, to develop a new option for treating BGOO. METHODS AND ANALYSIS: This is an ongoing prospective, single-centre, single-blind randomised controlled trial. The study will be conducted from January 2022 to December 2025, and 50 patients will be enrolled. The participants will be randomly assigned in a 1:1 ratio to either the experimental (stomach-partitioning gastrojejunostomy with distal selective vagotomy) or control groups (conventional gastrojejunostomy with highly selective vagotomy). We will collect baseline characteristics, laboratory tests, auxiliary examinations, operation, postoperative conditions and follow-up data. Follow-up will last for 3 years. The main outcome is the incidence of delayed gastric emptying within 30 days after surgery. Secondary outcomes include the efficacy indicator (consisting of serum gastrin level, pepsinogen level, 13C breath test, gastrointestinal quality of life index, operation time, blood loss and postoperative recovery), a safety evaluation index (consisting of complications and mortality within 30 days after surgery) and follow-up data (consisting of the incidence of primary ulcer progression in 3 years after surgery, and the gastroscopy results in 1 and 3 years after surgery). ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Beijing Friendship Hospital, Capital Medical University (no. 2021-P2-274-02). The study conformed to the provisions of the Declaration of Helsinki (as revised in 2013). Written informed consent will be obtained prior to study enrolment. The results of this study will be published in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2100052197.

Is vagotomy necessary in palliative surgery for incurable advanced gastric cancer?: a retrospective case-control study.

BACKGROUND: The interplay between the nervous system and cancer plays an important role in the initiation and progression of gastric cancer. Few studies have presented evidence that the sympathetic nervous system inhibits the occurrence and development of gastric cancer while the parasympathetic nervous system promotes the growth of gastric cancer. To investigate the effect of vagotomy, which is the resection of a parasympathetic nerve innervating the stomach, on the progression of gastric cancer, a retrospective study was conducted comparing the prognosis of simple palliative gastrojejunostomy (PGJ) and palliative gastrojejunostomy with vagotomy (PGJV). METHODS: From January 01, 2000, to December 31, 2021, the medical records of patients who underwent PGJ or PGJV because of gastric outlet obstruction due to incurable advanced gastric cancer at the Yeungnam University Medical Center were retrospectively reviewed. Patients were divided into two groups: locally unresectable gastric cancer (LUGC) or gastric cancer with distant metastasis (GCDM), according to the reason for gastrojejunostomy, and factors affecting overall survival (OS) were analyzed. RESULTS: There was no significant difference in surgical outcomes and postoperative complications between the patients with PGJV and patients with PGJ. In univariate analysis, vagotomy was not a significant factor for OS in the GCDM group (HR 1.14, CI 0.67-1.94, p value 0.642), while vagotomy was a significant factor for OS in the LUGC group (HR 0.38, CI 0.15-0.98, p value 0.045). In multivariate analysis, when vagotomy is performed together with PGJ for LUGC, the OS can be significantly extended (HR 0.25, CI 0.09-0.068, p value 0.007). CONCLUSIONS: When PGJ for LUGC was performed with vagotomy, additional survival benefits could be achieved with low complication risk. However, to confirm the effect of vagotomy on the growth of gastric cancer, further prospective studies using large sample sizes are essential.

Role of the parasympathetic nervous system in cancer initiation and progression

The nervous system plays an important role in cancer initiation and progression. Accumulated evidences clearly show that the sympathetic nervous system exerts stimulatory effects on carcinogenesis and cancer growth. However, the role of the parasympathetic nervous system in cancer has been much less elucidated. Whereas retrospective studies in vagotomized patients and experiments employing vagotomized animals indicate the parasympathetic nervous system has an inhibitory effect on cancer, clinical studies in patients with prostate cancer indicate it has stimulatory effects. Therefore, the aim of this paper is a critical evaluation of the available data related to the role of the parasympathetic nervous system in cancer (AU)

STRUCTURAL BASES OF GASTROINTESTINAL MOTILITY CHANGES IN PARKINSON'S DISEASE: STUDY IN RATS.

BACKGROUND: Gastrointestinal disorders are frequently reported in patients with Parkinson's disease whose disorders reduce the absorption of nutrients and drugs, worsening the clinical condition of patients. However, the mechanisms involved in modifying gastrointestinal pathophysiology have not yet been fully explained. AIM: To evaluate its effects on gastrointestinal motility and the involvement of the vagal and splanchnic pathways. METHODS: Male Wistar rats (250-300 g, n = 84) were used and divided into two groups. Group I (6-OHDA) received an intrastriatal injection of 6-hydroxydopamine (21 µg/animal). Group II (control) received a saline solution (NaCl, 0.9%) under the same conditions. The study of gastric emptying, intestinal transit, gastric compliance and operations (vagotomy and splanchnotomy) were performed 14 days after inducing neurodegeneration. Test meal (phenol red 5% glucose) was used to assess the rate of gastric emptying and intestinal transit. RESULTS: Parkinson's disease delayed gastric emptying and intestinal transit at all time periods studied; however, changes in gastric compliance were not observed. The delay in gastric emptying was reversed by pretreatment with vagotomy and splanchnotomy+celiac gangliectomy, thus suggesting the involvement of such pathways in the observed motor disorders. CONCLUSION: Parkinson's disease compromises gastric emptying, as well as intestinal transit, but does not alter gastric compliance. The delay in gastric emptying was reversed by truncal vagotomy, splanchnotomy and celiac ganglionectomy, suggesting the involvement of such pathways in delaying gastric emptying.

Role of the parasympathetic nervous system in cancer initiation and progression.

The nervous system plays an important role in cancer initiation and progression. Accumulated evidences clearly show that the sympathetic nervous system exerts stimulatory effects on carcinogenesis and cancer growth. However, the role of the parasympathetic nervous system in cancer has been much less elucidated. Whereas retrospective studies in vagotomized patients and experiments employing vagotomized animals indicate the parasympathetic nervous system has an inhibitory effect on cancer, clinical studies in patients with prostate cancer indicate it has stimulatory effects. Therefore, the aim of this paper is a critical evaluation of the available data related to the role of the parasympathetic nervous system in cancer.

Long-Term Evaluation of the Vagal Denervation by Cardioneuroablation Using Holter and Heart Rate Variability.

BACKGROUND: Several disorders present reflex or persistent increase in vagal tone that may cause refractory symptoms even in a normal heart patient. Cardioneuroablation, the vagal denervation by radiofrequency ablation of the neuromyocardial interface, was developed to treat these conditions without pacemaker implantation. A theoretical limitation could be the reinnervation, that naturally grows in the first year, that could recover the vagal hyperactivity. This study aims to verify the vagal denervation degree in the chronic phase after cardioneuroablation. Additionally, it intends to investigate the arrhythmias behavior after cardioneuroablation. METHODS: Prospective longitudinal study with intrapatient comparison of 83 very symptomatic cases without significant cardiopathy, submitted to cardioneuroablation, 49 (59%) male, 47.3±17 years old, having vagal paroxysmal atrial fibrillation 58 (70%) or neurocardiogenic syncope 25 (30%), New York Heart Association class0.05) suggesting that the reinnervation has halted. There was also an important reduction in all bradyarrhythmias and tachyarrhythmias pre-cardioneuroablation versus post-cardioneuroablation (P<0.01). CONCLUSIONS: There is an important and significant vagal and sympathetic denervation after 2 years of cardioneuroablation with a significant reduction in bradyarrhythmia and tachyarrhythmia in the whole group. There were no complications.

Vagotomy and subsequent risk of inflammatory bowel disease: a nationwide register-based matched cohort study.

BACKGROUND: The vagus nerve provides essential parasympathetic innervation to the gastrointestinal system and is known to have anti-inflammatory properties. AIMS: To explore the relationship between vagotomy and the risk of inflammatory bowel disease (IBD) and its major categories: Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A matched cohort comprising 15 637 patients undergoing vagotomy was identified through the Swedish Patient Register from 1964 to 2010. Each vagotomised patient was matched for birth year and gender with 40 nonvagotomised individuals on the date of vagotomy. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for IBD using flexible parametric models adjusted for matching variables, year of vagotomy, birth country, chronic obstructive pulmonary disease and comorbidity index. RESULTS: We observed 119 (0.8%) patients with vagotomy developed IBD compared to 3377 (0.5%) IBD cases in nonvagotomised individuals. The crude incidence of IBD (per 1000 person-years) was 0.38 for vagotomised patients and 0.25 for nonvagotomised individuals. We observed a time-dependent elevated risk of IBD associated with vagotomy, for instance, the HR (95% CI) was 1.80 (1.40-2.31) at year 5 and 1.49 (1.14-1.96) at year 10 post-vagotomy. The association appeared to be stronger for truncal than selective vagotomy and limited to CD (HR was 3.63 [1.94-6.80] for truncal and 2.06 [1.49-2.84] for selective vagotomy) but not UC (1.36 [0.71-2.62] for truncal and 1.25 [0.95-1.63] for selective vagotomy). CONCLUSIONS: We found a positive association between vagotomy and later IBD, particularly for CD. The finding indirectly underlines the beneficial role of the vagal tone in IBD.

Relation of Fractionated Atrial Potentials With the Vagal Innervation Evaluated by Extracardiac Vagal Stimulation During Cardioneuroablation.

BACKGROUND: Vagal hyperactivity is directly related to several clinical conditions as reflex/functional bradyarrhythmias and vagal atrial fibrillation (AF). Cardioneuroablation provides therapeutic vagal denervation through endocardial radiofrequency ablation for these cases. The main challenges are neuromyocardium interface identification and the denervation control and validation. The finding that the AF-Nest (AFN) ablation eliminates the atropine response and decreases RR variability suggests that they are related to the vagal innervation. METHOD: Prospective, controlled, longitudinal, nonrandomized study enrolling 62 patients in 2 groups: AFN group (AFN group 32 patients) with functional or reflex bradyarrhythmias or vagal AF treated with AFN ablation and a control group (30 patients) with anomalous bundles, ventricular premature beats, atrial flutter, atrioventricular nodal reentry, and atrial tachycardia, treated with conventional ablation (non-AFN ablation). In AFN group, ablation delivered at AFN detected by fragmentation/fractionation of the endocardial electrograms and by 3-dimensional anatomic location of the ganglionated plexus. Vagal response was evaluated before, during, and postablation by 5 s noncontact vagal stimulation at the jugular foramen, through the internal jugular veins (extracardiac vagal stimulation [ECVS]), analyzing 15 s mean heart rate, longest RR, pauses, and atrioventricular block. All patients had current guidelines arrhythmia ablation indication. RESULTS: Preablation ECVS induced sinus pauses, asystole, and transient atrioventricular block in both groups showing a strong vagal response (P=0.96). Postablation ECVS in the AFN group showed complete abolishment of the cardiac vagal response in all cases (pre/postablation ECVS=P<0.0001), demonstrating robust vagal denervation. However, in the control group, vagal response remained practically unchanged postablation (P=0.35), showing that non-AFN ablation promotes no significant denervation. CONCLUSIONS: AFN ablation causes significant vagal denervation. Non-AFN ablation causes no significant vagal denervation. These results suggest that AFNs are intrinsically related to vagal innervation. ECVS was fundamental to stepwise vagal denervation validation during cardioneuroablation. Visual Overview A visual overview is available for this article.

In vivo positron emission tomography imaging of decreased parasympathetic innervation in the gut of vagotomized patients.

BACKGROUND: Parasympathetic neuropathy is a key feature in many common disorders, including diabetes, neurological disorders, and cancers, but few objective methods exist for assessing damage to the parasympathetic nervous system, particularly in the gastrointestinal system. This study aimed to validate the use of 11 C-donepezil positron emission tomography (PET) to assess parasympathetic integrity in a group of vagotomized patients. METHODS: Sixteen healthy controls and 12 patients, vagotomized due to esophagectomy, underwent 11 C-donepezil PET, measurement of colonic transit time, quantification of plasma pancreatic polypeptide (PP), and assessment of subjective long-term symptoms. KEY RESULTS: Vagotomized patients had significantly decreased PET signal in the small intestine and colon compared with healthy controls (5.7 [4.4-7.9] vs 7.4 [4.5-11.3], P = .01 and 1.4 [1.1-2.1] vs 1.6 [1.4-2.4], P < .01, respectively). Vagotomized patients also displayed a significantly increased colonic transit time (2.9 ± 0.9 h vs 1.9 ± 0.8 h), P < .01 and increased volumes of the small intestine and colon (715 ccm [544-1177] vs 443 ccm [307-613], P < .01 and 971 ccm [713-1389] vs 711 ccm [486-1394], P = .01, respectively). Patients and controls did not differ in PP ratio levels after sham feeding, but PP ratio at 10 minutes. after sham feeding and PET signal intensity in the small intestine was positively correlated (P = .03). CONCLUSIONS AND INFERENCES: We found significantly decreased 11 C-donepezil signal in the intestine of vagotomized patients, supporting that 11 C-donepezil PET is a valid measure of intestinal parasympathetic denervation.

Structural bases of gastrointestinal motility changes in parkinson's disease: study in rats / Bases estruturais das alterações da motilidade gastrintestinal na doença de parkinson: estudo em ratos

ABSTRACT Background: Gastrointestinal disorders are frequently reported in patients with Parkinson's disease whose disorders reduce the absorption of nutrients and drugs, worsening the clinical condition of patients. However, the mechanisms involved in modifying gastrointestinal pathophysiology have not yet been fully explained. Aim: To evaluate its effects on gastrointestinal motility and the involvement of the vagal and splanchnic pathways. Methods: Male Wistar rats (250-300 g, n = 84) were used and divided into two groups. Group I (6-OHDA) received an intrastriatal injection of 6-hydroxydopamine (21 µg/animal). Group II (control) received a saline solution (NaCl, 0.9%) under the same conditions. The study of gastric emptying, intestinal transit, gastric compliance and operations (vagotomy and splanchnotomy) were performed 14 days after inducing neurodegeneration. Test meal (phenol red 5% glucose) was used to assess the rate of gastric emptying and intestinal transit. Results: Parkinson's disease delayed gastric emptying and intestinal transit at all time periods studied; however, changes in gastric compliance were not observed. The delay in gastric emptying was reversed by pretreatment with vagotomy and splanchnotomy+celiac gangliectomy, thus suggesting the involvement of such pathways in the observed motor disorders. Conclusion: Parkinson's disease compromises gastric emptying, as well as intestinal transit, but does not alter gastric compliance. The delay in gastric emptying was reversed by truncal vagotomy, splanchnotomy and celiac ganglionectomy, suggesting the involvement of such pathways in delaying gastric emptying.

RESUMO Racional: Distúrbios gastrintestinais são frequentemente relatados em pacientes com doença de Parkinson cujos distúrbios reduzem a absorção de nutrientes e fármacos, agravando o quadro clínico dos pacientes. No entanto, os mecanismos envolvidos na alteração da fisiopatologia gastrintestinal ainda não foram totalmente elucidados. Objetivo: Avaliar os seus efeitos sobre a motilidade gastrintestinal e o envolvimento das vias vagal e esplâncnica. Métodos: Ratos Wistar machos (250-300 g, n=84) foram utilizados e divididos em dois grupos. O grupo I (6-OHDA) recebeu injeção intraestriatal de 6-hidroxidopamina (21 µg/animal). O grupo II (controle) recebeu solução salina (NaCl, 0,9%) nas mesmas condições. O estudo do esvaziamento gástrico, trânsito intestinal, complacência gástrica e operações (vagotomia e esplancnotomia) foram realizadas 14 dias após a indução da neurodegeneração. Refeição teste (vermelho de fenol+glicose 5%) foi utilizada para avaliar a taxa de esvaziamento gástrico e o trânsito intestinal. Resultados: A doença de Parkinson retardou o esvaziamento gástrico e o trânsito intestinal em todos os tempos estudados; porém, alterações da complacência gástrica não foram observadas. O retardo do esvaziamento gástrico foi revertido por pré-tratamento com vagotomia e esplancnotomia+gangliectomia celíaca, sugerindo assim, o envolvimento de tais vias nos distúrbios motores observados. Conclusão: A doença de Parkinson compromete o esvaziamento gástrico, bem como o trânsito intestinal, mas não altera a complacência gástrica. O retardo do esvaziamento gástrico foi revertido pela vagotomia troncular, esplancnotomia e gangliectomia celíaca, sugerindo o envolvimento de tais vias no retardo do esvaziamento gástrico.

Anterior subdiaphragmatic vagotomy decreases the IgA antibody response in the small intestines of BALB/c mice.

To assess the impact of vagotomy on the IgA-response, male BALB/c mice underwent anterior vagotomy or a sham procedure were sacrificed on day 14 post-operation and the proximal and distal small-gut segments were dissected. In intestinal lavages IgA/IgM antibodies were analysed by ELISA; in Peyer's-patches and lamina-propria cell suspensions the intracellular IgA-associated interleukins (ILs) and pro-inflammatory cytokines in CD4+ T cells were analysed by cytofluorometry. Vagotomy reduced the IgA or increased the IgM antibody concentration in both segments and reduced or increased the lamina- propria CD4+ T cell pro-inflammatory cytokine responses in the distal or proximal segments, respectively. Data show the role of the vagus nerve on the IgA response.

GLP-1 induces alpha cell proliferation and overrides leptin suppression induced by negative energy balance in vagotomized rats.

Glucagon-like peptide-1 (GLP-1) influences energy balance by exerting effects on food intake and glucose metabolism, through mechanisms that are partially dependent on the vagal pathway. The aim of this study was to characterize the effects of chronic GLP-1 stimulation on energy homeostasis and glucose metabolism in the absence of vagal innervation Truncal vagotomized (VGX) and sham operated rats (SHAM) received an intraperitoneal GLP-1 infusion (3.5 pmol/kg/min) trough mini-osmotic pumps. To dissect the effects derived from vagal denervation on food intake, an additional group was included consisting of sham operated rats that were PAIR FED to VGX. Food intake and body weight were recorded throughout the experimental period, while the percentage of white and brown adipose tissue, fasting glucose, insulin, gastro-intestinal hormonal profile, hypothalamic, and BAT gene expression were assessed at endpoint. VGX rats had significantly lower food intake, body weight gain, and leptin levels when compared with SHAM rats. Despite having similar body weight, PAIR-FED rats had lower fasting leptin, insulin and insulin resistance, while having higher ghrelin levels than VGX. GLP-1 infusion did not influence food intake or body weight, but was associated with lower leptin levels in VGX and lower pancreatic α-cells ki-67 staining in SHAM. Concluding, this study corroborates that the vagus nerve may modulate whole body energy homeostasis by acting in peripheral signals. Our data suggest that in the absence of vagal or parasympathetic tonus, GLP-1 mediated inhibition of cell proliferation markers in α-cells is prevented, meanwhile leptin suppression, associated with a negative energy balance, is partially overridden.

Pain-free survival after vagoglossopharyngeal complex sectioning with or without microvascular decompression in glossopharyngeal neuralgia.

OBJECTIVE: Glossopharyngeal neuralgia (GN) is a rare pain condition in which patients experience paroxysmal, lancinating throat pain. Multiple surgical approaches have been used to treat this condition, including microvascular decompression (MVD), and sectioning of cranial nerve (CN) IX and the upper rootlets of CN X, or a combination of the two. The aim of this study was to examine the long-term quality of life and pain-free survival after MVD and sectioning of the CN X/IX complex. METHODS: A combined retrospective chart review and a quality-of-life telephone survey were performed to collect demographic and long-term outcome data. Quality of life was assessed by means of a questionnaire based on a combination of the Barrow Neurological Institute pain intensity scoring criteria and the Brief Pain Inventory-Facial. Kaplan-Meier analysis was performed to determine pain-free survival. RESULTS: Of 18 patients with GN, 17 underwent sectioning of the CN IX/X complex alone or sectioning and MVD depending on the presence of a compressing vessel. Eleven of 17 patients had compression of CN IX/X by the posterior inferior cerebellar artery, 1 had compression by a vertebral artery, and 5 had no compression. One patient (6%) experienced no immediate pain relief. Fifteen (88%) of 17 patients were pain free at the last follow-up (mean 9.33 years, range 5.16-13 years). One patient (6%) experienced throat pain relapse at 3 months. The median pain-free survival was 7.5 years ± 10.6 months. Nine of 18 patients were contacted by telephone. Of the 17 patients who underwent sectioning of the CN IX/X complex, 13 (77%) patients had short-term complaints: dysphagia (n = 4), hoarseness (n = 4), ipsilateral hearing loss (n = 4), ipsilateral taste loss (n = 2), and dizziness (n = 2) at 2 weeks. Nine patients had persistent side effects at latest follow-up. Eight of 9 telephone respondents reported that they would have the surgery over again. CONCLUSIONS: Sectioning of the CN IX/X complex with or without MVD of the glossopharyngeal nerve is a safe and effective surgical therapy for GN with initial pain freedom in 94% of patients and an excellent long-term pain relief (mean 7.5 years).

Quantification of acute parasympathetic denervation during cryoballoon ablation by using extracardiac vagal stimulation.

AIMS: The purpose of this study was to systematically quantify the level of acute parasympathetic denervation in a stepwise fashion by means of extracardiac vagal stimulation (ECVS) by positioning a quadripolar catheter in the internal jugular vein, in a cohort of patients undergoing second-generation cryoballoon ablation for paroxysmal atrial fibrillation. METHODS: Fifty patients with symptomatic paroxysmal atrial fibrillation, having undergone extracardiac vagal stimulation before and after ablation by means of second-generation cryoballoon second-generation cryoballoon ablation, were included. RESULTS: The extracardiac vagal stimulation performed preablation provoked cardioinhibitory responses in all patients with mean pause duration of 10130.6 ± 3280.0 ms. At the end of the procedure, the VRs were significantly diminished with mean pause of 1687.5 ms ± 2183.7 ms (P = 0.00 compared with the pause before the procedure). CONCLUSION: The ECVS proved to be a reproducible, feasible and reliable method to quantify the degree of parasympathetic denervation during CB-A. In all patients, significant cardiac parasympathetic denervation could be observed at the end of the procedure. Responses to ECVS were more specific to quantify the vagal denervation than the increase in the heart rate. However larger studies are needed to confirm this observation.

A comparative study of subsequent liver cirrhosis risk in non-Helicobacter pylori-infected peptic ulcer patients with and without vagotomy: An Asian population cohort study.

OBJECTIVES: Hepatic parasympathetic nerves branch off the vagus nerve. The vagal and hepatic nervous systems are important in liver physiological processes and some diseases such as diabetes, obesity, and liver cirrhosis. We were interested in vagal nerve integrity and subsequent diseases in peptic ulcer patients. Herein, we used National Health Insurance database in Taiwan and retrospectively assessed the risk of developing liver cirrhosis in peptic ulcer patients with and without complications by surgical treatments. METHODS: A cohort of 357 423 peptic ulcer patients without Helicobacter pylori, hepatitis B/C virus infection, and alcoholism from 2001 to 2008 was established. A randomly selected cohort of 357 423 people without peptic ulcer that matched by age, gender, comorbidities, and index year was used for comparison. The risks of developing liver cirrhosis were assessed both in cohorts and in peptic ulcer patients with and without vagotomy at the end of 2011. RESULTS: Peptic ulcer patients were with higher incidence of liver cirrhosis than those without peptic ulcer (2.63 vs 0.96 per 1000 person-years) and with a 2.79-fold adjusted hazard ratio (HR) (95% confidence interval = 2.66-2.93) based on the multivariable Cox proportional hazards regression analysis. Comparing with different peptic ulcer management strategies, the HR value for subsequent liver cirrhosis risk was the lowest in vagotomy group (HR = 0.46, 95% confidence interval = 0.33-0.64). CONCLUSIONS: Peptic ulcer patients have an increased risk of developing liver cirrhosis. Moreover, there were association of vagotomy and decreased risk of subsequent liver cirrhosis in complicated peptic ulcer patients. However, further studies are warranted.

Does vagotomy protect against multiple sclerosis?

OBJECTIVES: To examine the association between vagotomy and multiple sclerosis. METHODS: We conducted a matched cohort study of all patients who underwent truncal or super-selective vagotomy and a comparison cohort, by linking Danish population-based medical registries (1977-1995). Hazard ratios (HRs) for multiple sclerosis, adjusting for potential confounders were computed by means of Cox regression analysis. RESULTS: Median age of multiple sclerosis onset corresponded to late onset multiple sclerosis. No association with multiple sclerosis was observed for truncal vagotomy (0-37 year adjusted HR=0.91, 95% confidence interval [CI]: 0.48-1.74) or super-selective vagotomy (0-37 year adjusted HR=1.28, 95% CI: 0.79-2.09) compared with the general population. INTERPRETATION: We found no association between vagotomy and later risk of late onset multiple sclerosis.

Influences of Vagotomy on Gut Ischemia-Reperfusion Injury in Mice.

BACKGROUND: How vagotomy affects host responses to gut ischemia-reperfusion (I/R) is unclear. MATERIALS AND METHODS: Experiment 1: male Institute of Cancer Research mice (n = 22) were assigned to the I/R or the vago-I/R group. The I/R mice underwent 45-min superior mesenteric artery (SMA) occlusion. The vago-I/R mice received vagotomy before SMA occlusion. Survival was observed for 48 h.Experiment 2: mice (n = 55) were divided into four groups (Sham, vago, I/R, vago-I/R). Sham and vago groups did not undergo gut I/R. Mice were killed at 3 or 6 h after reperfusion, and cytokine levels in the plasma, jejunum, and ileum were evaluated. In addition, gut histology at 6 h was examined.Experiment 3: mice (n = 24) were divided into four groups as in Experiment 2. The small intestine was harvested at 3 h after reperfusion and the tissue was cultured ex vivo for 3 h. Cytokine levels of the culture supernatant were then measured. RESULTS: Experiment 1: survival was significantly worse with vago-I/R than I/R.Experiment 2: along with severe gut injury, vago-I/R increased IL-6 and monocyte chemoattractant protein-1 (MCP-1) in plasma, IFN-γ in the jejunum and MCP-1 in the ileum, as compared with I/R. Significant positive correlations were noted between plasma and intestinal levels of pro-inflammatory cytokines (IL-6, MCP-1, and TNF-α).Experiment 3: MCP-1 in the jejunal culture medium was higher in the vago-I/R than in the I/R group. CONCLUSIONS: Vagotomy worsens survival after gut I/R, together with increases in pro-inflammatory cytokines in both plasma and the gut in association with severe intestinal tissue damage.

Vagotomy and subsequent development of diabetes - A nested case-control study.

BACKGROUND: Vagal signaling is involved in gastric emptying and the secretion and effect of a number of hormones regulating gluco-metabolic processes and, thus, crucial for metabolic homeostasis. PURPOSE: We hypothesized that vagotomy would increase the risk of developing type 2 diabetes and examined the association between vagotomy and subsequent development of diabetes. METHODS: A nested case-control study was conducted with information on cases and controls from the Danish National Patient Registry. Cases included individuals with a diabetes diagnosis subsequent (>12months) to the first registration of vagotomy and/or upper gastrointestinal disease in the period 1977-2011. Controls had no subsequent diagnosis of diabetes and were matched by incidence density sampling, age and gender. Logistic regression analyses were conducted. RESULTS: 501,724 diabetes patients and 1,375,567 matched controls were included in the analysis. Vagotomy was performed on 2772 individuals and 148,489 individuals had an upper gastrointestinal diagnosis. In this combined population, 30,902 were diagnosed with diabetes. The mean follow-up was 16years. The unadjusted odds ratio for developing diabetes following vagotomy was 0.64 (95% confidence interval (CI): 0.58-0.71) and did not change in an adjusted analysis (0.64, 95% CI: 0.58-0.70). When restricting the multivariate-adjusted analysis to patients with type 2 diabetes and type 1 diabetes, respectively, the multivariate odds ratios were 0.79 (95% CI: 0.70-0.89) and 0.75 (95% CI 0.53-1.08), respectively. CONCLUSION: Vagotomy was associated with a significantly decreased risk of developing type 2 diabetes in a population of patients with upper gastrointestinal disease.

Perturbations of Respiratory Rhythm and Pattern by Disrupting Synaptic Inhibition within Pre-Bötzinger and Bötzinger Complexes.

The pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes are the brainstem compartments containing interneurons considered to be critically involved in generating respiratory rhythm and motor pattern in mammals. Current models postulate that both generation of the rhythm and coordination of the inspiratory-expiratory pattern involve inhibitory synaptic interactions within and between these regions. Both regions contain glycinergic and GABAergic neurons, and rhythmically active neurons in these regions receive appropriately coordinated phasic inhibition necessary for generation of the normal three-phase respiratory pattern. However, recent experiments attempting to disrupt glycinergic and GABAergic postsynaptic inhibition in the pre-BötC and BötC in adult rats in vivo have questioned the critical role of synaptic inhibition in these regions, as well as the importance of the BötC, which contradicts previous physiological and pharmacological studies. To further evaluate the roles of synaptic inhibition and the BötC, we bilaterally microinjected the GABAA receptor antagonist gabazine and glycinergic receptor antagonist strychnine into the pre-BötC or BötC in anesthetized adult rats in vivo and in perfused in situ brainstem-spinal cord preparations from juvenile rats. Muscimol was microinjected to suppress neuronal activity in the pre-BötC or BötC. In both preparations, disrupting inhibition within pre-BötC or BötC caused major site-specific perturbations of the rhythm and disrupted the three-phase motor pattern, in some experiments terminating rhythmic motor output. Suppressing BötC activity also potently disturbed the rhythm and motor pattern. We conclude that inhibitory circuit interactions within and between the pre-BötC and BötC critically regulate rhythmogenesis and are required for normal respiratory motor pattern generation.

Effect of Vagus Nerve Injury on the Outcome of Antireflux Surgery: An Extensive Literature Review.

BACKGROUND: Vagus nerve injury (VNI) is a feared complication of antireflux surgery (ARS). The impact of VNI on the functional outcomes of ARS has not yet been evaluated systematically. The aim of this review was to evaluate the impact of VNI on functional and clinical outcome of ARS. METHODS: A systematic search was performed until March 2015, using the following online databases: MEDLINE, Embase and the Cochrane Register of Controlled Clinical Trials. Eight studies remained available for assessment. Articles were divided into 2 groups: (a) one with unintended, accidental VNI and (b) one group comparing ARS with and without intended vagotomy. RESULTS: The prevalence of unintended, accidental VNI ranged from 10 to 42% after ARS. No clear differences were seen in outcome for reflux control between the VNI and vagus nerve intact group. A higher prevalence of diarrhea, nausea and vomiting was observed in the VNI group. CONCLUSION: VNI is a feared but neglected complication of ARS. Larger prospective studies that objectively assess vagus nerve integrity before and after ARS are needed.