Rates of Recurrent Marginal Ulcer in Gastric Bypass Patients Undergoing Revisional Surgery.

INTRODUCTION: The rate of marginal ulcer (MU) following primary Roux-en-Y Gastric Bypass (RYGB) is approximately .6-16%. Few studies have evaluated recurrence rates following surgical revision for MU. The primary aim of this study was to determine the rate of MU recurrence following revision. The secondary aim was to evaluate the impact of truncal vagotomy (TV) on the recurrence rates and analyze potential risk factors associated with the recurrence of MU after revision. METHODS: We conducted a retrospective cohort study examining data at a single tertiary academic medical center. Adult patients with a history of RYGB who underwent gastrojejunostomy revision for recurrent MU between the years of 2003-2020 were included. We sought to determine our overall rate of MU following revision, with and without TV. Additionally, we examined the association of risk factors with MU recurrence. Fisher's exact test was used to determine the statistical significance of recurrence rates between the groups. RESULTS: We included 90 patients in the study. The overall recurrence rate for MU was 16.7%. Of the 90 patients, 35 (35.4%) patients underwent TV at the time of revision. The recurrence rate of MU after GJ revision with TV was 14.3% in comparison to those without TV, 18.2% (P = .775). Smoking, steroid, alcohol use, history of cardiac surgery/intervention, and helicobacter pylori were not significantly associated with recurrent MU following revision. CONCLUSIONS: The rate of recurrence after revision for MU is high. Adding TV trended towards decreased MU recurrence after revisional surgery, however not significant. Larger studies are needed to evaluate risk factors associated with recurrent MU after revision.

Video- and Robotic-Assisted Thoracoscopic Truncal Vagotomy.

A subset of patients with marginal ulcers after Roux-en-Y gastric bypass (RNYGB) is refractory to medical management. Here we report a retrospective review of a single institution cohort (N = 10) of video- or robotic-assisted thoracoscopic (VATS or RATS) truncal vagotomies performed between 2013 and 2018. All patients had recurrent marginal ulcers following RNYGB complicated by bleeding or perforation, refractory to medical management for a median of 3.5 months prior to undergoing truncal vagotomy. With a median of 23 months' follow-up, only three patients had continued symptoms (70% symptom resolution) post-operatively. Only one patient who had repeat endoscopy after the procedure had documented endoscopic evidence of recurrent marginal ulcer (83% endoscopic resolution). VATS or RATS truncal vagotomy is a safe and effective method to treat complicated marginal ulceration after RNYGB. After an average duration of unsuccessful medical treatment lasting three months, vagotomy led to successful resolution in 70-83% of patients.

Metabolic effects of truncal vagotomy when combined with bariatric-metabolic surgery.

Bariatric-metabolic surgery (BMS) in patients with obesity frequently leads to remission of concurrent type 2 diabetes mellitus (T2DM), even before body weight loss takes place. This is probably based on the correction of a dysmetabolic cycle in the gastrointestinal physiology of T2DM that includes increased vagus-dependent exocrine pancreatic secretion (EPS) and, hence, amplified digestion and nutrient absorption. The resultant chronic exposure of tissues to high plasma levels of glucose, fatty acids and amino acids causes tissue resistance to the actions of insulin and, at a later stage, ß-cell dysfunction and reduction of insulin release. We hypothesize that the addition of a surgical truncal vagotomy (TV) may improve and solidify the beneficial results of BMS on T2DM by stably decreasing EPS, - hence reducing the digestion and absorption of nutrients -, and increasing incretin secretion as a result of increased delivery of unabsorbed nutrients to the distal intestine. This hypothesis is supported by surgical data from gastrointestinal malignancies and peptic ulcer operations that include TV, as well as by vagal blockade studies. We suggest that TV may result in a stable reduction of EPS, and that its combination with the appropriate type of BΜS, may enhance and sustain the salutary effects of the latter on T2DM.

The Genus Parabacteroides Is a Potential Contributor to the Beneficial Effects of Truncal Vagotomy-Related Bariatric Surgery.

PURPOSE: Evidences about the gut microbiota role in weight loss after bariatric surgery (BS) are growing. The objective of this study was to observe the changes of gut microbiota after sleeve gastrectomy (SG) and SG plus truncal vagotomy (SG-TV) and identify specific microbes that may contribute to the improvement of obesity after surgeries. MATERIALS AND METHODS: Forty high-fat diet-induced obesity (DIO) mice were randomized to SG, SG-TV, or sham operation (SH) groups. Body weight (BW) and fast blood glucose (FBG) were measured before and 1, 2, 4, 8, and 12 weeks post-operatively. Fecal samples were collected before and at post-operative week 12 and profiled using 16S rRNA relative and absolute quantitative sequencing. RESULTS: After the surgery, the SG and SG-TV surgeries significantly reduce BW and FBG levels compared with SH, and the SG-TV achieved better effects than SG. A decreasing trend in alpha diversity of gut microbiota and significant changes in taxonomic composition were observed after surgeries. Then, we identified a set of microbes and pathways significantly different in abundance after BS. The genus Parabacteroides and one pathway (polyketide sugar unit biosynthesis) increased in SG-TV group specially, which was also negatively correlated with BW and FBG. CONCLUSION: SG and SG-TV indeed achieve effects of weight loss, but TV could enhance the efficacy of SG. The identified different microbes and pathways, like Parabacteroides, polyketide sugar unit biosynthesis, may partly mediate the beneficial effects of BS, and thus possibly contribute to the development of novel bacteria-based therapeutic approaches.

Short term effects of experimental gastric outlet obstruction and truncal vagotomy on gut hormones.

Gastric outlet obstruction (GOO) is caused mainly by pyloric or duodenal blockage; gastric surgery and vagotomy are effective treatments. We investigated the short term effects of experimental GOO and truncal vagotomy (TV) on gut hormone levels. We used 8-week-old male Wistar rats divided randomly into four groups: control, GOO, TV, and GOO + TV. At the end of the experiment, blood and tissue samples of the pylorus and fundus were obtained for biochemical and immunohistochemical analysis. Gastric motility decreased in the TV group, but there was no difference in food intake compared to the control group; water consumption and urine output were increased. Feces excretion and food intake decreased due to loss of food movement from the stomach of GOO and GOO + TV rats. Levels of insulin and ghrelin were lower than for the control group, but levels of cholecystokinin were higher. Leptin and glucagon-like peptide 1 levels were increased in the GOO group, while somatostatin was decreased. Leptin immunostaining levels were decreased in the GOO + TV group. Gastrin and neuropeptide Y levels were lower in the GOO and GOO + TV groups compared to the other groups. We found that both gut hormone levels related to gastric motility and metabolism, and immunohistochemical staining of the stomach tissue were altered by TV and GOO. Measuring changes in gut hormones following gastric surgery could be useful for monitoring the effectiveness of treatment.

Neurotensin secretion after Roux-en-Y gastric bypass, sleeve gastrectomy, and truncal vagotomy with pyloroplasty.

OBJECTIVE: Neurotensin (NT) is released from enteroendocrine cells and lowers food intake in rodents. We evaluated postprandial NT secretion in humans after surgeries associated with accelerated small intestinal nutrient delivery, and after Roux-en-Y gastric bypass (RYGB) when glucagon-like peptide-1 (GLP-1) signalling and dipeptidyl peptidase 4 (DPP-4) were inhibited, and during pharmacological treatments influencing entero-pancreatic functions. METHODS: We measured NT concentrations in plasma from meal studies: (I) after truncal vagotomy with pyloroplasty (TVP), cardia resection +TVP (CTVP), and matched controls (n = 10); (II) after RYGB, sleeve gastrectomy (SG), and in matched controls (n = 12); (III) after RYGB (n = 11) with antagonism of GLP-1 signalling using exendin(9-39) and DPP-4 inhibition using sitagliptin; (IV) after RYGB (n = 11) during a run-in period and subsequent treatment with, sitagliptin, liraglutide (GLP-1 receptor agonist), verapamil (calcium antagonist), acarbose (alpha glucosidase inhibitor), and pasireotide (somatostatin analogue), respectively. RESULTS: (I) NT secretion was similar after TVP/CTVP (p = 0.9), but increased vs. controls (p < 0.0001). (II) NT secretion was increased after RYGB vs. SG and controls (p < 0.0001). NT responses were similar in SG and controls (p = 0.3), but early postprandial NT concentrations were higher after SG (p < 0.05). (III) Exendin (9-39) and sitagliptin did not change NT responses vs placebo (p > 0.2), but responses were lower during sitagliptin vs. exendin(9-39) (p = 0.03). (IV) Pasireotide suppressed NT secretion (p = 0.004). Sitagliptin tended to lower NT secretion (p = 0.08). Liraglutide, verapamil, and acarbose had no effect (p > 0.9). CONCLUSION: Neurotensin secretion is increased after surgeries associated with accelerated gastric emptying and lowered by pasireotide.

Decreased risk of liver and intrahepatic cancer in non-H. pylori-infected perforated peptic ulcer patients with truncal vagotomy: a nationwide study.

The vagal nervous system is central to the physiological responses and systemic diseases of the liver. We evaluated the subsequent risk of liver and intrahepatic cancer (HCC/ICC) in non-H. pylori (HP)-infected perforated peptic ulcer (PPU) patients with and without vagotomy. Hospitalized PPU patients who underwent simple closure or truncal vagotomy/pyloroplasty (TVP) in the National Health Insurance Research Database from 2000 to 2008 were enrolled. The exclusion criteria included: (1) Multiple surgeries for PPU were received at the same admission; (2) Any cancer history; (3) Previous peptic ulcer-associated surgery; (4) HP infection history; (5) Viral hepatitis infection history; (6) Follow-up duration < 1 year; and (7) Age < 18 years. The risks of developing HCC/ICC in PPU patients with and without vagotomy were assessed at the end of 2013. To balance the baseline condition between groups, we used the propensity score matched method to select study subjects. Cox proportional hazard regression was used to estimate the hazard ratio and 95% confidence interval (CI) of HCC/ICC. Before propensity score matching, 675 simple suture patients and 54 TVP patients had HCC/ICC, which corresponded to incidences of 2.11 and 0.88 per 1000 person-years, respectively. After propensity score matching, 145 simple suture patients and 54 TVP patients experienced HCC/ICC, which corresponded to incidences of 1.45 and 0.88 per 1000 person-years, respectively. The TVP patients had a 0.71 (95% CI 0.54-0.95)- and 0.69 (95% CI 0.49-0.97)-fold risk of developing HCC/ICC compared to simple suture patients before and after propensity score matching. Our findings reported that, in the Asian population, TVP decreases the risk of HCC/ICC in non-HP-infected PPU patients compared to simple closure patients. However, further studies are warranted.

S043 mythbuster: truncal vagotomy and gastric drainage procedures.

INTRODUCTION: You are sitting for your oral surgery board exam and the examiner asks what you do when you realize that you have accidentally cut the posterior vagus nerve during a hiatal hernia repair. Is the answer to proceed with a gastric drainage procedure correct? The prevailing dogma seems to be that inadvertent vagotomy will produce gastric stasis/paresis and the stomach will not empty and hence should be accompanied by a gastric drainage procedure. This report presents clinical outcomes of 49 patients who underwent truncal vagotomy without a drainage procedure (pyloroplasty or gastrojejunostomy). METHODS: 49 patients underwent truncal vagotomy with laparoscopic adjustable gastric banding in an IRB (Investigational Review Board)-approved clinical trial to determine if the addition of a vagotomy would increase achieved weight loss when compared to gastric banding alone. The details of this trial were presented at SAGES (Martin and Earle in Surg Endosc 25:2522-2525, 2011) in 2010. The patients in this study have been followed for over ten years and their histories were examined to look for evidence of gastric stasis or intractable diarrhea or if they required further surgery for these complaints. RESULTS: 49 patients have been followed for a mean of 10.9 years. All except one have experienced a loss of hunger and cessation of gastric borborygmus. One patient showed mild delayed gastric emptying after developing diabetes. Two other patients with DM carry a diagnosis of gastroparesis. No patient has experienced intractable diarrhea. Five patients have had revisions to sleeve gastrectomy or gastric bypass for weight loss failure or esophageal dilatation and GERD. CONCLUSIONS: Review of these truncal vagotomy patients without drainage procedures at 10 years does not support the myth that the stomach will not empty after vagotomy and a gastric drainage procedure should always accompany truncal vagotomy.

Increased risk of subsequent benign prostatic hyperplasia in non-Helicobacter pylori-infected peptic ulcer patients: a population-based cohort study.

The vagus nerve plays an essential role in homeostasis and inflammation. Clinically, peptic ulcer patients without helicobacter pylori (HP) infection may provide a population for studying the effect of vagal hyperactivity. There were interests in the association of gastrointestinal disease and urogenital disorders. Herein, we try to investigate subsequent risk of benign prostatic hyperplasia (BPH) in non-HP infected peptic ulcer patients. We identified 17,672 peptic ulcer admission male patients newly diagnosed in 1998-2007 from Taiwan Health Insurance Database, and 17,672 male comparison without peptic ulcer, frequency matched by age, and index-year. We assessed subsequent incidence of BPH in each cohort by the end of 2013, and then compared the risk of developing BPH between individuals with and without peptic ulcer. In addition, peptic ulcer patients underwent surgery were also examined. There were 2954 peptic ulcer patients and 2291 comparisons noted with the occurrence of BPH (25.35 and 16.70 per 1000 person-years, respectively). Compared to comparisons, peptic ulcer patients had a 1.45- and 1.26-fold BPH risk in multivariable Cox model and Fine and Gray model (95% CI 1.37-1.54 and 1.19-1.34). In age-stratified analysis, the highest risk of BPH was in 45-59 years (interaction p < 0.05). Regarding surgery types, peptic ulcer patients who underwent simple suture surgery (i.e.: with integrated vagus nerve) had a significant higher BPH risk than comparison (HR 1.50 and 95% CI 1.33-1.74; SHR 1.26 and 95% CI 1.07-1.48), while patients underwent truncal vagotomy/pyloroplasty showed a lower incidence of BPH. In this study, non-HP-infected male peptic ulcer patients were found to have an increased risk of subsequent BPH. Indicating that there might be a role of vagus nerve. Based on the limitations of retrospective nature, further studies are required.

Percutaneous CT-Guided Cryovagotomy.

There are a number of pathologic conditions in the human body that may be modified by the interruption of neural signaling, both related to pain and otherwise. Many of these treatments currently involve implantable neuromodulation or frank surgical neural ligation, representing opportunities for the implementation of percutaneous device-mediated cryoneurolysis in interventional radiology. Computed tomography-guided cryovagotomy for the management of mild to moderate obesity represents one such opportunity currently under investigation. This procedure is designed to attenuate hunger signals by targeting the posterior vagal trunk using computed tomography for cryoablation with a needle, based on historical surgical and electrical vagotomy experience. Future investigations of this technique and others will expand and iterate the concept of percutaneous, image-guided cryoneurolysis as potential management for a wide variety of clinical challenges.

Thoracoscopic truncal vagotomy versus surgical revision of the gastrojejunal anastomosis for recalcitrant marginal ulcers.

INTRODUCTION: Marginal ulcer is a common complication following Roux-en-Y gastric bypass with incidence rates between 1 and 16%. Most marginal ulcers resolve with medical management and lifestyle changes, but in the rare case of a non-healing marginal ulcer there are few treatment options. Revision of the gastrojejunal (GJ) anastomosis carries significant morbidity with complication rates ranging from 10 to 50%. Thoracoscopic truncal vagotomy (TTV) may be a safer alternative with decreased operative times. The purpose of this study is to evaluate the safety and effectiveness of TTV in comparison to GJ revision for treatment of recalcitrant marginal ulcers. METHODS: A retrospective chart review of patients who required surgical intervention for non-healing marginal ulcers was performed from 1 September 2012 to 1 September 2017. All underwent medical therapy along with lifestyle changes prior to intervention and had preoperative EGD that demonstrated a recalcitrant marginal ulcer. Revision of the GJ anastomosis or TTV was performed. Data collected included operative time, ulcer recurrence, morbidity rate, and mortality rate. RESULTS: Twenty patients were identified who underwent either GJ revision (n = 13) or TTV (n = 7). There were no 30-day mortalities in either group. Mean operative time was significantly lower in the TTV group in comparison to GJ revision (95.7 ± 16 vs. 227.5 ± 89 min, respectively, p = 0.0022). Recurrence of ulcer was not significant between groups and occurred following two GJ revisions (15%) and one TTV (14%). Complication rates were not significantly different with 62% in the GJ revision group and 57% in the TTV group. Approximately 38% (5/13) of GJ revisions and 28% (2/7) of TTV patients experienced complications with Clavien-Dindo scores > 3. There was no difference in postoperative symptoms between both groups. CONCLUSIONS: Our results demonstrate that thoracoscopic vagotomy may be a better alternative with decreased operative times and similar effectiveness. However, further prospective observational studies with a larger patient population would be beneficial to evaluate complication rates and ulcer recurrence rates between groups.

MALT Lymphoma, Stress Ulcer and Cholinergic Nerves from the Viewpoint of Bilateral and Unilateral Truncal Vagotomy and Substance P.

BACKGROUND: Vagal nerve plays an important role in the stomach function. The cholinergic nerves are the most abundantly distributed nerves in the gastric tissue. It has recently been reported that the vagal nerve is significantly related to both gastric cancer development and progression. However, its relation to the mesenchymal tumor, including MALT lymphoma, is not known. In this study, we investigated the effect of unilateral truncal vagotomy on gastric MALT lymphoma development by using Helicobacter heilmannii-infected mouse model as well as that of bilateral truncal vagotomy on stress-induced ulcer formation. METHODS: In the first part of this study, the distribution of the cholinergic nerves in the rat gastric mucosa and the effect of bilateral truncal vagotomy, as well as various kinds of agents acting on autonomic nerves in rats, were investigated by the histochemical and macroscopic method. In the second part, we employed MALT lymphoma formation in C57BL/6NCrl mice that were infected with Helicobacter heilmannii. A total of 38 infected mice underwent unilateral vagotomy under microscopy. The mice were randomized into 4 groups from which samples were collected; 2, 3, 4 and 6 months after infection. Both the anterior and posterior sides of the stomachs were sampled from each mouse for pathological and immunohistochemical analyses. RESULTS: The bilateral truncal vagotomy significantly suppressed the restraint-induced gastric ulcer formation in rats, while bethanechol, and 6-hydroxydopamine led to an increase of the gastric ulcer formation. In the unilateral truncal vagotomy study using MALT lymphoma, the thickness of the gastric mucosa was reduced in the vagotomized side compared to the non-vagotomized side. Furthermore, the gastric MALT lymphoma was more prominently found in the vagotomized anterior side of stomach compared with that in the non-vagotomized posterior side of stomach. Substance P-immunoreactive nerves markedly increased surrounding the MALT lymphoma and the neurokinin-1 receptor immunoreactive lymphocytes increased within the MALT lymphoma in the vagotomized side. In conclusion, vagotomy enhanced gastric MALT lymphoma development possibly through the substance P-neurokinin-1 receptor pathway.

Subdiaphragmatic vagotomy promotes tumor growth and reduces survival via TNFα in a murine pancreatic cancer model.

This study analyses the effects of vagotomy on tumor growth and survival in a murine, pancreatic cancer model in wild-type and TNFα-knockout (-/-) mice.Throughout many operative procedures in the upper gastrointestinal tract the partial or complete transection of the vagus nerve or its local nerve fibers is unavoidable. Thereby its anti-inflammatory effects in residual tumor tissue may get lost. This effect may be mediated by tumor-associated macrophages (TAM) secreting TNFα.In an orthotopic murine pancreatic cancer model subdiaphragmatic vagotomy versus sham surgery was performed. The impact on tumor growth was monitored in wild type and TNFα -/- mice using MRI. TAMs as well as expression levels of TNFα were analyzed using immunohistochemistry. The role of TNFα on tumor growth and migration was examined in vitro. Vagotomised mice showed increased tumor growth with macroscopic features of invasive growth and had a shorter survival time. The loss of vagal modulation led to significantly increased TNFα levels in tumors and considerably elevated numbers of TAMs. In vitro TNFα significantly stimulated growth (p < 0.05) and migration (p < 0.05) of pancreatic cancer cells. TNFα -/- mice survived significantly longer after tumor implantation (p < 0.05), with vagotomy not affecting the prognosis of these animals (p > 0.05).Vagotomy can increase tumor growth and worsen survival in a murine pancreatic cancer model mediated through TAMs and TNFα. Hence, the suppression of TAMs and the modulation of TNFα dependent pathways could offer new perspectives in immunotherapies of pancreatic cancer patients especially with remaining vital tumor cells and lost vagal modulation.

Revision using totally hand-sewn gastrojejunostomy and truncal vagotomy for refractory marginal ulcer after laparoscopic Roux-en-y gastric bypass: a case series.

BACKGROUND: Marginal ulcer (MU) is not infrequent after laparoscopic Roux-en-Y gastric bypass (LRYGB). Medication plus lifestyle modification remains the mainstay solution. Patients with refractory MU may be candidates for revisional surgery. OBJECTIVE: To summarize our experience of revisional surgery for treating refractory MU after LRYGB. SETTING: University hospital, Taiwan. METHODS: A retrospective analysis was performed for 11 patients with refractory MU undergoing totally hand-sewn gastrojejunostomy and truncal vagotomy at our institution between August 2005 and May 2015. The mean follow-up after surgery was 28.0±16.2 months (range, 10-48 mo); 9 patients (81.8%) were followed up more than 1 year after. RESULTS: The mean age of the cohort (7 males; 4 females) was 39.5±16.0 years (range, 19-66 yr), with a mean initial body mass index of 37.5±9.3 kg/m2 (range, 32.1-57 kg/m2). Intractability was the dominant manifestation (100%); 8 patients (72%) had stricture at the gastrojejunostomy. The mean interval from initial LRYGB to refractory MU and revisional surgery was 10.2±7.7 months (range, 4-28 mo) and 38.7±21.6 months (range, 10-67 mo), respectively. The average operation time was 150.4±59.8 minutes (range, 80-300 min), and the average length of hospital stay was 4.2±1.4 days (range, 2-7 d). The 9 patients with more than 1 year follow-up all achieved endoscopic resolution of the refractory MU. CONCLUSIONS: Although longer follow-up is warranted, revisional surgery with totally hand-sewn gastrojejunostomy and truncal vagotomy can be an effective solution for refractory MU.

Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer.

CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) expand in the spleen during cancer and promote progression through suppression of cytotoxic T cells. An anti-inflammatory reflex arc involving the vagus nerve and memory T cells is necessary for resolution of acute inflammation. Failure of this neural circuit could promote procarcinogenic inflammation and altered tumour immunity. Here we show that splenic TFF2, a secreted anti-inflammatory peptide, is released by vagally modulated memory T cells to suppress the expansion of MDSCs through CXCR4. Splenic denervation interrupts the anti-inflammatory neural arc, resulting in the expansion of MDSCs and colorectal cancer. Deletion of Tff2 recapitulates splenic denervation to promote carcinogenesis. Colorectal carcinogenesis could be suppressed through transgenic overexpression of TFF2, adenoviral transfer of TFF2 or transplantation of TFF2-expressing bone marrow. TFF2 is important to the anti-inflammatory reflex arc and plays an essential role in arresting MDSC proliferation. TFF2 offers a potential approach to prevent and to treat cancer.