Impact of body mass index on minimally invasive ventral hernia repair: an ACS-NSQIP analysis.

PURPOSE: Body mass index (BMI) ≥ 35 kg/m2 is a known independent risk factor for complications following open ventral hernia repair (VHR). We sought to examine the relationship between BMI and minimally invasive VHR. METHODS: The ACS-NSQIP database was queried for all patients age ≥ 18 years undergoing minimally invasive VHR (2005-2015). Patients were stratified into seven BMI classes: underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (25-29.9), obese (30-34.5), severely obese (35-39.9), morbidly obese (40-49.9), and super obese (BMI ≥ 50), as well as by hernia type (reducible vs. strangulated) and time of repair (initial vs. recurrent). Multivariate logistic regression was employed to assess the risk of complication by BMI class. RESULTS: A total of 55,180 patients met inclusion criteria, and 61.4% had a BMI > 30 kg/m2. When stratified by BMI class, we found significant differences in age, gender, race, comorbidities, and pre-operative characteristics across groups. The overall complication rate was 4.0%, ranging from 3.0% for normal BMI patients, to 6.9% for patients with a BMI ≥ 50 kg/m2. Recurrent repairs and strangulated hernias both demonstrated higher complication rates. All complications (surgical and medical) were significantly associated with BMI class after adjustment (p < 0.0001). Patients with a BMI ≥ 50 kg/m2 had a 1.4 times greater risk for complications than patients with normal BMIs (18-24.9 kg/m2, p = 0.01). CONCLUSION: BMI ≥ 50 kg/m2 was determined to be an independent risk factor for surgical and medical complications after minimally invasive VHR.

Lymph node evaluation and survival after curative-intent resection of duodenal adenocarcinoma: A matched cohort study.

BACKGROUND: Lymph node (LN) metastasis in patients with duodenal adenocarcinoma is associated with poor prognosis; however, the optimal extent of LN assessment and the interaction between LN assessment and adjuvant systemic therapy is poorly understood. METHODS: Resected non-metastatic duodenal adenocarcinoma patients (n = 1743) were identified in the National Cancer Database (1998-2011). Logistic regression analysis identified covariates associated with LN metastasis. The influence of increasing LN cut-off points on overall survival (OS) was analysed using the log-rank test and Cox proportional hazards modelling. Adjuvant chemotherapy (AC) and surgery alone cohorts were matched (1:1) by propensity scores based on the likelihood of nodal metastasis or survival hazard on Cox modelling. OS in the matched cohort was compared by Kaplan-Meier estimates. RESULTS: LN metastases were present in 865 (49.6%) patients. Increasing LN assessment was associated with an increased likelihood of nodal involvement (P = 0.008). In node-negative patients, increasing LN assessment was associated with a decreased risk of death, with the largest actuarial survival differences observed for ≥15 LN (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.48-0.82, P = 0.001). In the propensity score-matched cohort of node-negative patients, AC was associated with non-significant improvements in 5-year actuarial (66.1% versus 58.7%, HR 0.79, 95% CI 0.53-1.18, P = 0.249), and did not vary by adequacy of LN counts (<15 LNs: HR 0.79, 95% CI 0.51-1.24, P = 0.305; ≥15 LNs: HR 0.90, 95% CI 0.35-2.30, P = 0.900). CONCLUSIONS: The extent of LN identification has prognostic significance in resected node-negative duodenal adenocarcinoma, but cannot be implicated in the selection of node-negative patients for AC.

Re-examining the BMI threshold for bariatric surgery in the USA.

BACKGROUND: The optimal BMI threshold above which gastric bypass surgery should be offered to obese patients is controversial. The objective of this study was to compare the impact of Roux-en-Y gastric bypass (RYGB) vs. diet and exercise (D&E) on life expectancy to find the BMI at which patients experience an improvement in their life expectancy by undergoing surgery. METHODS: A Markov state transition model was designed to implement a decision tree that simulated the lives of obese patients. Life expectancies following RYGB and 2 years of D&E were estimated and compared. Ten thousand patients' lives were simulated in each weight-loss intervention group in the model. In addition to base case analysis (45 kg/m(2) BMI pre-intervention), sensitivity analysis of initial BMI at the start of the study was completed. Markov model parameters were extracted from the literature. RESULTS: The impact of RYGB on survival relative to D&E depended on the patient's initial BMI. Compared to patients who underwent 2 years of "optimal" diet and exercise (7 % total body weight loss/year), RYGB improved long-term survival for patients above a BMI of 31.3 kg/m(2). CONCLUSIONS: Roux-en-Y gastric bypass can improve long-term survival for patients with class I obesity. This study suggests that RYGB should not be reserved solely for patients with class II or III obesity.

Trends and perioperative outcomes of inpatient antireflux surgery in the United States, 1993-2006.

Antireflux surgery is an effective treatment for gastroesophageal reflux disease, but postoperation complications and durability may be problematic. The objective of the study was to determine whether inpatient antireflux surgery continued to decline in the United States due to concerns about its long-term effectiveness and the popularity of gastric bypass surgery and to assess recent changes in its perioperative outcomes. Using the Nationwide Inpatient Sample, we identified adult patients undergoing inpatient antireflux surgery during 1993-2006 and compared the trends of inpatient antireflux surgery with inpatient gastric bypass surgery. Perioperative complications included laceration, splenectomy, transfusion, esophageal dilation, total parenteral nutrition, and infection. Inpatient antireflux surgery increased from 9173 in 1993 to 32 980 in 2000 (+260%) but then decreased to 19 668 in 2006 (-40%). Compared with 2000, patients undergoing inpatient antireflux surgery in 2006 were older (49.9 ± 32.4 vs. 54.6 ± 33.6 years) and had a longer length of stay (3.1 ± 10.0 vs. 3.7 ± 13.4 days), more complications (4.7% vs. 6.1%), and higher mortality (0.26% vs. 0.54%) (all P < 0.05). Compared with inpatient gastric bypass surgery, length of stay was longer and mortality was higher for inpatient antireflux surgery in 2006, but neither was significant controlling for age. In 2006, perioperative outcomes of inpatient antireflux surgery were better in high-volume hospitals (all P < 0.01). Inpatient antireflux surgery continued to decline in the United States from 2000 to 2006, concomitant with a dramatic increase in inpatient gastric bypass surgery. Older patient age and worsening perioperative outcomes for inpatient antireflux surgery suggest increased medical complexity and possibly a larger share of reoperations over time. Designating centers of excellence for antireflux surgery based on local expertise may improve outcomes.

Comparison of outcomes following open and laparoscopic esophagomyotomy for achalasia.

BACKGROUND: Minimally invasive esophagomyotomy is replacing open surgery for achalasia, but data comparing these procedures performed by the same surgical team are sparse. The purpose of this study was to compare the morbidity and clinical outcome following laparoscopic and open esophagomyotomy. METHODS: Twelve consecutive patients referred for elective surgery between August 1995 and August 1997 underwent laparoscopic myotomy and partial fundoplication. They were compared to a group of 10 patients chosen from a larger pool of 20 patients who had open surgery during the same period performed by our own group. The mean length of follow-up in the laparoscopic group was 16 months; in the open group, it was 60 months. Both groups had similar demographics and clinical features. Each patient had at least one previous pneumatic dilatation. Inpatient records were reviewed. Patients were interviewed using a symptom assessment and patient satisfaction questionnaire. RESULTS: As compared to the open operation, laparoscopic esophagomyotomy with partial fundoplication resulted in significantly (p < 0.05) less blood loss (50 +/- 26 cc versus 220 +/- 127 cc), parenteral narcotic use (2.1 +/- 1.0 days versus 5.3 +/- 1.4 days), time in hospital (2.7 +/- 1.0 days versus 8.8 +/- 2.6 days), and time off work (19 +/- 16 days versus 85 +/- 60 days). There were similar results for the laparoscopic and open groups in the improvement in dysphagia (92% versus 90%) and patient satisfaction with surgery (84% versus 80%). CONCLUSIONS: Laparoscopic esophagomyotomy for achalasia results in symptomatic improvement and high patient satisfaction comparable to the open procedure but with significantly less morbidity.

Laparoscopic resection of esophageal epiphrenic diverticulum.

Symptomatic esophageal epiphrenic diverticula are usually repaired with a diverticulectomy and esophagomyotomy via a left thoracotomy with substantial postoperative pain and morbidity. If a laparoscopic approach could be shown to be safe and effective, the decrease in postoperative pain and potentially shorter hospital stay would make this technique beneficial. We report three cases repaired via a transabdominal approach. The first two cases were done laparoscopically. The third case was attempted laparoscopically and completed via a midline laparotomy, demonstrating that thoracotomy is not necessary even if laparoscopy is not possible. All three patients had long-standing debilitating symptoms refractory to standard nonsurgical therapies (botulinum toxin injection, pneumatic dilation, antispasmodic medication) with abnormal esophageal motility. There was one intraoperative complication of a left pneumothorax that required neither laparotomy nor thoracostomy. An esophagram on the first postoperative day demonstrated no extravasation and good flow into the stomach. The postoperative course was uneventful for all three patients, with the laparoscopic patients discharged on the second postoperative day and the laparotomy patient discharged on the seventh postoperative day. In conclusion, laparoscopic repair of symptomatic esophageal epiphrenic diverticula is a safe and effective technique with minimal postoperative pain and morbidity. It should be considered as an alternative to the traditional transthoracic approach, and may become the standard technique.

Acute experimental colitis decreases colonic circular smooth muscle contractility in rats.

Distal colitis decreases the contractility of the underlying circular smooth muscle. We examined how time after injury and lesion severity contribute to the decreased contractility and how colitis alters the calcium-handling properties of the affected muscle. Distal colitis was induced in rats by intrarectal administration of 4% acetic acid. Contractile responses to acetylcholine, increased extracellular potassium, and the G protein activator NaF were determined for circular muscle strips from sham control and colitic rats at days 1, 2, 3, 7, and 14 postenemas. Acetylcholine stimulation of tissues from day 3 colitic rats was performed in a zero calcium buffer, in the presence of nifedipine, and after depletion of intracellular stores of calcium. The colitis was graded macroscopically as mild, moderate, or severe. Regardless of agonist, maximal decrease in force developed 2 to 3 days posttreatment, followed by a gradual return to control by day 14. The inhibitory effect of colitis on contractility increased with increasing severity of inflammation. Limiting extracellular calcium influx had a greater inhibitory effect on tissues from colitic rats; intracellular calcium depletion had a greater inhibitory effect on tissues from control animals. The data suggest that both lesion severity and time after injury affect the contractile response of circular smooth muscle from the inflamed distal colon. Impaired utilization of intracellular calcium may contribute to the decreased contractility.

Acute experimental distal colitis alters colonic transit in rats.

Data from humans with active distal colitis suggest that the proximal colon exhibits increased contractile activity and delayed transit, whereas the distal colon shows decreased contractile activity and rapid transit. The present study used the acetic acid rat model of experimental colitis to determine the effect of distal colitis on total and regional colonic transit in vivo and on the in vitro contractility of circular smooth muscle from the proximal and distal colon. Distal colitis was induced in rats by intracolonic administration of 4% acetic acid; sham control rats received saline enemas. Control and colitic rats were studied 2 days postenemas. Total colon transit was determined by calculating the geometric center of distribution of a radiolabeled marker (51Cr) instilled into the proximal colon. Regional transit was assessed by expressing the radioactivity in the cecum, proximal and distal colon, and excreted stool as a percent of total radioactivity. Muscle strips from the proximal and distal colon were stimulated with 100 microM acetylcholine (ACh) and 60 mM KCl and the tension was expressed as kilograms per square centimeter. Distal colitis was characterized by decreased total colon transit, increased retention of marker in the cecum and proximal colon, and decreased retention of marker in the distal colon. In vitro contractility studies revealed that distal colitis increased proximal colon circular smooth muscle contractility and decreased distal colon circular smooth muscle contractility to both ACh and potassium. Distal colitis is associated with regional differences in colonic circular smooth muscle contractility, which may contribute to delayed transit in the proximal colon and rapid transit in the distal colon.

Laparoscopic resection of gastric leiomyosarcoma.

Wedge resection with a normal margin of stomach is generally considered adequate therapy for gastric leiomyosarcoma. We report here four patients with gastric leiomyosarcoma managed laparoscopically. The technique is described. There were no operative complications and all patients have been followed for 7 to 56 months. Three patients are free of disease and one patient with a high grade tumor is alive with liver metastases at 2 yars postoperatively. From this experience we conclude the following: 1) Laparoscopic wedge resection of gastric leiomyosarcoma is straightforward and easily accomplished without violation of standard surgical oncologic principles. 2) Intraoperative endoscopy is helpful in locating and manipulating the tumor, and aids in ensuring lumenal adequacy and staple line integrity. 3) Preoperative localizing studies may be misleading and should not discourage laparoscopic evaluation and treatment.

Effects of polyunsaturated fatty acids on bile acid-induced gastric mucosal injury.

Arachidonic acid is a polyunsaturated fatty acid precursor to prostaglandin formation in the stomach. When applied topically to gastric mucosa it prevents injury from a variety of damaging agents, similar to the effects observed with exogenous prostaglandins. Alternatively, fatty acids could act as mild irritants and protect the gastric mucosa in an adaptive cytoprotective process. This study was undertaken to ascertain whether arachidonic acid attenuates gastric injury from bile acid by acting as a mild irritant to the gastric epithelium or by increasing biosynthesis of cytoprotective prostaglandins. Accordingly, adult anesthetized rat stomachs were pretreated for 30 min with either topical 1 mM arachidonic acid, docusahexaenoic acid or eicosatrienoic acid prior to injury with topical 5 mM acidified taurocholate. In a second set of experiments using a similar protocol, the role of prostaglandins was evaluated by giving indomethacin (5 mg/kg/sc) 30 min prior to fatty acid pretreatment. Mucosal injury was assessed by measuring net transmucosal ion fluxes, the appearance of DNA into the gastric lumen, and histology. Gastric luminal PGE2 content was determined by radioimmunoassay. Pretreatment with topical arachidonic acid, but not docusahexaenoic acid or eicosatrienoic acid, significantly (P < 0.05) decreased bile acid induced net luminal ion fluxes, DNA accumulation and histologic injury scores, an effect negated by indomethacin. Further, pretreatment with arachidonic acid was associated with increased luminal PGE2 content, an effect also abolished by indomethacin. Thus, arachidonic acid does not act as a mild irritant, but protects the gastric mucosa from bile acid injury through a mechanism involving increased bio-availability of substrate for prostaglandin formation.

Isoproterenol-induced gastric mucosal protection from bile acid. Role of endogenous prostaglandins.

Topical isoproterenol is a potent protective agent against bile acid-induced gastric mucosal injury in hypotensive and normotensive rats. This study was undertaken to ascertain what role endogenous prostaglandins and gastric mucosal blood flow play in isoproterenol-induced protection. Accordingly, anesthetized, fasted rats were given the cyclooxygenase inhibitor, indomethacin (5 mg/kg subcutaneously), 30 min prior to topical pretreatment with 3 ml of intragastric saline, isoproterenol (3 microM), or 16,16-dimethyl prostaglandin E2 (3 microM) for 15 min. Gastric injury was induced with topical 5 mM acidified taurocholate and damage assessed by measuring net transmucosal ion fluxes, the appearance of DNA into the gastric lumen, and histology of the gastric epithelium. In a separate set of experiments, the effects of topical isoproterenol on gastric mucosal blood flow (laser Doppler flowmetry) and luminal PGE2 concentrations (125I radioimmunoassay) were examined. Pretreatment with topical isoproterenol or 16,16-dimethyl prostaglandin E2 significantly decreased bile acid-induced net luminal ion fluxes and DNA accumulation, suggesting mucosal protection. The protective effect of isoproterenol, but not 16,16-dimethyl prostaglandin E2, was negated by indomethacin (corroborated by histology). Further, isoproterenol did not significantly alter gastric mucosal blood flow, but did augment luminal PGE2 concentrations, an effect also abolished by indomethacin. Thus, isoproterenol appears to protect the gastric mucosa from the damaging effects of bile acid through a mechanism that requires the synthesis and release of cytoprotective endogenous prostaglandins.

Foregut revascularization via retrograde splenic artery perfusion after resection of a juxtaceliac mycotic aneurysm: complicated by pancreatic infarction because of cholesterol emboli.

A 66-year-old woman had development of a rapidly enlarging juxtaceliac mycotic aneurysm after therapy for lumbar osteomyelitis and a psoas abscess. The aneurysm was repaired through a thoracoabdominal approach with a Dacron aortic graft sewn end to end to the thoracic aorta and end to side to the infrarenal aorta. Perfusion was restored after oversewing the abdominal aorta above the superior mesenteric artery and oversewing the celiac trunk. After reperfusion the foregut remained critically ischemic despite a patent superior mesenteric artery. Foregut reperfusion was achieved by removing the spleen and anastomosing the distal splenic artery to the aortic graft. Recovery was complicated by infarction of the body of the pancreas because of cholesterol emboli, resulting in a large pleural effusion. After undergoing a subtotal pancreatectomy that preserved the splenic artery, the patient recovered without additional complications. During 8 years of follow-up, the patient has normoglycemia and has had no further infections complications. The distal splenic artery offers an excellent inflow for foregut revascularization; however, the pancreas is intolerant of atheromatous emboli.

The role of calcitonin gene-related peptide and nitric oxide in gastric mucosal hyperemia and protection.

It has been suggested that capsaicin-induced hyperemia and mucosal protection occurs via calcitonin-gene-related peptide (CGRP) release from gastric afferent sensory neurons and nitric oxide (NO)-mediated vasodilation. The purpose of this study was to determine whether capsaicin and/or bile acid induced hyperemia is mediated by CGRP and/or NO. Male Sprague-Dawley rats (280-350 g) were anesthetized, and the glandular stomach (blood supply intact) was chambered between two plastic rings. Animals were divided into six groups. Normal saline (groups 1 and 4), the NO inhibitor N-nitro-L-arginine methyl ester (L-NAME; 3.75 mg/ml, groups 2 and 5), or the CGRP antagonist hCGRP8-37 (0.047 mg/ml, groups 3 and 6) was continuously infused intraarterially (ia) close to the stomach at a rate of 0.034 ml/min for 1 hr via a catheter inserted retrogradely into the splenic artery. Fifteen minutes after the onset of this infusion, the gastric mucosa was topically exposed to neutral saline solution for 15 min, followed by 160 microM capsaicin for 15 min. The mucosa was then injured by a 15-min exposure to either 5 mM acidified taurocholate (ATC, pH 1.2) in groups 1-3 or 10 mM ATC in groups 4-6. Gastric mucosal blood flow (ml/min/100 g) was continuously measured (laser doppler), and injury was assessed by measuring net transmucosal H+ flux, luminal accumulation of DNA, and histologic grading (0 = no injury to 3 = severe) by an independent observer. Intraarterial infusion of L-NAME significantly blocked the hyperemic response of topical capsaicin while having minimal effect on bile acid-induced hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Capsaicin-induced gastric hyperemia and protection are NO- dependent.

Topical treatment of gastric mucosa with capsaicin (cap) increases gastric mucosal blood flow (GMBF) and protects the mucosa from injury by acidified bile salts. The purpose of this study was to test the hypothesis that this hyperemia related "cytoprotection" is mediated by nitric oxide. Male Sprague-Dawley rats were anesthetized and the glandular stomach (blood supply intact) was chambered between two plastic rings. Animals were divided into four groups. All groups received a 5-min topical saline exposure. Groups 1 and 2 received iv saline or nitro-L-arginine methyl ester (L-NAME, 25 mg/kg iv), a specific nitric oxide inhibitor, 5 min prior to baseline treatment, followed by a 15-min preinjury period of saline and a 15-min injury period of 10 mM acidified taurocholate (ATC, pH 1.2). Groups 3 and 4 were treated as above except topical cap (160 microM) was used during the preinjury period. GMBF was measured with a laser Doppler flowmeter (ml/min/100 g tissue). Injury was assessed grossly (grade 0-3), histologically (grade 0-3), and by measuring DNA content of a 5-min N-acetylcysteine wash (DNAE). Baseline GMBF of 30 +/- 1.5 significantly decreased to 15 +/- 1.2 in group 1 versus group 2 (P < 0.05). When topical ATC was used GMBF increased to 59 +/- 4.9 and 25 +/- 2.8, respectively. Injury by grade and DNAE was not significantly different between these groups. GMBF during cap exposure was 42 +/- 4 and 22 +/- 2 in groups 3 and 4, respectively. Graded histologic and gross injuries were significantly worse in group 4 compared to group 3 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Capsaicin-induced gastric mucosal hyperemia and protection: the role of calcitonin gene-related peptide.

BACKGROUND: Topical capsaicin augments gastric mucosal blood flow and is cytoprotective. This phenomenon is blocked by nitric oxide (NO) synthase and cyclooxygenase inhibition. Capsaicin-sensitive neurons store and release calcitonin gene-related peptide (CGRP). The purpose of this investigation was to study the effects of a CGRP antagonist on capsaicin-induced hyperemia and protection and to determine the role of NO and the cytoprotective prostaglandin PGE2 in this process. METHODS: The glandular stomachs in male Sprague-Dawley rats (280 to 350 gm) were chambered with the blood supply intact. Animals were divided into four groups. Normal saline solution (group 1) or the CGRP antagonists hCGRP8-37 (groups 2 through 4, 0.047 mg/ml) were continuously infused intraarterially via a retrograde splenic artery catheter at a rate of 0.034 ml/min after rats were given an intravenous bolus of either NSS (groups 1 and 2), L-arginine (group 3), or D-arginine (group 4) (200 mg/kg). The gastric mucosa was then topically exposed to normal saline solution (pH 7.4), followed by 160 mumol/L capsaicin and then 100 mmol/L acidified taurocholate (pH 1.2), each for 15 minutes. Gastric mucosal blood flow (ml/min/100 gm tissue) was continuously measured (laser Doppler) and mucosal injury was assessed. Luminal PGE2 production was measured during the bile acid injury period by radioimmunoassay. RESULTS: The CGRP antagonist hCGRP8-37 significantly inhibits capsaicin-induced hyperemia and its associated mucosal cytoprotection and also significantly decreases luminal mucosal PGE2 production. Pretreatment with L-arginine, but not D-arginine, reverses these effects of CGRP antagonism. CONCLUSIONS: CGRP is a mediator of capsaicin-induced hyperemia and protection. This effect may be dependent on both NO and PGE2 production.

Topical prostaglandin E2 and isoproterenol reduce bile acid-induced gastric mucosal injury in shocked rats.

In shocked animals, topical application of bile acids at low pH to gastric mucosa results in gross mucosal injury. Both systemic prostaglandins and isoproterenol reduce this injury, but side effects may limit their clinical usefulness. The purpose of this study was to determine the effect of topical pretreatment with isoproterenol and prostaglandin E2 on gastric mucosal injury induced by low concentrations of bile acid in shocked and normotensive rats. Mucosal injury was assessed by measuring net transmucosal ion fluxes (H+,K+) and luminal accumulation of DNA (DNAE), a sensitive and specific indicator of gastric mucosal cell exfoliation. In this model of mucosal injury, pretreatment with prostaglandin E2 or isoproterenol significantly and dose dependently decreased luminal hydrogen loss, potassium gain, and DNA accumulation in both shocked and normotensive animals. Thus, both topical prostaglandin E2 and isoproterenol reduce gastric mucosal injury caused by low concentrations of bile acid in shocked and normotensive rats, findings corroborated by histology. These findings provide a physiologic basis for the possible use of these agents as prophylaxis or treatment of stress gastritis and gastroduodenal ulcer in the critically ill patient.

Sensory neuron-mediated gastric mucosal protection is blocked by cyclooxygenase inhibition.

BACKGROUND: Sensory neurons have been proposed to play a critical role in the protection of the gastric mucosa from a variety of necrotizing agents. The purposes of this study were (1) to investigate the effect of topical capsaicin, a sensory neuron stimulant, on the gastric mucosal injury caused by the topical application of low concentrations of bile acid and (2) to determine whether local neuronal blockade with topical lidocaine or cyclooxygenase blockade with systemic indomethacin has any effect during pretreatment with capsaicin. METHODS: Before injury with topical 5 mmol/L acidified taurocholate (pH 1.2) rat stomachs were pretreated with either vehicle or capsaicin (160 mmol/L), both with and without prior administration of either lidocaine (1%) or indomethacin (5 mg/kg subcutaneously). Injury was assessed by measuring net transmucosal ion fluxes, the appearance of deoxyribonucleic acid into the gastric lumen, and gross and histologic injury scores. RESULTS: Pretreatment with topical capsaicin significantly (p < 0.05) decreased bile acid-induced net luminal ion fluxes and luminal deoxyribonucleic acid accumulation, an effect blocked by both lidocaine and indomethacin. CONCLUSIONS: Thus both local neuronal blockade and cyclooxygenase inhibition block the protective effect of capsaicin, findings corroborated by gross and histologic injury analysis. This study suggests that sensory neurons may mediate gastric mucosal protection from bile acid injury by increasing synthesis of endogenous prostaglandins.

Effect of local acid-base status on gastric mucosal blood flow and surface cell injury by bile acid.

Topical application of 5 mM sodium taurocholate (5 TC, pH 1.2) to canine gastric mucosa results in luminal hydrogen ion (H+) loss and surface epithelial cell (SEC) injury. However, gross mucosal injury does not occur because of a protective increase in gastric mucosal blood flow (GMBF). The mechanism of this blood flow response is unknown. To test the hypothesis that mucosal acid-base status influences mucosal blood flow and surface cell injury, three groups of dogs with vascularized chambered gastric mucosae were studied during two sequential 30-min periods. Mucosae were exposed during period I to topical acidified isotonic saline (ATS, pH 1.2), and during period II to topical 5 TC. During both periods, group A (n = 5) received close intraarterial (ia) NaCl (0.15 M), group B (n = 5) close ia HCO3 (0.32 M), and group C (n = 4) close ia HCl (0.2 N). Parameters evaluated during both ATS and 5 TC periods included the luminal accumulation of DNA (DNAE, a sensitive marker of SEC exfoliation), luminal H+ loss, and GMBF measured using radiolabeled microspheres. Gastric venous pH was also measured. It was found that, compared to the NaCl group, the HCO3 group had no increase in GMBF after 5 TC exposure. Simultaneously, however, SEC loss was reduced by 48%, 604 +/- 72 with NaCl versus 314 +/- 59 micrograms/30 min DNA with HCO3, P < 0.025. Infusion of ia HCl generated a large increase in GMBF without an increase in SEC injury compared to ia NaCl. Thus, mucosal acid-base status is an important modulator of mucosal blood flow which is itself critically important to gastric mucosal protection during bile acid induced injury.

Sphincterlike thoracoabdominal high pressure zone after esophagogastrectomy.

BACKGROUND: The contribution of the crural diaphragm to the gastroesophageal high pressure zone (HPZ) may be important in prevention of gastroesophageal reflux. The purpose of this study was to investigate the manometric characteristics of the thoracoabdominal junction in patients after surgical removal of the lower esophageal sphincter. METHODS: Ten patients with prior esophagogastrectomy were studied manometrically. RESULTS: Esophageal manometry showed a HPZ and pressure inversion point distal to the anastomosis in 9 of 10 patients. Midrespiratory and end expiratory pressures were 14 +/- 7 and 6 +/- 4 mm Hg above intra-abdominal pressure, respectively. Breath holding caused inhibition of the phasic pressure component. This HPZ relaxed partially in response to deglutition (60% +/- 22%) and contracted in response to increased intra-abdominal pressure induced by either leg lifts or abdominal compression (delta HPZ/delta intra-abdominal pressure = 1.87 +/- 0.64 and 1.96 +/- 0.40, respectively). CONCLUSIONS: This study shows an HPZ at the thoracoabdominal junction after surgical removal of the lower esophageal sphincter. We suggest that this sphincterlike HPZ is due to the crural diaphragm.