Individual inactivation of the sphincteric component of the gastroesophageal barrier causes reflux esophagitis in piglets

Background/Purpose: The lower esophageal sphincter and the diaphragmatic crural sling form the gastroesophageal barrier. This work shows that division of the sphincteric component alone suffices to induce reflux esophagitis in piglets. Methods: Male piglets underwent either sham operation (n = 7) or extramucosal myotomy of the gastroesophageal junction (n = 8). Before and 1 week after the operation, pull-through manometry was performed under sedation. Pressures taken on the 4 quadrants at 20 1-mm intervals on both time endpoints were compared by pairwise Wilcoxon tests. The distal esophagus was studied histologically after 8 weeks. Results: The pressure profiles did not change after sham operation. In contrast, they were significantly flattened in the distal half of the high-pressure zone after myotomy reflecting disappearance of the sphincteric component of the barrier. Esophagitis was seen in all myotomized piglets but in none from the sham group. Conclusions: Lower esophageal sphincter myotomy alone with preservation of the crural sling induces reflux esophagitis in piglets. This animal, widely available and not too costly, is an excellent model for gastroesophageal research.     

Gastroesophageal scintigraphy to assess the severity of gastroesophageal reflux disease.

Thirty-six (36) patients with symptomatic gastroesophageal reflux were studied. Symptoms of heartburn, regurgitation and dysphagia were scored as to their severity and compared to quantitative tests of gastroesophageal reflux. Patients were studied with the acid reflux test, fiberoptic endoscopy, esophageal mucosal biopsy with a pinch forceps, esophageal manometry and radioisotopic gastroesophageal scintigraphy. Symptoms were scored according to an arbitrary grading system as mild, moderate, or severe. There were significant correlations between symptoms scores and both the degree of endoscopic esophagitis and the gastroesophageal reflux indices as measured by the radioisotopic scintiscan, but not with the degree of histologic esophagitis or lower esophageal sphincter pressure. Review of the findings suggests the following profile for patients who might require antireflux surgery: severe symptoms, presence of endoscopic esophagitis; resting lower esophageal sphincter pressure below 10 mmHg; and gastroesophageal reflux index above 10%.     

Low body mass index as a barrier to lung transplant in cystic fibrosis

RationaleLow body mass index (BMI) may influence lung transplant decisions for patients with advanced cystic fibrosis (CF) lung disease.ObjectiveDetermine whether patients with advanced CF lung disease and BMI ≤17 kg/m² are less likely to be listed for lung transplant or have a higher risk of death without listing compared to those with higher BMI.MethodsUsing merged United Network for Organ Sharing and CF Foundation Patient Registries, we identified adults with onset of advanced lung disease (FEV₁ ≤ 40% predicted) between May-2005 and December-2016. We analyzed survival using competing risks regression with cause-specific risks of listing for lung transplant and death without listing. BMI ≤ 17 kg/m² was our predictor.Measurements and main resultsAmong 5,121 CF patients with advanced lung disease, 23% were listed for lung transplant (n = 1,201), 23% died without listing (n = 1,190), and 44% were alive without listing (n = 2,730) as of December-2016. Patients with BMI ≤ 17 kg/m² were less likely to be listed for transplant (HR 0.69; 95% CI 0.57, 0.83) and more likely to die without listing (HR 1.63; 95% CI 1.41, 1.88). We identified important regional variations in the likelihood of referral and listing, based on BMI.ConclusionsPatients with advanced CF lung disease and BMI ≤ 17 kg/m² are less likely to be listed for lung transplant and have a higher risk of dying without listing, compared to those with higher BMI. Regional differences suggest access to transplant for malnourished CF patients may be limited by location.     

Effects of esophageal shortening on the gastroesophageal barrier: an experimental study on the causes of reflux in esophageal atresia

BACKGROUND/PURPOSE: Gastroesophageal reflux (GER) is frequently recognized after surgical repair of esophageal atresia. The aim of this study was to test the hypothesis that one or more components of the gastroesophageal pressure barrier are weakened by esophageal anastomosis under tension. METHODS: Lower esophageal sphincter pressure (LESP), crural sling pressure (CSP), and the length of the intraabdominal segment of the esophagus (LIAE) were measured by pull-through perfusion manometry in 20 rats before and after resection of 15 mm of the cervical esophagus, and in eight rats before and after esophageal transection (control group). RESULTS: This manouver decreased the LESP from 44.9+/-17.4 to 30.9+/-12.3 mm Hg and the LIAE from 17.9+/-2.8 to 15.8+/-2.4 mm (P < .05) in experimental animals, whereas they did not significantly change in controls. CSP did not change significantly. CONCLUSIONS: Anastomosis of the esophagus under tension in this model decreases significantly the lower esophageal sphincter tone and length of the intraabdominal esophagus, but it does not change the crural sling pressure. Postoperative reflux in patients operated on for esophageal atresia might be in part, caused by this mechanism.     

Delivery of radiofrequency energy to the gastroesophageal junction (Stretta procedure) for the treatment of gastroesophageal reflux disease

Background Radiofrequency (RF) energy treatment is increasingly offered before invasive surgical procedures for selected patients with gastroesophageal reflux disease (GERD).Methods Thirty-two patients undergoing the Stretta procedure were prospectively evaluated with upper endoscopy, manometry, 24-hour pH testing, SF-36 surveys, and GERD-specific questionnaires (GERD HRQL).Results Significant clinical improvement was observed in 91% of patients (29/32). Mean heartburn and GERD HRQL scores decreased (p = 0.001 and p = 0.003, respectively), and physical SF-36 increased (p = 0.05). At a minimum follow-up of 12 months, median esophageal acid exposure decreased (p = 0.79) and was normalized in eight patients. Median lower esophageal sphincter (LES) pressure was unchanged. Esophagitis healed in six of eight patients, but two patients with nonerosive disease developed asymptomatic grade A esophagitis during follow-up. At 12 months, 56% of patients were off proton pump inhibits. Morbidity was minimal.Conclusions RF delivery to LES is safe and significantly improves symptoms and quality of life in selected GERD patients.     

Failure of the Nissen fundoplication to control gastroesophageal reflux in esophageal atresia patients

During the 5-year period from 1981 to 1985, Nissen fundoplication was performed on 13 esophageal atresia patients. One patient with Down's syndrome died because of cardiac malformation 2 weeks after the operation and is excluded from the analysis. Nine of the remaining 12 patients had the usual malformation with distal fistula, while three had isolated atresia. In eight patients there was a long gap between the segments, and in five Livaditis myotomy was necessary. The median age of the patients at the fundoplication was 1.3 years (range, 4.5 months to 10.6 years). The main clinical manifestations were anastomotic stricture (six patients), respiratory complications (three patients), vomiting and difficulties in feeding (two patients), and esophagitis only (one patient). Altogether nine patients had preoperative distal esophagitis. Mean follow-up time was 4.1 years (range, 2.0 to 6.4 years). All patients primarily benefited from the operation. Routine control endoscopy 3 to 8 months after the operation showed a competent fundoplication in all patients. However, in five patients the reflux later recurred, and endoscopy revealed a partially disrupted fundal wrap and esophagitis. Four patients underwent refundoplication and one is waiting for it as of this writing. Four patients had Barrett's esophagus at the last endoscopic control. There was one late death due to cardiac failure. In conclusion, although the short-term results of Nissen fundoplication in esophageal atresia patients are good, the risk for late recurrence is high. Regular long-term follow-up is therefore necessary.     

A current assessment of endoluminal approaches to the treatment of gastroesophageal reflux disease

Over the past decade, a number of endoscopic techniques have been developed as alternatives to medical and surgical treatment of gastroesophageal reflux disease (GERD). The driving force was to provide an outpatient transoral, endoscopic procedure effective in controlling reflux in a portion of patients with GERD. Three major technologies emerged, although each use different approaches to augment the barrier function of the lower esophageal sphincter, mechanisms may be similar. These include Endocinch which tightens the gastroesophageal junction via a set of suture plications around the lower esophageal sphincter, Stretta, which delivers radiofrequency energy at the cardia, and Enteryx, which is an inert polymer injected into the muscle layer of the gastroesophageal junction. To date, the underlying mechanism of action of these procedures has not been completely elucidated, although each alters the compliance of the GEJ and thus its ability to respond to a "refluxogenic stress". The target population currently consists of proton pump inhibitor-dependent GERD patients, with little or no hiatal hernia and without severe esophagitis or Barrett's. The Stretta procedure is the only procedure to date to be subjected to a sham-controlled trial. Registries of complications suggest that these techniques are relatively safe, but serious morbidity including rare mortality have been reported. All can be performed on an outpatient basis. Future comparative studies with predetermined end points, validated outcome measures, prolonged follow-up, and complete complication registries are needed to determine the role of endoscopic procedures in the clinical practice of patients with GERD. Evolution of the current technologies will almost certainly occur, and a commonly performed, efficacious endoscopic antireflux procedure is likely to emerge.     

胃食管反流病诊断及外科治疗的探讨

胃食管反流病十分常见,其诊断主要依靠病史及辅助检查,由于发病率高,保守药物治疗仅能起到缓解症状作用,因而导致患者生活质量显著降低,故外科手术治疗逐渐成为人们关注的热点.因此,术前对于胃食管反流病的诊断及如何选择抗反流手术就显得尤为重要.     

Medical treatment of gastroesophageal reflux disease does not prevent the development of Barrett's metaplasia and poor esophageal body motility

Objective: Duodenal contents refluxing into the esophagus may be involved in the pathophysiology of gastroesophageal reflux disease (GERD). This study was performed to investigate whether medical treatment of GERD aimed at suppression of gastric acid production can prevent the development of complications, such as Barrett's metaplasia or poor esophageal body motility.Design: Retrospective study.Setting: University hospital.Patients: 138 GERD patients were analyzed regarding the development of Barrett's metaplasia or poor esophageal body motility, despite intermittent or continuous treatment with H₂ blockers or omeprazole.Main outcome measures: The rate of patients with Barrett's metaplasia or poor esophageal body motility with or without effective medical treatment.Results: Barrett's metaplasia was found in 33.8% of patients receiving medical treatment, although it was not present when treatment was induced. This rate was 21.9% among patients who were not receiving therapy (not significant). In all, 41.9% of patients with medication had impaired esophageal body motility compared with 59.3% of patients not receiving treatment (P<0.05), but these patients had a significantly shorter history of GERD.Conclusions: Medical treatment with H₂ blockers or omeprazole does not prevent the development of Barrett's metaplasia or poor esophageal body motility.     

Use of radiofrequency ablation of the lower esophageal sphincter to treat recurrent gastroesophageal reflux disease

Purpose

Recurrent gastroesophageal reflux disease (GERD) after gastroesophageal surgery is a troublesome problem. Reoperative surgery often is complicated by adhesions and recurrence. Radiofrequency ablation or energy delivery (RF or the Stretta procedure) is a new method for treating GERD. This study is the first report describing the use of the Stretta procedure in pediatric patients.

Methods

Six patients who underwent previous gastroesophageal surgery presented with recurrent GERD. Medical records were reviewed and the severity of reflux graded using a modified scoring system. All underwent RF and were graded for GERD at 6 months postprocedure.

Results

Mean operating time was 80 ± 12 minutes. Mean age at initial operation was 12 ± 4 years and for the RF, 18.0 ± 3.4 years. All patients were discharged as outpatients. Early complications occurred in one child with self-resolving acute gastric distension. Five of 6 patients were completely asymptomatic at 3 months after the procedure, and 3 stopped anti secretory agents. One patient was improved but still symptomatic and needed a redo fundoplication. Another required a repeat application of RF 10 months after the initial one. Mean GERD score pre-Stretta was 5.2 ± 1.0, which improved to 1.6 ± 1.9 at 6 months postprocedure (P < .05; paired t test).

Conclusions

Use of RF treatment of the lower esophageal sphincter is a potentially successful modality to treat recurrent GERD in children. Long-term follow-up is required.     

Electrical stimulation of the lower esophageal sphincter to address gastroesophageal reflux disease after sleeve gastrectomy

Background

Laparoscopic sleeve gastrectomy (LSG) can result in de novo and worsen preexisting gastroesophageal reflux disease (GERD). Post-LSG patients with GERD refractory to proton pump inhibitors (PPI) usually undergo more invasive, anatomy-altering Roux-en-Y gastric bypass surgery. Lower esophageal sphincter (LES) electrical stimulation (ES) preserves the anatomy and has been shown to improve outcomes in GERD patients.

Length of the esophagus in patients with gastroesophageal reflux disease and Barrett's esophagus compared to controls

BACKGROUND: It is a current opinion among surgeons that the esophagus is shorter in patients with reflux disease and particularly in those with complicated Barrett's esophagus. However, objective evidence of this is scarce. Therefore we attempted to determine the occurrence and magnitude of this phenomenon among our patients. METHODS: One hundred ninety control subjects, 77 patients with severe erosive esophagitis, 74 with Barrett's esophagus, and 29 with complicated Barrett's esophagus (ulcer, stenosis) were grouped according to height. The length of the esophagus was determined by standard manometric study, measuring the distance from the crycopharingeal sphincter to the distal limit of the lower esophageal sphincter. Values were expressed in cm as the mean +/- SD. RESULTS: The esophageal length according to height was 1 to 2 cm shorter in patients compared to controls, but these differences were not significant. CONCLUSIONS: No differences were found between patients with progressive severity of the disease. This study confirms that the presence of a so-called "short esophagus" does not exist or is not relevant in our patients with gastroesophageal reflux disease, including those with complicated Barrett's esophagus.     

Outcome after intestinal transplantation: results from one center's 9-year experience; discussion 1031-2

HYPOTHESIS: Outcomes after intestinal transplantation have improved during the past decade with refinements in surgical techniques as well as advances in immunosuppression and antimicrobial therapy. DESIGN: Retrospective analysis. SETTING: Tertiary care medical center, August 1991 through December 2000. PATIENTS: Adult (5) and pediatric (12) patients with intestinal failure. All developed complications from long-term total parenteral nutrition therapy. Median age was 8.6 years and median weight was 22 kg. INTERVENTIONS: Primary intestinal transplantation with (n = 14) or without (n = 3) the liver. MAIN OUTCOME MEASURES: Patient and graft survival, viral infections, rejection, and nutritional autonomy. RESULTS: Twenty-one intestinal grafts were transplanted into the 17 recipients. All donors were cadaveric and were matched by ABO blood group and size. Patient survival at 1 and 3 years was 63% and 55%, respectively. Death-censored graft survival at 1 and 3 years was 73% and 55%, respectively. There were 1.5 acute cellular rejection episodes per graft and 3 grafts were lost to rejection. Incidences of infection with the Epstein-Barr virus and cytomegalovirus were negligible with aggressive prophylaxis and preemptive therapy. Nutritional autonomy was achieved in 69% of grafts surviving more than 30 days after intestinal transplantation. CONCLUSIONS: Intestinal transplantation is now the standard of therapy for patients with intestinal failure and complications resulting from total parenteral nutrition. Outcomes have markedly improved since initiation of the program. Aggressive immunosuppression as well as prophylaxis and preemptive antiviral therapy have led to low incidences of acute cellular rejection, Epstein-Barr virus, and cytomegalovirus. Finally, nutritional autonomy can be achieved after successful intestinal transplantation.