Elimination Of Reflux Research Articles

Reduction of Interleukin 8 Gene Expression in Reflux Esophagitis and Barrett's Esophagus With Antireflux Surgery

Chronic inflammation of esophageal mucosa secondary to refluxed gastric juice increases gene expression of interleukin 8 (IL-8). Antireflux surgery can reduce this overexpression. Prospective analysis of archival paraffin-embedded tissue. Academic tertiary medical center. One hundred eight patients with reflux symptoms were classified according to pH monitoring and endoscopic and histologic findings. Twenty patients did not have reflux or mucosal injury; 47 had reflux disease (16 esophagitis and 31 Barrett's esophagus), 20 had dysplasia, and 21 had adenocarcinoma. Microdissection was performed to exclude inflammatory cells and stromal tissue. After RNA isolation and reverse transcription, IL-8 messenger RNA expression was measured using quantitative real-time polymerase chain reaction. All patients with reflux disease had Nissen fundoplication with biopsies at matched levels within the esophagus preoperation and postoperation. Expression of IL-8 was increased in patients with reflux compared with those without reflux. Patients with the highest IL-8 expression were those with Barrett's dysplasia and adenocarcinoma (P<.001). In patients with reflux, Nissen fundoplication led to significantly decreased IL-8 expression compared with preoperative levels in esophagitis (P = .01) and Barrett's esophagus (P = .03). Interleukin 8 messenger RNA expression increases during the progression of reflux disease from normal squamous mucosa to esophageal adenocarcinoma. Elimination of reflux with Nissen fundoplication significantly reduces IL-8 expression in both squamous and Barrett's mucosa. These results demonstrate that effective antireflux surgery can modulate the gene expression of esophageal mucosa and may impact the natural history of reflux disease.

Varisolve® polidocanol microfoam compared with surgery or sclerotherapy in the management of varicose veins in the presence of trunk vein incompetence: European randomized controlled trial

Objective: To compare the safety and efficacy of Varisolve® 1% polidocanol microfoam sclerosant with alternative treatments for patients with varicose veins and trunk vein incompetence. Methods: An open-label, multicentre, prospective trial of 710 patients randomized to receive either Varisolve® or alternative treatment (surgery or sclerotherapy). The endpoint was ultrasound-determined occlusion of trunk vein(s) and elimination of reflux, analysed against a non-inferiority hypothesis. Results: Overall, non-inferiority was demonstrated with 83.4% efficacy for Varisolve® compared with 88.1% for alternative treatment at three months, and the corresponding magnitudes were 78.9 and 80.4% at 12 months. Surgery was superior to Varisolve®, but the success rate of 68.2% for Varisolve® (surgery 87.2%) was poor compared with 93.8% success for Varisolve® achieved in those randomized to Varisolve® or sclerotherapy. Varisolve® was superior to sclerotherapy at 12 months ( P = 0.001). Deep vein thrombosis occurred in 11/437 (2.5%) after Varisolve®, in 1/125 (0.8%) after sclerotherapy and in none after surgery. No pulmonary emboli were detected. Conclusion: Overall, Varisolve® was non-inferior to alternative treatment. Surgery was more efficacious, but Varisolve® caused less pain and patients returned to normal more quickly. The Varisolve® technique is a useful additional treatment for varicose veins and trunk vein incompetence.

Antireflux Surgery Normalizes Cyclooxygenase-2 Expression in Squamous Epithelium of the Distal Esophagus

In some patients GERD presents with heartburn and regurgitation symptoms but a relative paucity of endoscopic and clinical findings, while in others symptoms may be minor or absent yet there is significant mucosal damage on endoscopy including the presence of Barrett's esophagus. The initial injury of gastroesophageal reflux is to the squamous esophageal mucosa, but while substantial research has been devoted to determining which genes are involved in the progression of Barrett's to dysplasia and cancer, little is known about the gene expression alterations in the squamous mucosa of patients with reflux. We hypothesized that the expression of cyclooxygenase-2 (Cox-2) might be increased in the squamous esophageal mucosal of patients with reflux, and might be a molecular indicator of reflux injury. Further, we hypothesized that Cox-2 expression in the squamous mucosa would be reduced following the elimination of reflux with an antireflux operation. Biopsies of the distal esophageal squamous mucosa were taken 3 cm above the squamocolumnar junction (SCJ) in 28 GERD patients before and after Nissen fundoplication. Following microdissection and RNA isolation, quantitative real-time PCR was used to measure Cox-2 gene expression in paraffin-embedded (N = 16) and fresh frozen (N = 12) tissue. Biopsies from patients (paraffin N = 15, frozen N = 14) with normal acid exposure and no evidence of mucosal injury were analyzed as controls. Median Cox-2 expression in the squamous epithelium from paraffin embedded biopsies in patients with reflux disease was significantly increased compared to controls (p = 0.04). The presence of esophagitis or Barrett's esophagus did not significantly alter the expression of Cox-2 compared to patients with nonerosive reflux disease (NERD). After antireflux surgery median Cox-2 expression values were significantly reduced (p = 0.0003) and were normalized to levels similar to controls without reflux (p = 0.74). Similar results were observed in the prospectively obtained fresh frozen tissue. Cox-2 gene expression is increased in the distal esophageal squamous mucosa of most patients with GERD, and the elevation was similar whether there was mucosal injury in the form of esophagitis or Barrett's or no visible mucosal injury. This suggests that increased Cox-2 expression may serve as a molecular marker of reflux disease. The increased Cox-2 expression in patients with reflux was usually normalized following antireflux surgery. These findings demonstrate for the first time that gene expression can be altered by surgical correction of reflux. Thus, in addition to symptom control and improvement in the quality of life, perhaps future studies assessing the efficacy of antireflux therapy should also focus on the impact of the therapy on gene expression in the esophageal squamous mucosa.

Quality Improvement Guidelines for Placement of Esophageal Stents

Esophageal cancer is now the sixth leading cause of death from cancer worldwide. During the past three decades, important changes have occurred in the epidemiologic patterns associated with this disease. Due to the distensible characteristics of the esophagus, patients may not recognize any symptoms until 50% of the luminal diameter is compromised, explaining why cancer of the esophagus is generally associated with late presentation and poor prognosis. Esophageal cancer has a poor outcome, with an overall 5 year survival rate of less than 10%, and fewer than 50% of patients are suitable for resection at presentation. As a result palliation is the best option in this group of patients. The aims of palliation are maintenance of oral intake, minimizing hospital stay, relief of pain, elimination of reflux and regurgitation, and prevention of aspiration. For palliative care, current treatment options include thermal ablation, photodynamic therapy, radiotherapy, chemotherapy, chemical injection therapy, argon beam or bipolar electrocoagulation therapy, enteral feeding (nasogastric tube/percutaneous endoscopic gastrostomy), and intubation (self-expanding metal stents (SEMS) or semi-rigid prosthetic tubes) with different success and complications rates.

Editorial comment

The appropriate treatment of patients with PBS has produced controversy between those who advocate early surgical rehabilitation and those who believe that surgical remodeling of the urinary tract should be considered only when required by the patient's deteriorating clinical course. The resolution of this controversy has been confounded by the rarity and broad variation in the severity of this disorder. Comparisons of the relative merits of these approaches remain based on patient series in which one or the other method has been applied. This report describes the management of a diverse group of patients and cannot fully resolve this debate. However, this large patient series does confirm that a comprehensive surgical approach can yield very good long-term results. Improved upper tract drainage and elimination of reflux in this series translated into less urinary stasis and a lower incidence of urinary tract infection. Of the 32 patients, 30 demonstrated stable or improved renal function at a mean follow-up of 5 years. Of note, these results were achieved only after several patients had undergone multiple procedures. The authors' approach may have been more aggressive than that applied by others in that 16 of these patients were considered to display category III features. Most often these patients still require orchiopexy but are less likely to require urinary tract reconstruction. Reflux, particularly when associated with urinary tract infection, progressive dilation of the urinary tract, or worsening renal function, would represent the usual indication for intervention and may have emerged in this group. Comprehensive surgical treatment of prune belly syndrome: 17 years' experience with 32 patientsUrologyVol. 64Issue 4PreviewTo describe the results of comprehensive surgical management of prune belly syndrome. Full-Text PDF Reply by the authorsUrologyVol. 64Issue 4PreviewWe thank the reviewer for his very thoughtful comments. It is important to stress that most of the patients underwent surgery at the time of their referral, and our main objective was to treat all abnormalities during only one procedure that included tailored urinary tract reconstruction, orchiopexy, abdominoplasty, and circumcision, as soon as possible. Full-Text PDF

Polydimethylsiloxane Injection Versus Open Surgery for the Treatment of Vesicoureteral Reflux in Complete Duplex Systems

We compared the efficacy of subureteral polydimethylsiloxane injection (Macroplastique, Uroplasty, Inc., Minneapolis, Minnesota) versus open surgery for correction of varying degrees of reflux in complete duplex systems. Between 1997 and 2000 polydimethylsiloxane injection was performed in 15 females (22 refluxing moieties). Mean patient age at presentation and at surgery was 54 and 94 months, respectively. Extravesical common sheath reimplantation (ECSR) was performed in 34 children (bilateral 10) with a mean age at presentation and at surgery of 31 and 57 months, respectively. Voiding cystourethrography and ultrasound were performed at 3 months. In cases of persistent reflux repeat voiding cystourethrography was performed at followup. We then analyzed the surgical outcome for both groups. Mean followup for the injection and ECSR groups was 12 and 15 months, respectively. The success rate per moiety after injection was 68% at 3 months, which increased to 81.8% at 12 months. One patient had contralateral vesicoureteral reflux and none had de novo hydronephrosis, urinary tract infection or complications postoperatively. The success rate of ECSR was 95.5% at 3 months, which improved to 97.7% at an average of 15 months (p <0.04). After ECSR transient contralateral vesicoureteral reflux was seen in 4 renal units, de novo hydronephrosis was seen in 2 units and 4 patients had urinary tract infections. Although endoscopic subureteral polydimethylsiloxane injection was simple and successful in more than 80% of patients with low grade vesicoureteral reflux in duplex systems, it is less effective than surgery with regard to elimination of reflux.

Durability of reflux-elimination by a minimal invasive CHIVA procedure on patients with varicose veins. A 3-year prospective case study

Objectives: to assess the outcome of a conservative and haemodynamic method for insufficient veins on an ambulatory basis (French acronym, “CHIVA”) with preservation of the greater saphenous vein (GSV) for treatment of primary varicose veins. Methods: duplex incompetence of the sapheno-femoral junction (SFJ) and the GSV trunk, with the re-entry perforating point located on a GSV tributary was demonstrated in 58 patients with varices (58 limbs). The re-entry point was defined as the perforator, whose compression of the superficial vein above its opening eliminates reflux in the GSV. Duplex scanning was performed preoperatively and at 7 days, and patients were followed prospectively at 1, 3, 6, 12, 24, and 36 months after CHIVA. Operation consisted in flush ligation and division from the GSV of the tributary containing the re-entry perforating vein (no additional high ligation is included). If reflux returned, SFJ interruption was performed in a second surgical procedure. Results: the GSV diameter showed an average reduction from 6.6 to 3.9 mm 36 months after surgery. Reflux in the GSV system was demonstrated in all but five (8%) patients. Of the 53 patients with recurrent reflux, 46 underwent SFJ interruption. Conclusions: elimination of reflux in the GSV after the interruption of insufficient collaterals is only temporary.Eur J Vasc Endovasc Surg 25, 159–163 (2003)

Predictive factors of Barrett esophagus: multivariate analysis of 502 patients with gastroesophageal reflux disease.

Risk factors for the presence and extent of Barrett esophagus (BE) can be identified in patients with gastroesophageal reflux disease (GERD). Case-comparison study. University tertiary referral center. Five hundred two consecutive patients with GERD documented by 24-hour esophageal pH monitoring and with complete demographic, endoscopic, and physiological evaluation, divided in groups according to the presence and extent of BE (328 patients without BE and 174 with BE [67 short-segment BE and 107 long-segment BE]). Clinical, endoscopic, and physiological data, studied by multivariate analysis, to identify the independent predictors of the presence and extent of BE. Seven factors were identified as predictors of BE. They were abnormal bile reflux (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.9-9.7), hiatal hernia larger than 4 cm (OR, 4.1; 95% CI, 2.1-8.0), a defective lower esophageal sphincter (OR, 2.7; 95% CI, 1.4-5.4), male sex (OR, 2.6; 95% CI, 1.6-4.3), defective distal esophageal contraction (OR, 2.2; 95% CI, 1.4-3.5), abnormal number of reflux episodes lasting longer than 5 minutes (OR, 2.2; 95% CI, 1.1-4.6), and GERD symptoms lasting for more than 5 years (OR, 2.1; 95% CI, 1.4-3.2). Only abnormal bile reflux (OR, 4.8; 95% CI, 1.7-13.2) was identified as a predictor of short-segment BE (baseline, no BE). Three factors were identified as predictors of long-segment BE (baseline short-segment BE). They were hiatal hernia larger than 4 cm (OR, 17.8; 95% CI, 4.1-76.6), a defective lower esophageal sphincter (OR, 16.9; 95% CI, 1.6-181.4), and an abnormal longest reflux episode (OR, 8.1; 95% CI, 2.8-24.0). Among patients with GERD, specific factors are associated with the presence and extent of BE. Elimination of reflux with an antireflux operation in patients with 1 or more of these factors may prevent the future development of BE.

Reflux elimination without any ablation or disconnection of the saphenous vein. A haemodynamic model for venous surgery.

to investigate the possibility of the haemodynamic suppression of reflux in the greater saphenous vein (GSV) without any high ligation and/or stripping procedure. prospective study; single group of patients. forty patients affected by primary chronic venous insufficiency of all clinical classes, with demonstrated duplex incompetence both of the sapheno-femoral junction (SFJ) and the GSV trunk, with the re-entry perforator located on a GSV tributary. The re-entry point was defined as the perforator, whose finger compression of the superficial vein above its opening eliminates reflux in the GSV. air-plethysmographic parameters as well as duplex scanning were performed both preoperatively, and 1 and 6 months later, respectively. Operation consisted in flush ligation and division from the GSV of the tributary containing the re-entry perforating vein. duplex investigation demonstrated both a forward flow and reflux disappearance in the GSV in 100% and 85% of the cases after 1 and 6 months, respectively. All air-plethysmographic parameters, with the exception of Ejection Fraction, improved significantly: Venous Volume changed from 150+/-9 ml to 114+/-7 ml (p <0.0001), Venous Filling Index from 4.9+/-0.5 ml/s to 2.3+/-0.2 ml/s ( p <0.0001), and Residual Volume Fraction from 42+/-3 ml to 30+/-2 ml ( p <0.0001). this study demonstrates that reflux in the GSV system is supported by a gradient of pressure between the anatomical point of reflux and the point of re-entry in the deep veins. Disconnection of the flow to the re-entry perforator without high ligation of the sapheno-femoral junction suppresses GSV reflux.

An update in the palliative management of malignant dysphagia

Background: Oesophageal cancer is generally associated with late presentation and poor prognosis. Therefore palliative surgery has been largely superseded by less invasive non-surgical techniques. Once palliation is indicated, the aims of the management should be: the maintenance of oral intake, minimizing hospital stay, relief of pain, elimination of reflux and regurgitation and the prevention of aspiration. Methods: This study was a review of all published English language data on the palliation of malignant dysphagia between 1994–1999. The Medline and Bids databases were searched and other references were derived from the material perused. Results and Conclusions: Palliative treatment for oesophageal cancer should be individualized and relate to tumour stage, size and location, the patient's medical condition and his/her personal wishes. The palliative treatment largely includes self-expanding metal stents (SEMS), laser (including photodynamic therapy (PDT)) or a combination of the two to relieve symptoms, this may be employed with or without other treatments such as radiotherapy/chemotherapy (RT/CT) with the aim of reducing tumour bulk and possibly prolonging survival. A multi-disciplinary approach is vital in patients with advanced oesophageal cancer.

Endoscopic treatment of children with vesico-ureteric reflux.

Endoscopic subureteric injection of tissue-augmenting substances has become an alternative to long-term antibiotic prophylaxis and open surgery in the treatment of children with vesico-ureteric reflux. Successful elimination of reflux in about 80% of patients after a single injection (and in 90% after a repeat) has been achieved using the foreign-body non-degradable substances Teflon and silicone. Few patients have required open surgery and recurrence of reflux after initial successful treatment has occurred in only 5-10%. Concern has arisen, however, about possible distant migration and granuloma formation after injection of particulate plastic materials. Cross-linked bovine collagen is a biodegradable alternative substance, but with a lower response rate of 60% after the first treatment and a recurrence rate of 10-20%. Dextranomer in sodium hyaluronan is a new biological substance with microparticles with a response rate of 69% after the first injection. Biological substances have caused few complications. Present literature on injection treatment unfortunately focuses on elimination of reflux, with little attention to subsequent frequency of pyelonephritis or to the long-term development of the kidneys. Furthermore, there are no controlled, randomized studies with subureteric injection as one of the treatment alternatives. Thus, although having the advantage of being a minimally invasive procedure that can be performed on an outpatient basis, this technique needs to be tested in a large prospective study with the long-term renal outcome as the main end-point.

Diameter-reflux relationship in perforating veins of patients with varicose veins

Purpose: Treatment of chronic venous valvular insufficiency requires understanding of the hemodynamics of perforating veins. To preserve normal veins or veins that can function normally once primary sources of valvular insufficiency are removed, a better understanding of the diameter-reflux relationship is desirable. We measured reflux and diameters in 500 perforating veins of patients with varicose veins (C 2E PA SPP R). Methods: Color flow duplex ultrasonography scanning was performed with the patient standing. Perforating veins were mapped medially in the thigh and medially, laterally, and posteriorly in the calf. Reflux was defined as reverse flow that lasted longer than 0.5 seconds. Diameters were measured on B-mode transverse projections at the crossing of the fascia. Competent versus incompetent vein diameters were compared by means of Student t test, one-way analysis of variance, and Bonferroni t test. Results: Diameters of competent and incompetent perforators averaged 2.5 ± 0.9 mm (n = 17) and 4.7 ± 1.9 mm (n = 17) at the medial thigh ( P < .0002), 2.2 ± 0.8 mm (n = 179) and 3.7 ± 1.0 mm (n = 210) at the medial calf ( P < .0001), 2.2 ± 0.6 mm (n = 13) and 3.5 ± 0.8 mm (n = 37) at the posterior calf ( P < .0001), and 2.1 ± 0.8 mm (n = 9) and 3.3 ± 0.7 mm (n = 18) at the lateral calf ( P < .003), respectively. Perforating vein diameters of 3.5 mm or larger in the calf and thigh were associated with reflux in more than 90% of the cases. Conclusion: An enlargement in the diameter of the perforating veins of 1 to 1.5 mm in the calf or 2 mm in the thigh of patients with varicose veins could be the difference between normal flow and reflux. Further studies are needed to confirm if elimination of reflux in patients with primary varicosity will transform incompetent perforators to competent ones. (J Vasc Surg 1999;30:867-75.)

Saphenectomy in the presence of chronic venous obstruction.

The results of saphenectomy in patients with morphologic and functional obstruction were compared with those in patients without obstruction. Excision of secondary saphenous varices associated with deep venous obstruction has long been considered contraindicated for fear of compromising its collateral contribution. Recent advances in accurate functional assessment of venous obstruction make it possible to test this concept. Saphenectomy was carried out in 51 limbs without morphologic or functional obstruction and 64 limbs with varying grades of venous obstruction. Significant deep venous obstruction on ascending venography was present in the latter group. Functional assessment of obstruction was based on the arm/foot venous pressure differential technique, outflow fraction measurements, and outflow resistance calculations. Valve reconstruction was carried out in conjunction with saphenectomy in 81% of cases. Saphenectomy was clinically well tolerated in both groups, and there was no difference in outcome as measured by objective tests for obstruction; improvement in reflux and calf venous pump function was largely similar. Among seven limbs with severe preoperative venous obstruction (grade III or IV), five (70%) had significantly improved obstructive grading, presumably as a result of elimination of reflux flow. The traditional admonition against removal of secondary varices should be reexamined. Saphenectomy may be indicated in postthrombotic syndrome with mixed obstruction/reflux. The procedure is clinically well tolerated and without malsequelae. Improvement in reflux parameters without significant worsening of objective measures of obstruction is documented in this group.

Efficacy of the Nissen fundoplication in the management of gastroesophageal reflux following esophageal atresia repair

From January 1974 to December 1988, 80 patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) were treated at the C.S. Mott Children's Hospital with division of their TEF and esophagoesophagostomy. Thirty-four in this group developed gastroesophageal reflux (GER). After an unsuccessful trial of medical management, 21 underwent Nissen fundoplication, and an additional child with refractory GER died intraoperatively before completion of her fundoplication. Following fundoplication, only eight patients had an uncomplicated course with elimination of reflux and no postoperative dysphagia. Wrap disruption and recurrent reflux occurred in 7 of the 21 (33%), a markedly higher incidence than the 10% figure seen in 220 children without EA who have undergone fundoplication at this institution. Upward tension on the wrap due to the presence of a shortened esophagus probably predisposes to an increased frequency of fundoplication failure in the EA child. In addition, postoperative dysphagia requiring prolonged gastrostomy feedings complicated eight otherwise successful initial or redo-fundoplications. Prolonged dysphagia in this group is likely related to the inability of the dyskinetic esophagus, common in EA, to overcome the increased resistance caused by the Nissen fundoplication. Three deaths (14%) from complications related to antireflux surgery occurred in the series. Although 15 of the 21 children (71%) eventually had excellent long-term results following initial or redo-fundoplication with elimination of reflux and normalization of oral intake, morbidity and mortality were clearly significant. Due to the high incidence of postoperative dysphagia and recurrent reflux, the transabdominal Nissen fundoplication may not be appropriate in EA patients.

VESICAL DEFENSES AGAINST INFECTION.

The normal urinary tract is protected from infection both by its ability to empty itself and by its intrinsic defense mechanisms. If micturition is abnormal or if reflux occurs, the defense mechanisms are overwhelmed and infection may become established. Restoration of normal voiding and elimination of reflux will allow eradication of infection.