Gastroesophageal Reflux Disease Research: 2002-2006
        
J Pineal Res. 2006 Oct;41(3):195-200.
Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole.
Pereira RD.
Depto. de Farmacia-Universidade Estadual da Paraiba, Av das Baraunas, 351/Campus Universitario, Bodocongo/Campina Grande-PB-Brazil-CEP 58109-753, Brazil.

The prevalence of gastroesophageal reflux disease (GERD) is increasing. GERD is a chronic disease and its treatment is problematic. It may present with various symptoms including heartburn, regurgitation, dysphagia, coughing, hoarseness or chest pain. The aim of this study was to investigate if a dietary supplementation containing: melatonin, l-tryptophan, vitamin B6, folic acid, vitamin B12, methionine and betaine would help patients with GERD, and to compare the preparation with 20 mg omeprazole. Melatonin has known inhibitory activities on gastric acid secretion and nitric oxide biosynthesis. Nitric oxide has an important role in the transient lower esophageal sphincter relaxation (TLESR), which is a major mechanism of reflux in patients with GERD. Others biocompounds of the formula display anti-inflammatory and analgesic effects. A single blind randomized study was performed in which 176 patients underwent treatment using the supplement cited above (group A) and 175 received treatment of 20 mg omeprazole (group B). Symptoms were recorded in a diary and changes in severity of symptoms noted. All patients of the group A (100%) reported a complete regression of symptoms after 40 days of treatment. On the other hand, 115 subjects (65.7%) of the omeprazole reported regression of symptoms in the same period. There was statiscally significant difference between the groups (P < 0.05). This formulation promotes regression of GERD symptoms with no significant side effects.

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Digestion. 2006 Aug 29;74(1):1-14 [Epub ahead of print]
Endoscopic Therapy for Gastroesophageal Reflux Disease: A Systematic Review.
Sgouros SN, Bergele C.
Department of Gastroenterology, Athens Naval Hospital, Athens, Greece.

The high prevalence of gastroesophageal reflux disease (GERD) in Western societies has accelerated the need for new modalities of treatment. Currently, medical and surgical therapies are widely accepted among patients and physicians. The minimally invasive treatment revolution, however, has stimulated several new endoscopic techniques for GERD. Up to now, the data is limited and further studies are necessary to compare the advantages and disadvantages of the various endoscopic techniques to medical and laparoscopic management of GERD. This systematic review reports the efficacy and durability of various endoscopic therapies for GERD whilst the potential for widespread use of these techniques is also discussed. Despite the limited number of studies and remarkable differences between various trials, strict criteria were used for the pooled data presented and an effort was made to avoid bias by including only studies that used off-antisecretory medication scoring as baseline and intent to treat. Copyright (c) 2006 S. Karger AG, Basel.

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Dig Dis Sci. 2006 Aug 22; [Epub ahead of print]
Intravenous Pantoprazole as Initial Treatment in Patients With Gastroesophageal Reflux Disease and a History of Erosive Esophagitis: A Randomized Clinical Trial.
Pratha V, Hogan DL, Lynn RB, Field B, Metz DC.
Clinical Applications Laboratories, 3330 Third Ave, Suite 330, San Diego, California, 92103, USA, dhogan@calincresearch.com.

We sought to evaluate safety and efficacy of IV pantoprazole when used as initial therapy in patients with gastroesophageal reflux disease (GERD) and a history of erosive esophagitis (EE) in a double-blind, placebo-controlled, randomized, parallel-group study. Patients were randomized to 7 days of once-daily IV or oral pantoprazole (40 mg) or placebo. Efficacy variables included maximal acid output, basal acid output, and changes from baseline in frequency/severity of GERD symptoms, and frequency of antacid usage. Seventy-eight patients were randomized (n=26/27/25 [IV/oral/placebo]). Mean maximal acid output was 8.4, 6.3, and 20.9 mEq/h for IV or oral pantoprazole, and placebo, respectively. For pantoprazole versus placebo, maximal and basal acid output were significantly lower (P<.001) and there was a numerical trend toward improved GERD and antacid usage. Both treatments were well tolerated. In conclusion, IV/oral pantoprazole were similarly effective in suppressing basal and pentagastrin-stimulated gastric acid secretion in GERD patients with a history of EE.

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Schweiz Rundsch Med Prax. 2006 Aug 2;95(31-32):1179-83.
[Gastroesophageal reflux disease and dyspepsia—drug therapy]
[Article in German]
Grater H.
Klinik fur Onkologie, Gastroenterologie und Allgemeine Innere Medizin, Stadtische Kliniken Esslingen.

Proton pump inhibitors (PPI) are the antisecretory drugs of choice to manage GERD-related problems. The therapeutic goal in patients with non erosive reflux disease (NERD) and low-grade-GERD is to relieve symptoms, therefore PPI are given "on demand". Severe GERD requires long term treatment to heal lesions and to prevent relapses and complications. Barrett's esophagus has to be regarded as a precancerous lesion, therefore surveillance strategy is required. Functional dyspepsia is a common reason for upper gastrointestinal symptoms. If there are no alarming symptoms, you can omit endoscopy in younger patients. The treatment is empirical and symptom driven. Psychologic therapy is a promising avenue in some patients.

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Paediatr Drugs. 2006;8(4):265-70.
Ranitidine (Zantac®) Syrup versus Ranitidine Effervescent Tablets (Zantac®) (EFFERdose®) in Children: A Single-Center Taste Preference Study.
Ameen VZ, Pobiner BF, Giguere GC, Carter EG.
Clinical Pharmacology and Discovery Medicine, Research and Development, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.

BACKGROUND: The histamine H(2) receptor antagonist ranitidine is US FDA-approved for the treatment of gastroesophageal reflux disease and healing of erosive esophagitis in children >/=1 month of age. A low-dose strength of ranitidine is now available in a citrus-flavored 25mg effervescent tablet (dissolved in 5mL of water); this formulation was developed to facilitate use in infants and smaller children. Ranitidine syrup is available in a peppermint-flavored 15 mg/mL formulation. OBJECTIVE: To compare taste preferences for ranitidine (Zantac®) syrup and ranitidine effervescent tablets dissolved in water (Zantac®) EFFERdose®) in healthy children aged 4-8 years and their adult caregivers. STUDY DESIGN AND METHODS: A randomized, single-blind, crossover, taste test trial was conducted in 102 children and 102 parents/legal guardians. All subjects received a single 45mg dose of each formulation. After tasting both preparations children were asked: "Now that you have tasted both medicines, which one of these medicines do you think tastes better?" Adults were asked four questions to assess whether they would administer the medication to the children. RESULTS: Seventy-one percent (72/102) of the children preferred the taste of the ranitidine effervescent tablets compared with 29% (30/102) who preferred the syrup (p < 0.001). The majority of adults (71%) responded that they would prefer to administer the effervescent formulation based on taste. Adverse events consistent with product labeling were mild and were reported in four children and three adults: headache (n = 3), drowsiness (n = 1), abdominal pain/cramps (n = 2), and bloating/gas (n = 1). CONCLUSION: The taste of the ranitidine effervescent formulation dissolved in water is preferred over the ranitidine syrup. Better taste acceptance may facilitate ease of administration and compliance in pediatric patients.

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Pediatrics. 2006 Aug;118(2):746-52.
Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a systematic review.
Hibbs AM, Lorch SA.
Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. annamariahibbs@hotmail.com

OBJECTIVES: Metoclopramide is a commonly used drug to treat gastroesophageal reflux disease in infants. Given its widespread use and growing concern about toxicity in this population, we conducted a systematic review of metoclopramide for the treatment of gastroesophageal reflux disease in infants. METHODS: We performed a systematic search of PubMed and bibliographies of relevant review articles. We included cohort, case-control, and intervention studies of the efficacy, effectiveness, or toxicity of metoclopramide therapy for gastroesophageal reflux disease in infants. We excluded case reports, case series, review articles, and abstracts. RESULTS: Twelve articles met our inclusion criteria. Of these, 11 were prospective trials, and 5 were randomized, blinded clinical trials. Study size ranged from 6 to 77 patients. Eight studies showed patient improvement with metoclopramide in at least 1 measured outcome; 1 study showed worsening symptoms with metoclopramide. Of the 5 randomized, blinded trials, 2 showed no effect of metoclopramide on any outcome, and 2 showed a significant placebo effect. Four studies commented on adverse effects of therapy, with irritability being the most frequently reported potential adverse effect of therapy. Other reported adverse effects included dystonic reactions, drowsiness, oculogyric crisis, emesis, and apnea. Among studies, there was marked heterogeneity in the patient populations, dosing, and outcomes studied. Therefore, a meta-analysis was not performed. We both agreed on a US Preventive Service Task Force rating of "poor" for the level of evidence, leading to an "inconclusive" recommendation for the safety and efficacy of metoclopramide in infants. CONCLUSIONS: The current literature is insufficient to either support or oppose the use of metoclopramide for gastroesophageal reflux disease in infants. In the future, large blinded randomized clinical trials are needed to determine the efficacy and toxicity of metoclopramide in this population.

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Dig Dis Sci. 2006 Aug;51(8):1307-12. Epub 2006 Jul 27.
A very low-carbohydrate diet improves gastroesophageal reflux and its symptoms.
Austin GL, Thiny MT, Westman EC, Yancy WS Jr, Shaheen NJ.
Division of Gastroenterology and Hepatology and the Center for Esophageal Diseases and Swallowing, University of North Carolina, Chapel Hill, North Carolina, USA.

Obese patients with gastroesophageal reflux disease (GERD) may experience resolution of symptoms utilizing a very low-carbohydrate diet. The mechanism of this improvement is unknown. This studied aimed to prospectively assess changes in distal esophageal acid exposure and GERD symptoms among obese adults initiating a very low-carbohydrate diet. We studied obese individuals with GERD initiating a diet containing less than 20 g/day of carbohydrates. Symptom severity was assessed using the GERD Symptom Assessment Scale-Distress Subscale (GSAS-ds). Participants underwent 24-hr esophageal pH probe testing and initiated the diet upon its completion. Within 6 days, a second pH probe test was performed. Outcomes included changes in the Johnson-DeMeester score, percentage total time with a pH<4 in the distal esophagus, and GSAS-ds scores. Eight participants were enrolled. Mean Johnson-DeMeester score decreased from 34.7 to 14.0 (P=0.023). Percentage time with pH<4 decreased from 5.1% to 2.5% (P=0.022). Mean GSAS-ds score decreased from 1.28 to 0.72 (P=0.0004). These data suggest that a very low-carbohydrate diet in obese individuals with GERD significantly reduces distal esophageal acid exposure and improves symptoms.

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Drugs. 2006;66 Suppl 1:7-13; discussion 29-33.
Non-erosive reflux disease and atypical gastro-oesophageal reflux disease manifestations: treatment results.
Galmiche JP.
Department of Gastroenterology and Hepatology, CIC INSERM-CHU, Nantes University, France. jeanpaul.galmiche@chu-nantes.fr

Gastro-oesophageal reflux disease (GERD) is a widespread complex disorder that may be responsible for a variety of different symptoms and clinical features. Despite the presence of symptoms, the majority of patients do not have endoscopic lesions of oesophagitis. Non-erosive reflux disease (NERD) is a chronic, relapsing condition that can adversely affect the quality of life despite the absence of mucosal breaks at endoscopy. In many patients GERD is associated with extra-oesophageal or atypical manifestations, including cough, asthma, laryngitis or non-cardiac chest pain. Acid suppression with proton pump inhibitors (PPI) remains the mainstay of GERD therapy. However, patients with NERD and extra-oesophageal manifestations are often poorly responsive to PPI therapy. Accurate diagnosis followed by adequate PPI dosage and compliance with therapy are essential for the successful control of NERD and extra-oesophageal manifestations. The better detection and characterization of acid and non-acid reflux episodes using developing technologies, such as combined pH-impedance monitoring, is extending our understanding of the pathophysiology of NERD and the extra-oesophageal manifestations of GERD, and will lead to the improved management of these often poorly responsive conditions. This article reviews the treatment results and outlines approaches to the evaluation, diagnosis and therapy of NERD and atypical GERD manifestations.

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South Med J. 2006 Jul;99(7):735-41; quiz 742, 752.
Management of gastroesophageal reflux disease.
Liu JJ, Saltzman JR.
Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.

Gastroesophageal reflux disease is the most common and expensive digestive disease with complex and multi-factorial pathophysiologic mechanisms. Transient inappropriate relaxation of the lower esophageal sphincter is the predominant mechanism in the majority of patients with mild to moderate disease. Hiatal hernias and a reduced lower esophageal sphincter pressure have a significant role in patients with moderate to severe disease. Typical manifestations of gastroesophageal reflux disease include heartburn, regurgitation, and dysphagia. Atypical symptoms, such as noncardiac chest pain, pulmonary manifestations of asthma, cough, aspiration pneumonia, or ENT manifestations of globus and laryngitis, can be seen in patients with or without typical symptoms of gastroesophageal reflux disease. Endoscopy and ambulatory pH tests are best to evaluate the anatomic and physiologic impact ofgastroesophageal reflux disease. Complications of chronic gastroesophageal reflux disease include peptic strictures and Barrett metaplasia. Barrett esophagus is a major risk factor for esophageal adenocarcinoma, and upper endoscopy with surveillance biopsies is recommended for patients with Barrett esophagus. Medical therapy with anti-secretory agents (H2 blockers and proton pump inhibitors) is effective for most patients with gastroesophageal reflux disease. Surgical fundoplications and endoscopic treatment modalities are mechanical treatment options for patients with gastroesophageal reflux disease.

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Surg Endosc. 2006 Apr;20 Suppl 2:S500-2. Epub 2006 Mar 16.
Endoluminal surgery: past, present and future.
Ponsky JL.
Case Western Reserve University, Cleveland, Ohio, USA. jponsky@yahoo.com

Flexible endoscopy has evolved from a diagnostic tool practiced predominantly by gastroenterologists to a minimally invasive surgical tool. Therapeutic endoluminal procedures have become the standard of care for many gastric, biliary, pancreatic and colonic maladies. New technologies are under investigation for endoscopic treatment of gastroesophageal reflux, morbid obesity, and ablation of premalignant tissue. In the future flexible endoscopes may play a role in "natural orifice" surgery, performing operations through the mouth or rectum without the need for external incisions.

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Am Surg. 2006 Mar;72(3):207-12.
Laparoscopic Nissen fundoplication offers high patient satisfaction with relief of extraesophageal symptoms of gastroesophageal reflux disease.
Rakita S, Villadolid D, Thomas A, Bloomston M, Albrink M, Goldin S, Rosemurgy A.
Department of Surgery, University of South Florida College of Medicine, Tampa, Florida, USA.

Nissen fundoplication is applied for patients with gastroesophageal reflux disease (GERD), usually because of symptoms of esophageal injury. When presenting symptoms are extraesophageal, there is less enthusiasm for operative control of reflux because of concerns of etiology and efficacy. This study was undertaken to evaluate the efficacy of laparoscopic Nissen fundoplication in palliating extraesophageal symptoms of GERD. Patients were asked to score their symptoms before and after laparoscopic Nissen fundoplication on a Likert scale (0 = never/none to 5 = always/every time I eat). A total of 322 patients with extraesophageal symptoms (asthma, cough, gas/bloat, chest pain, and odynophagia) of 4 to 5 were identified and analyzed. After fundoplication, all extraesophageal symptom scores improved (P < 0.0001 for all, Wilcoxon matched-pairs test). Likewise, postoperative symptoms were noted to be greatly improved or resolved in 67 per cent to 82 per cent of patients for each symptom. Furthermore, after fundoplication, patients were less likely to modify their dietary (82% vs 49%) or sleeping habits (70% vs 28%) to avoid initiating/ exacerbating symptoms. Although extraesophageal symptoms are conventionally thought to be inadequately palliated by surgery, this study documents excellent relief of extraesophageal symptoms after laparoscopic Nissen fundoplication, denotes high patient satisfaction, and encourages application of laparoscopic Nissen fundoplication.

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Am J Gastroenterol. 2006 Mar;101(3):440-5.
Endoscopic treatment for atypical manifestations of gastroesophageal reflux disease.
Liu JJ, Carr-Locke DL, Osterman MT, Li X, Maurer R, Brooks DC, Ashley SW, Saltzman JR.
Division of Gastroenterology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.

OBJECTIVES: Atypical manifestations are common in patients with gastroesophageal reflux disease (GERD). The aim of this study was to evaluate the response of atypical manifestations of GERD to endoscopic antireflux treatment. METHODS: Patients with atypical manifestations of GERD including hoarseness, cough, wheezing, and non-cardiac chest pain were studied. Endoscopic antireflux treatment consisted of placement of sutures below the squamo-columnar junction. Clinical response was defined as complete resolution of the atypical symptom. Patients were followed clinically for up to 3 yr after the procedure. Short-term response was evaluated within 6 months of the procedure, and long-term follow-up was determined 1-3 yr after the procedure. RESULTS: Forty-three patients met the inclusion criteria; four patients underwent repeat procedures during the study period and were excluded from the analysis. Long-term follow-up was available in all 39 patients. Short-term response counts were: hoarseness, 12 of 19 patients, cough, 17 of 19; wheezing, 8 of 9; and chest pain, 13 of 18. Long-term follow-up of patients (mean of 18 months) for these symptoms was not significantly different compared to short-term response. CONCLUSIONS: Endoscopic suturing of the gastroesophageal junction appears to be a possible treatment option for atypical manifestations of GERD and future studies are needed to determine its role in management.

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Am J Gastroenterol. 2006 Mar;101(3):431-6. Comment in: Am J Gastroenterol. 2006 Mar;101(3):437-9.
Comparison of transesophageal endoscopic plication (TEP) with laparoscopic Nissen fundoplication (LNF) in the treatment of uncomplicated reflux disease.
Mahmood Z, Byrne PJ, McMahon BP, Murphy EM, Arfin Q, Ravi N, Weir DG, Reynolds JV.
Department of Surgery & Medicine, Trinity Centre for Health Sciences, St James's Hospital, Dublin 8, Ireland.

BACKGROUND: Transesophageal endoscopic plication (TEP) is a novel endotherapeutic approach in the management of gastroesophageal reflux disease (GERD). This non-randomized prospective study compares TEP with laparoscopic Nissen fundoplication (LNF). METHODS: Twenty-four consecutive patients treated with LNF, and 27 managed by TEP were studied. Symptom severity scores, endoscopy, 24 h esophageal pH and esophageal manometry and quality-of-life assessments were obtained pre- and posttreatment. RESULTS: In the LNF group the mean age was 36 yr (17-68) compared with 39 yr (22-62) in the TEP group. Symptom scoring, acid regurgitation score, reduction in the requirements of proton pump inhibitors (PPIs), and quality of life remained significantly improved in both groups at a median of 1 yr [10-18 months] follow-up post procedure. However, the improvement was significantly better in symptom score (p= 0.0383) and the control of acid reflux in the LNF group (p= 0.0007). Post-procedure dysphagia was more common in the LNF group. CONCLUSION: Both techniques improved symptom score, acid regurgitation, quality of life, and reduced the requirements for PPIs. The control of heartburn and acid reflux was better for LNF. TEP, like LNF, is a safe and effective method of management of symptomatic GERD but further developments are necessary to ensure control of esophageal acid reflux.

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Am J Gastroenterol. 2006 Mar;101(3):422-30. Comment in: Am J Gastroenterol. 2006 Mar;101(3):437-9.
Endoluminal gastroplasty (EndoCinch) versus endoscopic polymer implantation (Enteryx) for treatment of gastroesophageal reflux disease: 6-month results of a prospective, randomized trial.
Domagk D, Menzel J, Seidel M, Ullerich H, Pohle T, Heinecke A, Domschke W, Kucharzik T.
Department of Medicine B, University of Muenster, Albert-Schweitzer-Strasse 33, D-48129 Muenster, Germany.

OBJECTIVES: The aim of this study was to compare and determine the efficiency and safety of two newly introduced endoscopic antireflux procedures in the treatment of gastroesophageal reflux disease (GERD). METHODS: In a prospective, randomized trial, endoluminal gastroplasty (EndoCinch) was compared with polymer injection (Enteryx) employing 51 consecutive patients dependent on proton pump inhibitor therapy. Follow-up evaluation included drug consumption, symptoms, quality-of-life scoring, endoscopy, pH monitoring, manometry, and documentation of adverse events. RESULTS: Twenty-six patients were assigned to EndoCinch treatment, 23 patients received Enteryx implantation, and two patients dropped out before applying endoscopic therapy. At 6 months, proton pump inhibitor therapy could be stopped or dosage was reduced by > or =50% in 20 of 26 (77%) EndoCinch-treated patients and in 20 of 23 patients treated by Enteryx (87%, p= 0.365), which differed significantly in both groups compared to the pre-interventional status (p < 0.0001). Esophageal acid reflux (pH < 4) decreased from 14.5% to 9.6% in EndoCinch-treated patients (p= 0.071) and from 15.5% to 13.9% in patients treated by Enteryx (p= 0.930). Heartburn symptom score, modified DeMeester score, gastrointestinal life quality index, and SF-36 physical health survey score improved significantly in both groups postinterventionally (p < 0.0001). Approximately 25% of the patients in both groups required retreatment in an attempt to achieve symptom control. CONCLUSIONS: This is the first prospective, randomized study directly comparing two endoscopic anti-GERD techniques. EndoCinch and Enteryx seem to be equally successful in the treatment of GERD significantly reducing the proton pump inhibitor dosages, and also by improving symptoms of patients. Both endoluminal antireflux procedures may be promising therapeutic options; long-term evaluation will have to show if the positive initial results can be maintained.

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Arch Surg. 2006 Mar;141(3):289-92; discussion 292.
Laparoscopic fundoplication in elderly patients with gastroesophageal reflux disease.
Tedesco P, Lobo E, Fisichella PM, Way LW, Patti MG.
Department of Surgery and Anesthesia, University of California, San Francisco, USA.

HYPOTHESIS: It is unclear if age should be considered a factor in the choice of treatment for gastroesophageal reflux disease (GERD) and if fundoplication in elderly patients is as safe and effective as it is in younger patients. We hypothesized that the outcome of laparoscopic antireflux operations in patients younger than 65 years is similar to that of patients 65 years and older. DESIGN: Retrospective review of findings from a prospectively acquired database. SETTING: University-based tertiary care center. PATIENTS: Three hundred four consecutive patients underwent laparoscopic fundoplication for GERD. Two hundred forty-one patients were younger than 65 years (group A; median age, 46 years), and 63 patients were 65 years or older (group B; median age, 69 years). MAIN OUTCOME MEASURES: Presence, duration, and severity of GERD symptoms; presence of a hiatal hernia or esophageal stricture; duration of operation; incidence of complications; and length of hospital stay. RESULTS: Elderly patients more often had regurgitation and respiratory symptoms in addition to heartburn. Hiatal hernias were more common among elderly patients (77% vs 51%). The duration of the operation was similar for the 2 groups. The incidence of intraoperative and postoperative complications was low and similar in the 2 groups. The median hospital stay was 24 hours for each group. Heartburn resolved in approximately 90% of patients in each group. CONCLUSIONS: Elderly patients more often had hiatal hernias and respiratory symptoms. Laparoscopic antireflux surgery was as safe in elderly patients as it was in younger patients, and clinical outcomes were as good.

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Schweiz Rundsch Med Prax. 2006 Mar 29;95(13):483-7.
[Long-term treatment of patients with symptomatic gastroesophageal reflux disease comparing costs and efficacy over 6 months of treatment with Nexium On-Demand Treatment or Nexium continuous treatment. An open, randomised multi-center study]
[Article in German]
Beglinger C, Thalmann C, Szucs T, Michetti P.
Gastroenterologie, Universitatsspital Basel. beglinger@tmr.ch

This open, randomized study (ONE: On-demand Nexium Evaluation) compared the two long-term management options with esomeprazole 20 mg--continuous daily or on-demand treatment--in endoscopically uninvestigated patients seeking primary care for symptoms suggestive of gastroesophageal reflux disease (GERD) who demonstrated complete relief of symptoms after four weeks of initial treatment with esomeprazole 40 mg. In total 1904 patients were randomized. During 26 weeks 913 patients received continuous daily therapy with esomeprazole 20 mg, once daily, while 991 patients were treated with esomeprazole 20 mg on-demand. The continuous therapy offered slightly better relief of the symptom heartburn, however esomeprazole 20 mg taken on-demand was associated with lower direct medical costs. Esomeprazole was generally well tolerated.

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Minerva Chir. 2006 Feb;61(1):9-15.
Surgical therapy for patients with extraesophageal symptoms of gastroesophageal reflux disease.
Bresadola V, Dado G, Favero A, Terrosu G, Barriga Sainz M, Bresadola F.
Department of General Surgery, University of Udine, Udine, Italy.

AIM: The last 20 years have seen a systematic reappraisal of the physiopathology and diagnosis of gastroesophageal reflux disease (GERD) and its associated typical symptoms, while less attention has been paid to correlating GERD with certain extraesophageal symptoms and the value of surgery for their treatment. The aim of this study was to determine the clinical and physiopathological features and the outcome of surgery, in a group of patients who underwent laparoscopic fundoplication for GERD with atypical symptoms, and to compare the results with another group of patients operated for GERD with typical symptoms. METHODS: Two hundred and forty-one patients were evaluated for GERD at our Digestive Physiopathology outpatients surgery from January 2001 to January 2003. Of the 36 patients who underwent laparoscopic fundoplication, 23 had the typical symptoms of GERD and 13 had atypical symptoms. Twelve months after surgery, these patients were compared in terms of 24-h pH monitoring, esophageal manometry, regression of symptoms and degree of satisfaction. RESULTS: Postoperatively, patients with atypical symptoms had a smaller increase in effective peristalsis (P=0.06) and a more limited improvement in symptoms (54% vs 91%, P=0.001), and they expressed less satisfaction with the surgical treatment (5.9 vs 8.2, P=0.003). CONCLUSIONS: The results of surgery in GERD patients with atypical symptoms are worse than in those with typical symptoms. A careful preoperative work-up, based on 24-h pH monitoring, is fundamental for patients with atypical symptoms, who also need to be informed of the high likelihood of surgery proving clinically unsuccessful.

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Rev Med Suisse. 2006 Feb 22;2(54):518-20, 523-5.
[How to deal with gastroesophageal reflux in childhood]
[Article in French]
Schuler Barazzoni M, Belli DC, Schappi M.
Service de gastro-enterologie et transplantation pediatriques, Departement de pediatrie, HUG, Hopital des Enfants 1211 Geneve 14. mirjam.schuler@hcuge.ch

Gastroesophageal reflux is frequent source of consultation at the paediatrician's room, although most GER resolve spontaneously in infancy. In most cases, after a thorough anamnesis and a full physical examination prokinetic and anti-acid medications are started, as well as postural change, without the assistance of a specialist. When reflux is complicated by either oesophagitis, respiratory symptoms, failure to thrive or when the above treatment fail, further investigations need to be undertaken. Their option will depend on the clinical presentation. Rarely GER will lead to surgery.

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Surg Endosc. 2006 Jan 2; [Epub ahead of print]
Five-year results of laparoscopic Toupet fundoplication as the primary surgical repair in GERD patients: Is it durable?
Zehetner J, Holzinger F, Breuhahn T, Geppert C, Klaiber C.
Department of Surgery, Aarberg Hospital, Aarberg, Switzerland, joerg.zehetner@akh.linz.at.

INTRODUCTION: Most surgeons operate on gastroesophageal reflux disease (GERD) patients using the concept of "tailored approach," which depends on esophageal motility. We have abandoned this concept and performed laparoscopic Toupet fundoplication in all patients suffering from GERD, independent of their esophageal motility. METHODS: In a prospective trial we have assessed and evaluated our 5-year results of the first 100 consecutive patients treated with laparoscopic Toupet fundoplication. All patients were evaluated preoperatively by endoscopy and 24-h pH manometry. The patients were followed up clinically 1, 2, 6, 12 and 60 months postoperatively. The course of clinical DeMeester score, appearance and treatment of wrap-related side-effects as well as long-term outcome and patient satisfaction were evaluated. RESULTS: The 5-year follow-up rate was 87%. Laparoscopic Toupet fundoplication achieved a 5-year healing rate of GERD in 85%. Of all operated patients, 3.5% had to be reinstalled on a regular PPI treatment because of postoperative GERD reappearance. The median clinical DeMeester score decreased from 4.27 +/- 1.5 points preoperatively to 0.47 +/- 0.9 points 5 years postoperatively (p < 0.0005). Because of persistent postoperative dysphagia, 5% of the patients required endoscopic dilatation therapy. Persistent postoperative gas-bloat syndrome occurred in 1.1%. Wrap dislocation was identified in 3.4% of patients. Reoperation rate was 5%. Total morbidity rate was 19.5% and operative related mortality rate was 0%. Overall, 96.6% of patients were pleased with their outcome at late follow-up, and 95.4% of patients stated they would consider undergoing laparoscopic fundoplication again if necessary. CONCLUSION: Our long-term results showing a low recurrence and morbidity rate of laparoscopic Toupet fundoplication encourage us to continue to perform this procedure as the primary surgical repair in all GERD patients, independent of their esophageal motility. Laparoscopic Toupet fundoplication has proven to be a safe and successful therapeutic option in GERD patients.

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Surg Endosc. 2006 Jan;20(1):159-65. Epub 2005 Dec 7.
Clinical results of laparoscopic fundoplication at ten years after surgery.
Dallemagne B, Weerts J, Markiewicz S, Dewandre JM, Wahlen C, Monami B, Jehaes C.
Department of Digestive Surgery, CHC-Les Cliniques Saint Joseph, Belgium. bernard.dallemagne@skynet.be

BACKGROUND: Several studies have demonstrated laparoscopic antireflux surgery (LAS) for the treatment of gastroesophageal reflux disease (GERD) to be efficient at short- and midterm follow-up evaluations. The aim of this study was to evaluate the results for LAS 10 years after surgery. METHODS: The 100 consecutive patients who underwent LAS by a single surgeon in 1993 were entered into a prospective database. Nissen fundoplication was performed for 68 patients, and partial posterior fundoplication (modified Toupet procedure) was performed for 32 patients. Evaluations of the outcome were made 5 and 10 years after surgery. A structured symptom questionnaire and upper gastrointestinal barium series were used at 5 years. The same questionnaire and an added quality-of-life questionnaire (the Gastrointestinal Quality of Life Index [GIQLI]) were used at 10 years. RESULTS: Seven patients died of unrelated causes during the 10-year period. Four patients underwent revision surgery: one patient for persistent dysphagia and three patients for recurrent reflux symptoms. Three patients were lost to any follow-up study. At 5 years, 93% of the patients were free of significant reflux symptoms. At 10 years, 89.5% of the patients still were free of significant reflux (93.3% after Nissen, 81.8% after Toupet). Major side effects (flatulence and abdominal distension) were related to "wind" problems. The GIQLI scores at 10 years were significantly better than the preoperative scores of the patients under medical therapy with proton pump inhibitors. CONCLUSIONS: Elimination of GERD symptoms improved quality of life and eliminated the need for daily acid suppression in most patients. These results, apparent 5 years after the operation, still were valid at 10 years.

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Dis Esophagus. 2006;19(1):1-4.
Nonsurgical factors affecting symptomatic outcomes of antireflux surgery.
Velanovich V.
Division of General Surgery, Henry Ford Hospital, Detroit, Michigan, USA.

SUMMARY. A small number of patients will have persistent or new symptoms after antireflux surgery for gastroesophageal reflux disease (GERD). Most of these symptoms are due to recurrent reflux or some complication or side-effect of the operation. However, a few of these patients will be symptomatic without objective findings to explain these symptoms. The purpose of this review is to highlight potential non-surgical factors that may proceed to a poor symptomatic outcome after antireflux surgery. These factors include underlying esophageal pathophysiology, issues related to chronic pain and pain perception, personality and psychoemotional disorders, functional esophageal and/or bowel disorders, and the nocebo phenomenon. Awareness of these other causes can lead to more appropriate treatments.

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Pharm World Sci. 2005 Dec;27(6):432-5.
Treatment of gastroesophageal reflux disease.
Pettit M.
Clinical Pharmacy Unit, Royal Sussex Country Hospital, University of Brighton, Eastern Road, Brighton, BN2 5BE, UK, Pettit@bsuh.nhs.uk.

AIM OF THE REVIEW AND METHODS: This review brings together information on the treatment of gastroesophageal reflux disease. Published manuscripts were identified from Medline. The articles were then screened for relevance prior to inclusion in the review. RESULTS AND CONCLUSION: Up to 40% of people in Western countries are estimated to regularly experience heartburn, the most characteristic symptom of gastroesophageal reflux disease (GERD). Treatment options available for GERD range from over-the-counter (OTC) antacids to proton pump inhibitors (PPIs) and anti-reflux surgery. Many patients self-medicate with OTC medications such as antacids and low-dose histamine H(2)-receptor antagonists (H(2)RA) to relieve episodic or food-related symptoms of GERD, and may not seek medical advice unless symptoms persist or worsen. However, GERD is a chronic disease that frequently affects health-related quality of life and, if not properly managed, the complications of GERD may include erosive oesophagitis (EO), Barrett's oesophagus and adenocarcinoma. Adequate control of acid secretion is key to the successful treatment of the condition. OTC medications provide effective symptom relief to about one quarter of patients suffering from GERD. H(2)RAs can also provide effective symptomatic relief, particularly in patients with milder GERD, but become less-effective over time. PPIs are the agents of choice for the suppression of gastric acid production and have become the mainstay of therapy for acid-related diseases. PPIs produce significantly faster and more complete symptomatic relief, significantly faster and more complete healing of erosive GERD compared with H(2)RAs and are also significantly more effective at preventing relapse of EO. There are a number of existing guidelines for the treatment of GERD. Recommendation for initial therapy consist of general measures, such as lifestyle advice in combination with antacids and/or alginates. When general measures fail, the next step is empirical therapy. Two options exist for the expirical treatment of GERD, so-called "step-up" or "step-down" therapy. There are no clear data to support either treatment strategy as a universal approach to all patients; consequently, physicians must always choose the course best suited to the individual patient.

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Am Surg. 2005 Nov;71(11):950-3; discussion 953-4.
Amelioration of gastroesophageal reflux symptoms following Roux-en-Y gastric bypass for clinically significant obesity.
Nelson LG, Gonzalez R, Haines K, Gallagher SF, Murr MM.
Department of Surgery, Interdisciplinary Obesity Treatment Group, University of South Florida Health Sciences Center, Tampa, Florida 33601, USA.

Symptoms of gastroesophageal reflux disease (GERD) are frequent in patients with clinically significant obesity and are reported to improve after Roux-en-Y gastric bypass (RYGB). The purpose of this study is to determine timing and duration of improvement of GERD symptoms in patients undergoing RYGB. Prospectively collected data from patients who underwent RYGB from January 1998 to August 2004 were analyzed. Patients answered a standardized questionnaire pre- and postoperatively inquiring about frequency of GERD symptoms (none, one episode/ week, one episode/day, more than one episode/day) and medication use. Of 606 patients undergoing RYGB, 239 patients (39%) reported GERD symptoms preoperatively (mean age 43 +/- 1 years; body mass index 51 +/- 1 kg/m2). Of these, 89 per cent of patients reported improved at 3 months post-op and 94 per cent of patients 9 months post-op (P < 0.001). Medication usage decreased from 30 per cent to 3 per cent by 3 months and 5 per cent beyond 9 months (P < 0.001). Percentage of excess weight loss was 18 +/- 1 per cent and 75 +/- 2 per cent at 3 and 9 months, respectively. Symptoms of GERD significantly improve and use of antireflux medications is reduced after RYGB independent of weight loss. RYGB may be the treatment of choice for GERD in obese patients.

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Rev Gastroenterol Disord. 2005;5 Suppl 2:S18-30.
Intravenous proton pump inhibitor therapy: a rationale for use.
Armstrong D.
Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada.

Proton pump inhibitors (PPIs) are used widely in the management of acid-related disorders and, for the majority of patients, oral therapy is highly effective. Not all patients with acid-related disorders respond completely to standard, once-daily PPI therapy, but most nonresponders will generally respond to an increase in the dose or frequency of PPI therapy. At equivalent doses, oral and intravenous (IV) PPIs produce comparable acid suppression; thus there are very few clinical indications for IV PPI therapy. IV PPIs are an appropriate substitute for oral PPIs, at an equivalent dose, for patients with, for example, gastroesophageal reflux disease, peptic ulceration, or Zollinger-Ellison syndrome, who cannot take oral medication. For patients with nonvariceal, upper gastrointestinal hemorrhage, profound acid suppression (gastric pH . 6.0) optimizes clot stability and reduces the risk of rebleeding; this is achieved most effectively with an initial IV PPI bolus followed by a continuous infusion. High-dose, IV PPI therapy is beneficial and cost-effective in patients who have a high-risk lesion at endoscopy and it should be preceded by effective endoscopic hemostasis if possible. IV PPIs, preoperatively and in the intensive care setting, effectively reduce gastric acidity, but there are no convincing data that this confers any significant clinical benefit compared with other therapeutic strategies.

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Schweiz Rundsch Med Prax. 2005 Nov 30;94(48):1899-906.
[Gastroesophageal reflux disease]
[Article in German]
Grater H.
Klinik fur Onkologie, Gastroenterologie und Aligemeine Innere Medizin, Stadtische Kliniken Esslingen.

Gastroesophageal reflux disease (GERD) includes different manifestations of esophageal and extraesophageal affections, such as erosive reflux disease, Barrett's esophagus, laryngitis and even pulmonary diseases. Typical symptoms are heartburn and acid regurgitation, but there are a lot of atypical disturbances like hoarseness or chronic cough. Endoscopy is the most important diagnostic procedure for elderly patients and for those with atypical symptoms. Younger people without alarming symptoms can be tested for GERD by treatment with proton pump inhibitors (PPI). The therapeutic approach depends on the endoscopic findings. PPI are preferred drugs to manage most GERD-related problems. Anti reflux surgery is appropriate for selected patients. Long-term followup data will help to define the benefit of new endoscopic procedures. Barrett's esophagus has to be regarded as a precancerous lesion, therefore surveillance strategy is required.

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Dis Esophagus. 2005;18(6):370-3.
Histamine-2 receptor antagonists at night improve gastroesophageal reflux disease symptoms for patients on proton pump inhibitor therapy.
Rackoff A, Agrawal A, Hila A, Mainie I, Tutuian R, Castell DO.
Digestive Diseases Center, Medical University of South Carolina, Charleston, South Carolina 29425, USA. rackoff@musc.edu

While night-time symptoms of gastroesophageal reflux disease (GERD) are common, considerable controversy exists regarding the use of histamine-2 receptor antagonists (H2Ras) for night-time reflux control. Some studies have suggested possible tolerance to H2RA while others have suggested that long-term efficacy of gastric acid control can be maintained with night-time H2RA use. The aim of this study was to identify if GERD patients have sustained symptom improvement with long-term use of night-time H2RA. Records of 56 consecutive GERD patients on twice daily proton pump inhibitor (PPI) and night-time H2RA therapy were reviewed. During a phone interview patients were asked a 5-item questionnaire, which included overall assessment of symptoms, night-time symptoms, sleep disturbance, duration and frequency of therapy. Of the 56 patients, 39 (31 women, mean age 56) completed the questionnaire (15 were not reached and 2 did not recall enough information). All respondents had taken night-time H2RA for at least 1 month (28/39 patients with > 6 months duration) with 33/39 patients taking H2RAs every night. The addition of H2RA led to an improvement in overall symptoms in 28/39 (72%) patients, improvement in night-time reflux symptoms in 25/34 (74%) patients and improvement of GERD-associated sleep disturbance in 18/27 (67%) patients. Five (13%) patients had stopped the H2RA on their own, stating that its efficacy waned after 1 month. Our results suggest that the majority of patients report persistent improvement in GERD symptoms from night-time H2RA use and that possible clinically important tolerance to H2RAs occurs in a small number of patients. Further prospective, placebo-controlled studies may help confirm that there is a role for night-time H2RAs in GERD symptom control.

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Drugs. 2005;65 Suppl 1:59-66.
Maintenance therapy in gastro-oesophageal reflux disease.
Bixquert M.
Department of Medicine, University of Valencia, Spain. miguel.bixquert@uv.es

Gastro-oesophageal reflux disease (GORD) is a chronic condition. Symptom control and the maintenance of healing of erosive oesophagitis, if present, are important topics. In patients responding to a proton pump inhibitor (PPI) and showing no treatment symptoms it is appropriate to consider long-term treatment strategies, whether continuous, intermittent or on demand. Maintenance PPI therapy is well tolerated for up to 10 years of continuous use. Furthermore, tachyphylaxis does not occur during long-term maintenance PPI therapy. Previous concerns about risks of long-term PPI therapy in Heliobacter pylori-negative or H. pylori-positive patients have not materialized, while no cases of intestinal metaplasia with dysplasia or adenocarcinoma were found. The choice between medical and surgical therapy should depend upon informed patient preference. The optimal candidate for antireflux surgery is a young patient, with typical GORD symptoms, with erosive oesophagitis, with previous complete symptom resolution on acid-suppression therapy and unable to undergo continuous therapy, or alternatively in patients with regurgitation predominating over heartburn as long as the surgical procedures are conducted by an expert surgical team. Endoscopic therapy for erosive GORD should currently be regarded as experimental. The endoscopic procedures are safe, although they remain untested in patients with severe erosive oesophagitis and/or significant hiatal hernia.

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Langenbecks Arch Surg. 2005 Nov 18;:1-8 [Epub ahead of print]
Long-term experience of treating 185 patients with gastroesophageal reflux disease (GERD) by anti-reflux surgery respecting the functional-morphological restoration of the esophagus.
Horstmann R, Classen C, Rottgermann S, Langer M, Palmes D.
Department of Surgery, Herz Jesu-Krankenhaus Muenster-Hiltrup, Westfalenstrasse 109, 48151, Muenster, Germany, chirurgie@herz-jesu-kh-ms.de.

BACKGROUND: According to anatomical investigations the whole esophagus plays a crucial role as reflux barrier in the pathogenesis of gastroesophageal reflux disease (GERD). Morphologically, the spirally arranged muscle fibres present a tension-dependent "stretch closure" and in the event of any reduction of tension, as for example caused by an axial hiatus hernia, the organ may become inefficient. The aim of this study was to evaluate quality of life as the main success criterion after anti-reflux surgery based strictly on the restoration of functional morphology. METHODS: Between January 1999 and December 2000, 185 patients with GERD were treated by surgery in accordance with functional-morphological principles. After dissecting the mediastinum, the gastroesophageal junction was displaced into the abdomen with consecutive retensioning the esophagus. The esophageal hiatus was reconstructed with non-absorbable single knot sutures and strengthened with alloplastic material. The application of a 180 degrees fundus cuff around the posterior esophageal circumference served as a "spacer" and also restored the angle of His. Preoperatively, all patients underwent endoscopy, pH metry and manometry. During postoperative follow-up, recurrence rate and quality of life were evaluated via a disease-specific scale. RESULTS: Preoperatively, 85% of the patients had an elevated DeMeester Score with a median of 81.4; 64% had reflux esophagitis and 37% had reduced lower esophageal sphincter pressure. All 185 operations were performed without conversion in a median operating time of 74 min. In one patient a lesion of the esophagus was treated during the operation; two patients had lesions of the splenic capsule which were also dealt with during the operation. Postoperatively, pleural effusions occurred in 15 patients and puncture was deemed necessary in one subject. Ninety-three percent were followed up for a median of 45 months and the recurrence rate was 2.3%. The quality of life index was 81.6+/-12.4 points preoperatively, and had significantly improved to 125.2+/-12.7 points in the follow-up. CONCLUSION: Through the functional-morphological concept of anti-reflux surgery comprising the restoration of the tension-dependent "stretch closure" of the esophagus, significant long-term improvement in quality of life with a low recurrence rate and perioperative morbidity can be achieved.

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Dig Dis Sci. 2005 Nov;50(11):2009-18.
Efficacy of rabeprazole in the treatment of symptomatic gastroesophageal reflux disease.
Kahrilas PJ, Miner P, Johanson J, Mao L, Jokubaitis L, Sloan S.
Northwestern University Feinberg School of Medicine, Chicago, Illinois.

The purpose of this study was to assess the rapidity of symptom relief and 4-week efficacy of rabeprazole 20 mg in patients with moderately severe nonerosive gastroesophageal reflux disease. Data were analyzed from 2 similarly designed, double-blind, placebo-controlled, multicenter, U.S. trials. After a 2-week placebo run-in period, patients (N = 261) were randomized to 4 weeks of rabeprazole 20 mg once daily or placebo. Patients kept symptom diaries and scored symptom severity. Median time to first 24-hour heartburn-free interval was 3.5 days for the rabeprazole group compared with 19.5 days for the placebo group (P </= .0002). Complete heartburn relief at week 4 was 32% with rabeprazole and 3.8% with placebo (P </= .001). Rabeprazole also significantly improved other GERD-associated symptoms (e.g., regurgitation, belching, early satiety) by week 4 compared with placebo (P </= .05). Rabeprazole provides fast and potent relief from heartburn and other symptoms of nonerosive gastroesophageal reflux disease.

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Arch Surg. 2005 Oct;140(10):946-51.
Laparoscopic antireflux surgery: five-year results and beyond in 1340 patients.
Pessaux P, Arnaud JP, Delattre JF, Meyer C, Baulieux J, Mosnier H.
Department of Digestive Surgery, University Hospital, CHU Angers, 4 Rue Larrey, 49033 Angers Cedex 01, France.

BACKGROUND: Although the long-term results of open fundoplication for gastroesophageal reflux disease are well documented, few reports exist on the long-term results of laparoscopic fundoplication. DESIGN: Retrospective study with clinical evaluation or mailed survey for patients unable to return to the hospital center. SETTING: Multicenter studies (ie, private medical centers, institutional hospitals, and university hospitals). PATIENTS: Between January 1992 and December 1998, 2684 patients with gastroesophageal reflux disease underwent laparoscopic fundoplication in 31 hospital centers. Outcome data covering a period of 5 or more years after surgery were available for 1340 patients: 711 who underwent complete fundoplication, 559 who underwent partial posterior fundoplication, and 70 who underwent partial anterior fundoplication. MAIN OUTCOME MEASURES: Evaluation of clinical and quality-of-life actions used to treat the symptoms of gastroesophageal reflux disease. RESULTS: The overall residual severe dysphagia rate was 5.1% (n = 68). A further surgical procedure was required for 59 patients (4.4%) for a total of 63 interventions. Subsequent operation was performed laparoscopically in 32 cases (50.8%). Twelve of these procedures were for the repair of a paraesophageal hiatus hernia, 11 were for dysphagia (4 because of a tight esophageal hiatus and 7 for conversion of Nissen fundoplication to a posterior partial fundoplication procedure), 31 were for recurrent reflux (wrap undone), 2 were for intestinal obstruction (adhesiolysis), 1 was for incisional hernia, 1 was for abdominal abscess (drainage), and 1 was for gastroparesis (pyloroplasty). The recurrence rate was 10.1% (n = 136), and 122 patients (9.1%) resumed taking antisecretory medication. Gas bloat syndrome was present in 101 patients (7.5%). A total of 93.1% of the patients were satisfied (Visick classification, grades 1 and 2) and 6.9% were unsatisfied, with no difference among the 3 procedures. CONCLUSION: After 5 years of experience, laparoscopic fundoplication remains an effective antireflux procedure.

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Curr Opin Pharmacol. 2005 Oct 5; [Epub ahead of print]
Gastroesophageal reflux disease.
Armstrong D.
Division of Gastroenterology, HSC-2F55, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario Canada L8N 3Z5.

Gastroesophageal reflux disease (GERD) is increasingly common worldwide; symptoms differ between individuals and endoscopically visible injury is present in only about 50% of cases. Although GERD is a disorder of gastrointestinal motility and structure, the most effective therapy is based on the use of acid antisecretory drugs. Proton pump inhibitors (PPIs), the most effective class of acid suppression agents to date, have revolutionised the management of GERD. However, PPIs do have some shortcomings and recent developments include documentation of increased healing rates with more prolonged acid suppression, more prolonged acid suppression with a new PPI (tenatoprazole) and more rapid onset of acid suppression with a new class of drugs, the reversible, potassium-competitive acid blockers. Studies with motility agents, such as the 5-HT(4) partial agonist tegaserod and the GABA(B) agonist baclofen, indicate that motility is important in the pathogenesis of GERD but, for several reasons, it will be a challenge to develop new classes of drug that outperform current PPIs with respect to efficacy, broad applicability and safety.

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Eur J Intern Med. 2005 Oct;16(6):391-401.
Gastroesophageal reflux.
Zamir D.
Department of Internal Medicine D, Barzilai Medical Center, Ashkelon, 78306, Israel.

Gastroesophageal reflux disease (GERD) is the most common disease of the gastrointestinal system. Heartburn, regurgitation, and dysphagia are the most common symptoms of GERD. However, chest pain, chronic cough, laryngitis, hoarseness, and other otolaryngologic manifestation can be the primary manifestations of the disease. Endoscopy, barium studies, and especially pH monitoring and therapeutic trials may help in establishing the diagnosis of GERD. The introduction of H2 antagonists and especially of proton pump inhibitors (PPI) has brought symptomatic relief in most patients. However, surgical procedures, especially laparoscopic fundoplication, are still required in some patients. Barrett's esophagitis is the most common complication of GERD and is associated with a high prevalence of esophageal adenocarcinoma. Whether or not treatment with either PPIs or H2 antagonists can prevent this complication is still under investigation.

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Int J Clin Pract. 2005 Oct;59(10):1204-9.
Recent advances in the treatment of GERD in the elderly: focus on proton pump inhibitors.
Pilotto A, Franceschi M, Paris F.
IRCCS, Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo, Italy. alberto.pilotto@libero.it

The prevalence of gastroesophageal reflux disease (GERD) increases with age, and older people are more likely to develop severe disease. Studies of elderly patients with GERD indicate differences in presentation and diagnosis, compared with GERD in younger adults. Indeed, an older patient with GERD may present with atypical symptoms such as dysphagia, vomiting, weight loss, anaemia and anorexia, and less frequently with typical symptoms such as heartburn or acid regurgitation. These findings are attributed to pathophysiological changes in esophageal function that occur with age. Therefore, GERD in elderly patients is more likely to be poorly diagnosed or undiagnosed. Although few studies have concentrated specifically on elderly patients, the proton pump inhibitors (PPIs) have been shown to be more effective than histamine receptor antagonists for healing reflux esophagitis and for preventing its recurrence when they are given as maintenance therapy. In addition, the PPIs seem to be safe both in short- and in long-term therapy of elderly patients with GERD.

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Surg Endosc. 2005 Oct;19(10):1309-14. Epub 2005 Aug 11.
European multicenter survey on the laparoscopic treatment of gastroesophageal reflux in patients aged less than 12 months with supraesophageal symptoms.
Mattioli G, Bax K, Becmeur F, Esposito C, Heloury Y, Podevin G, Lima M, MacKinlay GA, Goessler A, Tovar JA, Valla J, Tuo P, Nahum L, Ottonello G, Sacco O, Gentilino V, Pini-Prato A, Caponcelli E, Jasonni V.
Pediatric Surgery, Gaslini Research Institute, University of Genova, Italy. girolamomattoli@ospedale-gaslini.ge.it

BACKGROUND: This multicenter survey includes neonates and infants who underwent surgery for primary gastroesophageal reflux (GER) who presented with supraesophageal symptoms of unknown origin with a minimum of 12 months postoperative follow-up. METHODS: A total of 726 patients underwent GER surgery in 10 European Centers in the period 1998-2002. Respiratory symptoms were present in 204 patients (28%); 135 patients (17%) had surgery under 1 year of age, and 46 of them (6.3%) because of respiratory symptoms. Surgery was performed without any previous medical treatment in 10 cases (21%). The type of procedure included 37 complete 360 degrees wraps (80%) (Nissen, 12, and Rossetti, 25) and nine partial wraps (20%) (Thal five, Lortat Jacob one, Toupet one, others two). Gastrostomy was associated in 17 cases (37%) (6 PEG and 11 modified Stamm). No gastric emptying procedures were recorded. RESULTS: No major intraoperative complications were reported. Six patients developed complications (13%) and a redo operation was performed in three (6.5%). Respiratory outcome after antireflux surgery was good in 35 patients (76%) and fair with significantly improved respiratory symptoms in 11 (24%). CONCLUSIONS: This multicenter survey underlines that GER has to be suspected and aggressively treated in infants with difficult-to-treat supraesophageal symptoms, and also in high-risk cases, in order to prevent major complications.

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Clin Gastroenterol Hepatol. 2005 Sep;3(9):831-9.
Endoscopic antireflux procedures: a good wrap?
Wakelin DE, Sampliner RE.
Section of Gastroenterology, Southern Arizona VA Health Care System and University of Arizona Health Sciences Center, 3601 S. 6th Avenue, Tucson, AZ 85723, USA.

BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD) is prevalent worldwide. Until recently patients and physicians have had a choice between long-term medical therapy, usually in the form of proton pump inhibitors (PPIs), or surgical fundoplication. During the past several years, endoscopic antireflux therapies have been approved for GERD patients to potentially obviate the risks of surgery and avoid long-term medication use. The objective of this review was to critically evaluate existing literature on endoscopic antireflux therapies with regards to efficacy and safety. METHODS: A review of human studies by using Pub Med was performed. RESULTS: Injectable LES implants, endoscopically placed gastric plications, and radio frequency energy application to the LES comprise the 3 modes of antireflux therapies. These techniques received approval by the Food and Drug Administration on the basis of symptomatic evidence supplied by numerous uncontrolled trials. As a group, these techniques have demonstrated efficacy less than medical and surgical options, and yet they carry a rare but significant risk of serious complications and even death. CONCLUSIONS: The field is still evolving at this stage, and there is a need for more randomized sham and placebo-controlled trials to better define the subjective and objective outcomes of these endoscopic procedures. At this time endoscopic antireflux procedures should be used with caution after discussing risks and benefits with the patient.

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Am J Gastroenterol. 2005 Sep;100(9):1914-22.
Effect of esomeprazole on nighttime heartburn and sleep quality in patients with GERD: a randomized, placebo-controlled trial.
Johnson DA, Orr WC, Crawley JA, Traxler B, McCullough J, Brown KA, Roth T.
Eastern VA School of Medicine, Norfolk, Virginia, USA.

OBJECTIVES: Sleep disturbances are common in patients with gastroesophageal reflux disease (GERD). This study examined the effects of esomeprazole on nighttime heartburn, GERD-related sleep disturbances, sleep quality, work productivity, and regular activities. METHODS: This multicenter, randomized, double-blind, placebo-controlled trial included adults with GERD-associated sleep disturbances and moderate-to-severe nighttime heartburn (recorded by patient diary during screening). Patients received oral esomeprazole 40 mg (n = 220) or 20 mg (n = 226) or placebo (n = 229) once daily for 4 wk. The primary outcome was relief of nighttime heartburn. Secondary outcomes included resolution of sleep disturbances, sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and work productivity measured by the Work Productivity and Activity Impairment Questionnaire. RESULTS: Nighttime heartburn was relieved in 53.1% (111/209), 50.5% (111/220), and 12.7% (28/221) of patients who received esomeprazole 40 mg, esomeprazole 20 mg, and placebo, respectively. Differences (95% CI) versus placebo were 40.5% (32.4%, 48.5%) and 37.8% (29.9%, 45.7%) and were highly significant (p < 0.0001). GERD-related sleep disturbances resolved in significantly more (p < 0.0001) patients who received esomeprazole 40 (73.7%) or 20 mg (73.2%) than in those who received placebo (41.2%). Both esomeprazole groups had greater PSQI global score changes from baseline (p < 0.0001 vs placebo) and more (p < 0.0001 vs placebo) work hours saved per week per patient compared with baseline (esomeprazole 40 mg, 11.6 h; esomeprazole 20 mg, 12.3 h; placebo, 6.2 h). CONCLUSIONS: Esomeprazole reduced nighttime heartburn and GERD-related sleep disturbances and improved sleep quality and work productivity.

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Digestion. 2005;72(2-3):76-85. Epub 2005 Aug 19.
On-demand therapy with pantoprazole 20 mg as effective long-term management of reflux disease in patients with mild GERD: the ORION trial.
Scholten T, Dekkers CP, Schutze K, Korner T, Bohuschke M, Gatz G.
Medizinische Klinik des Allgemeinen Krankenhauses Hagen, Hagen, Germany. scholten@akh-hagen.de

AIMS: To compare safety and efficacy of on-demand pantoprazole 20 mg/40 mg versus placebo in the long-term management of patients with mild gastroesophageal reflux disease (GERD) after heartburn relief. METHODS: A total of 634 patients with endoscopically confirmed GERD grade 0/I and heartburn were included. During the acute phase, patients were treated with pantoprazole 20 mg once daily for 4 weeks. Those patients relieved from heartburn entered the long-term phase, and were randomly assigned to either treatment group pantoprazole 20 mg, 40 mg or placebo. Over 6 months, patients took study medication on demand (antacids as rescue medication) and discontinued the drug once symptoms abated. RESULTS: After 4 weeks a total of 87.1%/90.0% of patients were free of heartburn (ITT/PP), and entered the subsequent long-term phase. The perceived average daily symptom load (placebo: 3.93, pantoprazole 20 mg: 2.91, pantoprazole 40 mg: 2.71, ITT) and the number of antacid tablets taken (average number, placebo: 0.68, pantoprazole 20 mg: 0.45, pantoprazole 40 mg: 0.33, ITT) were significantly higher in the placebo than in both pantoprazole groups (p<0.0001), with no statistically significant difference between the two pantoprazole groups. The discontinuation rate due to insufficient control of heartburn was significantly lower in both pantoprazole groups compared to placebo (placebo: 10.9, pantoprazole 20 mg: 2.8, pantoprazole 40 mg: 0.9, ITT). CONCLUSIONS: Our findings favor on-demand treatment with pantoprazole 20 mg for the long-term management of heartburn in patients with uncomplicated GERD (grade 0/I) with superiority to placebo. Copyright (c) 2005 S. Karger AG, Basel.

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Thorac Surg Clin. 2005 Aug;15(3):405-15.
Lower esophageal sphincter injections for the treatment of gastroesophageal reflux disease.
Watson TJ, Peters JH.
Division of Thoracic and Foregut Surgery, Department of Surgery, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box Surgery, Rochester, NY 14642, USA. thomas_watson@urmc.rochester.edu

Endoscopic therapies for the control of GERD offer the potential for significant symptomatic improvement while obviating many of the potential drawbacks associated with long-term medical therapy with acid suppressive or neutralizing medications and traditional antireflux surgery. Such endoluminal therapies are intended to be safe with a brief learning curve, easily administered in an outpatient setting without the need for general anesthesia, reproducible, and durable. LES injection therapies share the common theoretic method of action of bulking at the GEJ, leading to loss of sphincter compliance and distensibility. In the case of Enteryx, this sustained effect has been demonstrated to be secondary to chronic inflammation, fibrosis, and encapsulation resulting from a foreign body response to the injectate. Available data suggest that a majority of patients respond to LES injection therapies, as demonstrated by a decreasing usage of PPIs after implantation, the ability of many patients to terminate PPI use completely, and improved GERD-HRQOL scores. Responses seem reasonably durable in follow-up assessment up to 24 months post treatment. Although there may be some placebo effect associated with treatment, patients injected with Enteryx respond better than a control group of sham-treated subjects. Individuals treated with LES injections, however, represent a select subgroup of the overall population of refluxers. Study subjects, by and large, have had uncomplicated GERD with typical reflux symptoms of heartburn or regurgitation that have responded to PPIs. Patients who have severe anatomic derangements, such as esophageal strictures, persistent esophagitis, Barrett's esophagus, or sizeable hiatal hernias, are excluded from clinical trials, as are patients who have severe motility disorders or significant comorbid conditions. Similarly, patients who have responded poorly to PPIs and those who have primarily extraesophageal manifestations of GERD have not been studied. Outcomes to date have been assessed over the short to medium term; long-term outcome studies are lacking. The durability of response, therefore, remains largely unknown, as does the incidence of any long-term complications or side effects. A postmarket study to assess the long-term safety and durability of Enteryx therapy up to 36 months is under way, as required by the FDA, with a target enrollment of 300 patients. Detailed cost analyses have yet to be reported. Such data are important not only for comparing the various endoluminal therapies but also for comparison to standard medical therapy and antireflux surgery. At present, no randomized trials are completed that compare injection therapies to other accepted treatments of GERD. The ability to perform fundoplication safely and effectively after failed LES injection therapy is not well known, in that the number of subsequent surgical cases is small and the results largely anecdotal to date. Likewise, the ability to use LES injection as salvage therapy after failed fundoplication has not been tested. The data regarding endoluminal injection therapies are similar to those after endoscopic plication and radiofrequency application to the LES, in that a definite symptomatic response is observed, but the objective documentation of diminished esophageal acid exposure lags behind. Esophageal acid exposure is normalized in a minority of treated subjects and improved in an additional subgroup, whereas the rate of symptomatic response exceeds these objective improvements. The reasons for this disconnect are the subject of much speculation and controversy. A placebo effect has been discussed, but clearly more factors are at play. Perhaps a study effect also is important, in that patients enrolled in clinical trials for GERD control may be more likely to modify their dietary and lifestyle habits in an effort to bring about symptom relief. Maybe the understanding of the perception of reflux events is lacking, and these endoluminal therapies work mainly by altering the perception of reflux more than the amount of reflux itself. A recent technologic review of injection therapies for GERD concludes that the "data for Enteryx are as compelling as those of any other open-label evaluation of an endoluminal therapy for GERD". There is much to be learned about all endoluminal techniques. For now, LES injections are promising therapies lacking supportive evidence of long-term safety and efficacy. The available data justify their use only in patients who have GERD symptoms responsive to PPIs and who do not have significant comorbidities or complications associated with GERD. Whether or not the role of LES injection techniques will be expanded to include more complicated cases, patients who are partially responsive to PPIs, combination therapy with other endoluminal techniques, or salvage therapy after failed fundoplication awaits further study.

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Am J Gastroenterol. 2005 Aug;100(8):1844-52.
Antireflux surgery outcomes in pediatric gastroesophageal reflux disease.
Diaz DM, Gibbons TE, Heiss K, Wulkan ML, Ricketts RR, Gold BD.
Pediatric Gastroenterology and Nutrition, Emory University School of Medicine, Atlanta, Georgia.

OBJECTIVES: Antireflux surgery is performed frequently in children with gastroesophageal reflux disease (GERD). Few comparative studies exist which assess the indications for and short- or long-term outcome of open Nissen fundoplication (ONF) and laparoscopic Nissen fundoplication (LNF) for pediatric GERD. We investigated the frequency of reoperation and factors that might influence its occurrence. METHODS: We performed a retrospective, follow up cohort study of all children </=5 years, who underwent LNF or ONF at our institution from January 1, 1997 to December 31, 2002, where five pediatric surgeons perform fundoplication. Mean follow up time was 36.2 months. The following information was obtained: surgical indications, hospital course data, and long-term surgical outcomes. Data were analyzed using univariate and multiple logistic regressions. RESULTS: Overall, 456 (150 [32.9%] ONF vs. 306 [67.1%] LNF) cases were analyzed. Reoperation was performed in 55 (12.06%), LNF 43 (14.05%), and ONF 12 (8%). The mean interim to reoperation for LNF was 11 months compared to 17 months for ONF (p= 0.007). The reoperation rate at 12 and 24 months were 10.5%, 13.4% and 4%, 6.7% respectively, when LNF was compared to ONF (p= 0.01). The multivariate analysis showed that initial LNF and prematurity were the main predictors for reoperation. CONCLUSIONS: The majority of reoperations for both LNF and ONF occurred in the first year after initial operation; LNF had a significantly higher reoperation rate than ONF. The probability of reoperation for LNF and ONF increases with the presence of comorbidities, especially prematurity and chronic respiratory conditions. (Am J Gastroenterol 2005;100:1844-1852).

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J Long Term Eff Med Implants. 2005;15(4):375-88.
Management of gastroesophageal reflux disease: medications, surgery, or endoscopic therapy? (Current status and trends).
Zhi XT, Kavic SM, Park AE.
Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, P. R. China.

Gastroesophageal reflux disease (GERD) is a common chronic disorder in the Western world. The basic cause of GERD has been well characterizedthe fundamental defect is a loss of integrity of the gastroesophageal barrier. What is less clear is the most appropriate means of addressing this reflux. GERD has a variety of symptoms, ranging from typical presentations of heartburn and regurgitation (without esophagitis) to atypical presentations, such as severe erosive esophagitis and its associated complications. Because of its symptomatic diversity, physicians may select from a variety of therapeutic approaches. Medical therapy aims at decreasing acidity by suppressing proton secretion and has been well established. Available medications include antacids and alginates, H2-receptor antagonists, motility agents, and proton pump inhibitors (PPIs). Antireflux surgery, commonly performed laparoscopically, aims at reinforcing and repairing the defective barrier through plication of the gastric fundus. The earliest performed successful procedures were the Nissen and Toupet fundoplications, to which several modifications have since been made. It has been demonstrated in preliminary studies and long-term outcomes of such open surgery and preliminary studies of such laparoscopic surgery that antireflux surgery is an effective approach, with overall outcomes superior to those achieved with medications. The precise indications for the surgical treatment of patients with GERD, however, remain controversial. In recent years, endoscopic intraluminal antireflux approaches have attracted the attention of physicians, surgeons, and commercial companies, especially after the approval of two endoscopic intraluminal methods by the United States FDA in 2000. The common element is prevention of acid reflux by construction of a functional or controlled barrier in the lower esophageal sphincter zone. Three main methods are currently employed: endoscopic intraluminal valvuloplasty, endoscopic radiofrequency therapy, and endoscopic injection or implantation of foreign material. The endoluminal suturing method is highly demanding technically, and its short-term results are encouraging, although largely dependent on the experience of the endoscopist. Several prospective cohort studies have shown that the radiofrequency procedure (Stretta(R)) significantly improves GERD symptoms and quality of life while reducing esophageal acid exposure and eliminating the need for antisecretory medications in the majority of patients within 6-12 months. Most recently, some researchers have studied the endoluminal implantation of polymers, such as Plexiglastrade mark (polymethyl-methylacrylate), Gatekeeper(R) hydrogel, and Enteryx(R) (ethylene vinyl alcohol copolymer). The preliminary results of these studies showed that the implantation method was feasible and safe; however, the only multicenter trial related to outcome that has been published has included just 1 year of follow-up. Here, we review the treatment of GERD: medical, surgical, and endoscopic. In addition, we provide an algorithm based on symptoms and response to treatment for management of these patients.

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Can J Gastroenterol. 2005 Jul;19(7):425-7.
Should we test for Helicobacter pylori before treating gastroesophageal reflux disease?
Moayyedi P.
McMaster University, Hamilton, Canada.

Gastroesophageal reflux disease (GERD) is a common problem in childhood. The cause is uncertain but because the incidence of GERD is increasing in developed countries and the prevalence of Helicobacter pylori is decreasing, it has been suggested that this infection protects against GERD. Observational data from 95 children, however, suggest that H pylori eradication does not have a deleterious effect on GERD and this is supported by randomized controlled trials in adults. H pylori eradication may also reduce the efficacy of proton pump inhibitor therapy in infected patients. There are no data from children but inferences from randomized controlled trials in adults suggest this effect is likely to be modest and of uncertain clinical significance. H pylori is an important risk factor for distal gastric adenocarcinoma. It is likely that treating the infection in childhood will prevent pre-malignant changes associated with H pylori from developing in the future. A meta-analysis of four randomized controlled trials suggest that there is a statistically significant impact on healing of chronic gastritis after one year compared with placebo (RR of chronic gastritis: 0.27; 95% CI 0.23 to 0.32). H pylori eradication is therefore recommended in children with GERD that are having an endoscopy. However, when the diagnosis of GERD is being made clinically or by pH monitoring, it is not necessary to screen for H pylori.

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Can J Gastroenterol. 2005 Jul;19(7):399-408.
Canadian Helicobacter Study Group Consensus Conference: Update on the approach to Helicobacter pylori infection in children and adolescents - An evidence-based evaluation.
Jones NL, Sherman P, Fallone CA, Flook N, Smaill F, van Zanten SV, Hunt R, Thomson A.
The Hospital for Sick Children, Toronto, Canada.

As an update to previously published recommendations for the management of Helicobacter pylori infection, an evidence-based appraisal of 14 topics was undertaken in a consensus conference sponsored by the Canadian Helicobacter Study Group. The goal was to update guidelines based on the best available evidence using an established and uniform methodology to address and formulate recommendations for each topic. The degree of consensus for each recommendation is also presented. The clinical issues addressed and recommendations made were: population-based screening for H pylori in asymptomatic children to prevent gastric cancer is not warranted; testing for H pylori in children should be considered if there is a family history of gastric cancer; the goal of diagnostic interventions should be to determine the cause of presenting gastrointestinal symptoms and not the presence of H pylori infection; recurrent abdominal pain of childhood is not an indication to test for H pylori infection; H pylori testing is not required in patients with newly diagnosed gastroesophageal reflux disease; H pylori testing may be considered before the use of long-term proton pump inhibitor therapy; testing for H pylori infection should be considered in children with refractory iron deficiency anemia when no other cause has been found; when investigation of pediatric patients with persistent or severe upper abdominal symptoms is indicated, upper endoscopy with biopsy is the investigation of choice; the 13C-urea breath test is currently the best noninvasive diagnostic test for H pylori infection in children; there is currently insufficient evidence to recommend stool antigen tests as acceptable diagnostic tools for H pylori infection; serological antibody tests are not recommended as diagnostic tools for H pylori infection in children; first-line therapy for H pylori infection in children is a twice-daily, triple-drug regimen comprised of a proton pump inhibitor plus two antibiotics (clarithromycin plus amoxicillin or metronidazole); the optimal treatment period for H pylori infection in children is 14 days; and H pylori culture and antibiotic sensitivity testing should be made available to monitor population antibiotic resistance and manage treatment failures.

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Ann Chir. 2005 Jul 5; [Epub ahead of print]
[The outcomes of laparoscopic fundoplication for gastro-oesophageal reflux disease. Long term results.]
[Article in French]
Dan S, Brigand C, Pierrard F, Rohr S, Meyer C.
Service de chirurgie generale et digestive, Centre de chirurgie viscerale et de transplantation, CHU de Strasbourg, Hautepierre, avenue Moliere, 67098 Strasbourg, France.

Introduction. - The aim of this study was to evaluate the long term efficacy of laparoscopic treatement of gastroesophageal reflux disease (GERD). Patient and methods. - Between 1(st) January 1992 and 31 December 1996, 161 patients underwent complete or partial laparoscopic fundoplication for a symptomatic GERD. One hundred and twenty three patients were submitted to Nissen-Rossetti fundoplication, 26 patients to Nissen fundoplication and 12 patients to a partial posterior Toupet fundoplication.141 patients were evaluated at 3 months, 2-years and 5-years. Since undergoing the operation, four patients died of unrelated causes, 16 patients could not be contacted for follow up (10%). pH monitoring and oesophageal manometry were performed preoperatively and at 3 months postoperatively. The patients were evaluated 2 and 5-years after surgery by specific phone questionnaire. Results. - There was no mortality, the morbidity rate was 1.2% and the conversion rate was 5%. Incidence of dysphagia 3 months after surgery was 23.4%, and 5-years after 12%; 12% of patients had recurrent symptoms at 5 years. Conclusion. - The overall satisfaction rate at 5 years was 91.4%. Nissen-Rossetti fundoplication seems to have better results at 5-years regarding postoperative dysphagia and symptoms recurrence.

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Gastrointest Endosc. 2005 Jul;62(1):24-30.
Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett's cancer and high-grade intraepithelial neoplasia.
Pech O, Gossner L, May A, Rabenstein T, Vieth M, Stolte M, Berres M, Ell C.
Department of Medicine II, HSK Wiesbaden, Teaching Hospital of the University of Mainz, Germay.

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has proven to be safe and effective in patients with early neoplasia in Barrett's esophagus. However, long-term results in patients with high-grade intraepithelial neoplasia (HGIN) or with early cancer are still lacking. METHODS: The aim of the study was to evaluate the efficacy of ALA-PDT and the survival of patients with early Barrett's neoplasia. ALA-PDT was carried out in 66 patients. Protoporphyrin IX induced by oral administration of ALA (60 mg/kg body weight orally applied 4-6 hours before PDT) was used as the photosensitizer. Acid suppression was maintained in all patients. RESULTS: Between September 1996 and September 2002, 667 patients with early neoplasia in Barrett's esophagus were referred for local endoscopic therapy. A total of 558 patients fulfilled the criteria for local endoscopic therapy, and 66 patients (mean [standard deviation] age 61.4 [10.2] years) with HGIN (group A; n = 35) and early adenocarcinoma (group B; n = 31) were treated by PDT. A total of 82 ALA-PDT were performed. A total of 34 of the 35 patients in group A (97%) and all patients in group B (100%) achieved a complete response during a median follow-up period of 37 months (interquartile range 23-55) (not significant). One local recurrence was observed in group A and 10 in group B (p < 0.005). Seven patients died during follow-up; but, all deaths were not tumor related. No major complications were observed. Disease-free survival in patients with HGIN was 89%, and, in patients with mucosal cancer, it was 68%. The calculated 5-year survival was 97% in group A and 80% in group B, but there occurred no death related to Barrett's neoplasia. CONCLUSIONS: The excellent long-term results of PDT with ALA in patients with HGIN or mucosal cancer might offer PDT with ALA as an alternative to surgical esophagectomy and endoscopic resection, especially in cases with multifocal Barrett's neoplasia.

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Curr Opin Gastroenterol. 2005 Jul;21(4):490-7.
Endoscopic therapeutic esophageal interventions: what is new? What needs further study? What can we forget?
Siersema PD.
Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. p.siersema@erasmusmc.nl

PURPOSE OF THIS REVIEW: Endoscopic esophageal interventions form an important part of gastrointestinal endoscopy. This article reviews the most notable results of esophageal endoscopy and interventions published in 2004. RECENT FINDINGS: Both argon plasma coagulation and photodynamic therapy were shown to have high success rates in removing Barrett's epithelium. After ablative treatment, residual Barrett's esophagus still poses an increased esophageal cancer risk and is a concern. Endoscopic resection is now an accepted alternative to surgical resection of early-stage squamous cell and adenocarcinoma of the esophagus. Four studies convincingly demonstrated that covered plastic stents could be used in the initial therapy of patients with refractory benign esophageal strictures, and anastomotic leaks after esophageal surgery. Evidence was presented that intraluminal radiotherapy (brachytherapy) is a valuable alternative to stent placement in patients with malignant dysphagia. It has become clear that injections with botulinum toxin at the gastroesophageal junction in patients with achalasia are often only temporarily effective. It was shown that endoluminal gastroplication produced good symptomatic results; however, data on the reduction of esophageal acid exposure were less impressive. Finally, the first results of endoscopic implantation of expandable antireflux prostheses (Gatekeeper Reflux Repair System, Medtronic Europe, Tolochenaz, Switzerland) in the distal esophageal submucosa were reported. SUMMARY: In 2004, new data on available esophageal therapeutic techniques became available. In addition, new information on an old established technique (brachytherapy for malignant dysphagia) and a new device (Gatekeeper system for the prevention of reflux) were presented.

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Curr Opin Gastroenterol. 2005 Jul;21(4):461-5.
Barrett's esophagus.
Bonino JA, Sharma P.
Division of Gastroenterology and Hepatology University of Kansas School of Medicine and Veterans Affairs Medical Center, Kansas City, Missouri 64128-2295, USA. psharma@kumc.edu

PURPOSE OF REVIEW: Significant advances have been made over the past year to identify individuals with Barrett's esophagus, who are at increased risk of malignant transformation. We summarize some of the important advances in that regard including: improved understanding in areas of epidemiology of those with Barrett's esophagus, identification of the pathways responsible for dysplastic and metaplastic development, selection of patient populations who would most benefit from surveillance protocols, and identification of biomarkers signifying progression of metaplastic changes. RECENT FINDINGS: Barrett's esophagus is being better recognized in patients presenting with extra-esophageal symptoms of gastroesophageal reflux such as chronic cough and asthma. Recent reports from some surgical series further suggest the importance of gastric and even duodenal reflux in the etiology of esophageal metaplastic development. In vitro experiments using acidic environments, to stimulate MAPK pathways, suggest an etiology for increased COX-2 expression. There appears to be a select group of individuals with familial predilection for the development of Barrett's esophagus. Retrospective studies continue to show apparent survival benefit in individuals with Barrett's esophagus undergoing surveillance endoscopy. Endoscopic ablative therapy may provide clinicians an attractive alternative to surgical resection in individuals with high-grade esophageal dysplasia and early adenocarcinoma. SUMMARY: The past year has brought many advances in the epidemiology, pathogenesis, surveillance, and treatment of those with Barrett's esophagus. Clinicians will benefit from review of these advances, and use of the most up-to-date data to ensure better patient outcomes.

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Rev Esp Enferm Dig. 2005 May;97(5):328-37.
Surgery for gastroesophageal reflux disease: a comparative study between the open and laparoscopic approaches.
[Article in English, Spanish]
Trullenque Juan R, Torres Sanchez T, Marti Martinez E, Martinez Abad M, Trullenque Peris R, Delgado Gomis F.
Service of General Surgery, Hospital Dr. Peset, 46017 Valencia, Spain. ramtrull@yahoo.es

OBJECTIVE: Given the demonstrated effectiveness of medical treatment together with the eminent acceptance of the laparoscopic approach, the indications of surgery in the treatment of gastroesophageal reflux disease (GERD) are currently subject to continuous controversy. To participate in this debate, we have the following work hypothesis: "The results of the 360 masculine short and floppy laparoscopic fundoplication are superior to those of open surgery". CLINICAL DESIGN: Prospective, clinical, non-randomized study. PATIENTS: Our work was developed between November 1991 and December 1998 by means of a prospective, non-randomized clinical rehearsal with two groups of patients: Group I (n = 75): 360 degree short and floppy laparoscopic fundoplication in Hospital Dr. Peset, Valencia (Spain). Group II (n = 28): 360 degree short and floppy, open fundoplication in Hospital General, Valencia (Spain).We evaluated the preoperative parameters and found no differences, which allows us to know that both groups were comparable. RESULTS: The analysis of peroperative results (morbidity and surgical time) and of clinical follow-up (every three months and later annually) and instrumental follow-up (TEGD, upper digestive endoscopy, pHmetry and manometry) show no differences, while the postoperative analysis shows statistically significant (s.s.) differences regarding recovery (pain, oral intake, hospital stay and return to previous activities). CONCLUSIONS: The results of the 360 degree short and floppy laparoscopic fundoplication are similar to those of the open approach, but favor the former approach with a better postoperative tolerance.

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Dis Esophagus. 2005;18(2):75-86.
Molecular targets for treatment of Barrett's esophagus.
Feagins LA, Souza RF.
Department of Medicine, Dallas VA Medical Center and University of Texas Southwestern Medical School, Dallas 75216, USA.

SUMMARY. Esophageal cancer is one of the most deadly forms of gastrointestinal cancer with a mortality rate exceeding 90%. The major risk factors for esophageal adenocarcinoma are gastroesophageal reflux disease (GERD) and its sequela, Barrett's esophagus. GERD commonly leads to esophagitis. In a minority of patients however, ongoing GERD leads to replacement of esophageal squamous mucosa with metaplastic, intestinal-type Barrett's mucosa. In the setting of continued peptic injury, Barrett's mucosa can give rise to esophageal adenocarcinoma. Despite the widespread use of potent acid suppressive therapies for patients with GERD, the incidence of esophageal adenocarcinoma, among white men in the USA, the UK and Europe has continued to rise. Cancers in Barrett's esophagus arise through a sequence of genetic events that endow the cells with six essential physiologic hallmarks of cancer as described by Hanahan and Weinberg in 2000. These cancer hallmarks include the ability to proliferate without exogenous stimulation, to resist growth-inhibitory signals, to avoid triggering the programmed death mechanism (apoptosis), to resist cell senescence, to develop new vascular supplies (angiogenesis), and to invade and metastasize. While the acquisition of these essential attributes is not specific to the neoplastic progression of Barrett's esophagus, this review will focus on the genetic alterations that occur in Barrett's cells that contribute to the acquisition of each of the hallmarks. Moreover, potential diagnostic and therapeutic strategies for Barrett's patients aimed at each of these cancer hallmarks will be reviewed.

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Endoscopy. 2005 May;37(5):470-8.
Endoscopic treatment of gastroesophageal reflux disease.
Annese V, Caletti G, Cipolletta L, Costamagna G, D'Onofrio V, Leandro G, Koch M, Pace F, Penagini R, Repici A, Ricci E, Vigneri S, Zaninotto G.
U.O. Gastroenterologia, Ospedale CSS-IRCCS, San Giovanni Rotondo, Italy.

Gastroesophageal reflux disease is a common chronic disorder which has a severe effect on the patient's quality of life. In view of the high cost of medical therapy and the limitations of surgery, a variety of endoscopic techniques have been developed for the treatment of this condition, and these have shown apparently encouraging results, at least in the short term. However, promising results have been obtained in only around two-thirds of patients over a short-term follow-up period of about 6 months. Moreover, several inconsistencies have emerged between the efficacy of this form of treatment in improving symptoms and quality of life and a lack of improvement of objective parameters, such as lower esophageal sphincter pressure and esophageal acid exposure. The authors strongly endorse the need for comprehensive evaluation of clinical evidence on this topic. After an extensive evaluation of existing literature, we suggest that controlled studies are urgently needed in order to clarify the potential of endoscopic therapy, either in terms of cost-effectiveness or in comparison with standard therapy. Meanwhile, with regard to current practice, the use of endoscopic treatment should be limited to clinical trials, which should incorporate the provision of comprehensive and unbiased information to study patients.

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Am J Gastroenterol. 2005 May;100(5):1002-8.
Fundoplication and the risk of esophageal cancer in gastroesophageal reflux disease: a veterans affairs cohort study.
Tran T, Spechler SJ, Richardson P, El-Serag HB.
Department of Medicine, Baylor College of Medicine, Houston, Texas.

BACKGROUND AND AIMS: It has been proposed that fundoplication can reduce the risk of esophageal cancer in patients with gastroesophageal reflux disease (GERD). In this cohort study, we assessed the effect of fundoplication on the incidence of esophageal cancer. METHODS: We identified all Veterans Affairs (VA) patients with GERD who had fundoplication between 1986 and 1990 and matched (1-2) to controls with GERD and no fundoplication and to controls with no GERD. We calculated incidence rates for esophageal cancer through October 2002 and examined the effect of fundoplication on the risk of esophageal cancer using Kaplan-Meier survival analysis and Cox proportional hazard analysis. We calculated and adjusted for the propensity score for receiving fundoplication. RESULTS: We identified 946 patients who had fundoplication, 1,892 patients who had GERD without fundoplication, and 5,676 patients with no GERD. The mean age was 55 yr and 97.5% were men in all three groups. During a follow-up of 11,156 patient-years (PY), there were eight cases of esophageal cancer (72/100,000) in the fundoplication group. During a follow-up of 20,115 PY, there were eight cases of esophageal cancer (40/100,000) in the GERD without fundoplication group. During a follow-up of 59,439 PY, no patients in the group with no GERD developed esophageal cancer. The Kaplan-Meier analysis showed no significant difference in cumulative esophageal cancer rates between the fundoplication group and the GERD no-fundoplication group. The adjusted hazard ratio of esophageal cancer with fundoplication was 1.88 (95% CI: 0.70-5.03). CONCLUSIONS: GERD is a risk factor for esophageal cancer, but there is insufficient evidence that fundoplication reduces that risk. (Am J Gastroenterol 2005;100:1002-1008).

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Cochrane Database Syst Rev. 2005 Apr 18;2:CD004823.
Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults.
Chang A, Lasserson T, Gaffney J, Connor F, Garske L.
Respiratory Medicine, Royal Children's Hospital, Herston Road, Herston, Brisbane, Queensland, AUSTRALIA, 4029.

BACKGROUND: Cough is a very common symptom presenting to medical practitioners. Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. However cough and GORD are common ailments and their co-existence by chance is high. Also cough can induce reflux episodes. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H(2) antagonist and proton pump inhibitors (PPI)) and fundoplication. OBJECTIVES: To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease i.e. non-specific chronic cough. SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register Collaboration and Cochrane Airways Group, MEDLINE and EMBASE databases, review articles and reference lists of relevant articles were searched. The date of last search was 4th April 2004. SELECTION CRITERIA: All randomised controlled trials on GORD treatment for cough in children and adults without primary lung disease. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. Two independent reviewers selected, extracted and assessed data for inclusion. Authors were contacted for further information. Data was analysed as "intention to treat" as well as "treatment received". Paediatric and adults data were considered separately. Sensitivity analyses were performed. MAIN RESULTS: 11 studies (3 paediatric, 8 adults; 383 participants) were included. None of the paediatric studies could be included in meta-analysis. In adults, analysis on use of H(2) antagonist, motility agents and conservative treatment for GORD were not possible (from lack of data) and there were no controlled studies on fundoplication as an intervention. Five adult studies comparing PPI (2-3 months) to placebo were analysed for various outcomes in the meta-analysis. Enrolment of subjects for two studies were primarily from medical clinics and another three studies were otolaryngeal clinic patients. Using "intention to treat", pooled data from three studies resulted in no significant difference between treatment and placebo in total resolution of cough. Pooled data revealed no significant improvement in cough outcomes (end of trial or change in cough scores). Significant differences were only found in sensitivity analysis. A significant improvement in change of cough scores was found in end of intervention (2-3 months) in those receiving PPI with a standardised mean difference of -0.41 (95%CI -0.75, -0.07) using GIV analysis on cross over trials. Two studies reported improvement in cough after 5 days to 2 weeks of treatment. Significant heterogeneity was found between studies using omeprazole and other PPIs. AUTHORS' CONCLUSIONS: There is insufficient evidence to definitely conclude that GORD treatment with PPI is beneficial for cough associated with GORD in adults. The beneficial effect was only seen in sub-analysis and its effect was small. The optimal duration of such a trial of therapy to evaluate response could not be ascertained in the meta-analysis although two RCTs reported significant change by two weeks of therapy. Clinicians should be cognisant of a period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Data in children are inconclusive. Future paediatric and adult studies are needed whereby studies should be double blind, randomised controlled, parallel design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non acid reflux whilst on therapy.

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Am J Gastroenterol. 2005 Mar;100(3):537-42.
Reversibility of GERD ultrastructural alterations and relief of symptoms after omeprazole treatment.
Calabrese C, Bortolotti M, Fabbri A, Areni A, Cenacchi G, Scialpi C, Miglioli M, Di Febo G.
Dipartimento di Medicina Interna e Gastroenterologia, Sezione di Anatomia Patologica, Universita di Bologna, Italy.

BACKGROUND: Dilation of intercellular spaces (DIS) of human esophageal epithelium, evident at transmission electron microscopy (TEM), is an early marker of damage caused by gastroesophageal reflux, but its reversibility after therapy has not been investigated. AIM: To evaluate whether omeprazole can induce the healing of DIS. METHODS: Thirty-eight symptomatic patients, 22 with nonerosive reflux disease (NERD) and 16 with erosive esophagitis (EE), classified on the basis of 24-h pH monitoring, were enrolled. During upper gastrointestinal endoscopy, six biopsies from apparently normal mucosa were taken within the lower 5 cm of the esophagus for histological and TEM analysis. One hundred computer measurements were taken on TEM photomicrographs of the specimens in each patient. After 3 months of omeprazole 40 mg/die a further endoscopy with biopsies was performed. In patients with persistent heartburn and/or incomplete ultrastructural recovery of esophageal epithelium, a new endoscopy was performed after 3 more months of treatment. RESULTS: After 3 months of therapy, 35 patients (92.1%) showed a complete recovery of DIS and resolution of heartburn. Three patients required 3 more months of therapy because of an incomplete recovery of the epithelium correlated with sporadic heartburn. Healing of the mucosa was achieved in two patients, whereas one had an incomplete recovery of DIS with persistent heartburn. CONCLUSIONS: Three and six months of omeprazole therapy led to a complete recovery of DIS in 92.1% and 97.4% of cases, respectively. No significant differences of DIS between NERD and EE were noted. Complete recovery of DIS was accompanied by regression of heartburn in all cases.

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Eur J Cardiothorac Surg. 2005 Mar;27(3):357-60.
The incidence of gastroesophageal reflux after transthoracic esophagocardio-myotomy without fundoplication: a long term follow-up.
Lindenmann J, Maier A, Eherer A, Matzi V, Tomaselli F, Smolle J, Smolle-Juettner FM.
Department of Surgery, Division of Thoracic- and Hyperbaric Surgery, University Medical School Graz, Auenbruggerplatz 29, 8036 Graz, Austria. jo.lindenmann@meduni-graz.at

OBJECTIVE: Evaluation of the long term results of Heller's myotomy performed over a lateral thoracotomy without additional fundoplication. Methods: Forty patients (17 males, 23 females; mean age 43.2 years; range: 14-63 years) were operated between 1985 and 2000. Preoperative evaluation included clinical scoring of symptoms, esophagogram, endoscopy, manometry and 24-h ph-metry. At the follow-up investigation, the preoperative evaluation was repeated in all patients, adding a histological workup of the distal esophageal mucosa. The mean duration of follow-up after surgery was 10.3 years, ranging from 3-16 years. RESULTS: The clinical scores improved significantly: Excellent relief from dysphagia was present in 86%, little or no regurgitation was found in 79%, little or no retrosternal spasms were reported by 72% of the patients. Esophagogram showed an overall esophageal dilatation in all patients but no significant obstruction at the esophagogastric junction. Endoscopically, 2.5% had candida-esophagitis, 5% showed signs of a GERD I, 92.5% had a macroscopically insuspect esophageal mucosa. Histologically, 53% showed a mild chronic inflammation. Manometry demonstrated distinct hypomotility of the esophagus in all cases, yet no elevated pressure of the lower sphincter; pH-metry showed moderate reflux in 46%. CONCLUSIONS: Transthoracic cardiomyotomy is a valid method for the treatment of achalasia, but it will not improve the esophageal motility, which slowly deterioriates in these cases. The patient's subjective assessment of the postoperative result was positive in the majority of cases. Although fundoplication was not done in any of these patients, none of them showed signs of clinically relevant reflux.

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J Pediatr Gastroenterol Nutr. 2005 Mar;40(3):319-27.
Efficacy and safety of lansoprazole in adolescents with symptomatic erosive and non-erosive gastroesophageal reflux disease.
Fiedorek S, Tolia V, Gold BD, Huang B, Stolle J, Lee C, Gremse D.
The Pediatric Clinic, P.A., North Little Rock, AR 72117, USA. scfiedorek@thepediatric.com

OBJECTIVES: To assess the efficacy and safety of lansoprazole in the treatment of adolescents with symptomatic, endoscopically proven, non-erosive gastroesophageal reflux disease and erosive esophagitis. METHODS: Adolescents between 12 and 17 years of age with esophagitis were enrolled in this open-label trial and treated with lansoprazole 15 mg (non-erosive) or 30 mg (erosive) once daily for 8 weeks. If unhealed at week 8, those with erosive esophagitis were treated with an additional 4 weeks of lansoprazole 30 mg once daily. RESULTS: Lansoprazole produced a significant reduction from baseline in the median percentage of days with reflux symptoms (91 to 43% in the 64 adolescents with non-erosive disease and 85 to 16% in the 23 adolescents with erosive esophagitis, P < or = 0.001 for each comparison). At week 8, mucosal healing had occurred in 95% (21 of 22) of those with erosive esophagitis. Treatment-related adverse events were reported by 19% of patients with non-erosive and 4% of patients with erosive esophagitis. Headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%) were the most frequently reported adverse events. One patient discontinued treatment early because of dizziness and vomiting. An elevation in mean serum gastrin from baseline (59 pg/mL at pretreatment to 80 pg/mL at final visit) was observed. CONCLUSION: Lansoprazole 15 mg or 30 mg once daily reduced symptoms of gastroesophageal reflux in adolescents with non-erosive gastroesophageal reflux disease and erosive esophagitis, respectively. Lansoprazole 30 mg once daily for 8 weeks was effective in healing erosive esophagitis. Both treatment regimens were considered safe.

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J Pediatr. 2005 Mar;146(3 Suppl):S3-12.
Decisions in diagnosing and managing chronic gastroesophageal reflux disease in children.
Hassall E.
Division of Pediatric Gastroenterology, BC Children's Hospital/University of British Columbia, Vancouver, Canada.

Gastroesophageal reflux disease (GERD) presents in different ways in children, most commonly with vomiting, or with esophageal symptoms such as regurgitation, heartburn, or dysphagia. Extraesophageal symptoms and signs also frequently occur. Less well recognized is that abdominal pain is a relatively common mode of presentation. Although abdominal pain is common in school-aged children, GERD and other acid-related disorders such as peptic ulcer disease are relatively uncommon causes of such. A careful history will usually determine whether an acid-related disorder is in the differential diagnosis of abdominal pain. Early detection and treatment of GERD in children may prevent, attenuate, or heal complications such as failure to thrive or feeding refusal as well as pulmonary, ear-nose-and-throat disorders, erosive esophagitis, and peptic stricture. In children with persistent or severe symptoms and/or complications of GERD such as erosive esophagitis, the major treatment options are pharmacologic management with acid-suppressing medication, specifically proton pump inhibitors (PPIs), or antireflux surgery. For many patients, PPI treatment offers advantages over surgery. When given in adequate doses, PPIs can safely effect relief of GERD symptoms and healing of esophagitis in children. Antireflux surgery may work well in selected patients, but it carries significant risk of morbidity, including high failure rates, even in the short term. Some postoperative studies report that more than 60% of patients are back on medical treatment with proton pump inhibitors for recurrence of GERD symptoms, and a similar percentage have new symptoms that were not present before surgery. Death is uncommon but does occur and is an unacceptable risk in an otherwise healthy, low-risk individual. Laparoscopic surgery may have some disadvantages compared with open surgery, including a higher rate of redo operations. Studies show that many children undergo surgery for unclear indications, often with few preoperative diagnostic studies. The availability of highly effective medical therapy, together with more careful selection of patients for surgery, may result in better patient outcomes, with much lower operative rates.

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Ther Umsch. 2005 Feb;62(2):96-9.
[Laparoscopic fundoplication for gastroesophageal reflux disease (GERD)]
[Article in German]
Wehrli H.
Zentrum fur Viszeralchirurgie, Klinik Hirslanden, Zurich. hwehrli@freesurf.ch

Laparoscopic fundoplication became the gold standard in the surgical therapy of GERD. In comparison with open procedures, laparoscopic antireflux surgery has a lower morbidity rate, a better early and late postoperative outcome and is more cost-effective. Antireflux surgery can be performed after a critical evalutation of the patient including gastroscopy, biopsy, 24h-pH-manometry and after a long lasting conservative medical treatment. Indications for antireflux surgery are given by a failed medical treatment, an insufficient compliance, complications of GERD, i.e. stenosis, Barrett-esophagus and atypical reflux symptoms like chronic cough, hoarseness or thoracic pain with presence of a pathological pH-monitoring. Laparoscopic 360 degrees Nissen-fundoplication with crurorrhaphy is our standard procedure, whereas the 270 degrees Toupet technique in our tailored approach is the technique of choice for esophageal motility disorders. Results of antireflux surgery published in literature are discussed and compared with our own ten years experience with 124 cases of laparoscopic fundoplication.

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Mo Med. 2005 Jan-Feb;102(1):67-9.
Laparoscopic Nissen fundoplication in a community hospital: analysis of 202 patients.
Tucker LE, Blatt C, Richardson NL, Richardson DT, Cassat JD, Riechers TB.
Department of Medicine, Division of Gastroenterology, St. John's Mercy Hospital, Washington, Missouri, USA.

We analyzed 202 patients undergoing Laparoscopic Nissen fundoplication. One hundred and three patients (90.6%) had typical reflux symptoms. Hiatal hernias were present in 84.6%. Most patients had erosive esophagitis; sixty-four patients (31.6%) had strictures. Complications occurred in 38 patients (18.8%), with major complications in 15 patients (7.4%). Major complications included bleeding in six, two requiring transfusion, slipped Nissen in three, pneumothorax in two, and esophageal leak in two patients. Eleven patients had postoperative dysphagia that responded to dilation therapy within three months. There was no mortality.

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Curr Treat Options Gastroenterol. 2005 Feb;8(1):71-83.
Robotic Laparoscopic Fundoplication.
Stefanidis D, Korndorffer JR, Scott DJ.
Tulane Center for Minimally Invasive Surgery, Tulane University Health Sciences Center, 1430 Tulane Ave., SL-22, New Orleans, LA 70112-2699, USA.. dscott@tulane.edu.

Gastroesophageal reflux disease is a very common disorder, and both medical and surgical treatments have shown outstanding results. Whereas proton pump inhibitors are the mainstay of treatment, laparoscopic fundoplication has become a very attractive alternative due to its efficacy and low morbidity. There are defined patient categories that may benefit more from laparoscopy than medical therapy, but a conclusive comparison between the two is lacking. Robotic laparoscopic fundoplication can be performed safely without increased morbidity. Potential advantages include enhanced precision, improved dexterity, and remote telesurgical applications. Disadvantages include increased cost and prolonged operative times. Further studies and more long-term outcome data are needed to fully evaluate the procedure. Robotic surgery is currently in its infancy and not cost effective but has a very promising future. With further development of automatization and miniaturization features, robotic surgery may prove more efficient than conventional laparoscopy.

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Curr Treat Options Gastroenterol. 2005 Feb;8(1):51-57.
Enteryx Implant for Gastroesophageal Reflux Disease.
Johnson DA.
Eastern Virginia School of Medicine, 844 Kempsville Road, Norfolk, VA 23502, USA. dajevms@aol.com.

Although pharmacologic therapy is safe and effective for gastroesophageal reflux disease (GERD), patients requiring chronic drug treatment often seek alternatives. Surgical alternatives to chronic drug treatment are associated with increased morbidity and long-term failure rates in more than 50% of surgically treated patients. Newer endoluminal therapies using modifications of standard endoscopy techniques are under evaluation as alternatives to chronic drug treatment or surgical intervention for GERD. Appropriate patient selection is KEY. Patients considered for any endoluminal therapy should have well documented GERD and demonstrated appropriate and successful response to medical therapy with a proton pump inhibitor (PPI). The Enteryx implant is an injectable biocompatible polymer approved by the US Food and Drug Administration for the management of GERD symptoms. Clinical trial data indicate that the Enteryx procedure is a safe and effective GERD treatment that manages symptoms of GERD and addresses the underlying anatomic and functional aspects of the disorder. Multicenter clinical trials have shown that the Enteryx procedure safely and effectively eliminates or significantly reduces PPI use in approximately 84% of patients at 1 year and 72% of patients at two years. The risk-benefit profile of this procedure and alternative treatment options should be carefully evaluated for each patient considered a candidate for Enteryx and all endoluminal therapies. Randomized-controlled studies comparing the Enteryx procedure to placebo and cost-effective analyses comparing treatment options will further define the use of the Enteryx implant in patients with GERD.

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Am J Gastroenterol. 2005 Jan;100(1):190-200.
Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease.
DeVault KR, Castell DO.
Department of Medicine, Mayo Clinic College of Medicine, Jacksonville, FL, USA.

Guidelines for the diagnosis and treatment of gastroesophageal reflux disease (GERD) were published in 1995 and updated in 1999. These and other guidelines undergo periodic review. Advances continue to be made in the area of GERD, leading us to review and revise previous guideline statements. GERD is defined as symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. These guidelines were developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee, and approved by the Board of Trustees. Diagnostic guidelines address empiric therapy and the use of endoscopy, ambulatory reflux monitoring, and esophageal manometry in GERD. Treatment guidelines address the role of lifestyle changes, patient directed (OTC) therapy, acid suppression, promotility therapy, maintenance therapy, antireflux surgery, and endoscopic therapy in GERD. Finally, there is a discussion of the rare patient with refractory GERD and a list of areas in need of additional study.

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Obes Surg. 2004 Nov-Dec;14(10):1373-80.
Laparoscopic gastric bypass after antireflux surgery for the treatment of gastroesophageal reflux in morbidly obese patients:
initial experience.
Raftopoulos I, Awais O, Courcoulas AP, Luketich JD.
Department of Surgery, Division of Thoracic and Foregut Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA. raftopoulosi@upmc.edu

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) has been proven effective against gastroesophageal reflux disease (GERD) in morbidly obese patients. We present our experience with revision of antireflux procedures to LRYGBP in obese patients with recurrent GERD, weight gain or a combination of both and discuss the indications and technical considerations involved. METHODS: Between June 2000 and December 2003, 7 morbidly obese patients with a mean BMI of 37.5 kg/m(2) underwent revision of an antireflux procedure to LRYGBP by our group. Important steps of the revision include dissection of the diaphragmatic crura and gastroesophageal fat pad, reduction and repair of hiatal hernia, and complete take-down of the wrap to avoid stapling over the fundoplication which can create an obstructed, septated pouch. RESULTS: Mean operative time was 6 hr 12 min and length of stay was 4.8 days. There were 3 major complications postoperatively and no deaths. During follow-up, 5 patients developed anastomotic strictures and 2 patients were re-explored for gastric remnant herniation and intestinal obstruction. At a mean follow-up of 24 (3-44) months, mean excess weight loss was 70.7% and 14/20 (70%) co-morbid conditions were improved or resolved. GERD evaluation with the GERD-HRQL scale showed a significant reduction of GERD scores postoperatively (P =0.006). CONCLUSIONS: Although LRYGBP after antireflux surgery is a technically more difficult procedure with a higher morbidity, it is feasible and effective for the treatment of recurrent GERD and worsening obesity with the additional advantage of weight loss and improvement of co-morbidities.

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Best Pract Res Clin Gastroenterol. 2004;18 Suppl:55-66.
GERD 2004: issues from the past and a consensus for the future.
Modlin I, Kidd M.
Department of Surgery, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520-8062, USA. imodlin@optonline.net

In the early 1900's, gastroesophageal reflux disease (GERD) was an almost unknown entity with less than 200 cases reported worldwide. Currently the disease is regarded as almost endemic with as much as 25% of the population in some countries exhibiting signs or symptoms of reflux. Early therapies directed at chemical neutralization (milk drip, antacids) were of modest effect and required constant administration for efficacy. The introduction of histamine 2 receptor antagonists in the 1970's dramatically improved the management of GERD, but was limited by problems of tachyphylaxis and adverse events. The advent of the PPI class of drugs revolutionized medical care of GERD, given their efficacy and safety profile. As a consequence, the surgical approach with its pronounced dependence on individual operator skill and its high morbidity and even mortality has fallen into disregard. Thus, modest surgical outcome results as compared to the efficacy of PPIs has led to the widespread recognition that pharmacological therapy for GERD represents the platinum standard of care and the current consensus is that the PPI class of drugs provide the safest and most effective form of therapy for GERD. Furthermore, it is apparent based on acid suppression, symptom relief and healing rates, that all PPIs are on a milligram for milligram basis similarly efficacious for the management of GERD. While a consensus exists in regard to the current management of GERD with PPIs there is little agreement as to the management of the associated mucosal metaplastic process. At this time there is inadequate understanding of the biological basis of the mucosal transformation and minimal information about the mechanistic regulation of this event and its perpetuation. A future consensus thus requires the identification of the appropriate tools to detect Barrett's early, identify the specific molecular markers associated with neoplastic transformation and establish a definitive therapeutic algorithm.

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Dis Esophagus. 2004;17(4):274-8.
Comparison of efficacy of pantoprazole alone versus pantoprazole plus mosapride in therapy of gastroesophageal reflux disease: a randomized trial.
Madan K, Ahuja V, Kashyap PC, Sharma MP.
Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

SUMMARY The present study aimed to compare the efficacy for the therapy of GERD of pantoprazole alone with a combination of pantoprazole and mosapride. The study was a prospective, randomized trial involving 68 patients suffering heartburn and/or regurgitation at least twice a week for 6 weeks. Sixty-one patients consented to be randomized to receive either pantoprazole 40 mg b.i.d. (n = 33, group A) or pantoprazole 40 mg b.i.d. plus mosapride 5 mg t.d.s. (n = 28, group B) for 8 weeks. Twenty-four-hour esophageal pH-metry and endoscopy were conducted at recruitment and endoscopy was repeated at 8 weeks in all the patients studied. There were no differences in symptomatic responses to therapy between the groups (69.7% vs 89.2%; P = 0.11). The mean symptom score after 8 weeks was significantly lower in group B (3.78 +/- 3.62 vs 1.67 +/- 2.09; P = 0.009). Nonerosive esophagitis was present in 29 patients. In patients with nonerosive GERD there was no significant difference in symptomatic response to either regimen (17/20 in group A and 7/9 in group B responded; P = 0.63). In erosive esophagitis, symptomatic responses occurred more frequently in group B, 18/19 (94.7%), than in group A, 6/13 (46.2%; P = 0.003). However endoscopic healing of esophagitis occurred equally with either regimen (6/11, 54.5% in group A; 12/17, 70.5% in group B; P = 0.44). In nonerosive GERD, the addition of mosapride offers no benefit over pantoprazole alone. A combination of pantoprazole and mosapride is more effective than pantoprazole alone in providing symptomatic relief to patients with erosive GERD.

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Schweiz Rundsch Med Prax. 2004 Nov 17;93(47):1963-9.
[Reflux disease therapy]
[Article in German]
Allescher HD.
Zentrum fur Innere Medizin, Gastroenterologie, Hepatologie und Stoffwechsel, Klinikum Garmisch-Partenkirchen. hans.allescher@klinikum-gap.de

The frequency of gastroesophageal reflux disease is on a constant rise in western countries. Reflux therapy can be subdivided into the treatment of acute erosive reflux esophagitis and the subsequent recurrence prophylaxis, and into the treatment of non-erosive reflux disease as well as the atypical reflux symptoms. Based on conventional large-scale studies, a highly effective therapy is available which offers virtually complete acid blockade using proton pump inhibitors (PPI) of the prazole type. Used for acute treatment, they offer a cure for reflux esophagitis and freedom from symptoms in approx. 90% of the cases, while also showing high efficacy in recurrence prophylaxis. Conversely, the rate of side effects, particularly serious ones, is very low and the long-term safety of this therapy has been good. Since the risk of erosive reflux esophagitis recurring is > 80% without PPI therapy, the majority of the patients will require a long-term, potentially even life-long therapy with PPI. Other therapeutic options are being discussed as alternatives to such long-term prophylaxis. In selected cases, surgical therapy by laparoscopic fundoplication is one option. Alternatively, endoscopical anti-reflux procedures are increasingly coming into use; their merit in long-term prophylaxis however, cannot yet be evaluated. Whenever PPI therapy does not lead to complete freedom from symptoms, an alternative therapeutic approach should be given consideration even in patients with atypical reflux symptoms. The therapy of the Barrett's esophagus, a potentially long-term sequelae of reflux disease, will not be dealt with in this overview, as it is the subject of a separate presentation.

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Schweiz Rundsch Med Prax. 2004 Nov 17;93(47):1951-7.
[Barrett's esophagus]
[Article in German]
Neuhaus H.
Medizinische Klinik, Evangelisches Krankenhaus Dusseldorf. medizinischeklinik@evk-duesseldorf.de

The diagnosis of Barrett's esophagus is rendered based on proof of intestinal metaplasia in the tubular portion of the esophagus. Barrett's develops in a percentage of patients with gastroesophageal reflux disease; risk factors include a long history of the disease, age over 40 years and Caucasian skin. Specifics about a genetic predisposition have not become known to date. Each year, around one out of every 200 patients with Barrett's epithelium develop adenocarcinoma of the esophagus, the incidence of which has risen dramatically over the past two decades. Apart from the early stages, the prognosis for this type of Barrett's carcinoma is extremely unfavorable, even after esophagectomy. It therefore appears sensible to examine patients with a long history of reflux and/or frequently recurrent reflux symptoms and to develop screening strategies for timely detection of persons with Barrett's esophagus along with subsequent monitoring. This would involve regular endoscopic studies accompanied by biopsies aimed at excluding or demonstrating the intraepithelial neoplasms that count as direct precursors to cancer. Treatment of nonneoplastic Barrett's esophagus can be symptomatic. Although theoretically logical, the benefits of normalizing esophageal acid exposure have not been proven. When high-grade intraepithelial neoplasms or mucosal carcinomas have been confirmed, local endoscopical resection and/or ablation appear sufficient, since the risk of lymph node metastasis is extremely low. Previous studies on this subject have been very promising, but should be continued and/or verified. Definitive therapy of more advanced tumor stages is currently given according to multimodal concepts established in an interdisciplinary manner.

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Eur J Cardiothorac Surg. 2004 Nov;26(5):875-80.
Redo antireflux surgery--the importance of a tailored approach.
Khan OA, Kanellopoulos G, Field ML, Knowles KR, Beggs FD, Morgan WE, Duffy JP.
Thoracic Unit, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK. omarkhan@iname.com

OBJECTIVE: Although several studies have examined early outcome following redo antireflux surgery, there is little data on the long-term efficacy of these procedures. We reviewed our experience of these operations in order to assess the long-term results which can be achieved by choosing redo antireflux procedures based on the results obtained from pre-operative oesophageal function testing. METHODS: The case notes of 26 patients who underwent a repeat antireflux procedure between 1981 and 2000 were reviewed. Clinical history, examination, endoscopy, pH studies, oesophageal manometry and video barium contrast studies were performed on all patients prior to re-operation. In all cases, a standardised pre-formulated algorithm, based on the results of the pre-operative oesophageal function tests, was used to determine the choice of surgical procedure. Post-operatively, patients were classified into three groups: Group A (those with no symptoms), Group B (symptoms controlled by medication) and Group C (symptoms refractory to medical treatment). Patients in Groups B and C underwent repeat oesophageal function studies. RESULTS: In all cases, the indication for re-operation was gastro-oesophageal reflux symptoms refractory to medical treatment. Twenty-one patients (81%) underwent a left thoracotomy, of whom 11 patients (42%) underwent a gastroplasty. The mean follow-up period was 8.27 years (range 1.5-19.8 years), after which 14 patients (54%) were classified as Group A; 10 patients (38%) as Group B; and 2 patients (8%) as Group C. Within Groups B and C, manometry showed that re-operation had increased basal lower oesophageal sphincter pressure (4.6 vs 12.7 mmHg, pre- vs post-operative P=0.03), and in all, but one case pH studies showed no evidence of recurrent acid reflux. CONCLUSIONS: Redo antireflux surgery can provide complete symptomatic relief in approximately 50% of patients and symptomatic improvement over 90% of patients. We advocate a tailored approach in the selection of re-operative procedures based on the results of pre-operative oesophageal function testing.

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Surgery. 2004 Oct;136(4):786-94.
Delivery of radiofrequency energy to the lower esophageal sphincter improves symptoms of gastroesophageal reflux.
Go MR, Dundon JM, Karlowicz DJ, Domingo CB, Muscarella P, Melvin WS.
Department of Surgery, The Ohio State University Medical Center, Columbus, Ohio 43210, USA.

BACKGROUND: The Stretta procedure has been proposed as a novel therapeutic alternative to antireflux surgery for gastroesophageal reflux disease (GERD). Early reports indicated improvement in GERD symptoms overall, but improvement in patients who have poor outcome after surgery remains unclear. METHODS: Patients with reflux who did not have a hiatal hernia were offered the procedure. All were administered a GERD Health Related Quality of Life survey at preprocedure and at greater than 3 months postprocedure. Differences in pre- and postprocedure responses were deemed significant with the use of the Wilcoxon rank sum test with P <.05. RESULTS: Fifty patients underwent the Stretta procedure. There were no complications. All were evaluated postprocedure, with 74% completing a postprocedure survey. Overall heartburn score improved from 3.19 (scale, 0-5) preprocedure to 1.74 postprocedure (P=.0012). Overall symptoms satisfaction score improved from 3.92 to 1.63 (P=.0001). Symptoms satisfaction score of patients who failed antireflux surgery improved from 3.5 to 1.75 (P=.0166), and, in those with a body mass index >30, it improved from 4.11 to 1.56 (P=.0024). Four patients went on to have antireflux surgery after having the Stretta procedure. CONCLUSIONS: Stretta improves heartburn symptoms both overall and in patients with poor outcome after antireflux surgery, with a low procedural risk. It may have a role in the treatment of patients with primary reflux and in those who have failed antireflux surgery or who are a high risk for surgery.

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Chirurg. 2004 Oct 20 [Epub ahead of print]
[Conventional and minimally invasive surgical methods for gastroesophageal reflux.]
[Article in German]
Fuchs KH.
Klinik fur Visceral-, Gefass- und Thoraxchirurgie, Markus-Krankenhaus, Frankfurter Diakonie-Kliniken.

The introduction of minimally invasive techniques has had great influence on the indication and surgical therapy for gastroesophageal reflux disease. This analysis is an overview of the current evidence-based status and a critical reprisal of open and laparoscopic antireflux surgery.Results: The analysis of randomized trials showed an advantage for patients after laparoscopy for total and partial fundoplication because of reduced morbidity, shorter postoperative hospitalization due to faster recovery, and significantly fewer scar and wound problems. The functional results of open and laparoscopic techniques were similar. Five-year follow-up results for the latter showed effective reflux control in at least 85% of patients. Randomized trials regarding technical variations did not show an advantage for division of the short gastric vessel. A bougie for the cardia calibration can prevent postoperative dysphagia after fundoplication.

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Minerva Chir. 2004 Oct;59(5):427-35.
Endoscopic therapy for gastroesophageal reflux disease: can it replace antireflux surgery?
Oleynikov D, Oelschlager B, Dibaise J.
Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA.

This article addresses emergent endoluminal technologies currently available for the treatment of gastroesophageal reflux disease (GERD) and compares it to the laparoscopic Nissen fundoplication. To date the mainstay of GERD therapy has been achieved with either open or laparoscopic fundoplication or life-long medical treatment. Endoluminal treatment modalities attempt to augment the gastroesophageal junction (GEJ) function by various techniques. We searched the Medline database from 1980 to 2004 for studies on endoscopic GERD techniques and laparoscopic fundoplications. Product investigators were contacted for data presented in abstract form only. Endoluminal management of GERD include using radiofrequency energy, injection of biocompatible polymers and endoluminal sutures to alter the GEJ and reduce reflux. Early results while encouraging, should be evaluated thoroughly and with caution before widespread use can be advocated. Endoscopic treatment of GERD has future promise, however, more experience and perhaps further refinement in techniques and technology must occur before widespread clinical application can be encouraged.

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Internist (Berl). 2004 Oct 7 [Epub ahead of print]
[Reflux disease management-more than acid reduction?]
[Article in German]
Frieling T.
Medizinische Klinik II, Klinikum Krefeld.

Because gastroesophageal reflux disease (GERD) is a motility disorder, acid reduction with proton pump inhibitors (PPI) remains a symptomatic therapy with a recurrence rate of over 90% after discontinuation of acid suppression. This "therapeutic dilemma" becomes obvious in patients not responding sufficiently to the conventional medication (therapy resistance, necessity of high PPI doses, volume reflux). In this manuscript we analyze additional factors that may play a role in the pathogenesis and interpretation of GERD. These additional factors include gastroesophageal motility and esophageal barrier functions as well as duodenogastroesophageal reflux and Helicobacter pylori infection. In addition, basic problems in interpretation of therapeutic success such as placebo effect, spontaneous remission of GERD, the role of sensory function and subjective interpretation of symptoms and the overlap between physiological and pathological reflux as well as functional disorders will be discussed.

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Am J Med. 2004 Sep 6;117 Suppl 5A:56S-62S.
Extraesophageal symptoms: what role for the proton pump inhibitors?
Nord HJ.
Division of Digestive Diseases and Nutrition, University of South Florida, College of Medicine, Tampa, Florida 33606-3568, USA.

The esophageal complications of gastroesophageal reflux disease (GERD) are well described and include erosive esophagitis, stricture, Barrett esophagus, and adenocarcinoma. Primary care physicians often encounter patients with "extraesophageal" manifestations of GERD in the absence of heartburn. Patients may present with symptoms involving the pulmonary system, noncardiac chest pain, and ear, nose, and throat disorders. The diagnosis of reflux disease in these individuals may be challenging because, in addition to the absence of heartburn, endoscopy is often negative. Laryngoscopy and 24-hour dual-channel intraesophageal pH-metry may have greater diagnostic yields, but they are costly, invasive, and time-consuming. A trial of proton pump inhibitor (PPI) therapy is increasingly being considered a first-line diagnostic test in those with suspected reflux-related extraesophageal symptoms. The duration as well as dose of PPI should be based on the presenting symptoms, with patients having pulmonary manifestations often requiring twice-daily therapy for 2 to 3 months. In contrast, symptoms of reflux-related noncardiac chest pain may be relieved with a 1-week, standard-dose treatment trial. Patients who fail to experience symptom resolution or improvement should undergo further diagnostic evaluations including 24-hour esophageal pH studies while continuing their PPI therapy to establish persistent versus absent acid reflux. The role of fundoplication or other surgical/laparoscopic procedures in these patients has yet to be determined.

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Am J Med. 2004 Sep 6;117 Suppl 5A:49S-55S.
Managing gastroesophageal reflux disease for the lifetime of the patient: evaluating the long-term options.
Metz DC.
Department of Gastroenterology, Hospital of University of Pennsylvania, Philadelphia, Pennsylvania 19104-4283, USA.

Lifetime management goals of gastroesophageal reflux disease (GERD) are to control esophageal as well as extraesophageal symptoms, maintain a stable noninflamed esophageal mucosa, and prevent complications. Large randomized clinical trials and >16 years of worldwide experience have confirmed the high rate of efficacy and excellent safety profile of proton pump inhibitor (PPI) therapy in individuals with all grades of GERD, making these agents the mainstay of treatment. Despite these outcomes, some individuals may desire an alternative to pharmacologic therapy. In such patients, laparoscopic fundoplication may produce symptom relief and healing of esophagitis, but its invasiveness, cost, and inherent surgical risks have created an interest in a variety of endoscopic therapies for reflux disease. Several short-term uncontrolled trials of these endoscopic therapies have reported encouraging preliminary results; however, careful patient selection as well as clinician experience is critical for their success. In addition to clinician expertise with the procedure, success has been observed only in patients with nonerosive GERD and a hiatal hernia <3 cm, abnormal pH monitoring, and normal esophageal motility studies, as well as in those who have experienced at least partial symptom relief with PPI therapy. Endoscopic therapy should not be considered the standard of care in patients with erosive disease or large hiatal hernias.

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Am J Med. 2004 Sep 6;117 Suppl 5A:23S-29S.
Gastroesophageal reflux disease: could intervention in childhood reduce the risk of later complications?
Gold BD.
Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Gastroesophageal reflux (GER) is a ubiquitous disorder in infants. Whereas infants typically outgrow regurgitation by 1 year of age, the prevalence of gastroesophageal reflux disease (GERD) symptoms in those aged 3 to >18 years ranges from 1.8% to 22%. The pathophysiology of GERD in children is similar to that in adults. However, children may present with gastroesophageal and extraesophageal symptoms distinct from classic heartburn. In addition to a growing awareness of the high prevalence of the disorder, increasing evidence supports GERD being a lifelong condition in some individuals that begins in childhood. Although the diagnostic workup in children compared with adults may differ, studies suggest that the early detection and treatment of GERD in childhood may result in better adult disease outcomes, improved quality of life, and decreased overall healthcare burden. Studies of proton pump inhibitor therapy in children confirm high rates of mucosal healing and GER symptom resolution, even in children whose symptoms did not respond to H2-receptor therapy or fundoplication procedures. Omeprazole, lansoprazole, and esomeprazole are formulated as capsules containing enteric-coated granules that can be sprinkled onto applesauce or other soft foods. Lansoprazole is also formulated as strawberry-flavored granules for suspension. These as well as other alternative dosing formulations expand the ability to administer these agents to children. Moreover, long-term studies in adults and in children demonstrate that these agents are safe and well tolerated, even at the higher milligram per kilogram doses that are often required in pediatric patients because of their greater hepatic metabolic capacity.

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Am J Med. 2004 Sep 6;117 Suppl 5A:14S-22S.
Therapeutic choices in reflux disease: defining the criteria for selecting a proton pump inhibitor.
Freston JW.
University of Connecticut Health Center, Farmington, Connecticut 06030-1111, USA.

Gastroesophageal reflux disease (GERD) is among the most common disorders of the gastrointestinal tract, with symptoms affecting a substantial proportion of the US population on a daily basis. Heartburn and related symptoms arise from a number of pathophysiologic mechanisms, including dilated intercellular spaces, increased duration of acid reflux, greater proximal extent of reflux, and esophageal sensitivity. Chronic reflux may result in serious complications, such as esophageal erosions or ulceration, stricture, and Barrett esophagus. The goals of GERD therapy are to relieve patients' symptoms and prevent complications. Proton pump inhibitors (PPIs) represent the most effective treatment option for GERD, relieving symptoms, healing erosions, and maintaining a healed mucosa. Differences in the pharmacokinetics and pharmacodynamics among the PPIs may result in differences in intragastric pH holding time as well as the onset of symptom relief. Lansoprazole and esomeprazole produce similar degrees and onset of symptom relief, with both providing greater symptom relief as compared with omeprazole. Although manufactured as capsules containing enteric-coated granules, lansoprazole, omeprazole, and esomeprazole maintain their high level of pharmacologic efficacy when the capsule contents are emptied into soft foods or various liquids. Lansoprazole and pantoprazole also are manufactured as intravenous formulations, and lansoprazole is available as strawberry-flavored granules for oral suspension and as an orally disintegrating tablet. These alternative routes of administration are particularly beneficial in the management of acid-related disorders in infants, children, the elderly, and patients of all ages who have difficulty swallowing or are unable to swallow intact capsules or tablets and those in the critical care setting.

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Dig Dis. 2004;22(2):161-70.
Surgery of gastroesophageal reflux disease: a competitive or complementary procedure?
Lundell L.
Division of Surgery, Karolinska University Hospital, Huddinge, Stockholm, Sweden. lars.lundell@kus.se

The management of chronic gastroesophageal reflux disease (GERD) has both been simplified and immensely improved by the development of modern medical therapies. These are built entirely on the concept of profound acid inhibition, which is very successful in a substantial proportion of GERD patients. Despite the efficacy of proton pump inhibitors (PPIs) some failures are unavoidable, and some patients experience incomplete control of major GERD symptoms on ordinary dosing of PPIs. Although the safety profile of PPIs is very reassuring, some people express some concern about the safety of drug treatment extending beyond 10 years especially when alternative therapeutic strategies are available. Some patients complain of alleged respiratory complications to severe reflux, and in those situations as well as in cases with e.g. Barrett's esophagus, a complete control of reflux also incorporating the duodenal components in the refluxate may be warranted. In all those situations antireflux surgery can be considered indicated for the treatment of chronic GERD and thus be looked upon as complementary to medical therapy. Furthermore, some patients who have their GERD symptoms under control on PPIs still want to have an operation to avoid dependency on drugs. Hence in none of these clinical situations does antireflux surgery play a competitive role in relation to medical therapy. However, in the very few randomized clinical trials in which a head-to-head comparison has been completed between medical and surgical therapy, the latter has been found to be somewhat more effective in terms of reflux control. The other side of the coin is that antireflux surgery has some side effects that signify the importance of this surgery being performed in specialized centers. Copyright 2004 S. Karger AG, Basel

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Dig Dis. 2004;22(2):148-60.
Treatment of gastroesophageal reflux disease in adults: an individualized approach.
Galmiche JP, Stephenson K.
Department of Gastroenterology and Hepatology, CIC INSERM-CHU, Nantes, France. jeanpaul.galmiche@chu-nantes.fr

Until the 1990s, most therapeutic trials in gastroesophageal reflux disease (GERD) focussed upon endoscopic lesions. In fact the correlation between patient symptoms and both the presence and grade of esophagitis is very poor. The classical criteria for the assessment of therapeutic efficacy in GERD have therefore been revised, and there is now a consensus that the relief of symptoms and the long-term control of the disease are the primary aims of therapy for the majority of patients. Proton pump inhibitors (PPIs) represent the mainstay of therapy for patients with non-erosive reflux disease (NERD) as well as esophagitis. Although a stepwise strategy has been recommended in the past, a step-down strategy (starting with a full-dose PPI) appears to be a more cost-effective approach. There are as yet insufficient data to establish the clear superiority of one PPI over others. PPIs have a number of limitations. Symptom relief is significantly inferior in NERD than in erosive esophagitis. The heterogeneity of the NERD group may be one of the most influential factors, but the role of esophageal hypersensitivity has been suggested especially in patients with normal acid exposure. The role of non-acid reflux should also be scrutinized. Long-term control of the disease can be achieved by drug therapy, anti-reflux surgery and now with a variety of endoscopic procedures. The different drug management strategies can be divided into (i) continuous maintenance therapy and (ii) discontinuous therapy which can again be divided into two categories, intermittent and on-demand drug therapy. A case-by-case approach is recommended to determine the personal therapeutic needs and preferences of each individual. Many patients with NERD or mild esophagitis do not require continuous maintenance therapy and recent studies have shown excellent results with different PPI on-demand therapy regimens. Finally when making a choice between different long-term strategies both the clinician and the informed patient have to consider efficacy, safety, tolerability and cost. The potential efficacy of new drugs, especially the GABA(B) agonists and the fast onset acid suppressors, as well as the cost-effectiveness of non-drug strategies (surgery and endoluminal therapies) should be further evaluated. Copyright 2004 S. Karger AG, Basel

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Curr Treat Options Gastroenterol. 2004 Aug;7(4):273-278.
Noncardiac Chest Pain.
Wong WM, Fass R.
Southern Arizona VA Health Care System, 3601 South Sixth Avenue (1-111G-1), Tucson, AZ 85723, USA. Ronnie.fass@med.va.gov

Noncardiac chest pain (NCCP) is a common condition with significant morbidity and economic implications. Psychological factors, gastroesophageal reflux disease (GERD), alteration in pain perception, and esophageal dysmotility play an important role in the pathogenesis of the disorder. Proton pump inhibitor (PPI) therapy is the most effective medical intervention for the treatment of GERD-related NCCP, as well as the most cost-effective diagnostic strategy for this condition. Pain modulators such as tricyclic antidepressants, trazodone, and selective serotonin reuptake inhibitors infer a visceral analgesic effect and consequently are the treatment of choice for patients with non-GERD-related NCCP. Furthermore, cognitive behavioral therapy has also been shown to be useful in the management of subset of patients with non-GERD-related NCCP. Newer therapeutic modalities and interventions such as lower esophageal sphincter injection of botulinum toxin in NCCP patients with spastic esophageal motility disorders, theophylline, and 5-HT4 receptor agonists may supplement or replace current treatment for non-GERD-related NCCP. Future compounds may include new visceral analgesics or medications that interfere with the development of peripheral or central sensitization.

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Chirurg. 2004 Jul 1 [Epub ahead of print]
[Endoscopic therapy methods for gastroesophageal reflux]
[Article in German]
Schumacher B, Neuhaus H.
Evangelisches Krankenhaus Dusseldorf.

Gastroesophageal reflux disease (GERD) is prevalent in 10% of the population. In addition to the established therapy, endoscopic antireflux procedures have been developed to improve the gastroesophageal reflux barrier. This can achieved by endoscopically placed sutures, application of radio frequency energy, or injection of biocompatible materials. These new techniques might be effective in some patients with GERD. To date, there are limited data on the effectiveness and safety of these methods. During a follow-up of 1-2 years, subjective parameters improved in 70-75% of the test patients such that no antisecretory treatment was required. Further, randomized, placebo-controlled studies are needed for objective evaluation of these promising new methods.

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Curr Opin Otolaryngol Head Neck Surg. 2004 Jun;12(3):191-6.
The endoscopic radiofrequency approach to management of GERD.
Lutfi RE, Torquati A, Richards WO.
Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

PURPOSE OF REVIEW: Endoscopic treatment has been recently introduced as a new option for treating gastroesophageal reflux disease. In this article the authors review the radiofrequency approach known as the Stretta procedure, as more evidence has linked reflux to upper airway disease. RECENT FINDINGS: Since 1968, when laryngeal disorders were linked to gastroesophageal reflux disease, more upper airway diseases such as chronic laryngitis, subglottic stenosis, and even laryngeal carcinoma were found to be occasionally caused by extraesophageal reflux. Most otolaryngologists treat these patients with proton pump inhibitors, which improve symptoms in two thirds of patients. Antireflux surgery remains the treatment of choice, relieving symptoms in more than 90% of patients. Endoscopic treatment has recently emerged as an option for treatment of gastroesophageal reflux disease. The Stretta procedure delivers radiofrequency energy to the gastroesophageal junction. This has proved to be effective in controlling reflux by inhibiting transient, inappropriate lower esophageal sphincter relaxation, increasing postprandial lower esophageal spincter pressure, and decreasing lower esophageal sphincter compliance. Stretta is among the earliest endoscopic technologies to be approved by the Food and Drug Administration for the treatment of reflux. It has the longest term follow-up published to this date, and the most durable effect. It is performed under intravenous sedation on an outpatient basis and has a low incidence of complications. SUMMARY: The Stretta procedure is an endoscopic, noninvasive modality for the treatment of gastroesophageal reflux disease. It should be considered in the treatment of reflux-related upper airway diseases.

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Curr Gastroenterol Rep. 2004 Jun;6(3):213-9.
Gastroesophageal reflux disease and baclofen: is there a light at the end of the tunnel?
Wise J, Conklin JL.
Department of Internal Medicine, Cedars-Sinai Medical Center, 8635 West Third Street, Suite 770W, Los Angeles, CA 90048, USA.

Transient lower esophageal sphincter relaxations (TLESRs) are rapid and prolonged relaxations of the lower esophageal sphincter (LES) that are not associated with swallowing. They are the mechanism by which most gastroesophageal reflux episodes occur in normal people and in patients with esophagitis. Transient LES relaxations appear to be mediated by a vagovagal reflex initiated by gastric distention. Baclofen is a g-aminobutyric acid (GABA) derivative that inhibits the production of TLESRs by acting as a GABA(B) receptor agonist at one or more loci along the vagovagal reflex arc. Animal and human studies suggest that baclofen decreases the number of reflux events and amount of esophageal acid exposure. Baclofen or another GABA(B) receptor agonist may be clinically useful in treatment of gastroesophageal reflux disease.

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BMJ. 2004 Jun 12;328(7453):1417. Epub 2004 May 04.
Randomised controlled trial of effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux: Bristol helicobacter project.
Harvey RF, Lane JA, Murray LJ, Harvey IM, Donovan JL, Nair P; Bristol Helicobacter Project.
Frenchay Hospital, North Bristol NHS Trust, Bristol BS16 1LE. richard.harvey1@virgin.net

OBJECTIVES: To investigate the effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux. DESIGN: Cross sectional study, followed by a randomised placebo controlled trial. SETTING: Seven general practices in Bristol, England. PARTICIPANTS: 10,537 people, aged 20-59 years, with and without H pylori infection (determined by the (13)C-urea breath test). MAIN OUTCOME MEASURES: Prevalence of heartburn and gastro-oesophageal acid reflux at baseline and two years after treatment to eradicate H pylori infection. RESULTS: At baseline, H pylori infection was associated with increased prevalence of heartburn (odds ratio 1.14, 95% confidence interval 1.05 to 1.23) but not reflux (1.05, 0.97 to 1.14). In participants with H pylori infection, active treatment had no effect on the overall prevalence of heartburn (0.99, 0.88 to 1.12) or reflux (1.04, 0.91 to 1.19) and did not improve pre-existing symptoms of heartburn or reflux. CONCLUSIONS: H pylori infection is associated with a slightly increased prevalence of heartburn but not reflux. Treatment to eradicate H pylori has no net benefit in patients with heartburn or gastro-oesophageal reflux.

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Surg Endosc. 2004 Jun;18(6):879-97. Epub 2004 Apr 27.
Evaluation of quality of life after laparoscopic surgery: evidence-based guidelines of the European Association for Endoscopic Surgery.
Korolija D, Sauerland S, Wood-Dauphinee S, Abbou CC, Eypasch E, Caballero MG, Lumsden MA, Millat B, Monson JR, Nilsson G, Pointner R, Schwenk W, Shamiyeh A, Szold A, Targarona E, Ure B, Neugebauer E; European Association for Endoscopic Surgery.
University Surgical Clinic, Clinical Hospital Center Zagreb, Zagreb, Kispaticeva 12, 10 000, Zagreb, Croatia.

BACKGROUND: Measuring health-related quality of life (QoL) after surgery is essential for decision making by patients, surgeons, and payers. The aim of this consensus conference was twofold. First, it was to determine for which diseases endoscopic surgery results in better postoperative QoL than open surgery. Second, it was to recommend QoL instruments for clinical research. METHODS: An expert panel selected 12 conditions in which QoL and endoscopic surgery are important. For each condition, studies comparing endoscopic and open surgery in terms of QoL were identified. The expert panel reached consensus on the relative benefits of endoscopic surgery and recommended generic and disease-specific QoL instruments for use in clinical research. RESULTS: Randomized trials indicate that QoL improves earlier after endoscopic than open surgery for gastroesophageal reflux disease (GERD), cholecystolithiasis, colorectal cancer, inguinal hernia, obesity (gastric bypass), and uterine disorders that require hysterectomy. For spleen, prostate, malignant kidney, benign colorectal, and benign non-GERD esophageal diseases, evidence from nonrandomized trials supports the use of laparoscopic surgery. However, many studies failed to collect long-term results, used nonvalidated questionnaires, or measured QoL components only incompletely. The following QoL instruments can be recommended: for benign esophageal and gallbladder disease, the GIQLI or the QOLRAD together with SF-36 or the PGWB; for obesity surgery, the IWQOL-Lite with the SF-36; for colorectal cancer, the FACT-C or the EORTC QLQ-C30/CR38; for inguinal and renal surgery, the VAS for pain with the SF-36 (or the EORTC QLQ-C30 in case of malignancy); and after hysterectomy, the SF-36 together with an evaluation of urinary and sexual function. CONCLUSIONS: Laparoscopic surgery provides better postoperative QoL in many clinical situations. Researchers would improve the quality of future studies by using validated QoL instruments such as those recommended here.

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Am J Med. 2004 Jun 1;116(11):740-8.
Lansoprazole in the treatment of functional dyspepsia: two double-blind, randomized, placebo-controlled trials.
Peura DA, Kovacs TO, Metz DC, Siepman N, Pilmer BL, Talley NJ.
University of Virginia, Charlottesville, Virginia, USA. DAP8V@hscmail.mcc.virginia.edu

PURPOSE: The efficacy of proton pump inhibitor therapy for symptom resolution in patients with functional dyspepsia remains controversial. This study was designed to compare the efficacy of lansoprazole with placebo in relieving upper abdominal discomfort in patients with functional dyspepsia. METHODS: We enrolled 921 patients with functional dyspepsia (defined as persistent or recurrent upper abdominal discomfort during the prior 3 months) and moderate upper abdominal discomfort on at least 30% of screening days; none of the patients had predominant symptoms suggestive of gastroesophageal reflux or endoscopic evidence of erosive or ulcerative esophagitis, or gastric or duodenal ulcer or erosion. Patients were assigned randomly to receive lansoprazole 15 mg (n = 305), lansoprazole 30 mg (n = 308), or placebo (n = 308) daily for 8 weeks. Patients recorded the frequency and severity of symptoms in daily diaries. RESULTS: At week 8, significantly (P <0.001) greater mean reductions in the percentage of days with upper abdominal discomfort were reported in patients treated with lansoprazole 15 mg (35%) or 30 mg (34%) compared with those treated with placebo (19%). Similarly, more patients treated with lansoprazole 15 mg (44%) or 30 mg (44%) reported complete symptom resolution (defined as no episodes of upper abdominal discomfort in the 3 days before the study visit) at 8 weeks than did placebo-treated patients (29%, P <0.001). Improvement of upper abdominal discomfort, however, was seen only in patients who had at least some symptoms of heartburn at enrollment. CONCLUSION: Lansoprazole, at a daily dose of 15 mg or 30 mg, is significantly better than placebo in reducing symptoms of persistent or recurrent upper abdominal discomfort accompanied by at least some symptoms of heartburn.

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J Clin Gastroenterol. 2004 May-Jun;38(5):390-402.
Gastroesophageal reflux disease: then and now.
Modlin IM, Moss SF, Kidd M, Lye KD.
Department of Gastroenterological Surgery, Yale University School of Medicine, New Haven, CT 06520-8062, USA. imodlin@optonline.net

Although Galen first described esophagitis almost 2000 years ago, its relation to acid was only recognized in the 19th century by Rokitansky. Considerably more interest in the symptoms and complications of esophagitis has been evident over the last century, as gastroesophageal reflux disease displaced peptic ulceration and became the principal acid-related disease of our times. Of particular interest has been the recognition of the clinical significance of the previously overlooked extraesophageal manifestations of the disease such as laryngitis, asthma, and sleep disturbance. The evolution of highly effective medical therapy has over the last decade drastically reduced the need for surgical intervention for control of symptoms except under select conditions, especially volume-related reflux and children with refractory symptoms. The proton pump inhibitor class of drugs is indisputably the most effective overall form of management, while individual proton pump inhibitors appear to be equivalent in their efficacy. Issues that remain to be resolved include the management of nonerosive gastroesophageal reflux disease, the long-term dependence of many patients on acid-suppressing medication, and the recognition of atypical manifestations and rare but serious complications of gastroesophageal reflux disease. In this respect, Barrett's esophagus still presents a major biologic and management conundrum for the physicians and scientists alike.

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Hepatogastroenterology. 2004 May-Jun;51(57):697-700.
Nissen fundoplication in infants and children: a long-term clinical study.
Zeid MA, Kandel T, el-Shobary M, Talaat AA, Fouad A, el-Enien AA, el-Badrawy T, el-Hak NG, el-Wahab MA, Ezzat F.
Gastroenterology Surgery Center, Mansoura University, Mansoura, Egypt. m_abu_zead@hotmail.com

BACKGROUND/AIMS: Infants and children who underwent open Nissen fundoplication for gastroesophageal reflux disease were retrospectively evaluated to assess the success and complications of this operation. METHODOLOGY: Twenty-six neurologically normal children (16 boys and 10 girls between 6 months and 11 years old) underwent Nissen fundoplication for intractable or complicated gastroesophageal reflux between October 1982 and February 2002. Before surgery and at follow-up visits, all children were subjected to thorough history, barium meal study and gastroscopy with multiple esophageal biopsies. The median follow-up period was 28 months (range: 11 months-19 years). RESULTS: Persistent vomiting or regurgitation since birth was the main symptom (24 patients, 92.3%), chest symptoms occurred in 5 patients (19.2%), malnutrition and retarded growth were found in 4 patients (15.4%), hematemesis and/or melena occurred in 2 patients (7.7%) and dysphagia due to esophageal stricture occurred in 4 patients (15.4%). There was no mortality. The mean hospital stay was 4.1 days. Twenty-two patients (84.6%) had no recurrent reflux. Reflux symptoms recurred in 4 cases (15.4%). One of these cases had no evidence of recurrent pathological reflux, 2 cases with preoperative stricture developed wrap disruption, recurrent reflux and re-stricture. Both refused a second operation. The fourth case developed melena and reflux esophagitis due to wrap herniation through the hiatus and was successfully managed by a second operation. CONCLUSIONS: Nissen fundoplication is an effective operation to correct gastroesophageal reflux in infants and children when the drug therapy fails. The operation should be done before occurrence of complications to decrease the recurrence of reflux.

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Pediatr Surg Int. 2004 May;20(5):326-8. Epub 2004 May 12.
Results of the Mutaf procedure in patients with gastroesophageal reflux disease.
Sanal M, Korkmaz M, Karadag E, Kocabasoglu U, Konca Y, Guvenc H.
Kinderchirurgie, Anichstrasse 35, 6020, Innsbruck, Austria, alimsanal@mail.com

Operations to treat complicated gastroesophageal reflux disease (GERD) have become the third most commonly performed general surgical procedure in large pediatric centers, and many surgical techniques have come into use to prevent gastroesophageal reflux. This paper presents our experience with gastric tube cardioplasty, a new procedure described by Oktay Mutaf (Mutaf procedure). Eleven children with GERD were successfully operated on. The postoperative period was uneventful, and all patients were symptom-free.

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Br J Surg. 2004 May;91(5):552-9.
Randomized clinical trial of laparoscopic versus open fundoplication for gastro-oesophageal reflux.
Nilsson G, Wenner J, Larsson S, Johnsson F.
Department of Nursing, Lund University, Lund, Sweden. gunilla.nilsson@omv.lu.se

BACKGROUND: The aim of this study was to compare the long-term results of laparoscopic and open antireflux surgery in a randomized clinical trial by investigating subjective and objective outcomes. METHODS: Sixty patients with gastro-oesophageal reflux disease (GORD) were randomized to laparoscopic or open 360 degrees fundoplication. Subjective evaluation using disease-specific and generic questionnaires and structured interviews, and objective evaluation by endoscopy, oesophageal manometry and 24-h pH monitoring, were performed before operation and 1 month, 6 months and 5 years after surgery. RESULTS: Two patients in the laparoscopic group had reoperations for hiatal stricture; one patient in the open group had repair of an incisional hernia, and one patient in each group had surgery for intestinal obstruction. There were no differences in the subjective outcomes of diet, sleep, medication, patient satisfaction and symptoms of GORD after 5 years. Nor were there any differences in objective outcomes determined by endoscopy, manometry or 24-h pH monitoring. Well-being was decreased in all patients before operation but was restored to normal or above-normal values after fundoplication, regardless of the type of surgery. Seven of 28 patients in the open group had complaints regarding the scar. CONCLUSION: Elimination of GORD symptoms improved well-being and eliminated the need for daily acid suppression in most patients, no matter which procedure was employed. These results were apparent 1 month after the operation and were still valid 5 years later. Copyright 2004 British Journal of Surgery Society Ltd.

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Am Fam Physician. 2004 May 1;69(9):2113-8.
Barrett's esophagus.
Shalauta MD, Saad R.
Department of Family and Preventive Medicine, University of California, San Diego, School of Medicine, San Diego, California, USA. mshalauta@ucsd.edu

Gastroesophageal reflux disease (GERD) is a condition commonly managed in the primary care setting. Patients with GERD may develop reflux esophagitis as the esophagus repeatedly is exposed to acidic gastric contents. Over time, untreated reflux esophagitis may lead to chronic complications such as esophageal stricture or the development of Barrett's esophagus. Barrett's esophagus is a premalignant metaplastic process that typically involves the distal esophagus. Its presence is suspected by endoscopic evaluation of the esophagus, but the diagnosis is confirmed by histologic analysis of endoscopically biopsied tissue. Risk factors for Barrett's esophagus include GERD, white or Hispanic race, male sex, advancing age, smoking, and obesity. Although Barrett's esophagus rarely progresses to adenocarcinoma, optimal management is a matter of debate. Current treatment guidelines include relieving GERD symptoms with medical or surgical measures (similar to the treatment of GERD that is not associated with Barrett's esophagus) and surveillance endoscopy. Guidelines for surveillance endoscopy have been published; however, no studies have verified that any specific treatment or management strategy has decreased the rate of mortality from adenocarcinoma.

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J Clin Gastroenterol. 2004 Apr;38(4):332-40.
40 mg pantoprazole and 40 mg esomeprazole are equivalent in the healing of esophageal lesions and relief from gastroesophageal reflux disease-related symptoms.
Gillessen A, Beil W, Modlin IM, Gatz G, Hole U.
Ruhr-Universitat Bochum, Universitatsklinik Marienhospital Herne, Germany. Anton.Gillessen@ruhr-uni-bochum.de

BACKGROUND: Proton pump inhibitors are regarded as the most effective class of acid suppressive medication for gastroesophageal reflux disease treatment. There is considerable interest regarding the dose equivalence between various proton pump inhibitors. GOALS: To compare the efficacy of pantoprazole and esomeprazole with regard to healing and relief from gastroesophageal reflux disease-related symptoms. STUDY: Multicenter, randomized, double-blind study. Patients with gastroesophageal reflux disease grades B/C (Los Angeles classification) received 40 mg pantoprazole daily (n = 113) or 40 mg esomeprazole daily (n = 114). Healing (endoscopy) and relief from gastroesophageal reflux disease-related symptoms (direct questioning) were assessed at first and final visit (after 4, 6, 8, or 10 weeks of treatment). RESULTS: Overall healing in both treatment groups was 88% of patients (intention-to-treat population), 95% (pantoprazole), and 90% (esomeprazole) (per-protocol population); statistically, this indicates "at least equivalence" between treatments. Overall relief from gastroesophageal reflux disease-related symptoms was similar for pantoprazole (55%) and esomeprazole (51%, per-protoco). No correlation between healing and symptom relief was seen. The majority of reported adverse events were assessed as "not related" to the study drug. Pantoprazole and esomeprazole have comparably good safety and tolerability. CONCLUSION: In patients with gastroesophageal reflux disease, 40 mg pantoprazole daily and 40 mg esomeprazole daily are equally effective for healing of esophageal lesions and relieving gastroesophageal reflux disease-related symptoms.

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Gastroenterol Nurs. 2004 Mar-Apr;27(2):44-9.
Efficacy of esomeprazole in patients with acid-peptic disorders.
Beck J.
Aurora Sinai Medical Center, Milwaukee, WI, USA. jean.beck@aurora.org

Esomeprazole (Nexium) is a new proton pump inhibitor that provides more effective acid control compared with other proton pump inhibitors. In patients with gastroesophageal reflux disease, standard doses of esomeprazole maintain intragastric pH above 4 for significantly longer periods compared with standard doses of other proton pump inhibitors after 5 days of treatment. Esomeprazole is approved for the treatment of symptomatic gastroesophageal reflux disease, the healing of erosive esophagitis, and maintenance of healing. In clinical trials, esomeprazole 40 mg once daily for up to 8 weeks provided higher rates of healing of erosive esophagitis and a greater proportion of patients with sustained resolution of heartburn, than either omeprazole 20 mg or lansoprazole 30 mg once daily. For the maintenance of healing, esomeprazole 20 mg once daily provided significantly higher rates of maintained healing of erosive esophagitis after 6 months of treatment compared with lansoprazole 15 mg once daily. Esomeprazole is also approved for use as part of a triple-drug therapy regimen in combination with amoxicillin and clarithromycin for the eradication of Helicobacter pylori in patients with duodenal ulcer disease. The side effect profile of esomeprazole is similar to that of omeprazole. Many patients with acid-related disorders may benefit from the more rapid symptom relief, higher rates of healing of erosive esophagitis, and improved maintenance of healing that can be achieved with esomeprazole.

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J Clin Gastroenterol. 2004 Mar;38(3):209-17.
Endoluminal therapies for gastroesophageal reflux disease.
Behm BW, Stollman N.
East Bay Center for Digestive Health, 3300 Webster Street, Suite 312, Oakland, CA 94609, USA.

While medical therapy, particularly with proton pump inhibitors, is effective for the large majority of patients with reflux disease, there remains a subset of patients who are dissatisfied, due to cost, side effects of medications, or persistent symptoms such as regurgitation. For this population, surgical fundoplication has been, and remains, an appropriate option. A new class of endoluminal interventions, attempting to create a mechanical antireflux barrier, has emerged recently. Three such devices are currently approved and available, and a number of others are in various stages of evaluation. This article will review the approved technologies, as well as selected promising emerging ones. with particular emphasis on the scientific evidence available to date supporting their efficacy.

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Pol Merkuriusz Lek. 2004 Mar;16(93):275-8.
[Endoscopic treatment of gastroesophageal reflux disease--new possibilities]
[Article in Polish]
Piotrowska-Staworko G, Baniukiewicz A, Laszewicz W.
Klinika Gastroenterologii i Chorob Wewnetrznych Akademii Medycznej w Bialymstoku.

Gastro-esophageal reflux disease (GERD) is one of the most important problems of gastroenterology at present. The symptoms of GERD have negative influence of patients' life on a daily basis. The principal aim of reflux disease treatment is to eliminate or alleviate the symptoms, to heal tissue damages and to reduce the frequency and duration of recurrences. Lifestyle and dietary modification are of only limited value in GERD treatment. Proton pump inhibitors (PPI) are the mainstay of GERD pharmacotherapy for both initial episode and long-term management. Surgical treatment is indicated in: complicated GERD, in patients who need high effective dose of medication, young patients who need lifelong PPI, patients with big hiatus hernia. Laparoscopic Nissen fundoplication has become the operation of choice. Nevertheless patients who have undergone fundoplication may experience adverse post operative complication. The useful alternatives in the management of GERD may indeed eventually prove the new endoscopic methods of minimally invasive treatment which are currently under thorough evaluation. The most promising methods of endoscopic treatment of GERD have been discussed: radiofrequency ablation (the Streett's procedure), endoscopic gastroplasty, endoscopic implantation of biopolymer hydrogel prosthesis.

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Pol Merkuriusz Lek. 2004 Mar;16(93):217-9.
[Effectiveness of omeprazole therapy in children with gastroesophageal reflux diseases(GERD)]
[Article in Polish]
Czerwionka-Szaflarska M, Mierzwa G, Kuczynska R.
Katedra i Klinika Pediatrii, Alergologii i Gastroenterologii Akademii Medycznej w Bydgoszczy.

THE AIM: Of the study was retrospective analysis of omeprazole (Polprazol) therapy efficacy in children with GERD. MATERIAL AND METHODS: The analyzed group consisted of 78 children with gastroesophageal reflux disease. GERD was detected on the base of questionnaire, pH-metry and/or endoscopy. The questionnaire was conducted in all patients, 24-hour pH-metric examination in 47% and endoscopy in 53% children. Than omeprazole therapy was introduced (0.5-1.0 mg/kg daily). RESULTS: Before omeprazole therapy rebounding was observed in 94% children, heartburn in 84%, vomits in 38% and abdominal pain in 90% children. After 8 weeks of therapy analyzed symptoms were significantly reduced--rebounding was observed in 31% children, heartburn in 28% vomits in 5% and abdominal pain in 26% children. CONCLUSION: Omeprazole therapy is effective in children with gastroesophageal reflux disease.

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Drugs Today (Barc). 2004 Mar;40 Suppl A:3-8.
GERD 2003: issues from the past and a consensus for the future.
Modlin I, Kidd M.
Gastric Pathology Research Group, Department of Surgery, Yale University, School of Medicine, New Haven, CT 06520-8062, USA.

Gastroesophageal reflux disease (GERD) has evolved from a scarcely reported, little understood disease process just a century ago to a now highly prevalent disease with up to 25% of the population complaining of symptoms of reflux. Throughout history attempts have been made to delineate the esophagus and related pathologies, but it has not been until relatively recently that enough has been understood about its screening, diagnosis and treatment to make a substantial impact on sufferers. Although the use of antacids and thereafter histamine 2 receptor antagonists dramatically improved the management of GERD, it was the advent of the proton pump inhibitor (PPI) class of drugs that revolutionized medical care. Although the relationship of hiatus hernia to reflux was well accepted, the modest results of open fundoplication fell into further disregard given the efficacy of PPIs. The PPIs are currently the most effective form of therapy and are equivalent on a milligram for milligram basis. While currently no novel drugs or devices are of proven efficacy for GERD, the development of an acid-suppressive agent of equal efficiency to a PPI but with a more rapid onset of action and a greater duration of effectiveness would be of particular clinical utility for the future. (c) 2004 Prous Science

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Surg Today. 2004;34(6):506-9.
Laparoscopic nissen fundoplication for gastroesophageal reflux disease in Japan.
Takeyama S, Numata A, Nenohi M, Shibata Y, Okushiba S, Katoh H.
Department of Surgery, Asahikawa City Hospital, 1-1-65 Kinsei-cho, 070-8610, Asahikawa, Japan.

PURPOSEMETHODS. Between 1998 and 2001 we performed laparoscopic Nissen fundoplication in 23 patients to evaluate the efficiency of this technique. We examined the following four parameters pre- and postoperatively: symptoms, endoscopic findings, gastroesophagogram findings, and the results of intraesophageal 24-h pH monitoring. We also examined the operation time, blood loss, intraoperative complications, and postoperative complications. RESULTS. The operation was safely performed in all patients, regardless of age, and there were no intraoperative complications. Postoperatively, more than three parameters were effectively normalized in 17 (89.5%) of 19 patients. The only postoperative complications were delayed gastric emptying in three patients and persistent dysphagia in five patients. During follow-up, esophagitis recurred in two patients, one of whom underwent laparoscopic refundoplication, which normalized the condition. CONCLUSION. Laparoscopic Nissen fundoplication is highly effective for GERD and could become the standard surgical treatment in Japan.Laparoscopic antireflux surgery is the standard treatment for gastroesophageal reflux disease (GERD) in Western countries where this disorder is common; however, it has only recently been introduced in Japan. We examined the effectiveness of laparoscopic antireflux surgery in a small series of Japanese patients.

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Issues Emerg Health Technol. 2004 Mar;(54):1-4.
Endoscope-based treatments for gastroesophageal reflux disease.
Hailey D.

Endoscope-based products for the treatment of more severe forms of gastroesophageal reflux disease provide an alternative to the use of drugs or surgery. Results from case series have shown that selected patients benefit through relief of symptoms and reduction of medication. Reported adverse effects appear to be minor. Efficacy has been mostly assessed over short periods and there is little information on comparison with other treatments.Procedural skills and appropriate training in their use are required. These technologies are promising, but their place in health care is not established.

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Dtsch Med Wochenschr. 2004 Mar 26;129(13):671-5.
[Long-term course of reflux symptoms following Helicobacter pylori eradication]
[Article in German]
Peitz U, Raps S, Plein K, Leodolter A, Hotz Dagger J, Malfertheiner P.
Klinik fur Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke-Universitat Magdeburg.

BACKGROUND AND OBJECTIVE: Conflicting data regarding new onset or deterioration of gastroesophageal reflux disease (GORD) following eradication of Helicobacter pylori infection have been reported. Successful eradication therapy may influence gastric acid output. The study aimed to to investigate whether patients with pre-existing GORD or peptic ulcer disease may experience deterioration of GORD. PATIENTS AND METHODS: 75 consecutive patients of a prospective longitudinal study (median age 66 years, n = 45 males) had received successful H. pylori eradication therapy because of the following main diagnosis: peptic ulcer (n = 37), GORD (n = 16), functional dyspepsia (n = 22). Two to three years later, they had an interview regarding the course of their dyspeptic and reflux symptoms. Negative H. pylori status at present was confirmed by (13)C-urea breath test in all patients. Ten patients were excluded because of proton pump inhibitor treatment. RESULTS: Patients with deterioration of GORD (new onset or increasing reflux symptoms) were found significantly more frequently in the group with functional dyspepsia (36 %) compared to pre-existing GORD (16 %) or peptic ulcer disease (5 %). Improvement of pre-existing reflux complaints were reported mostly by patients with peptic ulcer disease. There was no significant impact of initial reflux manifestations like reflux symptoms or reflux oesophagitis on the course. CONCLUSIONS: During long-term follow-up after H. pylori eradication, patients experience improvement as frequently as deterioration of reflux symptoms. There is a tendency towards improvement of reflux symptoms if peptic ulcer disease had been the indication for eradication, but towards deterioration in patients with initial functional dyspepsia. A clinical relevant prediction, however, is not feasible.

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Gastrointest Endosc Clin N Am. 2003 Jan;13(1):157-65, xi.
The history and future of implantation therapy for gastroesophageal reflux disease.
Lehman GA.
Indiana University Medical Center, 550 North University Boulevard, Suite 4100, Indianapolis, IN 46202, USA. glehman@iupui.edu

The initial development of endoscopic implantation techniques for the treatment of gastroesophageal reflux disease in the 1980s helped set the stage for current implantation techniques and studies, which now include more than 500 patients. The relative simplicity of these techniques adds to their attraction. Ultimately, multiple factors, including therapeutic efficacy durability, safety, simplicity, and cost-effectiveness, will determine clinical application of these techniques. This article focuses on transoral endoscopic implantation, although surgical, transcutaneous, and other endoscopic routes have been used as well.

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Gastrointest Endosc Clin N Am. 2003 Jan;13(1):147-55.
Clinical experience with the Stretta procedure.
Triadafilopoulos G.
Gastroenterology Section, VA Palo Alto Health Care System, (111-G1), 3801 Miranda Avenue, Palo Alto, CA 94304, USA. vagt@stanford.edu

The benchmarks in GERD therapy comprise the commonly prescribed anti-secretory drugs (H2RAs and PPIs) and anti-reflux surgery. Although drugs are typically safe, cost and patient compliance are challenges to long-term management. Furthermore, while heartburn may be controlled with aggressive medical therapy, other symptoms such as regurgitation may persist, reducing patient satisfaction and adversely affecting quality of life. Surgical anti-reflux procedures, most commonly laparoscopic Nissen fundoplication, improve GERD symptoms and normalize esophageal acid exposure in most patients. Patient perception of the potential risk of abdominal surgery and general anesthesia may limit willingness to undergo surgery resulting in only a small portion of GERD sufferers that actually undergo anti-reflux surgery each year. Overall, the Stretta procedure is well tolerated, with an acceptably low incidence of complications and obviates the need for anti-secretory drug therapy for most patients at the 6- and 12-month follow-up. GERD symptom scores, heartburn, satisfaction, and SF-36 scores significantly improve over the baseline and this effect lasts at least 12 months. The symptomatic improvement after Stretta at 12 months in one trial (GERD score, 27 to 9) is similar to that reported by Velanovich after fundoplication (GERD score, 27 to 3). Furthermore, the significant reduction in median esophageal acid exposure time (distal 10.6% to 6.2%, proximal 1.9% to 0.9%), provides objective evidence of an anti-reflux effect. Although the reported studies have been non-randomized, the objective improvement observed in esophageal acid exposure and the persistence of GERD symptom score improvement with repeated measure analysis over a course of 12 months make a significant placebo effect unlikely. Stretta is a promising new technology for the treatment of GERD that should be considered for patients who wish to discontinue a lifelong anti-secretory medication regimen or who have incomplete GERD symptom control on drugs, but are not yet accepting anti-reflux surgery.

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Gastrointest Endosc Clin N Am. 2003 Jan;13(1):103-8.
Wilson-Cook sewing device: the device, technique, and preclinical studies.
Rosen M, Ponsky J.
Center for Minimally Invasive Surgery, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

Endoscopic treatment of GERD is still in its infancy, however the potential benefits of an endoscopic treatment for GERD are great. These procedures can be performed on an outpatient basis, without the risks of general anesthesia. The absence of abdominal incisions eliminates the morbidity of wound infections and hernia formation. The procedures are certainly less painful than laparoscopic or open surgery for reflux disease. These procedures might even be more cost effective than long-term acid suppression. These benefits make endoscopic treatment for reflux disease an appealing alternative. While the ideal endoscopic therapy has not been developed, all of these approaches have promise for the future and with further study the role of endoscopic therapy for GERD will continue to be defined.

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Gastrointest Endosc Clin N Am. 2003 Jan;13(1):109-16, ix-x.
Endoscopic full-thickness plication: the device, technique, pre-clinical and early clinical experience.
Chuttani R.
Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA. rchuttan@caregroup.harvard.edu

The endoscopic full-thickness plication device is designed to inhibit reflux with a single plication near the gastroesophageal junction. Full-thickness plication of the proximal stomach may improve the competency of the gastroesophageal barrier by restoring the valvular mechanism of the gastroesophageal junction. Other potential mechanisms include alteration of the angle of His, and reduction of the compliance of the gastric cardia and fundus. The procedure is easily and safely performed and, in the human pilot study, has been shown to reduce symptoms and medication use associated with gastroesophageal reflux disease.

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Gastrointest Endosc Clin N Am. 2003 Jan;13(1):89-101.
Endoscopic suturing for gastroesophageal reflux disease: clinical outcome with the Bard EndoCinch.
Rothstein RI, Filipi CJ.
Section of Gastroenterology Dartmouth Hitchcock Medical Center, One Medical Drive, Lebanon, NH 03756, USA. richard.rothstein@dartmouth.edu

From a review of the single peer reviewed published report and the brief preliminary studies presented in abstract form, the BARD EndoCinch procedure seems safe and demonstrates an acceptable efficacy for symptom control during short-term follow-up. Most patients (about 2 out of 3) do well with improvement of GERD symptoms during the first post-procedural year. This benefit may wane over time. Objective benefit is lacking with the minority of treated individuals achieving normalization of 24-hour total acid exposure, and no significant effect has been seen in healing of esophagitis. This may focus the treatment towards that group of GERD patients with mild or non-erosive disease. The authors have no information that the endoscopic therapy could prevent reflux-related complications, and long-term data is awaited from accumulated clinical experience to establish the maintenance profile of this novel treatment. The outcomes from the sham trial, and long-term follow-up data will help to define the role of this anti-reflux therapy. The authors need additional studies to define the effect of endoluminal plication on the function of the lower esophageal sphincter to optimize its benefit for patients.

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Gastrointest Endosc Clin N Am. 2003 Jan;13(1):57-68.
Overview of medical therapy for gastroesophageal disease.
Ramakrishnan A, Katz PO.
Department of Medicine, Graduate Hospital, 1800 Lombard Street, Suite 501, Pepper Pavilion, Philadelphia, PA 19146, USA.

The last twenty years have seen an evolution of much improved strategies in the medical treatment of GERD. Current therapy is targeted at acid suppression, to deal with consequences of mucosal injury and afford resolution of symptoms. Given their modest efficacy, there is no longer much support for initial treatment with H2RAs. PPIs have been shown to provide the highest levels of symptom relief and esophageal healing, in addition to preventing relapse and complications. With this class of agents, the clinician is able to prescribe a drug that is as highly effective as surgery for the purpose intended, without worrying about long term sequelae of acid suppression. It appears that patients with extraesophageal GERD must be treated with higher doses of pharmacologic therapy, principally with the PPIs, for longer periods of time to achieve complete relief of symptoms when compared to patients with heartburn and erosive esophagitis. There is still no clear consensus as to whether aggressive acid suppression alters the natural history of Barrett's esophagus. Based on their initial success, it appears that the next generation of evolving medical therapies will continue to play an important role in the management of GERD. The outcome from medical therapy is the standard against which the results of the novel endoscopy anti-reflux treatments will be measured.

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Rev Gastroenterol Disord. 2003 Spring;3(2):59-69.
Optimizing medical therapy for gastroesophageal reflux disease: state of the art.
Katz PO.
Department of Medicine, Graduate Hospital, Philadelphia, PA, USA.

Potential interventions for gastroesophageal reflux disease include lifestyle modifications, antacids, mucosal protectants, prokinetic (promotility) agents, H2 receptor antagonists (H2RAs) and, the agents of choice in 2003, proton pump inhibitors (PPIs). This article reviews the current state of the art in use of these agents. Lifestyle changes, though sound in their intent and in many cases based on solid laboratory research, can today be considered only adjuncts to pharmacologic therapy. The mainstay of pharmacologic therapy in 2003 is antisecretory therapy. Both H2RAs and PPIs inhibit acid secretion and raise intragastric pH. H2RAs only block one receptor, have limited effect on acid reduction, and are relatively weak inhibitors of meal-stimulated acid secretion. PPIs provide superior control of intragastric pH over a 24-hour period compared with H2RAs and effect greater symptom relief and healing.

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Dig Dis Sci. 2003 Apr;48(4):657-62.
Reductions in symptom distress reported by patients with moderately severe, nonerosive gastroesophageal reflux disease treated with rabeprazole.
Damiano A, Siddique R, Xu X, Johanson J, Sloan S.
Covance Health Economics and Outcomes Services Inc., Gaithersburg, Maryland 20878, USA.

Gastroesophageal reflux disease (GERD) is characterized by heartburn and related symptoms that are distressing to patients and interfere with everyday functioning and well-being. A measure of symptom distress, the GERD Symptom Assessment Scale (GSAS), was included in two randomized, placebo-controlled trials of rabeprazole among patients with nonerosive GERD. The age (mean +/- SD) of the 223 patients was 43.5 +/- 11.9 years, and most were female (67%) and Caucasian (78%). Significantly greater reductions in symptom distress were observed among patients receiving rabeprazole 20 mg daily for 4 weeks relative to those receiving placebo (-0.62 vs -0.36, P < 0.0001). The magnitude of this treatment difference was comparable to the differences observed between levels of overall symptom improvement on the patient global rating (0.2 and 0.3 points; P < 0.0001). In conclusion, reducing symptom distress is an important goal of therapeutic interventions for GERD. Rabeprazole significantly reduced the distress associated with a broad range of GERD symptoms, and the magnitude of this effect was meaningful to patients.

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Br J Surg. 2003 May;90(5):560-2.
Day-case laparoscopic Nissen fundoplication.
Bailey ME, Garrett WV, Nisar A, Boyle NH, Slater GH.
Minimal Access Therapy Training Unit, Royal Surrey County Hospital, Egerton Road, Guildford GU7 5XX, UK. meb@mattu.org.uk

BACKGROUND: The aim was to assess the acceptability and safety of day-case laparoscopic fundoplication for gastro-oesophageal reflux disease (GORD). METHODS: This prospective study commenced in December 1999 and lasted for 18 months. All patients had proven symptomatic GORD. Inclusion criteria were American Society of Anesthesiologists grade I or II with adequate home support. A standard anaesthetic, analgesic and antiemetic protocol was used. Patients were contacted by telephone on the night of discharge and arrangements were made for a nurse to visit the following day. Postoperative pain and nausea were assessed using visual analogue scores (scale 0-10) on a self-completion questionnaire. RESULTS: Twenty patients were included. There were no postoperative complications. All patients were discharged on the day of surgery. Median time to discharge was 6 h 30 min (range 4.5 to 9 h). One patient reattended casualty the following morning but none required readmission. There was no significant difference in median pain or nausea scores the evening after surgery or the next morning. All patients were satisfied with the information given and aftercare provided. All would recommend it to a friend and 19 of 20 would undergo the procedure as a day case again. CONCLUSION: This study suggests that day-case laparoscopic fundoplication is feasible. Patients find it acceptable and it appears safe. Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

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Drugs Today (Barc). 2003 Mar;39 Suppl A:21-8.
Endoscopic antireflux treatment: fact, fiction or future?
Hochberger J, Tex S, Maiss J, Muehldorfer S, Hahn EG.
Department of Medicine I, University of Erlangen, Erlangen, Germany. juehochber@aol.com

Medical therapy with proton pump inhibitors (PPIs), aside from surgery, is the established and most effective treatment approach for chronic gastroesophageal reflux disease (GERD). Recently developed endoscopic antireflux procedures may be an alternative for a subset of patients with uncomplicated, mild GERD. Given the perioperative morbidity and mortality risk of laparoscopic fundoplication, less invasive semi-surgical and flexible endoscopic techniques may be an option for patients who cannot or wish not to take long-term medication. These clinical procedures include endoscopic suturing devices, focal radiofrequency coagulation in the cardia and bioimplants. While many of these techniques have shown good results in preliminary studies, long-term results are not yet available and therefore all such procedures have to be considered experimental. Their effectiveness will need to be compared with that of established treatment forms.

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Drugs Today (Barc). 2003 Mar;39 Suppl A:15-20.
Management of gastroesophageal reflux disease.
Stanghellini V.
Department of Internal Medicine and Gastroenterology, University of Bologna, Italy.

Gastroesophageal reflux disease (GERD) is a frequent clinical condition which leads to reduced quality of life. Atypical manifestations of the disease can confound diagnosis, and even the typical symptoms of heartburn and regurgitation can lead to misinterpretation. Proton pump inhibitors (PPIs) are the standard treatment for GERD and the different formulations show equivalence on a milligram to milligram basis in terms of efficacy and tolerability. With standard dosing, 8 weeks of treatment has been shown to heal most patients. However, as GERD is a chronically relapsing disease, maintenance treatment with lower dose PPIs is frequently required. Pantoprazole is the only PPI found not to interact with the metabolism of other drugs and is therefore the treatment of choice especially for patients with co-morbidities and co-medication.

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J Gastroenterol. 2003 Mar;38 Suppl 15:13-9.
Therapeutic approaches to reflux disease, focusing on acid secretion.
Kinoshita Y, Adachi K, Fujishiro H.
Department of Internal Medicine II, Shimane Medical University, 89-1 Enya-cho, Izumo 693-8501, Japan.

Gastroesophageal reflux disease (GERD) is caused by a combination of esophageal motor dysfunction accompanied by maintained gastric acid secretion. Noninvasive medical treatment of GERD is mainly provided by inhibiting gastric acid secretion, because this is easier than restoring esophageal motor function by administration of drugs. Proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2RAs) are two major acid-suppressing drugs used for the treatment of GERD. PPIs have better characteristics for the long-term treatment of GERD, because they have a long-lasting, strong effect of raising intragastric pH and have no tachyphylaxis/tolerance phenomena on repeated dosing. Some patients with Helicobacter pylori-negative high-grade GERD may show nocturnal decreases in pH during treatment with PPIs and resistance to treatment with PPI. For these patients, addition of H2RAs to PPIs can be useful for controlling GERD, at least for short-term treatment. For long-term control of such cases, further studies are necessary.

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Am J Gastroenterol. 2003 Mar;98(3 Suppl):S49-55.
Rabeprazole-based therapy in the management of symptomatic gastroesophageal reflux disease.
Sloan S.
Department of Medical Affairs, Janssen Pharmaceutica Inc., 1125 Trenton-Harbourton Road, Titusville, NJ 08560-0200, USA.

Gastroesophageal reflux disease (GERD) is associated with several symptoms, such as heartburn, belching, and regurgitation, which arise from esophageal exposure to gastric acid. Symptoms may occur in the absence of endoscopically observed esophageal mucosal damage and inflammation. These patients represent the majority of those who present with GERD symptoms. Although acid suppression therapy is a logical approach to relieving GERD symptoms, it has been thought to relieve symptoms less reliably in patients with endoscopically negative, or symptomatic GERD than in those with erosive GERD. Two multicenter, randomized, double-blind, placebo-controlled clinical trials were conducted in the United States to evaluate the efficacy of rabeprazole sodium 10 mg and 20 mg compared with placebo for the relief of heartburn and other symptoms associated with symptomatic GERD. Results from these studies indicated that rabeprazole 10 or 20 mg once daily relieved heartburn within the first 1 or 2 days of treatment and also had significant positive effects on other GERD symptoms, including regurgitation, belching, bloating, satiety, and nausea. Overall, these results suggest that rabeprazole may hold a significant therapeutic advantage in the treatment of heartburn and other symptoms associated with endoscopically negative GERD, particularly in the majority of patients who often are treated empirically without, or before, endoscopic evaluation.

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Laryngorhinootologie. 2003 Feb;82(2):118-22.
[Gastroesophageal reflux -- a common illness?]
[Article in German]
Issing WJ.
Klinik und Poliklinik fur Hals-, Nasen- und Ohrenkranke, Klinikum Grosshadern, Ludwig-Maximilians-Universitat Munchen, Munich. wolfgang.issing@web.de

For a long time heartburn was not considered a symptom for serious illness. By now, however, it is accepted that the incidence of secondary carcinoma of the esophagus caused by chronic GERD has increased dramatically since the nineteen-seventies. Mechanisms leading to GERD are complex and its incidence is not necessarily pathological. However pathological reflux in the lower esophagus (pH lower than 4 in 6 % of 24 hours), caused by decreased sphinctertonus, impaired peristalsis and clearance of the esophagus, may lead to complications. Helicobacter pylori may play a key role in GERD. There is strong evidence for a protective effect of Hp-infection in the development of GERD. In pangastritis, caused by Hp-infection, gastric acid production is inhibited resulting in a reduction of stomach-acid-concentration. This may be caused by either the chronic infection itself and the resulting atrophy of the stomach-mucosa, by the ammonia-producing HP-bacteria, or an increase in acid re-absorbtion of gastric epithelium. Laryngopharyngeal reflux (LPR) often results in atypical manifestations with oral, pharyngeal, laryngeal, and pulmonary disorders. Laryngopharyngeal reflux is known to contribute to posterior acid laryngitis and laryngeal contact ulceration or granuloma formation, laryngeal cancer, chronic hoarseness, pharyngitis, asthma, pneumonia, nocturnal choking, and dental diseases. Today, PPI are the medication of choice in both acute and long-term (prophylactic) therapy of GERD. The so called "step-up-strategy" of medication is no longer recommended. Here, patients were first treated with antacids, then prokinetics followed by H2-blockers and finally low-dose PPI. Only in the case of persisting symptoms medication was further increased to high-dose PPI therapy. In the past this increase in medication lead to a prolonged healing process and consequently to higher medication costs. Studies have shown that a "step-down"-therapy, beginning with high dose PPI, is highly preferable, since it is much more effective. Depending on the degree of the symptoms, however, medication may also be applied "on-demand". The BfArM has approved this kind of medication application only for Esomeprazol (Nexium mups 20 mg).

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J Fam Pract. 2003 Mar;52(3):240-7.
Gastroesophageal reflux disease.
Howden CW, Chey WD.
Division of Gastroenterology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.

Heartburn on 2 or more days a week warrants medical attention, as patients are likely to suffer from gastroesophageal reflux disease (GERD). Chronic GERD can lead to the development of complications including erosive esophagitis, stricture formation, and Barrett's esophagus, which increases the risk of esophageal adenocarcinoma. A trial with a proton pump inhibitor (PPI) is the quickest and most cost-effective way to diagnose GERD, and is at least as sensitive as 24-hour intra-esophageal pH monitoring. As PPIs only bind to actively secreting proton pumps, they should be dosed 30 to 60 minutes before a meal. Despite these recommendations, a recent survey of over 1000 US primary care physicians found that 36% instructed their patients to take a PPI with or after a meal or did not specify the timing of dosing. The patients who will have the best response to surgical therapy for GERD are those who had clearly documented acid reflux with typical symptoms, and who have responded to PPI treatment. Unfortunately, the same survey found that most physicians recommend antireflux surgery for patients in whom medical therapy has failed.

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Aliment Pharmacol Ther. 2003 Feb;17 Suppl 1:53-7.
Overview: initial and long-term management of gastro-oesophageal reflux disease.
Dent J, Talley NJ.
Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. jdent@mail.rah.sa.gov.au

Initial management of gastro-oesophageal reflux disease aims to confirm a symptom-based diagnosis, to relieve symptoms, to reassure the patient as to the treatable nature of reflux disease, and to initiate risk management and healing of oesophagitis. The aims of long-term management include adequate control of symptoms, prevention of complications, and improvement of quality of life. Management options in terms of use of proton pump inhibitors are either daily therapy (maintenance), intermittent courses of therapy (for example, 4 weeks, then cease and observe), or on-demand therapy. This overview discusses the advantages and disadvantages of these different strategies for the management of reflux disease.

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Aliment Pharmacol Ther. 2003 Feb;17 Suppl 1:18-20.
Review article: initial therapy of reflux disease with esomeprazole.
Dent J.
Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. jdent@mail.rah.sa.gov.au

Large clinical trials in patients with reflux oesophagitis have shown esomeprazole, 40 mg once daily, to be convincingly superior in the healing of oesophagitis when compared with both omeprazole, 20 mg once daily, and lansoprazole, 30 mg once daily. The greatest advantage for esomeprazole is with healing of the more severe grades of oesophagitis. Esomeprazole, 40 mg once daily, has also been shown to be significantly superior in the treatment of heartburn. Studies in endoscopy-negative patients, or in both oesophagitis and endoscopy-negative patients, have demonstrated good efficacy for esomeprazole, with high levels of symptom control achieved in the first 7 days of therapy.

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Aliment Pharmacol Ther. 2003 Feb;17 Suppl 1:10-5; discussion 16-7.
Review article: gastric acidity--comparison of esomeprazole with other proton pump inhibitors.
Hatlebakk JG.
Department of Medicine, Haukeland Sykehus, University of Bergen, N-5021 Bergen, Norway. jhat@haukeland.no

Gastric acid suppression is the most effective medical therapy to control acidic gastro-oesophageal reflux: individuals in whom therapy fails usually have inadequate acid suppression. Twenty-four-hour intragastric pH-metry measures the percentage of time that gastric pH is above 4 or 3, the critical thresholds for tissue damage and symptom generation in the distal oesophagus. Effective medical therapy must control gastric acidity throughout the daytime, including the postprandial period. It is therefore useful to report the percentage of patients in whom gastric acidity is controlled above pH 4 for at least 16 out of 24 h. Esomeprazole was compared with standard-dose proton pump inhibitors in healthy volunteers and patients with gastro-oesophageal reflux disease. Esomeprazole, 40 mg daily, was significantly more effective at controlling gastric acidity above pH 4 for more than 16 h than lansoprazole, 30 mg daily (38% of individuals vs. 5%, respectively). Esomeprazole, 40 mg daily, also suppressed gastric acidity more effectively and in more individuals than pantoprazole, 40 mg daily, and rabeprazole, 20 mg daily. Esomeprazole, 20 mg daily, was significantly more effective at controlling gastric acidity than lansoprazole, 15 mg daily. The improved acid control with esomeprazole compared with other proton pump inhibitors is likely to result in superior healing rates and improved symptom relief, with fewer therapy-resistant patients.

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Lancet. 2003 Mar 29;361(9363):1119-21.
Endoluminal therapies for gastro-oesophageal reflux disease.
Galmiche JP, Bruley des Varannes S.
Department of Gastroenterology and Hepatology, CIC INSERM, CHU Nantes, 44093, Nantes, France. galmiche@easynet.fr <galmiche@easynet.fr>

CONTEXT: Gastro-oesophageal reflux disease (GORD) is a common chronic disorder that has severe impact on quality of life and often requires continuous acid-suppression therapy. Proton-pump inhibitors (PPIs) are extremely effective but expensive, and do not restore the normal antireflux barrier at the gastro-oesophageal junction. Antireflux surgery, even with the laparoscopic approach, has not proven more cost-effective than maintenance therapy with PPIs. Postoperative morbidity is substantial, especially when procedures are done outside expert centres. In the past few years several endoscopic techniques have been developed to treat chronic GORD on an outpatient basis. These techniques include radiofrequency-energy delivery and endoscopic suturing, although other approaches are now under development. STARING POINT: Two prospective open-label studies have recently reported 1-year follow-up of GORD patients treated either by radiofrequency-energy delivery (G Triadafilopoulos and colleagues Gastrointest Endosc 2002; 55:149-56) or endoscopic suturing (Z Mahmood and colleagues Gut 2003; 52:34-39). In a US multicentre trial, Triadafilopoulos and colleagues delivered radiofrequency energy to the cardia and distal oesophagus in patients with chronic heartburn, regurgitation or both (the Stretta procedure). All patients were on continuous acid-suppression therapy, but none had severe oesophagitis or hiatus hernia of more than 2 cm. At 12 months, 94 patients available for follow-up showed significant improvement in GORD symptoms, quality of life, and oesophageal acid-exposure. The need for PPI therapy fell from 98% to 30% of patients. In the Mahmood study, 26 similar patients had endoscopic suturing in a single centre. After 1 year, symptoms and quality of life improved and the need for PPIs was reduced to 36% from 100%. In both studies, only minor complications occurred, none of which required specific therapeutic intervention. WHERE NEXT? An effective outpatient procedure to treat chronic GORD would represent a major step forward. However, further studies are needed before an endoscopic approach can be adopted, as none of the published trials are well-controlled studies. Longer follow-up is needed to ensure that relapses do not occur rapidly, complications do not occur more frequently with less skilled operators, or that endoscopic-induced changes do not complicate or compromise subsequent antireflux surgery. Comparative studies of the cost-effectiveness of endoscopic therapy should also include medical strategies such as intermittent or on-demand PPI therapy.

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Dig Liver Dis. 2002 Dec;34(12):870-7.
On-demand proton pump inhibitor therapy in patients with gastro-oesophageal reflux disease.
Pace F, Pallotta S, Bianchi Porro G.
Gastrointestinal Unit, L. Sacco University Hospital, University of Milan, Italy.

On-demand therapy is an established modality in long-term therapy with histamine-2-receptor antagonists, in cases of mild non-erosive gastro-oesophageal reflux disease. In the literature, only a few studies have specifically addressed the problem of proton pump inhibitors on-demand treatment. The evidence, so far, available suggests that this might be an effective modality of long-term treatment in the majority of patients with non-erosive gastro-oesophageal reflux disease. This treatment modality appears to be the most cost-effective and the best tolerated medical regimen for gastro-oesophageal reflux disease. It also seems to be able to restore the impairment of health-related quality of life due to gastro-oesophageal reflux disease symptoms. Although the current standard of care for patients with non-erosive gastro-oesophageal reflux disease is maintenance therapy with daily administration of a proton pump inhibitor agent, on-demand therapy, with the same drug, may be a reasonable long-term choice. The ideal proton pump inhibitors for such treatment will be those with a more rapid onset of action, more profound acid inhibition, more predictable therapeutic effect and less drug-drug interactions. Newer proton pump inhibitors, like esomeprazole, the S-chiral isomer of omeprazole, are promising drugs for on-demand treatment of gastro-oesophageal reflux disease.

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Kongressbd Dtsch Ges Chir Kongr. 2002;119:184-7.
[Laparoscopic fundoplication--what is proven?]
[Article in German]
Stein HJ.
Chirurgische Klinik und Poliklinik, Klinikum rechst der Isar der Technischen Universitat Munchen, Ismaningerstrasse 22, 81675 Munchen. stein@nt1.chir.med.tu-muenchen.de

Laparoscopic fundoplication has become a popular procedure but several questions remain unresolved. Although randomised trials suggest that antireflux surgery is a good alternative to continuous medical therapy, the selection of patients for surgery remains crucial to achieve success. There is currently no proof that antireflux surgery will reduce the risk for developing esophageal adenocarcinoma. Complications, side effects and failures appear to be higher after a laparoscopic approach as compared to conventional open surgery, particularly in un-experienced hands. Partial fundoplications and tailored approaches have so far not shown convincingly better results than those that can be achieved by short and floppy 360 fundoplication.

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Eur J Gastroenterol Hepatol. 2002 Sep;14 Suppl 1:S5-9.
Proton pump inhibitors in the elderly population.
Whitaker M.
Didsbury Medical Centre, 645 Wilmslow Road, Didsbury, Manchester M20 6BA, UK. mark.whitaker@gp-p84678.nhs.uk

Accurate diagnosis and effective treatment of acid-related diseases, including gastro-oesophageal reflux disease (GORD), are important health care priorities, particularly in the elderly. Both the prevalence and severity of GORD are increased in older individuals. The reason for the age-related increase in the prevalence of GORD is not completely understood, but it appears to result from both age-related changes in physiology and effects of the medications often taken by older people. The diagnosis of GORD in the elderly is also difficult because of its potential atypical presentation in these patients, as well as the overlap between GORD symptoms and those of other chronic conditions, including coronary artery disease and chronic obstructive pulmonary disease. Proton pump inhibitors (PPIs) are now considered the treatment of choice for patients with GORD, and these drugs have excellent efficacy and safety profiles. One of the newer drugs in this class, rabeprazole, may be particularly suited for use in older patients. Rabeprazole requires no dosing adjustment in the elderly or in patients with renal insufficiency or mild-to-moderate hepatic disease. It is also relatively free of clinically significant drug-drug interactions, which strongly differentiates rabeprazole from omeprazole, the prototype PPI. Overall, the clinical and pharmacokinetic profiles for rabeprazole suggest that it is an excellent first choice for the management of older patients with GORD.

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Eur J Surg. 2002;168(8-9):441-5.
Repeat antireflux surgery: effectiveness of a toupet partial posterior fundoplication.
Johnsson E, Lundell L.
Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.

OBJECTIVE: To report the feasibility and efficacy of posterior partial fundoplication for patients with recurrent reflux after previous antireflux operations. DESIGN: Prospective non-randomised single hospital study. SETTING: University hospital, Sweden. PATIENTS: 32 consecutive patients who required reoperation after failure of previous operations for gastro-oesophageal reflux disease. MAIN OUTCOME MEASURES: Control of symptoms, oesophageal acid reflux. RESULTS: Most patients were referred for reoperation because of recurrent reflux, but six patients had a symptomatic intrahoracic herniation of the wrap with a life-threatening perforation in one patient. Three patients had recurrent reflux within 6 months of the operation and another two were classified as failures. The remaining 27 (84%) were classified as having a successful outcome during a mean follow-up period of 20 months. CONCLUSION: A posterior partial fundoplication can be done safely in a repeat operation for patients whose antireflux operation has failed.

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Gastroenterol Clin North Am. 2002 Dec;31(4 Suppl):S89-109.
Surgical and endoscopic treatment of gastroesophageal reflux disease.
Waring JP.
Digestive Healthcare of Georgia, 95 Collier Road, Suite 4075, Atlanta, GA 30309, USA.

There is no evidence to advocate medical or surgical therapy as the best therapy for GERD. The decision to have antireflux surgery must be individualized. All patients taking long-term medications for GERD should receive advice on the safety and wisdom of staying on that therapy and information on antireflux surgery. Fundoplication should be considered in three circumstances [4]: 1. Patients who are intolerant of PPI therapy because of side effects should be considered for surgery. This situation will be less common now with five PPIs, however. 2. Patients who are poorly responsive to PPI therapy should be considered for surgery. This situation is probably not common, given the effectiveness of the currently available PPIs. It is more common in patients with atypical GERD. The gastroenterologist should be as certain as possible that the patient not only has GERD, but also that the patient's symptoms are reflux related. 3. Surgery should be considered when patients desire a permanent solution to free them of the need to take medications. These patients must be warned about the potential suboptimal results, including the frequent need for medication within a few years of having the procedure and the small but real possibility of becoming worse after the operation. Even in experienced hands, 1% to 2% of patients are worse after the procedure. A careful preoperative evaluation to ensure that the patient's symptoms are reflux related and that the right operative procedure is performed offers the patient the best opportunity for success. Widespread use of endoscopic therapy for GERD is probably still several years away. The best endoscopic therapy is yet to be determined, but it will need to be safe, effective, and easy to use.

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Rev Gastroenterol Disord. 2002 Fall;2(4):189-99.
Esomeprazole: update and clinical review.
Baker DE.
College of Pharmacy, Washington State University, Spokane, Washington, USA.

The U.S. Food and Drug Administration's Nonprescription Drugs Advisory Committee and Gastroenterological Drugs Advisory Committee recommended approval of omeprazole as an over-the-counter treatment of heartburn in patients who have at least two episodes of heartburn each week. The consumer studies that have been conducted indicate that the majority of patients understand the proposed labeling and could use the proposed label to determine if the omeprazole therapy was appropriate for them. Esomeprazole is an effective agent in the treatment of gastroesophageal reflux disease (GERD) and erosive esophagitis. Newer studies continue to support its efficacy and safety in the treatment of these conditions. Several of the most recent studies have included comparisons with other proton pump inhibitors. The results of these studies indicate that all the proton pump inhibitors are effective in treating GERD and erosive esophagitis and that some patients would benefit from esomeprazole therapy.

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