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