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Reiter AJ, Farina DA, Fronza JS, Komanduri S. Magnetic sphincter augmentation: considerations for use in Barrett's esophagus. Dis Esophagus 2023; 36:doac096. [PMID: 36575922 PMCID: PMC10267686 DOI: 10.1093/dote/doac096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 11/11/2022] [Accepted: 11/23/2022] [Indexed: 12/29/2022]
Abstract
Barrett's esophagus (BE) occurs in 5-15% of patients with gastroesophageal reflux disease (GERD). While acid suppressive therapy is a critical component of BE management to minimize the risk of progression to esophageal adenocarcinoma, surgical control of mechanical reflux is sometimes necessary. Magnetic sphincter augmentation (MSA) is an increasingly utilized anti-reflux surgical therapy for GERD. While the use of MSA is listed as a precaution by the United States Food and Drug Administration, there are limited data showing effective BE regression with MSA. MSA offers several advantages in BE including effective reflux control, anti-reflux barrier restoration and reduced hiatal hernia recurrence. However, careful patient selection for MSA is necessary.
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Affiliation(s)
- Audra J Reiter
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Domenico A Farina
- Department of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Jeffrey S Fronza
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Srinadh Komanduri
- Department of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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2
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Shibli F, Sandhu DS, Fass R. The Discrepancy Between Subjective and Objective Clinical Endpoints in Gastroesophageal Reflux Disease. J Clin Gastroenterol 2022; 56:375-383. [PMID: 35324484 DOI: 10.1097/mcg.0000000000001687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
Therapeutic outcome in gastroesophageal reflux disease (GERD) is commonly determined by both subjective and objective clinical endpoints. Clinicians frequently use symptom improvement as a key benchmark of clinical success, in conjunction with normalization of objective parameters such as esophageal acid exposure and inflammation. However, GERD therapeutic trials have demonstrated that a substantial number of patients rendered asymptomatic, whether through medical, surgical, or endoscopic intervention, continue to have persistent abnormal esophageal acid exposure and erosive esophagitis. The opposite has also been demonstrated in therapeutic trials, where patients remained symptomatic despite normalization of esophageal acid exposure and complete resolution of esophageal inflammation. Moreover, there is no substantive evidence that symptomatic response to antireflux treatment requires complete esophageal mucosal healing or normalization of esophageal acid exposure. Thus, it appears that a certain level of improvement in objective parameters is needed to translate into meaningful changes in symptoms and health-related quality of life of GERD patients. This supports the need to reconsider the commonly used "hard" clinical endpoints to evaluate therapeutic trials in GERD.
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Affiliation(s)
- Fahmi Shibli
- Division of Gastroenterology and Hepatology, The Esophageal and Swallowing Center, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH
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Farina DA, Condon A, Komanduri S, Muthusamy VR. A Practical Approach to Refractory and Recurrent Barrett's Esophagus. Gastrointest Endosc Clin N Am 2021; 31:183-203. [PMID: 33213795 DOI: 10.1016/j.giec.2020.09.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Endoscopic eradication therapy (EET) is recommended for patients with Barrett's esophagus (BE)-associated neoplasia and is effective in achieving complete eradication of intestinal metaplasia (CE-IM). However, BE that is refractory to EET, defined as partial or no improvement in dysplasia after less than or equal to 3 ablative sessions, and the development of recurrence post-EET is not uncommon. Identification of refractory BE or recurrent intestinal metaplasia should prompt esophageal physiologic testing and modification of antireflux strategy, as appropriate. In patients who ultimately fail standard EET despite optimization of reflux control, salvage EET with alternate modalities may need to be considered.
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Affiliation(s)
- Domenico A Farina
- Department of Gastroenterology and Hepatology, Northwestern University, 676 North St. Clair Street, Arkes Pavilion Suite 1400, Chicago, IL 60611, USA
| | - Ashwinee Condon
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, 200 UCLA Medical Plaza, Room 330-37, Los Angeles, CA 90095, USA
| | - Srinadh Komanduri
- Department of Gastroenterology and Hepatology, Northwestern University, 676 North St. Clair Street, Arkes Pavilion Suite 1400, Chicago, IL 60611, USA
| | - V Raman Muthusamy
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, 200 UCLA Medical Plaza, Room 330-37, Los Angeles, CA 90095, USA.
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Trad KS, Barnes WE, Prevou ER, Simoni G, Steffen JA, Shughoury AB, Raza M, Heise JA, Fox MA, Mavrelis PG. The TEMPO Trial at 5 Years: Transoral Fundoplication (TIF 2.0) Is Safe, Durable, and Cost-effective. Surg Innov 2018; 25:149-157. [PMID: 29405886 PMCID: PMC5946656 DOI: 10.1177/1553350618755214] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Questions remain about the therapeutic durability of transoral incisionless fundoplication (TIF). In this study, clinical outcomes were evaluated at 5 years post-TIF 2.0. METHODS A total of 63 chronic gastroesophageal reflux disease (GERD) sufferers with troublesome symptoms refractory to proton pump inhibitor (PPI) therapy, absent or ≤2 cm hiatal hernia, and abnormal esophageal acid exposure were randomized to the TIF group or PPI group. Following the 6-month evaluation, all patients in the PPI group elected for crossover to TIF; therefore, all 63 patients underwent TIF 2.0 with EsophyX2 device. Primary outcome was elimination of daily troublesome regurgitation and atypical symptoms at the 5-year follow-up. Secondary outcomes were improvement in symptom scores, PPI use, reoperations, and patient health satisfaction. The cost-effectiveness of TIF 2.0 was also estimated. RESULTS Of 63 patients, 60 were available at 1 year, 52 at 3 years, and 44 at 5 years for evaluation. Troublesome regurgitation was eliminated in 88% of patients at 1 year, 90% at 3 years, and 86% at 5 years. Resolution of troublesome atypical symptoms was achieved in 82% of patients at 1 year, 88% at 3 years, and 80% at 5 years. No serious adverse events occurred. There were 3 reoperations by the end of the 5-year follow-up. At the 5-year follow-up, 34% of patients were on daily PPI therapy as compared with 100% of patients at screening. The total GERD Health-related quality-of-life score improved by decreasing from 22.2 to 6.8 at 5 years ( P < .001). CONCLUSION In this patient population, the TIF 2.0 procedure provided safe and sustained long-term elimination of troublesome GERD symptoms.
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Affiliation(s)
- Karim S Trad
- 1 The George Washington University School of Medicine and Health Science, Washington, DC, USA.,2 The George Washington University Medical Faculty Associates, Washington, DC, USA
| | - William E Barnes
- 3 Livingston Hospital and Healthcare Services, Inc, CAH, Salem, KY, USA
| | - Elizabeth R Prevou
- 2 The George Washington University Medical Faculty Associates, Washington, DC, USA
| | - Gilbert Simoni
- 4 Advanced Gastroenterology, Inc, Thousand Oaks, CA, USA
| | - Jennifer A Steffen
- 2 The George Washington University Medical Faculty Associates, Washington, DC, USA
| | - Ahmad B Shughoury
- 5 Saint Mary Medical Center, Hobart, IN, USA.,6 Internal Medicine Associates, Merrillville, IN, USA
| | - Mamoon Raza
- 7 Indiana Medical Research, Elkhart, IN, USA.,8 Unity Surgical Hospital, Mishawaka, IN, USA
| | | | - Mark A Fox
- 10 Crossville Medical Group, Crossville, TN, USA.,11 Cumberland Medical Center, Crossville, TN, USA
| | - Peter G Mavrelis
- 5 Saint Mary Medical Center, Hobart, IN, USA.,6 Internal Medicine Associates, Merrillville, IN, USA
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5
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Response to TNF-α Is Increasing Along with the Progression in Barrett's Esophagus. Dig Dis Sci 2017; 62:3391-3401. [PMID: 29086334 DOI: 10.1007/s10620-017-4821-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Accepted: 10/20/2017] [Indexed: 01/20/2023]
Abstract
BACKGROUND AND AIMS Barrett's esophagus, a metaplasia resulting from a long-standing reflux disease, and its progression to esophageal adenocarcinoma (EAC) are characterized by activation of pro-inflammatory pathways, induced by cytokines. METHODS An in vitro cell culture system representing the sequence of squamous epithelium (EPC1 and EPC2), Barrett's metaplasia (CP-A), dysplasia (CP-B) to EAC (OE33 and OE19) was used to investigate TNF-α-mediated induction of interleukin-8 (IL-8). RESULTS IL-6 and IL-8 expressions are increasing with the progression of Barrett's esophagus, with the highest expression of both cytokines in the dysplastic cell line CP-B. IL-8 expression in EAC cells was approx. 4.4-fold (OE33) and eightfold (OE19) higher in EAC cells than in squamous epithelium cells (EPC1 and EPC2). The pro-inflammatory cytokine TNF-α increased IL-8 expression in a time-, concentration-, and stage-specific manner. Furthermore, TNF-α changed the EMT marker profile in OE33 cells by decreasing the epithelial marker E-cadherin and increasing the mesenchymal marker vimentin. The anti-inflammatory compound curcumin was able to repress proliferation and to activate apoptosis in both EAC cell lines. CONCLUSION The increased basal expression levels of IL-8 with the progression of Barrett's esophagus constrain NFκB activation and its contribution in the manifestation of Barrett's esophagus. An anti-inflammatory compound, such as curcumin, could create an anti-inflammatory microenvironment and thus potentially support an increase chemosensitivity in EAC cells.
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6
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Baldaque-Silva F, Vieth M, Debel M, Håkanson B, Thorell A, Lunet N, Song H, Mascarenhas-Saraiva M, Pereira G, Lundell L, Marschall HU. Impact of gastroesophageal reflux control through tailored proton pump inhibition therapy or fundoplication in patients with Barrett’s esophagus. World J Gastroenterol 2017; 23:3174-3183. [PMID: 28533674 PMCID: PMC5423054 DOI: 10.3748/wjg.v23.i17.3174] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Revised: 12/02/2016] [Accepted: 01/11/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the impact of upwards titration of proton pump inhibition (PPI) on acid reflux, symptom scores and histology, compared to clinically successful fundoplication.
METHODS Two cohorts of long-segment Barrett’s esophagus (BE) patients were studied. In group 1 (n = 24), increasing doses of PPI were administered in 8-wk intervals until acid reflux normalization. At each assessment, ambulatory 24 h pH recording, endoscopy with biopsies and symptom scoring (by a gastroesophageal reflux disease health related quality of life questionnaire, GERD/HRLQ) were performed. Group 2 (n = 30) consisted of patients with a previous fundoplication.
RESULTS In group 1, acid reflux normalized in 23 of 24 patients, resulting in improved GERD/HRQL scores (P = 0.001), which were most pronounced after the starting dose of PPI (P < 0.001). PPI treatment reached the same level of GERD/HRQL scores as after a clinically successful fundoplication (P = 0.5). Normalization of acid reflux in both groups was associated with reduction in papillary length, basal cell layer thickness, intercellular space dilatation, and acute and chronic inflammation of squamous epithelium.
CONCLUSION This study shows that acid reflux and symptom scores co-vary throughout PPI increments in long-segment BE patients, especially after the first dose of PPI, reaching the same level as after a successful fundoplication. Minor changes were found among GERD markers at the morphological level.
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7
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Thota PN, Hajifathalian K, Benjamin T, Runkana A, Lopez R, Sanaka MR. Lack of incremental effect of histamine receptor antagonists over proton pump inhibitors on the risk of neoplastic progression in patients with Barrett's esophagus: a cohort study. J Dig Dis 2017; 18:143-150. [PMID: 28188977 DOI: 10.1111/1751-2980.12457] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 02/04/2017] [Accepted: 02/05/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Long-term acid suppression reduces the risk of progression to esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). Given recent reports about the harmful effects of using chronic proton pump inhibitors (PPI) there is renewed interest in alternative methods of acid suppression. Hence, we studied the effect of H2 receptor antagonists (H2 RA) on the risk of progression to neoplasia in our BE cohort. METHODS This is a retrospective analysis of prospectively collected data of patients in our BE registry from 2002 to 2015. Patients' characteristics, endoscopic findings, such as the length of BE, hiatal hernia size and histological findings and patients' use of medications such as PPI, aspirin, H2 RA, metformin and antihyperlipidemic agents were studied. RESULTS The cohort consisted of 1466 patients with a mean age of 61 ± 13 years. The patients had a predominance of male sex (76.7% [1118/1457]) and Caucasian race (96.6% [1209/1252]). After excluding prevalent high-grade dysplasia (HGD) or EAC, 1025 patients had a median follow up of 43.6 months during which 57 patients progressed to HGD or EAC. PPI use (56% in progressors vs 69% in non-progressors; P = 0.007) but not H2 RA use (12% progressors vs 19% in non-progressors P = 0.162) was associated with lower risk of neoplastic progression. On multivariate analysis, there was no synergistic effect of addition of H2 RA to PPI on risk of neoplastic progression to HGD or EAC (relative risk 0.33; confidence intervals 0.05-2.29, P = 0.262). CONCLUSION H2 RA do not seem to have a chemopreventive role in patients with BE.
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Affiliation(s)
- Prashanthi N Thota
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
| | | | - Tanmayee Benjamin
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
| | - Ashok Runkana
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
| | - Rocio Lopez
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA
| | - Madhusudhan R Sanaka
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
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Chueca E, Apostolova N, Esplugues JV, García-González MA, Lanas Á, Piazuelo E. Proton Pump Inhibitors Display Antitumor Effects in Barrett's Adenocarcinoma Cells. Front Pharmacol 2016; 7:452. [PMID: 27932981 PMCID: PMC5122752 DOI: 10.3389/fphar.2016.00452] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Accepted: 11/11/2016] [Indexed: 12/14/2022] Open
Abstract
Recent evidence has reported that proton pump inhibitors (PPIs) can exert antineoplastic effects through the disruption of pH homeostasis by inhibiting vacuolar ATPase (H+-VATPase), a proton pump overexpressed in several tumor cells, but this aspect has not been deeply investigated in EAC yet. In the present study, the expression of H+-VATPase was assessed through the metaplasia-dysplasia-adenocarcinoma sequence in Barrett's esophagus (BE) and the antineoplastic effects of PPIs and cellular mechanisms involved were evaluated in vitro. H+-VATPase expression was assessed by immunohistochemistry in paraffined-embedded samples or by immunofluorescence in cultured BE and EAC cell lines. Cells were treated with different concentrations of PPIs and parameters of citotoxicity, oxidative stress, and autophagy were evaluated. H+-VATPase expression was found in all biopsies and cell lines evaluated, showing differences in the location of the pump between the cell lines. Esomeprazole inhibited proliferation and cell invasion and induced apoptosis of EAC cells. Production of reactive oxygen species (ROS) seemed to be involved in the cytotoxic effects observed since the addition of N-acetylcysteine significantly reduced esomeprazole-induced apoptosis in EAC cells. Esomeprazole also reduced intracellular pH of tumor cells, whereas only disturbed the mitochondrial membrane potential in OE33 cells. Esomeprazole induced autophagy in both EAC cells, but also triggered a blockade in autophagic flux in the metastatic cell line. These data provide in vitro evidence supporting the potential use of PPIs as novel antineoplastic drugs for EAC and also shed some light on the mechanisms that trigger PPIs cytotoxic effects, which differ upon the cell line evaluated.
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Affiliation(s)
- Eduardo Chueca
- CIBERehdMadrid, Spain; Instituto de Investigación Sanitaria AragónZaragoza, Spain
| | - Nadezda Apostolova
- CIBERehdMadrid, Spain; Department of Pharmacology, University of ValenciaValencia, Spain
| | - Juan V Esplugues
- CIBERehdMadrid, Spain; Department of Pharmacology, University of ValenciaValencia, Spain
| | - María A García-González
- CIBERehdMadrid, Spain; Instituto de Investigación Sanitaria AragónZaragoza, Spain; CIBA, Instituto Aragonés de Ciencias de la SaludZaragoza, Spain
| | - Ángel Lanas
- CIBERehdMadrid, Spain; Instituto de Investigación Sanitaria AragónZaragoza, Spain; Department of Medicine, Psychiatry and Dermatology, University of ZaragozaZaragoza, Spain
| | - Elena Piazuelo
- CIBERehdMadrid, Spain; Instituto de Investigación Sanitaria AragónZaragoza, Spain; CIBA, Instituto Aragonés de Ciencias de la SaludZaragoza, Spain
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9
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Visrodia K, Singh S, Krishnamoorthi R, Ahlquist DA, Wang KK, Iyer PG, Katzka DA. Systematic review with meta-analysis: prevalent vs. incident oesophageal adenocarcinoma and high-grade dysplasia in Barrett's oesophagus. Aliment Pharmacol Ther 2016; 44:775-84. [PMID: 27562355 DOI: 10.1111/apt.13783] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2016] [Revised: 07/20/2016] [Accepted: 08/05/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND The proportion of oesophageal adenocarcinoma that is detected concurrently with initial Barrett's oesophagus diagnosis is not well studied. AIM To compare the proportion of prevalent adenocarcinoma vs. incident adenocarcinoma found during surveillance of Barrett's. METHODS We performed a systematic search of MEDLINE, EMBASE and Web of Science (from their inception to 31 May 2015) for cohort studies in adults with Barrett's (nondysplastic Barrett's ± Barrett's with low-grade dysplasia) with minimum average follow-up of 3 years, and providing numbers of prevalent adenocarcinoma detected (concurrently with Barrett's diagnosis and up to 1 year afterwards) vs. incident adenocarcinoma detected (greater than 1 year after Barrett's diagnosis). Pooled weighted proportions of prevalent and incident adenocarcinoma were calculated, using a random effects model. RESULTS On meta-analysis of 13 studies reporting on 603 adenocarcinomas in 9657 Barrett's patients, 85.1% of adenocarcinomas were classified as prevalent [95% confidence interval (CI), 78.1-90.2%) and 14.9% as incident (95% CI, 9.8-21.9%), with substantial heterogeneity (I(2) = 66%). Among nine studies reporting on 787 high-grade dysplasia and oesophageal adenocarcinomas in 8098 Barrett's patients, the proportion of prevalent high-grade dysplasia-oesophageal adenocarcinoma was similar at 80.5% (95% CI, 68.1-88.8%, I(2) = 87%). These results remained stable across multiple subgroup analyses including study quality, setting, duration of follow-up and presence of baseline dysplasia. CONCLUSIONS In our meta-analysis, four of five patients diagnosed with adenocarcinoma or high-grade dysplasia at index endoscopy or within 1 year of Barrett's follow-up were considered to be prevalent cases. Continued efforts are needed to identify patients with Barrett's before the development of adenocarcinoma.
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Affiliation(s)
- K Visrodia
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - S Singh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.,Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.,Division of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA
| | - R Krishnamoorthi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - D A Ahlquist
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - K K Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - P G Iyer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - D A Katzka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
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Martínek J, Akiyama JI, Vacková Z, Furnari M, Savarino E, Weijs TJ, Valitova E, van der Horst S, Ruurda JP, Goense L, Triadafilopoulos G. Current treatment options for esophageal diseases. Ann N Y Acad Sci 2016; 1381:139-151. [PMID: 27391867 DOI: 10.1111/nyas.13146] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Revised: 05/15/2016] [Accepted: 05/24/2016] [Indexed: 02/06/2023]
Abstract
Exciting new developments-pharmacologic, endoscopic, and surgical-have arisen for the treatment of many esophageal diseases. Refractory gastroesophageal reflux disease presents a therapeutic challenge, and several new options have been proposed to overcome an insufficient effectiveness of proton pump inhibitors. In patients with distal esophageal spasm, drugs and endoscopic treatments are the current mainstays of the therapeutic approach. Treatment with proton pump inhibitors (or antireflux surgery) should be considered in patients with Barrett's esophagus, since a recent meta-analysis demonstrated a 71% reduction in risk of neoplastic progression. Endoscopic resection combined with radiofrequency ablation is the standard of care in patients with early esophageal adenocarcinoma. Mucosal squamous cancer may also be treated endoscopically, preferably with endoscopic submucosal dissection. Patients with upper esophageal cancer often refrain from surgery. Robot-assisted, thoracolaparoscopic, minimally invasive esophagectomy may be an appropriate option for these patients, as the robot facilitates a good overview of the upper mediastinum. Induction chemoradiotherapy is currently considered as standard treatment for patients with advanced squamous cell carcinoma, while the role of neoadjuvant therapy for adenocarcinoma remains controversial. A system for defining and recording perioperative complications associated with esophagectomy has been recently developed and may help to find predictors of mortality and morbidity.
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Affiliation(s)
- Jan Martínek
- Department of Hepatogastroenterology, IKEM, Prague, Czech Republic.
| | - Jun-Ichi Akiyama
- Division of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Zuzana Vacková
- Department of Hepatogastroenterology, IKEM, Prague, Czech Republic
| | - Manuele Furnari
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Teus J Weijs
- Department of Surgery, Diakonessenhuis Utrecht, Utrecht, the Netherlands
| | - Elen Valitova
- Department of Upper Gastrointestinal Tract Disorders, Clinical Scientific Centre, Moscow, Russia
| | - Sylvia van der Horst
- Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Jelle P Ruurda
- Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Lucas Goense
- Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
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11
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Control of acid and duodenogastroesophageal reflux (DGER) in patients with Barrett's esophagus. Am J Gastroenterol 2015; 110:1143-8. [PMID: 26032153 DOI: 10.1038/ajg.2015.161] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Accepted: 04/14/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Symptom eradication in patients with Barrett's esophagus (BE) does not guarantee control of acid or duodenogastroesophageal reflux (DGER). Continued reflux of acid and/or DGER may increase risk of neoplastic progression and may decrease the likelihood of columnar mucosa eradication after ablative therapy. To date, no study has addressed whether both complete acid and DGER control is possible in patients with BE. This prospective study was designed to assess the effect of escalating-dose proton pump inhibitor (PPI) therapy on esophageal acid and DGER. METHODS Patients with BE (≥3 cm in length) underwent simultaneous ambulatory prolonged pH and DGER monitoring after at least 1 week off PPI therapy followed by testing on therapy after 1 month of twice-daily rabeprazole (20 mg). In those with continued acid and/or DGER, the tests were repeated after 1 month of double-dose (40 mg twice daily) rabeprazole. The primary study outcome was normalization of both acid and DGER. Symptom severity was assessed on and off PPI therapy employing a four-point ordinal scale. RESULTS A total of 29 patients with BE consented for pH monitoring, of whom 23 also consented for both pH and DGER monitoring off and on therapy (83% male; mean age 58 years; mean body mass index 29; mean Barrett's length 6.0 cm). Median (interquartile range) total % time pH <4 and bilirubin absorbance >0.14 off PPI therapy were 18.4 (11.7-20.0) and 9.7 (5.0-22.2), respectively. In addition, 26/29 (90%) had normalized acid and 18/23 (78%) had normalized DGER on rabeprazole 20 mg. Among those not achieving normalization on 20 mg twice daily, 3/3 (100%) had normalized acid and 4/5 (80%) had normalized DGER on rabeprazole 40 mg twice daily. All subjects had symptoms controlled on rabeprazole 20 mg twice daily. Univariate analysis found no predictor for normalization of physiologic parameters based on demographics. CONCLUSIONS Symptom control does not guarantee normalization of acid and DGER at standard dose of twice-daily PPI therapy. Normalization of acid and DGER can be achieved in 79% of BE patients on rabeprazole 20 mg p.o. twice daily, and in the majority of the remainder at high-dose twice-daily PPI. In patients undergoing ablative therapy, pH or DGER monitoring may not be needed to ensure normalization of reflux if patients are treated with high-dose PPI therapy.
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12
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Dickman R, Maradey-Romero C, Gingold-Belfer R, Fass R. Unmet Needs in the Treatment of Gastroesophageal Reflux Disease. J Neurogastroenterol Motil 2015; 21:309-19. [PMID: 26130628 PMCID: PMC4496897 DOI: 10.5056/jnm15105] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 06/17/2015] [Accepted: 06/18/2015] [Indexed: 12/13/2022] Open
Abstract
Gastroesophageal reflux disease (GERD) is a highly prevalent gastrointestinal disorder. Proton pump inhibitors have profoundly revolutionized the treatment of GERD. However, several areas of unmet need persist despite marked improvements in the ther-apeutic management of GERD. These include the advanced grades of erosive esophagitis, nonerosive reflux disease, main-tenance treatment of erosive esophagitis, refractory GERD, postprandial heartburn, atypical and extraesophageal manifestations of GERD, Barrett's esophagus, chronic protein pump inhibitor treatment, and post-bariatric surgery GERD. Consequently, any fu-ture development of novel therapeutic modalities for GERD (medical, endoscopic, or surgical), would likely focus on the afore-mentioned areas of unmet need.
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Affiliation(s)
- Ram Dickman
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio,
USA
| | - Carla Maradey-Romero
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio,
USA
| | - Rachel Gingold-Belfer
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio,
USA
| | - Ronnie Fass
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio,
USA
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Trad KS, Barnes WE, Simoni G, Shughoury AB, Mavrelis PG, Raza M, Heise JA, Turgeon DG, Fox MA. Transoral incisionless fundoplication effective in eliminating GERD symptoms in partial responders to proton pump inhibitor therapy at 6 months: the TEMPO Randomized Clinical Trial. Surg Innov 2015; 22:26-40. [PMID: 24756976 PMCID: PMC4361451 DOI: 10.1177/1553350614526788] [Citation(s) in RCA: 107] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Incomplete control of troublesome regurgitation and extraesophageal manifestations of chronic gastroesophageal reflux disease (GERD) is a known limitation of proton pump inhibitor (PPI) therapy. This multicenter randomized study compared the efficacy of transoral incisionless fundoplication (TIF) against PPIs in controlling these symptoms in patients with small hiatal hernias. METHODS Between June and August 2012, 63 patients were randomized at 7 US community hospitals. Patients in the PPI group were placed on maximum standard dose (MSD). Patients in the TIF group underwent esophagogastric fundoplication using the EsophyX2 device. Primary outcome was elimination of daily troublesome regurgitation or extraesophageal symptoms. Secondary outcomes were normalization of esophageal acid exposure (EAE), PPI usage and healing of esophagitis. RESULTS Of 63 randomized patients (40 TIF and 23 PPI), 3 were lost to follow-up leaving 39 TIF and 21 PPI patients for analysis. At 6-month follow-up, troublesome regurgitation was eliminated in 97% of TIF patients versus 50% of PPI patients, relative risk (RR) = 1.9, 95% confidence interval (CI) = 1.2-3.11 (P = .006). Globally, 62% of TIF patients experienced elimination of regurgitation and extraesophageal symptoms versus 5% of PPI patients, RR = 12.9, 95% CI = 1.9-88.9 (P = .009). EAE was normalized in 54% of TIF patients (off PPIs) versus 52% of PPI patients (on MSD), RR = 1.0, 95% CI = 0.6-1.7 (P = .914). Ninety percent of TIF patients were off PPIs. CONCLUSION At 6-month follow-up, TIF was more effective than MSD PPI therapy in eliminating troublesome regurgitation and extraesophageal symptoms of GERD.
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Affiliation(s)
- Karim S Trad
- The George Washington University School of Medicine and Health Sciences, Washington, DC, USA Reston Surgical Associates, Reston, VA, USA
| | - William E Barnes
- Livingston Hospital and Healthcare Services, Inc, CAH, Salem, KY, USA
| | | | - Ahmad B Shughoury
- Saint Mary Medical Center, Hobart, IN, USA Internal Medicine Associates, Merrillville, IN, USA
| | - Peter G Mavrelis
- Saint Mary Medical Center, Hobart, IN, USA Internal Medicine Associates, Merrillville, IN, USA
| | - Mamoon Raza
- Indiana Medical Research, Elkhart, IN, USA Unity Surgical Hospital, Mishawaka, IN, USA
| | | | - Daniel G Turgeon
- The George Washington University School of Medicine and Health Sciences, Washington, DC, USA Reston Surgical Associates, Reston, VA, USA
| | - Mark A Fox
- Crossville Medical Group, Crossville, TN, USA Cumberland Medical Center, Crossville, TN, USA
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de Jonge PJF, Spaander MC, Bruno MJ, Kuipers EJ. Acid suppression and surgical therapy for Barrett's oesophagus. Best Pract Res Clin Gastroenterol 2015; 29:139-50. [PMID: 25743462 DOI: 10.1016/j.bpg.2014.11.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2014] [Revised: 10/12/2014] [Accepted: 11/02/2014] [Indexed: 02/09/2023]
Abstract
Gastro-oesophageal reflux disease is a common medical problem in developed countries, and is a risk factor for the development of Barrett's oesophagus and oesophageal adenocarcinoma. Both proton pump inhibitor therapy and antireflux surgery are effective at controlling endoscopic signs and symptoms of gastro-oesophageal reflux in patients with Barrett's oesophagus, but often fail to eliminate pathological oesophageal acid exposure. The current available studies strongly suggest that acid suppressive therapy, both pharmacological as well as surgical acid suppression, can reduce the risk the development and progression in patients with Barrett's oesophagus, but are not capable of complete prevention. No significant differences have been found between pharmacological and surgical therapy. For clinical practice, patients should be prescribed a proton pump inhibitor once daily as maintenance therapy, with the dose guided by symptoms. Antireflux surgery can be a good alternative to proton pump inhibitor therapy, but should be primarily offered to patients with symptomatic reflux, and not to asymptomatic patients with the rationale to protect against cancer.
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Affiliation(s)
- Pieter J F de Jonge
- Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, The Netherlands.
| | - Manon C Spaander
- Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, The Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, The Netherlands
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, The Netherlands
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The effects of transoral incisionless fundoplication on chronic GERD patients: 12-month prospective multicenter experience. Surg Laparosc Endosc Percutan Tech 2014; 24:36-46. [PMID: 24487156 DOI: 10.1097/sle.0b013e3182a2b05c] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE This study aimed to assess the impact of transoral incisionless fundoplication (TIF) on patients with chronic gastroesophageal reflux disease (GERD) at 12-month follow-up. METHODS Clinical outcomes of 100 consecutive patients with chronic GERD who underwent TIF between January 2010 and February 2011 were analyzed. RESULTS There were no major complications reported. Esophageal acid exposure was normalized in 14/27 (52%) of patients who underwent 12-month pH testing. Seventy-four percent of all patients were off proton pump inhibitors versus 92% on daily proton pump inhibitors before TIF, P<0.001. Daily bothersome heartburn and regurgitation symptoms were eliminated in 66/85 (78%) and 48/58 (83%) of patients. Median reflux symptom index score was reduced from 20 (0 to 41) to 5 (0 to 44), P<0.001. Two patients reported de novo dysphagia and 1 patient reported bloating (scores 0 to 3). Six patients underwent revision; 5 laparoscopic Nissen fundoplication and 1 TIF. CONCLUSIONS TIF provided a safe and effective therapeutic option for carefully selected patients with chronic GERD.
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Heartburn, Barrett's oesophagus and cancer: implications for primary care. Br J Gen Pract 2014; 64:120-1. [PMID: 24567627 DOI: 10.3399/bjgp14x677383] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
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Mejia A, Kraft WK. Acid peptic diseases: pharmacological approach to treatment. Expert Rev Clin Pharmacol 2014; 2:295-314. [PMID: 21822447 DOI: 10.1586/ecp.09.8] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Acid peptic disorders are the result of distinctive, but overlapping pathogenic mechanisms leading to either excessive acid secretion or diminished mucosal defense. They are common entities present in daily clinical practice that, owing to their chronicity, represent a significant cost to healthcare. Key elements in the success of controlling these entities have been the development of potent and safe drugs based on physiological targets. The histamine-2 receptor antagonists revolutionized the treatment of acid peptic disorders owing to their safety and efficacy profile. The proton-pump inhibitors (PPIs) represent a further therapeutic advance due to more potent inhibition of acid secretion. Ample data from clinical trials and observational experience have confirmed the utility of these agents in the treatment of acid peptic diseases, with differential efficacy and safety characteristics between and within drug classes. Paradigms in their speed and duration of action have underscored the need for new chemical entities that, from a single dose, would provide reliable duration of acid control, particularly at night. Moreover, PPIs reduce, but do not eliminate, the risk of ulcers in patients taking NSAIDs, reflecting untargeted physiopathologic pathways and a breach in the ability to sustain an intragastric pH of more than 4. This review provides an assessment of the current understanding of the physiology of acid production, a discussion of medications targeting gastric acid production and a review of efficacy in specific acid peptic diseases, as well as current challenges and future directions in the treatment of acid-mediated diseases.
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Affiliation(s)
- Alex Mejia
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 1170 Main Building, 132 South 10th Street, Philadelphia, PA 19107-5244, USA, Tel.: +1 203 243 7501
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18
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Watson JT, Moawad FJ, Veerappan GR, Bassett JT, Maydonovitch CL, Horwhat JD, Wong RKH. The dose of omeprazole required to achieve adequate intraesophageal acid suppression in patients with gastroesophageal junction specialized intestinal metaplasia and Barrett's esophagus. Dig Dis Sci 2013; 58:2253-60. [PMID: 23824407 DOI: 10.1007/s10620-013-2763-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2013] [Accepted: 06/14/2013] [Indexed: 12/17/2022]
Abstract
BACKGROUND The mainstay of medical therapy for Barrett's esophagus is normalization of esophageal acid exposure with proton pump inhibitors (PPIs). However, the optimal dose and whether once daily or twice daily is required for acid suppression is unknown. AIM The purpose of this study was to assess whether adequate intra-esophageal acid suppression could be achieved with once daily versus twice daily omeprazole in patients with gastroesophageal specialized intestinal metaplasia (GEJSIM), short-segment (SSBE) and long-segment Barrett's esophagus (LSBE). METHODS Patients with GEJSIM and Barrett's esophagus underwent upper endoscopy with 48-h wireless pH capsule while on once daily 20 mg omeprazole for at least 1 week. If intra-esophageal acid was not adequately controlled, defined as pH value <4 for greater than 4.2 % of the time during the second 24-h period, omeprazole was increased to twice daily for 1 week and upper endoscopy with wireless pH capsule was repeated. RESULTS A total of 36 patients completed the study (10 patients had GEJSIM, 16 patients had SSBE, and 10 patients had LSBE). Normalization of intraesophageal pH was achieved in 28 patients (78 %) with once daily PPI and eight patients required twice daily PPI. There was no significant difference between the three groups in the proportion of patients requiring high dose PPI (GEJSIM 10 %, SSBE 25 %, LSBE 30 %, p = 0.526). CONCLUSIONS The majority of patients with Barrett's esophagus were controlled with once daily low dose PPI and only a minority required twice daily dosing, regardless of the length of Barrett's mucosa.
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Affiliation(s)
- Joshua T Watson
- Gastroenterology Service, Department of Medicine, Walter Reed National Military Medical Center, 8901 Wisconsin Ave., Bethesda, MD 20889, USA
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Abstract
Barrett's esophagus (BE) is a well-established pre-malignant lesion for esophageal adenocarcinoma, a condition that carries a dismal five-year overall survival rate of less than 15%. Among several available methods to eliminate BE, radiofrequency ablation (RFA) provides the most efficient modality, since it has been demonstrated to successfully eradicate BE with or without dysplasia with acceptable safety, efficacy and durability profiles. In conjunction with proton pump therapy, this new technology has quickly become the standard care for patients with dysplastic BE. However, several technical questions remain about how to deploy RFA therapy for maximum effectiveness and long-term favorable outcomes for all stages of the disease. These include how to select patient for therapy, what the best protocol for RFA is, when to use other modalities, such as endoscopic mucosal resection, and what should be considered for refractory BE. This review addresses these questions with the perspective of the best available evidence matched with the authors' experience with the technology.
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Affiliation(s)
- Junichi Akiyama
- National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku, Tokyo, 162-8655, Japan, El Camino GI Medical Associates, Mountain View, CA 94040, USA and Division of Gastroenterology, Stanford University Medical Center, Stanford, CA 94305, USA
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20
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Shaheen NJ, Kim HP, Bulsiewicz WJ, Lyday WD, Triadafilopoulos G, Wolfsen HC, Komanduri S, Chmielewski GW, Ertan A, Corbett FS, Camara DS, Rothstein RI, Overholt BF. Prior fundoplication does not improve safety or efficacy outcomes of radiofrequency ablation: results from the U.S. RFA Registry. J Gastrointest Surg 2013; 17:21-p.29. [PMID: 22965650 DOI: 10.1007/s11605-012-2001-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2012] [Accepted: 08/06/2012] [Indexed: 01/31/2023]
Abstract
BACKGROUND Ongoing gastroesophageal reflux may impair healing and re-epithelialization after radiofrequency ablation (RFA) of Barrett's esophagus (BE). Because prior fundoplication may improve reflux control, our aim was to assess the relationship between prior fundoplication and the safety/efficacy of RFA. METHODS We assessed the U.S. RFA Registry, a nationwide registry of BE patients receiving RFA at 148 institutions, to compare the safety and efficacy of ablation between those with prior fundoplication and those with medical management (proton pump inhibition). RESULTS Among 5,537 patients receiving RFA, 301 (5.4 %) had prior fundoplication. Of fundoplication subjects, 1.0 % developed stricture and 1.0 % were hospitalized after RFA. Rates of stricture, bleeding, and hospitalization were not statistically different (p = ns) between patients with and without prior fundoplication. Complete eradication of intestinal metaplasia and complete eradication of dysplasia were achieved in 71 % and 87 % of fundoplication patients, and 73 % and 87 % of patients without fundoplication, respectively (p = ns for both). Patients with prior fundoplication needed similar numbers of RFA sessions for eradication compared with those without fundoplication. CONCLUSIONS Radiofrequency ablation, with or without prior fundoplication, is safe and effective in eradicating BE. Prior fundoplication was associated with similar adverse event and efficacy rates when compared with medical management.
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Affiliation(s)
- Nicholas J Shaheen
- University of North Carolina School of Medicine, 130 Mason Farm Rd, CB#7080, Chapel Hill, NC 27599-7080, USA.
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Akiyama J, Marcus SN, Triadafilopoulos G. Effective intra-esophageal acid control is associated with improved radiofrequency ablation outcomes in Barrett's esophagus. Dig Dis Sci 2012; 57:2625-32. [PMID: 22878916 DOI: 10.1007/s10620-012-2313-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2012] [Accepted: 07/05/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Endoscopic radiofrequency ablation (RFA) is a promising new treatment of Barrett's esophagus (BE). Adjunctive intra-esophageal pH control with proton pump inhibitors and/or anti-reflux surgery is generally recommended to optimize squamous re-epithelialization after ablation. AIMS The aims of this study were to examine the association between intra-esophageal pH control and RFA outcomes and to identify predictive factors to achieve complete elimination (CE) of BE following RFA. METHODS We retrospectively studied the outcomes of BE patients treated with RFA. Esophageal acid exposure (EAE) was assessed utilizing 24-h pH monitoring on therapy. CE was endoscopically defined as no area suspicious for residual metaplasia following RFA. RESULTS Of 45 patients (33 men; mean age 61.6, mean BE length C4.1 M4.6) examined for EAE, 29 % exhibited moderate-severe EAE despite therapy. Reduction in BE surface area and CE rate were higher in the normal-mild EAE group compared with the moderate-severe EAE group (99 vs. 95 %, p = 0.02; 44 vs. 15 %, p = 0.09, respectively). Using univariate analysis, age, gender, race, aspirin/NSAIDs use, baseline worst histology, baseline BE surface area, and the number or types of RFA had no correlation with CE. By multivariate multiple logistic regression analysis, normal-mild EAE and smaller hiatal hernia were independent factors associated with CE. CONCLUSIONS Effective intra-esophageal pH control is associated with improved RFA outcomes of BE. Normal to mild EAE and smaller hiatal hernia are predictive factors to achieve CE. Given the frequent persistence of acid reflux despite therapy in BE patients, in order to maximize the RFA effects esophageal pH optimization and hernia repair should be considered.
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Affiliation(s)
- Junichi Akiyama
- El Camino GI Medical Associates, 2490 Hospital Drive, Suite 211, Mountain View, CA 94040, USA
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Muls V, Eckardt AJ, Marchese M, Bastens B, Buset M, Devière J, Louis H, Rajan A, Daniel MA, Costamagna G. Three-year results of a multicenter prospective study of transoral incisionless fundoplication. Surg Innov 2012; 20:321-30. [PMID: 22968006 DOI: 10.1177/1553350612459275] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND To date, there are no long-term data on the use of transoral incisionless fundoplication (TIF) for the treatment of chronic gastroesophageal reflux disease (GERD). We sought to prospectively evaluate the long-term safety and durability of TIF in a multi-center setting. METHODS A longitudinal per protocol (PP) and a modified intention-to-treat (mITT) analysis at 1 and 3 years consisted of symptom evaluation using the GERD health-related quality of life (GERD-HRQL) questionnaire, medication use, upper gastrointestinal endoscopy, and pH-metry. RESULTS Of 79 patients previously reported at 1 year, 12 were lost to follow-up, and 1 died from an unrelated cause. The remaining 66 patients were followed up and analyzed (mITT). Of 66 patients, 12 underwent revisional procedures, leaving 54 patients for PP analysis at a median of 3.1 years (range = 2.9-3.6). No adverse events related to TIF were reported at 2- or 3-year follow-up. On PP analysis, median GERD-HRQL score off proton pump inhibitors (PPIs) improved significantly to 4 (range 0-32) from both off (25 [13-38], P < .0001) and on (9 [0-22], P < .0001) PPIs. Discontinuation of daily PPIs was sustained in 61% (mITT) and 74% (PP) of patients. Of 11 patients with pH data at 3 years (PP), 9 (82%) remained normal. Based on mITT analysis, 9/23 (39%) remained normal at 3 years. CONCLUSIONS The clinical outcomes at 3 years following TIF, patient satisfaction, healing of erosive esophagitis, and cessation of PPI medication support long-term safety and durability of the TIF procedure for those with initial treatment success. Although complete normalization of pH studies occurred in a minority of patients, successful cases showed long-term durability.
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Affiliation(s)
- Vinciane Muls
- Department of Digestive Endoscopy, Centre Hospitalier Universitaire St Pierre, Brussels, Belgium.
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Bell RCW, Mavrelis PG, Barnes WE, Dargis D, Carter BJ, Hoddinott KM, Sewell RW, Trad KS, DaCosta Gill B, Ihde GM. A prospective multicenter registry of patients with chronic gastroesophageal reflux disease receiving transoral incisionless fundoplication. J Am Coll Surg 2012; 215:794-809. [PMID: 22939637 DOI: 10.1016/j.jamcollsurg.2012.07.014] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2012] [Revised: 07/18/2012] [Accepted: 07/20/2012] [Indexed: 12/19/2022]
Abstract
BACKGROUND This study was undertaken to validate previously reported safety and symptomatic outcomes of transoral incisionless fundoplication (TIF), evaluate the relative benefit of TIF within different gastroesophageal reflux disease (GERD) subgroups, and to determine predictors of success in community settings. STUDY DESIGN Between January 2010 and February 2011, 100 consecutive patients who underwent TIF procedures at 10 centers were enrolled in this prospective, open-label, multicenter, single-arm study. Symptom improvement and objective outcomes of TIF were analyzed at 6-month follow-up. RESULTS One hundred TIF procedures were performed. No complications were reported. Median GERD symptom duration was 9 years (range 1 to 35 years) and median duration of proton pump inhibitor (PPI) use was 7 years (1 to 20 years). Maximal medical therapy resulted in incomplete symptom control for 92% of patients; GERD Health-Related Quality of Life (GERD-HRQL) total score was normalized in 73%. Median heartburn and regurgitation scores improved significantly, from 18 (range 0 to 30) and 15 (range 0 to 30) on PPIs before TIF to 3 (range 0 to 25) and 0 (range 0 to 25), respectively; p < 0.001. Median Reflux Symptom Index scores were reduced after TIF from 24 (range 14 to 41) to 7 (range 0 to 44); p < 0.001. Eighty percent of patients were completely off PPIs after TIF vs 92% of patients on PPIs before TIF. Preoperative factors associated with clinical outcomes were less severe heartburn (total GERD-HRQL ≤ 30, p = 0.02) and the presence of esophagitis (p < 0.02). CONCLUSIONS Transoral incisionless fundoplication is safe and effective in multiple community-based settings in the treatment of medically refractory GERD, as demonstrated by an absence of complications, excellent symptom relief, and complete cessation of PPIs at 6-month follow-up.
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24
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Gerson LB, Mitra S, Bleker WF, Yeung P. Control of intra-oesophageal pH in patients with Barrett's oesophagus on omeprazole-sodium bicarbonate therapy. Aliment Pharmacol Ther 2012; 35:803-9. [PMID: 22356659 DOI: 10.1111/j.1365-2036.2012.05016.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2011] [Revised: 11/08/2011] [Accepted: 01/17/2012] [Indexed: 12/27/2022]
Abstract
BACKGROUND Approximately 30-40% of patients with Barrett's oesophagus (BE) patients manifest abnormal oesophageal pH profiles despite proton pump inhibitor (PPI) therapy. AIM To determine control of oesophageal reflux using Bravo pH monitoring in patients BE on omeprazole-sodium bicarbonate oral suspension powder (Ome-NaBic) 40 mg twice daily. METHODS Initial pH monitoring off PPI for 1 week was performed. All patients underwent repeat pH testing on Ome-NaBic administered before breakfast and at bedtime after 21-28 days of therapy depending upon the prior PPI therapy. The goal was to enroll 30 subjects, however, the trial was terminated prematurely when the sponsor lost financing due to a change in business strategy. RESULTS A total of 88 patients responded to the study invitation, 27 patients signed informed consent, and 21 patients underwent pH testing of PPI. A total of 15 patients completed the protocol (13 men, 2 women). Demographic information for patients completing at least one Bravo study included a mean (±s.d.) age 62 ± 9 years; body mass index 31 ± 8 kg/m(2) (range 23-48); mean BE length of 2.6 ± 2 cm; 9 (43%) patients with long segment BE. All (100%) patients demonstrated normalisation of supine pH on both days of Ome-NaBic therapy. One patient (6%) demonstrated abnormal upright reflux on the second day of monitoring on Ome-NaBic therapy; all the other patients demonstrated normal pH scores on therapy. CONCLUSIONS Administration of twice daily Ome-NaBic demonstrated control of nocturnal oesophageal reflux in 100% of patients with Barrett's oesophagus, and complete control of oesophageal pH during 97% of the 24-h recording periods.
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Affiliation(s)
- L B Gerson
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, CA, USA.
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25
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Owens VL, Katzka DA, Lutzke LS, Wang KK, Smyrk TC. Endoscopic ablative therapy for Barrett's esophagus: a potential cause of eosinophilic esophagitis. Dis Esophagus 2012; 25:33-9. [PMID: 21668572 DOI: 10.1111/j.1442-2050.2011.01214.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Markedly increased esophageal eosinophils are associated with allergy- or reflux-based eosinophilic esophagitis. Other known disorders that cause this entity are unusual. To characterize the clinical, endoscopic, and histological findings of patients who develop marked esophageal eosinophilic infiltration after ablative therapy for Barrett's dysplasia. All patients who underwent endoscopic ablation of Barrett's esophagus between 1991 and 2009 with photodynamic therapy or radio frequency were screened for a pathologic descriptor of 'eosinophils' on biopsy. Patients whose biopsies demonstrated >15 eosinophils per high power (HPF) field in squamous epithelium after ablation were reviewed and included in the study group. Thirteen of 385 (3.4%) patients underwent ablation for Barrett's esophagus and subsequently had large numbers of intraepithelial eosinophils. All patients had long segment Barrett's (mean 8.0 cm) with low- or high-grade dysplasia or adenocarcinoma. All had undergone photodynamic therapy as their form of ablation. No patients had typical symptoms or endoscopic findings of eosinophilic esophagitis. Eleven patients were on proton pump inhibitors. The time between ablation and onset of esophageal eosinophilia ranged from 83 to 692 days. Intraepithelial eosinophil counts ranged from 30 to 150/HPF (mean 90). The majority of cases showed eosinophilic degranulation, spongiosis, increased papillary height, and basal zone thickening. The natural history of esophageal eosinophilia was variable after ablation, persisting consistently or sporadically on biopsy for up to 6 years. Ablation for Barrett's dysplasia can be followed rarely by eosinophil infiltrates with a histological resemblance to allergy-based eosinophilic esophagitis, but lacking dysphagia. The pathophysiology is unknown.
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Affiliation(s)
- V L Owens
- Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA
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Richter JE, Penagini R, Tenca A, Pohl D, Dvorak K, Goldman A, Savarino E, Zentilin P, Savarino V, Watson JT, Wong RKH, Pace F, Casini V, Peura DA, Herzig SJ, Kamiya T, Pelosini I, Scarpignato C, Armstrong D, DeVault KR, Bechi P, Taddei A, Freschi G, Ringressi MN, Degli'Innocenti DR, Castiglione F, Masini E, Hunt RH. Barrett's esophagus: proton pump inhibitors and chemoprevention II. Ann N Y Acad Sci 2011; 1232:114-39. [PMID: 21950810 DOI: 10.1111/j.1749-6632.2011.06048.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The following on proton pump inhibitors (PPIs) and chemoprevention in relation to Barrett's esophagus includes commentaries on 48-h pH monitoring, pH-impedence, bile acid testing, dyspepsia, long/short segment Barrett's esophagus, nonerosive reflux disease (NERD), functional heartburn, dual-release delivery PPIs, immediate-release PPIs, long-term PPI use, prokinetic agents, obesity, baclofen, nocturnal acid breakthrough, nonsteroidal anti-inflammatory drugs (NSAIDs), and new PPIs.
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Affiliation(s)
- Joel E Richter
- Department of Medicine, Temple University, Philadelphia, Pennsylvania, USA
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Kastelein F, Spaander MCW, Biermann K, Vucelic B, Kuipers EJ, Bruno MJ. Role of acid suppression in the development and progression of dysplasia in patients with Barrett's esophagus. Dig Dis 2011; 29:499-506. [PMID: 22095018 DOI: 10.1159/000331513] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Barrett's esophagus (BE) usually develops in patients with gastroesophageal reflux disease and therefore it has been suggested that esophageal acid exposure plays an import role in the initiation of BE and its progression towards esophageal adenocarcinoma (EAC). The mechanisms whereby acid exposure causes BE are not completely revealed and the potential role of esophageal acid exposure in carcinogenesis is unclear as well. Since acid exposure is thought to play an important role in the progression of BE, therapies aimed at preventing the development of EAC have primarily focused on pharmacological and surgical acid suppression. In clinical practice, acid suppression is effective in relieving reflux symptoms and decreases esophageal acid exposure in most patients. However, in some individuals, pathological acid exposure persists and these patients continue to be at risk for developing dysplasia or EAC. To date, published trials suggest that acid suppression is able to prevent the development and progression of dysplasia in patients with BE, but definite and compelling proof is still lacking. This article reviews the mechanisms of acid-induced carcinogenesis in BE and the role of acid suppression in the prevention of neoplastic progression.
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Affiliation(s)
- F Kastelein
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
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Seguro FCBC, Santo MA, Szachnowicz S, Maluf Filho F, Kishi HS, Falcão AM, Nasi A, Sallum RAA, Cecconello I. Use of multiple channel pH monitoring for evaluation of ultra-distal reflux in patients after fundoplication for treatment of Barrett's esophagus. Dis Esophagus 2011; 24:381-7. [PMID: 21309910 DOI: 10.1111/j.1442-2050.2010.01160.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Dysplasia and esophageal adenocarcinoma may arise in patients with Barrett's esophagus after fundoplication esophageal pH monitoring showing no acid in esophagus. This suggests the need to develop methodology to evaluate the occurrence of ultra-distal reflux (1cm above the LES). The objective of the study was to compare acid exposition in three different levels: 5cm above the upper border of the LES, 1cm above the LES and in the intrasphincteric region. Eleven patients with Barrett's esophagus after Nissen fundoplication with no clinical, endoscopic and radiologic evidence of reflux were selected. Four-channel pH monitoring took place: channel A, 5cm above the upper border of the LES; channel B, 1cm above the LES; channel C, intrasphincteric; channel D, intragastric. The results of channels A, B and C were compared. There was significant increase in number of reflux episodes and a higher fraction of time with pH <4.0 in channel B compared to channel A. There was significant decrease in fraction of time with pH <4.0 in channel B compared to channel C. Two cases of esophageal adenocarcinoma were diagnosed in the studied patients. The region 1cm above the upper border of the LES is more exposed to acid than the region 5cm above the upper border of the LES, although this exposure occurred in reduced levels. The region 1cm above the upper border of the LES is less exposed to acid than the intrasphincteric region.
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Affiliation(s)
- F C B C Seguro
- Digestive Surgery Divison, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil.
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Abstract
Barrett's esophagus (BE) is the premalignant lesion of esophageal adenocarcinoma (EAC) defined as specialized intestinal metaplasia of the tubular esophagus that results from chronic gastroesophageal reflux. Which patients are at risk of having BE and which are at further risk of developing EAC has yet to be fully established. Many aspects of the management of BE have changed considerably in the past 5 years alone. The aim of this review is to define the critical elements necessary to effectively manage individuals with BE. The general prevalence of BE is estimated at 1.6-3% and follows a demographic distribution similar to EAC. Both short-segment (<3 cm) and long-segment (≥3 cm) BE confer a significant risk for EAC that is increased by the development of dysplasia. The treatment for flat high-grade dysplasia is endoscopic radiofrequency ablation therapy. The benefits of ablation for non-dysplastic BE and BE with low-grade dysplasia have yet to be validated. By understanding the intricacies of the development, screening, surveillance, and treatment of BE, new insights will be gained into the prevention and early detection of EAC that may ultimately lead to a reduction in morbidity and mortality in this patient population.
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de Bortoli N, Martinucci I, Piaggi P, Maltinti S, Bianchi G, Ciancia E, Gambaccini D, Lenzi F, Costa F, Leonardi G, Ricchiuti A, Mumolo MG, Bellini M, Blandizzi C, Marchi S. Randomised clinical trial: twice daily esomeprazole 40 mg vs. pantoprazole 40 mg in Barrett's oesophagus for 1 year. Aliment Pharmacol Ther 2011; 33:1019-27. [PMID: 21385192 DOI: 10.1111/j.1365-2036.2011.04616.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Barrett's oesophagus is regarded as the most important risk factor for development of oesophageal adenocarcinoma. According to current guidelines, treatment should be limited to symptomatic Barrett's oesophagus. AIM To evaluate the expression of Ki67, cyclooxygenase-2 (COX-2) and apoptosis in Barrett's oesophagus after 12 months of double-dose proton pump inhibitor therapy. The effectiveness of esomeprazole and pantoprazole was also compared. METHODS Seventy-seven nondysplastic Barrett's oesophagus patients underwent baseline upper endoscopy. Patients were then randomised into two groups: one group was allocated to receive esomeprazole 40 mg b.d. and the other group pantoprazole 40 mg b.d. for 12 months. A follow-up endoscopy was performed at the end of treatment. Sixty-five of 77 patients agreed to undergo oesophageal manometry and 24-h pH-metry. Barrett's oesophagus biopsies, obtained at baseline and after treatment, were analysed using immunohistochemistry to assess Ki67 and COX-2 expression; apoptosis was evaluated using TUNEL. RESULTS In the esomeprazole group, a significant decrease in Ki67 and COX-2 expression, as well as an increase in apoptosis, were observed (P < 0.05). By contrast, in the pantoprazole group Ki67, COX-2 and apoptosis did not vary significantly from baseline. By 24-h oesophageal pH-monitoring, a normal acid exposure time was recorded in patients treated with esomeprazole, while those allocated to pantoprazole displayed abnormal acid exposure (P < 0.05). CONCLUSIONS Treatment of Barrett's oesophagus patients with high-dose esomeprazole, but not pantoprazole, promoted a decrease in proliferative markers, concomitantly with a decrease in apoptotic cell death. Moreover, esomeprazole allowed a better oesophageal acid control than pantoprazole.
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Affiliation(s)
- N de Bortoli
- Gastroenterology Unit, Department of Internal Medicine, University of Pisa, Italy
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Ravi K, Katzka DA, Smyrk TC, Prasad GA, Romero Y, Francis DL, Lutzke L, Tian J, Wang KK. Prevalence of esophageal eosinophils in patients with Barrett's esophagus. Am J Gastroenterol 2011; 106:851-7. [PMID: 21304498 DOI: 10.1038/ajg.2011.7] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Recent studies have demonstrated high esophageal eosinophil counts in patients with GERD similar to eosinophilic esophagitis (EoE) yet the frequency of esophageal eosinophilia in GERD is unknown. Our aim was to determine the prevalence of dense esophageal eosinophilia in patients with Barrett's esophagus as a manifestation of GERD. METHODS The Mayo Clinic pathology database was reviewed for patients diagnosed with Barrett's esophagus from January to December 2008 with squamous mucosa obtained during endoscopic surveillance. Clinical, endoscopic, and histologic findings were reviewed. Patients with ≥15 eosinophils per high powered field were identified and compared to those without esophageal eosinophilia. RESULTS Two hundred patients with Barrett's esophagus and squamous tissue obtained at the time of biopsy were identified. Fourteen of the 200 patients (7%) had ≥15 eosinophils per high powered field. Demographics, symptoms, and proton pump inhibitor therapies were similar between those with and without esophageal eosinophilia. Endoscopic features suggestive of EoE were found in the squamous mucosa of 2 patients with and 7 patients without esophageal eosinophilia. Use of photodynamic, radiofrequency ablation, or monopolar electrocoagulation therapy for ablation of Barrett's mucosa was not associated with a higher rate of esophageal eosinophilia. Basal cell hyperplasia, papillary elongation, and spongiosis occurred frequently in association with esophageal eosinophilic infiltration. CONCLUSIONS High esophageal eosinophil counts were found in 7% of this cohort of 200 patients with Barrett's esophagus and likely underestimates prevalence. The finding of esophageal eosinophilia in this cohort was independent of proton pump inhibitor use, features of EoE, or endoscopic therapy for Barrett's esophagus. Further studies are needed to assess if these findings are applicable to all patients with GERD.
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Affiliation(s)
- Karthik Ravi
- Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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Abstract
Esophageal adenocarcinoma is increasing in incidence. The main risk factor is the premalignant condition of Barrett's esophagus. There is great interest in chemoprevention to prevent or slow malignant transformation. There are many agents proposed as playing a role in chemoprevention; however, none is licensed for this role as yet. Aspirin possesses many favorable qualities for chemoprevention and is the focus of the largest randomized control trial in this field.
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Affiliation(s)
- Janusz A Jankowski
- Digestive Diseases Centre, Leicester Royal Infirmary, Infirmary Square, Leicester, LE1 5WW, UK.
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33
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Patti MG, Herbella FAM. Role of minimally invasive surgery in the modern treatment of Barrett's esophagus. Gastrointest Endosc Clin N Am 2011; 21:135-44. [PMID: 21112503 DOI: 10.1016/j.giec.2010.09.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Gastroesophageal reflux disease (GERD) is a highly prevalent disease. Population studies have demonstrated that a significant proportion of individuals weekly experience GERD symptoms. Barrett's esophagus (BE), defined by the presence of intestinal metaplasia (columnar epithelium with goblet cells), is considered a consequence of chronic reflux. This review defines the role of surgery in the modern treatment of BE, taking into consideration the pathophysiology of the disease and the new endoscopic procedures available at present.
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Affiliation(s)
- Marco G Patti
- Department of Surgery, University of Chicago, 5841 South Maryland Avenue, Room G-201, Chicago, IL 60637, USA.
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O'Connell K, Velanovich V. Effects of Nissen fundoplication on endoscopic endoluminal radiofrequency ablation of Barrett's esophagus. Surg Endosc 2010; 25:830-4. [PMID: 20676687 DOI: 10.1007/s00464-010-1270-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2010] [Accepted: 07/02/2010] [Indexed: 01/09/2023]
Abstract
BACKGROUND Endoscopic endoluminal radiofrequency ablation is achieving increasing acceptance as a mode of eliminating Barrett's metaplasia and, thus, reducing the risk of developing esophageal adenocarcinoma. It is believed that reducing exposure of the esophageal epithelium to acid is essential to achieve long-term ablation of Barrett's esophagus. However, it is unclear whether use of proton pump inhibitors or antireflux operations are more effective to accomplish this goal. METHODS All patients who underwent endoscopic endoluminal radiofrequency ablation with the BARRx device (BARRx Medical, Sunnyvale, CA) were reviewed for date of initial ablation, length of Barrett's epithelium, presence or performance of Nissen fundoplication, all follow-up endoscopy and treatment, and posttreatment biopsy results. Patients were categorized by presence of Nissen fundoplication and presence of Barrett's metaplasia or dysplasia by biopsy at least 12 months following ablation and at last endoscopic follow-up. Data were analyzed by Fisher's exact test and Mann-Whitney U-test. RESULTS Of 77 patients ablated, 47 had documented endoscopic follow-up at 12 months or longer following the ablation. Of these, 19 patients had Nissen fundoplication before, at the same time, or after ablation. Median length of Barrett's epithelium, with interquartile range (IQR), was 3 (2-12) cm in patients with fundoplication compared with 3 (2-7) cm without fundoplication (P = NS). Median follow-up was 15 (12-24) months in fundoplication patients compared with 12.5 (12-17) months without (P = NS). One of 19 patients with fundoplication had persistent or recurrent Barrett's epithelium, compared with 7 of 28 without fundoplication (P = 0.03). Of patients without fundoplication, those who had persistent or recurrent Barrett's had median Barrett's length of 10 cm (6-12 cm) compared with 3 cm (2-5 cm) in patients who had ablated Barrett's (P = 0.03). Follow-up length was similar in those with ablated epithelium, 15 months (12-19 months), compared with those with persistent or recurrent Barrett's, 12 months (12-13 months) (P = NS). CONCLUSIONS Patients who had fundoplication in conjunction with endoluminal radiofrequency ablation were more likely to achieve durable ablation compared with patients who were treated with proton pump inhibitor therapy. It appears that patients with long-segment Barrett's esophagus are at higher risk for persistent or recurrent Barrett's metaplasia. Consideration should be given for an antireflux operation in patients with long-segment Barrett's esophagus and planned endoluminal radiofrequency ablation.
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Affiliation(s)
- Kathleen O'Connell
- Division of General Surgery, Henry Ford Hospital, Detroit, MI 48202, USA
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Jovov B, Orlando GS, Tobey NA, Brown KL, Djukic Z, Carson JL, Brighton LE, Orlando RC. Ion transport and barrier function in a telomerase-immortalized human nondysplastic, Barrett's cell line (BAR-T). Dis Esophagus 2009; 22:386-95. [PMID: 19673046 DOI: 10.1111/j.1442-2050.2008.00907.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Barrett's specialized columnar epithelium (SCE) replaces reflux-damaged squamous epithelium. The benefits of SCE lie in its superior protection of the esophagus against further reflux damage. It was shown that this protection is dependent on ion transport and barrier function of SCE. The risks of SCE lie in its higher predisposition to malignant transformation. An understanding of underlying mechanisms of both processes would benefit considerably from greater knowledge of the structure and function of native SCE - the latter recently advanced by the availability of a telomerase-immortalized, nonneoplastic, human Barrett's cell line (BAR-T). Some of BAR-T characteristics for growth and differentiation have been described recently, but not its capacity to serve as a model for ion transport and barrier function of SCE. To determine the latter, BAR-T cells were grown in enriched media, seeded on permeable supports, and subjected to electrical, biochemical, and morphologic study. HET-1A (esophageal epithelial cell line), a nonneoplastic, human esophageal squamous cell line, was also studied for comparison. BAR-T, but not HET-1A cells in HEPES Ringer solution behaved as polarized monolayers with the capacity for ion transport and barrier function. This was evident electrically with a volt-ohm meter (EVOM),which recorded in BAR-T a resting potential difference of 2.0 +/- 0.2 mV, Isc of 17.4 +/- 3.3 microAmps/cm2 and resistance of 103 +/- 12 ohms x cm2. Further, Isc in BAR-T was inhibitable by exposure to Na-free solution, serosal ouabain, and luminal 4-acetamido4'-isothiocyano-2,2'-stilbenedisulfonic acid. Expression of tight junction genes were determined in BAR-T and HET-1A cells using quantitative reverse transcriptase-polymerase chain reaction, with expression of zonula occludens-1 (ZO-1) set at 1 as reference. Claudins 1, 4, and 12 were prominently expressed in BAR-T (0.2-0.6 of ZO-1), while claudins 1, 11, and 12 were prominently expressed in HET-1A(0.1-0.8 of ZO-1). BAR-T, but not HET-1A, expressed claudins 4, 8, 16, 18, and 23, and HET-1A, but not BAR-T, expressed claudins 11, 15, and 20. Protein expression of prominently expressed claudins in BAR-T correlated with mRNA expression. Immunofluorescence and confocal microscopy localized claudins 1 and 4 in BAR-T to cell membranes and claudin 18, specifically to the tight junction. Membrane polarization was also documented in BAR-T by immunolocalization of NaK,ATPase to the basolateral membrane. BAR-T, but not HET-1A cells grown on permeable supports form a polarized monolayer with both ion transport and barrier function. Since a number of features of BAR-T are similar to Barrett's SCE and distinct from HET-1A, the BAR-T cell line represents a valuable resource for the study of ion transport and barrier function of nondysplastic SCE.
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Affiliation(s)
- Biljana Jovov
- Department of Medicine/Gastroenterology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
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36
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Gatenby PAC, Ramus JR, Caygill CPJ, Fitzgerald RC, Charlett A, Winslet MC, Watson A. The influence of symptom type and duration on the fate of the metaplastic columnar-lined Barrett's oesophagus. Aliment Pharmacol Ther 2009; 29:1096-105. [PMID: 19222408 DOI: 10.1111/j.1365-2036.2009.03969.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Prolonged gastro-oesophageal reflux resulting in columnar metaplasia of the oesophagus is the main risk factor for oesophageal adenocarcinoma. AIM To examine the duration of symptoms and associations of different symptoms with the development of columnar-lined oesophagus, dysplasia and adenocarcinoma. METHODS UK multicentre cohort study of patients with columnar-lined oesophagus whose date of symptom onset (1082 patients) and/or types of symptoms reported (1681 patients) were documented. Follow-up was examined by analysis of histological reports from the registering centers. RESULTS Symptoms of dysphagia/odynophagia and nausea/vomiting were associated with development of dysplasia. High-grade dysplasia and adenocarcinoma were associated with dysphagia/odynophagia and weight loss. Median duration from symptom onset to detection of columnar-lined oesophagus without intestinal metaplasia: 2.6 years, columnar-lined oesophagus with intestinal metaplasia: 5.0 years, indefinite changes for dysplasia: 19.3 years and low-grade dysplasia: 30.0 years. One tenth of patients had developed high-grade dysplasia at 9.6 years and one tenth had developed adenocarcinoma at 13.8 years from symptom onset. CONCLUSIONS In patients with columnar-lined oesophagus, symptoms of dysphagia/odynophagia and nausea/vomiting were associated with a higher risk of development of dysplasia and adenocarcinoma. There is a trend for longer duration of symptoms to the detection of dysplasia.
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Affiliation(s)
- P A C Gatenby
- University Department of Surgery, Division of Surgery and Interventional Science, University College Medical School, London, UK.
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37
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Gatenby PAC, Ramus JR, Caygill CPJ, Charlett A, Winslet MC, Watson A. Treatment modality and risk of development of dysplasia and adenocarcinoma in columnar-lined esophagus. Dis Esophagus 2008; 22:133-42. [PMID: 19018855 DOI: 10.1111/j.1442-2050.2008.00886.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Columnar metaplasia is the precursor lesion for esophageal adenocarcinoma, resulting from prolonged gastroesophageal reflux. The influence of the efficacy of reflux control on the development of neoplastic change in columnar-lined esophagus is not established. This study compares the rate of development of dysplasia and adenocarcinoma in patients with columnar metaplasia of the esophagus between patients treated pharmacologically and those treated with antireflux surgery. This study is a retrospective review of a cohort of patients enrolled in a multicenter national registry involving 738 patients from seven UK centers. Forty-one were treated with antireflux surgery, 42 with H2 receptor antagonist, 532 with proton pump inhibitor, and 114 with a combination of these medications. Nine had none of these medications or surgery. Total follow-up was 3697 years. Mean age and follow-up for patients treated medically were 61.6 and 4.96 years and surgically were 50.5 and 6.19 years, respectively. No patient in the surgical group developed high-grade dysplasia (HGD) or adenocarcinoma. Twenty patients treated medically developed adenocarcinoma and 10 developed HGD. Hazards ratio comparing pharmacological to surgical therapy for development of all grades of dysplasia and adenocarcinoma 1.77 (P = 0.272). Log rank test comparing antireflux surgery to pharmacological therapy for development of HGD or adenocarcinoma P = 0.1287 and for adenocarcinoma P = 0.2125. Although there was a trend towards greater efficacy of antireflux surgery over pharmacological therapy in reducing the development of dysplasia and adenocarcinoma, this did not reach statistical significance.
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Affiliation(s)
- Piers A C Gatenby
- UK National Barrett's Oesophagus Registry, University Department of Surgery, Royal Free and University College Medical School, Royal Free Campus, London, UK.
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38
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Badreddine RJ, Wang KK. Barrett's esophagus: pathogenesis, treatment, and prevention. Gastrointest Endosc Clin N Am 2008; 18:495-512, ix. [PMID: 18674699 DOI: 10.1016/j.giec.2008.05.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Esophageal adenocarcinoma is the most common type of esophageal cancer seen in the United States and Western Europe. Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma and is believed to be found in 6% to 12% of patients undergoing endoscopy for gastroesophageal reflux disease and in more than 1% of all patients undergoing endoscopy. This article focuses on the pathogenesis, treatment, and prevention of BE.
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Affiliation(s)
- Rami J Badreddine
- Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
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39
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Gerson LB, Triadafilopoulos G, Sahbaie P, Young W, Sloan S, Robinson M, Miner PB, Gardner JD. Time esophageal pH < 4 overestimates the prevalence of pathologic esophageal reflux in subjects with gastroesophageal reflux disease treated with proton pump inhibitors. BMC Gastroenterol 2008; 8:15. [PMID: 18498663 PMCID: PMC2409349 DOI: 10.1186/1471-230x-8-15] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2008] [Accepted: 05/23/2008] [Indexed: 01/23/2023] Open
Abstract
Background A Stanford University study reported that in asymptomatic GERD patients who were being treated with a proton pump inhibitor (PPI), 50% had pathologic esophageal acid exposure. Aim We considered the possibility that the high prevalence of pathologic esophageal reflux might simply have resulted from calculating acidity as time pH < 4. Methods We calculated integrated acidity and time pH < 4 from the 49 recordings of 24-hour gastric and esophageal pH from the Stanford study as well as from another study of 57 GERD subjects, 26 of whom were treated for 8 days with 20 mg omeprazole or 20 mg rabeprazole in a 2-way crossover fashion. Results The prevalence of pathologic 24-hour esophageal reflux in both studies was significantly higher when measured as time pH < 4 than when measured as integrated acidity. This difference was entirely attributable to a difference between the two measures during the nocturnal period. Nocturnal gastric acid breakthrough was not a useful predictor of pathologic nocturnal esophageal reflux. Conclusion In GERD subjects treated with a PPI, measuring time esophageal pH < 4 will significantly overestimate the prevalence of pathologic esophageal acid exposure over 24 hours and during the nocturnal period.
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Lao-Sirieix P, Corovic A, Jankowski J, Lowe A, Triadafilopoulos G, Fitzgerald RC. Physiological and molecular analysis of acid loading mechanisms in squamous and columnar-lined esophagus. Dis Esophagus 2008; 21:529-38. [PMID: 18840137 DOI: 10.1111/j.1442-2050.2007.00807.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
SUMMARY Barrett's esophagus (BE) may be an adaptive cellular response to repeated acid exposure. The aims of this study were to compare intracellular acid loading in BE cells with normal squamous esophageal cells. Primary squamous and BE cells were obtained endoscopically and cultured for up to 24 h. Barrett's adenocarcinoma cell lines TE7 and OE-33 were compared with a normal esophageal (NE) cell line OE-21. Extracellular pH was lowered to 6.0 using HCl; specific ion exchangers were blocked pharmacologically and pH microfluorimetry was performed using 2'7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. The effect of prolonged acid preincubations and repeated acid exposure on acid loading and recovery were examined. Acid loading was greater in primary BE than NE cells (DeltapHi -0.22 +/- 0.08 vs.-0.13 +/- 0.01) and maximal in the BE carcinoma cell line TE7 (DeltapHi -0.30 +/- 0.01). Whereas TE7 cells were able to recover fully from repeated acid exposure, OE-21 cells remained profoundly acidic. BE primary and transformed cells utilize DIDS inhibitable sodium-independent chloride/bicarbonate exchange as well as sodium/hydrogen ion exchange for acid loading. In contrast, SE only requires sodium-independent chloride/bicarbonate exchange for acidification. The degree of acid loading is greater in BE than NE cells and it occurs via dual ion exchangers similar to gastric mucosa. Only Barrett's epithelial cells can maintain a physiological pHi following prolonged and repeated reflux exposure, which may confer a teleological advantage.
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Affiliation(s)
- P Lao-Sirieix
- Cancer Cell Unit, Hutchison, MRC Research Center, Cambridge, UK
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42
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Boolchand V, Sampliner RE. Risk for cancer in Barrett's esophagus: medical versus surgical therapy. Curr Gastroenterol Rep 2007; 9:189-94. [PMID: 17511915 DOI: 10.1007/s11894-007-0017-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Esophageal adenocarcinoma associated with Barrett's esophagus has been increasing in incidence over the past three decades. Our understanding of the risks for the development of esophageal adenocarcinoma in Barrett's esophagus is evolving. Newer treatment options for Barrett's esophagus are being developed in all areas, including endoscopic therapy, surgery, and chemoprevention trials.
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Affiliation(s)
- Vikram Boolchand
- Southern Arizona VA Healthcare System, 3601 South 6th Avenue, Section of Gastroenterology 111G-1, Tucson, AZ 85723, USA.
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43
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Frazzoni M, Manno M, De Micheli E, Savarino V. Efficacy in intra-oesophageal acid suppression may decrease after 2-year continuous treatment with proton pump inhibitors. Dig Liver Dis 2007; 39:415-21. [PMID: 17379591 DOI: 10.1016/j.dld.2007.01.023] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2006] [Revised: 01/25/2007] [Accepted: 01/30/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND Long-term intra-oesophageal acid suppression with proton pump inhibitors represents a management option for Barrett's oesophagus and severe reflux oesophagitis, but its stability over time has not been adequately assessed. AIM Our aim was to evaluate prospectively the efficacy of proton pump inhibitors in suppressing intra-oesophageal acidity after 2-year continuous treatment. METHODS Forty-five patients with Barrett's oesophagus or severe reflux oesophagitis on a proton pump inhibitor regimen (once or twice daily) that normalised the total percentage acid exposure time were re-evaluated by means of 24-h oesophageal pH-monitoring after 2-year of continuous unmodified treatment. RESULTS A significant rise in the total percentage acid exposure time was observed at 2-year follow-up (P=0.029), owing to an increased value in 27 (60%) cases (9 on a twice daily regimen), higher than normal in 10 of them (22% of the whole group) (3 on a twice daily regimen). In 18 patients (40%) the total percentage acid exposure time was stable or decreased. Heartburn remained efficiently suppressed in all patients. CONCLUSIONS The efficacy of proton pump inhibitors in suppressing intra-oesophageal acidity during continuous treatment may decrease over time, up to abnormal levels of oesophageal acid exposure in a minority of cases. This may occur without heartburn recurrence and with both once and twice daily regimens.
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Affiliation(s)
- M Frazzoni
- Internal Medicine and Gastroenterology Unit, New S. Agostino Hospital, Viale Giardini 1355, 41100 Modena, Italy.
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Abstract
Investigations and technical advances have enhanced our understanding and management of gastroesophageal reflux disease. The recognition of the prevalence and importance of patients with endoscopy-negative reflux disease as well as those refractory to proton pump inhibitor therapy have led to an increasing need for objective tests of esophageal reflux. Guidelines for esophageal reflux testing are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Issues regarding the utilization of conventional, catheter-based pH monitoring are discussed. Improvements in the interpretation of esophageal pH recordings through the use of symptom-reflux association analyses as well as limitations gleaned from recent studies are reviewed. The clinical utility of pH recordings in the proximal esophagus and stomach is examined. Newly introduced techniques of duodenogastroesophageal reflux, wireless pH capsule monitoring and esophageal impedance testing are assessed and put into the context of traditional methodology. Finally, recommendations on the clinical applications of esophageal reflux testing are presented.
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Affiliation(s)
- Ikuo Hirano
- Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611-2951, USA
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Feagins LA, Zhang HY, Hormi-Carver K, Quinones MH, Thomas D, Zhang X, Terada LS, Spechler SJ, Ramirez RD, Souza RF. Acid has antiproliferative effects in nonneoplastic Barrett's epithelial cells. Am J Gastroenterol 2007; 102:10-20. [PMID: 17266684 DOI: 10.1111/j.1572-0241.2006.01005.x] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES For patients with Barrett's esophagus, physicians commonly prescribe antisecretory medications in dosages above those required to heal reflux esophagitis because acid has been shown to have proproliferative and antiapoptotic effects on Barrett's cancer cells and on Barrett's mucosal explants. For a number of reasons, these model systems may not be ideal for determining the effects of acid on benign Barrett's epithelial cells, however. We studied the effects of acid on proliferation and apoptosis in a nonneoplastic, telomerase-immortalized Barrett's epithelial cell line. METHODS Barrett's cells were treated with two 3-minute exposures to acidic media. Cell growth was determined using cell counts, proliferation was studied by flow cytometry, cell viability was determined by trypan blue staining, and apoptosis was assessed by TUNEL and Annexin V. The expression levels of p53 and p21 were determined by Western blotting. p53 siRNA was used to study the effect of p53 inhibition on total cell numbers after acid exposure. RESULTS Acid exposure significantly decreased total cell numbers at 24 h without affecting either cell viability or apoptosis. Acid exposure resulted in cell cycle prolongation that was associated with greater expression of p53, but not p21. The acid-induced decrease in total cell numbers was abolished by p53 RNAi. CONCLUSIONS Acid exposure has p53-mediated, antiproliferative effects in nonneoplastic Barrett's epithelial cells. These findings contradict the results of prior in vitro and ex vivo studies. We speculate that the prescription of antisecretory medications in dosages beyond those required to heal gastroesophageal reflux disease (GERD) symptoms and endoscopic signs could be detrimental. Controlled, prospective clinical trials are needed to determine the optimal level of acid suppression for patients with Barrett's esophagus.
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Affiliation(s)
- Linda A Feagins
- Department of Medicine, Dallas VA Medical Center, University of Texas-Southwestern Medical School, Dallas, Texas 75216, USA
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Spechler SJ, Sharma P, Traxler B, Levine D, Falk GW. Gastric and esophageal pH in patients with Barrett's esophagus treated with three esomeprazole dosages: a randomized, double-blind, crossover trial. Am J Gastroenterol 2006; 101:1964-71. [PMID: 16848802 DOI: 10.1111/j.1572-0241.2006.00661.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND It has been suggested that patients with Barrett's esophagus (BE) are unusually resistant to the antisecretory effects of proton pump inhibitors (PPIs). OBJECTIVES To compare intragastric and intraesophageal acidity in patients with BE receiving esomeprazole 40 mg three times daily (t.i.d.), esomeprazole 40 mg twice daily (b.i.d.), and esomeprazole 20 mg t.i.d. METHODS In this randomized, double-blind, three-way crossover study, patients with long-segment BE received each of the three esomeprazole dosages for 5 days separated by 10-14-day washout periods. Intragastric and intraesophageal pHs were measured for 24 h on day 5. RESULTS Among 31 patients with evaluable pH data, intragastric pH was >4.0 for 88.4%, 81.4%, and 80.4% of day 5 after treatment with esomeprazole 40 mg t.i.d., 40 mg b.i.d., and 20 mg t.i.d., respectively. Esomeprazole 40 mg t.i.d. was significantly more effective than the other dosages (p < 0.01). Intraesophageal pH was <4.0 for mean values of <5% of the monitoring period with all the three dosing regimens, but esophageal pH remained <4.0 for >5% of the time in 16%, 23%, and 19% of patients receiving esomeprazole 40 mg t.i.d., 40 mg b.i.d., and 20 mg t.i.d., respectively. All dosages were well tolerated. CONCLUSIONS All the three esomeprazole dosages significantly decreased intragastric acidity and reduced esophageal acid exposure to mean normal values in the total group of patients with BE. However, abnormal esophageal acid exposure continued in 16-23% of patients despite the significant decrease in gastric acidity. These results suggest that the apparent "PPI resistance" described in patients with BE may be caused by their profound reflux diathesis rather than by gastric resistance to the antisecretory effects of PPIs.
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Affiliation(s)
- Stuart J Spechler
- Dallas Department of Veterans Affairs Medical Center, University of Texas Southwestern Medical Center, Dallas, Texas 75216, USA
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Katz PO, Scheiman JM, Barkun AN. Review article: acid-related disease--what are the unmet clinical needs? Aliment Pharmacol Ther 2006; 23 Suppl 2:9-22. [PMID: 16700899 DOI: 10.1111/j.1365-2036.2006.02944.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Proton pump inhibitors have dramatically improved the management options available for patients with acid-related disorders. In patients with gastro-oesophageal reflux disease, currently available proton pump inhibitors provide an excellent outcome for the majority; however, they do not provide optimal pH control in many. Proton pump inhibitors co-therapy reduces, but does not eliminate, the risk of gastrointestinal ulcers and complications in patients taking non-steroidal anti-inflammatory drugs, while in patients with upper gastrointestinal bleeding, it may be difficult to reach and maintain the current therapeutic target of intragastric pH of 6-7. This article reviews the effectiveness of current antisecretory therapy in these three acid-related diseases and areas of unmet clinical need. The potential role of a proton pump inhibitor with an extended duration of action and enhanced acid control from a single daily dose, particularly improved control at night, is discussed. Finally, therapy that could be administered without regard to time of day and/or food intake would offer dosing flexibility and thus have a positive effect on patients' compliance.
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Affiliation(s)
- P O Katz
- Division of Gastroenterology, Albert Einstein Medical Center, Philadelphia, PA 19141, USA.
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Peters JH. The importance of symptom assessment in the surgical treatment of gastroesophageal reflux disease and Barrett's esophagus. Surg Endosc 2006; 20 Suppl 2:S456-61. [PMID: 16544061 DOI: 10.1007/s00464-006-0041-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2006] [Accepted: 01/30/2006] [Indexed: 02/07/2023]
Abstract
The "art" and science of symptom assessment in the evaluation of patients with gastroesophageal reflux disease has been under emphasized. In fact, it is critical to judgements regarding surgical versus non-surgical therapy and is much more difficult than meets the eye. Many symptoms thought to be secondary to gastroesophageal reflux are not, and some, such as asthma cough and chest pain, which are commonly thought secondary to other causes, are indeed symptoms of reflux. Diagnostic studies are helpful but far from perfect, ultimately requiring the clinician's expert judgement as the key factor in determining a successful outcome. The following outlines both an approach to the assessment of symptoms and when possible, clinical studies shedding light on their cause and interpretation.
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Affiliation(s)
- J H Peters
- Division of Thoracic and Foregut Surgery, Department of Surgery, University of Rochester, Rochester, NY, USA.
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Cooper BT, Chapman W, Neumann CS, Gearty JC. Continuous treatment of Barrett's oesophagus patients with proton pump inhibitors up to 13 years: observations on regression and cancer incidence. Aliment Pharmacol Ther 2006; 23:727-33. [PMID: 16556174 DOI: 10.1111/j.1365-2036.2006.02825.x] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND There is little evidence that treatment of patients with Barrett's oesophagus with proton pump inhibitors over periods up to 6 years results in major regression of Barrett's oesophagus. AIM To determine if longer periods of treatment with proton pump inhibitors lead to significant regression of Barrett's oesophagus, and to determine the incidence of oesophageal adenocarcinoma in the proton pump inhibitor-treated patients. METHODS We analysed prospectively-collected data on Barrett's oesophagus patients treated with proton pump inhibitors for 1-13 years. RESULTS 188 patients with Barrett's oesophagus and intestinal metaplasia, were treated for 1-13 years with a proton pump inhibitor (966 years of treatment; mean 5.1 years). No change in length was seen during treatment but 48% of patients developed squamous islands (25% after 1-3 years; 100% at 12-13 years). Squamous islands correlated with treatment duration and male sex but not with proton pump inhibitor dose or patient age. Six patients developed dysplasia and three males developed adenocarcinoma during treatment (cancer incidence 0.31%). CONCLUSIONS Proton-pump inhibitor treatment over 1-13 years does not shorten the Barrett's oesophagus segment but squamous islands appear in many patients. The incidence of oesophageal adenocarcinoma was low in these proton pump inhibitor-treated patients compared with published series.
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Affiliation(s)
- B T Cooper
- Gastroenterology Unit, City Hospital, Birmingham, UK.
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Katz PO. Review article: intragastric and oesophageal pH monitoring in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2006; 23 Suppl 1:3-11. [PMID: 16483265 DOI: 10.1111/j.1365-2036.2006.02801.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Treatment of gastro-oesophageal reflux disease with acid suppressive therapy is based on the principle that effective control of intragastric pH (a marker of acid control) leads to healing of erosive oesophagitis and relief of gastro-oesophageal reflux disease-associated symptoms. Most patients with gastro-oesophageal reflux disease can be managed successfully with current antisecretory therapy. In difficult-to-treat patients, oesophageal pH monitoring is a useful technique to assess pH control and to investigate the association of reflux with refractory symptoms. Intragastric pH monitoring allows direct assessment of acid suppression achieved with an agent, and is the most useful for head-to-head comparisons of antisecretory therapies, evaluating variability in individual gastric pH response, assessing dose timing and food effect, and determining alternate dosing strategies; as such, it is useful in the research laboratory, and may be useful clinically to guide clinicians in dose titration and in evaluating the effect of switching agents. This article reviews these and other uses of these tests in an effort to explore the question of how to optimally use oesophageal pH monitoring and gastric pH monitoring in patient management.
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Affiliation(s)
- P O Katz
- Division of Gastroenterology, Albert Einstein Medical Center, Philadelphia, PA 19141, USA.
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