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Pompeu CMR, Sales TMAL, Nicolau LAD, de Souza Matos ACR, Borsaro AAF, Coutinho TAA, Nogueira LFA, Távora FRF, Souza MÂNE, Siffrim D, de Souza MHLP. Mucosal integrity of the larynx and hypopharynx and the response to proton pump inhibitors in patients with laryngopharyngeal reflux. Eur Arch Otorhinolaryngol 2025; 282:2159-2164. [PMID: 39891692 DOI: 10.1007/s00405-025-09214-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 01/07/2025] [Indexed: 02/03/2025]
Abstract
PURPOSE To evaluate whether impairment of integrity of laryngeal and hypopharyngeal mucosa in laryngopharyngeal reflux (LPR) could be related to response to proton pump inhibitors (PPIs). METHODS Chronic hoarseness with Reflux Finding Score (RFS) > = 7 was evaluated using the Reflux Disease Questionnaire (RDQ) and Reflux Symptoms Index (RSI). Upper endoscopy was performed and samples of the laryngeal posterior commissure were collected to evaluate ex vivo laryngeal mucosal integrity by transepithelial resistance (TER) using Ussing chamber. In vivo, hypopharyngeal integrity was measured using intraluminal impedance. Clinical responders scored < 13 and had a drop of at least 50% in the initial RSI after 8 weeks of pantoprazole. RESULTS Eighteen patients completed the protocol, Esophagitis was detected in 28% of the patients, and one patient presented acid exposure above 6%. After treatment, 66.67% responded to PPI. Laryngeal basal TER and TER drops after the weakly acidid challenge showed no difference between PPI responders and non-responders. Hypopharyngeal basal impedance was similar between the groups. After acid exposure test, there was a lower impedance in non-responders. CONCLUSION In laryngopharyngeal reflux, hypopharyngeal mucosal integrity was lower in PPI non-responders. These preliminary results suggest that the weaker laryngopharyngeal mucosa in refractory LPR may require new therapies aimed at improving barrier function. LEVEL OF EVIDENCE N/A.
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Zhang T, Tang X. Untangling immune cell contributions in the progression from GERD to Barrett's esophagus and esophageal cancer: Insights from genetic causal analysis. Int Immunopharmacol 2025; 150:114271. [PMID: 39965389 DOI: 10.1016/j.intimp.2025.114271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/30/2025] [Accepted: 02/07/2025] [Indexed: 02/20/2025]
Abstract
BACKGROUND Esophageal adenocarcinoma (EAC) is a rapidly increasing malignancy with significant morbidity and mortality. The progression from gastroesophageal reflux disease (GERD) to Barrett's esophagus (BE) and ultimately to EAC is thought to be influenced by chronic inflammation and immune cell dynamics. Despite the observed correlations in observational studies, the causal relationships between immune cell phenotypes and this disease continuum remain unclear. METHODS This study utilized a two-sample Mendelian Randomization (MR) approach to investigate the causal roles of 731 distinct immune cell phenotypes in the GERD-BE-EAC continuum. The analysis leveraged genome-wide association study (GWAS) data for immune phenotypes from a Sardinian cohort and data for GERD, BE, and EAC from the FinnGen and Open GWAS databases. A comprehensive set of MR methods, including inverse variance weighted (IVW), MR-Egger, and weighted median estimators, was employed to assess causality. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy, ensuring the robustness of the findings. RESULTS The study revealed complex and multifaceted roles of immune cells across the GERD-BE-EAC continuum. In GERD, 34 immune phenotypes were found to be causally associated with either increased or decreased risk. Protective effects were observed in phenotypes such as Unswitched Memory B cells, while others like CD45RA- CD4+ T cells were linked to an elevated risk. In the context of BE, 28 immune phenotypes demonstrated significant causal associations, with the majority being protective, including Unswitched Memory B cells and CD62L on Granulocytes. Conversely, certain phenotypes, such as CD24 on Transitional B cells, were identified as risk factors for BE. For EAC, 34 immune phenotypes were implicated, with various B cell subsets, particularly those expressing BAFF-R and CD24, associated with an increased risk, while Switched Memory B cells and specific myeloid cell phenotypes showed protective effects. CONCLUSIONS This study provides novel insights into the complex role of immune cells in the pathogenesis of EAC, revealing a dynamic interplay where certain immune phenotypes may be protective in early stages but become risk-enhancing in later stages of disease progression. These findings highlight the potential of immune cell phenotypes to serve as biomarkers for early detection and targeted therapeutic interventions across the GERD-BE-EAC continuum. Further research is warranted to validate these findings in diverse populations and to explore the underlying mechanisms driving these immune-mediated effects.
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Affiliation(s)
- Tai Zhang
- Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Peking University Health Science Center, Beijing 100091, China; Peking University Health Science Center, Beijing 100191, China
| | - Xudong Tang
- Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Peking University Health Science Center, Beijing 100091, China; Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
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Mattern S, Hollfoth V, Bag E, Ali A, Riemenschneider P, Jarboui MA, Boldt K, Sulyok M, Dickemann A, Luibrand J, Fusco S, Franz-Wachtel M, Singer K, Goeppert B, Schilling O, Malek N, Fend F, Macek B, Ueffing M, Singer S. An AI-assisted morphoproteomic approach is a supportive tool in esophagitis-related precision medicine. EMBO Mol Med 2025; 17:441-468. [PMID: 39901020 PMCID: PMC11903792 DOI: 10.1038/s44321-025-00194-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 01/14/2025] [Accepted: 01/14/2025] [Indexed: 02/05/2025] Open
Abstract
Esophagitis is a frequent, but at the molecular level poorly characterized condition with diverse underlying etiologies and treatments. Correct diagnosis can be challenging due to partially overlapping histological features. By proteomic profiling of routine diagnostic FFPE biopsy specimens (n = 55) representing controls, Reflux- (GERD), Eosinophilic-(EoE), Crohn's-(CD), Herpes simplex (HSV) and Candida (CA)-esophagitis by LC-MS/MS (DIA), we identified distinct signatures and functional networks (e.g. mitochondrial translation (EoE), immunoproteasome, complement and coagulations system (CD), ribosomal biogenesis (GERD)), and pathogen-specific proteins for HSV and CA. Moreover, combining these signatures with histological parameters in a machine learning model achieved high diagnostic accuracy (100% training set, 93.8% test set), and supported diagnostic decisions in borderline/challenging cases. Applied to a young patient representing a use case, the external GERD diagnosis could be revised to CD and ICAM1 was identified as highly abundant therapeutic target. This resulted in CyclosporinA as a personalized treatment recommendation by the local multidisciplinary molecular inflammation board. Our integrated AI-assisted morphoproteomic approach allows deeper insights in disease-specific molecular alterations and represents a promising tool in esophagitis-related precision medicine.
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Affiliation(s)
- Sven Mattern
- Department of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany
- Center for Personalized Medicine (ZPM), Tübingen, Germany
| | - Vanessa Hollfoth
- Department of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany
| | - Eyyub Bag
- Department of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany
| | - Arslan Ali
- Department of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany
| | | | - Mohamed A Jarboui
- Core Facility for Medical Proteomics, Institute for Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Tübingen, Germany
| | - Karsten Boldt
- Core Facility for Medical Proteomics, Institute for Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Tübingen, Germany
| | - Mihaly Sulyok
- Department of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany
| | - Anabel Dickemann
- Department of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany
| | - Julia Luibrand
- Department of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany
| | - Stefano Fusco
- Center for Personalized Medicine (ZPM), Tübingen, Germany
- Department of Internal Medicine I, University of Tübingen, Tübingen, Germany
| | | | - Kerstin Singer
- Department of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany
| | - Benjamin Goeppert
- Institute of Pathology and Neuropathology, Hospital RKH Kliniken Ludwigsburg, Ludwigsburg, Germany
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Oliver Schilling
- Institute of Pathology, University Medical Center Freiburg, Faculty of Medicine - University of Freiburg, Freiburg, Germany
- Center for Personalized Medicine (ZPM), Freiburg, Germany
| | - Nisar Malek
- Center for Personalized Medicine (ZPM), Tübingen, Germany
- Department of Internal Medicine I, University of Tübingen, Tübingen, Germany
| | - Falko Fend
- Department of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany
| | - Boris Macek
- Proteome Center Tübingen, University of Tübingen, Tübingen, Germany
| | - Marius Ueffing
- Core Facility for Medical Proteomics, Institute for Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Tübingen, Germany
| | - Stephan Singer
- Department of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany.
- Center for Personalized Medicine (ZPM), Tübingen, Germany.
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Franchi A, Agaimy A. Granulation tissue-like spindle cell (sarcomatoid) carcinoma of the head and neck: a deceptively bland-looking underdiagnosed malignancy. Virchows Arch 2024; 484:799-806. [PMID: 38403668 PMCID: PMC11106124 DOI: 10.1007/s00428-024-03770-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/16/2024] [Accepted: 02/20/2024] [Indexed: 02/27/2024]
Abstract
The diagnosis of head and neck spindle cell squamous carcinoma (SC-SCC) is often challenging. Lesions with a prominent inflammatory infiltrate and reactive vessels may have a granulation tissue-like appearance, therefore being difficult to distinguish from reactive lesions, like contact ulcers, post-intubation granulomas, inflammatory pseudotumors, or benign vascular lesions. In this study, we analyzed the clinicopathological features of a series of 17 head and neck SC-SCC with granulation tissue-like appearance. All patients, but two, were males, ranging in age between 57 and 80 years. The larynx was the most frequently affected site (n = 12), followed by the tongue (n = 4). One tumor was hypopharyngeal. Most consult cases were submitted with benign suggestion or because of unexpected recurrences of granulation tissue polyps. Histologically, all lesions consisted of an ulcerated polypoid proliferation of moderately to markedly atypical spindle cells, with a minor component of conventional invasive or in situ squamous carcinoma. At least one cytokeratin cocktail was positive in 13 cases. The staining was limited to a few neoplastic cells in most cases. Positivity for p63, p40, and cytokeratins 5/6 was detected only in the conventional squamous cell carcinoma component, when present. ALK1 was negative in all cases. Sixteen cases were tested for p53 and all showed aberrant expression (12 diffusely positive and 4 of null-phenotype). The diagnosis of granulation tissue-like SC-SCC is challenging due to the close clinical and histological overlap with several benign conditions. Since the expression of epithelial markers is limited, the use of an immunohistochemical panel including p53 is recommended.
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Affiliation(s)
- Alessandro Franchi
- Section of Anatomic Pathology, Department of Translational Research, University of Pisa, 56124, Pisa, Italy.
| | - Abbas Agaimy
- Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Comprehensive Cancer Center (CCC) Erlangen-EMN, 91054, Erlangen, Germany
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5
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Clark CM, Abdel-Aty Y, Rives H, Sulica L. De Novo Granuloma of the Membranous Vocal Fold: A Marker of Occult Malignancy. Otolaryngol Head Neck Surg 2024; 170:468-473. [PMID: 37925620 DOI: 10.1002/ohn.570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 08/28/2023] [Accepted: 09/15/2023] [Indexed: 11/06/2023]
Abstract
OBJECTIVE De novo occurrence of granuloma (granulation tissue) on the membranous vocal fold is not readily explained by usual causes of granuloma at the vocal process. We describe a series of patients. STUDY DESIGN Case series. SETTING Single academic institution. METHODS Cases were identified over a 16-year period. All patients exhibited granulation tissue on pathology. Demographic details, presentation, treatment, histology, and clinical outcomes were recorded. RESULTS Five patients (mean age: 74.0 ± 6.1 years, 40.0% male, 40.0% former smokers) underwent a biopsy. Persistent or recurrent granulation led to a second biopsy in 4 patients an average of 1423.5 days later, revealing a new diagnosis of squamous cell carcinoma (SCC) in situ in one and mild dysplasia in another. Further persistence or recurrence led to a third biopsy or excision an average of 302.3 days later in 3 patients, demonstrating SCC in situ in 1. An average of 2.5 biopsies were required with a mean time to SCC in situ diagnosis of 919.5 days from presentation. Two patients continued to demonstrate persistent granulation tissue on histology. CONCLUSION The membranous vocal fold is an atypical location for granuloma and portends a risk of occult malignancy. The occurrence of de novo granuloma at this site should prompt close long-term clinical surveillance with a low threshold for biopsy. Consideration should be given to tissue collection in the operating room to adequately sample the lesion's base. Concern should persist even after a negative biopsy, and serial observation with repeat biopsy as needed should be pursued.
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Affiliation(s)
- Christine M Clark
- Department of Otolaryngology-Head and Neck Surgery, The Sean Parker Institute for the Voice, Weill Cornell Medical College/NewYork-Presbyterian Hospital, New York City, New York, USA
| | - Yassmeen Abdel-Aty
- Department of Otolaryngology-Head and Neck Surgery, University of South Florida, Tampa, Florida, USA
| | - Hal Rives
- Department of Otolaryngology-Head and Neck Surgery, The Sean Parker Institute for the Voice, Weill Cornell Medical College/NewYork-Presbyterian Hospital, New York City, New York, USA
| | - Lucian Sulica
- Department of Otolaryngology-Head and Neck Surgery, The Sean Parker Institute for the Voice, Weill Cornell Medical College/NewYork-Presbyterian Hospital, New York City, New York, USA
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Girard C, Faure C. Contribution of Histology to the Diagnosis of GER. GASTROESOPHAGEAL REFLUX IN CHILDREN 2022:217-227. [DOI: 10.1007/978-3-030-99067-1_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Li K, Chen WY, Li YY, Wang TL, Tan MJ, Chen Z, Chen H. Laryngopharyngeal reflux disease management for recurrent laryngeal contact granuloma: A case report. World J Clin Cases 2021; 9:1989-1995. [PMID: 33748251 PMCID: PMC7953387 DOI: 10.12998/wjcc.v9.i8.1989] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 01/05/2021] [Accepted: 01/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Laryngeal contact granuloma (LCG) is difficult to treat and frequently associated with high persistence and recurrence, despite the availability of both surgical and pharmacological treatment options. An appropriate strategy is therefore needed to help patients with multiple recurrences of LCG to potentially avoid unnecess-ary surgery.
CASE SUMMARY We describe the case of a 34-year-old male patient with recurrent LCG in which a good response was achieved through successful management of laryngophar-yngeal reflux disease using a combination pharmacotherapeutic regimen consisting of anti-reflux therapy, pepsin secretion inhibition, bile acid neutralization, and lifestyle modifications. This patient underwent surgery to excise the granuloma, then relapsed, underwent a second surgery, which was followed by a second recurrence. The granuloma then disappeared after 9 mo of combined treatment with ilaprazole enteric-coated capsules (10 mg qd), mosapride tablets (5 mg tid) and compound digestive enzyme capsules (2 tablets). The drug regimen was discontinued after one year, and no recurrence of the lesion has been reported during the one-year follow-up period.
CONCLUSION We report a combination of pharmacotherapeutics and lifestyle modifications for the management of laryngopharyngeal reflux disease to address recurring LCG.
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Affiliation(s)
- Kai Li
- Department of Otorhinolaryngology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, China
| | - Wen-Yong Chen
- Department of Otorhinolaryngology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, China
| | - Yun-Ying Li
- Department of Otorhinolaryngology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, China
| | - Tu-Lu Wang
- Department of Otorhinolaryngology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, China
| | - Meng-Jia Tan
- Department of Otorhinolaryngology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, China
| | - Zong Chen
- Department of Otorhinolaryngology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, China
| | - Hai Chen
- Department of Otorhinolaryngology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, China
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Chang W, Xu W, Cheng L. Treatment of Laryngeal Contact Granuloma: Surgical Therapy or Conservative Treatment. ORL J Otorhinolaryngol Relat Spec 2019; 81:348-353. [PMID: 31694031 DOI: 10.1159/000503975] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 10/07/2019] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Despite the fact that there are many treatment alternatives, laryngeal contact granuloma has a high tendency of persistence, spontaneous disappearance without treatment, and recurrence. A comparison of the effects of conservative treatment and surgical therapy on laryngeal contact granuloma was made in a retrospective review. METHODS A total of 124 patients with laryngeal contact granuloma were divided into 2 groups according to treatment: simple surgical excision (n = 36) and conservative treatment (n = 84). Additionally, the reflux finding score (RFS) and the reflux symptom index (RSI) were utilized to assess the disease. RESULTS A total of 124 patients, with a median age of 48.5 years, ranging from 9 to 74 years, were recruited (107 male, 17 female). According to the diagnostic criteria for laryngeal reflux (RSI >13 or RFS >7), there were 67 cases, accounting for 54.03% of the total. Surgery was effective in 15 patients (15/36, 41.67%), and conservative treatment was effective in 62 patients (62/84, 73.81%). The 2 groups had statistically significant differences. CONCLUSIONS Conservative treatment, which is a comprehensive anti-reflux therapy, is better than surgical therapy and plays an important role in the treatment of laryngeal contact granuloma.
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Affiliation(s)
- Wei Chang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Wen Xu
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China,
| | - Liyu Cheng
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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Durkes A, Sivasankar MP. In vivo investigation of acidified pepsin exposure to porcine vocal fold epithelia. Laryngoscope 2015; 126:E12-7. [PMID: 26153224 DOI: 10.1002/lary.25478] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Revised: 05/07/2015] [Accepted: 06/08/2015] [Indexed: 12/21/2022]
Abstract
OBJECTIVES/HYPOTHESIS The study objective was to investigate epithelial changes in response to direct, repeated, acidified pepsin exposures in an in vivo porcine model. We hypothesized that 12 acidified pepsin applications to simulate reflux would elicit a vocal fold response characterized by inflammation, epithelial proliferation, and increased intercellular space, as well as changes in the gene expression of epithelial junctional proteins, ion transporter proteins, and proinflammatory cytokines. STUDY DESIGN Prospective, in vivo study. METHODS Pigs received acidified pepsin (pH = 4) or saline (sham) applied directly to vocal folds. Larynges were collected following three exposures per week for 4 weeks. Vocal fold tissue morphology, collagen, and elastin were evaluated histologically. Gene expression of E-cadherin, zona occludens-1, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, interleukin-1β, tumor necrosis factor-α, and interferon-γ were measured. Ultrastructural alterations, epithelial intercellular space diameter, and microridge height were measured using transmission electron microscopy. RESULTS There were no significant differences in histology, gene transcripts, epithelial ultrastructure, intercellular space, and microridge height after acidified pepsin exposure. CONCLUSIONS Twelve simulated reflux challenges were insufficient to elicit epithelial changes, demonstrating the resistance of healthy vocal folds to direct, repeated acidified pepsin exposures. These data increase our understanding of healthy vocal fold defenses and lay the groundwork for a prospective, uninjured, nonsurgical, laryngopharyngeal reflux model where pigs can be exposed directly to acidified pepsin.
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Affiliation(s)
- Abigail Durkes
- Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, U.S.A
| | - M Preeti Sivasankar
- Department of Speech, Language, and Hearing Sciences, Purdue University, West Lafayette, Indiana, U.S.A
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Münster M, Kook P, Araujo R, Hörauf A, Vieth M. [Determination of hyperregeneratory esophagopathy in dogs with clinical signs attributable to esophageal disease]. TIERAERZTLICHE PRAXIS AUSGABE KLEINTIERE HEIMTIERE 2015; 43:147-55. [PMID: 25993916 DOI: 10.15654/tpk-140765] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Accepted: 02/23/2015] [Indexed: 11/13/2022]
Abstract
OBJECTIVE It was hypothesized that typical characteristics of hyperregeneratory esophagopathy (HRE) in humans such as basal cell hyperplasia and elongation of stromal papillae are also histologically detectable in canine esophageal epithelium, and that these changes are associated with clinical signs and endoscopic findings suggesting gastroesophageal reflux (GER). MATERIAL AND METHODS Sixty-five adult dogs with clinical signs attributable to esophageal disease underwent esophagoscopy and biopsy. Clinical signs suggesting GER (regurgitation, ptyalism, painful discomfort) were prospectively evaluated through a questionnaire. Endoscopic mucosal alterations suggesting GER such as minimal endoscopic changes and obvious mucosal defects were assessed via video endoscopy. Biopsy specimens obtained from the esophageal squamous epithelium were evaluated histologically. The squamous epithelium's substructures of esophageal biopsies were quantitatively assessed through microscopic morphometry. RESULTS Esophageal squamous epithelium was considered normal in 48 dogs, and HRE was detected histologically in 17 dogs; both pathognomonic changes (basal cell hyperplasia, elongation of stromal papillae) were consistently present. Morphometrically assessed stromal papillary length and basal cell layer thickness was significantly (each, p < 0.0001) higher in the 17 dogs with HRE than in the 48 dogs without HRE, respectively. Overall, clinical signs suggesting GER were significantly (p = 0.02) more frequently encountered and regurgitation was significantly (p = 0.009) more common in the 17 dogs with HRE than in the 48 dogs without HRE. Similarly, endoscopic changes were significantly (p = 0.002) more frequently observed and minimal endoscopic changes suggesting GER were significantly (p = 0.004) more common in 17 dogs with HRE than in the 48 dogs without HRE. CONCLUSION AND CLINICAL RELEVANCE Typical characteristics of hyperregeneratory esophagopathy in humans are also histologically detectable in canine esophageal epithelium. Histological changes are associated with clinical signs and endoscopic findings suggesting GER.
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Affiliation(s)
- M Münster
- Michael Münster, Tierärztliche Gemeinschaftspraxis Dres. Hörauf und Münster, Hatzfeldstraße 6, 51069 Köln, E-Mail:
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11
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Cui R, Zhang H, Zhou L, Lu J, Xue Y, Wang Y, Yan X, Lin L, Lin S. Diagnostic value of dilated intercellular space and histopathologic scores in gastroesophageal reflux disease. Dis Esophagus 2014; 28:530-7. [PMID: 25130660 DOI: 10.1111/dote.12256] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The aim of this paper is to investigate the diagnostic value of histopathologic score and the dilated intercellular space (DIS) in patients with gastroesophageal reflux disease (GERD) and functional heartburn (FH). Participants with GERD symptoms including reflux esophagitis, non-erosive reflux disease (NERD), Barrett's esophagus (BE), functional heartburn (FH), along with a control group with atypical GERD-like symptom (Sym-C), and asymptomatic healthy volunteers (H-C) were administered GERD questionnaire, and subjected to endoscopy and biopsies, as well as 24-hour pH-impedance monitoring. Biopsies were evaluated using standards from the 2011 Esohisto Project after Hematoxylin-Eosin staining. DIS was measured quantitatively under light microscopy. Among the total of 565 participants with qualified biopsy specimens, the mean DIS of the reflux esophagitis (RE) group was significantly wider compared with the other five groups. DIS in patients with GERD-like symptoms was significantly wider compared with the H-C. No significant differences were observed between NERD and FH. Results from 24-hour pH-impedance monitoring indicated that only the DIS of patients with acid reflux or the amount of acid reflux episodes in patients with DIS was significantly wider compared with patients with nonacid reflux or patients without DIS (P < 0.001). With DIS = 0.9 μm as the cutoff value, the sensitivity and specificity were 62.6% and 54.1%, respectively. Using the total histopathologic score > 3 as the diagnostic criterion, the sensitivity and specificity were 71.7% and 47.4%. DIS is closely associated with GERD and acid reflux. The diagnostic value of histological scores in lower esophagus in GERD is very similar to that of the quantitative measurement of DIS.
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Affiliation(s)
- R Cui
- Department of Gastroenterolgy, Third Hospital of Peking University, Beijing, China
| | - H Zhang
- Department of Gastroenterolgy, Third Hospital of Peking University, Beijing, China
| | - L Zhou
- Department of Gastroenterolgy, Third Hospital of Peking University, Beijing, China
| | - J Lu
- Department of Gastroenterolgy, Third Hospital of Peking University, Beijing, China
| | - Y Xue
- Department of Gastroenterolgy, Third Hospital of Peking University, Beijing, China
| | - Y Wang
- Department of Gastroenterolgy, Third Hospital of Peking University, Beijing, China
| | - X Yan
- Department of Gastroenterolgy, Third Hospital of Peking University, Beijing, China
| | - L Lin
- Department of Gastroenterolgy, Third Hospital of Peking University, Beijing, China
| | - S Lin
- Department of Gastroenterolgy, Third Hospital of Peking University, Beijing, China
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12
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Bellizzi AM, Nardone G, Compare D, Bor S, Capanoglu D, Farré R, Neumann H, Neurath MF, Vieth M, Chen H, Chen X. Tissue resistance in the normal and diseased esophagus. Ann N Y Acad Sci 2013; 1300:200-212. [DOI: 10.1111/nyas.12248] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Andrew M. Bellizzi
- Department of Pathology, University of Iowa Hospitals and Clinics; University of Iowa Carver College of Medicine; Iowa City Iowa
| | - Gerardo Nardone
- Department of Clinical and Experimental Medicine; Gastroenterology Unit; University “Federico II” Naples Italy
| | - Debora Compare
- Department of Clinical and Experimental Medicine; Gastroenterology Unit; University “Federico II” Naples Italy
| | - Serhat Bor
- Sect Gastroenterology, Ege Reflux Study Group; Ege University School of Medicine; Bornova Turkey
| | - Doga Capanoglu
- Sect Gastroenterology, Ege Reflux Study Group; Ege University School of Medicine; Bornova Turkey
| | - Ricard Farré
- Translational Research Center for Gastrointestinal Disorders; KU Leuven Leuven Belgium
| | - Helmut Neumann
- Department of Medicine I; University of Erlangen-Nuremberg; Erlangen Germany
| | - Markus F. Neurath
- Department of Medicine I; University of Erlangen-Nuremberg; Erlangen Germany
| | - Michael Vieth
- Institute of Pathology; Klinikum Bayreuth Bayreuth Germany
| | - Hao Chen
- Cancer Research Program; JLC-BBRI, North Carolina Central University; Durham North Carolina
| | - Xiaoxin Chen
- Cancer Research Program; JLC-BBRI, North Carolina Central University; Durham North Carolina
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing; University of North Carolina; Chapel Hill North Carolina
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13
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Miwa H, Takubo K, Shimatani T, Furuta T, Oshima T, Tanaka J, Aida J, Ito M, Kurosawa S, Joh T, Wada T, Habu Y, Watanabe Y, Hongo M, Chiba T, Kinoshita Y. Histology of symptomatic gastroesophageal reflux disease: is it predictive of response to proton pump inhibitors? J Gastroenterol Hepatol 2013; 28:479-87. [PMID: 22989221 DOI: 10.1111/j.1440-1746.2012.07266.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/27/2012] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM To examine the differences in esophageal histopathology between non-erosive reflux disease (NERD) and reflux esophagitis (RE), and to investigate whether baseline esophageal histopathology can predict the therapeutic response to proton pump inhibitors (PPIs). METHOD The subjects comprised 94 patients with NERD (n = 71) or mild RE (n = 23). Tissue was biopsied from 5 cm above the squamo-columnar junction (SCJ), and the degree or presence of nine histopathological markers was assessed. The patients were treated with rabeprazole (RPZ) 10 mg once daily for 4 weeks. If complete heartburn relief was not achieved, RPZ was increased to 10 mg twice daily for another 2 weeks, and then to 20 mg twice daily for another 2 weeks if heartburn remained. RESULTS Features of esophageal histopathology 5 cm above the SCJ differed between NERD and RE patients. The esophageal histopathology in patients unresponsive to RPZ was characterized by Protein Gene Product (PGP) 9.5 negativity in those with NERD, and intraepithelial bleeding in those with RE. In addition, the combination of dilated intercellular spaces (DIS) (+)/PGP 9.5 (-) was indicative of strong resistance to PPI therapy in NERD patients. CONCLUSION The therapeutic efficacy of PPI can be predicted from the features of biopsied esophageal tissue. Factors predictive of resistance to treatment with PPI are negativity for PGP 9.5 in NERD patients and intraepithelial bleeding in RE patients.
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Affiliation(s)
- Hiroto Miwa
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
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14
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Abstract
Gastroesophageal reflux disease (GERD) affects 20-30% of the population in Western countries, and is one of the most common clinical problems in daily practice. GERD-associated functional and structural abnormalities are caused by recurrent exposure of the esophagus to acidic and nonacidic refluxate of gastric contents (containing duodenal and intestinal proteases as well as acid and gastric pepsin) from the stomach. Major progress has been made in the understanding of the molecular pathogenesis of GERD-associated mucosal inflammation, suggesting a complex and multifactorial pathogenesis and immune-mediated effects. This Review summarizes the complexity of mucosal pathogenesis, including microscopic changes, mucosal inflammation and GERD-specific molecular mediators, in the context of the clinical features and pathophysiological characteristics of GERD. The abnormal exposure of the esophagus to luminal contents leads to chronic mucosal inflammation that is characterized by the release of IL-8 specifically, as well as other proinflammatory mediators, from the esophageal mucosa. Evidence from animal studies indicates a stepwise inflammatory response by the epithelium, which attracts immune effector cells to infiltrate the mucosa. From bench to bedside, these novel molecular findings might provide new treatment options beyond current acid-suppressive therapy and the principle of inhibition of transient lower esophageal sphincter relaxation.
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15
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Fiocca R, Mastracci L, Milione M, Parente P, Savarino V. Microscopic esophagitis and Barrett's esophagus: the histology report. Dig Liver Dis 2011; 43 Suppl 4:S319-30. [PMID: 21459338 DOI: 10.1016/s1590-8658(11)60588-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Gastro-esophageal reflux disease (GERD) is the most common digestive disease in industrialized countries (Europe and North America) and is associated with microscopic changes in the squamous epithelium. However, biopsy is not presently included in the routine diagnostic flow chart of GERD. In contrast, esophageal biopsy is mandatory when diagnosing Barrett's esophagus. High quality histology reports are necessary to provide information on diagnosis and can also be important for research and epidemiological studies. It has been evident for decades that pathology reports vary between institutions and even within a single institution. Standardization of reporting is the best way to ensure that information necessary for patient management is included in pathology reports. This paper details the histological criteria for diagnosing GERD-associated microscopic esophagitis, other forms of esophagitis with specific features and columnar metaplasia in the lower esophagus (Barrett's esophagus). It provides a detailed description of appropriate sampling criteria, individual lesions and how they contribute to the histology report.
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Affiliation(s)
- Roberto Fiocca
- Department of Anatomic Pathology, University of Genova and S. Martino University Hospital, Genoa, Italy.
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16
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Nwokediuko SC, Ijoma U, Okafor O. Esophageal Intraepithelial Neutrophil Infiltration is Common in Nigerian Patients With Non-Erosive Reflux Disease. Gastroenterology Res 2011; 4:20-25. [PMID: 27957008 PMCID: PMC5139796 DOI: 10.4021/gr284e] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/12/2011] [Indexed: 12/26/2022] Open
Abstract
Background Non-erosive reflux disease (NERD) is a variant of gastroesophageal reflux disease (GERD) in which patients with typical reflux symptoms have no evidence of erosive esophagitis at endoscopy. An objective diagnostic tool for NERD remains an unmet need for clinicians and researchers. This study was designed to determine the types of histological alterations seen in Nigerian patients with NERD. Methods This was a prospective cross-sectional study in which mucosal biopsy was taken from the lower esophagus in patients with NERD. Similar biopsy was also taken from patients with nonulcer dyspepsia who served as controls. The materials were processed and examined histologically. Results There were 68 patients with NERD and 60 patients with nonulcer dyspepsia. Intraepithelial neutrophil infiltration was significantly more frequent in patients with NERD compared to those with nonulcer dyspepsia (47.1% vs 13.3%, P = 0.0326). Epithelial proliferative chnges in the form of basal cell hyperplasia and papilla elongation were minimal (11.8% and 3.3% respectively). Conclusions Nigerian patients with NERD have a high degree of esophageal intraepithelial neutrophil infiltration and a low prevalence of epithelial proliferative changes. This may be related to the relative rarity of Barrett’s esophagus in Nigerians.
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Affiliation(s)
| | - Uchenna Ijoma
- Department of Medicine, University of Nigeria Teaching Hospital, Ituku/Ozalla, PMB 01129 Enugu, Nigeria
| | - Okechukwu Okafor
- Department of Morbid Anatomy, University of Nigeria Teaching Hospital, Ituku/Ozalla, PMB 01129 Enugu, Nigeria
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17
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Weber K, Germann PG, Iwata H, Hardisty J, Kaufmann W, Rosenbruch M. Lesions in the Larynx of Wistar RccHan: WIST Rats. J Toxicol Pathol 2009; 22:229-46. [PMID: 22271998 PMCID: PMC3234598 DOI: 10.1293/tox.22.229] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2009] [Accepted: 07/14/2009] [Indexed: 11/25/2022] Open
Abstract
Specific regions in the rat larynx exhibit cellular changes in response to
inhaled xenobiotics. These regions include the base of the epiglottis, ventral
pouch, and medial surfaces of the vocal processes of the arytenoid
cartilages. 1 , 2 In order to collect information on the usefulness of
trimming techniques, the influence of different vehicles, the impact of
different application routes in toxicity studies, and differences between
induced vs. spontaneous lesions, the data obtained from a large number of
inhalation and non-inhalation studies performed in Wistar RCCHanTM:
Wist rats at Harlan Laboratories Ltd Switzerland, all evaluated or reviewed by
the same pathologist, were compiled for a detailed review. The value of
different trimming techniques was deemed to be greatest for transverse and
sagittolongitudinal section techniques, as compared to horizontolongitudinally
section techniques. The comparison of lesions encountered in control rats of
inhalation studies treated with different vehicles did not reveal differences in
the type, distribution pattern, incidence and/or severity of spontaneous
lesions. The types of lesions were also independent of different application
routes in non-inhalation studies compared to inhalation studies. The pattern of
spontaneous lesions in the rodent larynx was determined by degenerative and
inflammatory lesions starting most often in the submucosal glands by desiccated
secretion followed by mineralization and local inflammation or were induced by
impacted foreign bodies. Squamous metaplasia was recorded in the respiratory
epithelium overlaying the ventral gland as a spontaneous lesion in male Wistar
rats from inhalation studies with a maxim of 20.0% in an inhalation oncogenicity
study. Induced metaplastic changes recorded in the larynx were reversible. Other
induced lesions in inhalation studies consisted of submucosal edema, necrosis,
inflammation and/or granuloma. Induced lesions in non-inhalation studies were
found to be exclusively related to reflux laryngitis or food impaction. It is
concluded, that in rodents induced lesions of the larynx differ in type,
distribution pattern, severity and incidence from spontaneous lesions.
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Affiliation(s)
- Klaus Weber
- Harlan Laboratories Ltd., Zelgliweg 1, 4452 Itingen,
Switzerland
| | | | - Hijiri Iwata
- Harlan Laboratories Ltd., Zelgliweg 1, 4452 Itingen,
Switzerland
| | - Jerry Hardisty
- EPL Experimental Pathology Laboratories Inc., Research Triangle
Park, North Carolina 27709, USA
| | - Wolfgang Kaufmann
- Experimental Toxicology and Ecology, BASF SE, GV/TD–Z 470,
D-67056 Ludwigshafen, Germany
| | - Martin Rosenbruch
- Bayer Schering Pharma AG, GDD-GED-GTOX-Pathology & Clinical
Pathology, P.O. Box 101709, D-42096 Wuppertal, Germany
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18
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Abstract
Gastroesophageal reflux disease (GERD) is a common disease frequently encountered by surgical pathologists. Although the pathogenesis and clinical features of the disease have been studied for years, many unanswered questions remain. Typical clinical symptoms along with the endoscopic findings, pH monitoring, and biopsies, all support the diagnosis. However, these tests may yield conflicting findings, and at present there is no gold standard for the diagnosis of GERD. In patients with normal or nearly normal endoscopic findings (nonerosive reflux disease), the major diagnostic burden lies with the histology. The histologic diagnosis of GERD is based on a combination of findings, including basal cell hyperplasia, papilla elongation, inflammation, and dilatation of intercellular spaces. However, these features exhibit varying sensitivity and specificity, and minimal biopsy criteria for the diagnosis of reflux esophagitis have not been rigorously tested in well-characterized patient populations. However, given the high prevalence of GERD, pathologists face esophageal mucosal biopsies daily and must recognize the diagnostic strengths and limitations of histologic features of reflux esophagitis. Future studies and new techniques may improve the diagnostic strength of histology and establish meaningful minimal criteria for the diagnosis of reflux esophagitis.
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19
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An endoscopic grading system for vocal process granuloma. The Journal of Laryngology & Otology 2008; 122:1092-5. [DOI: 10.1017/s0022215108001722] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
AbstractBackground:A reliable grading system allows the clinician to classify disease severity, monitor progress and evaluate treatment efficacy. There is no currently accepted grading system for vocal process granuloma of the larynx.Aim:To evaluate the reliability of a new grading system for vocal process granuloma.Methods:All vocal process granuloma images from a digital laryngeal image library were abstracted. Granulomas were graded on a one to four system, as follows: grade one, sessile, non-ulcerative granuloma limited to vocal process; grade two, pedunculated or ulcerated granuloma limited to vocal process; grade three, granuloma extending past vocal process but not crossing midline of airway in fully abducted position; and grade four, granuloma extending past vocal process and past the midline of the airway in the fully abducted position. The granulomas were additionally graded A if unilateral and B if bilateral. Two laryngologists and two otolaryngology residents rated the granulomas on two separate occasions. Intra- and inter-observer reliability was evaluated with the kappa (κ) test statistic.Results:Thirty-five vocal process granulomas were identified. The percentage intra-observer agreement for the two laryngologists was 97 and 100 per cent (κ = 0.94 and 1.00, respectively). The percentage inter-observer agreement between the two laryngologists was 91 per cent (κ = 0.83). The percentage intra-observer agreement for the two residents was 89 and 91 per cent (κ = 0.83 and 0.77, respectively). The percentage inter-observer agreement between the two residents was 83 per cent (κ = 0.67).Conclusions:The proposed grading system for vocal process granuloma displayed excellent intra- and inter-observer reliability among residents and experienced laryngologists.
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Sabri MT, Hussain SZ, Shalaby TM, Orenstein SR. Morphometric histology for infant gastroesophageal reflux disease: evaluation of reliability in 497 esophageal biopsies. J Pediatr Gastroenterol Nutr 2007; 44:27-34. [PMID: 17204949 DOI: 10.1097/01.mpg.0000243424.01593.11] [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] [Indexed: 01/22/2023]
Abstract
OBJECTIVES We sought to determine the reliability of morphometric measurements on infant esophageal biopsies using a light microscope with eyepiece micrometer. METHODS We measured epithelial thickness, basal layer thickness (B), papillary height (P) and epithelial lymphocyte and eosinophil numbers on approximately 500 existing esophageal suction biopsies from infants previously evaluated for reflux esophagitis. We tested these measurements for interobserver, test-retest and internal consistency reliability. RESULTS Infants ages 0.25 to 23.75 (median, 6.25) months provided 497 biopsies. Both investigators scoring the biopsies independently judged 93% of them scorable. Of the biopsies scored by both, the 2 readings were within 0.15 of each other for P in 97% and for B in 81%. In addition to these correlative measures of consistency, categoric measures demonstrated that 373 (89%) of the 420 scorable biopsies with visible papillae produced agreement as to P being abnormal (317, 85%) or normal (56, 15%). Similarly, 360 (78%) of the 463 scorable biopsies produced agreement as to B being abnormal (339, 94%) or normal (21, 6%). P values were 0.17 to 0.94 (median, 0.67), and B values were 0.13 to 0.91 (median, 0.34). Lymphocytes numbered 0 to 40 (median 5) per high-power field. Only 12% had any eosinophils; none of those with completely normal morphometrics had any eosinophils; and only 2% had >5 eosinophils per high-power field. CONCLUSIONS Simple quantitative esophageal histological morphometric parameters are reliably measurable on suction biopsies from infants using a light microscope fitted with an ocular micrometer, even by nonpathologists.
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Affiliation(s)
- Mahmoud T Sabri
- Pediatric Gastroenterology, Geisinger Medical Center, Danville, PA, USA
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21
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Eckley CA, Costa HO. Estudo comparativo do pH e do volume salivar em indivíduos com laringofaringite crônica por doença do refluxo gastroesofágica antes e após o tratamento. ACTA ACUST UNITED AC 2006. [DOI: 10.1590/s0034-72992006000100010] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
INTRODUÇÃO: A Doença do Refluxo Gastroesofágico (DRGE) é a doença digestiva mais prevalente da atualidade e, recentemente, tem sido implicada em uma gama de alterações do seguimento laringofaríngeo (RLF). No entanto, pouco se sabe dos mecanismos fisiopatológicos destas manifestações supraesofágicas da DRGE. Os achados clínicos contraditórios e recentes pesquisas sugerem haver deficiências na capacidade de defesa deste seguimento. Uma das principais responsáveis pela homeostase da mucosa oral e do trato digestivo é a saliva com seu conteúdo orgânico e inorgânico. Tanto alterações do pH quanto do volume salivar já foram correlacionados com os sintomas e sinais sugestivos da DRGE e RLF. Estudo recente de nossa autoria demonstra diminuição estatisticamente significante do pH salivar de indivíduos com RLF quando comparado a controles sem a doença. Outro estudo constatou correlação entre a redução do volume X pH da saliva em indivíduos com DRGE, estando esta redução diretamente relacionada aos níveis de pH esofágico constatados durante pH-metria esofágica de 24 horas. OBJETIVOS: Avaliar como se comportam o pH e volume da saliva em um mesmo indivíduo com DRGE e RLF antes e após o tratamento clínico. MATERIAL E MÉTODO: Vinte e três pacientes com RLF tiveram o pH e volume da saliva total testados antes e após receberem tratamento com droga bloqueadora de bomba de prótons durante 12 semanas. RESULTADOS: Houve uma diferença estatisticamente significante (p<0,001) entre o pH da saliva antes e após o tratamento, estando este maior após o controle clínico da doença. O volume de saliva no paciente tratado foi significativamente maior do que no paciente pré-tratamento (p=0.009). DISCUSSÃO: Os achados sugerem que o pH salivar é influenciado pela presença de refluxo gastroduodenal à região laringofaríngea. Caso estudos futuros com populações maiores realmente comprovem esta correlação, poderemos cogitar a possibilidade de usar a mensuração do pH salivar, que é feita de forma rápida e não invasiva, como um meio de diagnosticar e avaliar o comportamento e controle do Refluxo Laringofaríngeo.
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22
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Devaney KO, Rinaldo A, Ferlito A. Vocal process granuloma of the larynx-recognition, differential diagnosis and treatment. Oral Oncol 2006; 41:666-9. [PMID: 16023983 DOI: 10.1016/j.oraloncology.2004.11.002] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2004] [Accepted: 11/15/2004] [Indexed: 02/06/2023]
Abstract
The vocal process granuloma is a nonneoplastic lesion that most often develops in the vicinity of the posterior vocal cords, adjacent to the vocal process. It may be an ulcerated region of the cord, or it may manifest as a nodular polypoid lesion. Causative factors include gastroesophageal reflux, intubation trauma, and vocal abuse. This lesion may be mistaken on clinical or pathologic grounds for carcinoma, although thorough microscopic examination usually permits a correct diagnosis. Despite its name, vocal process granuloma is not a true granulomatous process in a pathologic sense (inasmuch as it lacks aggregates of mononuclear and multinucleated histiocytes)-rather, it is a reactive/reparative process, in which an intact or ulcerated squamous epithelium is underlaid by granulation tissue or fibrosis. Treatment of vocal process granuloma centers around conservative voice therapy, coupled with treatment of any underlying inciting cause (such as gastroesophageal reflux). While it may recur locally (particularly if the original inciting cause persists), vocal process granuloma has no premalignant potential.
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23
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Eckley CA, Costa HO. Comparative study of salivary pH and volume in adults with chronic laryngopharyngitis by gastroesophageal reflux disease before and after treatment. Braz J Otorhinolaryngol 2006; 72:55-60. [PMID: 16917554 PMCID: PMC9445775 DOI: 10.1016/s1808-8694(15)30035-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2005] [Accepted: 09/13/2005] [Indexed: 01/20/2023] Open
Abstract
INTRODUCTION Gastroesophageal Reflux Disease (GERD) is the most prevalent digestive disease of the modern society and has been associated with abnormalities in the larynx and pharynx (LPR). Nonetheless, little is known about the mechanisms involved in this atypical form of the disease. Contradictory clinical data suggest a defense deficit at this segment. Saliva with its organic and inorganic components is responsible for the homeostasis of the oral mucosa and the digestive tract. Salivary pH and volume abnormalities have been linked to laryngopharyngeal symptoms of GERD and LPR. In a recent study we demonstrated significant salivary pH reduction in patients with LPR. Another study found correlation between reduced salivary pH and volume directly related to esophageal pH-metry results. AIM To evaluate salivary pH and volume before and after clinical treatment of LPR. MATERIAL AND METHOD Twenty-three adults with LPR had total fasting saliva tested before and after a 12-week course of oral proton pump inhibitor. RESULTS A statistically significant difference was found in salivary pH before and after treatment with increase of pH values after control of the disease (p<0.001). Salivary volumes of treated patients were also significantly higher than in pre-treated patients (p=0.009). DISCUSSION These findings suggest that salivary pH and volume are influenced by the presence of gastroesophageal contents and that salivary pH monitoring can potentially become a cost-effective method for diagnosing and controlling LPR.
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Numanoglu A, Millar AJW, Brown RA, Rode H. Gastroesophageal reflux strictures in children, management and outcome. Pediatr Surg Int 2005; 21:631-4. [PMID: 16075235 DOI: 10.1007/s00383-005-1479-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/15/2005] [Indexed: 10/25/2022]
Abstract
UNLABELLED Esophageal reflux (GER) strictures are frequently diagnosed late and require a prolonged management programme depending on the severity of the stricture. Management protocols include medical therapy, bouginage, fundoplication, stricture resection and even interposition grafting. Our preferred method is to delay the anti-reflux surgery until the esophagitis is medically controlled, adequate enteral intake with weight gain is achieved and the oesophageal narrowing adequately dilated. We review the results of the approach over a 27-year period (1977-2004). METHOD Thirty-one children were treated (mean age at diagnosis 35 months). Diagnosis of GERD was made on barium meal and confirmed by pH studies, gastroesophageal scintigraphy and oesophagoscopy. Stenosed site, its length and nature (i.e. response to dilatation) were documented. Dilatations were carried by prograde, balloon and string-guided techniques. Three fundoplication techniques were used (Boix-Ochoa, Toupet and Nissen). RESULTS Twenty-two strictures were in the lower third, seven in the mid-third and two in the upper third of the oesophagus. Thirteen (42%) had associated hiatus hernia (HH). Twenty (64%) had a stricture length>3 cm. Twelve strictures were so severe (tight) as to require gastrostomy and string-guided dilatation. An average 5.5 dilatations were required prior to surgery. Only six children did not require post-surgery dilatation. Twelve required more than five post-operative dilatations. Reasons for stricture persistence were identified as failed reflux surgery in seven, candida oesophagitis in two, HIV infection in one and severity of fibrosis in three (two requiring stricture resection). At average follow-up of 5 years, all patients have restored growth without further symptoms. CONCLUSION Strictures are a major complication of GER requiring prolonged and intensive management in most cases. Reasons for persistence of stricture after anti-reflux surgery can be identified and require early intervention. Long-term follow-up is essential but results have been good in our hands.
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Affiliation(s)
- A Numanoglu
- Department of Paediatric Surgery, Red Cross Children's Hospital, Klipfontein Rd., Rondebosch, 7700 Cape Town, South Africa.
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25
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Wu DC, Wu IC, Lee JM, Hsu HK, Kao EL, Chou SH, Wu MT. Helicobacter pylori infection: a protective factor for esophageal squamous cell carcinoma in a Taiwanese population. Am J Gastroenterol 2005; 100:588-93. [PMID: 15743356 DOI: 10.1111/j.1572-0241.2005.40623.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIM Many researchers have reported the inverse relationship between Helicobacter pylori (H. pylori) infection and esophageal adenocarcinoma risk, but very few studies have examined the association between H. pylori infection and the development of esophageal squamous-cell carcinoma (ESCC). Therefore, the aim of this study is to evaluate the relationship between H. pylori infection and ESCC risk. METHOD Subjects were cancer cases, pathologically proven to have ESCC, in two large medical centers in Kaohsiung metropolitan of southern Taiwan between August 2000 and May 2003. Controls were from the healthy subjects who lived in Kaohsiung metropolitan and voluntarily participated in one large multiyear of gene-environmental study. In total, 127 cases (116 males and 11 females) and 171 controls (161 males and 10 females) were recruited in the same period of time for interviews. H. pylori seropositivity was determined by an enzyme-linked immunosorbant assay measuring IgG. RESULTS A total of 28 (22.1%) and 74 (43.3%) out of 127 cases and 171 controls, respectively, had positive H. pylori infection. After adjusting for other covariates, subjects with positive H. pylori infections had a significantly reduced risk (adjusted odds ratio (AOR) = 0.51; 95% CI = 0.27-0.96; p= 0.037) of developing ESCC than those without. This result was even more pronounced in the groups of younger subjects, nonsmokers, or nondrinkers. In addition, among the 117 cancer patients who provided information about site of cancer lesion, the present study found that subjects with cancer lesions in the lower third of the esophagus had significantly fewer positive H. pylori infections (AOR = 0.34; 95% CI = 0.14-0.80; p= 0.013) than controls. CONCLUSION Our findings suggest that H. pylori infection may protect against the development of ESCC. Additional studies are needed to confirm these findings.
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Affiliation(s)
- Deng-Chyang Wu
- Department of Gastroentology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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Leonard R, Kendall K. Effects of voice therapy on vocal process granuloma: a phonoscopic approach. Am J Otolaryngol 2005; 26:101-7. [PMID: 15742262 DOI: 10.1016/j.amjoto.2004.08.010] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
PURPOSE This study reviewed the effects of a voice therapy program in patients who had failed other treatments for vocal process granuloma related to laryngopharyngeal reflux. The program was offered to 16 patients, all of whom demonstrated contact of the vocal processes at the site of pathology on voicing. During an initial evaluation, each patient was counseled regarding the need for voice conservation and improved vocal hygiene. Of the 16 patients, 10 agreed to undergo voice therapy and were subsequently enrolled in the treatment program. METHODS The primary therapy objective was to modify each patient's vocal fold contact pattern so that a small gap remained between the vocal processes during voicing. A "phonoscopic" approach to therapy was used. That is, the clinician and the patient were able to observe the larynx endoscopically while also listening to the voice. This combined aural and visual approach enabled the clinician to guide the patient toward the treatment objective with precision and provided patients with immediate feedback regarding their progress. RESULTS Of the 10 patients who underwent therapy, 8 were able to achieve the treatment objective, and all 8 experienced resolution of pathology or a marked reduction in its extent. Six patients who did not undergo treatment, and the 2 who were unable to achieve the treatment objective, demonstrated minimal or no improvement, or worsening of their pathology, over the same period. CONCLUSIONS The treatment program described may be of value to similar patients with resistant granuloma related to extraesophageal reflux.
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Affiliation(s)
- Rebecca Leonard
- Department of Otolaryngology/Head and Neck Sugery, University of California, Davis, Medical School/Center, Sacramento, CA 95817, USA.
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Impact of hiatal hernia on histological pattern of non-erosive reflux disease. BMC Gastroenterol 2005; 5:2. [PMID: 15638947 PMCID: PMC546187 DOI: 10.1186/1471-230x-5-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2004] [Accepted: 01/09/2005] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Hiatus hernia (HH) has major pathophysiological effects favoring gastroesophageal reflux and hence contributing to esophageal mucosa injury, especially in patients with severe gastroesophageal disease. However, prospective studies investigating the impact of HH on the esophageal mucosa in non-erosive reflux disease (NERD) are lacking. This study evaluated the association between the presence of (HH) and the histological findings in symptomatic patients with NERD. METHODS Fifty consecutive patients with gastroesophageal reflux disease (GERD) were enrolled. After conventional endoscopy, Lugol solution was applied and biopsy specimens were obtained. Histological parameters including basal zone hyperplasia, papillary length and cellular infiltration were evaluated. The chi-square test with Yates' correlation was used for comparing discrete parameters between groups. However, Fisher's exact probability test was used where the expected frequencies were lower than 5. Wilcoxon's test for unpaired samples was preferred in cases of semi-quantitative parameters. RESULTS The presence of HH along with more severe findings (0.01 <P < 0.05) was confirmed in 18 patients. NERD was observed in 29 (58%) patients. Basal zone hyperplasia and loss of glycogen accompanied HH in all cases, and the correlation was significant in NERD (P < 0.001). The remaining histological patterns were similar between erosive reflux disease and NERD in the presence of HH. CONCLUSION The presence of HH is correlated with more severe endoscopy findings, and predisposes for severe histological abnormality in cases of NERD.
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Benaixa JP, Esteban F, González-Pérez JM, Martínez-Garrido R. Tratamiento de los granulomas de laringe con medicación anti-reflujo extraesofágico. ACTA OTORRINOLARINGOLOGICA ESPANOLA 2003; 54:501-5. [PMID: 14671922 DOI: 10.1016/s0001-6519(03)78441-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To asses the role of Gastroesophageal reflux in the genesis of laryngeal granulomas. PATIENTS AND METHODS Prospective series of 7 patients diagnosed of posterior laryngeal granuloma, 5 were male, and 2 female, ages ranging between 46 and 65 years, (only three with symptoms of gastroesophageal reflux), who followed an antireflux protocol (recommendations, omeprazol 20 mg, cisapride 20 mg, almagato 4000 mg daily). RESULTS All cases did well, showing complete healing of the larynx 60 days after the beginning of treatment. CONCLUSIONS Gastroesophageal reflux is an important factor in the genesis of posterior laryngeal granulomas. It seems appropriate to start an antireflux regimen before surgery, which can be chosen for non responders or cases with severe respiratory symptoms, hoarseness, or for definitive diagnosis.
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Affiliation(s)
- J P Benaixa
- Servicio de Otorrinolaringología, Hospitales Universitarios Virgen del Rocío, Sevilla.
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Cappell MS, Friedel D. The role of esophagogastroduodenoscopy in the diagnosis and management of upper gastrointestinal disorders. Med Clin North Am 2002; 86:1165-216. [PMID: 12510452 DOI: 10.1016/s0025-7125(02)00075-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Esophagogastroduodenoscopy has revolutionized the clinical management of upper gastrointestinal diseases. Millions of EGDs are performed annually in the United States for many indications, such as gastrointestinal bleeding, abdominal pain, dysphagia, or surveillance of premalignant lesions. Esophagogastroduodenoscopy is very safe, with a low risk of serious complications such as perforation, cardiopulmonary arrest, or aspiration pneumonia. It is a highly sensitive and specific diagnostic test, especially when combined with endoscopic biopsy. Esophagogastroduodenoscopy is increasingly being used therapeutically to avoid surgery. New endoscopic technology such as endosonography, endoscopic sewing, and the endoscopic videocapsule will undoubtedly extend the frontiers and increase the indications for endoscopy.
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Affiliation(s)
- Mitchell S Cappell
- Division of Gastroenterology, Department of Medicine, Woodhull Medical Center, Department of Medicine, State University of New York, Downstate Medical School, Brooklyn, NY, USA
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Marambaia O, Andrade NA, Varela D, Juncal M. Refluxo laringofaringeano: estudo prospectivo correlacionando achados laringoscópicos precoces com a phmanometria de 24 horas de 2 canais. ACTA ACUST UNITED AC 2002. [DOI: 10.1590/s0034-72992002000400012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Introdução: Manifestações laríngeas do refluxo gastro-esofágico são problemas cada vez mais comuns. Estudos revelam alta associação com sensação de "globus", rouquidão crônica e com tosse crônica. Seu diagnóstico e tratamento diferem da clássica doença do refluxo gastro-esofágico. Os achados à endoscopia laríngea de hiperemia e edema de estruturas glóticas, espessamento do espaço interaritenóideo, granulomas, pólipos, edema de Reinke, estenose subglótica sugerem uma investigação diagnóstica completa através da pHmanometria de 24 horas, exame de maior sensibilidade e especificidade. Objetivo: correlacionar achados clínicos e laringoscópicos precoces sugestivos de refluxo gastro-esofágico com resultados da pHmanometria de 24 horas. Avaliar terapia medicamentosa e modificações dietéticas. Forma de estudo: Clínico prospectivo. Material e Método: pacientes adultos com queixas crônicas: tosse seca, "globus", sialorréia, disfonia, pigarro, halitose e engasgos. Foram excluídos pacientes com outras patologias de vias aéreas. Endoscopia laríngea descartava aqueles que apresentassem lesões laríngeas mais avançadas. Encaminhamento à pHmanometria e iniciado tratamento clínico. Resultados: 83,6% apresentaram refluxo patológico. Sintomas mais freqüentes: disfonia (72,5%), pigarro (60,8%), tosse (29,4%), "globus" (23,5%) e sialorréia (19,6%). Associação de sintomas: dois (67,4%); três (41,2%) e quatro (21,5%). 49 pacientes iniciaram tratamento com omeprazol (20 mg) e dieta: 83,7% cursaram com melhora dos sintomas após 6 meses. Em 95,9% dos pacientes tratados houve melhora laringoscópica. Conclusões: Houve uma correlação importante entre história clínica e endoscopia laríngea com achados à pHmanometria de 24 horas. Outros estudos poderão fortalecer a telescopia laríngea para o diagnóstico do refluxo laringofaríngeo e seu acompanhamento. É necessária abordagem multidisciplinar, além de um aumento do grau de suspeição do especialista.
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Affiliation(s)
- O. Marambaia
- Escola de Medicina e Saúde Pública; Santa Casa da Misericórdia da Bahia
| | - N. A. Andrade
- Escola de Medicina e Saúde Pública; Santa Casa da Misericórdia da Bahia
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Marambaia O, Andrade NA, Varela D, Juncal M. Refluxo laringofaringeano: estudo prospectivo correlacionando achados laringoscópicos precoces com a pHmanometria de 24 horas de 2 canais. ACTA ACUST UNITED AC 2002. [DOI: 10.1590/s0034-72992002000100014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Introdução: Manifestações laríngeas do refluxo gastro-esofágico são problemas cada vez mais comuns. Estudos revelam alta associação com sensação de "globus", rouquidão crônica e com tosse crônica. Seu diagnóstico e tratamento diferem da clássica doença do refluxo gastro-esofágico. Os achados à endoscopia laríngea de hiperemia e edema de estruturas glóticas, espessamento do espaço interaritenóideo, granulomas, pólipos, edema de Reinke, estenose subglótica sugerem uma investigação diagnóstica completa através da pHmanometria de 24 horas, exame de maior sensibilidade e especificidade. Objetivos: correlacionar achados clínicos e laringoscópicos precoces sugestivos de refluxo gastro-esofágico com resultados da pHmanometria de 24 horas. Avaliar terapia medicamentosa e modificações dietéticas. Forma de estudo: clínico prospectivo randomizado. Método: 61 pacientes adultos com queixas crônicas: tosse seca, "globus", sialorréia, disfonia, pigarro, halitose e engasgos. Foram excluídos pacientes com outras patologias de vias aéreas. Endoscopia laríngea descartava aqueles que apresentassem lesões laríngeas mais avançadas. Encaminhamento à pHmanometria e iniciado tratamento clínico. Resultados: 83,6% apresentaram refluxo patológico. Sintomas mais freqüentes: disfonia (72,5%), pigarro (60,8%), tosse (29,4%), "globus" (23,5%) e sialorréia (19,6%). Associação de sintomas: dois (67,4%); três (41,2%) e quatro (21,5%). 49 pacientes iniciaram tratamento com omeprazol (20 mg) e dieta: 83,7% cursaram com melhora dos sintomas após 6 meses. Em 95,9% dos pacientes tratados houve melhora laringoscópica. Conclusões: Houve uma correlação importante entre história clínica e endoscopia laríngea com achados à pHmanometria de 24 horas. Outros estudos poderão fortalecer a telescopia laríngea para o diagnóstico do refluxo laringofaríngeo e seu acompanhamento. É necessária abordagem multidisciplinar, além de um aumento do grau de suspeição do especialista.
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Affiliation(s)
- O. Marambaia
- Escola de Medicina e Saúde Pública; Santa Casa da Misericórdia da Bahia
| | - N. A. Andrade
- Escola de Medicina e Saúde Pública; Santa Casa da Misericórdia da Bahia
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Abstract
A common condition, gastroesophageal reflux disease (GERD) involves the reflux of gastric contents into the esophagus. GERD may contribute to asthma, noncardiac chest pain, and other problems. This article presents trends in GERD management, including pathophysiology, diagnosis, and treatment. The authors also explore lifestyle modifications, pharmacologic therapy, and gastroenterology referral.
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Affiliation(s)
- Sherry W Ray
- Chattanooga Gastroenterology, P.C., Tennessee, USA
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Bian YS, Osterheld MC, Fontolliet C, Bosman FT, Benhattar J. p16 inactivation by methylation of the CDKN2A promoter occurs early during neoplastic progression in Barrett's esophagus. Gastroenterology 2002; 122:1113-21. [PMID: 11910361 DOI: 10.1053/gast.2002.32370] [Citation(s) in RCA: 138] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The potential role of p16 inactivation by CDKN2A/p16 promoter hypermethylation and/or loss of heterozygosity (LOH) of the CDKN2A gene was investigated in neoplastic progression of Barrett's esophagus. METHODS CDKN2A promoter hypermethylation was studied by methylation sensitive single-strand conformation analysis and sequencing using bisulfite modified DNA in Barrett's esophageal adenocarcinomas, premalignant lesions, and normal squamous esophageal epithelium. All of the lesions of interest were sampled by microdissection from paraffin-embedded fixed tissue sections. RESULTS No methylation of the CDKN2A promoter was found in normal esophageal squamous cell epithelia, whereas methylation was detected in 18 of 22 (82%) adenocarcinomas and 10 of 33 (30%) premalignant lesions, including 4 of 12 (33%) samples with intestinal metaplasia only. LOH at the CDKN2A gene locus was found in 68% of adenocarcinomas and in 55% of premalignant lesions. Of 28 samples without p16 immunoreactivity, 25 (89%) showed CDKN2A promoter hypermethylation with or without LOH of CDKN2A. Only 2 (8%) samples expressing p16 protein were found to be methylated; these showed a mixture of completely methylated and unmethylated CDKN2A promoters. In 7 of 19 (37%) informative samples without LOH of CDKN2A, the CDKN2A promoter was found to be methylated at both alleles. Loss of p16 protein expression was strongly associated with CDKN2A promoter hypermethylation (P < 0.00001), but not with LOH (P = 0.33). CONCLUSIONS Our results indicate that methylation of the CDKN2A promoter is the predominant mechanism for p16 inactivation. This hypermethylation is a very common event in esophageal adenocarcinoma and occurs as early as metaplasia.
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Affiliation(s)
- Yan-Song Bian
- Institute of Pathology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
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Abraham SC, Singh VK, Yardley JH, Wu TT. Hyperplastic polyps of the esophagus and esophagogastric junction: histologic and clinicopathologic findings. Am J Surg Pathol 2001; 25:1180-7. [PMID: 11688578 DOI: 10.1097/00000478-200109000-00009] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Hyperplastic polyps of the esophagus and esophagogastric junction region (EGJ) are uncommon lesions characterized by hyperplastic epithelium (foveolar-type, squamous, or both) with variable amounts of inflamed stroma. They have been reported almost exclusively in the radiologic and clinical literature as occurring predominantly in association with gastroesophageal reflux disease (GERD). Comprehensive histologic and clinicopathologic evaluation of these polyps, their association with background mucosal pathology, and their association with Barrett's esophagus has not been previously performed. We studied 30 hyperplastic polyps from 27 patients and characterized the histologic, endoscopic, and clinical features of both the polyps and the background esophagus. Hyperplastic polyps were most common in the region of the EGJ (67%), followed by the distal esophagus (30%) and mid-esophagus (3%). Most (80%) were composed of predominantly cardiac-type mucosa, predominantly squamous mucosa (17%), or an admixture (3%). Intestinal metaplasia of the polyp was present in only 7% and low-grade dysplasia in only 3%. In the majority of cases (67%) hyperplastic polyps were associated with concurrent or recent ulcers or erosive esophagitis. In most cases (48%) esophageal injury was associated with GERD, but other potential etiologies included medications, infection, anastomotic or polypectomy sites, vomiting, and photodynamic therapy. Four patients (15%) had Barrett's esophagus, three of whom had or developed dysplastic Barrett's mucosa. These results underscore the pathogenesis of esophageal/EGJ region hyperplastic polyps as a mucosal regenerative response to surrounding mucosal injury. Careful clinical history and biopsy of the nonpolypoid mucosa are essential for determining the clinicopathologic context in which the polyps have developed.
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Affiliation(s)
- S C Abraham
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
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Bian YS, Osterheld MC, Bosman FT, Benhattar J, Fontolliet C. p53 gene mutation and protein accumulation during neoplastic progression in Barrett's esophagus. Mod Pathol 2001; 14:397-403. [PMID: 11353048 DOI: 10.1038/modpathol.3880324] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The aim of the present study was to characterize expression and mutation of p53 during the neoplastic progression from Barrett's esophagus to adenocarcinoma and to test the reliability of immunohistochemistry for p53 overexpression as an indicator of p53 mutation in this context. The association of both gene mutation and protein accumulation with clinicopathological findings and survival was also studied. A total of 77 samples from 30 esophagectomy specimens with Barrett's esophagus and adenocarcinoma of patients in longitudinal clinical follow-up were analyzed. Different lesions (intestinal metaplasia, dysplasia, and adenocarcinoma) as well as normal squamous-cell esophageal epithelia were sampled from formalin-fixed, paraffin-embedded tissues by microdissection. Mutations in p53 Exons 5 to 9 were detected by polymerase chain reaction-single-strand conformation polymorphisms (PCR-SSCP) and confirmed by direct DNA sequencing. Nuclear accumulation of p53 protein was analyzed immunohistochemically from tissue sections adjacent to those used for microdissection. p53 gene mutations were found in 17 and p53 protein accumulation were found in 20 tumor samples. Of the 17 adenocarcinomas with a p53 mutation, 16 stained positive for p53 protein. p53 mutations were detected significantly more frequently in high-grade dysplastic than in low-grade dysplastic lesions (77% versus 29%, P < 0.01). In contrast, nuclear accumulation of p53 was detected in 85% of high-grade and 71% of low-grade dysplastic lesions. In eight cases with p53 mutation, the mutation identified in the tumors was also detected in premalignant lesions, mainly in high-grade dysplasia. In four cases of p53-mutated tumors, clones with different p53 mutations were detected in premalignant lesions. Neither p53 mutations nor p53 protein accumulations were found in metaplastic lesions. In summary, we found that p53 mutations occurred mainly during the transition from low-grade to high-grade dysplasia in the neoplastic progression of Barrett's esophagus but not in the nondysplastic Barrett's mucosa. Mutational analysis of p53 by PCR-SSCP and p53 accumulation by immunohistochemistry were mostly concordant in adenocarcinoma and high-grade dysplastic lesions but frequently discordant in low-grade dysplastic lesions. No correlation between p53 gene mutation or p53 accumulation and clinicopathological findings was observed in this study.
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Affiliation(s)
- Y S Bian
- Institute of Pathology, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland
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