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Li D, Li C, Yan Y, Liu M. Esophageal papillomatosis: an exceedingly rare disease. Orphanet J Rare Dis 2023; 18:99. [PMID: 37120568 PMCID: PMC10149006 DOI: 10.1186/s13023-023-02703-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 04/20/2023] [Indexed: 05/01/2023] Open
Abstract
If esophageal papilloma (EP) is a rare condition, esophageal papillomatosis (EPS) is a distinct rarity. To date, only 53 well documented cases have been described in English literature. However, the number of reports on EPS significantly increased to over 40 cases during the past 20 years. Perhaps, this is due to the broad use of endoscopy and related research achievements. Most of the cases are individual and it seems that there are no associations between them. And up to now no guidelines can be followed. To further understand this exceedingly rare disease, we had a comprehensive review of the epidemiology, etiology, clinical manifestations, pathogenesis, treatment, and clinical course of EPS.
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Affiliation(s)
- Dandan Li
- Department of Gastrointestinal Medicine (Endoscopy Center), Jilin University, China-Japan Union Hospital, 126 Xiantai Street, Erdao, Changchun, 130033, People's Republic of China.
| | - Changfeng Li
- Department of Gastrointestinal Medicine (Endoscopy Center), Jilin University, China-Japan Union Hospital, 126 Xiantai Street, Erdao, Changchun, 130033, People's Republic of China
| | - Yuxing Yan
- Department of Gastrointestinal Medicine (Endoscopy Center), Jilin University, China-Japan Union Hospital, 126 Xiantai Street, Erdao, Changchun, 130033, People's Republic of China
| | - Minya Liu
- Department of Gastrointestinal Medicine (Endoscopy Center), Jilin University, China-Japan Union Hospital, 126 Xiantai Street, Erdao, Changchun, 130033, People's Republic of China
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Vageli DP, Doukas PG, Doukas SG, Tsatsakis A, Judson BL. Noxious Combination of Tobacco Smoke Nitrosamines with Bile, Deoxycholic Acid, Promotes Hypopharyngeal Squamous Cell Carcinoma, via NFκB, In Vivo. Cancer Prev Res (Phila) 2022; 15:297-308. [PMID: 35502554 DOI: 10.1158/1940-6207.capr-21-0529] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 12/15/2021] [Accepted: 02/21/2022] [Indexed: 11/16/2022]
Abstract
Tobacco smoking is the most known risk factor for hypopharyngeal cancer. Bile reflux has recently been documented as an independent risk factor for NFκB-mediated hypopharyngeal squamous cell carcinoma. However, the carcinogenic effect of tobacco smoke on the hypopharynx and its combination with bile has not yet been proven by direct evidence. We investigated whether in vivo chronic exposure (12-14 weeks) of murine (C57Bl/6J) hypopharyngeal epithelium to tobacco smoke components (TSC) [N-nitrosamines; 4-(N-Methyl-N-Nitrosamino)-1-(3-pyridyl)-1-butanone (0.2 mmol/L), N-nitrosodiethylamine (0.004 mmol/L)], as the sole drinking fluid 5 days per week, along with topically applied (two times/day) bile [deoxycholic acid (0.28 mmol/L)], can accelerate a possible TSC-induced neoplastic process, by enhancing NFκB activation and the associated oncogenic profile, using histologic, IHC, and qPCR analyses. We provide direct evidence of TSC-induced premalignant lesions, which can be exacerbated by the presence of bile, causing invasive carcinoma. The combined chronic exposure of the hypopharynx to TSC with bile causes advanced NFκB activation and profound overexpression of Il6, Tnf, Stat3, Egfr, Wnt5a, composing an aggressive phenotype. We document for the first time the noxious combination of bile with a known risk factor, such as tobacco smoke nitrosamines, in the development and progression of hypopharyngeal cancer, via NFκB, in vivo. The data presented here encourage further investigation into the incidence of upper aerodigestive tract cancers in smokers with bile reflux and the early identification of high-risk individuals in clinical practice. This in vivo model is also suitable for large-scale studies to reveal the nature of inflammatory-associated aerodigestive tract carcinogenesis and its targeted therapy. PREVENTION RELEVANCE Early assessment of bile components in refluxate of tobacco users can prevent the chronic silent progression of upper aerodigestive tract carcinogenesis. This in vivo model indicates that bile reflux might have an additive effect on the tobacco-smoke N-nitrosamines effect and could be suitable for large-scale studies of diagnostic and therapeutic interventions.
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Affiliation(s)
- Dimitra P Vageli
- The Yale Larynx Laboratory, Department of Surgery (Otolaryngology), Yale School of Medicine, New Haven, Connecticut
| | - Panagiotis G Doukas
- The Yale Larynx Laboratory, Department of Surgery (Otolaryngology), Yale School of Medicine, New Haven, Connecticut
| | - Sotirios G Doukas
- The Yale Larynx Laboratory, Department of Surgery (Otolaryngology), Yale School of Medicine, New Haven, Connecticut
- Department of Toxicology, Department of Forensic Sciences and Laboratory of Toxicology, Medical School, University of Crete, Heraklion, Greece
- Department of Medicine, Rutgers/Saint Peter's University Hospital, New Brunswick, New Jersey
| | - Aristidis Tsatsakis
- Department of Toxicology, Department of Forensic Sciences and Laboratory of Toxicology, Medical School, University of Crete, Heraklion, Greece
| | - Benjamin L Judson
- The Yale Larynx Laboratory, Department of Surgery (Otolaryngology), Yale School of Medicine, New Haven, Connecticut
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Doukas SG, Vageli DP, Sasaki CT. NF-κB inhibition reverses acidic bile-induced miR-21, miR-155, miR-192, miR-34a, miR-375 and miR-451a deregulations in human hypopharyngeal cells. J Cell Mol Med 2018. [PMID: 29516639 PMCID: PMC5908126 DOI: 10.1111/jcmm.13591] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
We previously demonstrated that acidic bile activates NF-κB, deregulating the expression of oncogenic miRNA markers, in pre-malignant murine laryngopharyngeal mucosa. Here, we hypothesize that the in vitro exposure of human hypopharyngeal cells to acidic bile deregulates cancer-related miRNA markers that can be reversed by BAY 11-7082, a pharmacologic NF-κB inhibitor. We repetitively exposed normal human hypopharyngeal primary cells and human hypopharyngeal keratinocytes to bile fluid (400 μmol/L), at pH 4.0 and 7.0, with/without BAY 11-7082 (20 μmol/L). We centred our study on the transcriptional activation of oncogenic miR-21, miR-155, miR-192, miR-34a, miR-375, miR-451a and NF-κB-related genes, previously linked to acidic bile-induced pre-neoplastic events. Our novel findings in vitro are consistent with our hypothesis demonstrating that BAY 11-7082 significantly reverses the acidic bile-induced oncogenic miRNA phenotype, in normal hypopharyngeal cells. BAY 11-7082 strongly inhibits the acidic bile-induced up-regulation of miR-192 and down-regulation of miR-451a and significantly decreases the miR-21/375 ratios, previously related to poor prognosis in hypopharyngeal cancer. This is the first in vitro report that NF-κB inhibition reverses acidic bile-induced miR-21, miR-155, miR-192, miR-34a, miR-375 and miR-451a deregulations in normal human hypopharyngeal cells, suggesting that acidic bile-induced events are directly or indirectly dependent on NF-κB signalling.
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Affiliation(s)
- Sotirios G Doukas
- The Yale Larynx laboratory, Department of Surgery, Yale School of Medicine, New Haven, CT, USA
| | - Dimitra P Vageli
- The Yale Larynx laboratory, Department of Surgery, Yale School of Medicine, New Haven, CT, USA
| | - Clarence T Sasaki
- The Yale Larynx laboratory, Department of Surgery, Yale School of Medicine, New Haven, CT, USA
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Kapoor H, Lohani KR, Lee TH, Agrawal DK, Mittal SK. Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma-Past, Present, and Future. Clin Transl Sci 2015. [PMID: 26211420 DOI: 10.1111/cts.12304] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long-standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5-year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett's esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett's esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett's esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett's carcinogenesis.
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Affiliation(s)
- Harit Kapoor
- Department of Surgery and Center for Clinical & Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA
| | - Kush Raj Lohani
- Department of Surgery and Center for Clinical & Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA
| | - Tommy H Lee
- Department of Surgery and Center for Clinical & Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA
| | - Devendra K Agrawal
- Department of Surgery and Center for Clinical & Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA
| | - Sumeet K Mittal
- Department of Surgery and Center for Clinical & Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA
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Wang RH. From reflux esophagitis to Barrett’s esophagus and esophageal adenocarcinoma. World J Gastroenterol 2015; 21:5210-5219. [PMID: 25954094 PMCID: PMC4419061 DOI: 10.3748/wjg.v21.i17.5210] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Revised: 01/19/2015] [Accepted: 02/11/2015] [Indexed: 02/06/2023] Open
Abstract
The occurrence of gastroesophageal reflux disease is common in the human population. Almost all cases of esophageal adenocarcinoma are derived from Barrett’s esophagus, which is a complication of esophageal adenocarcinoma precancerous lesions. Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett’s esophagus. The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia, which is closely associated with the development of esophageal adenocarcinoma. However, the exact mechanism of injury is not completely understood. Various animal models of the developmental mechanisms of disease, and theoretical and clinical effects of drug treatment have been widely used in research. Recently, animal models employed in studies on gastroesophageal reflux injury have allowed significant progress. The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results. In this article, various modeling methods are reviewed, with discussion of the major findings on the developmental mechanism of Barrett’s esophagus, which should help to develop better prevention and treatment strategies for Barrett’s esophagus.
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Hindmarsh A, Belshaw N, Mehta S, Johnson IT, Rhodes M. Can the rat be used as a valid model of human esophageal adenocarcinoma? Dis Esophagus 2012; 25:159-65. [PMID: 21819480 DOI: 10.1111/j.1442-2050.2011.01228.x] [Citation(s) in RCA: 2] [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
Animal models of Barrett's metaplasia and esophageal adenocarcinoma are important to further characterize the disease and test potential therapies. This paper reviews the development of the surgical model of esophageal adenocarcinoma in the rat and considers whether this model provides a biologically accurate representation of Barrett's esophagus and esophageal adenocarcinoma in humans.
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Affiliation(s)
- A Hindmarsh
- Department of Upper GI Surgery, Norfolk and Norwich University Hospital, Norwich, UK.
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Bigolin AV, Grossi JV, Maeso Montes JH, Nicola R, Cavazzola LT. Radiological evaluation of the patency of duodenal-esophageal anastomosis during a long postoperative follow-up: effectiveness of an alkaline reflux model in rats. Clin Exp Gastroenterol 2011; 4:197-202. [PMID: 22016580 PMCID: PMC3190287 DOI: 10.2147/ceg.s22944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2011] [Indexed: 11/23/2022] Open
Abstract
Background: Performing experimental studies has played an important role in acquiring knowledge about esophageal carcinogenesis. In this context, the choice of a more reliable experimental model requires proof of its effectiveness in order to lend greater credibility to the results. The objective of this study was to evaluate the patency of duodenal-esophageal anastomosis during long-term postoperative follow-up in rats. Methods: This was an experimental study in which 45 female Wistar rats were used. A side-to-side anastomosis was performed, going from the anterior side of the esophagus to the second duodenal portion. A standardized radiological technique was used to carry out a contrasted radiological study of the esophagus, stomach, and duodenum during weeks 4, 12, 20, and 30 after surgery. Different contrast media were used, and the animals were divided into groups, ie, group 1 (100% barium sulfate), group 2 (50% barium sulfate), and group 3 (60% aqueous iodinated contrast media). Contrast radiographs were taken in each group at weeks 4, 12, 20, and 30 after the surgical procedure. The radiographic images were evaluated by two radiologists who were blinded regarding the contrast groups. Macroscopic evaluation of each animal was compared with the radiological findings. Results: Postoperative mortality was 13.33%. The remaining animals were divided into study groups. All the contrast radiological examinations showed evidence of the location of the esophagus, stomach, and proximal portion of the intestine, and demonstrated the laterolateral relationship of the distal esophagus and the duodenum in the epigastric region. Patency of the anastomosis was observed at each examination period. The different contrast media used were able to demonstrate this outcome shortly after the first phase of injection. Necropsies corroborated the radiological findings. Conclusion: Regardless of the contrast agent used, contrasted radiography revealed that side-to-side duodenal-esophageal anastomosis in rats allowed patent communication during long-term postoperative follow-up.
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Kruel CRP, Pinto LFR, Blanco TCM, Barja-Fidalgo TC, Melo LL, Kruel CDP. Evaluation of the heme oxygenase-1 expression in esophagitis and esophageal cancer induced by different reflux experimental models and diethylnitrosamine. Acta Cir Bras 2010; 25:304-10. [DOI: 10.1590/s0102-86502010000300015] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2009] [Accepted: 03/15/2010] [Indexed: 01/29/2023] Open
Abstract
PURPOSE: To study the expression of heme-oxygenase-1 (HO-1), an enzyme induced by oxidative stress, in specimens obtained from an experimental model in rats that evaluated the role of gastric and duodenal reflux in esophageal carcinogenesis. METHODS: Esophageal specimens embedded in paraffin obtained from different experimental groups of rats were used for immunohistochemistry analysis of HO-1 expression. The rats had been divided into the following groups and were killed after 22 weeks: (1) cardioplasty to induce acid reflux; (2) esophagoduodenal anastomosis to induce duodenal reflux; (3) no treatment; (4) cardioplasty + diethylnitrosamine (DEN); (5) esophagoduodenal anastomosis + DEN; and (6) DEN. The study sample comprised 3 specimens from each group with the most severe histopathological lesions found on each study branch. RESULTS: The expression of HO-1 was seen only in rat specimens submitted to esophagoduodenal anastomosis (Groups 2 and 5), and the analysis of mean fluorescence intensity revealed a significant increase of HO-1 expression (4.8 and 4.6 fold, respectively) when compared with the control group (Group 3) (p<0.05). The main target for HO-1 induction was the inflammatory cells inside the tumor or in subepithelial areas. Rats exposed to gastric reflux had no HO-1 expression. CONCLUSION: Reflux esophagitis induced by reflux of duodenal contents, which provoked considerable oxidative stress, may play an important role in esophageal carcinogenesis. Acid reflux did not induce oxidative stress in this experimental model.
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Grossi JVM, Nicola RF, Bigolin AV, Montes JHM, Lima JNCD, Kraemer R, Cavazzola L. Description of the technique of upper gastrointestinal series radiological examination for the evaluation of the esophagus, stomach and duodenum of Wistar female rats. Acta Cir Bras 2009; 24:490-5. [PMID: 20011836 DOI: 10.1590/s0102-86502009000600012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2009] [Accepted: 07/28/2009] [Indexed: 11/22/2022] Open
Abstract
PURPOSE To evaluate the anatomy of female Wistar rats and the workability of contrast radiography as a technique to investigate the gastrointestinal series. METHODS Eight adult female Wistar rats were undergone to the contrast radiography as anteroposterior incidence and as posterior incidence in profile. The radiological examination was conducted at a 45 degrees angle to the radiological table. Film-focus distance (FFD) was 100 cm, film-object distance (FOD) was 0 cm, and object-focus distance (OFD) was 100 cm. An orogastric probe was used to inject barium contrast at 5-min intervals, for a total of four applications. After the radiological examination, animals were necropsy for confirmation of the radiological findings, and the radiographs were the absence of the normal anatomy variations inspected and described by an experienced radiologist. RESULTS All the radiographs produced achieved satisfactory results in terms of position, exposure, location and quality. The upper esophageal sphincter (UES) was identified in the esophagus at the nerve C2, the lower esophageal sphincter (LES) was identified between spinal cord segments L1 and L2, the thoracic-abdominal junction was observed at T10, the esophageal-gastric junction (EGJ) at T13-L1, with the abdominal portion in the epigastric region. The stomach was observed mostly in the epigastric region, left hypochondrium, left and mesogastric flank. The duodenum findings presented higher variation, with most findings identified in the epigastric region, right hypochondrium, right flank and mesogastric ileal fossa at T13-L5. CONCLUSION Contrast radiology is useful and may be employed to assess the anatomy of the animal being studied. The experimental model described afforded to fully identify all organs investigated, as well as other occasional relevant findings. No anatomical anomalies in the subsequent necropsy, confirming the radiographic findings.
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Affiliation(s)
- João Vicente Machado Grossi
- Experimental Laboratory, Institute of Basic Health Sciences, Brazilian Lutheran University (ULBRA), Porto Alegre - RS, Brazil.
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Lu S, Lowe AW, Triadafilopoulos G, Hsiung PL, Hao Y, Crawford JM, Wang TD. Endoscopic evaluation of esophago-gastro-jejunostomy in rat model of Barrett's esophagus. Dis Esophagus 2009; 22:323-30. [PMID: 19473210 PMCID: PMC3221518 DOI: 10.1111/j.1442-2050.2008.00909.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Endoscopy can be used to monitor the onset of metaplastic transformation and to observe the progression of neoplasia in small animal models of Barrett's esophagus. By avoiding animal sacrifice, the natural history of this disease can be studied in a longitudinal fashion. We aim to characterize the endoscopic features of esophageal mucosa at various stages of the metaplasia-dysplasia-carcinoma sequence in a rat reflux model of Barrett's for comparison with histology. Acid and bile reflux was produced by introducing a side-to-side esophago-gastro-jejunostomy in Sprague-Dawley rats. Endoscopic examination of the distal esophagus was performed in 24 surgically altered and 4 control rats, between weeks 24 and 36 after the operation in 4-week intervals, and all rats were biopsied and sacrificed at 36 weeks. Endoscopic images were classified based on the surface mucosal patterns of the distal esophagus and then compared with histology. The endoscopic appearance was classified as: (i) normal, characterized by a smooth surface; (ii) intestinal metaplasia, defined as elevated plaques/ridges, deep grooves, and thin linear folds; (iii) dysplasia, indicated by coarse folds/grooves, meshlike villi, and foveolar appearance; and (iv) carcinoma, suggested by irregular-shaped mass lesions with ulcerations. The endoscopic criteria for intestinal metaplasia yielded a sensitivity of 100% in comparison with histology. Intestinal metaplasia with high-grade dysplasia was found in two rats and with low-grade dysplasia in three rats. Both focally invasive squamous cell carcinoma and invasive adenocarcinoma were found in one rat. Small animal endoscopy in a rat model of Barrett's esophagus can be used to perform surveillance, classify mucosal patterns, observe the onset of intestinal metaplasia, and monitor the progression of neoplastic transformation, representing a useful tool for studying the natural history of this disease.
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Affiliation(s)
- Shaoying Lu
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Dr, Alway Bldg, Rm M211, Stanford, California, USA, 94305,Department of General Surgery, First Affiliated Hospital, Medical School of Xi’an Jiaotong University, 277 West Yanta Road, Xi'an Shaanxi, People’s Republic of China, 710061
| | - Anson W Lowe
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Dr, Alway Bldg, Rm M211, Stanford, California, USA, 94305
| | - George Triadafilopoulos
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Dr, Alway Bldg, Rm M211, Stanford, California, USA, 94305
| | - Pei-Lin Hsiung
- Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Dr, Alway Bldg, Rm M211, Stanford, California, USA, 94305
| | - Ying Hao
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Dr, Alway Bldg, Rm M211, Stanford, California, USA, 94305
| | - James M Crawford
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, P.O. Box 100275, Gainesville, Florida, USA, 32610
| | - Thomas D Wang
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Dr, Alway Bldg, Rm M211, Stanford, California, USA, 94305,Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, 109 Zina Pitcher Place, BSRB 1522, Ann Arbor, MI USA, 48109
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Murphy JO, Ravi N, Byrne PJ, McDonald GSA, Reynolds JV. Neither Antioxidants nor COX-2 Inhibition Protect Against Esophageal Inflammation in an Experimental Model of Severe Reflux. J Surg Res 2008; 145:33-40. [PMID: 17727884 DOI: 10.1016/j.jss.2006.07.053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2006] [Revised: 06/19/2006] [Accepted: 07/17/2006] [Indexed: 01/27/2023]
Abstract
BACKGROUND Reflux-induced injury and oxidative stress result in esophageal inflammation and the potential for progression to intestinal metaplasia and adenocarcinoma. Proton-pump inhibitors represent the standard medical approach, but anti-inflammatories and antioxidants offer novel therapeutic possibilities. MATERIALS AND METHODS Six weeks after an esophagojejunostomy reflux procedure, female Wistar rats (n = 100) were randomized to receive either an antioxidant (vitamin C, 8 mg or 28 mg/day), a cyclooxygenase-2 (COX-2) inhibitor (rofecoxib, 1 mg/day), or no therapy. After sacrifice 16 weeks later, esophageal injury was scored using pathologic and image analysis scoring. RESULTS Esophagitis was present in all 63 animals completing the study and was severe in 27 (43%). No animal developed metaplasia or tumor. The extent of inflammation and esophageal ulceration were not significantly different between experimental groups. CONCLUSIONS In this model of reflux injury, antioxidants and COX-2 inhibitors failed to ameliorate the severe inflammation induced. Further experimental designs should evaluate these novel approaches in less severe experimental models.
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Affiliation(s)
- James O Murphy
- Department of Surgery, St. James's Hospital and Trinity College, Dublin, Ireland
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Murphy JO, Ravi N, Byrne PJ, McDonald GSA, Reynolds JV. Neither Antioxidants nor COX-2 Inhibition Protect Against Esophageal Inflammation in an Experimental Model of Severe Reflux. J Surg Res 2007; 142:20-7. [PMID: 17543990 DOI: 10.1016/j.jss.2007.01.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2006] [Indexed: 01/27/2023]
Abstract
BACKGROUND Reflux-induced injury and oxidative stress result in esophageal inflammation and the potential for progression to intestinal metaplasia and adenocarcinoma. Proton-pump inhibitors represent the standard medical approach, but anti-inflammatories and antioxidants offer novel therapeutic possibilities. MATERIALS AND METHODS Six weeks after an esophagojejunostomy reflux procedure, female Wistar rats (n = 100) were randomized to receive either an antioxidant (vitamin C, 8 mg or 28 mg/day), a cyclooxygenase-2 (COX-2) inhibitor (rofecoxib, 1 mg/day), or no therapy. After sacrifice 16 weeks later, esophageal injury was scored using pathologic and image analysis scoring. RESULTS Esophagitis was present in all 63 animals completing the study and severe in 27 (43%). No animal developed metaplasia or tumor. The extent of inflammation and esophageal ulceration were not significantly different between experimental groups. CONCLUSIONS In this model of reflux injury, antioxidants and COX-2 inhibitors failed to ameliorate the severe inflammation induced. Further experimental designs should evaluate these novel approaches in less severe experimental models.
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Affiliation(s)
- James O Murphy
- Department of Surgery, St James's Hospital and Trinity College, Dublin, Ireland
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Li Y, Wo JM, Su RR, Ray MB, Jones W, Martin RCG. Esophageal injury with external esophageal perfusion. J Surg Res 2005; 129:107-13. [PMID: 15921698 DOI: 10.1016/j.jss.2005.04.018] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2005] [Revised: 03/03/2005] [Accepted: 04/10/2005] [Indexed: 12/27/2022]
Abstract
BACKGROUND External esophageal perfusion (EEP) with the idea that esophageal perfusion can be controlled with a single ingredient at a constant rate and concentration, might be used to dissect the injurious role of gastro-duodenal secretions for the progression from esophagitis to Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). This study is to evaluate the EEP rat model for esophagitis induced by using a micro-osmotic pump with bile perfusion. METHODS Eighteen adult rats underwent the EEP procedure. Bile (0.5% bovine bile, pH 7.4) was used as perfusion agent and three types of perfusions were performed: 1 week perfusion, 2 weeks perfusion, and 4 weeks perfusion compared to saline perfusion and sham operation. Histological changes, cell proliferation, apoptosis, 8-hydroxy-deoxyguanosine (8-OH-dG) and Manganese superoxide dismutase (MnSOD) were observed after perfusion and compared. RESULTS The bile perfusion for 1 week, 2 weeks, and 4 weeks induced mucosa infiltration of inflammatory cells, basal cell hyperproliferation, and papillae hypertrophy in all animals. Histopathology and cellular changes consistent with the findings associated with reflux esophagitis. The apoptotic index, the proliferating index, and expression of 8-OH-dG were significantly increased in the esophageal mucosa compared to controls. MnSOD expression was decreased with bile perfusion compared to saline controls. CONCLUSIONS The external esophageal perfusion model enabled precise control of the injurious agent. It induced the typical histological injury and cellular changes seen in severe reflux esophagitis. The cellular changes in apoptosis, proliferation and anti-oxidant defense make this model unique for reflux esophagitis studies. Further studies are needed to induce Barrett's esophagus and esophageal adenocarcinoma.
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Affiliation(s)
- Yan Li
- Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA
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Abstract
PURPOSE: To develop an experimental model of gastroesophageal reflux in rats. METHODS: Sixty Wistar rats underwent surgery and were assigned to one of the three groups of twenty animals each. The animals in group A underwent total esophageal myectomy and, in group (B), underwent partial myectomy. The third group was the control group (C). A contrast radiographic study of the esophagus was performed to evaluate gastroesophageal reflux. The anatomopathological study of the esophagus was used to evaluate esophagitis. RESULTS: During the 30-day postoperative follow-up, 14 animals in group A presented with reflux of barium in the esophagus. The presence of barium in the esophagus was observed in 7 animals in group B and in 2 animals in the control group. The result of the histopathology examination was controversial. A marked weight loss in the rats undergoing total myectomy was observed, however there was no significant statistical difference. CONCLUSION: Total myectomy in the lower third of the esophagus caused gastroesophageal reflux in the majority of the animals.
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Abstract
Columnar-lined lower esophagus (CLE) or Barrett's esophagus (BE) is caused by chronic reflux of the gastrointestinal tract and can progress to invasive adenocarcinoma. However, the pathophysiology, cell of origin, and management of this condition is incompletely understood. This review evaluates the role of in vivo models in resolving these debates. A search was performed on the Ovid and Pub Medline for 1964-2001 and Cochrane Collaboration. The keywords used were adenocarcinoma, animal model, Barrett's esophagus, columnar-lined esophagus, esophageal neoplasms, and esophageal carcinogenesis. All relevant papers were scrutinized and an attempt at tabulation was made. In vivo models have been used at several stages of debate on the pathophysiology of BE. They provide conclusive evidence for its acquired nature secondary to duodenogastroesophageal reflux. The cell of origin of experimental BE may arise from adjacent columnar epithelium, basal layer multipotent cells, or esophageal glands. Experimental work on BE is lacking in assessing therapeutic modalities.
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Affiliation(s)
- Y Koak
- Department of Surgery, Royal Free and University College School of Medicine, Rowland Hill Street, London, UK.
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Netzer P, Gut A, Brundler R, Gaia C, Halter F, Inauen W. Influence of pantoprazole on oesophageal motility, and bile and acid reflux in patients with oesophagitis. Aliment Pharmacol Ther 2001; 15:1375-84. [PMID: 11552908 DOI: 10.1046/j.1365-2036.2001.01069.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Reflux of duodeno-gastric juice into the oesophagus appears to be involved in the pathogenesis of both reflux oesophagitis and oesophageal adenocarcinoma. Although proton pump inhibitors have been shown to decrease acid reflux and heal oesophagitis, their effect on biliary reflux and motility is less clear. AIM To investigate whether pantoprazole also reduces bile reflux and whether this is paralleled by a change in oesophageal motility. METHODS Combined 24-h measurements of intraoesophageal bilirubin concentration, pH and pressure were performed in 18 symptomatic patients with endoscopically proven reflux oesophagitis before and on day 28 of treatment with pantoprazole, 40 mg/day, under standardized conditions. A reflux symptom score was determined initially and every 2 weeks thereafter. After 56 days on medication, a control endoscopy was performed. RESULTS The symptom score and the acid and bile reflux improved significantly, whereas the motility parameters did not change during the study period. Helicobacter pylori-positive patients had a significantly higher bile reflux time (32.1 +/- 4.3%) than H. pylori-negative patients (16.3 +/- 3.1%) (P=0.009). The endoscopic healing rate was 89%. The cough symptoms disappeared in three of four patients. CONCLUSIONS The proton pump inhibitor pantoprazole decreases both acid and bile reflux. The decrease of bile reflux cannot be explained by increased oesophageal clearance as oesophageal motility did not improve with therapy. Interestingly, H. pylori infection of the stomach was associated with higher levels of oesophageal bile reflux.
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Affiliation(s)
- P Netzer
- Gastrointestinal Unit, Inselspital, University of Berne, Switzerland
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