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Honing J, Tan WK, Lu VYZ, Gourgiotis V, Gianfrancesco IM, Schumacher AA, Vishwanathan S, Cheah C, Modolell I, Sujendran V, Fitzgerald RC, di Pietro M. Surveillance of Barrett's Esophagus Patients in an Expert Center is Associated With Low Disease-Specific Mortality. United European Gastroenterol J 2025; 13:220-228. [PMID: 39949075 PMCID: PMC11975633 DOI: 10.1002/ueg2.12759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 10/07/2024] [Accepted: 11/04/2024] [Indexed: 04/09/2025] Open
Abstract
INTRODUCTION Specialist guidelines recommend endoscopic surveillance for Barrett's esophagus to reduce mortality related to esophageal adenocarcinoma, but the setting for optimal Barrett's esophagus monitoring is unclear. We assessed progression rate and disease-specific mortality in a large cohort of patients followed up at a single Barrett's esophagus expert center. METHODS For this prospective longitudinal single center cohort study, we recruited patients with a previous diagnosis of Barrett's esophagus between 2004 and 2022. Endoscopists were trained in Barrett's esophagus surveillance standards and image-enhanced techniques, and biopsies were reviewed by expert pathologists. Exclusion criteria were a single surveillance endoscopy, high-grade dysplasia, or esophageal adenocarcinoma at or within 12 months from index endoscopy and patients with < 12 months follow-up. The primary outcome was the neoplastic progression rate of Barrett's esophagus with intestinal metaplasia to high-grade dysplasia/esophageal adenocarcinoma. Secondary outcomes included cancer stage and disease-specific mortality, risk factors for progression and progression rate in patients with Barrett's esophagus with only gastric metaplasia or irregular z-line and intestinal metaplasia (IZL-IM). RESULTS A total of 1932 patients were recruited, of which 969 were included in the primary analysis with a median follow-up of 5.8 years. Of these, 109 developed high-grade dysplasia or esophageal adenocarcinoma with a progression rate of 1.63%/year. Overall, 48 patients received an esophageal adenocarcinoma diagnosis, of which 89,5% (43/48) had stage 1%, and 0.3% patients (3/969) had disease-specific mortality. Multivariate analysis showed that age, alcohol consumption, esophagitis, Barrett's esophagus length, hiatus hernia length, low-grade dysplasia and neutrophil/lymphocyte ratio were risk factors for progression. The rate of progression in patients with Barrett's esophagus-gastric metaplasia or IZL-IM was 0.06%/year. CONCLUSIONS Endoscopic surveillance in an expert Barrett's esophagus center leads to a high neoplastic progression rate, and a low rate of disease-specific mortality. Further research to correlate disease-specific mortality and cancer stage with dysplasia detection rate is warranted to develop diagnostic quality indicators specific for Barrett's esophagus.
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Affiliation(s)
- Judith Honing
- Early Cancer InstituteUniversity of CambridgeCambridgeUK
- Erasmus Medical CenterErasmus UniversityRotterdamThe Netherlands
| | - W. Keith Tan
- Early Cancer InstituteUniversity of CambridgeCambridgeUK
- Department of GastroenterologyCambridge University Hospital NHS Foundation TrustCambridgeUK
| | | | | | | | | | | | - Calvin Cheah
- Early Cancer InstituteUniversity of CambridgeCambridgeUK
| | - Ines Modolell
- Department of GastroenterologyCambridge University Hospital NHS Foundation TrustCambridgeUK
| | - Vijay Sujendran
- Cambridge Oesophagogastric CentreCambridge University Hospital NHS Foundation TrustCambridgeUK
| | | | - Massimiliano di Pietro
- Early Cancer InstituteUniversity of CambridgeCambridgeUK
- Department of GastroenterologyCambridge University Hospital NHS Foundation TrustCambridgeUK
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Nokamatye YY, Kamsu GT, Ndebia EJ. Comparative Analysis of Oral Prevotella intermedia, Tannerella forsythia, Streptococcus sanguinis, and Streptococcus mutans in Patients with Esophageal Squamous Cell Carcinoma and Healthy Controls in Mthatha, South Africa. BACTERIA 2025; 4:11. [DOI: 10.3390/bacteria4010011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2025]
Abstract
The microbiome plays a crucial role in cancer development, influencing fundamental processes such as cell proliferation, apoptosis, immune system regulation, and host metabolism. Recent studies have highlighted a possible relationship between esophageal cancer and the oral microbiota, making oral microflora a possible risk factor. The bacteria Prevotella intermedia, Tannerella forsythia, Streptococcus sanguinis, and Streptococcus mutans, implicated in various oral pathologies, were of interest in this study, which was initiated to examine their potential role in the etiology of esophageal squamous cell carcinoma (ESCC). To achieve this, a case-control design was used, with whole saliva samples collected from 24 healthy controls and 24 patients with esophageal squamous cell carcinoma. DNA was then extracted, and real-time PCR was performed to quantify the presence of the targeted bacteria in both groups. The results showed that all the bacteria studied were present in the saliva of both patients with ESCC and healthy controls. However, expression levels were significantly higher in patients with ESCC. Specifically, a marked increase in the presence of P. intermedia, T. forsythia, S. sanguinis, and S. mutans was observed in the patients with cancer compared to the healthy controls. In short, this study highlights a significant imbalance in the microbial flora, with an increased abundance of selected bacteria in patients with ESCC. The monitoring of these bacteria could thus be exploited to track patients who are at risk. Their integration into diagnostic and therapeutic strategies would offer new prospects for the early diagnosis and improved prognosis of patients at risk of ESCC.
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Affiliation(s)
- Yolanda Yolisa Nokamatye
- Department of Human Biology, Faculty of Medicine and Health Sciences, Walter Sisulu University, Mthatha 5100, South Africa
| | - Gabriel Tchuente Kamsu
- Department of Human Biology, Faculty of Medicine and Health Sciences, Walter Sisulu University, Mthatha 5100, South Africa
| | - Eugene Jamot Ndebia
- Department of Human Biology, Faculty of Medicine and Health Sciences, Walter Sisulu University, Mthatha 5100, South Africa
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Massironi S. Advancements in Barrett's esophagus detection: The role of artificial intelligence and its implications. World J Gastroenterol 2024; 30:1494-1496. [PMID: 38617459 PMCID: PMC11008413 DOI: 10.3748/wjg.v30.i11.1494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 01/27/2024] [Accepted: 02/27/2024] [Indexed: 03/21/2024] Open
Abstract
Artificial intelligence (AI) is making significant strides in revolutionizing the detection of Barrett's esophagus (BE), a precursor to esophageal adenocarcinoma. In the research article by Tsai et al, researchers utilized endoscopic images to train an AI model, challenging the traditional distinction between endoscopic and histological BE. This approach yielded remarkable results, with the AI system achieving an accuracy of 94.37%, sensitivity of 94.29%, and specificity of 94.44%. The study's extensive dataset enhances the AI model's practicality, offering valuable support to endoscopists by minimizing unnecessary biopsies. However, questions about the applicability to different endoscopic systems remain. The study underscores the potential of AI in BE detection while highlighting the need for further research to assess its adaptability to diverse clinical settings.
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Affiliation(s)
- Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca, Monza 20900, Italy
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Malkani N, Rashid MU. Systemic Diseases and Gastrointestinal Cancer Risk. JOURNAL OF CANCER & ALLIED SPECIALTIES 2023; 9:473. [PMID: 37575213 PMCID: PMC10405983 DOI: 10.37029/jcas.v9i2.473] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 06/15/2023] [Indexed: 08/15/2023]
Abstract
Importance Gastrointestinal (GI) cancers are the second leading cause of cancer-related deaths worldwide. Observations The global challenges GI cancers pose are high, especially in middle- and low-income countries. Patients with these cancers present with symptoms of poor appetite, weight loss, heartburn, abdominal pain, fatigue and anaemia. Several risk factors contribute to GI cancers, including age, gender, obesity, pathogenic infections, smoking cigarettes, alcohol consumption and dietary habits. Most of these cancers are sporadic. However, some patients are at high risk due to a family history of GI cancers. Systemic diseases affect multiple organs, and their chronic occurrence elicits inflammatory responses at various sites. These diseases also contribute to GI cancers. Conclusion and Relevance In this review, we discuss that untreated systemic diseases, including diabetes, hepatitis, acquired immune deficiency syndrome, ulcers and hypertension, can potentially lead to GI cancers if they remain untreated for a longer period. Systemic diseases initiate oxidative stress, inflammatory pathways and genetic manipulations, which altogether confer risks to GI cancers. Here, we describe the association between systemic diseases and their underlying mechanisms leading to GI cancers.
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Affiliation(s)
- Naila Malkani
- Department of Zoology, Government College University, Lahore, Punjab, Pakistan
| | - Muhammad Usman Rashid
- Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan
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Xie W, An L, Liu Z, Wang X, Fu X, Ma J. Therapeutic Effect of Polaprezinc on Reflux Esophagitis in the Rat Model. Dig Dis Sci 2023:10.1007/s10620-023-07990-6. [PMID: 37335414 DOI: 10.1007/s10620-023-07990-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 05/24/2023] [Indexed: 06/21/2023]
Abstract
BACKGROUND/AIMS To explore the protective effects and therapeutic mechanism of Esomeprazole (PPI), polaprezinc granule (PZ), and PPI + PZ on reflux esophagitis (RE) in the rat model. METHODS Wistar rats were randomly divided into 9 groups, which contain the control group, the acid cessation group (0.7% HCl, Q3D × 4), and the acid persistence group (0.7% HCl, Q3D × 11). PPI was administered by gavage at 8 mg·kg-1 body weight and PZ was administered by gavage at 120 mg·kg-1 body weight once a day for 15 days. The gastric cardia tissue of the feeding tube was observed under the light microscope, and the levels of interleukin-8 (IL-8) and prostaglandin E2 (PGE2) were measured by ELISA. The expression of EGFR, Akt, p-Akt, and p-mTOR was detected by Western blot. RESULTS The ELISA results showed that the levels of IL-8 and PGE2 were significantly increased in the model group, but decreased in all groups after treatment. In the acid cessation group, PZ treatment had the most significant effect on reducing IL-8 levels and PPI + PZ treatment had the most significant effect on reducing PGE2 levels. In the acid persistence group, the PPI treatment had the most significant effect on reducing the levels of IL-8 and PGE2, and the PZ treatment could also significantly reduce their levels, close to the normal value. Western blot results showed that the expression of PI3K/Akt/mTOR pathway protein was increased in the model group, while its expression was decreased after treatment. CONCLUSIONS Polaprezinc has a significant therapeutic effect on RE in rats, which can reduce the levels of IL-8 and PGE2 and downregulate the expression of PI3K/Akt/mTOR signal pathway protein. The efficacy of polaprezinc in the treatment of reflux esophagitis is comparable to that of PPI, and the combination of them is more effective in the reflux esophagitis treatment.
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Affiliation(s)
- Wenbo Xie
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130000, China
| | - Lu An
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130000, China
| | - Zhaoyang Liu
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xindi Wang
- Liaoning University of Traditional Chinese Medicine, Shenyang, 110000, Liaoning Province, China
| | - Xueqi Fu
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130000, China
| | - Junfeng Ma
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130000, China.
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Lang CCJ, Lloyd M, Alyacoubi S, Rahman S, Pickering O, Underwood T, Breininger SP. The Use of miRNAs in Predicting Response to Neoadjuvant Therapy in Oesophageal Cancer. Cancers (Basel) 2022; 14:1171. [PMID: 35267476 PMCID: PMC8909542 DOI: 10.3390/cancers14051171] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 02/18/2022] [Accepted: 02/21/2022] [Indexed: 12/12/2022] Open
Abstract
Oesophageal cancer (OC) is the ninth most common cancer worldwide. Patients receive neoadjuvant therapy (NAT) as standard of care, but less than 20% of patients with oesophageal adenocarcinoma (OAC) or a third of oesophageal squamous cell carcinoma (OSCC) patients, obtain a clinically meaningful response. Developing a method of determining a patient's response to NAT before treatment will allow rational treatment decisions to be made, thus improving patient outcome and quality of life. (1) Background: To determine the use and accuracy of microRNAs as biomarkers of response to NAT in patients with OAC or OSCC. (2) Methods: MEDLINE, EMBASE, Web of Science and the Cochrane library were searched to identify studies investigating microRNAs in treatment naïve biopsies to predict response to NAT in OC patients. (3) Results: A panel of 20 microRNAs were identified as predictors of good or poor response to NAT, from 15 studies. Specifically, miR-99b, miR-451 and miR-505 showed the strongest ability to predict response in OAC patients along with miR-193b in OSCC patients. (4) Conclusions: MicroRNAs are valuable biomarkers of response to NAT in OC. Research is needed to understand the effects different types of chemotherapy and chemoradiotherapy have on the predictive value of microRNAs; studies also require greater standardization in how response is defined.
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Affiliation(s)
| | | | | | | | | | | | - Stella P. Breininger
- Cancer Research UK Center, Faculty of Medicine, School of Cancer Science, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK; (C.C.J.L.); (M.L.); (S.A.); (S.R.); (O.P.); (T.U.)
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7
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Schmidt M, Hackett RJ, Baker AM, McDonald SAC, Quante M, Graham TA. Evolutionary dynamics in Barrett oesophagus: implications for surveillance, risk stratification and therapy. Nat Rev Gastroenterol Hepatol 2022; 19:95-111. [PMID: 34728819 DOI: 10.1038/s41575-021-00531-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/24/2021] [Indexed: 12/13/2022]
Abstract
Cancer development is a dynamic evolutionary process characterized by marked intratumoural heterogeneity at the genetic, epigenetic and phenotypic levels. Barrett oesophagus, the pre-malignant condition to oesophageal adenocarcinoma (EAC), is an exemplary system to longitudinally study the evolution of malignancy. Evidence has emerged of Barrett oesophagus lesions pre-programmed for progression to EAC many years before clinical detection, indicating a considerable window for therapeutic intervention. In this Review, we explore the mechanisms underlying clonal expansion and contraction that establish the Barrett oesophagus clonal mosaicism over time and space and discuss intrinsic genotypic and extrinsic environmental drivers that direct the evolutionary trajectory of Barrett oesophagus towards a malignant phenotype. We propose that understanding and exploiting the evolutionary dynamics of Barrett oesophagus will identify novel therapeutic targets, improve prognostic tools and offer the opportunity for personalized surveillance programmes geared to prevent progression to EAC.
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Affiliation(s)
- Melissa Schmidt
- Evolution and Cancer Laboratory, Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany
| | - Richard J Hackett
- Clonal Dynamics in Epithelia Group; Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Ann-Marie Baker
- Evolution and Cancer Laboratory, Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Stuart A C McDonald
- Clonal Dynamics in Epithelia Group; Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Michael Quante
- Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany
- Department of Medicine II, Universitaetsklinikum Freiburg, Freiburg, Germany
| | - Trevor A Graham
- Evolution and Cancer Laboratory, Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
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Novel In Vivo Mouse Cryoablation Model to Explore Unique Therapeutic Approaches for Premalignant Columnar Lesions. Methods Protoc 2021; 4:mps4010006. [PMID: 33526760 PMCID: PMC7838933 DOI: 10.3390/mps4010006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 12/29/2020] [Accepted: 12/30/2020] [Indexed: 11/16/2022] Open
Abstract
Patients with epithelial metaplasias have an increased risk of developing malignancies. In Barrett’s esophagus, neo-columnar epithelium develops proximal to the squamous-columnar junction (SCJ) in the esophagus as the result of prolonged exposure to bile and acid reflux. Patients require lifetime periodic surveillance, due to lack of effective eradication therapies. The shortage of innovative treatment options is mostly attributable to the paucity of adequate in vivo models of neo-columnar epithelium regeneration. This protocol describes the generation of a cryoablation model to study regeneration of neo-epithelia at the SCJ. Cryoablation of the columnar and squamous mucosa at the SCJ was achieved through local application of liquid N2O in wild-type and reporter mice in combination with acid suppression. Acid suppression alone, showed restoration of the SCJ with normal histological features of both the neo-columnar and neo-squamous epithelium within 14 days. As a proof of principle, mice were treated with mNoggin, an inhibitor of bone morphogenetic proteins (BMPs), which are involved in the development of columnar epithelia. Local application of mNoggin to the ablated area at the SCJ significantly reduced the development of the neo-columnar mucosa. Although this model does not faithfully recapitulate the exact characteristics of Barrett’s esophagus, it is a well-suited tool to study the mechanisms of therapeutic inhibition of neo-columnar regeneration. It therefore represents an efficient and easy platform to test novel pharmacological therapies for treatment of neo-epithelial lesions at the SCJ.
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Correia ACP, Calpe S, Mostafavi N, Hoefnagel SJM, Sancho-Serra MDC, de Koning PS, Krishnadath KK. Detection of circulating BMP5 as a risk factor for Barrett's esophagus. Sci Rep 2020; 10:15579. [PMID: 32968094 PMCID: PMC7511298 DOI: 10.1038/s41598-020-70760-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Accepted: 06/08/2020] [Indexed: 12/11/2022] Open
Abstract
Barrett's esophagus (BE) predisposes for the malignant condition of esophageal adenocarcinoma (EAC). Since BE patients have few or no symptoms, most of these patients are not identified and not included in surveillance programs. These BE patients are at risk of developing advanced-stage EAC. At present, non-invasive tests to identify BE patients from the general population are lacking. We and others showed that Bone Morphogenetic Protein 4 (BMP4), and other BMPs are upregulated in BE. We aimed to determine if circulating BMPs can be identified and used as blood biomarkers to identify BE patients at high risk in the general population. In this study, we could detect the different BMPs in the blood of 112 BE patients and 134 age- and sex-matched controls. Concentration levels of BMP2, BMP4, and BMP5 were elevated in BE patients, with BMP2 and BMP5 significantly increased. BMP5 remained significant after multivariate analysis and was associated with an increased risk for BE with an OR of 1.49 (p value 0.01). Per log (pg/mL) of BMP5, the odds of having BE increased by 50%. Future optimization and validation studies might be needed to prove its utility as a non-invasive method for the detection of BE in high-risk populations and screening programs.
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Affiliation(s)
- Ana C P Correia
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Center, Location AMC, Amsterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands
| | - Silvia Calpe
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Center, Location AMC, Amsterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands
| | - Nahid Mostafavi
- Department of Gastroenterology and Hepatology, Subdivision Statistics, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands
| | - Sanne Johanna Maria Hoefnagel
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Center, Location AMC, Amsterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands
| | - Maria Del Carmen Sancho-Serra
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Center, Location AMC, Amsterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands.,Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
| | - Patricia S de Koning
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands
| | - Kausilia K Krishnadath
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Center, Location AMC, Amsterdam, The Netherlands. .,Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands.
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Establishing spectrochemical changes in the natural history of oesophageal adenocarcinoma from tissue Raman mapping analysis. Anal Bioanal Chem 2020; 412:4077-4087. [PMID: 32333079 PMCID: PMC7320044 DOI: 10.1007/s00216-020-02637-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 03/26/2020] [Accepted: 04/02/2020] [Indexed: 12/17/2022]
Abstract
Raman spectroscopy is a fast and sensitive technique able to identify molecular changes in biological specimens. Herein, we report on three cases where Raman microspectroscopy was used to distinguish normal vs. oesophageal adenocarcinoma (OAC) (case 1) and Barrett’s oesophagus vs. OAC (cases 2 and 3) in a non-destructive and highly accurate fashion. Normal and OAC tissues were discriminated using principal component analysis plus linear discriminant analysis (PCA-LDA) with 97% accuracy (94% sensitivity and 100% specificity) (case 1); Barrett’s oesophagus vs. OAC tissues were discriminated with accuracies ranging from 98 to 100% (97–100% sensitivity and 100% specificity). Spectral markers responsible for class differentiation were obtained through the difference-between-mean spectrum for each group and the PCA loadings, where C–O–C skeletal mode in β-glucose (900 cm−1), lipids (967 cm−1), phosphodioxy (1296 cm−1), deoxyribose (1456 cm−1) and collagen (1445, 1665 cm−1) were associated with normal and OAC tissue differences. Phenylalanine (1003 cm−1), proline/collagen (1066, 1445 cm−1), phospholipids (1130 cm−1), CH2 angular deformation (1295 cm−1), disaccharides (1462 cm−1) and proteins (amide I, 1672/5 cm−1) were associated with Barrett’s oesophagus and OAC tissue differences. These findings show the potential of using Raman microspectroscopy imaging for fast and accurate diagnoses of oesophageal pathologies and establishing subtle molecular changes predisposing to adenocarcinoma in a clinical setting.
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Mor A, Kobus K, Leszczyńska U, Reszeć J. Differentiating dysplasia markers in Barrette sophagus and adenocarcinoma. POSTEP HIG MED DOSW 2019. [DOI: 10.5604/01.3001.0013.5643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Barrett’s esophagus (BE) is the only known precursor of esophageal adenocarcinoma (EAC). This precancerous lesion can transform into low-grade and high-grade dysplasia, which may develop in the EAC. Therefore, the issues of dysplasia detection and monitoring and early diagnostics for the presence of EAC foci are extremely important factors in the surveillance of patients with BE progression. Histopathological examinations are regarded as the gold standard in the BE progression evaluation. They posses a large clinical utility in the identification of dysplasia and cancer risk stratification in patients with the BE. However, this method is a very subjective, and is heavily dependent on the knowledge and experience of the person conducting it. Therefore, it seems to be important to implement in the BE progression diagnostics sensitive and specific biomarkers that could be used as complementary tests. They could improve detection, stratification and monitoring of the progression of BE and the detection of the EAC early stages. Literature data concerning markers distinguishing between different stages of Barrett’s-related dysplasia and cancer is very scarce. In this article there we collected and characterized the most important data. Apart from this, there is a fairly large group of proteins and genes. Their expression levels allow for the detection of changes during the development of the BE progression. No studies have been carried out yet for their usefulness in differentiating between types of BE-related dysplasia and EAC, but we know that some of them could be useful as auxiliary markers differentiating between different stages of dysplasia and EAC. The article discusses those with the greatest potential.
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Affiliation(s)
- Adrian Mor
- Zakład Patomorfologii Lekarskiej Uniwersytetu Medycznego w Białymstoku, Białystok, Polska
| | - Krzysztof Kobus
- Samodzielny Publiczny Zakład Opieki Zdrowotnej w Sokółce, Oddział Chirurgii, Sokółka, Polska
| | - Urszula Leszczyńska
- Zakład Patomorfologii Lekarskiej Uniwersytetu Medycznego w Białymstoku, Białystok, Polska
| | - Joanna Reszeć
- Zakład Patomorfologii Lekarskiej Uniwersytetu Medycznego w Białymstoku, Białystok, Polska
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Ge Y, Westphalen CB, Ma WW, Vega KJ, Weygant N. Implications for Tumor Microenvironment and Epithelial Crosstalk in the Management of Gastrointestinal Cancers. JOURNAL OF ONCOLOGY 2019; 2019:4835318. [PMID: 32082375 PMCID: PMC7012231 DOI: 10.1155/2019/4835318] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 09/23/2019] [Accepted: 10/12/2019] [Indexed: 02/08/2023]
Abstract
Rapid advances in technology are revealing previously unknown organization, cooperation, and limitations within the population of nontumor cells surrounding the tumor epithelium known as the tumor microenvironment (TME). Nowhere are these findings more pertinent than in the gastrointestinal (GI) tract where exquisite cell specialization supports a complex microenvironmental niche characterized by rapid stemness-associated cell turnover, pathogen sensing, epithelial orchestration of immune signaling, and other facets that maintain the complex balance between homeostasis, inflammation, and disease. Here, we summarize and discuss select emerging concepts in the precancerous microenvironment, TME, and tumor epithelial-TME crosstalk as well as their implications for the management of GI cancers.
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Affiliation(s)
- Yang Ge
- Dept of Oncology, Beijing Chao-Yang Hospital, Capital Medical Univ., Beijing, China
| | | | - Wen Wee Ma
- Dept of Oncology, Mayo Clinic, Minneapolis, MN, USA
| | - Kenneth J. Vega
- Dept of Gastroenterology, Augusta University, Augusta, GA, USA
| | - Nathaniel Weygant
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, China
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Deng Y, Pan L, Qian W. Associations between the severity of reflux esophagitis in children and changes in oxidative stress, serum inflammation, vasoactive intestinal peptide and motilin. Exp Ther Med 2019; 18:3509-3513. [PMID: 31602227 PMCID: PMC6777312 DOI: 10.3892/etm.2019.7978] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 06/13/2019] [Indexed: 12/25/2022] Open
Abstract
Changes in the levels of serum oxidative stress indexes, gastrointestinal hormones and inflammatory factors in children with different severity of reflux esophagitis (RE) were detected. Sixty child patients diagnosed with gastroesophageal reflux disease (GERD) via gastroscopy were selected and divided into non-erosive reflux disease group (NERD group, n=12) and RE group (n=48) according to whether there was esophageal mucosal injury. In RE group, the patients were further divided into grade I RE group (n=15), grade II RE group (n=18) and grade III RE group (n=15) based on the severity of mucosal injury. None of the child patients took PPI and domperidone within 2 weeks before enrollment. The content of malondialdehyde (MDA) and total superoxide dismutase (T-SOD) in the esophageal mucosa was detected. The changes in the levels of serum vasoactive intestinal peptide (VIP), motilin, interleukin-1β (IL-1β), IL-8 and tumor necrosis factor-α (TNF-α) were determined. The DeMeester score was the highest in grade III RE group, followed by grade II RE group, grade I RE group and NERD group (P<0.05). The content of MDA in the esophageal mucosa was higher in RE group than that in NERD group, and the T-SOD activity declined with the increased severity of injury (P<0.05). In the three RE groups, the level of plasma VIP was significantly higher, while the motilin level was remarkably lower than those in NERD group (P<0.05). With the increased severity of disease, the expression levels of serum IL-1β, IL-8 and TNF-α in RE group were gradually raised (P<0.05). RE patients have strong oxidative stress and inflammatory response, an increased level of serum VIP, a regulator of gastrointestinal motility, and a decreased level of motilin. Controlling the changes in the above factors using effective treatment means can improve the development of GERD.
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Affiliation(s)
- Yingqin Deng
- Department of Pediatrics, Changzhou Jintan District People's Hospital, Changzhou, Jiangsu 213200, P.R. China
| | - Li Pan
- Department of Pediatrics, Changzhou Jintan District People's Hospital, Changzhou, Jiangsu 213200, P.R. China
| | - Wenjie Qian
- Department of Pediatrics, Changzhou Jintan District People's Hospital, Changzhou, Jiangsu 213200, P.R. China
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14
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Wallner B, Björ O, Andreasson A, Vieth M, Schmidt PT, Hellström PM, Forsberg A, Talley NJ, Agreus L. Z-line alterations and gastroesophageal reflux: an endoscopic population-based prospective cohort study. Scand J Gastroenterol 2019; 54:1065-1069. [PMID: 31453726 DOI: 10.1080/00365521.2019.1656775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background and study aims: Barrett's esophagus is a premalignant condition in the distal esophagus associated with esophageal adenocarcinoma. Since gastroesophageal reflux is known to be of etiological importance in both Barrett's esophagus and esophageal adenocarcinoma, we aimed to study which endoscopic alterations at the Z-line can be attributed to a previous history of reflux symptoms. Patients and methods: From 1988, a population cohort in Sweden has been prospectively studied regarding gastrointestinal symptoms, using a validated questionnaire. In 2012, the population was invited to undergo a gastroscopy and participate in the present study. In order to determine which endoscopic alterations that can be attributed to a previous history of gastroesophageal reflux, three different endoscopic definitions of columnar-lined esophagus (CLE) were used: (1) ZAP I, An irregular Z-line with a suspicion of tongue-like protrusions; (2) ZAP II/III, Distinct, obvious tongues of metaplastic columnar epithelium; (3) CLE ≥1 cm, The Prague C/M-classification with a minimum length of 1 cm. Results: A total of 165 community subjects were included in the study. Of these, 40 had CLE ≥ 1 cm, 99 had ZAP I, and 26 had ZAP II/III. ZAP II/III was associated with an over threefold risk of previous GER symptoms (OR: 3.60, CI: 1.49-8.70). No association was found between gastroesophageal reflux and ZAP I (OR: 2.06, CI: 0.85-5.00), or CLE ≥1 cm (OR: 1.64, CI: 0.77-3.49). Conclusions: In a general community, the only endoscopic alteration to the Z-line definitely linked to longstanding GER symptoms was the presence of obvious tongues of metaplastic columnar epithelium (ZAP II/III).
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Affiliation(s)
- Bengt Wallner
- Department of Surgical and Perioperative Sciences, Umeå University , Surgery , Sweden
| | - Ove Björ
- Department of Radiation Science, Oncology, Umeå University , Umeå , Sweden
| | - Anna Andreasson
- Department of Medicine Solna, Karolinska Institutet , Stockholm , Sweden.,Stress Research Institute, Stockholm University , Stockholm , Sweden
| | | | - Peter T Schmidt
- Department of Medicine Solna, Karolinska Institutet , Stockholm , Sweden
| | - Per M Hellström
- Department of Medical Sciences, Uppsala University , Uppsala , Sweden
| | - Anna Forsberg
- Department of Medicine Solna, Karolinska Institutet , Stockholm , Sweden
| | - Nicholas J Talley
- Faculty of Medicine, University of Newcastle , Newcastle , Australia
| | - Lars Agreus
- Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet , Stockholm , Sweden
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15
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Münch NS, Fang HY, Ingermann J, Maurer HC, Anand A, Kellner V, Sahm V, Wiethaler M, Baumeister T, Wein F, Einwächter H, Bolze F, Klingenspor M, Haller D, Kavanagh M, Lysaght J, Friedman R, Dannenberg AJ, Pollak M, Holt PR, Muthupalani S, Fox JG, Whary MT, Lee Y, Ren TY, Elliot R, Fitzgerald R, Steiger K, Schmid RM, Wang TC, Quante M. High-Fat Diet Accelerates Carcinogenesis in a Mouse Model of Barrett's Esophagus via Interleukin 8 and Alterations to the Gut Microbiome. Gastroenterology 2019; 157:492-506.e2. [PMID: 30998992 PMCID: PMC6662596 DOI: 10.1053/j.gastro.2019.04.013] [Citation(s) in RCA: 104] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 04/03/2019] [Accepted: 04/06/2019] [Indexed: 01/10/2023]
Abstract
BACKGROUND & AIMS Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Progression from BE to cancer is associated with obesity, possibly due to increased abdominal pressure and gastroesophageal reflux disease, although this pathogenic mechanism has not been proven. We investigated whether environmental or dietary factors associated with obesity contribute to the progression of BE to EAC in mice. METHODS Tg(ED-L2-IL1RN/IL1B)#Tcw mice (a model of BE, called L2-IL1B mice) were fed a chow (control) or high-fat diet (HFD) or were crossbred with mice that express human interleukin (IL) 8 (L2-IL1B/IL8 mice). Esophageal tissues were collected and analyzed for gene expression profiles and by quantitative polymerase chain reaction, immunohistochemistry, and flow cytometry. Organoids were established from BE tissue of mice and cultured with serum from lean or obese individuals or with neutrophils from L2-IL1B mice. Feces from mice were analyzed by 16s ribosomal RNA sequencing and compared to 16s sequencing data from patients with dysplasia or BE. L2-IL1B were mice raised in germ-free conditions. RESULTS L2-IL1B mice fed an HFD developed esophageal dysplasia and tumors more rapidly than mice fed the control diet; the speed of tumor development was independent of body weight. The acceleration of dysplasia by the HFD in the L2-IL1B mice was associated with a shift in the gut microbiota and an increased ratio of neutrophils to natural killer cells in esophageal tissues compared with mice fed a control diet. We observed similar differences in the microbiomes from patients with BE that progressed to EAC vs patients with BE that did not develop into cancer. Tissues from dysplasias of L2-IL1B mice fed the HFD contained increased levels of cytokines that are produced in response to CXCL1 (the functional mouse homolog of IL8, also called KC). Serum from obese patients caused organoids from L2-IL1B/IL8 mice to produce IL8. BE tissues from L2-IL1B mice fed the HFD and from L2-IL1B/IL8 mice contained increased numbers of myeloid cells and cells expressing Cxcr2 and Lgr5 messenger RNAs (epithelial progenitors) compared with mice fed control diets. BE tissues from L2-IL1B mice raised in germ-free housing had fewer progenitor cells and developed less dysplasia than in L2-IL1 mice raised under standard conditions; exposure of fecal microbiota from L2-IL1B mice fed the HFD to L2-IL1B mice fed the control diet accelerated tumor development. CONCLUSIONS In a mouse model of BE, we found that an HFD promoted dysplasia by altering the esophageal microenvironment and gut microbiome, thereby inducing inflammation and stem cell expansion, independent of obesity.
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Affiliation(s)
- Natasha Stephens Münch
- Department of Internal Medicine, Technical University of Munich, Germany,Chair of Molecular Nutritional Medicine, Technical University of Munich, Germany
| | - Hsin-Yu Fang
- Department of Internal Medicine, Technical University of Munich, Germany
| | - Jonas Ingermann
- Department of Internal Medicine, Technical University of Munich, Germany,Chair of Molecular Nutritional Medicine, Technical University of Munich, Germany
| | - H. Carlo Maurer
- Department of Internal Medicine, Technical University of Munich, Germany,Irvine Cancer Research Center, Columbia University, New York, USA
| | - Akanksha Anand
- Department of Internal Medicine, Technical University of Munich, Germany
| | - Victoria Kellner
- Department of Internal Medicine, Technical University of Munich, Germany
| | - Vincenz Sahm
- Department of Internal Medicine, Technical University of Munich, Germany
| | - Maria Wiethaler
- Department of Internal Medicine, Technical University of Munich, Germany
| | - Theresa Baumeister
- Department of Internal Medicine, Technical University of Munich, Germany
| | - Frederik Wein
- Department of Internal Medicine, Technical University of Munich, Germany
| | - Henrik Einwächter
- Department of Internal Medicine, Technical University of Munich, Germany
| | - Florian Bolze
- Chair of Molecular Nutritional Medicine, Technical University of Munich, Germany,EKFZ – Else Kröner-Fresenius Center for Nutritional Medicine, Technical University of Munich, Germany,ZIEL – Institute of Food & Health, Technical University of Munich, Germany
| | - Martin Klingenspor
- Chair of Molecular Nutritional Medicine, Technical University of Munich, Germany,EKFZ – Else Kröner-Fresenius Center for Nutritional Medicine, Technical University of Munich, Germany,ZIEL – Institute of Food & Health, Technical University of Munich, Germany
| | - Dirk Haller
- Chair of Nutrition and Immunology; Technical University of Munich, Germany
| | - Maria Kavanagh
- Department of Surgery, Trinity Translational Medicine Institute, Trinity College Dublin, Ireland
| | - Joanne Lysaght
- Department of Surgery, Trinity Translational Medicine Institute, Trinity College Dublin, Ireland
| | - Richard Friedman
- Irvine Cancer Research Center, Columbia University, New York, USA
| | | | | | | | | | - James G. Fox
- Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Mark T. Whary
- Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Yoomi Lee
- Irvine Cancer Research Center, Columbia University, New York, USA
| | - Tony Y. Ren
- Irvine Cancer Research Center, Columbia University, New York, USA
| | | | | | - Katja Steiger
- Institute of Pathology, Technical University of Munich, Germany
| | - Roland M. Schmid
- Department of Internal Medicine, Technical University of Munich, Germany
| | - Timothy C. Wang
- Irvine Cancer Research Center, Columbia University, New York, USA
| | - Michael Quante
- Department of Internal Medicine, Technical University of Munich, Germany.
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16
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Abstract
The cost-effectiveness of screening and surveillance for Barrett's esophagus continues to evolve as the incidence of esophageal adenocarcinoma increases, biomarkers enhance the identification of individuals at highest risk for developing cancer, and endoscopic eradication of Barrett's esophagus improves. Screening to detect Barrett's esophagus may be cost-effective in selected high-risk groups based on age, race, sex and other factors such as symptoms of heartburn. Currently, endoscopic eradication therapy for Barrett's esophagus and high-grade dysplasia is a cost-effective intervention, while endoscopic therapy for non-dysplastic Barrett's esophagus is not a cost-effective strategy. As diagnosis of low-grade dysplasia improves, endoscopic eradication therapy may also prove to be a cost-effective intervention.
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Affiliation(s)
- John M Inadomi
- Division of Gastroenterology, Department of Medicine, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356424, Seattle, WA, 98195, USA.
| | - Nina Saxena
- Division of Gastroenterology, Department of Medicine, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356424, Seattle, WA, 98195, USA
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17
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Abstract
Oesophageal cancer remains one of the least explored malignancies. However, in recent years its increasing incidence and poor prognosis have stimulated interest from the cancer community to understand the pathways to the initiation and progression of the disease. Critical understanding of the molecular processes controlling changes in stem cell fate and the cross-talk with their adjacent stromal neighbours will provide essential knowledge on the mechanisms that go awry in oesophageal carcinogenesis. Advances in lineage tracing techniques have represented a powerful tool to start understanding changes in oesophageal cell behaviour in response to mutations and mutagens that favour tumour development. Environmental cues constitute an important factor in the aetiology of oesophageal cancer. The oesophageal epithelium is a tissue exposed to harsh conditions that not only damage the DNA of epithelial cells but also result in an active stromal reaction, promoting tumour progression. Ultimately, cancer represents a complex interplay between malignant cells and their microenvironment. Indeed, increasing evidence suggests that the accumulation of somatic mutations is not the sole cause of cancer. Instead, non-cell autonomous components, coming from the stroma, can significantly contribute from the earliest stages of tumour formation. The realisation that stromal cells play an important role in cancer has transformed this cellular compartment into an attractive and emerging field of research. It is becoming increasingly clear that the tumour microenvironment provides unique opportunities to identify early diagnostic and prognostic markers, as well as potential therapeutic strategies that may synergise with those targeting tumour cells. This chapter compiles recent observations on oesophageal epithelial stem cell biology, and how environmental and micro-environmental changes may lead to oesophageal disease and cancer.
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Affiliation(s)
- Maria P Alcolea
- Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Tennis Court Road, CB2 1QR, Cambridge, UK
- Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Hills Road, CB2 0XZ, Cambridge, UK
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18
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Faqih A, Broman KK, Huang LC, Phillips SE, Holzman MD, Pierce RA, Poulose BK, Yachimski PS. Frequency of endoscopic surveillance for Barrett's esophagus is influenced by health insurance status: results from a population-based analysis. Dis Esophagus 2017; 30:1-8. [PMID: 28881902 DOI: 10.1093/dote/dox080] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Indexed: 12/11/2022]
Abstract
Factors that influence the frequency of surveillance endoscopy for nondysplastic Barrett's esophagus are not well understood. The objective of this study is to assess factors which influence the frequency of endoscopic surveillance for Barrett's esophagus, including health insurance/third-party payer status. Cases of nondysplastic Barrett's esophagus undergoing esophagogastroduodenoscopy with biopsy were identified using longitudinal data from the Healthcare Utilization Project database in 2005-2006 and followed through 2011. The threshold for appropriate surveillance utilization was defined as two to four surveillance esophagogastroduodenoscopies over a standardized 5-year period. Patients' insurance status was designated as either Medicare, Medicaid, private, or noninsured. 36,676 cases of nondysplastic Barrett's esophagus were identified. Among these, 4,632 patients (12.6%) underwent between two and four surveillance esophagogastroduodenoscopies in 5 years of follow-up versus 31,975 patients (87.3%) who underwent fewer than two esophagogastroduodenoscopies during follow-up. Multivariate analysis found that Barrett's patients insured through Medicaid (OR 1.273; 95% CI = 1.065-1.522) or without insurance (OR = 2.453; 95% CI = 1.67-3.603) were at increased likelihood of being under-surveilled. This study identified a difference in frequency of surveillance esophagogastroduodenoscopy for Barrett's esophagus by payer status. Patients without health insurance and those whose primary insurance was Medicaid were at increased odds for under-surveillance. These data suggest that a more robust system for tracking and ensuring longitudinal follow-up of patients with Barrett's esophagus, with attention to the uninsured and underinsured population, may be needed to ensure optimal surveillance.
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Affiliation(s)
- A Faqih
- Department of Surgery.,Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | | | | | | | | | | | | | - P S Yachimski
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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19
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Abstract
Oesophageal cancer is the sixth most common cause of cancer-related death worldwide and is therefore a major global health challenge. The two major subtypes of oesophageal cancer are oesophageal squamous cell carcinoma (OSCC) and oesophageal adenocarcinoma (OAC), which are epidemiologically and biologically distinct. OSCC accounts for 90% of all cases of oesophageal cancer globally and is highly prevalent in the East, East Africa and South America. OAC is more common in developed countries than in developing countries. Preneoplastic lesions are identifiable for both OSCC and OAC; these are frequently amenable to endoscopic ablative therapies. Most patients with oesophageal cancer require extensive treatment, including chemotherapy, chemoradiotherapy and/or surgical resection. Patients with advanced or metastatic oesophageal cancer are treated with palliative chemotherapy; those who are human epidermal growth factor receptor 2 (HER2)-positive may also benefit from trastuzumab treatment. Immuno-oncology therapies have also shown promising early results in OSCC and OAC. In this Primer, we review state-of-the-art knowledge on the biology and treatment of oesophageal cancer, including screening, endoscopic ablative therapies and emerging molecular targets, and we discuss best practices in chemotherapy, chemoradiotherapy, surgery and the maintenance of patient quality of life.
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Affiliation(s)
- Elizabeth C. Smyth
- Department of Gastrointestinal Oncology, Royal Marsden Hospital, London & Sutton. United Kingdom
| | - Jesper Lagergren
- Division of Cancer Studies, King's College London, United Kingdom
- Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden
| | | | - Florian Lordick
- University Cancer Center Leipzig, University Medicine Leipzig, Leipzig, Germany
| | - Manish A. Shah
- Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York-Presbyterian Hospital, New York. United States
| | - Pernilla Lagergren
- Surgical care science, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden
| | - David Cunningham
- Department of Gastrointestinal Oncology, Royal Marsden Hospital, London & Sutton. United Kingdom
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20
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Saxena N, Inadomi JM. Effectiveness and Cost-Effectiveness of Endoscopic Screening and Surveillance. Gastrointest Endosc Clin N Am 2017; 27:397-421. [PMID: 28577764 DOI: 10.1016/j.giec.2017.02.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Guidelines for the screening and surveillance of Barrett's esophagus continue to evolve as the incidence of esophageal adenocarcinoma increases, identification of individuals at highest risk for cancer improves, and management of dysplasia evolves. This article reviews related studies and economic analyses. Advances in diagnosis offer promising strategies to help focus screening efforts on those individuals who are most likely to develop esophageal adenocarcinoma.
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Affiliation(s)
- Nina Saxena
- Division of Gastroenterology, Department of Medicine, University of Washington School of Medicine, 1959 Northeast Pacific Street, Box 356424, Seattle, WA 98195, USA
| | - John M Inadomi
- Division of Gastroenterology, Department of Medicine, University of Washington School of Medicine, 1959 Northeast Pacific Street, Box 356424, Seattle, WA 98195, USA.
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21
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Thota PN, Arora Z, Benjamin T, Pagadala M, Lopez R, Sanaka MR. Influence of body mass index on the prevalence and progression of dysplasia in Barrett's esophagus: a retrospective analysis (.). Scand J Gastroenterol 2016; 51:1288-93. [PMID: 27460942 DOI: 10.1080/00365521.2016.1208271] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE High body mass index (BMI) is a risk factor for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Our aim was to determine if prevalence of dysplasia in BE varies by BMI and study the effect of BMI on progression to high-grade dysplasia (HGD) or EAC. MATERIALS AND METHODS This is a retrospective review of patients with endoscopic evidence of BE confirmed by presence of intestinal metaplasia on histology from January 2000 to December 2012 at Cleveland Clinic. Patient demographics, BMI and endoscopic findings such as length of BE, dysplasia in BE and size of hiatal hernia were reviewed. Dysplasia was classified as no dysplasia (NDBE), low-grade dysplasia (LGD), HGD and EAC. RESULTS In this cohort of 1239 patients, average BMI was 29.8 ± 6 kg/m(2). There were 228 (18.4%) in group with BMI <25, 236 (19%) in BMI group 25-27.4, 262 (21.1%) in BMI 27.5-29.9, 303 (24.5%) in BMI 30-34.9, 126 (10.2%) in BMI 35-39.9 and 86 (6.8%) in BMI ≥40. Lower BMI groups had lower prevalence of dysplasia while higher BMI groups had higher prevalence of dysplasia (p = 0.002). During mean follow up of 31.6 ± 26 months, there were 14 cases of HGD/EAC in NDBE group and 29 cases of HGD/EAC in LGD group. BMI or BMI change was not associated with progression to HGD/EAC in NDBE. CONCLUSIONS High BMI was associated with higher prevalence of dysplasia in BE. But once in a surveillance program, higher BMI is not associated with progression of dysplasia in NDBE.
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Affiliation(s)
- Prashanthi Nagavenkata Thota
- a Center of Excellence for Barrett's Esophagus, Digestive Disease Institute, Cleveland Clinic , Cleveland , OH , USA
| | - Zubin Arora
- a Center of Excellence for Barrett's Esophagus, Digestive Disease Institute, Cleveland Clinic , Cleveland , OH , USA
| | - Tanmayee Benjamin
- a Center of Excellence for Barrett's Esophagus, Digestive Disease Institute, Cleveland Clinic , Cleveland , OH , USA
| | - Mangesh Pagadala
- a Center of Excellence for Barrett's Esophagus, Digestive Disease Institute, Cleveland Clinic , Cleveland , OH , USA
| | - Rocio Lopez
- b Department of Biostatistics , JJ North-3, Cleveland Clinic , Cleveland , OH , USA
| | - Madhusudhan Rao Sanaka
- a Center of Excellence for Barrett's Esophagus, Digestive Disease Institute, Cleveland Clinic , Cleveland , OH , USA
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22
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Golger D, Probst A, Messmann H. Barrett's esophagus: lessons from recent clinical trials. Ann Gastroenterol 2016; 29:417-423. [PMID: 27708506 PMCID: PMC5049547 DOI: 10.20524/aog.2016.0070] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2016] [Accepted: 05/17/2016] [Indexed: 12/11/2022] Open
Abstract
Data from recent studies cast doubt on former recommendations on diagnosis and management of Barrett’s esophagus. Based on latest research findings several Gastroenterological Associations actualized their guidelines and international experts compiled consensus statements as practical help for clinicians. In this review we discuss recent trials and their impact on clinical practice, current recommendations and persisting controversies in Barrett’s esophagus.
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Affiliation(s)
- Daniela Golger
- Department of Gastroenterology, Klinikum Augsburg, Germany
| | - Andreas Probst
- Department of Gastroenterology, Klinikum Augsburg, Germany
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23
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Arora Z, Garber A, Thota PN. Risk factors for Barrett's esophagus. J Dig Dis 2016; 17:215-21. [PMID: 26929263 DOI: 10.1111/1751-2980.12332] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Revised: 02/04/2016] [Accepted: 02/17/2016] [Indexed: 12/11/2022]
Abstract
Barrett's esophagus (BE) is a well-recognized precursor of esophageal adenocarcinoma (EAC) and is defined as ≥1 cm segment of salmon-colored mucosa extending above the gastroesophageal junction into the tubular esophagus with biopsy confirmation of metaplastic replacement of the normal squamous epithelium by intestinal-type columnar epithelium. The incidence of both BE and EAC has been increasing over the past few decades. As a result, preventing the development of BE by identifying and understanding its modifiable and non-modifiable risk factors may help reduce the incidence of EAC. Over the recent past, a tremendous amount of progress has been made towards improving our knowledge of risk factors and pathogenesis of BE. This article reviews the evidence for the various risk factors for developing BE.
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Affiliation(s)
- Zubin Arora
- Department of Gastroenterology/Hepatology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Ari Garber
- Department of Gastroenterology/Hepatology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Prashanthi N Thota
- Department of Gastroenterology/Hepatology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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24
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Abstract
Epigastric pain is an extremely common complaint in the emergency department and has an associated broad differential diagnosis. In the differential it is important to consider cardiac causes that may be mistaken for gastrointestinal disorders as well as various serious intra-abdominal causes. This article highlights the limitations in laboratory testing and guides providers through the appropriate considerations for advanced imaging. Special attention is focused on acute pancreatitis, esophageal emergencies, and peptic ulcer disease/gastritis and their associated complications.
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Affiliation(s)
- Patrick Robinson
- Virginia Tech Carilion Emergency Medicine Residency, Department of Emergency Medicine, 1 Riverside Circle, 4th Floor, Roanoke, VA 24016, USA.
| | - John C Perkins
- Virginia Tech Carilion Emergency Medicine Residency, Department of Emergency Medicine, Virginia Tech Carilion School of Medicine, 1 Riverside Circle, 4th Floor, Roanoke, VA 24016, USA
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25
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Sundriyal D, Shirsi N, Kotwal S, Kumar S, Mithran Parthasarthy K, Gupta M. Adenocarcinoma of Cervical Esophagus Arising in the Barrett's Mucosa. Indian J Surg Oncol 2015; 6:127-9. [PMID: 26405420 DOI: 10.1007/s13193-015-0382-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Accepted: 02/03/2015] [Indexed: 01/10/2023] Open
Abstract
Carcinoma of esophagus encompasses mainly two different histopathologic subtypes, squamous cell carcinoma and adenocarcinoma. Adenocarcinoma is the most common cancer seen. It usually arises in association with Barrett's esophagus and is localised in the distal third of the esophagus while squamous cell carcinoma predominates in the middle third. Carcinoma arising in the proximal third (cervical) of the esophagus is almost always squamous in origin. We report a case of adenocarcinoma arising in the cervical esophagus.
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Affiliation(s)
- Deepak Sundriyal
- Department of Medical Oncology, Dharamshila Hospital & Research Centre, Vasundhara Enclave, New Delhi, 110096 India ; 79, Sector 12, Dwarka New Delhi, 110078 India
| | - Nikhil Shirsi
- Department of Medical Oncology, Dharamshila Hospital & Research Centre, New Delhi, India
| | - Sumedha Kotwal
- Department of Pathology, Dharamshila Hospital & Research Centre, New Delhi, India
| | - Sushil Kumar
- Department of Surgical Oncology, Dharamshila Hospital & Research Centre, New Delhi, India
| | - K Mithran Parthasarthy
- Department of Medical Oncology, Dharamshila Hospital & Research Centre, New Delhi, India
| | - Mahesh Gupta
- Gastroenterology, Dharamshila Hospital & Research Centre, New Delhi, India
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26
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Tytgat GNJ. Reflections on esophageal columnar metaplasia (Barrett)-ANNO 2015. J Dig Dis 2015; 16:55-7. [PMID: 25529483 DOI: 10.1111/1751-2980.12224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Esophageal columnar metaplasia (ECM) (Barrett's esophogus) continues to generate clinical and basic attention. Yet many questions remain unanswered and global consensus on important issues is often still lacking. This article discusses a selection of certain recent findings and reflects on some remaining uncertainties of this intriguing disease.
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Inadomi JM. Cost considerations in implementing a screening and surveillance strategy for Barrett's oesophagus. Best Pract Res Clin Gastroenterol 2015; 29:51-63. [PMID: 25743456 DOI: 10.1016/j.bpg.2014.12.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Revised: 11/27/2014] [Accepted: 12/11/2014] [Indexed: 01/31/2023]
Abstract
There is increasing concern over the rising costs of healthcare leading to debate regarding the use of resources to implement preventive strategies. Oesophageal adenocarcinoma and its precursor, Barrett's oesophagus provides an excellent opportunity to highlight this issue since cancer is uncommon even among individuals with documented Barrett's oesophagus. This review provides a brief introduction to economic analysis in healthcare and summarizes published studies of the cost-effectiveness of strategies to reduce mortality from cancer. Current best estimates highlight the cost-effectiveness of endoscopic ablation among patients with Barrett's oesophagus and high-grade dysplasia and the low cost-effectiveness of ablation among patients without dysplasia. The cost-effectiveness of ablation among patients with Barrett's and low-grade dysplasia is poorly defined due to the ambiguity of diagnosing dysplasia, the unknown risk of cancer among patients with low-grade dysplasia, and the uncertain durability of ablation to maintain remission from metaplasia and dysplasia and prevent cancer.
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Affiliation(s)
- John M Inadomi
- Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, United States; Department of Health Services, School of Public Health, University of Washington, United States.
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Gindea C, Birla R, Hoara P, Caragui A, Constantinoiu S. Surveillance in Barrett esophagus. J Med Life 2014; 7 Spec No. 3:61-67. [PMID: 25870698 PMCID: PMC4391418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
The only known precursor of the esophageal adenocarcinoma (EAC) is represented by the Barrett's esophagus (BE). EAC incidence has increased sharply in the last 4 decades. The annual conversion rate of BE to cancer is small but significant; therefore the identification of patients at a higher risk of cancer represents a dilemma. The endoscopic surveillance of BE aims to detect dysplasia and in particular high-grade dysplasia and intramucosal cancers that can be endoscopically treated before progressing to invasive cancer with lymph node metastases. Using standard white light endoscopy (WLE), these high-risk lesions are often subtle and hard to detect. In addition to high-definition standard endoscopy, chromoendoscopy (CE), virtual chromoendoscopy (e.g. narrow band imaging), and confocal laser endomicroscopy might increase the diagnostic efficiency for the detection of dysplastic lesions and can also increase the diagnostic efficiency for the detection of BE dysplasia or cancer. This ability to detect subtle mucosal abnormalities that harbor high-grade dysplasia (HGD) or intramucosal carcinoma might enable endoscopists skilled in the assessment of BE to perform targeted rather than random biopsies. The standard protocol will remain the careful examination by using conventional high-resolution endoscopes, combined with a longer inspection time, which is associated with an increased detection of dysplasia until these modalities have been demonstrated to enhance efficiency or be cost effective. Many of the limitations of the current clinical standard may be overcome in the future by the use of multi-modal imaging combined with molecular information.
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Affiliation(s)
- C Gindea
- "Carol Davila" University of Medicine and Pharmacy, Bucharest; "Sf. Maria" Clinical Hospital, General and Esophageal Surgery Department, Bucharest, Romania
| | - R Birla
- "Carol Davila" University of Medicine and Pharmacy, Bucharest; "Sf. Maria" Clinical Hospital, General and Esophageal Surgery Department, Bucharest, Romania
| | - P Hoara
- "Carol Davila" University of Medicine and Pharmacy, Bucharest; "Sf. Maria" Clinical Hospital, General and Esophageal Surgery Department, Bucharest, Romania
| | - A Caragui
- "Carol Davila" University of Medicine and Pharmacy, Bucharest; "Sf. Maria" Clinical Hospital, General and Esophageal Surgery Department, Bucharest, Romania
| | - S Constantinoiu
- "Carol Davila" University of Medicine and Pharmacy, Bucharest; "Sf. Maria" Clinical Hospital, General and Esophageal Surgery Department, Bucharest, Romania
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