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Lee FJ, Tsai MC, Chen CL, Wong MW, Yen HH, Wu JY, Chung CS, Tseng PH, Tsai YN, Hsieh MT, Chang CY. Increased Prevalence of Barrett's Esophagus in Taiwan: A Prospective Multicenter Study. J Gastroenterol Hepatol 2025. [PMID: 40300615 DOI: 10.1111/jgh.16992] [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: 11/19/2024] [Revised: 02/26/2025] [Accepted: 04/21/2025] [Indexed: 05/01/2025]
Abstract
BACKGROUND AND AIM With rising rates of esophageal adenocarcinoma (EAC) in Western countries, Barrett's esophagus (BE) has become a growing concern. The increasing prevalence of chronic gastroesophageal reflux disease (GERD) in Taiwan suggests a potential rise in BE cases as well. A 2007 large-scale study reported a BE prevalence of 1.06% in Taiwan. Our multicenter prospective study aims to evaluate the current prevalence of BE and identify key risk factors in this region. METHOD We assessed outpatients undergoing upper gastrointestinal endoscopy for various symptoms, obtaining biopsies from endoscopically suspected esophageal metaplasia (ESEM) at least 1 cm above the gastroesophageal junction. Quadrant biopsies were taken every 2 cm, with BE confirmed by histological evidence of specialized intestinal metaplasia. RESULTS Among 8697 subjects, the prevalence of BE was 2.6%. GERD symptoms, erosive esophagitis (EE), and hiatal hernia (HH) were present in 52.5%, 27.3%, and 7.85% of subjects, respectively. Of 751 with ESEM, 228 were diagnosed with BE, predominantly short-segment BE (78.1%). Multivariate analysis identified significant risk factors for BE: age > 50 (OR = 1.59), male gender (OR = 2.27), alcohol consumption (OR = 1.70), GERD symptoms (OR = 1.45), EE (OR = 1.94), and HH (OR = 2.49) (all p < 0.01). CONCLUSION The prevalence of BE was identified as 2.6%, representing a significant increase compared with 2007. Significant risk factors include age more than 50, male gender, alcohol use, GERD symptoms, EE, and HH.
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Affiliation(s)
- Fu-Jen Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei City, Taiwan
- School of Medicine, Fu Jen Catholic University College of Medicine, New Taipei City, Taiwan
| | - Ming-Chang Tsai
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chien-Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
| | - Ming-Wun Wong
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Hsu-Heng Yen
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Jeng-Yih Wu
- Faculty of College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chen-Shuan Chung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Ping-Huei Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ying-Nan Tsai
- Division of Gastroenterology and Hepatology, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Ming-Tsung Hsieh
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chi-Yang Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei City, Taiwan
- School of Medicine, Fu Jen Catholic University College of Medicine, New Taipei City, Taiwan
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Ko MT, Thomas T, Holden E, Beales ILP, Alexandre L. The Association Between Obesity and Malignant Progression of Barrett's Esophagus: A Systematic Review and Dose-Response Meta-Analysis. Clin Gastroenterol Hepatol 2025; 23:726-738.e28. [PMID: 39237080 DOI: 10.1016/j.cgh.2024.07.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 07/09/2024] [Accepted: 07/10/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND AND AIMS Obesity is a risk factor for both Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). However, it is unclear whether obesity drives the malignant progression of BE. We aimed to assess whether obesity is associated with high-grade dysplasia (HGD) or cancer in patients with BE. METHODS We searched MEDLINE and EMBASE from inception through April 2024 for studies reporting the effect of body mass index (BMI) on the progression of nondysplastic BE or low-grade dysplasia (LGD) to HGD or EAC. A 2-stage dose-response meta-analysis was performed to estimate the dose-response relationship between BMI with malignant progression. Study quality was appraised using a modified Newcastle-Ottawa scale. RESULTS Twenty studies reported data on 38,565 patients (74.4% male) in total, of whom 1684 patients were diagnosed with HGD/cancer. Nineteen studies were considered moderate to high quality. Eight cohort studies reported data on 6647 male patients with baseline nondysplastic BE/LGD, of whom 555 progressed to HGD/EAC (pooled annual rate of progression, 0.02%; 95% confidence interval [CI], 0.01%-0.03%), and 1992 female patients with baseline nondysplastic BE/LGD, with 110 progressors (pooled annual rate of progression, 0.01%; 95% CI, 0.01%-0.02%). There was no significant difference in pooled annual rate of progression between males and females (P = .15). Each 5-kg/m2 increase in BMI was associated with a 6% increase in the risk of malignant progression (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001; I2= 0%). CONCLUSION Our meta-analysis provides some evidence that obesity as measured by BMI is associated with malignant progression of BE with a dose-response relationship. This finding requires confirmation in future high-quality cohort studies. Future risk prediction models could incorporate measures of obesity to potentially improve risk stratification in patients with BE. PROSPERO, Number: CRD42017051046.
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Affiliation(s)
- Mie Thu Ko
- Norwich Epidemiology Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Department of Gastroenterology, Norfolk & Norwich University Hospital NHS Foundation Trust, Norwich, United Kingdom
| | - Tom Thomas
- Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom
| | - Emily Holden
- Norwich Epidemiology Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom
| | - Ian L P Beales
- Norwich Epidemiology Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Department of Gastroenterology, Norfolk & Norwich University Hospital NHS Foundation Trust, Norwich, United Kingdom
| | - Leo Alexandre
- Norwich Epidemiology Centre, Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Department of Gastroenterology, Norfolk & Norwich University Hospital NHS Foundation Trust, Norwich, United Kingdom.
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Byrne CJ, Brennan P, Carberry J, Cotton J, Dillon JF. Long-term risk factors for developing Barrett's oesophagus in patients with gastro-oesophageal reflux disease: a longitudinal cohort study. BMJ Open Gastroenterol 2024; 11:e001307. [PMID: 38519048 DOI: 10.1136/bmjgast-2023-001307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 02/25/2024] [Indexed: 03/24/2024] Open
Abstract
BACKGROUND AND AIMS Several characteristics are known to affect the risk of Barrett's oesophagus (BO) in the general population, with symptomatic gastro-oesophageal reflux disease (GORD) being a critical risk factor. In this study, we examined factors that influence BO development in people living with GORD. DESIGN People living with GORD were recruited from an endoscopy unit with lifestyle, medical and prescribing history collected. Logistic regression analysis was undertaken to assess the effects of multiple parameters on the likelihood of developing BO. RESULTS 1197 participants were recruited. Most were Caucasian (n=1188, 99%), had no formal educational qualifications (n=714; 59.6%) and lived with overweight (mean body mass index >25 kg/m2). Many lived in areas of least socioeconomic resource (n=568; 47.4%). 139 (11.6%) had BO at baseline. In adjusted baseline analysis (n=1197), male sex (adjusted OR, aOR 2.04 (95% CI 1.92 to 4.12), p≤0.001), increasing age (aOR 1.03 (95% CI 1.01 to 1.04), p≤0.0001) and proton pump inhibitor use (aOR 3.03 (95% CI 1.80 to 5.13), p≤0.0001) were associated with higher odds of BO. At follow-up (n=363), 22 (6.1%) participants developed BO; male sex (aOR 3.18 (95% CI 1.28 to 7.86), p=0.012), pack-years cigarettes smoked (aOR 1.04 (95% CI 1.00 to 1.08), p=0.046) and increased alcohol intake (aOR 1.02 (95% CI 1.00 to 1.04), p=0.013), were associated with increased odds of BO. CONCLUSION Male sex, pack-years cigarettes smoked, and increasing alcohol intake, were independently associated with increased odds of developing BO over 20-year follow-up. These results align with research linking male sex and smoking with BO and extend this by implicating the potential role of alcohol in developing BO, which may require communication through public health messaging.
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Affiliation(s)
- Christopher J Byrne
- Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
- Directorate of Public Health, NHS Tayside, Dundee, UK
| | - Paul Brennan
- Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
- Department of Gastroenterology, NHS Tayside, Dundee, UK
| | - James Carberry
- Department of Gastroenterology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
| | - James Cotton
- Department of Gastroenterology, NHS Tayside, Dundee, UK
| | - John F Dillon
- Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
- Department of Gastroenterology, NHS Tayside, Dundee, UK
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Li N, Zhang G, Zhang X, Liu Y, Kong Y, Wang M, Ren X. A rapid-floating natural polysaccharide gel-raft with double-effect for the treatment of gastroesophageal reflux disease. Int J Biol Macromol 2024; 261:129667. [PMID: 38272401 DOI: 10.1016/j.ijbiomac.2024.129667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 01/14/2024] [Accepted: 01/20/2024] [Indexed: 01/27/2024]
Abstract
Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal condition characterized by regurgitating stomach contents into the esophagus, causing mucosal damage or erosion. Clinical physical protection treatment mainly relies on the use of floating rafts. Bletilla striata (BS) is widely regarded as the first-choice drug for treating digestive tract injuries in Chinese Medicine. The rapid-floating gel-raft (B-R) was prepared via a one-step swelling method using natural BS polysaccharide and glyceryl monooleate. Panax notoginseng saponins (PNS) were loaded to further prepare P/B-R according to clinical experience. Possessing hydrophobic dense, stratified porous structure and stable rheological properties, an outperforming floating performance of P/B-R was proven compared with Gaviscon® (alginate-antacid formulation) in vitro. In vivo imaging results showed that P/B-R can retain and adhere to the gastric mucosa of rats for up to 90 min, protecting and repairing the mucosa. Besides physical protection in situ, the systemic effects of antioxidant and anti-inflammatory actions for treating GERD were achieved through the intestinal release of PNS. Acid-labile PNS was protected by P/B-R against gastric acid, attaining the desired release and permeability. A significantly effective mucosa injury protective effect of P/B-R was found in ethanol-induced gastric damage model on rats. Moreover, P/B-R exhibits excellent biosafety at the cellular level.
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Affiliation(s)
- Na Li
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Guoqin Zhang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Xueyan Zhang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Yi Liu
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Yan Kong
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Meng Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin 301617, PR China..
| | - Xiaoliang Ren
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
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Sadafi S, Azizi A, Pasdar Y, Shakiba E, Darbandi M. Risk factors for gastroesophageal reflux disease: a population-based study. BMC Gastroenterol 2024; 24:64. [PMID: 38317085 PMCID: PMC10840240 DOI: 10.1186/s12876-024-03143-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 01/21/2024] [Indexed: 02/07/2024] Open
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) in the long term reduces the quality of life, leading to digestive diseases. The present study aims to determine the risk factors for GERD. METHOD This study was conducted on 9,631 adults aged 35-65 years. The demographic characteristics, behavioral habits, nutritional intake, physical activity, anthropometric indices, and GERD data were extracted from the databank related to the Ravansar non-communicable diseases (RaNCD). Statistical analysis was performed using logistic regression models. RESULTS The prevalence of GERD was 10.99% (n = 1,058). The GERD was higher among older age and women. After adjusting for age and sex, the odds of GERD among current smokers was 23% higher than non-smokers. Drinking increased odds of GERD (OR: 1.51; 95% CI: 1.13, 1.99). The odds of GERD among depressed individuals were 46% higher than non-depressed. In addition, a significant relationship was observed between the high intake of sweets and desserts with increased GERD (OR: 1.02, 95% CI: 1.01, 1.03). Further, high intake of fiber (OR: 0.98, 95% CI: 0.97, 0.99) and dairy (OR: 0.99, 95% CI: 0.98, 0.99) was related to reducing the odds of GERD. Furthermore, a significant relationship was reported between the waist hip ratio (WHR) and visceral fat area (VFA) with increased odds of GERD. Finally, the physical activity level was inversely related to GERD. CONCLUSION Based on the results, smoking, alcohol, inactivity, high intake of sweets and desserts, low intake of fiber, depression, visceral fat, and obesity are considered as risk factors for GERD. Modifying lifestyle and behavioral habits prevent GERD.
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Affiliation(s)
- Sepehr Sadafi
- Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Social Development and Health Promotion Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ali Azizi
- Social Development and Health Promotion Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Department of Community and Family Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Yahya Pasdar
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ebrahim Shakiba
- Social Development and Health Promotion Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mitra Darbandi
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Ergun P, Kipcak S, Bor S. Epigenetic Alterations from Barrett's Esophagus to Esophageal Adenocarcinoma. Int J Mol Sci 2023; 24:ijms24097817. [PMID: 37175524 PMCID: PMC10178512 DOI: 10.3390/ijms24097817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 04/17/2023] [Accepted: 04/23/2023] [Indexed: 05/15/2023] Open
Abstract
Barrett's esophagus (BE) is a disease entity that is a sequela of chronic gastroesophageal reflux disease that may result in esophageal adenocarcinoma (EAC) due to columnar epithelial dysplasia. The histological degree of dysplasia is the sole biomarker frequently utilized by clinicians. However, the cost of endoscopy and the fact that the degree of dysplasia does not progress in many patients with BE diminish the effectiveness of histological grading as a perfect biomarker. Multiple or more quantitative biomarkers are required by clinicians since early diagnosis is crucial in esophageal adenocancers, which have a high mortality rate. The presence of epigenetic factors in the early stages of this neoplastic transformation holds promise as a predictive biomarker. In this review, current studies on DNA methylations, histone modifications, and noncoding RNAs (miRNAs) that have been discovered during the progression from BE dysplasia to EAC were collated.
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Affiliation(s)
- Pelin Ergun
- Ege Reflux Study Group, Division of Gastroenterology, Faculty of Medicine, Ege University, 35040 Izmir, Türkiye
- Department of Medical Biochemistry, Faculty of Medicine, Ege University, 35040 Izmir, Türkiye
| | - Sezgi Kipcak
- Ege Reflux Study Group, Division of Gastroenterology, Faculty of Medicine, Ege University, 35040 Izmir, Türkiye
- Department of Medical Biology, Faculty of Medicine, Ege University, 35040 Izmir, Türkiye
| | - Serhat Bor
- Ege Reflux Study Group, Division of Gastroenterology, Faculty of Medicine, Ege University, 35040 Izmir, Türkiye
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Maev IV, Bordin DS, Barkalova EV, Ovsepyan MA, Valitova ER, Kalashnikova NG, Andreev DN. Features of the Parameters of 24-Hours pH-Impedance and High-Resolution Esophageal Manometry in Patients with Barrett's Esophagus on Proton Pump Inhibitors. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2023; 33:24-39. [DOI: 10.22416/1382-4376-2023-33-1-24-39] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
Аim: to identify predictors of insufficient effectiveness of proton pump inhibitors based on the evaluation of the results of 24-hour pH-impedance and high-resolution esophageal manometry in patients with Barrett's esophagus.Materials and methods. 52 patients with histologically confirmed Barrett's esophagus who are on therapy with proton pump inhibitors were examined. All patients underwent daily pH-impedance and high-resolution esophageal manometry.Results. According to daily pH-impedance, group 1 consisted of 37 patients who responded satisfactorily to antisecretory therapy, group 2 of 15 patients who demonstrated insufficient response to acid-suppressive therapy, 11 of whom had no clinical manifestations. The total number of reflux averaged 55 in group 1 and 106 in group 2. The average number of acid reflux in group 1 was 5.68, in group 2 — 48.5. The average number of non-acid reflux prevailed in patients of group 2 and averaged 58, in group 1 the indicator averaged 47. Evaluation of the results of high-resolution esophageal manometry showed that violations of the structure and function of the esophago-gastric junction were detected in 21 patients out of 52. Disorders of the motility of the thoracic esophagus were detected in 31 patients out of 52. When comparing the frequency of motor disorders from the thoracic esophagus in groups 1 and 2, no significant differences were obtained. However, significantly more frequent registration of violations of the structure and/or function of the esophago-gastric junction was found in the group with unsatisfactory effectiveness of proton pump inhibitors.Conclusion. In a number of patients with Barrett's esophagus, there is an insufficient effect of acid-suppressive therapy and at the same time an asymptomatic course of the disease, which may increase the risk of its progression. Predictors of insufficiently successful treatment of patients with Barrett's esophagus may be both insufficient pharmacological effect of proton pump inhibitors themselves, and motility disorders that cause the presence of non-acid reflux, decreased esophageal clearance, which in turn may cause the patient's symptoms to persist and adversely affect the condition of the esophageal mucosa.
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Affiliation(s)
- I. V. Maev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - D. S. Bordin
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry; Moscow Clinical Scientific and Practical Center named after A. S. Loginov; Tver State Medical University
| | - E. V. Barkalova
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - M. A. Ovsepyan
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - E. R. Valitova
- Moscow Clinical Scientific and Practical Center named after A. S. Loginov
| | - N. G. Kalashnikova
- Moscow Clinical Scientific and Practical Center named after A. S. Loginov
| | - D. N. Andreev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
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Maev IV, Bordin DS, Barkalova EV, Ovsepyan MA, Valitova ER, Kalashnikova NG, Andreev DN. Features of the Parameters of 24-Hours pH-Impedance and High-Resolution Esophageal Manometry in Patients with Barrett's Esophagus on Proton Pump Inhibitors. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2023; 33:24-39. [DOI: https:/doi.org/10.22416/1382-4376-2023-33-1-24-39] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
Аim: to identify predictors of insufficient effectiveness of proton pump inhibitors based on the evaluation of the results of 24-hour pH-impedance and high-resolution esophageal manometry in patients with Barrett's esophagus.Materials and methods. 52 patients with histologically confirmed Barrett's esophagus who are on therapy with proton pump inhibitors were examined. All patients underwent daily pH-impedance and high-resolution esophageal manometry.Results. According to daily pH-impedance, group 1 consisted of 37 patients who responded satisfactorily to antisecretory therapy, group 2 of 15 patients who demonstrated insufficient response to acid-suppressive therapy, 11 of whom had no clinical manifestations. The total number of reflux averaged 55 in group 1 and 106 in group 2. The average number of acid reflux in group 1 was 5.68, in group 2 — 48.5. The average number of non-acid reflux prevailed in patients of group 2 and averaged 58, in group 1 the indicator averaged 47. Evaluation of the results of high-resolution esophageal manometry showed that violations of the structure and function of the esophago-gastric junction were detected in 21 patients out of 52. Disorders of the motility of the thoracic esophagus were detected in 31 patients out of 52. When comparing the frequency of motor disorders from the thoracic esophagus in groups 1 and 2, no significant differences were obtained. However, significantly more frequent registration of violations of the structure and/or function of the esophago-gastric junction was found in the group with unsatisfactory effectiveness of proton pump inhibitors.Conclusion. In a number of patients with Barrett's esophagus, there is an insufficient effect of acid-suppressive therapy and at the same time an asymptomatic course of the disease, which may increase the risk of its progression. Predictors of insufficiently successful treatment of patients with Barrett's esophagus may be both insufficient pharmacological effect of proton pump inhibitors themselves, and motility disorders that cause the presence of non-acid reflux, decreased esophageal clearance, which in turn may cause the patient's symptoms to persist and adversely affect the condition of the esophageal mucosa.
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Affiliation(s)
- I. V. Maev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - D. S. Bordin
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry; Moscow Clinical Scientific and Practical Center named after A. S. Loginov; Tver State Medical University
| | - E. V. Barkalova
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - M. A. Ovsepyan
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - E. R. Valitova
- Moscow Clinical Scientific and Practical Center named after A. S. Loginov
| | - N. G. Kalashnikova
- Moscow Clinical Scientific and Practical Center named after A. S. Loginov
| | - D. N. Andreev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
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Montoro-Huguet MA. Dietary and Nutritional Support in Gastrointestinal Diseases of the Upper Gastrointestinal Tract (I): Esophagus. Nutrients 2022; 14:4819. [PMID: 36432505 PMCID: PMC9697263 DOI: 10.3390/nu14224819] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/06/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022] Open
Abstract
The esophagus is the centerpiece of the digestive system of individuals and plays an essential role in transporting swallowed nutrients to the stomach. Diseases of the esophagus can alter this mechanism either by causing anatomical damage that obstructs the lumen of the organ (e.g., peptic, or eosinophilic stricture) or by generating severe motility disorders that impair the progression of the alimentary bolus (e.g., severe dysphagia of neurological origin or achalasia). In all cases, nutrient assimilation may be compromised. In some cases (e.g., ingestion of corrosive agents), a hypercatabolic state is generated, which increases resting energy expenditure. This manuscript reviews current clinical guidelines on the dietary and nutritional management of esophageal disorders such as severe oropharyngeal dysphagia, achalasia, eosinophilic esophagitis, lesions by caustics, and gastroesophageal reflux disease and its complications (Barrett's esophagus and adenocarcinoma). The importance of nutritional support in improving outcomes is also highlighted.
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Affiliation(s)
- Miguel A. Montoro-Huguet
- Unit of Gastroenterology, Hepatology & Nutrition, University Hospital San Jorge, 22005 Huesca, Spain;
- Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- Aragón Health Sciences Institute (IACS), 50009 Zaragoza, Spain
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Ilic M, Ilic I. Epidemiology of stomach cancer. World J Gastroenterol 2022; 28:1187-1203. [PMID: 35431510 PMCID: PMC8968487 DOI: 10.3748/wjg.v28.i12.1187] [Citation(s) in RCA: 190] [Impact Index Per Article: 63.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/30/2021] [Accepted: 02/15/2022] [Indexed: 02/06/2023] Open
Abstract
Despite a decline in incidence and mortality during the last decades, stomach cancer is one of the main health challenges worldwide. According to the GLOBOCAN 2020 estimates, stomach cancer caused approximately 800000 deaths (accounting for 7.7% of all cancer deaths), and ranks as the fourth leading cause of cancer deaths in both genders combined. About 1.1 million new cases of stomach cancer were diagnosed in 2020 (accounting for 5.6% of all cancer cases). About 75% of all new cases and all deaths from stomach cancer are reported in Asia. Stomach cancer is one of the most lethal malignant tumors, with a five-year survival rate of around 20%. There are some well-established risk factors for stomach cancer: Helicobacter pylori infection, dietary factors, tobacco, obesity, and radiation. To date, the most important way of preventing stomach cancer is reduced exposure to risk factors, as well as screening and early detection. Further research on risk factors can help identify various opportunities for more effective prevention. Screening programs for stomach cancer have been implemented in a few countries, either as a national or opportunistic screening of high-risk individuals only. Generally, due to its high aggressiveness and heterogeneity, stomach cancer still remains a severe global health problem.
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Affiliation(s)
- Milena Ilic
- Department of Epidemiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
| | - Irena Ilic
- Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
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Akbari A, Ashtari S, Tabaiean SP, Mehrdad‐Majd H, Farsi F, Shojaee S, Agah S. Overview of epidemiological characteristics, clinical features, and risk factors of gastric cancer in Asia‐Pacific region. Asia Pac J Clin Oncol 2022; 18:493-505. [PMID: 35073453 DOI: 10.1111/ajco.13654] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 06/20/2021] [Indexed: 01/01/2023]
Affiliation(s)
- Abolfazl Akbari
- Colorectal Research Center Iran University of Medical Sciences Tehran Iran
| | - Sara Ashtari
- Gastroenterology and Live Diseases Research Center Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Seidamir Pasha Tabaiean
- Colorectal Research Center Iran University of Medical Sciences Tehran Iran
- Department of Internal Medicine School of Medicine Iran University of Medical Sciences Tehran Iran
| | - Hassan Mehrdad‐Majd
- Cancer Molecular Pathology Research Center Mashhad University of Medical Sciences Mashhad Iran
| | - Farnaz Farsi
- Department of Nutrition School of public health Iran University of Medical Sciences Tehran Iran
| | - Sajad Shojaee
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Shahram Agah
- Colorectal Research Center Iran University of Medical Sciences Tehran Iran
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12
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ten Kate CA, de Klein A, de Graaf BM, Doukas M, Koivusalo A, Pakarinen MP, van der Helm R, Brands T, IJsselstijn H, van Bever Y, Wijnen RM, Spaander MC, Brosens E. Intrinsic Cellular Susceptibility to Barrett's Esophagus in Adults Born with Esophageal Atresia. Cancers (Basel) 2022; 14:cancers14030513. [PMID: 35158780 PMCID: PMC8833471 DOI: 10.3390/cancers14030513] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 01/01/2022] [Accepted: 01/10/2022] [Indexed: 11/25/2022] Open
Abstract
Simple Summary We investigated the increased prevalence of Barrett’s esophagus in adults with esophageal atresia. A higher polygenic risk score and disturbances in inflammatory, stress response and oncological pathways upon acid exposure suggest a genetic susceptibility and increased induction of inflammatory processes. Although further research is required to explore this hypothesis, this could be a first-step into selecting patients that are more at risk to develop Barrett’s esophagus and/or esophageal carcinoma. Currently, an endoscopic screening and surveillance program is in practice in our institution for patients born with esophageal atresia, to early detect (pre)malignant lesions. Since recurrent endoscopies can be a burden for the patient, selecting patients by for example genetic susceptibility would allow to only include those at risk in future practice. Abstract The prevalence of Barrett’s esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than in the general population and presents at a younger age (34 vs. 60 years). This is (partly) a consequence of chronic gastroesophageal reflux. Given the overlap between genes and pathways involved in foregut and BE development, we hypothesized that EA patients have an intrinsic predisposition to develop BE. Transcriptomes of Esophageal biopsies of EA patients with BE (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 10, BE-only) were compared by RNA expression profiling. Subsequently, we simulated a reflux episode by exposing fibroblasts of 3 EA patients and 3 controls to acidic conditions. Transcriptome responses were compared to the differential expressed transcripts in the biopsies. Predisposing single nucleotide polymorphisms, associated with BE, were slightly increased in EA/BE versus BE-only patients. RNA expression profiling and pathway enrichment analysis revealed differences in retinoic acid metabolism and downstream signaling pathways and inflammatory, stress response and oncological processes. There was a similar effect on retinoic acid signaling and immune response in EA patients upon acid exposure. These results indicate that epithelial tissue homeostasis in EA patients is more prone to acidic disturbances.
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Affiliation(s)
- Chantal A. ten Kate
- Department of Pediatric Surgery and Intensive Care Children, Erasmus MC-Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (C.A.t.K.); (H.I.); (R.M.H.W.)
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, 3000 CA Rotterdam, The Netherlands;
- Department of Clinical Genetics, Erasmus MC Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (A.d.K.); (B.M.d.G.); (R.v.d.H.); (T.B.); (Y.v.B.)
| | - Annelies de Klein
- Department of Clinical Genetics, Erasmus MC Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (A.d.K.); (B.M.d.G.); (R.v.d.H.); (T.B.); (Y.v.B.)
| | - Bianca M. de Graaf
- Department of Clinical Genetics, Erasmus MC Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (A.d.K.); (B.M.d.G.); (R.v.d.H.); (T.B.); (Y.v.B.)
| | - Michail Doukas
- Department of Pathology, Erasmus MC, 3000 CA Rotterdam, The Netherlands;
| | - Antti Koivusalo
- Department of Pediatric Surgery, University of Helsinki, Children’s Hospital, 281, 000290 Helsinki, Finland; (A.K.); (M.P.P.)
| | - Mikko P. Pakarinen
- Department of Pediatric Surgery, University of Helsinki, Children’s Hospital, 281, 000290 Helsinki, Finland; (A.K.); (M.P.P.)
| | - Robert van der Helm
- Department of Clinical Genetics, Erasmus MC Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (A.d.K.); (B.M.d.G.); (R.v.d.H.); (T.B.); (Y.v.B.)
| | - Tom Brands
- Department of Clinical Genetics, Erasmus MC Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (A.d.K.); (B.M.d.G.); (R.v.d.H.); (T.B.); (Y.v.B.)
| | - Hanneke IJsselstijn
- Department of Pediatric Surgery and Intensive Care Children, Erasmus MC-Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (C.A.t.K.); (H.I.); (R.M.H.W.)
| | - Yolande van Bever
- Department of Clinical Genetics, Erasmus MC Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (A.d.K.); (B.M.d.G.); (R.v.d.H.); (T.B.); (Y.v.B.)
| | - René M.H. Wijnen
- Department of Pediatric Surgery and Intensive Care Children, Erasmus MC-Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (C.A.t.K.); (H.I.); (R.M.H.W.)
| | - Manon C.W. Spaander
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, 3000 CA Rotterdam, The Netherlands;
| | - Erwin Brosens
- Department of Clinical Genetics, Erasmus MC Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (A.d.K.); (B.M.d.G.); (R.v.d.H.); (T.B.); (Y.v.B.)
- Correspondence: ; Tel.: +31-10-70-37643
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13
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Maev IV, Barkalova EV, Andreev DN, Ovsepian MA, Movtaeva PR, Zayratyants OV. [Complex assessment of esophageal acidification and motor function in patients with Barrett's esophagus on antisecretory therapy]. TERAPEVT ARKH 2021; 93:1463-1469. [PMID: 36286674 DOI: 10.26442/00403660.2021.12.201278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 01/14/2022] [Indexed: 11/22/2022]
Abstract
AIM To determine predictors of insufficient effectiveness of proton pump inhibitors based on the parameters of 24-hours pH-impedance and features of motor function of the esophagus in patients with Barrett's esophagus. MATERIALS AND METHODS 17 patients with histologically verified Barrett's esophagus undergoing acid-suppressive therapy were examined. All patients underwent 24-hours pH-impedance and high-resolution esophageal manometry. RESULTS According to daily pH-impedance, group 1 consisted of 11 patients with an adequate response to antisecretory therapy, group 2 6 patients with insufficient effectiveness of antisecretory therapy, 5 of whom had no clinical manifestations. The total number of reflux averaged 52 and 91, respectively, in groups 1 and 2. The average number of acid reflux in group 1 was 4.36, in group 2 40.5. The average number of non-acid reflux prevailed in patients of group 2, averaging 58, compared with group 1, where the average was 47. According to the results of high-resolution esophageal manometry, when assessing the structure and function of the esophageal-gastric junction, violations were detected in 6 out of 17 patients. Disorders of the motor function of the thoracic esophagus were detected in 10 out of 17 patients. The tone of the lower esophageal sphincter in group 1 patients was significantly higher in comparison with patients in group 2. CONCLUSION A number of patients with Barrett's esophagus have insufficient effectiveness of antisecretory therapy, which may not manifest itself clinically and thereby increase the risk of progression. There was a tendency to more frequent motor disorders in the group with insufficient effectiveness of antisecretory therapy, as well as significantly lower tone of the lower esophageal sphincter, which may be a potential predictor of suboptimal effectiveness of antisecretory therapy.
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Affiliation(s)
- I V Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - E V Barkalova
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - D N Andreev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - M A Ovsepian
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - P R Movtaeva
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - O V Zayratyants
- Yevdokimov Moscow State University of Medicine and Dentistry
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14
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Brosens E, Brouwer RWW, Douben H, van Bever Y, Brooks AS, Wijnen RMH, van IJcken WFJ, Tibboel D, Rottier RJ, de Klein A. Heritability and De Novo Mutations in Oesophageal Atresia and Tracheoesophageal Fistula Aetiology. Genes (Basel) 2021; 12:genes12101595. [PMID: 34680991 PMCID: PMC8535313 DOI: 10.3390/genes12101595] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 10/03/2021] [Accepted: 10/05/2021] [Indexed: 01/12/2023] Open
Abstract
Tracheoesophageal Fistula (TOF) is a congenital anomaly for which the cause is unknown in the majority of patients. OA/TOF is a variable feature in many (often mono-) genetic syndromes. Research using animal models targeting genes involved in candidate pathways often result in tracheoesophageal phenotypes. However, there is limited overlap in the genes implicated by animal models and those found in OA/TOF-related syndromic anomalies. Knowledge on affected pathways in animal models is accumulating, but our understanding on these pathways in patients lags behind. If an affected pathway is associated with both animals and patients, the mechanisms linking the genetic mutation, affected cell types or cellular defect, and the phenotype are often not well understood. The locus heterogeneity and the uncertainty of the exact heritability of OA/TOF results in a relative low diagnostic yield. OA/TOF is a sporadic finding with a low familial recurrence rate. As parents are usually unaffected, de novo dominant mutations seems to be a plausible explanation. The survival rates of patients born with OA/TOF have increased substantially and these patients start families; thus, the detection and a proper interpretation of these dominant inherited pathogenic variants are of great importance for these patients and for our understanding of OA/TOF aetiology.
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Affiliation(s)
- Erwin Brosens
- Department of Clinical Genetics, Erasmus University Medical Center-Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (H.D.); (Y.v.B.); (A.S.B.); (A.d.K.)
- Correspondence:
| | - Rutger W. W. Brouwer
- Department of Cell Biology, Center for Biomics, Erasmus University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands; (R.W.W.B.); (W.F.J.v.I.)
| | - Hannie Douben
- Department of Clinical Genetics, Erasmus University Medical Center-Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (H.D.); (Y.v.B.); (A.S.B.); (A.d.K.)
| | - Yolande van Bever
- Department of Clinical Genetics, Erasmus University Medical Center-Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (H.D.); (Y.v.B.); (A.S.B.); (A.d.K.)
| | - Alice S. Brooks
- Department of Clinical Genetics, Erasmus University Medical Center-Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (H.D.); (Y.v.B.); (A.S.B.); (A.d.K.)
| | - Rene M. H. Wijnen
- Department of Pediatric Surgery, Erasmus University Medical Center-Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (R.M.H.W.); (D.T.)
| | - Wilfred F. J. van IJcken
- Department of Cell Biology, Center for Biomics, Erasmus University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands; (R.W.W.B.); (W.F.J.v.I.)
| | - Dick Tibboel
- Department of Pediatric Surgery, Erasmus University Medical Center-Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (R.M.H.W.); (D.T.)
| | - Robbert J. Rottier
- Departments of Pediatric Surgery & Cell Biology, Erasmus University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands;
| | - Annelies de Klein
- Department of Clinical Genetics, Erasmus University Medical Center-Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands; (H.D.); (Y.v.B.); (A.S.B.); (A.d.K.)
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15
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Dynamic switch of immunity and antitumor effects of metformin in rat spontaneous esophageal carcinogenesis. Cancer Immunol Immunother 2021; 71:777-789. [PMID: 34398301 PMCID: PMC8921146 DOI: 10.1007/s00262-021-03027-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 07/29/2021] [Indexed: 11/17/2022]
Abstract
Chronic inflammation contributes to tumor development by creating a local microenvironment that facilitates neoplastic transformation and potentiates the progression of cancer. Esophageal cancer (EC) is an inflammation-associated malignancy with a poor prognosis. The nature of the switch between chronic inflammation of the esophagus and EC-related immunological changes remains unclear. Here, we examined the dynamic alterations of immune cells at different stages of chronic esophagitis, Barrett’s esophagus (BE) and EC using an esophageal spontaneous carcinogenesis rat model. We also investigated the anticancer effects of metformin. To stimulate EC carcinogenesis, chronic gastroduodenal reflux esophagitis via esophagojejunostomy was induced in 120 rats in metformin-treated and non-treated (control) groups. After 40 weeks, BE and EC developed in 96.7% and 63.3% of the control group, and in 66.7% and 23.3% of the metformin-treated group, respectively. Flow cytometric analysis demonstrated that the balance of M1/M2-polarized or phospho-Stat3-positive macrophages, regulatory T, cytotoxic T, natural killer (NK), NK T cells, and Th17 T cells was dynamically changed at each stage of the disease and were resolved by metformin treatment. These findings clarify the immunity in esophageal carcinogenesis and suggest that metformin could suppress this disease by improving the immunosuppressive tumor microenvironment and immune evasion.
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16
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Barkalova EV, Pirogov SS, Andreev DN, Ovsepyan MA, Maev IV, Kaprin AD. Asymptomatic Barrett’s Oesophagus-Complicated Gastroesophageal Reflux Disease at Ineffective Antisecretory Therapy. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2021; 31:46-53. [DOI: 10.22416/1382-4376-2021-31-2-46-53] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Aim. A clinical description of gastroesophageal reflux disease (GERD) complicated by Barrett’s oesophagus (BO) at inadequate antisecretory therapy and the assessment of functional tests in control of conservative treatment.Key points. A 63-yo patient with no complaints in a proton pump inhibitor (PPI) therapy was admitted for a follow-up examination for BO-complicated GERD using oesophagogastroduodenoscopy (OGDS) with biopsy, high-resolution oesophageal manometry and 24-h pH-impedance. Endoscopy revealed signs of BO (long segment C1M3), erosive reflux oesophagitis (grade B in Los Angeles classification). Non-contractile oesophagus in manometry. Antisecretory therapy was stated ineffective and subject to correction in 24-h pH-impedance.Conclusion. Asymptomatic BO-complicated GERD patients comprise a special cohort. The main challenge to prevent progression into oesophageal adenocarcinoma is an adequate personalised patient management leveraging the modern diagnostic techniques, control of antisecretory treatment and its correction a situ.
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Affiliation(s)
- E. V. Barkalova
- Yevdokimov Moscow State University of Medicine and Dentistry
| | | | - D. N. Andreev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - M. A. Ovsepyan
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - I. V. Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
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Moodi M, Tavakoli T, Tahergorabi Z. Crossroad between Obesity and Gastrointestinal Cancers: A Review of Molecular Mechanisms and Interventions. Int J Prev Med 2021; 12:18. [PMID: 34084315 PMCID: PMC8106288 DOI: 10.4103/ijpvm.ijpvm_266_20] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Accepted: 09/12/2020] [Indexed: 12/28/2022] Open
Abstract
The burden of gastrointestinal (GI) cancer is increasing worldwide, and in the past decade, cancer had entered the list of chronic debilitating diseases whose risk is substantially increased by hypernutrition. Obesity may increase the risk of cancer by the imbalance of various mechanisms including insulin and insulin-like growth factor1 (IGF-I) signaling, systemic inflammation, immune dysregulation, tumor angiogenesis, adipokines secretion, and intestinal microbiota that usually act interdependently. An increased understanding of the mechanisms underlying obesity-GI cancer link can provide multiple opportunities for cancer prevention. This review discusses various mechanisms involved molecular mechanisms linking obesity with GI cancers including esophagus, stomach, colorectal and hepatocellular. Furthermore, an optional intervention such as diet restriction and exercise is described, which may be preventive or therapeutic in GI cancer.
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Affiliation(s)
- Mitra Moodi
- Social Determinants of Health Research Center, Department of Health Education and Health Promotion, School of Health, Birjand University of Medical Sciences, Birjand, Iran
| | - Tahmineh Tavakoli
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Gasteroenterology Section, Department of Internal Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Zoya Tahergorabi
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Department of Physiology, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran
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18
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Lv J, Zhao HP, Dai K, Cheng Y, Zhang J, Guo L. Circulating exosomal miRNAs as potential biomarkers for Barrett's esophagus and esophageal adenocarcinoma. World J Gastroenterol 2020; 26:2889-2901. [PMID: 32587437 PMCID: PMC7304109 DOI: 10.3748/wjg.v26.i22.2889] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 03/26/2020] [Accepted: 05/26/2020] [Indexed: 02/06/2023] Open
Abstract
Exosomes, a class of extracellular vesicles, are small membrane-bound vesicles derived from almost all cell types that can play important roles in intercellular communication. Exosomes contain proteins, lipids, and nucleic acids that are obtained from the parental cells and participate in various pathophysiological processes, including cell growth, migration, inflammation, immune regulation, and tumor pathogenesis. Moreover, exosomes might be applied in clinical settings, such as diagnosis, treatment, and outcome prediction of diseases, including various cancers. The incidence rates of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) have increased in recent decades, and studies have proposed specific factors that may contribute to the development and progression of these diseases. However, how exosomes play a role in this pathological process needs to be clarified. Studies have identified candidate microRNAs (miRNAs) that might be related to BE/EAC. Further studies are needed to ascertain whether circulating exosomal miRNAs are altered before or after disease onset, which could also help understand the pathophysiology of and find potential targets for prevention, diagnosis, and therapy in BE/EAC. This review summarizes recent findings on the features of circulating exosomal miRNAs in BE/EAC, which could be valuable for the early diagnosis, therapeutic approaches, and outcome prediction of BE/EAC.
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Affiliation(s)
- Jing Lv
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - He-Ping Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Kun Dai
- Department of Clinical Laboratory, Yanliang Railway Hospital of Xi’an, Xi'an 710089, Shaanxi Province, China
| | - Yan Cheng
- Department of Gastroenterology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Jun Zhang
- Department of Gastroenterology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Lei Guo
- Department of Spinal Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
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He H, Chen N, Hou Y, Wang Z, Zhang Y, Zhang G, Fu J. Trends in the incidence and survival of patients with esophageal cancer: A SEER database analysis. Thorac Cancer 2020; 11:1121-1128. [PMID: 32154652 PMCID: PMC7180574 DOI: 10.1111/1759-7714.13311] [Citation(s) in RCA: 102] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 12/24/2019] [Accepted: 12/27/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Recent studies have indicated that the incidence of esophageal cancer has declined in the past decade in the U.S. However, trends in the incidence and survival have not been thoroughly examined. METHODS Data from 46 063 patients with esophageal cancer between 1973 and 2015 were collected from the Surveillance, Epidemiology, and End Results database. The trends in the age-adjusted incidence and survival were analyzed using joinpoint regression models. RESULTS The age-adjusted incidence of esophageal cancer increased from 5.55 to 7.44 per 100 000 person-years between 1973 and 2004. Later, it decreased at an annual percentage change of 1.23%. In the last 40 years, the strong male predominance increased slightly. Importantly, the percentage of patients with localized stage of squamous cell cancer decreased. It was observed that the incidence of esophageal squamous cell carcinoma declined since 1986, while the incidence of esophageal adenocarcinoma sharply increased since 1973 and surpassed the rate of squamous cell cancer, mainly due to the increase in the incidence among men. Consistently, the estimated 40-year limited-duration prevalence of esophageal adenocarcinoma was higher than that of esophageal squamous cell carcinoma. Additionally, we observed a modest but significant improvement in survival during the study period. CONCLUSION The incidence of esophageal squamous cell carcinoma has decreased significantly over the past four decades in the U.S., while the incidence of adenocarcinoma has increased, particularly among men. Overall, the long-term survival of patients with esophageal cancer is poor but it has improved over the past decades, especially for the localized disease. KEY POINTS Significant findings of the study The incidence of esophageal cancer has decreased at an annual percentage change of 1.23% since 2004. The incidence of esophageal adenocarcinoma has sharply increased since 1973 and surpassed the rate of squamous cell cancer, mainly due to the increase in the incidence among men. What this study adds There has been a shift in the prevalence of esophageal cancer histological subtypes over the past decades in the U.S. We found that the incidence of esophageal squamous cell carcinoma has continued to decrease, while the esophageal adenocarcinoma rate has continued to increase.
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Affiliation(s)
- Haiqi He
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Nanzheng Chen
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yue Hou
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhe Wang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yong Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Guangjian Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Junke Fu
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Deep principal dimension encoding for the classification of early neoplasia in Barrett's Esophagus with volumetric laser endomicroscopy. Comput Med Imaging Graph 2020; 80:101701. [PMID: 32044547 DOI: 10.1016/j.compmedimag.2020.101701] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 12/20/2019] [Accepted: 01/14/2020] [Indexed: 02/07/2023]
Abstract
Barrett cancer is a treatable disease when detected at an early stage. However, current screening protocols are often not effective at finding the disease early. Volumetric Laser Endomicroscopy (VLE) is a promising new imaging tool for finding dysplasia in Barrett's esophagus (BE) at an early stage, by acquiring cross-sectional images of the microscopic structure of BE up to 3-mm deep. However, interpretation of VLE scans is difficult for medical doctors due to both the size and subtlety of the gray-scale data. Therefore, algorithms that can accurately find cancerous regions are very valuable for the interpretation of VLE data. In this study, we propose a fully-automatic multi-step Computer-Aided Detection (CAD) algorithm that optimally leverages the effectiveness of deep learning strategies by encoding the principal dimension in VLE data. Additionally, we show that combining the encoded dimensions with conventional machine learning techniques further improves results while maintaining interpretability. Furthermore, we train and validate our algorithm on a new histopathologically validated set of in-vivo VLE snapshots. Additionally, an independent test set is used to assess the performance of the model. Finally, we compare the performance of our algorithm against previous state-of-the-art systems. With the encoded principal dimension, we obtain an Area Under the Curve (AUC) and F1 score of 0.93 and 87.4% on the test set respectively. We show this is a significant improvement compared to the state-of-the-art of 0.89 and 83.1%, respectively, thereby demonstrating the effectiveness of our approach.
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21
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Busby J, Karasneh R, Murchie P, McMenamin Ú, Gadalla SM, Camargo MC, Iversen L, Lee AJ, Spence AD, Cardwell CR. The role of 5α-reductase inhibitors in gastro-oesophageal cancer risk: A nested case-control study. Pharmacoepidemiol Drug Saf 2020; 29:48-56. [PMID: 31713940 PMCID: PMC8520491 DOI: 10.1002/pds.4909] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 08/08/2019] [Accepted: 09/17/2019] [Indexed: 12/26/2022]
Abstract
PURPOSE The strong male predominance of gastro-oesophageal cancer suggests that sex hormones play an important role. 5α-Reductase (5AR) inhibitors have antiandrogen effects and have been shown to decrease cancer cell proliferation and metastasis. We conducted the first epidemiologic investigation into the association between 5AR inhibitor use and gastro-oesophageal cancer risk. METHODS We conducted a nested case-control study within the Scottish Primary Care Clinical Information Unit Research database. Male cases diagnosed with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five male controls based on birth year, diagnosis year, and general practice. We used electronic prescribing records to ascertain medication use. We used conditional logistic regression to calculate odds ratios (ORs) for the association between 5AR inhibitor use and cancer risk, after adjusting for comorbidities and aspirin, statin, or proton pump inhibitor use. RESULTS The study included 2003 gastro-oesophageal cancer cases and 9650 controls. There was some evidence of reduced gastro-oesophageal cancer risk among 5AR inhibitor users (adjusted OR = 0.75; 95% CI, 0.56-1.02), particularly for finasteride (adjusted OR = 0.68; 95% CI, 0.50-0.94). These decreases were more marked among those who received at least 3 years of 5AR inhibitors (adjusted OR = 0.54; 95% CI, 0.27-1.05; P value = .071) or finasteride (adjusted OR = 0.49; 95% CI, 0.24-0.99; P value = .046). CONCLUSIONS We found evidence of reduced gastro-oesophageal cancer risk among users of 5AR inhibitors, particularly finasteride. However, larger epidemiological studies are required before randomised controlled trials are considered.
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Affiliation(s)
- John Busby
- Centre for Public Health, Queen’s University Belfast, Belfast, UK
| | - Reema Karasneh
- Centre for Public Health, Queen’s University Belfast, Belfast, UK
| | - Peter Murchie
- Academic Primary Care, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
| | - Úna McMenamin
- Centre for Public Health, Queen’s University Belfast, Belfast, UK
| | - Shahinaz M. Gadalla
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, USA
| | - M Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, USA
| | - Lisa Iversen
- Academic Primary Care, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
| | - Amanda J Lee
- Medical Statistics Team, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
| | - Andrew D. Spence
- Centre for Public Health, Queen’s University Belfast, Belfast, UK
| | - Chris R Cardwell
- Centre for Public Health, Queen’s University Belfast, Belfast, UK
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22
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Abstract
An organ-specific chronic inflammation–remodeling–carcinoma sequence has been proposed, mainly for the alimentary tract. As representative diseases, gastroesophageal reflux disease, chronic gastritis and inflammatory bowel disease (ulcerative colitis and Crohn’s disease of the colitis type) were adopted for this discussion. Tissue remodeling is such an important part of tumorigenesis in this sequence that an organ-specific chronic inflammation–remodeling–carcinoma sequence has been proposed in detail. Chronic inflammation accelerates the cycle of tissue injury and regeneration; in other words, cell necrosis (or apoptosis) and proliferation result in tissue remodeling in long-standing cases of inflammation. Remodeling encompasses epithelial cell metaplasia and stromal fibrosis, and modifies epithelial–stromal cell interactions. Further, the accumulation of genetic, epigenetic and molecular changes—as well as morphologic disorganization—also occurs during tissue remodeling. The expression of mucosal tissue adapted to chronic inflammatory injury is thought to occur at an early stage. Subsequently, dysplasia and carcinoma develop on a background of remodeling due to continuous, active inflammation. Accordingly, organ-specific chronic inflammation should be ameliorated or well controlled with appropriate monitoring if complete healing is unachievable.
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23
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Bulamu NB, Chen G, Ratcliffe J, Schloite A, Bright T, Watson DI. Health-Related Quality of Life Associated with Barrett's Esophagus and Cancer. World J Surg 2019; 43:1554-1562. [PMID: 30719557 DOI: 10.1007/s00268-019-04936-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Research assessing health-related quality of life (HRQoL) which can be applied to economic evaluation in Barrett's esophagus (BE) and esophageal cancer is limited. This study derived health state utilities for various 'stages' of BE and Cancer. METHODS A cross-sectional survey was conducted, including patients with non-dysplastic BE, low-grade dysplasia, high-grade dysplasia, or esophageal adenocarcinoma. HRQoL was assessed using generic instruments-EQ-5D-5L and SF-36, and a cancer-specific instrument-EORTC QLQ-C30. Outcomes were compared for health states following different treatments. Correlations and agreements for the three instruments were investigated using Spearman's correlation coefficient (r) and intraclass correlation coefficient (ICC). RESULTS A total of 97 respondents (80% male, mean age 68 years) returned questionnaires. The mean (standard deviation) health state utilities for the total sample were 0.79 (0.24) for the EQ-5D-5L, 0.57 (0.29) for the SF-6D (derived from SF-36) and 0.73 (0.20) for the QLU-C10D (derived from EORTC QLQ-C30). There were strong correlations (r > 0.80) and absolute agreement (except EQ-5D-5L and SF-6D with an ICC of 0.69) among the three instruments. No significant differences were observed for different stages of BE or interventions. However, following surgery for cancer patients reported better psychological well-being than those under surveillance or following endoscopic treatments. CONCLUSION HRQoL for BE surveillance and following cancer treatment was similar. Esophagectomy was associated with better psychological functioning, and this might be attributed to a reduction in the perceived risk of cancer. The correlation between the EORTC QLU-C10D and the other health state utility instruments supports the validity of this new instrument.
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Affiliation(s)
- Norma B Bulamu
- Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Adelaide, SA, 5041, Australia
| | - Gang Chen
- Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Adelaide, SA, 5041, Australia.
- Centre for Health Economics, Monash Business School, Monash University, Melbourne, Australia.
| | - Julie Ratcliffe
- Institute of Choice, Business School, University of South Australia, Adelaide, Australia
| | - Ann Schloite
- Discipline of Surgery, College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Tim Bright
- Discipline of Surgery, College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - David I Watson
- Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Adelaide, SA, 5041, Australia
- Discipline of Surgery, College of Medicine and Public Health, Flinders University, Adelaide, Australia
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24
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Revision of Sleeve Gastrectomy with Hiatal Repair with Gastropexy for Gastroesophageal Reflux Disease. Obes Surg 2019; 29:2381-2386. [PMID: 31001757 DOI: 10.1007/s11695-019-03853-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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25
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Altered T Cell Migratory Capacity in the Progression from Barrett Oesophagus to Oesophageal Adenocarcinoma. CANCER MICROENVIRONMENT 2019; 12:57-66. [PMID: 30834503 DOI: 10.1007/s12307-019-00220-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 02/07/2019] [Indexed: 02/07/2023]
Abstract
Oesophageal adenocarcinoma (OAC) is an inflammation-driven cancer with poor prognosis and incidence is increasing rapidly. OAC arises from gastro-oesophageal reflux disease (GORD) and reflux-induced Barrett oesophagus (BO). The role of T cells in this disease progression is not yet fully understood. We have previously demonstrated higher proportions of pro-tumour Th2 cells in BO tissue, implicating them in its pathogenesis. While a Th2 immune profile is thought to underlie the metaplastic transformation in BO and promote OAC development, our studies suggest that the abundance of Th2 cells in BO tissue is likely to occur through altered T cell recruitment. This study examined the chemokine networks governing T cell migration to oesophageal tissue during disease progression. Here, we have identified that circulating T cells in OAC patients, exhibit impaired migratory capacity with decreased frequencies of Th1-associated CXCR3+ and Th17-associated CCR6+ cells. Despite the abundance of Th1 chemokines RANTES (CCL5) and MIP-1α (CCL3) in OAC tumour, enrichments of intratumoural T cells expressing corresponding receptors were not observed. These data suggest that T cell infiltration of oesophageal tissue is compromised in OAC and suggest that future therapies targeting T cell trafficking should occur at the pre-neoplastic stage. This is supported by the finding that antagonism of Th2-biased CCR4 significantly reduces T cell migration in BO but not OAC patients. Since we have previously reported a predominant Th2 immune profile in BO, we suggest that chemokine receptor antagonism may be a viable treatment option to alleviate Th2-predominance in BO and interrupt progression to OAC.
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26
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Abstract
Obesity leads to many diseases including hypercholesterolemia, type-2 diabetes, hypertension, cardiovascular disease, and cancer. It is the fastest-growing lethal disease in the Western and developing countries. The link between obesity and cancer is relatively underappreciated among the general population. Obesity represents the number one risk factor for type-2 diabetes and a considerable body of epidemiological studies supports the relationship between type-2 diabetes and many cancers. In this review, we examine the obesity-type-2-diabetes-cancer relationships from a mechanistic perspective, and where appropriate, we highlight potential pharmaceutical and dietary interventions.
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Affiliation(s)
- Khosrow Kashfi
- Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, USA
- Graduate Program in Biology, City University of New York Graduate Center, New York, USA
| | - Casey L. Rosen
- Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, USA
| | - Melissa Aslan
- Department of Molecular Biology and Genetics, Gebze Technical University, Kocaeli Turkey
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27
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Talagala IA, Nawarathne M, Arambepola C. Novel risk factors for primary prevention of oesophageal carcinoma: a case-control study from Sri Lanka. BMC Cancer 2018; 18:1135. [PMID: 30454012 PMCID: PMC6245903 DOI: 10.1186/s12885-018-4975-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Accepted: 10/19/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Oesophageal carcinoma (OC) is one of the leading cancers in Sri Lanka. Its increasing incidence despite the implementation of various preventive activities addressing the conventional risk factors indicates the possibility of the existence of novel, country-specific risk factors. Thus, the identification of novel risk factors of OC specific to Sri Lanka is crucial for implementation of primary prevention activities. METHODS A case-control study was conducted among 49 incident cases of OC recruited from the National Cancer Institute, Maharagama using a non-probability sampling method, and unmatched hospital controls (n = 196) excluded of having OC recruited from the endoscopy unit of the National Hospital of Sri Lanka. Data were collected using an interviewer administered questionnaire. Risk factors for OC were assessed by odds ratio (OR) with 95% confidence interval (CI). The risk factors were adjusted for possible confounding by logistic regression analysis. RESULTS Of the study population, OC was common among males (69%) and the majority presented with squamous cell carcinoma (65%) at late stages (Stage IV: 45%; Stage III: 37%). Following adjusting for confounders, the risk factor profile for OC included; age > 65 years (OR = 4.0; 95% CI: 1.2-14.2); family history of cancer (OR = 5.04; 95% CI: 1.3-19.0); sub-optimal consumption of dietary fibre (OR = 3.58; 95% CI: 1.1-12.3); sub-optimal consumption of anti-oxidants (OR = 7.0; 95% CI: 2.2-22.5); over-consumption of deep fried food (OR = 6.68; 95% CI:2.0-22.6); 'high risk' alcohol drinking (OR = 11.7; 95% CI: 2.8-49.4); betel quid chewing (OR = 6.1; 95% CI: 2.0, 20.0); 'low' lifetime total sports and exercise activities (MET hours/week/year) (OR = 5.83; 95% CI: 1.5-23.0); agrochemicals exposure (OR = 6.57; 95% CI: 1.4-30.3); pipe-borne drinking water (OR = 5.62; 95% CI:1.7-18.9) and radiation exposure (OR = 4.64; 95% CI: 1.4-15.5). Significant effect modifications were seen between betel quid chewing and male sex (p = 0.01) and between ever exposure to radiation and age over 65 years (p = 0.04). CONCLUSIONS Risk profile for OC includes novel yet modifiable risk factors in relation to diet, occupation, environment and health. Primary prevention should target these to combat OC in Sri Lanka.
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Affiliation(s)
- Ishanka Ayeshwari Talagala
- National Programme for prevention and control of non-communicable diseases; Ministry of Health, Nutrition and Indigenous Medicine, Colombo, Sri Lanka
| | | | - Carukshi Arambepola
- Department of Community Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
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28
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Owen RP, White MJ, Severson DT, Braden B, Bailey A, Goldin R, Wang LM, Ruiz-Puig C, Maynard ND, Green A, Piazza P, Buck D, Middleton MR, Ponting CP, Schuster-Böckler B, Lu X. Single cell RNA-seq reveals profound transcriptional similarity between Barrett's oesophagus and oesophageal submucosal glands. Nat Commun 2018; 9:4261. [PMID: 30323168 PMCID: PMC6189174 DOI: 10.1038/s41467-018-06796-9] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 09/19/2018] [Indexed: 02/07/2023] Open
Abstract
Barrett's oesophagus is a precursor of oesophageal adenocarcinoma. In this common condition, squamous epithelium in the oesophagus is replaced by columnar epithelium in response to acid reflux. Barrett's oesophagus is highly heterogeneous and its relationships to normal tissues are unclear. Here we investigate the cellular complexity of Barrett's oesophagus and the upper gastrointestinal tract using RNA-sequencing of single cells from multiple biopsies from six patients with Barrett's oesophagus and two patients without oesophageal pathology. We find that cell populations in Barrett's oesophagus, marked by LEFTY1 and OLFM4, exhibit a profound transcriptional overlap with oesophageal submucosal gland cells, but not with gastric or duodenal cells. Additionally, SPINK4 and ITLN1 mark cells that precede morphologically identifiable goblet cells in colon and Barrett's oesophagus, potentially aiding the identification of metaplasia. Our findings reveal striking transcriptional relationships between normal tissue populations and cells in a premalignant condition, with implications for clinical practice.
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Affiliation(s)
- Richard Peter Owen
- Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK
| | - Michael Joseph White
- Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK
| | - David Tyler Severson
- Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK
| | - Barbara Braden
- Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK
| | - Adam Bailey
- Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK
| | - Robert Goldin
- Centre for Pathology, St Mary's Hospital, Imperial College, London, W2 1NY, UK
| | - Lai Mun Wang
- Department of Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 9DU, UK
| | - Carlos Ruiz-Puig
- Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK
| | | | - Angie Green
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
| | - Paolo Piazza
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
- Department of Medicine, Faculty of Medicine, Imperial College London, London, W12 0NN, UK
| | - David Buck
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
| | - Mark Ross Middleton
- Department of Oncology, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK
| | - Chris Paul Ponting
- MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK
| | - Benjamin Schuster-Böckler
- Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
| | - Xin Lu
- Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
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29
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Zhang W, Wang DH. Origins of Metaplasia in Barrett's Esophagus: Is this an Esophageal Stem or Progenitor Cell Disease? Dig Dis Sci 2018; 63:2005-2012. [PMID: 29675663 PMCID: PMC6783253 DOI: 10.1007/s10620-018-5069-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The incidence of esophageal adenocarcinoma has been increasing in Western countries over the past several decades. Though Barrett's esophagus, in which the normal esophageal squamous epithelium is replaced with metaplastic intestinalized columnar cells due to chronic damage from gastroesophageal reflux, is accepted as the requisite precursor lesion for esophageal adenocarcinoma, the Barrett's esophagus cell of origin and the molecular mechanism underlying esophageal epithelial metaplasia remain controversial. Much effort has been dedicated towards identifying the Barrett's esophagus cell of origin since this could lead to more effective prevention and treatment strategies for both Barrett's esophagus and esophageal adenocarcinoma. Previously, it was hypothesized that terminally differentiated esophageal squamous cells might undergo direct conversion into specialized intestinal columnar cells via the process of transdifferentiation. However, there is increasing evidence that stem and/or progenitor cells are molecularly reprogrammed through the process of transcommitment to differentiate into the columnar cell lineages that characterize Barrett's esophagus. Given that Barrett's esophagus originates at the gastroesophageal junction, the boundary between the distal esophagus and gastric cardia, potential sources of these stem and/or progenitor cells include columnar cells from the squamocolumnar junction or neighboring gastric cardia, native esophageal squamous cells, native esophageal cuboidal or columnar cells from submucosal glands or ducts, or circulating bone marrow-derived cells. In this review, we focus on native esophageal specific stem and/or progenitor cells and detail molecular mediators of transcommitment based on recent insights gained from novel mouse models and clinical observations from patients.
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Affiliation(s)
- Wei Zhang
- Esophageal Diseases Center, Department of Internal Medicine and the Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - David H. Wang
- Esophageal Diseases Center, Department of Internal Medicine and the Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA,Medical Service, Dallas VA Medical Center, Dallas, Texas, USA
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30
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Tipirneni KE, Rosenthal EL, Moore LS, Haskins AD, Udayakumar N, Jani AH, Carroll WR, Morlandt AB, Bogyo M, Rao J, Warram JM. Fluorescence Imaging for Cancer Screening and Surveillance. Mol Imaging Biol 2018; 19:645-655. [PMID: 28155079 DOI: 10.1007/s11307-017-1050-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The advent of fluorescence imaging (FI) for cancer cell detection in the field of oncology is promising for both cancer screening and surgical resection. Particularly, FI in cancer screening and surveillance is actively being evaluated in many new clinical trials with over 30 listed on Clinical Trials.gov . While surgical resection forms the foundation of many oncologic treatments, early detection is the cornerstone for improving outcomes and reducing cancer-related morbidity and mortality. The applications of FI are twofold as it can be applied to high-risk patients in addition to those undergoing active surveillance. This technology has the promise of highlighting lesions not readily detected by conventional imaging or physical examination, allowing disease detection at an earlier stage of development. Additionally, there is a persistent need for innovative, cost-effective imaging modalities to ameliorate healthcare disparities and the global burden of cancer worldwide. In this review, we outline the current utility of FI for screening and detection in a range of cancer types.
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Affiliation(s)
- K E Tipirneni
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | - E L Rosenthal
- Department of Otolaryngology, Stanford University, Stanford, CA, USA
| | - L S Moore
- Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - A D Haskins
- Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - N Udayakumar
- Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - A H Jani
- School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - W R Carroll
- Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - A B Morlandt
- Department of Oral and Maxillofacial Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | - M Bogyo
- Department of Pathology, Stanford University, Stanford, CA, USA
| | - J Rao
- Department of Radiology, Stanford University, Stanford, CA, USA
| | - Jason M Warram
- Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA. .,Departments of Otolaryngology, Neurosurgery, & Radiology, The University of Alabama at Birmingham, Birmingham, AL, USA.
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31
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Urbanska AM, Ponnazhagan S, Mozafari M. Pathology, Chemoprevention, and Preclinical Models for Target Validation in Barrett Esophagus. Cancer Res 2018; 78:3747-3754. [PMID: 29959150 DOI: 10.1158/0008-5472.can-18-0206] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 04/13/2018] [Accepted: 05/22/2018] [Indexed: 11/16/2022]
Abstract
Despite esophageal adenocarcinoma (EAC) being the most widespread among gastrointestinal cancers, with an 11-fold increase in the risk of cancer for patients with Barrett esophagus (BE), its prognosis is still poor. There is a critical need to better perceive the biology of cancer progression and identification of specific targets that are the hallmark of BE's progression. This review explores the established animal models of BE, including genetic, surgical and nonsurgical approaches, potential chemoprevention targets, and the reasoning behind their applications to prevent Barrett-related EAC. The key methodological features in the design feasibility of relevant studies are also discussed. Cancer Res; 78(14); 3747-54. ©2018 AACR.
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Affiliation(s)
- Aleksandra M Urbanska
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, New York
| | | | - Masoud Mozafari
- Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran.
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
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32
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Nieto T, Tomlinson CL, Dretzke J, Bayliss S, Price MJ, Dilworth M, Beggs AD, Tucker O. A systematic review of epigenetic biomarkers in progression from non-dysplastic Barrett's oesophagus to oesophageal adenocarcinoma. BMJ Open 2018; 8:e020427. [PMID: 29961009 PMCID: PMC6042533 DOI: 10.1136/bmjopen-2017-020427] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 04/16/2018] [Accepted: 05/03/2018] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVES The objective of this systematic review is to identify and summarise studies which examine epigenetic biomarkers in patients with Barrett's oesophagus (BO) and their association with progression to oesophageal adenocarcinoma (OADC). BO is a precursor lesion for OADC. There is no clinical test to predict patients who are likely to progress to OADC. An epigenetic biomarker could predict patients who are at high risk of progression from BO to OADC which could facilitate earlier diagnosis and spare those unlikely to develop cancer from regular invasive surveillance endoscopy. SETTING A systematic search was conducted of the following databases: MEDLINE, MEDLINE in Process, EMBASE, Cochrane Central, ISI Conference Proceedings Citation Index and the British Library's ZETOC. Studies were conducted in secondary and tertiary care settings. PARTICIPANTS All studies measuring epigenetic change in patients over 18 years old who progressed from non-dysplastic BO to OADC were included. Genetic, in vitro and studies which did not measure progression in the same patient cohort were excluded. Study inclusion and risk of bias of individual eligible studies were assessed in duplicate by two reviewers using a modified Quality in Prognostic Studies tool. RESULTS 14 studies met the inclusion criteria. 42 epigenetic markers were identified, and 5 studies developed models aiming to predict progression to OADC. CONCLUSIONS The evidence from this systematic review is suggestive of a role for p16 as an epigenetic biomarker for the progression of BO to OADC. PROSPERO NUMBER CRD42016038654.
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Affiliation(s)
- Tom Nieto
- Department of Surgery, University of Birmingham, Birmingham, UK
| | - Claire L Tomlinson
- Birmingham Clinical Trials Unit, Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Janine Dretzke
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Susan Bayliss
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Malcolm James Price
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Mark Dilworth
- Department of Surgery, Heart of England Foundation Trust and Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Andrew D Beggs
- Department of Surgery, University of Birmingham, Birmingham, UK
| | - Olga Tucker
- Department of Surgery, University of Birmingham, Birmingham, UK
- Department of Surgery, Heart of England Foundation Trust and Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
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33
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Zhang M, Zhang L, Cui M, Ye W, Zhang P, Zhou S, Wang J. miR-302b inhibits cancer-related inflammation by targeting ERBB4, IRF2 and CXCR4 in esophageal cancer. Oncotarget 2018; 8:49053-49063. [PMID: 28467773 PMCID: PMC5564748 DOI: 10.18632/oncotarget.17041] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Accepted: 04/04/2017] [Indexed: 01/23/2023] Open
Abstract
Cancer related inflammation (CRI) plays an important role in the development of esophageal cancer (EC), and the target gene analysis shows that miR-302b potential target genes closely correlated to CRI important signaling pathways. The present study was to evaluate the inhibition of miR-302b on CRI in EC and its mechanism. We found that the expression levels of miR-302b in EC cells were lower than that in Het-1A cells, while TE11 with the lowest expression and OE33 with the highest. Inflammatory stimuli at 48 h significantly reduced expression of miR-302b in EC cells, but had no effect in Het-1A. After up-regulation of miR-302b in TE11 and down-regulation of miR-302b in OE33, it was found that miR-302b reduced CRI key transcription factors and representative cytokines. Then, over-expressed of miR-302b significantly altered potential target genes protein expressions and there was a negative correlation between miR-302b and potential target genes protein expressions (ERBB4, IRF2 and CXCR4) in EC tissues. Then reporter gene analysis revealed that miR-302b post-transcriptionally regulated expression of target genes by specific area of 3′-UTR. Transfected by target genes shRNA plasmids together could get the same effects of miR-302b on protein expression of CRI key transcription factors. Furthermore, miR-302b was able to repress tumor growth and transcription factors protein expression in vivo. These finding suggests that miR-302b inhibits key transcription factors and cytokines by targeting ERBB4, IRF2 and CXCR4, implicating its role in the inhibition of CRI in EC.
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Affiliation(s)
- Mingxin Zhang
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China
| | - Lingmin Zhang
- Department of Anesthesiology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Manli Cui
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China
| | - Wenguang Ye
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China
| | - Pengjiang Zhang
- Second Department of Cadre's Ward, Lanzhou General Hospital of Chinese PLA, Lanzhou 730050, China
| | - Suna Zhou
- Department of Radiotherapy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China
| | - Jingjie Wang
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China
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van der Sommen F, Klomp SR, Swager AF, Zinger S, Curvers WL, Bergman JJGHM, Schoon EJ, de With PHN. Predictive features for early cancer detection in Barrett's esophagus using Volumetric Laser Endomicroscopy. Comput Med Imaging Graph 2018; 67:9-20. [PMID: 29684663 DOI: 10.1016/j.compmedimag.2018.02.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Revised: 01/22/2018] [Accepted: 02/27/2018] [Indexed: 02/07/2023]
Abstract
The incidence of Barrett cancer is increasing rapidly and current screening protocols often miss the disease at an early, treatable stage. Volumetric Laser Endomicroscopy (VLE) is a promising new tool for finding this type of cancer early, capturing a full circumferential scan of Barrett's Esophagus (BE), up to 3-mm depth. However, the interpretation of these VLE scans can be complicated, due to the large amount of cross-sectional images and the subtle grayscale variations. Therefore, algorithms for automated analysis of VLE data can offer a valuable contribution to its overall interpretation. In this study, we broadly investigate the potential of Computer-Aided Detection (CADe) for the identification of early Barrett's cancer using VLE. We employ a histopathologically validated set of ex-vivo VLE images for evaluating and comparing a considerable set of widely-used image features and machine learning algorithms. In addition, we show that incorporating clinical knowledge in feature design, leads to a superior classification performance and additional benefits, such as low complexity and fast computation time. Furthermore, we identify an optimal tissue depth for classification of 0.5-1.0 mm, and propose an extension to the evaluated features that exploits this phenomenon, improving their predictive properties for cancer detection in VLE data. Finally, we compare the performance of the CADe methods with the classification accuracy of two VLE experts. With a maximum Area Under the Curve (AUC) in the range of 0.90-0.93 for the evaluated features and machine learning methods versus an AUC of 0.81 for the medical experts, our experiments show that computer-aided methods can achieve a considerably better performance than trained human observers in the analysis of VLE data.
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Affiliation(s)
- Fons van der Sommen
- Department of Electrical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands; Department of Gastroenterology, Academic Medical Center, Postbus 22660, 1100 DD Amsterdam, The Netherlands.
| | - Sander R Klomp
- Department of Electrical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
| | - Anne-Fré Swager
- Department of Gastroenterology, Academic Medical Center, Postbus 22660, 1100 DD Amsterdam, The Netherlands.
| | - Svitlana Zinger
- Department of Electrical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
| | - Wouter L Curvers
- Department of Gastroenterology, Academic Medical Center, Postbus 22660, 1100 DD Amsterdam, The Netherlands; Department of Gastroenterology and Hepathology, Catharina Hospital, P.O. Box 1350, 5602ZA Eindhoven, The Netherlands.
| | - Jacques J G H M Bergman
- Department of Gastroenterology, Academic Medical Center, Postbus 22660, 1100 DD Amsterdam, The Netherlands.
| | - Erik J Schoon
- Department of Gastroenterology and Hepathology, Catharina Hospital, P.O. Box 1350, 5602ZA Eindhoven, The Netherlands.
| | - Peter H N de With
- Department of Electrical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
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Cook MB, Coburn SB, Lam JR, Taylor PR, Schneider JL, Corley DA. Cancer incidence and mortality risks in a large US Barrett's oesophagus cohort. Gut 2018; 67:418-529. [PMID: 28053055 PMCID: PMC5827961 DOI: 10.1136/gutjnl-2016-312223] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Revised: 12/01/2016] [Accepted: 12/04/2016] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Barrett's oesophagus (BE) increases the risk of oesophageal adenocarcinoma by 10-55 times that of the general population, but no community-based cancer-specific incidence and cause-specific mortality risk estimates exist for large cohorts in the USA. DESIGN Within Kaiser Permanente Northern California (KPNC), we identified patients with BE diagnosed during 1995-2012. KPNC cancer registry and mortality files were used to estimate standardised incidence ratios (SIR), standardised mortality ratios (SMR) and excess absolute risks. RESULTS There were 8929 patients with BE providing 50 147 person-years of follow-up. Compared with the greater KPNC population, patients with BE had increased risks of any cancer (SIR=1.40, 95% CI 1.31 to 1.49), which slightly decreased after excluding oesophageal cancer. Oesophageal adenocarcinoma risk was increased 24 times, which translated into an excess absolute risk of 24 cases per 10 000 person-years. Although oesophageal adenocarcinoma risk decreased with time since BE diagnosis, oesophageal cancer mortality did not, indicating that the true risk is stable and persistent with time. Relative risks of cardia and stomach cancers were increased, but excess absolute risks were modest. Risks of colorectal, lung and prostate cancers were unaltered. All-cause mortality was slightly increased after excluding oesophageal cancer (SMR=1.24, 95% CI 1.18 to 1.31), but time-stratified analyses indicated that this was likely attributable to diagnostic bias. Cause-specific SMRs were elevated for ischaemic heart disease (SMR=1.39, 95% CI 1.18 to 1.63), respiratory system diseases (SMR=1.51, 95% CI 1.29 to 1.75) and digestive system diseases (SMR=2.20 95% CI 1.75 to 2.75). CONCLUSIONS Patients with BE had a persistent excess risk of oesophageal adenocarcinoma over time, although their absolute excess risks for this cancer, any cancer and overall mortality were modest.
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Affiliation(s)
- Michael B Cook
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA
| | - Sally B Coburn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA
| | - Jameson R Lam
- Division of Research, Oakland Medical Center, Kaiser Permanente, Oakland, California, USA
| | - Philip R Taylor
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA
| | - Jennifer L Schneider
- Division of Research, Oakland Medical Center, Kaiser Permanente, Oakland, California, USA
| | - Douglas A Corley
- Division of Research, Oakland Medical Center, Kaiser Permanente, Oakland, California, USA
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Xiong YQ, Ma SJ, Hu HY, Ge J, Zhou LZ, Huo ST, Qiu M, Chen Q. Comparison of narrow-band imaging and confocal laser endomicroscopy for the detection of neoplasia in Barrett's esophagus: A meta-analysis. Clin Res Hepatol Gastroenterol 2018; 42:31-39. [PMID: 29277482 DOI: 10.1016/j.clinre.2017.05.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 04/19/2017] [Accepted: 05/12/2017] [Indexed: 02/07/2023]
Abstract
AIMS Barrett's esophagus (BE) predisposes to the development of esophageal neoplasia, including high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). A systematic literature review and meta-analysis were performed to assess the accuracy of within-patient comparisons of narrow band imaging (NBI) and confocal laser endomicroscopy (CLE) for diagnosis of HGD/EAC in patients with BE. METHODS The following databases were examined up to April 2016 without language restriction: PubMed, Embase, Medline, Web of Science and the Cochrane Library. The QUADAS-2 tool for assessing the quality of included studies was used. The meta-analysis included pooled additional detection rate (ADR), diagnostic accuracy, and 95% confidence intervals (CI). The I2 and Q-test were used to determine study heterogeneity. RESULTS Five studies involving 251 patients, reported within-patient comparisons of NBI and CLE, were eligible for meta-analysis. Compared with NBI, pooled ADR of CLE for per-lesion detection of neoplasia in patients with BE was 19.3% (95% CI: 0.05-0.33, I2=74.6%). The pooled sensitivity of NBI was 62.8% (95% CI: 0.56-0.69, I2=94.6%), which was lower (not significantly) than that of CLE (72.3%, 95% CI: 0.66-0.78, I2=89.3%). The pooled specificity of NBI and CLE were similar [85.3% (95% CI: 0.84-0.87, I2=92.1%) vs 83.8% (95% CI: 0.82-0.85, I2=96.8%)]. CONCLUSIONS When compared with NBI, CLE significantly increased the per-lesion detection rate of esophageal neoplasia, HGD, and EAC in BE patients. Whether CLE is superior to NBI in neoplasia detection at per-patient level needs to be further investigated.
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Affiliation(s)
- Yi-Quan Xiong
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangdong Provincial Key Laboratory of Tropical Disease Research, 1838 Guangzhou North Road, 510515 Guangzhou, China
| | - Shu-Juan Ma
- School of Public Health, Central South University, Changsha, 410008 Hunan, China
| | - Hao-Yue Hu
- Medical College, University of South China, 421000 Hengyang, China
| | - Jing Ge
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangdong Provincial Key Laboratory of Tropical Disease Research, 1838 Guangzhou North Road, 510515 Guangzhou, China
| | - Li-Zhi Zhou
- Department of Biostatistics, School of Public Health, Southern Medical University, 1838 Guangzhou North Road, 510515 Guangzhou, China
| | - Shu-Ting Huo
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangdong Provincial Key Laboratory of Tropical Disease Research, 1838 Guangzhou North Road, 510515 Guangzhou, China
| | - Min Qiu
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangdong Provincial Key Laboratory of Tropical Disease Research, 1838 Guangzhou North Road, 510515 Guangzhou, China
| | - Qing Chen
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangdong Provincial Key Laboratory of Tropical Disease Research, 1838 Guangzhou North Road, 510515 Guangzhou, China.
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Zhang C, Shen Y, Wang J, Zhou M, Chen Y. Identification of key pathways and genes in Barrett's esophagus using integrated bioinformatics methods. Mol Med Rep 2018; 17:3069-3077. [PMID: 29257318 PMCID: PMC5783528 DOI: 10.3892/mmr.2017.8274] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 11/14/2017] [Indexed: 12/30/2022] Open
Abstract
Barrett's esophagus (BE) is a premalignant lesion of esophageal adenocarcinoma. The aim of the present study was to investigate the possible mechanisms and biomarkers of BE. To identify the differentially expressed microRNAs (DEmiRNAs) and genes (DEGs) in BE, the miRNA expression profile GSE20099 and the gene expression profiles GSE26886, GSE13083 and GSE34619 were obtained from the Gene Expression Omnibus (GEO) database. DEGs and DEmiRNAs were screened for using the GEO2R tool. Using DAVID, functional and pathway enrichment analysis was performed to explore the biological function of identified DEGs. The protein‑protein interaction (PPI) network was detected using STRING and constructed by Cytoscape software. Furthermore, targets of identified DEmiRNAs were predicted by the miRecords database, then integrated with the identified DEGs to obtain key genes involved in BE. In total, 311 DEGs were identified. These genes were significantly enriched in the pancreatic secretion, metabolic pathways and cytochrome P450 drug metabolism pathways. In the PPI network, 16 hub genes, including keratin 16, cystic fibrosis transmembrane conductance regulator, involucrin, protein kinase C α and cadherin 17 were identified. Following integration of the predicted target genes of DEmiRNAs with DEGs, three key BE genes were identified: PRKCA, CDH17 and epiregulin. In conclusion, a comprehensive bioinformatics analysis of identified DEGs and DEmiRNAs was performed to elucidate potential pathways and biomarkers involved in the development of BE.
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Affiliation(s)
- Cong Zhang
- Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
| | - Yujie Shen
- Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
| | - Jiazheng Wang
- Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
| | - Mingxia Zhou
- Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
| | - Yingwei Chen
- Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, Shanghai 200092, P.R. China
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Wang R. Applications of acetic acid spray combined with narrow band imaging in diagnosis of early gastrointestinal cancers and precancerous lesions. Shijie Huaren Xiaohua Zazhi 2017; 25:2605-2614. [DOI: 10.11569/wcjd.v25.i29.2605] [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: 02/06/2023] Open
Abstract
Many new endoscopic techniques have been used for the diagnosis of early gastrointestinal cancers and precancerous lesions, such as magnifying endoscopy, narrow-band imaging (NBI), Fuji intelligent chromoendiscopy, i-scan imaging, confocal laser endomicroscopy, and chromoendoscopy (Lugol's iodine, indigo carmine, methylene blue, acetic acid, and crystal violet). Each technique has its own advantages and disadvantages (e.g., being expensive and prolonged examination duration). Spraying acetic acid onto the mucosal surface can enhance the recognition of mucosal surface architecture, and NBI has the advantage to display the microvascular morphology. Thus, acetic acid spray combined with NBI endoscopy can greatly improve the diagnosis of early gastrointestinal cancers and precancerous lesions. Since this combination has low cost and no adverse reactions, they can be used in primary hospitals without magnification endoscopy.
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Affiliation(s)
- Rong Wang
- Department of Gastroenterology, Guangming Hospital of Traditional Chinese Medicine of Shanghai Pudong New Area, Shanghai 201399, China
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Lim L, Streutker CJ, Marcon N, Cirocco M, Lao A, Iakovlev VV, DaCosta R, Wilson BC. A feasibility study of photoacoustic imaging of ex vivo endoscopic mucosal resection tissues from Barrett's esophagus patients. Endosc Int Open 2017; 5:E775-E783. [PMID: 28791328 PMCID: PMC5546898 DOI: 10.1055/s-0043-111790] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 05/02/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND AND STUDY AIMS Accurate endoscopic detection of dysplasia in patients with Barrett's esophagus (BE) remains a major clinical challenge. The current standard is to take multiple biopsies under endoscopic image guidance, but this leaves the majority of the tissue unsampled, leading to significant risk of missing dysplasia. Furthermore, determining whether there is submucosal invasion is essential for proper staging. Hence, there is a clinical need for a rapid in vivo wide-field imaging method to identify dysplasia in BE, with the capability of imaging beyond the mucosal layer. We conducted an ex vivo feasibility study using photoacoustic imaging (PAI) in patients undergoing endoscopic mucosal resection (EMR) for known dysplasia. The objective was to characterize the esophageal microvascular pattern, with the long-term goal of performing in vivo endoscopic PAI for dysplasia detection and therapeutic guidance. MATERIALS AND METHODS EMR tissues were mounted luminal side up. The tissues were scanned over a field of view of 14 mm (width) by 15 mm (depth) at 680, 750, and 850 nm (40 MHz acoustic central frequency). Ultrasound and photoacoustic images were simultaneously acquired. Tissues were then sliced and fixed in formalin for histopathology with hematoxylin and eosin staining. A total of 13 EMR specimens from eight patients were included in the analysis, which consisted of co-registration of the photoacoustic images with corresponding pathologist-classified histological images. We conducted mean difference test of the total hemoglobin distribution between tissue classes. RESULTS Dysplastic and nondysplastic BE can be distinguished from squamous tissue in 84 % of region-of-interest comparisons (42/50). However, the ability of intrinsic PAI to distinguish dysplasia from NDBE, which is the clinically important challenge, was only about 33 % (10/30). CONCLUSION We demonstrated the technical feasibility of this approach. Based on our ex vivo data, changes in total hemoglobin content from intrinsic PAI (i. e. without exogenous contrast) can differentiate BE from squamous esophageal mucosa. However, most likely intrinsic PAI is unable to differentiate dysplastic from nondysplastic BE with adequate sensitivity for clinical translation.
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Affiliation(s)
- Liang Lim
- Princess Margaret Cancer Centre, Toronto, Ontario, Canada,Corresponding author Liang Lim, PhD University Health Network – Princess Margaret Cancer Centre101 College StreetPMCRT #15-301V TorontoOntario M5G 1L7Canada
| | | | | | | | | | | | - Ralph DaCosta
- Princess Margaret Cancer Centre, Toronto, Ontario, Canada
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Choi YJ, Lee DH, Han KD, Yoon H, Shin CM, Park YS, Kim N. Joint Effects of Low Body Mass Index and Alcohol Consumption on Developing Esophageal Squamous Cell Cancer: a Korean Nationwide Population-Based Cohort Study. Asian Pac J Cancer Prev 2017; 18:1881-1887. [PMID: 28749616 PMCID: PMC5648394 DOI: 10.22034/apjcp.2017.18.7.1881] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Objective: In Korea, 95% of esophageal cancer (EC) was the squamous cell-type. We sought to determine the combined risk of alcohol consumption on developing esophageal squamous cell carcinoma (ESCC) in pre-diagnostic underweight subjects using Korean national data. Methods: We analyzed the clinical data from a total of 264,084 individuals aged 40 years or older, who received healthcare checkups arranged by the national insurance program, between 2003 and 2008 in Korea. Cox proportional hazards regression was used after adjusting confounding factors. Result: Newly diagnosed 278 EC was identified using the claims data during a median follow-up duration of 7.9 years. It was determined that underweight and obesity-compared with normal weight-were significantly associated with 73% increased risk and 30% decreased risk of EC, respectively. Weight gain reduced the risk of EC. Alcohol consumption increased risk for EC in a dose-dependent manner. Heavy alcohol consumption in individuals with underweight increased the risk of developing EC dramatically. Conclusion: Underweight was a risk factor for ESCC and alcohol consumption raised the risk synergistically with low BMI. Achieving normal range of BMI could reduce the risk of ESCC.
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Affiliation(s)
- Yoon Jin Choi
- Department of Internal Medicine and Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea.
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Soletti RC, Biasoli D, Rodrigues NALV, Delou JMA, Maciel R, Chagas VLA, Martins RAP, Rehen SK, Borges HL. Inhibition of pRB Pathway Differentially Modulates Apoptosis in Esophageal Cancer Cells. Transl Oncol 2017; 10:726-733. [PMID: 28734226 PMCID: PMC5521024 DOI: 10.1016/j.tranon.2017.06.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 06/21/2017] [Accepted: 06/21/2017] [Indexed: 01/06/2023] Open
Abstract
Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Current chemotherapy regimens include a combination of 5-fluorouracil (5-FU) and cisplatin, but more efficient therapy strategies are needed to increase 5-year survival. Alterations in the signaling pathway of the tumor suppressor gene Rb-1, which encodes a phosphoprotein (pRB) that negatively regulates the G1/S transition of the cell cycle, are present in 70% of all tumors, but its role in esophageal cancer is still unclear. Most of these are alterations leading to up-regulation of the activity of cyclin-dependent kinases (CDKs) to phosphorylate pRB, which suggests that keeping the wild type pRB phosphorylated might be advantageous. Besides proliferation, pRB also regulates apoptosis induced by tumor necrosis factor-alpha (TNF-α) and DNA-damage. We investigated the status of phosphorylation of pRB along esophageal tumorigenesis stages, as well as whether hyperphosphorylation of pRB could suppress apoptosis induced by cisplatin, 5-FU, or TNF-α in esophageal cancer cells. pRB phosphorylation increased progressively from normal esophageal tissue to metaplasia and adenocarcinoma, suggesting that pRB phosphorylation increases along esophageal tumor stages. When RB-1 was knocked down or CDK inhibitors reduced the levels of phosphorylated pRB, opposite apoptotic effects were observed, depending on the combination of drugs tested: whereas TNF-α- and cisplatin-induced apoptosis increased, 5-FU-induced apoptosis decreased. Taken together, these data suggest that pRB plays a role in esophageal adenocarcinoma and that, depending on the type of anti-cancer treatment, combining CDK inhibitors and chemotherapy has the potential to increase the sensitivity of esophageal cancer cells to cell death.
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Affiliation(s)
- Rossana C Soletti
- Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21949-590; Pharmacy Unit, State University of West Zone, Rio de Janeiro, Rio de Janeiro, Brazil.
| | - Deborah Biasoli
- Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21949-590.
| | - Nathassya A L V Rodrigues
- Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21949-590.
| | - João M A Delou
- Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21949-590.
| | - Renata Maciel
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ, Brazil.
| | - Vera L A Chagas
- Pathology Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
| | - Rodrigo A P Martins
- Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21949-590.
| | - Stevens K Rehen
- Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21949-590; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ, Brazil.
| | - Helena L Borges
- Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 21949-590.
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Lim L, Mastragostino R, Ng K, Zheng G, Wilson BC. Can photoacoustic imaging quantify surface-localized J-aggregating nanoparticles? JOURNAL OF BIOMEDICAL OPTICS 2017; 22:76008. [PMID: 28703256 DOI: 10.1117/1.jbo.22.7.076008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Accepted: 06/21/2017] [Indexed: 05/07/2023]
Abstract
We investigate the feasibility of photoacoustic (PA) imaging to quantify the concentration of surface-localized nanoparticles, using tissue-mimicking phantoms and imaging with a commercial PA instrument at 815 nm and a linear-array transducer at a center frequency of 40 MHz. The nanoparticles were J-aggregating porphysomes (JNP) comprising self-assembling, all-organic porphyrin-lipid micelles with a molar absorption coefficient of 8.7×108 cm−1 M−1 at this wavelength. The PA signal intensity versus JNP areal concentration followed a sigmoidal curve with a reproducible linear range of ∼17 fmol/mm2 to 11 pmol/mm2, i.e., ∼3 orders of magnitude with ±34% error. For physiologically-relevant conditions (i.e., optical scattering-dominated tissues: transport albedo >0.8) and JNP concentrations above ∼330 fmol/mm2, the PA signal depends only on the nanoparticle concentration. Otherwise, independent measurement of the optical absorption and scattering properties of the underlying tissue is required for accurate quantification. The implications for surface PA imaging, such as in the use of targeted nanoparticles applied topically to tissue as in endoscopic diagnosis, are considered.
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Affiliation(s)
- Liang Lim
- University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Robert Mastragostino
- University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Kenneth Ng
- University of Toronto, Department of Medical Biophysics, Toronto, Ontario, Canada
| | - Gang Zheng
- University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, CanadabUniversity of Toronto, Department of Medical Biophysics, Toronto, Ontario, Canada
| | - Brian C Wilson
- University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, CanadabUniversity of Toronto, Department of Medical Biophysics, Toronto, Ontario, Canada
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Abstract
Optimizing the management of colorectal cancer (CRC) risk in IBD requires a fundamental understanding of the evolutionary process underpinning tumorigenesis. In IBD, clonal evolution begins long before the development of overt neoplasia, and is probably accelerated by the repeated cycles of epithelial wounding and repair that are characteristic of the condition. Here, we review the biological drivers of mutant clone selection in IBD with particular reference to the unique histological architecture of the intestinal epithelium coupled with the inflammatory microenvironment in IBD, and the unique mutation patterns seen in IBD-driven neoplasia when compared with sporadic adenomas and CRC. How these data can be leveraged as evolutionary-based biomarkers to predict cancer risk is discussed, as well as how the efficacy of CRC surveillance programmes and the management of dysplasia can be improved. From a research perspective, the longitudinal surveillance of patients with IBD provides an under-exploited opportunity to investigate the biology of the human gastrointestinal tract over space and time.
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Affiliation(s)
- Chang-Ho R Choi
- Evolution and Cancer Laboratory, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Inflammatory Bowel Disease Unit, Level 4 St Mark's Hospital, Watford Road, London HA1 3UJ, UK
| | - Ibrahim Al Bakir
- Evolution and Cancer Laboratory, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
- Inflammatory Bowel Disease Unit, Level 4 St Mark's Hospital, Watford Road, London HA1 3UJ, UK
| | - Ailsa L Hart
- Inflammatory Bowel Disease Unit, Level 4 St Mark's Hospital, Watford Road, London HA1 3UJ, UK
| | - Trevor A Graham
- Evolution and Cancer Laboratory, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
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Busby J, Murchie P, Murray L, Iversen L, Lee AJ, Spence A, Watson MC, Cardwell CR. The effect of medications which cause inflammation of the gastro-oesophageal tract on cancer risk: a nested case-control study of routine Scottish data. Int J Cancer 2017; 140:1828-1835. [PMID: 28120338 DOI: 10.1002/ijc.30612] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 12/22/2016] [Accepted: 01/10/2017] [Indexed: 12/14/2022]
Abstract
Bisphosphonate, tetracycline and spironolactone use has been shown to increase gastro-oesophageal inflammation, an accepted risk factor for cancer. However, evidence of the effect of these medications on gastro-oesophageal cancer risk are mixed or missing entirely. Therefore, we conducted a nested case-control study using the Primary Care Clinical Information Unit Research (PCCIUR) database from Scotland. Cases with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five controls based on age, gender, year of diagnosis and general practice. Medication use was ascertained using electronic prescribing records. Conditional logistic regression was used to calculate odds ratios (ORs) for the association between medication use and cancer risk after adjustment for comorbidities and other medication use. A similar proportion of gastro-oesophageal cancer cases received bisphosphonates (3.9% vs. 3.5%), tetracycline (6.0% vs. 6.0%) and spironolactone (1.4% vs. 1.1%) compared with the controls. The adjusted ORs for the association between gastro-oesophageal cancer and bisphosphonates, tetracycline and spironolactone were 1.05 (95% CI: 0.85, 1.31), 0.99 (95% CI: 0.84, 1.17) and 1.04 (95% CI: 0.73, 1.49). Further analysis revealed bisphosphonates were associated with increased oesophageal cancer risk (1.34, 95% CI: 1.03, 1.74) but reduced gastric cancer risk (0.71, 95% CI: 0.49, 1.03), although there was no obvious dose-response relationship. Overall, there is little evidence that the use of bisphosphonate, tetracycline or spironolactone is associated with increased risk of gastro-oesophageal cancer. Our findings should reassure GPs and patients that these widely-used medications are safe with respect to gastro-oesophageal cancer risk.
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Affiliation(s)
- John Busby
- Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom
| | - Peter Murchie
- Academic Primary Care, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom
| | - Liam Murray
- Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom
| | - Lisa Iversen
- Academic Primary Care, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom
| | - Amanda J Lee
- Medical Statistics Team, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom
| | - Andrew Spence
- Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom
| | - Margaret C Watson
- Department of Pharmacy and Pharmacology, University of Bath, United Kingdom
| | - Chris R Cardwell
- Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom
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Nieto T, Tomlinson CL, Dretzke J, Bayliss S, Dilworth M, Beggs AD, Tucker O. Epigenetic biomarkers in progression from non-dysplastic Barrett's oesophagus to oesophageal adenocarcinoma: a systematic review protocol. BMJ Open 2016; 6:e013361. [PMID: 27927666 PMCID: PMC5168625 DOI: 10.1136/bmjopen-2016-013361] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION Barrett's oesophagus (BO), a metaplastic condition affecting the lower oesophagus due to long-standing gastro-oesophageal reflux and chronic inflammation, is a precursor lesion for oesophageal adenocarcinoma (OADC). There is no clinical test to predict which patients with BO will progress to OADC. The British Society of Gastroenterology recommends endoscopic surveillance of patients with BO. Epigenetic changes have been well characterised in the neoplastic progression of ulcerative colitis to colonic carcinoma, another gastrointestinal cancer associated with chronic inflammation. This systematic review protocol aims to identify and evaluate studies which examine epigenetic biomarkers in BO and their association with progression to OADC. METHODS AND ANALYSIS All prospective and retrospective primary studies, and existing systematic reviews investigating epigenetic markers including DNA methylation, histone modification, chromatin remodelling, micro and non-coding RNAs of all types will be eligible for inclusion. Eligible patients are those over the age of 18 with BO, BO with dysplasia, OADC or unspecified oesophageal cancer. A comprehensive search of bibliographic databases using combinations of text and index words relating to the population, prognostic markers and outcome will be undertaken with no language restrictions. Results will be screened by 2 independent reviewers and data extracted using a standardised proforma. The quality and risk of bias of individual studies will be assessed using the Quality in Prognostic Studies (QUIPS) tool. A narrative synthesis of all evidence will be performed with key findings tabulated. Meta-analysis will be considered where studies and reported outcomes are considered sufficiently homogeneous, both clinically and methodologically. Findings will be interpreted in the context of the quality of included studies. The systematic review will be reported according to PRISMA guidelines. ETHICS AND DISSEMINATION This is a systematic review of completed studies and no ethical approval is required. Findings from the full systematic review will be submitted for publication and presentation at national and international conferences which will inform future research on risk stratification in patients with BO. REVIEW REGISTRATION NUMBER CRD42016038654.
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Affiliation(s)
- T Nieto
- Department of Surgery, University of Birmingham, Birmingham, UK
| | - C L Tomlinson
- Birmingham Clinical Trials Unit, Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - J Dretzke
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - S Bayliss
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - M Dilworth
- Department of Surgery, Heart of England Foundation Trust and Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - A D Beggs
- Department of Surgery, University of Birmingham, Birmingham, UK
| | - O Tucker
- Department of Surgery, University of Birmingham, Birmingham, UK
- Department of Surgery, Heart of England Foundation Trust and Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
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46
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The evolution and outcome of surveillance of Barrett's oesophagus over four decades in a UK District General Hospital. Eur J Gastroenterol Hepatol 2016; 28:1365-1373. [PMID: 27571366 DOI: 10.1097/meg.0000000000000730] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
INTRODUCTION We present the long-term outcome of Barrett's oesophagus (BO) at a District General Hospital set against the increasing numbers of patients with gastro-oesophageal reflux disease (GORD). METHODS Data were collected prospectively over 37 years. Comparison of GORD without Barrett's (NoBO) versus BO was performed from 1/1/1977 to 31/12/2001 when the NoBO database closed and outcomes of all cases of BO diagnosed until 31/12/2011 and followed up until 31/12/2013 have been reported. RESULTS During the period 1977-2001 the number of GORD NoBO cases was 11 610, and that of BO cases was 764 (6.2% of all GORD); total number of BO cases in 1977-2011 was 1468. NoBO patients were younger than BO patients: 52.2 versus 61.6 years. There was a male predominance in both groups: NoBO 55% and BO 62% (P<0.0001). The prevalence of oesophageal adenocarcinoma (OAC) was 87/1468 (5.9%) BO cases. Its incidence was 54/1381 (3.9%); the mean interval between the diagnosis of BO and incident OAC was 9 years (range 13 months-25.4 years); there was one OAC per 192 patient-years of follow-up (0.52% per year). Mortality was significantly lower in 37 patients under endoscopic surveillance at the time OAC was diagnosed (51 vs. 88% P=0.0141) partly because of older age and comorbidity of the other 17, in whom serial endoscopy was contraindicated. A proportional hazards model to allow for age estimated that the hazard rate ratio was lower in the surveillance group; however, this difference did not reach statistical significance (0.64, 95% confidence interval 0.30-1.48, P=0.08). Excluding prevalent cancers from both groups, mortality in BO was double that in NoBO (47 vs. 24%). CONCLUSION These 37 years of observation suggest, but do not confirm, that endoscopic surveillance may reduce the risk of death from OAC. Modern technology is likely to yield better results, but larger prospective studies are needed to confirm the benefits.
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47
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Thrift AP, Anderson LA, Murray LJ, Cook MB, Shaheen NJ, Rubenstein JH, El-Serag HB, Vaughan TL, Schneider JL, Whiteman DC, Corley DA. Nonsteroidal Anti-Inflammatory Drug Use is Not Associated With Reduced Risk of Barrett's Esophagus. Am J Gastroenterol 2016; 111:1528-1535. [PMID: 27575711 PMCID: PMC5209791 DOI: 10.1038/ajg.2016.348] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Accepted: 07/22/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced risk of esophageal adenocarcinoma. Epidemiological studies examining the association between NSAID use and the risk of the precursor lesion, Barrett's esophagus, have been inconclusive. METHODS We analyzed pooled individual-level participant data from six case-control studies of Barrett's esophagus in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). We compared medication use from 1,474 patients with Barrett's esophagus separately with two control groups: 2,256 population-based controls and 2,018 gastroesophageal reflux disease (GERD) controls. Study-specific odds ratio (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models and were combined using a random-effects meta-analytic model. RESULTS Regular (at least once weekly) use of any NSAIDs was not associated with the risk of Barrett's esophagus (vs. population-based controls, adjusted OR=1.00, 95% CI=0.76-1.32, I2=61%; vs. GERD controls, adjusted OR=0.99, 95% CI=0.82-1.19, I2=19%). Similar null findings were observed among individuals who took aspirin or non-aspirin NSAIDs. We also found no association with highest levels of frequency (at least daily use) and duration (≥5 years) of NSAID use. There was evidence of moderate between-study heterogeneity; however, associations with NSAID use remained non-significant in "leave-one-out" sensitivity analyses. CONCLUSIONS Use of NSAIDs was not associated with the risk of Barrett's esophagus. The previously reported inverse association between NSAID use and esophageal adenocarcinoma may be through reducing the risk of neoplastic progression in patients with Barrett's esophagus.
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Affiliation(s)
- Aaron P. Thrift
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA,Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA
| | - Lesley A. Anderson
- Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland
| | - Liam J. Murray
- Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland
| | - Michael B. Cook
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Nicholas J. Shaheen
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Joel H. Rubenstein
- Center for Clinical Management Research, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan, USA,Barrett's Esophagus Program, Division of Gastroenterology Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Hashem B. El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA,Department of Medicine, Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas, USA
| | - Thomas L. Vaughan
- Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Jennifer L. Schneider
- Kaiser Permanente Division of Research, Oakland, California and San Francisco Medical Center, USA
| | - David C. Whiteman
- QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Douglas A. Corley
- Kaiser Permanente Division of Research, Oakland, California and San Francisco Medical Center, USA
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Li N, Pasricha S, Bulsiewicz WJ, Pruitt RE, Komanduri S, Wolfsen HC, Chmielewski GW, Corbett FS, Chang KJ, Shaheen NJ. Effects of preceding endoscopic mucosal resection on the efficacy and safety of radiofrequency ablation for treatment of Barrett's esophagus: results from the United States Radiofrequency Ablation Registry. Dis Esophagus 2016; 29:537-543. [PMID: 26121935 PMCID: PMC4977202 DOI: 10.1111/dote.12386] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The effects of preceding endoscopic mucosal resection (EMR) on the efficacy and safety of radiofrequency ablation (RFA) for treatment of nodular Barrett's esophagus (BE) is poorly understood. Prior studies have been limited to case series from individual tertiary care centers. We report the results of a large, multicenter registry. We assessed the effects of preceding EMR on the efficacy and safety of RFA for nodular BE with advanced neoplasia (high-grade dysplasia or intramucosal carcinoma) using the US RFA Registry, a nationwide study of BE patients treated with RFA at 148 institutions. Safety outcomes included stricture, gastrointestinal bleeding, and hospitalization. Efficacy outcomes included complete eradication of intestinal metaplasia (CEIM), complete eradication of dysplasia (CED), and number of RFA treatments needed to achieve CEIM. Analyses comparing patients with EMR before RFA to patients undergoing RFA alone were performed with Student's t-test, Chi-square test, logistic regression, and Kaplan-Meier analysis. Four hundred six patients were treated with EMR before RFA for nodular BE, and 857 patients were treated with RFA only for non-nodular BE. The total complication rates were 8.4% in the EMR-before-RFA group and 7.2% in the RFA-only group (P = 0.48). Rates of stricture, bleeding, and hospitalization were not significantly different between patients treated with EMR before RFA and patients treated with RFA alone. CEIM was achieved in 84% of patients treated with EMR before RFA, and 84% of patients treated with RFA only (P = 0.96). CED was achieved in 94% and 92% of patients in EMR-before-RFA and RFA-only group, respectively (P = 0.17). Durability of eradication did not differ between the groups. EMR-before-RFA for nodular BE with advanced neoplasia is effective and safe. The preceding EMR neither diminished the efficacy nor increased complication rate of RFA treatment compared to patients with advanced neoplasia who had RFA with no preceding EMR. Preceding EMR is not associated with poorer outcomes in RFA.
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Affiliation(s)
- N Li
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - S Pasricha
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - W J Bulsiewicz
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - R E Pruitt
- Nashville Gastrointestinal Specialists, Nashville, Tennessee, USA
| | - S Komanduri
- Northwestern University School of Medicine, Chicago, Illinois, USA
| | - H C Wolfsen
- Mayo Clinic Florida, Jacksonville, Florida, USA
| | | | - F S Corbett
- Gastroenterology Associates of Sarasota, Sarasota, Florida, USA
| | - K J Chang
- University of California at Irvine, Orange, California, USA
| | - N J Shaheen
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Krishnamoorthi R, Borah B, Heien H, Das A, Chak A, Iyer PG. Rates and predictors of progression to esophageal carcinoma in a large population-based Barrett's esophagus cohort. Gastrointest Endosc 2016; 84:40-46.e7. [PMID: 26772891 PMCID: PMC4912845 DOI: 10.1016/j.gie.2015.12.036] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2015] [Accepted: 12/30/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Rates of progression to esophageal adenocarcinoma in subjects with Barrett's esophagus (BE) are lower than previously estimated. Identification of predictors of progression will enable risk stratification of BE subjects, potentially making current surveillance programs more efficient. We aimed to assess the potential of demographic and lifestyle factors, obesity, and medications in predicting progression in BE. METHODS BE subjects were identified from the General Practice Research Database using validated diagnostic codes. BE subjects developing esophageal cancer (EC) 12 months after their index BE diagnosis were defined as progressors. Time-to-event analysis was used to assess the overall risk of progression to EC. Cox proportional hazards models and time-varying marginal structural models were used to assess predictors of progression. RESULTS Included in the analysis were 9660 BE patients. The mean age (SD) of the study subjects was 63 (13.5) years; 62.6% were men. One hundred three subjects (1.1%) progressed to EC. The mean (SD) follow-up since initial diagnosis was 4.8 (3.3) years. The incidence of EC was 2.23 per 1000 person-years of follow-up. Increasing age, male gender, and being overweight (body mass index, 25-29.9) were found to be independent predictors of progression. When time-varying models were used, proton pump inhibitor (PPI) and statin use were protective against progression. CONCLUSIONS In this large population-based cohort of patients with BE, increasing age, male gender, and being overweight predicted progression to EC, whereas PPI and statin use were protective against EC development. These factors may aid in developing a risk score to predict the risk of progression and chemopreventive strategies in patients with BE.
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Affiliation(s)
| | - Bijan Borah
- Division of Health Care Policy and Research, Mayo Clinic, Rochester, MN 55905
| | - Herbert Heien
- Division of Health Care Policy and Research, Mayo Clinic, Rochester, MN 55905
| | - Ananya Das
- Arizona Center for Digestive Health, Gilbert, AZ
| | - Amitabh Chak
- Division of Gastroenterology & Hepatology, Case Western Reserve University, Cleveland, OH
| | - Prasad G. Iyer
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905
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50
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Haverkamp L, Parry K, van Berge Henegouwen MI, van Laarhoven HW, Bonenkamp JJ, Bisseling TM, Siersema PD, Sosef MN, Stoot JH, Beets GL, de Steur WO, Hartgrink HH, Verspaget HW, van der Peet DL, Plukker JT, van Etten B, Wijnhoven BPL, van Lanschot JJ, van Hillegersberg R, Ruurda JP. Esophageal and Gastric Cancer Pearl: a nationwide clinical biobanking project in the Netherlands. Dis Esophagus 2016; 29:435-41. [PMID: 25824294 DOI: 10.1111/dote.12347] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Esophageal and gastric cancer is associated with a poor prognosis since many patients develop recurrent disease. Treatment requires specific expertise and a structured multidisciplinary approach. In the Netherlands, this type of expertise is mainly found at the University Medical Centers (UMCs) and a few specialized nonacademic centers. Aim of this study is to implement a national infrastructure for research to gain more insight in the etiology and prognosis of esophageal and gastric cancer and to evaluate and improve the response on (neoadjuvant) treatment. Clinical data are collected in a prospective database, which is linked to the patients' biomaterial. The collection and storage of biomaterial is performed according to standard operating procedures in all participating UMCs as established within the Parelsnoer Institute. The collected biomaterial consists of tumor biopsies, blood samples, samples of malignant and healthy tissue of the resected specimen and biopsies of recurrence. The collected material is stored in the local biobanks and is encoded to respect the privacy of the donors. After approval of the study was obtained from the Institutional Review Board, the first patient was included in October 2014. The target aim is to include 300 patients annually. In conclusion, the eight UMCs of the Netherlands collaborated to establish a nationwide database of clinical information and biomaterial of patients with esophageal and gastric cancer. Due to the national coverage, a high number of patients are expected to be included. This will provide opportunity for future studies to gain more insight in the etiology, treatment and prognosis of esophageal and gastric cancer.
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Affiliation(s)
- L Haverkamp
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - K Parry
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - H W van Laarhoven
- Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands
| | - J J Bonenkamp
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - T M Bisseling
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - P D Siersema
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - M N Sosef
- Department of Surgery, Atrium Medical Center Parkstad, Heerlen, The Netherlands
| | - J H Stoot
- Department of Surgery, Orbis Medical Center, Sittard, The Netherlands
| | - G L Beets
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - W O de Steur
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - H H Hartgrink
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | | | - D L van der Peet
- Department of Surgery, VU Medical Center, Amsterdam, The Netherlands
| | - J T Plukker
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - B van Etten
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - B P L Wijnhoven
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - J J van Lanschot
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - R van Hillegersberg
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - J P Ruurda
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
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