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A 73-year-old male patient was referred to us with a long Barrett's esophagus (BE). He had a history of pulmonary embolism under anticoagulant therapy. Esophagogastroduodenoscopy showed a C8M9 BE with no macroscopic lesions. Random biopsies from the BE revealed multifocal high-grade dysplasia. The case was discussed in a multidisciplinary team conference and the decision for full resection of BE with endoscopic submucosal dissection (ESD) was made. Considering the large ESD resection and the high risk of stricture, we developed a novel preventive technique: the "steroid lifting method" for submucosal injection during ESD. Complete circumferential ESD with en bloc resection was performed using the "steroid lifting method", without adverse events. Oral liquids were initiated on day 1 and the patient was discharged on day 4. Oral prednisolone (30 mg per day) was started and tapered for a total of 6 weeks. The pathological examination confirmed multifocal high-grade dysplasia, with radical and curative resection. The patient had neither stricture, dysphagia nor recurrence of Barrett's mucosa at the 2, 6, 12, and 24-month follow-up. International guidelines recommend oral prednisolone and triamcinolone injection to prevent stricture formation in large ESD of esophageal squamous cell carcinoma. However, there is no solid data on BE ESD. The risk factors for stricture formation and the optimal preventive management after large BE ESD is not known. The "steroid lifting method" might be an option in this context. Large prospective studies addressing stricture formation and preventive measures on BE ESD are necessary.
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BACKGROUND: The mainstay approach in endoscopic eradication therapy (EET) for dysplastic Barrett's esophagus (BE) includes the endoscopic resection of visible lesions, accompanied by ablation of the residual metaplastic epithelium. Cryoablation therapy is one such emerging ablation technique in this field. This systematic review with a meta-analysis aims to accumulate pooled data on cryoablation performance in the treatment of patients with BE and to compare this technique to the standard of care radiofrequency ablation (RFA). METHODS: The MEDLINE, Cochrane, and Scopus databases were searched until June 2024 for studies evaluating BE management using cryoablation for cumulative results. The primary outcome was the complete eradication of dysplasia (CED) and intestinal metaplasia (CEIM) in BE compared to RFA, while secondary outcomes included the respective pooled rates using cryoablation, recurrence, and adverse events, with a separate analysis for strictures. The meta-analyses were based on a random-effects model, and the results were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses by type of cryoablation were also performed. RESULTS: Twenty-three studies (1604 patients) were finally included, four of which were comparative. CED and CEIM did not differ significantly between cryoablation and RFA [OR= 0.95 (95%CI: 0.50-1.81) and OR = 0.57 (95%CI: 0.20-1.63), respectively)]. The pooled rates of CED, CEIM, and recurrence after cryoablation were 84.2% (95%CI: 79.1-89.3), 64.1% (95%CI: 49.2-79.0), and 8.3% (95%CI: 4.7-11.9), accompanied by high rates of heterogeneity. Adverse events were noted in 14.5% (95%CI: 9.9-19.2) of cases, and 6.5% (95%CI: 4.1-9.0) developed strictures. In the subgroup analysis, the cryoballoon achieved a reduction in heterogeneity in CED, adverse events, and stricture formation, whereas spray catheters provided homogenous results in terms of recurrence. CONCLUSIONS: Cryoablation provides equal outcomes compared to RFA in the treatment of patients with BE, with the cryoballoon achieving relatively homogenous rates of CED and adverse events.
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This study investigated methods for sampling bile acids in saliva, a potential non-invasive diagnostic biofluid. Bile acids have been implicated in causing damage and permanent changes to the esophageal mucosa and increasing the risk of developing Barrett's esophagus, a condition that can potentially progress to esophageal cancer. Three saliva collection methods were compared: spitting, Salivette® swabs, and Salivette Cortisol® swabs. Spitting emerged as the superior method with the highest recoveries and the least interference, likely due to Salivette swabs retaining bile acids or introducing unknown interferences. All saliva samples were analyzed by UHPLC-MS/MS using the Zorbax RRHD Eclipse Plus C18 column (3 × 50 mm, 1.8 µm) in gradient elution of 0.1 % formic acid in water and methanol. Saliva sample stability was assessed over 14 days, reflecting typical storage times. The levels of detected bile acids were stable for the measured period (RSD ≤ 22 %) and no degradation was observed. Bile acid levels in saliva fluctuated throughout the day, with the greatest changes observed for glycine-conjugated bile acids after meals. To minimize sampling variability, saliva collection by spitting after overnight fasting is recommended for future studies. Our findings are applicable for standardized bile acid sampling and are currently applied in a large clinical study evaluating bile acids as potential susceptibility markers for Barrett's esophagus diagnostics.
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Purpose: We evaluated the effect of optimization of the intraocular lens (IOL) power calculation formula SRK/T and Barrett Universal II (BU II) in long eyes (≥26 mm: group L) and short eyes (≤22 mm: group S) using axial length calculated from segmented refractive indices (SRI). Setting: Multicenter study at five sites in Japan. Design: Retrospective observational study. Methods: This study included 461 eyes of 461 patients (mean age 73.8 ± 8.4 years) who underwent cataract surgery. The predicted refractive error (PRE) was compared between the SRI (ARGOS) and the equivalent refractive index (ERI) biometers (IOLMasterTM700). The patients were randomly divided into two groups, a learning group and a validation group. The optimization constants were determined in the learning group, and the optimization constants were subsequently applied to the validation group and compared with the ERI biometer results. Results: Using both SRK/T and BU II, the validation group's PRE using optimization constants for the SRI biometer in group L was significantly smaller than that using the ERI biometer (p<0.001, p<0.01). In group L, the arithmetic PRE of Barrett UII formula with SRI showed a significant improvement after optimization compared to before optimization (p<0.0001). In group S, the arithmetic PRE of SRK/T and Barrett UII formula with SRI showed a significant improvement (p<0.0001, p<0.0001). Conclusion: In long and short eyes, the current study revealed that optimization of the SRK/T and Barrett formula constants for the SRI biometer was beneficial to achieve accurate refractive outcomes after cataract surgery.
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OBJECTIVES: Endoscopic resection is the preferred approach to treat early Barrett's neoplasia, reducing the need for surgical interventions. However, the best choice between endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) remains unclear. The study aimed to compare the efficacy and safety of EMR vs. ESD for early Barrett's neoplasia. METHODS: An electronic search was conducted in MEDLINE, Central Cochrane, EMBASE, and LILACS until November 2023. Studies comparing ESD vs. EMR in the treatment of patients with early Barrett's neoplasia were included. This study was performed according to the Preferred Report Items for Systematic Reviews and Meta-Analyses guidelines. The ROBIN-I tool was used to analyze the risk of bias and GRADE to measure the quality of the evidence. RESULTS: A total of 9352 patients from 15 observational studies were included. Patients undergoing ESD had significantly higher rates of en-bloc (odds ratio [OR] 25.96, 95% confidence interval [CI] 13.82, 48.74; I2 = 52%; P < 0.00001) and R0 (OR 5.10, 95% CI 3.29, 7.91; I2 = 73%; P < 0.00001) with a higher risk of adverse events, including bleeding, stricture formation, and perforation. In a subgroup analysis of patients who did not receive radiofrequency ablation, ESD had a lower recurrence rate than EMR (OR 0.22, 95% CI 0.05, 0.94; I2 = 88%; P = 0.04). CONCLUSION: Endoscopic submucosal dissection is more effective than EMR in treating early Barrett's neoplasia at the expense of higher adverse events rates.
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BACKGROUND AND AIM: 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 non-dysplastic BE or low-grade dysplasia (LGD) to HGD or EAC. A two-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. The review was registered (PROSPERO ID CRD42017051046). RESULTS: Twenty studies reported data on 38565 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 NDBE/LGD, of whom 555 progressed to HGD/EAC (pooled annual rate of progression 0.02%; 95% CI 0.01%-0.03%) and 1992 female patients with baseline NDBE/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=0.15). Each 5kg/m2 increase in BMI was associated with a 6% increase in the risk of malignant progression (adjusted OR 1.06; 95% CI 1.02-1.10; p<0.001; 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.
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Breath analysis, despite being an overlooked biomatrix, has a rich history in disease diagnosis. However, volatile organic compounds (VOCs) have yet to establish themselves as clinically validated biomarkers for specific diseases. As focusing solely on late-stage or malignant disease biomarkers may have limited relevance in clinical practice, the objective of this review is to explore the potential of VOC breath tests for the diagnosis of non-cancer diseases: (1) Precancerous conditions like gastro-esophageal reflux disease (GERD) and Barrett's esophagus (BE), where breath tests can complement endoscopic screening; (2) endoluminal diseases associated with autoinflammation and dysbiosis, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and coeliac disease, which currently rely on biopsy and symptom-based diagnosis; (3) chronic liver diseases like cirrhosis, hepatic encephalopathy, and non-alcoholic fatty liver disease, which lack non-invasive diagnostic tools for disease progression monitoring and prognostic assessment. A literature search was conducted through EMBASE, MEDLINE, and Cochrane databases, leading to an overview of 24 studies. The characteristics of these studies, including analytical platforms, disorder type and stage, group size, and performance evaluation parameters for diagnostic tests are discussed. Furthermore, how VOCs can be utilized as non-invasive diagnostic tools to complement existing gold standards is explored. By refining study designs, sampling procedures, and comparing VOCs in urine and blood, we can gain a deeper understanding of the metabolic pathways underlying VOCs. This will establish breath analysis as an effective non-invasive method for differential diagnosis and disease monitoring.
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Objectives: This study aims to verify the accuracy of a new calculation formula, Barrett true axial length formula (T-AL), and the optimized lens factor (LF) for predicting postoperative refraction after cataract surgery. Methods: We included 156 Japanese patients who underwent cataract surgery using Clareon monofocal intraocular lenses at our clinic between January 2022 and June 2023. Postoperative spherical equivalent was calculated using subjective refraction values obtained 1 month post-surgery. The LFs were optimized so that the mean prediction error (PE) of each calculation formula was zero (zero optimization). We calculated the mean absolute PE (MAE) to assess accuracy and used a Friedman test for statistical comparisons. The accuracy of T-AL and the optimized LFs was compared with that of the conventional Barrett Universal II formula for ARGOS (AR-B) and OA-2000 (OA-B) with equivalent refractive index. Results: For T-AL, AR-B, and OA-B, the MAEs ± standard deviations were 0.225 ± 0.179, 0.219 ± 0.168, and 0.242 ± 0.206 D, respectively. The Friedman test showed no statistically significant differences among the three groups. The device-optimized LFs were 2.248-2.289 (T-AL), 2.236-2.246 (AR-B), and 2.07-2.08 (OA-B); the corresponding zero-optimized LFs were 2.262-2.287 (T-AL), 2.287-2.303 (AR-B), and 2.160-2.170 (OA-B). Conclusion: There were no significant differences in prediction accuracy among the formulas. However, the accuracy of LF optimization varied by device, with T-AL being closest to the value under zero optimization. This suggests that T-AL is clinically useful for predicting an accurate postoperative refraction without zero optimization.
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Background: Although heartburn and reflux are frequently reported in ulcerative colitis [UC], the correlation between UC and gastroesophageal reflux disease [GERD], and its complications, esophageal stricture and Barrett's esophagus [BE], is not well understood. This study aims to examine the prevalence and associated risk of GERD and its complications within the UC population. Methods: We analyzed the National Inpatient Sample (NIS) dataset, consisting of 7,159,694 patients, comparing GERD patients with and without UC to those without GERD. We assessed the degree of colonic involvement in UC and the occurrence of esophageal complications. Bivariate analyses were conducted using the chi-squared test or Fisher exact test (two-tailed). Results: A higher prevalence of GERD (23.0% vs. 16.5%) and GERD phenotypes, such as non-erosive reflux disease (NERD) (22.3% vs. 16%) and erosive esophagitis (EE) (1.2% vs. 0.6%), was found in UC patients (p < 0.01), including pancolitis, proctitis, proctosigmoiditis, left-sided colitis, and indetermined UC (with undefined colonic involvement). UC patients were more likely to develop GERD (1.421), NERD (1.407), and EE (1.681) (p < 0.01). A higher prevalence of esophageal stricture (16.9 vs. 11.4 per 10,000 patients) and BE without dysplasia (94.5 vs. 39.3 per 10,000 patients) was found in UC (p < 0.05). The odds of developing BE without dysplasia were higher (1.892) in patients with UC (p < 0.01), including ulcerative pancolitis, proctitis, and indeterminate UC (OR of 1.657, 3.328, and 1.996, respectively) (p < 0.05). Conclusions: Our study demonstrates an increased risk of developing GERD and its complications in UC. This highlights the importance of vigilant monitoring and early intervention to minimize associated GERD-related risks in patients with UC.
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Electronic noses (eNoses) are electronic bionic olfactory systems that use sensor arrays to produce response patterns to different odors, thereby enabling the identification of various scents. Gastrointestinal diseases have a high incidence rate and occur in 9 out of 10 people in China. Gastrointestinal diseases are characterized by a long course of symptoms and are associated with treatment difficulties and recurrence. This review offers a comprehensive overview of volatile organic compounds, with a specific emphasis on those detected via the eNose system. Furthermore, this review describes the application of bionic eNose technology in the diagnosis and screening of gastrointestinal diseases based on recent local and international research progress and advancements. Moreover, the prospects of bionic eNose technology in the field of gastrointestinal disease diagnostics are discussed.
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Nariz Electrónica , Enfermedades Gastrointestinales , Compuestos Orgánicos Volátiles , Humanos , Enfermedades Gastrointestinales/diagnóstico , Compuestos Orgánicos Volátiles/análisisRESUMEN
The incidence of esophageal adenocarcinoma (EAC) has surged by 600% in recent decades, with a dismal 5-year survival rate of just 15%. Barrett's esophagus (BE), affecting about 2% of the population, raises the risk of EAC by 40-fold. Despite this, the transcriptomic changes during the BE to EAC progression remain unclear. Our study addresses this gap through comprehensive transcriptomic profiling to identify key mRNA signatures and genomic alterations, such as gene fusions. We performed RNA-sequencing on BE and EAC tissues from 8 individuals, followed by differential gene expression, pathway and network analysis, and gene fusion prediction. We identified mRNA changes during the BE-to-EAC transition and validated our results with single-cell RNA-seq datasets. We observed upregulation of keratin family members in EAC and confirmed increased levels of keratin 14 (KRT14) using immunofluorescence. More differentiated BE marker genes are downregulated during progression to EAC, suggesting undifferentiated BE subpopulations contribute to EAC. We also identified several gene fusions absent in paired BE and normal esophagus but present in EAC. Our findings are critical for the BE-to-EAC transition and have the potential to promote early diagnosis, prevention, and improved treatment strategies for EAC.
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BACKGROUND: The cancer risk for each length of Barrett's esophagus (BE) in Japanese is unknown. This nationwide, multi-institutional study aims to clarify the cancer risk by length of BE in the general Japanese population. METHODS: Consecutive subjects who underwent upper endoscopic screening at 17 centers between 2013 and 2017 and had at least one follow-up endoscopy by December 2022 were included. The presence/absence of BE and, if present, its length were retrospectively assessed using the retrieved endoscopic images recorded at baseline. Information on the subsequent occurrence of esophageal adenocarcinoma and other upper gastrointestinal cancers was also collected. Cancer incidence was calculated and expressed as %/year. RESULTS: A total of 33,478 subjects were enrolled, and 17,884 (53.4%), 10,641 (31.8%), 4889 (14.6%), and 64 (0.2%) were diagnosed as absent BE, BE < 1 cm, 1-3 cm, and ≥ 3 cm, respectively. During a median follow-up of 80 months, 11 cases of esophageal adenocarcinoma developed. The annual incidence of esophageal adenocarcinoma is 0%/year for absent BE, 0.0032 (0.00066-0.013)%/year for BE < 1 cm, 0.026 (0.011-0.054)%/year for 1-3 cm, and 0.58 (0.042-2.11)%/year for ≥ 3 cm, respectively. Meanwhile, the incidence of esophageal squamous cell carcinoma and gastric cancer were 0.039 (0.031-0.049)%/year and 0.16 (0.14-0.18)%/year, respectively. CONCLUSIONS: By enrolling a large number of subjects with long-term follow-up, this study demonstrated that the risk of cancer increased steadily with increasing length of BE in the Japanese population. Therefore, it is important to consider the length of BE when determining the management strategy for BE.
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INTRODUCTION: The incidence of esophageal cancers is increasing in many Western countries and the rate of missed esophageal cancers (MEC) at upper endoscopy is of concern. We aimed to calculate the MEC rate and identify factors associated with MEC. METHODS: This was a retrospective population-based cohort study including 613 patients diagnosed with esophageal cancer in Central Norway 2004-2021. MEC was defined as esophageal cancer diagnosed 6-36 months after a non-diagnostic upper endoscopy. Patient characteristics, tumor localization, histological type and cTNM stage were recorded. Symptoms, endoscopic findings, use of sedation and endoscopists experience at the endoscopy prior to esophageal cancer diagnosis and at the time of diagnosis were recorded. The association between these factors and MEC was assessed. RESULTS: Forty-nine (8.0%) of 613 cancers were MEC. There was a significant increase in annual numbers of esophageal cancer (p < 0.001) as well as of MEC (p = 0.009), but MEC rate did not change significantly (p = 0.382). The median time from prior upper endoscopy to MEC diagnosis was 22.9 (12.1-28.6) months. MEC patients were older and were diagnosed with disease with a lower cTNM stage and cT category than non-missed cancers, whereas tumor localization and histological type were similar between the groups. The use of sedation or endoscopist experience did not differ between the endoscopy prior to esophageal cancer diagnosis and at the time of diagnosis. High proportions of MEC patients had Barrett's esophagus (n = 25, 51.0%), hiatus hernia (n = 26, 53.1%), esophagitis (n = 10, 20.4%) or ulceration (n = 4, 8.2%). Significant proportions of MECs were diagnosed after inappropriate follow-up of endoscopic Barrett's esophagus, histological dysplasia or ulcerations. CONCLUSIONS: The annual number of MEC increased during the study period, while the MEC rate remained unchanged. Endoscopic findings related to gastroesophageal reflux disease such as esophagitis and Barrett's esophagus were identified in a high proportion of patients with subsequent MECs. Cautious follow-up of these patients could potentially reduce MEC-rate.
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Endoscopía del Sistema Digestivo , Neoplasias Esofágicas , Diagnóstico Erróneo , Diagnóstico Erróneo/estadística & datos numéricos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiología , Noruega/epidemiología , Endoscopía del Sistema Digestivo/estadística & datos numéricos , Estudios Retrospectivos , Humanos , Masculino , Femenino , AncianoRESUMEN
The z-line refers to the squamocolumnar junction which marks the transition between the normal stratified squamous epithelium of the distal esophagus and the columnar epithelium of the gastric cardia. An "irregular" z-line refers to an irregular appearing squamocolumnar junction characterized by the presence of columnar mucosa less than 1 cm in length that extends above the gastroesophageal junction. In contrast, Barrett's esophagus is diagnosed when columnar mucosa of at least 1 cm is seen in the distal esophagus extending above the gastroesophageal junction with biopsies demonstrating specialized intestinal metaplasia. Current guidelines recommend against taking routine biopsies from a normal or irregular z-line in the absence of visible abnormalities and advise against endoscopic surveillance in this patient population, in large part due to multiple studies demonstrating lack of progression to advanced neoplasia such as high-grade dysplasia or esophageal adenocarcinoma in patients with an irregular z-line. Despite these recommendations, a sizable number of patients without Barrett's esophagus undergo biopsies from the z-line and are subsequently recommended to have surveillance endoscopies. Furthermore, patients with an irregular z-line are often mislabelled as Barrett's esophagus resulting in significant downstream consequences including higher healthcare costs and reduced health-related quality of life. In this review, we highlight the importance of landmark identification of the distal esophagus and gastroesophageal junction at the time of endoscopy, share recommendations from current guidelines related to the z-line, examine rates of neoplastic progression in those with an irregular z-line, discuss consequences of routinely biopsying an irregular z-line, and highlight strategies on how to approach an irregular z-line if seen on endoscopy. A careful, high-quality endoscopic examination can help to identify visible abnormalities at the z-line, which, if present, should be targeted for biopsies to rule out dysplasia and neoplasia.
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Esófago de Barrett , Neoplasias Esofágicas , Humanos , Esófago de Barrett/patología , Esófago de Barrett/diagnóstico , Biopsia/métodos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/diagnóstico , Unión Esofagogástrica/patología , Esófago/patología , Adenocarcinoma/patología , Adenocarcinoma/diagnóstico , Cardias/patología , Esofagoscopía/métodosRESUMEN
Objectives: The selection of an appropriate formula for intraocular lens power calculation is crucial in phacoemulsification, particularly in pediatric patients. The most commonly used formulas are described and their accuracy evaluated in this study. Methods: This review includes papers evaluating the accuracy of intraocular lens power calculation formulas for children's eyes published from 2019-2024. The articles were identified by a literature search of medical and other databases (Pubmed/MEDLINE, Crossref, Google Scholar) using the combination of the following key words: "IOL power calculation formula", "pediatric cataract", "congenital cataract", "pediatric intraocular lens implantation", "lens power estimation", "IOL power selection", "phacoemulsification", "Hoffer Q", "Holladay 1", "SRK/T", "Barrett Universal II", "Hill-RBF", and "Kane". A total of 14 of the most recent peer-reviewed papers in English with the maximum sample sizes and the greatest number of compared formulas were considered. Results: The outcomes of mean absolute error and percentage of predictions within ±0.5 D and ±1.0 D were used to assess the accuracy of the formulas. In terms of MAE, Hoffer Q yielded the best result most often, just ahead of SRK/T and Barrett Universal II, which, together with Holladay 1, most often yielded the second-best outcomes. Considering patients with PE within ±1.0 D, Barrett Universal II most often gave the best results and Holladay 1 most often gave the second-best. Conclusions: Barrett Universal II seems to be the most accurate formula for intraocular lens calculation for children's eyes. Very good postoperative outcomes can also be achieved using the Holladay 1 formula. However, there is still no agreement in terms of formula choice.
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BACKGROUND: Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed first responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal reflux disease (GERD) and Barrett's Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE. GERD can incite or exacerbate allergies, sinusitis, bronchitis, and asthma. Disease features of the aerodigestive axis can overlap, often necessitating more invasive diagnostic testing and treatment modalities. This presents a need to develop novel non-invasive biomarkers of GERD, BE, airway hyperreactivity (AHR), treatment efficacy, and severity of symptoms. METHODS: Our observational case-cohort study will leverage the longitudinally phenotyped Fire Department of New York (FDNY)-WTC exposed cohort to identify Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN). Our study population consists of n = 4,192 individuals from which we have randomly selected a sub-cohort control group (n = 837). We will then recruit subgroups of i. AHR only ii. GERD only iii. BE iv. GERD/BE and AHR overlap or v. No GERD or AHR, from the sub-cohort control group. We will then phenotype and examine non-invasive biomarkers of these subgroups to identify under-diagnosis and/or treatment efficacy. The findings may further contribute to the development of future biologically plausible therapies, ultimately enhance patient care and quality of life. DISCUSSION: Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. The detection of the disease is further complicated by the invasiveness of conventional GERD diagnosis procedures and the limited availability of disease-specific biomarkers. The management of reflux is important, as it directly increases risk of cancer and negatively impacts quality of life. Therefore, it is vital to develop novel noninvasive disease markers that can effectively phenotype, facilitate early diagnosis of premalignant disease and identify potential therapeutic targets to improve patient care. TRIAL REGISTRATION: Name of Primary Registry: "Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BADBURN)". Trial Identifying Number: NCT05216133 . Date of Registration: January 31, 2022.
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Esófago de Barrett , Biomarcadores , Bomberos , Reflujo Gastroesofágico , Ataques Terroristas del 11 de Septiembre , Humanos , Esófago de Barrett/diagnóstico , Esófago de Barrett/etiología , Reflujo Gastroesofágico/diagnóstico , Biomarcadores/sangre , Estudios de Casos y Controles , Bomberos/estadística & datos numéricos , Ciudad de Nueva York , Exposición Profesional/efectos adversos , Material Particulado/efectos adversos , Material Particulado/análisis , Estudios Observacionales como Asunto , MasculinoRESUMEN
Background: Cholelithiasis or cholecystectomy may contribute to the development of gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) through bile reflux; however, current observational studies yield inconsistent findings. We utilized a novel approach combining meta-analysis and Mendelian randomization (MR) analysis, to assess the association between them. Methods: The literature search was done using PubMed, Web of Science, and Embase databases, up to 3 November 2023. A meta-analysis of observational studies assessing the correlations between cholelithiasis or cholecystectomy, and the risk factors for GERD, BE, and EACwas conducted. In addition, the MR analysis was employed to assess the causative impact of genetic pre-disposition for cholelithiasis or cholecystectomy on these esophageal diseases. Results: The results of the meta-analysis indicated that cholelithiasis was significantly linked to an elevated risk in the incidence of BE (RR, 1.77; 95% CI, 1.37-2.29; p < 0.001) and cholecystectomy was a risk factor for GERD (RR, 1.37; 95%CI, 1.09-1.72; p = 0.008). We observed significant genetic associations between cholelithiasis and both GERD (OR, 1.06; 95% CI, 1.02-1.10; p < 0.001) and BE (OR, 1.21; 95% CI, 1.11-1.32; p < 0.001), and a correlation between cholecystectomy and both GERD (OR, 1.04; 95% CI, 1.02-1.06; p < 0.001) and BE (OR, 1.13; 95% CI, 1.06-1.19; p < 0.001). After adjusting for common risk factors, such as smoking, alcohol consumption, and BMI in multivariate analysis, the risk of GERD and BE still persisted. Conclusion: Our study revealed that both cholelithiasis and cholecystectomy elevate the risk of GERD and BE. However, there is no observed increase in the risk of EAC, despite GERD and BE being the primary pathophysiological pathways leading to EAC. Therefore, patients with cholelithiasis and cholecystectomy should be vigilant regarding esophageal symptoms; however, invasive EAC cytology may not be necessary.
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BACKGROUND: The incidence of esophageal adenocarcinoma has recently increased in Asia, including Japan. A system to identify individuals at high risk for Barrett's esophagus (BE), a pre-cancerous condition of esophageal adenocarcinoma, among the general population is needed to perform endoscopic surveillance appropriately. We therefore developed risk prediction scores for BE at health checkups in Japan. METHODS: 4128 consecutive health checkup examinees were retrospectively enrolled from October 2021 to March 2022. A prediction score for BE was developed based on the linear transformation of ß-regression coefficients in a multivariable regression model incorporating BE predictors. Internal validation was performed by evaluating discrimination and calibration of the prediction model. RESULTS: Three prediction scores corresponding to BE based on its length were developed: all lengths, ≥ 1 cm, ≥ 2 cm. All scores were internally validated, and the model calibration was excellent. The performance of the prediction models was better for longer BE, with a c-statistic of 0.70 for BE ≥ 2 cm, than for shorter values. The prediction score for BE ≥ 2 cm yielded sensitivity and specificity of 52.9% and 78.6% in high-risk subjects and 91.2% and 29.3% in intermediate- or high-risk subjects, respectively. CONCLUSIONS: This prediction score can potentially increase the endoscopic detection of BE by identifying potentially high-risk individuals from the general population. This is the first report on developing a prediction score for BE that may suit the Japanese population.
Asunto(s)
Esófago de Barrett , Neoplasias Esofágicas , Humanos , Esófago de Barrett/epidemiología , Esófago de Barrett/patología , Esófago de Barrett/diagnóstico , Masculino , Japón/epidemiología , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Medición de Riesgo/métodos , Adulto , Sensibilidad y Especificidad , Esofagoscopía/métodos , Factores de Riesgo , Adenocarcinoma/epidemiología , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Incidencia , Valor Predictivo de las Pruebas , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Previous studies have suggested a potential association between irritability and the risk of various diseases. However, establishing a causal relationship has remained a significant challenge. To address this issue, we employed Mendelian randomization (MR), a sophisticated approach that leverages genotype data to emulate the conditions of randomized controlled trials. This method enables us to investigate the potential causal link between irritability and the susceptibility to esophageal diseases. METHODS: We conducted an extensive multivariable MR analysis using summary-level data from genome-wide association studies (GWAS) encompassing various esophageal diseases, including gastroesophageal reflux disease (GERD), esophageal cancer (EC), and Barrett's esophagus. Both univariable and multivariable MR analyses were performed to elucidate and confirm the causal association between genetically predicted irritability and the incidence of esophageal diseases. RESULTS: Based on our primary causal effects model utilizing MR analyses with the inverse-variance weighted (IVW) method, genetically predicted irritability was identified as a risk factor for GERD (OR = 2.413; 95 % CI: 1.678-3.470; P = 2.03E-06) and Barrett's esophagus (OR = 2.306; 95 % CI: 1.042-5.101; P = 0.039). However, irritability was not found to be associated with the risk of EC, even after adjusting for BMI, smoking initiation, and alcohol consumption. CONCLUSION: The multivariable MR analysis performed in this study demonstrated a causal relationship between irritability and esophageal diseases. It is imperative to acknowledge the need for further large-scale prospective studies to validate these findings.