[Application of novel non-endoscopic device in the screening and early diagnosis of esophageal cancer].

Esophageal cancer (EC) is a dreadful disease with a poor prognosis and poses heavy health burden worldwide. Developing effective methods to identify high-risk individuals is urgently needed for preliminary screening before endoscopy. The novel non-endoscopic device has the potential advantages of low cost, simple operation, and minimal invasiveness. Approximately 90% of participants can swallow the device successfully with high safety profiles, and sufficient esophageal exfoliated cells can be collected for cytological examination and biomarker detection. Cytological examination based on the device combined with trefoil factor 3 (TFF3) protein or DNA methylation examinations could effectively screen Barrett's esophagus-associated dysplasia and early esophageal adenocarcinoma, but large prospective studies are needed to further validate the diagnostic value of this device to improve the quality of evidence. Although the device-based cytological examination in combination with biomarker detection holds promise in the early screening of esophageal squamous dysplasia and early esophageal squamous cell carcinoma, related research is still in its infancy, and there is still a lack of sufficient evidence for population screening in China. Active research into the application of this novel non-endoscopic device in EC screening and early diagnosis is of great significance for optimizing EC screening strategies and improving the early diagnosis of EC.

Acceptability and Adequacy of a Non-endoscopic Cell Collection Device for Diagnosis of Barrett's Esophagus: Lessons Learned.

BACKGROUND: Endoscopic screening for Barrett's esophagus (BE) is common, costly, and underperformed in at-risk people. A non-endoscopic cell collection device can be used to collect esophageal cells, enabling BE screening. AIMS: This study assessed the acceptability and adequacy of a commercial non-endoscopic cell collection device in a US population. METHODS: Six sites enrolled patients with confirmed BE or heartburn/regurgitation for ≥ 6 months. Patients underwent administration of the device, consisting of a sponge encapsulated in a capsule. The capsule dwelled in the stomach for 7.5 min and was retracted via an attached suture. An adequate sample was ≥ 1 columnar cell by H&E staining. Sample quality was rated using a 0-5 scale, with 0 = no columnar cells and 5 = plentiful groups. Trefoil Factor 3 (TFF3) staining was performed. Accuracy was assessed using esophagogastroduodenoscopy (EGD)/biopsy as the gold standard. RESULTS: Of 191 patients, 99.5% successfully swallowed the device. Overall sample adequacy was 91% (171/188), with 84% (158/188) high quality. The detachment rate was 2/190 (1%). Overall sensitivity, specificity, and accuracy of the assay with TFF3 staining were 76%, 77%, and 76%. Sensitivity, specificity, and accuracy for ≥ 3 cm BE were 86%, 77%, and 82%. Asked if willing to repeat the procedure, 93% would, and 65% indicated a preference for the device over EGD. CONCLUSIONS: This study demonstrated a high rate of sample adequacy and promising acceptability of this non-endoscopic sampling device in a US population. Diagnostic characteristics suggest that non-endoscopic assessment of BE deserves further development as an alternative to endoscopy.

Methylation panel is a diagnostic biomarker for Barrett's oesophagus in endoscopic biopsies and non-endoscopic cytology specimens.

OBJECTIVE: Barrett's oesophagus is a premalignant condition that occurs in the context of gastro-oesophageal reflux. However, most Barrett's cases are undiagnosed because of reliance on endoscopy. We have developed a non-endoscopic tool: the Cytosponge, which when combined with trefoil factor 3 immunohistochemistry, can diagnose Barrett's oesophagus. We investigated whether a quantitative methylation test that is not reliant on histopathological analysis could be used to diagnose Barrett's oesophagus. DESIGN: Differentially methylated genes between Barrett's and normal squamous oesophageal biopsies were identified from whole methylome data and confirmed using MethyLight PCR in biopsy samples of squamous oesophagus, gastric cardia and Barrett's oesophagus. Selected genes were then tested on Cytosponge BEST2 trial samples comprising a pilot cohort (n=20 cases, n=10 controls) and a validation cohort (n=149 cases, n=129 controls). RESULTS: Eighteen genes were differentially methylated in patients with Barrett'soesophagus compared with squamous controls. Hypermethylation of TFPI2, TWIST1, ZNF345 and ZNF569 was confirmed in Barrett's biopsies compared with biopsies from squamous oesophagus and gastric cardia (p<0.05). When tested in Cytosponge samples, these four genes were hypermethylated in patients with Barrett's oesophagus compared with patients with reflux symptoms (p<0.001). The optimum biomarker to diagnose Barrett's oesophagus was TFPI2 with a sensitivity and specificity of 82.2% and 95.7%, respectively. CONCLUSION: TFPI2, TWIST1, ZNF345 and ZNF569 methylation have promise as diagnostic biomarkers for Barrett's oesophagus when used in combination with a simple and cost effective non-endoscopic cell collection device.

Non-endoscopic Screening for Esophageal Squamous Cell Carcinoma: Recent Advances.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common tumors in the gastrointestinal tract, and China has a high incidence area with a high burden on the disease. As early symptoms of ESCC are not obvious, the mortality rate is high, and it is often diagnosed in the intermediate and advanced stages. However, early screening and treatment may reduce morbidity and mortality. METHODS: Screening methods are divided into endoscopic and non-endoscopic screening. RESULTS: Endoscopic screening cannot be widely used because of its invasive nature and high cost. Currently, non-endoscopic screening consists primarily of tumor biomarkers and cytology, and tumor biomarkers including autoantibodies, circulating tumor cells, circulating tumor DNA, exosomes and serum metabolomics are more likely to be effective. But the efficiency of early diagnosis of esophageal cancer is low and the accuracy of screening needs to be improved. The aim of this study is to summarize advances in non-endoscopic esophageal cancer screening and strategies to provide a scientific basis and research idea for esophageal cancer prevention and control. CONCLUSIONS: Non-endoscopic screening is better than endoscopic screening. And the application of tumor biomarkers is much better than other non-endoscopic screening methods.

Expanding beyond endoscopy: A review of non-invasive modalities in Barrett's esophagus screening and surveillance.

Barrett's esophagus (BE) is a condition that results from replacement of the damaged normal squamous esophageal mucosa to intestinal columnar mucosa and is the most significant predisposing factor for development of esophageal adenocarcinoma. Current guidelines recommend endoscopic evaluation for screening and surveillance based on various risk factors which has limitations such as invasiveness, availability of a trained specialist, patient logistics and cost. Trans-nasal endoscopy is a less invasive modality but still has similar limitations such as limited availability of trained specialist and costs. Non-endoscopic modalities, in comparison, require minimal intervention, can be done in an office visit and has the potential to be a more ideal choice for mass public screening and surveillance, particularly in patents at low risk for BE. These include newer generations of esophageal capsule endoscopy which provides direct visualization of BE, and tethered capsule endomicroscopy which can obtain high-resolution images of the esophagus. Various cell collection devices coupled with biomarkers have been used for BE screening. Cytosponge, in combination with TFF3, as well as EsophaCap and EsoCheck have shown promising results in various studies when used with various biomarkers. Other modalities including circulatory microRNAs and volatile organic compounds that have demonstrated favorable outcomes. Use of these cell collection methods for BE surveillance is a potential area of future research.

Quantification of TFF3 expression from a non-endoscopic device predicts clinically relevant Barrett's oesophagus by machine learning.

BACKGROUND: Intestinal metaplasia (IM) is pre-neoplastic with variable cancer risk. Cytosponge-TFF3 test can detect IM. We aimed to 1) assess whether quantitative TFF3 scores can distinguish clinically relevant Barrett's oesophagus (BO) (C≥1 or M≥3) from focal IM pathologies (C<1, M<3 or IM of gastro-oesophageal junction); 2) whether TFF3 counts can be automated to inform clinical practice. METHODS: Patients from the Barett's oEsophagus Screening Trial 2 (BEST2) case-control and BEST3 randomised trials were used. For aim 1, TFF3-positive glands were scored manually and correlated with clinical diagnosis. For aim 2, machine learning approach was used to obtain TFF3 count and logistic regression with cross-validation was trained on the BEST2 dataset (n = 529) and tested in the BEST3 dataset (n = 158). FINDINGS: Patients with clinically relevant BO had higher mean TFF3 gland count compared to focal IM pathologies (mean difference 4.14; 95% confidence interval, CI 2.76-5.52, p < 0.001). The mean class-balanced validation accuracy was 0.84 (95% CI 0.77-0.90), and precision of 0.95 (95% CI 0.87-1.00) for detecting clinically relevant BO. Applying this model on BEST3 showed precision of 0.91 (95% CI 0.85-0.97) for focal IM pathologies with a class-balanced accuracy of 0.77 (95% CI 0.69-0.84). Using this model, 55% of patients (87/158) in BEST3 would fall below the threshold for clinically relevant BO and could avoid gastroscopy, while only missing 5.1% of patients (8/158). INTERPRETATION: Automated Cytosponge-TFF3 gland quantification may enable thresholds to be set to trigger confirmatory gastroscopy to minimize overdiagnosis of focal IM pathologies with very low cancer-associated risk. FUNDING: Cancer Research UK (12088/16893 and C14478/A21047).

Comparison of Endoscopic Discectomy Versus Non-Endoscopic Discectomy for Symptomatic Lumbar Disc Herniation: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review. OBJECTIVE: The authors aimed to systematically compare the effectiveness and safety of endoscopic discectomy (ED) with non-endoscopic discectomy (NED) for treatment of symptomatic lumbar disc herniation (LDH). METHODS: A systematic search was performed on PubMed, EMBASE, the Cochrane Library and China National Knowledge Infrastructure for randomized controlled trial from inception until August 13, 2020. Trials which investigated multiple operative approaches on lumbar disc herniation were identified without language restrictions. RESULTS: In total, 25 trials involving 2258 patients with symptomatic LDH were included. Twenty trials performed the comparison between ED and NED. Five trials performed the comparison between percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID). The operative time of micro-endoscopic discectomy (MED) was longer than open discectomy (OD). The length of hospital stay of percutaneous endoscopic lumbar discectomy (PELD) was shorter than fenestration discectomy (FD). Significant differences in intraoperative blood loss volumes were found between PELD with FD and MED with OD. The complication rate of PELD was lower than FD (PELD: 4.3%; FD: 14.6%) and the complication rate of full-endoscopic discectomy (FE) was lower than microscopic discectomy (MD) (FE: 13.4%; MD: 32.1%). CONCLUSIONS: PELD and FE have the advantage of limiting intraoperative damages. ED and NED can be both considered sufficient to achieve good clinical outcomes. PETD and PEID are able to achieve similar results but the learning curve of PETD was steeper. More independent high-quality RCTs with sufficiently large sample sizes performing cost-effectiveness analyzes are needed.

The Procedureless Elipse Gastric Balloon Program: Multicenter Experience in 1770 Consecutive Patients.

PURPOSE: The Elipse balloon is a novel, non-endoscopic option for weight loss. It is swallowed and filled with fluid. After 4 months, the balloon self-empties and is excreted naturally. Aim of the study was to evaluate safety and efficacy of Elipse balloon in a large, multicenter, population. MATERIALS AND METHODS: Data from 1770 consecutive Elipse balloon patients was analyzed. Data included weight loss, metabolic parameters, ease of placement, device performance, and complications. RESULTS: Baseline patient characteristics were mean age 38.8 ± 12, mean weight 94.6 ± 18.9 kg, and mean BMI 34.4 ± 5.3 kg/m2. Triglycerides were 145.1 ± 62.8 mg/dL, LDL cholesterol was 133.1 ± 48.1 mg/dL, and HbA1c was 5.1 ± 1.1%. Four-month results were WL 13.5 ± 5.8 kg, %EWL 67.0 ± 64.1, BMI reduction 4.9 ± 2.0, and %TBWL 14.2 ± 5.0. All metabolic parameters improved. 99.9% of patients were able to swallow the device with 35.9% requiring stylet assistance. Eleven (0.6%) empty balloons were vomited after residence. Fifty-two (2.9%) patients had intolerance requiring balloon removal. Eleven (0.6%) balloons deflated early. There were three small bowel obstructions requiring laparoscopic surgery. All three occurred in 2016 from an earlier design of the balloon. Four (0.02%) spontaneous hyperinflations occurred. There was one (0.06%) case each of esophagitis, pancreatitis, gastric dilation, gastric outlet obstruction, delayed intestinal balloon transit, and gastric perforation (repaired laparoscopically). CONCLUSION: The Elipse™ Balloon demonstrated an excellent safety profile. The balloon also exhibited remarkable efficacy with 14.2% TBWL and improvement across all metabolic parameters.

Non-endoscopic predictors of esophageal varices in children with chronic liver disease and their utility in resource-constrained countries.

BACKGROUND: Although endoscopy is the standard diagnostic screening test to identify esophageal varices in patients with chronic liver disease (CLD), selective endoscopy in patients who are at higher risk of having varices may be cost-effective in a resource-constrained country. The aim of this prospective study was to identify non-endoscopic parameters that may predict the presence of varices, especially high-risk esophageal varices in children with CLD. METHODS: From January 2016 through March 2018, consecutive children with CLD without a history of variceal bleeding were prospectively included. Esophagogastroduodenoscopy was done in all the children to detect and to grade esophageal varices. Both univariate and multivariate logistic regression analyses were done using SPSS version 22 to identify factors associated with esophageal varices. RESULTS: The mean age of 84 children was 9.7 ± 3.2 years (male 44). Esophageal varices were present in 71.4% of children and 55% of them had large varices. On univariate analysis, low platelet count (< 100,000/mm3) and splenomegaly were found to be associated with the presence of esophageal varices (p = 0.006 and 0.001, respectively) and large varices (p = 0.03 and 0.01, respectively). On multivariate analysis, both low platelet count and splenomegaly were independent predictors for the presence of esophageal varices (respectively, OR 11.21, 95% CI 1.2-96.9; and OR 11.39, 95% CI 3.19-40.59). CONCLUSIONS: Splenomegaly and low platelet count independently predict the presence of any grade of esophageal varices and can be used as screening tests to select children for endoscopy. This strategy may help in relieving medical, social, and economic costs in resource-constrained countries.

Non-endoscopic biopsy techniques: a review.

INTRODUCTION: Diseases of the stomach and small intestine account for approximately 20% of all gastrointestinal (GI)-related mortality. Biopsy of the stomach and small intestine remains a key diagnostic tool for most of the major diseases that affect the GI tract. While endoscopic means for obtaining biopsy is generally the standard of care, it has several limitations that make it less ideal for pediatric patients and in low resource areas of the world. Therefore, non-endoscopic means for obtaining biopsy samples is of interest in these settings. Areas covered: We review non-endoscopic biopsy techniques reported thus far, and critically examine their merits and demerits regarding their suitability for obtaining biopsy samples in non-sedated subjects. Expert commentary: Esophagogastroduodenoscopy (EGD) is the current standard for acquiring biopsy from the GI tract, however, its limitations include subject sedation, expensive endoscopy infrastructure, expert personnel, and a small but significant risk of complications. A less costly, minimally-invasive and non-endoscopic means for obtaining biopsy samples is therefore of interest for addressing these issues. Such a technology would be of significant impact in low- and middle-income countries where conducting endoscopy is challenging.

The management of the acute setting of pelvic fracture urethral injury (realignment vs. suprapubic cystostomy alone).

BACKGROUND: In patients with pelvic fracture urethral injury there are two options for management: First, to realign as an early primary realignment over a catheter; and second, to place a suprapubic tube with delayed urethroplasty of the inevitable stricture. METHODS: We reviewed previous reports from 1990 to the present, comparing early endoscopic realignment, early open realignment and suprapubic tube placement, to determine the rates of incontinence, erectile dysfunction and stricture formation. RESULTS: Twenty-nine articles were identified. The rates of erectile dysfunction, incontinence, and stricture formation, respectively, were: for early endoscopic realignment, 20.5%, 5.8% and 43.8%; for open realignment over a catheter, 16.7%, 4.7% and 48.9%; and for a suprapubic tube and delayed urethroplasty 13.7%, 5.0%, and 89.0%. A one-way anova showed no difference in the mean rate of erectile dysfunction (P = 0.53) or incontinence (P = 0.73), and only stricture formation was significantly different (P < 0.1). CONCLUSION: The rates of incontinence and erectile dysfunction are similar between the groups. Only the rate of stricture formation was higher in the suprapubic tube and delayed urethroplasty group.

None-endoscopic Screening for Esophageal Squamous Cell Carcinoma- A Review.

Esophageal cancer (EC) is the eighth most common cancer and sixth most frequent cause of cancer mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common type of EC. ESCC develops by progression from premalignant lesions, which are called esophageal squamous dysplasia (ESD). Prevention is the most effective strategy for controlling this disease. Generally, two methods may be defined for ESCC prevention. The aim of the first preventive method is to prevent the initiation of ESD by avoiding the known risk factors, or primary prevention. Secondary prevention focuses on detection of the disease in its early curable stage, thus preventing its progression into advanced stages. Endoscopy with iodine staining and biopsy is the diagnostic choice for ESD. However it is invasive and expensive, and not accepted by asymptomatic ESD cases. Therefore, it is necessary to find a non-endoscopic screening method. Despite the large number of studies conducted worldwide, no approved method has been developed for ESCC screening. Regarding the multi-factorial nature of ESCC, it is proposed that the use of a combination of various criteria, such as cytological examination, risk factors, genetic alteration, and molecular markers may result in the development of a comprehensive and effective ESCC screening program.