Advancements in Barrett's esophagus detection:The role of artificial intelligence and its implications

Artificial intelligence(AI)is making significant strides in revolutionizing the detection of Barrett's esophagus(BE),a precursor to esophageal adenocarcinoma.In the research article by Tsai et al,researchers utilized endoscopic images to train an AI model,challenging the traditional distinction between endoscopic and histological BE.This approach yielded remarkable results,with the AI system achieving an accuracy of 94.37%,sensitivity of 94.29%,and specificity of 94.44%.The study's extensive dataset enhances the AI model's practicality,offering valuable support to endoscopists by minimizing unnecessary biopsies.However,questions about the applicability to different endoscopic systems remain.The study underscores the potential of AI in BE detection while highlighting the need for further research to assess its adaptability to diverse clinical settings.

Alteration of the esophageal microbiota in Barrett's esophagus and esophageal adenocarcinoma

The incidence of esophageal adenocarcinoma(EAC) has increased in recent decades, and its 5-year survival rate is less than 20%. As a well-established precursor, patients with Barrett's esophagus(BE) have a persistent risk of progression to EAC. Many researchers have already identified some factors that may contribute to the development of BE and EAC, and the identified risks include gastroesophageal reflux(GER), male sex, older age, central obesity,tobacco smoking, Helicobacter pylori(H. pylori) eradication, and the administration of proton pump inhibitors(PPIs) and antibiotics. The human gut harbors trillions of microorganisms, the majority of which are bacteria. These microorganisms benefit the human host in many ways, such as helping in digestion, assisting in the synthesis of certain vitamins, promoting the development of the gastrointestinal immune system, regulating metabolism and preventing invasion by specific pathogens. In contrast, microbial dysbiosis may play important roles in various diseases, such as inflammation and cancers. The composition of the microbiota located in the normal esophagus is relatively conserved without distinct microbial preferences in the upper, middle and lower esophagus. Six major phyla constitute the esophageal microbiota, including Firmicutes,Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and TM7, similar to the oral microbiota. Streptococcus dominates the esophageal microbiota. However, the microbiota varies in different esophageal diseases compared to that in the healthy esophagus. The type Ⅰ microbiota, which is primarily composed of gram-positive bacteria, is closely associated with the normal esophagus, while type Ⅱ microbiota has enriched gram-negative bacteria and is mainly associated with the abnormal esophagus. These increased gram-negative anaerobes/microaerophiles include Veillonella, Prevotella, Haemophilus, Neisseria, Granulicatella and Fusobacterium, many of which are associated with BE. The microbial diversity in the esophagus is decreased in EAC patients, and Lactobacillus fermentum is enriched compared to that in controls and BE patients. Furthermore, the microbiota may be associated with BE and EAC by interacting with their risk factors, including central obesity, GER, H. pylori, administration of PPIs and antibiotics. Therefore, a large gap in research must be bridged to elucidate the associations among these factors. Some studies have already proposed several potential mechanisms by which the microbiota participates in human carcinogenesis by complicated interactions with the human host immune system and signaling pathways. The activation of the LPS-TLR4-NF-κB pathway may contribute to inflammation and malignant transformation. This exciting field of gastrointestinal microbiota allows us to unravel the mystery of carcinogenesis from another perspective. Further studies are needed to explore whether the microbiota changes before or after disease onset, to improve our understanding of the pathogenesis, and to find novel targets for prevention, diagnosis and therapy, which could offer more cost-effective and relatively safe choices.

From reflux esophagitis to Barrett's esophagus and esophageal adenocarcinoma

The occurrence of gastroesophageal reflux disease is common in the human population.Almost all cases of esophageal adenocarcinoma are derived from Barrett's esophagus,which is a complication of esophageal adenocarcinoma precancerous lesions.Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett's esophagus.The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia,which is closely associated with the development of esophageal adenocarcinoma.However,the exact mechanism of injury is not completely understood.Various animal models of the developmental mechanisms of disease,and theoretical and clinical effects of drug treatment have been widely used in research.Recently,animal models employed in studies on gastroesophageal reflux injury have allowed significant progress.The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results.In this article,various modeling methods are reviewed,with discussion of the major findings on the developmental mechanism of Barrett's esophagus,which should help to develop better prevention and treatment strategies for Barrett's esophagus.

Long-term follow-up after complete ablation of Barrett's esophagus with argon plasma coagulation

AIM: To report the long-term outcome of patients after complete ablation of non-neoplastic Barrett's esophagus (BE) with respect to BE relapse and development of intraepithelial neoplasia or esophageal adenocarcinoma. METHODS: In 70 patients with historically proven non neoplastic BE, complete BE ablation was achieved by argon plasma coagulation (APC) and high-dose proton pump inhibitor therapy (120 mg omeprazole daily). Sixty-six patients (94.4%) underwent further surveillance endoscopy. At each surveillance endoscopy four-quadrant biopsies were taken from the neo-squamous epithelium at 2 cm intervals depending on the pre-treatment length of BE mucosa beginning at the neo-Z-line, and from any endoscopically suspicious lesion. RESULTS: The median follow-up of 66 patients was 51 mo (range 9-85 mo) giving a total of 280.5 patient years. A mean of 6 biopsies were taken during surveillance endoscopies. In 13 patients (19.7%) tongues or islands suspicious for BE were found during endoscopy. In 8 of these patients (12.1%) non-neoplastic BE relapse was confirmed histologically giving a histological relapse rate of 3% per year. In none of the patients, intraepithelial neoplasia nor an esophageal adenocarcinoma was detected. Logistic regression analysis identified endoscopic detection of islands or tongues as the only positive predictor of BE relapse (P= 0.0004). CONCLUSION: The long-term relapse rate of non neoplastic BE following complete ablation with high-power APC is low (3% per year).

Free radicals and antioxidant systems in reflux esophagitis and Barrett's esophagus

AIM: Experimental studies suggest that free radicals are involved in acid and pepsin-induced damage of esophageal mucosa. The profile and balance between free radicals and antioxidant systems in human esophagitis are unknown. METHODS: Superoxide anion and its powerful oxidant reaction with nitric oxide (peroxynitrite) generation were determined in esophageal mucosal biopsies from 101 patients with different gastro-esophageal reflux diseases and 28 controls. Activity of both superoxide dismutase (SOD) and catalase, and reduced glutathione (GSH) levels, were also assessed. Expression of Cu,ZnSOD, MnSOD and tyrosine-nitrated MnSOD were analyzed by Western blot and/or immunohistochemistry. RESULTS: The highest levels of superoxide anion generation were found in patients with severe lesions of esophagitis. Peroxynitrite generation was intense in Barrett's biopsies, weaker in esophagitis and absent/weak in normal mucosa. Expression of Cu,ZnSOD and MnSOD isoforms were present in normal mucosa and increased according to the severity of the lesion, reaching the highest level in Barrett's esophagus. However, SOD mucosal activity significantly decreased in patients with esophagitis and Barrett's esophagus, which was, at least in part, due to nitration of its tyrosine residues. Catalase activity and GSH levels were significantly increased in mucosal specimens from patients with esophagitis and/or Barrett's esophagus. CONCLUSION: A decrease in SOD antioxidant activity leading to increased mucosal levels of superoxide anion and peroxynitrite radicals may contribute to the development of esophageal damage and Barrett's esophagus in patients with gastroesophageal reflux. Administration of SOD may be a therapeutic target in the treatment of patients with esophagitis and Barrett's esophagus.

Endoscopic ablation of Barrett's esophagus using high power setting argon plasma coagulation: A prospective study

AIM: This prospective study evaluated the effectiveness of 90 W argon plasma coagulation (APC) for the ablation of Barrett's esophagus (BE) that is considered to be the main risk factor for the development of esophageal adenocarcinoma.METHODS: The results from 25 patients, observed at the First Department of General Surgery, University of Verona, Italy, from October 2000 to October 2003, who underwent APC for histologically proven BE were prospectively analyzed.RESULTS: The ablation treatment was completed in all the patients but one (96%). The mean number of APC sessions needed to complete ablation was 1.6 (total number: 40). The eradication was obtained in the majority of cases by one session only (60%), two sessions were required in 24% of the cases and three or more in 16%.About 43% of the sessions were complicated. Retrosternal pain (22.5%) and fever (17.5%) were the most frequent symptoms. Only one major complication occurred, it was an hemorrhage due to ulcer formation on the treated esophagus that required urgent endoscopic sclerosis and admission. The follow-up was accomplished in all the patients with a mean period of 26.3 mo and 20 patients (84%) with a follow-up period longer than 24 mo. Only one patient showed a relapse of metaplastic mucosa 12 mo after the completion of ablation. The patient was hence re-treated and now is free from recurrence 33 mo later.CONCLUSION: High power setting (90 W) APC showed to be safe and effective. The effects persist at a mean follow-up period of two years with a comparable cost in term of complications with respect to standard power settings. Further studies with greater number of patients are required to confirm these results and to assess if ablation reduces the incidence of malignant progression.

Endoscopic options for treatment of dysplasia in Barrett's esophagus

Recent advances in the endoscopic treatment of dysplasia in Barrett's esophagus(BE) have allowed endoscopists to provide effective and durable eradication therapies. This review summarizes the available endoscopic eradication techniques for dysplasia in patients with BE including endoscopic mucosal resection, endoscopic submucosal dissection, photodynamic therapy, argon plasma coagulation, radiofrequency ablation and cryotherapy.

Recent developments in pathogenesis,diagnosis and therapy of Barrett's esophagus

The burden of illness from esophageal adenocarcinoma continues to rise in the Western world,and overall prognosis is poor.given that Barrett's esophagus(BE),a metaplastic change in the esophageal lining is a known cancer precursor,an opportunity to decreasedisease development by screening and surveillance might exist.This review examines recent updates in the pathogenesis of BE and comprehensively discusses known risk factors.Diagnostic definitions and challenges are outlined,coupled with an in-depth review of management.Current challenges and potential solutions related to screening and surveillance are discussed.The effectiveness of currently available endoscopic treatment techniques,particularly with regards to recurrence following successful endotherapy and potential chemopreventative agents are also highlighted.The field of BE is rapidly evolving and improved understanding of pathophysiology,combined with emerging methods for screening and surveillance offer hope for future disease burden reduction.

Gene expression in Barrett's esophagus and reflux esophagitis induced by gastroduodenoesophageal reflux in rats

AIM: To investigate the difference of gene expression profiles between Barrett's esophagus and reflux esophagitis induced by gastroduodenoesophageal reflux in rats.METHODS: Eight-week-old Sprague-Dawley rats were treated esophagoduodenostomy to produce gastroduodenoesophageal reflux, and another group received sham operation as control. Esophageal epithelial tissues were dissected and frozen in liquid nitrogen immediately for pathology 40 wk after surgery. The expression profiles of 4 096 genes in reflux esophagitis and Barrett's esophagus tissues were compared with normal esophageal epithelium by cDNA microarray.RESULTS: Four hundred and forty-eight genes in Barrett'sesophagus were more than three times different from those in normal esophageal epithelium, including 312 up regulated and 136 down-regulated genes. Two hundred and thirty-twogenes in RE were more than three times different from those in normal esophageal epithelium, 90up-regulated and 142 down-regulated genes. Compared to reflux esophagitis, there were 214 up-regulated and 142 down-regulated genes in Barrett's esophagus. CONCLUSION: Esophageal epithelium exposed excessively to harmful ingredients of duodenal and gastric reflux can develop esophagitis and Barrett's esophagus gradually.The gene expression level is different between reflux esophagitis and Barrett's esophagus and the differentially expressed genes might be related to the occurrence and development of Barrett's esophagus and the promotion or progression in adenocarcinoma.

Endoscopic mucosal resection of Barrett's esophagus detects high prevalence of subsquamous intestinal metaplasia

AIM:To report the prevalence of Subsquamous intestinal metaplasia(SSIM)in patients undergoing endoscopic mucosal resection(EMR)for staging of Barrett’s esophagus(BE).METHODS:Thirty-three patients with BE associated neoplasia underwent EMR at our institution between September 2009 and September 2011;22 of these patients met study inclusion criteria.EMR was targeted at focal abnormalities within the BE segment.EMR was performed in standardized fashion using a cap-assisted band ligation technique,and resection specimens were assessed for the presence of SSIM.Demographic and clinical data were analyzed to determine predictors of SSIM.RESULTS:SSIM was detected in 59%of patients.SSIM was detected in 73%of patients with short segment(<3 cm)BE,and in 45%of patients with longsegment(≥3 cm)BE(P=NS).There was no association between presence/absence of SSIM and age,gender,or stage of BE-associated neoplasia.CONCLUSION:EMR detects SSIM in a majority of patients with BE-associated neoplasia.While the longterm clinical significance of SSIM remains uncertain,these results highlight the importance of EMR as an optimal diagnostic tool for staging of BE and detection of SSIM,and should further limit concerns that SSIM is purely a post-ablation phenomenon.

Improved specimen adequacy using jumbo biopsy forceps in patients with Barrett's esophagus

AIM:To assess the sampling quality of four different forceps(three large capacity and one jumbo) in patients with Barrett's esophagus.METHODS:This was a prospective,single-blind study.A total of 37 patients with Barrett's esophagus were enrolled.Targeted or random biopsies with all four forceps were obtained from each patient using a diagnostic endoscope during a single endoscopy.The following forceps were tested:A:FB-220 K disposable large capacity;B:BI01-D3-23 reusable large capacity;C:GBF-02-23-180 disposable large capacity;and jumbo:disposable Radial Jaw 4 jumbo.The primary outcome measurement was specimen adequacy,defined as a well-oriented biopsy sample 2 mm or greater with the presence of muscularis mucosa.RESULTS:A total of 436 biopsy samples were analyzed.We found a significantly higher proportion of adequate biopsy samples with jumbo forceps(71%)(P < 0.001 vs forceps A:26%,forceps B:17%,and forceps C:18%).Biopsies with jumbo forceps had the largest diameter(median 2.4 mm)(P < 0.001 vs forceps A:2 mm,forceps B:1.6 mm,and forceps C:2mm).There was a trend for higher diagnostic yield per biopsy with jumbo forceps(forceps A:0.20,forceps B:0.22,forceps C:0.27,and jumbo:0.28).No complications related to specimen sampling were observed with any of the four tested forceps.CONCLUSION:Jumbo biopsy forceps,when used with a diagnostic endoscope,provide more adequate specimens as compared to large-capacity forceps in patients with Barrett's esophagus.

Circulating exosomal miRNAs as potential biomarkers for Barrett's esophagus and esophageal adenocarcinoma

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.

CARCINOMA ARISING IN BARRETT'S ESOPHAGUS (A REPORT OF 51 CASES)

Fifty-one patients with carcinoma arising in Barrett's esophagus were treated surgically from 1971 to 1990. This represented 10.2% of all treated cases with esophageal carcinoma during the same period. The mean age was 63 years. The most common symptom was dysphagia. According to PTNM staging, 18 were stage II,3 stage III and 3 stage IV. All patients were treated bysurgery. The 30-day hospital mortality was 3.98%. Theone, two and five-year survival rates were 45.9%, 25.0%and 13.6%, respectively. The 5-year survival rate wassignificantly greater for patrents with stage II (25.0%)than for parients with stage III + IV (4.s%) (P<0.05) andfor tumor length less than 6 cm (21%) than for tumorlength greater than 6 cm (0). The results indicate that thesurvival rate following resection is closely related to theclinical stage and tumor size.

Characteristics of Acid Reflux in Barrett's Esophagus

To determine the relationship between Barrett'sesophagus (BE) and features of ga stroesophageal acid reflux, 24 h esophageal pH monitoring was performed in 90 pa tients. The patients were divided into 3 groups: 31 subjects with BE, 21 with mi ld esophagitis and 38 with severe esophagitis. The following parameters were eva luated: the percentage time of pH<4; the number of reflux episodes over 5 min; t he duration of longest episodes and DeMeester score over total period and the au terior three parameters in erect and supine position . All these parameters in BE were significantly different from those with mild e sophagitis ( P <0.01) and not significantly different from those with severe esophagitis ( P >0.05). During supine position all the above parameters in BE were significantly different from those with reflux esophagitis ( P <0.05). It is concluded that the quantity of acid reflux is not an important factor in development of BE in gastroesophageal reflux (GER), and the acid reflux in supine position might be important in development of BE in GER.

Whole circumferential endoscopic submucosal dissection of superficial adenocarcinoma in long-segment Barrett's esophagus:A case report

BACKGROUND Esophageal adenocarcinoma(EAC)derived from long-segment Barrett’s esophagus(LSBE)is extremely rare in Asia.LSBE-related EAC is often difficult to diagnose in the horizontal extent.If the tumor has spread throughout the LSBE,whole circumferential endoscopic submucosal dissection(ESD)should be performed,which is difficult to complete safely.Additionally,whole circumferential ESD can bring refractory postoperative stenosis.We hereby report a case of EAC involving the whole circumference of the LSBE,achieving complete endoscopic removal without complications.CASE SUMMARY An 85-year-old man with the chief complaint of dysphagia underwent esophagogastroduodenoscopy.We suspected a flat-type cancerous lesion that extended the whole circumference of the LSBE(C 3.5,M 4.0)using narrow-band imaging magnification endoscopy(NBI-M).We achieved circumferential en bloc resection of the lesion safely with special ESD techniques.Histology of the ESD specimens demonstrated that the superficial EAC extended the whole circumference of the LSBE,and papillary or well-differentiated tubular adenocarcinoma was confined in the lamina propria mucosa showing a vertical negative margin.To prevent post-ESD stenosis,we performed endoscopic local injection of steroids,followed by oral administration of steroids.There was no evidence of esophageal refractory stenosis or tumor recurrence 30 mo after ESD.In summary,we experienced a rare case of LSBE-related EAC.The horizontal tumor extent was accurately diagnosed by NBI-M.Additionally,we achieve whole circumferential ESD safely without postoperative refractory stenosis.CONCLUSION NBI-M,ESD,and steroid therapy enabled the curative resection of superficial full circumferential LSBE-related EAC without refractory postoperative stenosis.

Update on management of Barrett's esophagus

Barrett's esophagus(BE)is a common condition thatdevelops as a consequence of gastroesophageal reflux disease.The significance of Barrett's metaplasia is that predisposes to cancer development.This article provides a current evidence-based review for the management of BE and related early neoplasia.Controversial issues that impact the management of patients with BE,including definition,screening,clinical aspects,diagnosis,surveillance,and management of dysplasia and early cancer have been assessed.

Pathologic and Clinical Analysis of Carcinosarcoma of Esophagus (20 Cases)

Objective:Carcinosarcoma of esophagus is an infrequent disease. Here, the pathologic data of larger specimens of this disease are reviewed and analyzed for studying its clinical characteristics in order to provide support information for clinical diagnosis. Methods: To review and study the clinical data of 20 patients of esophageal carcinosarcoma. Results: Most of esophageal carcinosarcoma grew like pileus or polypus in esophagus, a few of them were infiltrating. Microscopic examination of the resected specimens indicated that the tumor is composed of sarcomatous element and carcinomatous element (the main element), and the surface of such tumor was covered mostly by carcinoma tissues. The result of biopsy showed that the tumor is squamous cell carcinoma. X-ray examination indicated that there was polypus-like smooth and tidy filling defect in the esophagus of such patient, and its mucous membrane showed “daubing-trace” like characteristics. Conclusion: Carcinosarcoma of esophagus is a tumor of low invasion, which grows mainly in the esophageal lumen. The clinical symptoms of this tumor are different from those of esophagus carcinoma in certain degree. The “daubing-trace” like characteristics is typical of X-ray picture. The results of most endoscopic biopsies demonstrate squamous cell carcinoma or lower differentiation carcinoma, which are difficult for confirmed diagnosis before operation.

Role of nitric oxide in the pathogenesis of Barrett's-associated carcinogenesis

Barrett's esophagus(BE), a premalignant condition to Barrett's adenocarcinoma(BAC), is closely associated with chronic inflammation due to gastro-esophageal reflux. Caudal type homeobox 2(CDX2), a representative marker of BE, is increased during the metaplastic and neoplastic transformation of BE. Nitric oxide(NO) has been proposed to be a crucial mediator of Barrett's carcinogenesis. We previously demonstrated that CDX2 might be induced directly under stimulation of large amounts of NO generated around the gastroesophageal junction(GEJ) by activating epithelial growth factor receptor in a ligand-independent manner. Thus, we reviewed recent developments on the role of NO in Barrett's carcinogenesis. Notably, recent studies have reported that microbial communities in the distal esophagus are significantly different among groups with a normal esophagus, reflux esophagitis, BE or BAC, despite there being no difference in the bacterial quantity. Considering that microorganism components can be one of the major sources of large amounts of NO, these studies suggest that the bacterial composition in the distal esophagus might play an important role in regulating NO production during the carcinogenic process. Controlling an inflammatory reaction due to gastro-esophageal reflux or bacterial composition around the GEJ might help prevent the progression of Barrett's carcinogenesis by inhibiting NO production.

Multinational survey on the preferred approach to management of Barrett’s esophagus in the Asia-Pacific region

BACKGROUND Major societies provide differing guidance on management of Barrett’s esophagus(BE),making standardization challenging.AIM To evaluate the preferred diagnosis and management practices of BE among Asian endoscopists.METHODS Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis,surveillance and management of BE.RESULTS Five hundred sixty-nine of 1016(56.0%)respondents completed the survey,with most respondents from Japan(n=310,54.5%)and China(n=129,22.7%).Overall,the preferred endoscopic landmark of the esophagogastric junction was squamocolumnar junction(42.0%).Distal palisade vessels was preferred in Japan(59.0%vs 10.0%,P<0.001)while outside Japan,squamo-columnar junction was preferred(59.5%vs 27.4%,P<0.001).Only 16.3%of respondents used Prague C and M criteria all the time.It was never used by 46.1%of Japanese,whereas 84.2%outside Japan,endoscopists used it to varying extents(P<0.001).Most Asian endoscopists(70.8%)would survey long-segment BE without dysplasia every two years.Adherence to Seattle protocol was poor with only 6.3%always performing it.73.2%of Japanese never did it,compared to 19.3%outside Japan(P<0.001).The most preferred(74.0%)treatment of non-dysplastic BE was proton pump inhibitor only when the patient was symptomatic or had esophagitis.For BE with low-grade dysplasia,6-monthly surveillance was preferred in 61.9%within Japan vs 47.9%outside Japan(P<0.001).CONCLUSION Diagnosis and management of BE varied within Asia,with stark contrast between Japan and outside Japan.Most Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction,which is incorrect.Most also did not consistently use Prague criteria,and Seattle protocol.Lack of standardization,education and research are possible reasons.