Abstract
This study summarized the clinical characteristics and endoscopic findings in patients with long-segment Barrett’s esophagus through a retrospective analysis of the clinical data of three patients with long-segment Barrett’s esophagus. Data from patients, including demographic characteristics, medical history, endoscopy findings, pathological diagnosis, and esophageal sponge cytology results were analyzed, and a literature review was performed. Three patients were included; all were male with a mean age of 67.3 ± 7.1 years. Symptoms encompassed heartburn (3/3), acid reflux (2/3), belching (1/3), retrosternal pain (1/3), abdominal distension (1/3), and dysphagia (1/3). Risk factors included alcohol use (3/3), consumption of pickled and hot foods or beverages (3/3), smoking (1/3), and familial esophageal disease history (1/3). Endoscopically, Prague C & M criteria measurements were C13M15, C4M10, and C6M7, with long-segment Barrett’s esophagus lesions spanning the upper/middle/lower esophagus; all showed circumferential involvement and coexisted with gastroesophageal reflux disease. Concurrently, two patients presented with all the following three conditions: hiatal hernia, chronic atrophic gastritis, and Helicobacter pylori infection. Pathologically, one patient showed early intramucosal adenocarcinoma, whereas two had intestinal metaplasia. Sponge cytology identified grade 3 atypical cells in one patient and grade 2 hyperplasia in two patients. In conclusion, long-segment Barrett’s esophagus is strongly associated with gastroesophageal reflux disease and necessitates endoscopic surveillance, whereas sponge cytology screening has shown initial feasibility but requires standardized protocols and multicenter validation for clinical integration.
Introduction
Long-segment Barrett’s esophagus (LSBE) is a rare type of Barrett’s esophagus (BE), accounting for only 0.2% of all cases. 1 LSBE is frequently reported in European and American populations, 2 whereas short-segment Barrett’s esophagus (SSBE) is predominantly observed in Asian populations. Notably, reports of LSBE in Chinese populations remain scarce, with only a few global reports describing esophageal segments exceeding 10 cm. Consequently, comprehensive characterization of the endoscopic manifestations and clinical characteristics of LSBE is essential for optimizing therapeutic strategies.
BE is the primary precursor lesion for most esophageal adenocarcinomas (EACs); it confers a 30- to 125-fold increased risk of EAC development compared with that in the general population. 3 Chinese epidemiological data indicate a malignancy rate of approximately 0.61% in patients with BE. 4 Western clinical perspectives emphasize that EAC pathogenesis is predominantly associated with LSBE, whereas SSBE and ultra-short segment BE demonstrate minimal risk of progression to adenocarcinoma. 5
Emerging diagnostic modalities, such as esophageal sponge cytology, offer a simplified and cost-effective strategy for screening esophageal dysplasia. 6 Considering the protracted progression from Barrett’s metaplasia to malignancy, cost efficiency is a major consideration. However, limited evidence exists on the application of esophageal sponge cytology in Chinese populations, and no prior reports have assessed its utility in LSBE. This study aimed to analyze three patients with LSBE identified at our institution. Their clinical characteristics, endoscopic findings, and cytological results via esophageal sponge sampling were systematically assessed. These observations provide novel insights into informed diagnostic and management approaches for LSBE.
Methods
Patients
Patients diagnosed with LSBE via high-resolution endoscopy at Tongliao People’s Hospital between January 2023 and September 2024 were retrospectively enrolled. The inclusion criteria were as follows: (a) age 18 to 85 years, regardless of sex; (b) confirmed LSBE diagnosis based on the development and validation of an endoscopic grading system for BE: Prague C & M criteria. 7 The exclusion criteria were as follows: (a) incomplete clinical data, (b) esophageal-gastric varices or esophageal stricture, (c) coagulation disorders or requiring the continuous use of anticoagulants or antiplatelet agents, (d) advanced esophageal carcinoma diagnosis (T2 or higher stages) or pregnancy, and (e) contraindications for gastroscopy or mucosal biopsy. All patients signed consent forms for treatment and data publication, agreeing to the release of their data and images. We have de-identified all patient details. This study involves human participants and was approved by the Tongliao People’s Hospital Ethics Committee on 17 April 2025 (IRB:TYS-2025-34).
Endoscopic diagnosis
All endoscopic examinations adhered to a standardized protocol using high-definition white-light endoscopy (WLE) and electronic chromoendoscopy, such as narrow band imaging (NBI) and flexible spectral imaging color enhancement (FICE). Biopsies were systematically collected per the Seattle protocol. High-resolution endoscopy was performed using endoscopes from Olympus Corporation (Tokyo, Japan) (models GIF-H260, GIF-H290Z) or Fujifilm endoscopes by experienced endoscopists. The following parameters were documented: (a) lesion characteristics, including location, length, mucosal surface morphology, and Prague C & M criteria (C: extent of circumferential metaplasia; M: maximal extent of the metaplasia) and (b) comorbidities such as reflux esophagitis, hiatal hernia, and chronic gastritis (classified and mapped).
Sponge cytology for esophageal cell sampling
The sponge capsule (Figure 1) comprises an ingestible gelatin capsule covering a compressed polyurethane sponge mesh that is attached to a 60-cm line. This gelatin capsule measures approximately 26.79 mm in length and 9.50 mm in diameter. Sampling protocol: Before sampling, patients fast for 2 h and rinsed their mouths with water twice. The sampling device was inspected for line integrity, and the segment proximal to the blue marker was positioned in the oral cavity. The capsule was swallowed with room-temperature water, ensuring that the blue marker was positioned at the lips. After 2 min, 200 mL of warm water (55°C) was consumed to promote sponge expansion. Then, the line was gently withdrawn to retrieve the sponge, which was placed into the sample bottle. Demographic data, including name, sex, and age, were recorded and verified before sample submission.

Sponge cytology sampler. (a) Disposable lesion cell collector and (b) Capsule device: Edible gelatin capsule, approximately 26.79 mm in length and 9.50 mm in diameter. The sampler’s diameter after expansion is approximately 50.00 mm.
DNA ploidy analysis: DNA ploidy assessments detected early lesions with abnormal DNA content before morphological changes. DNA index (DI) was calculated to reflect nuclear DNA content, with results integrated into the morphological findings to improve diagnostic sensitivity.
Comprehensive risk assessment value: The risk value (RV) was derived from a large-scale artificial intelligence model based on multivariate data integration. It incorporated demographic factors, cytological features, and risk factor scoring parameters. The following risk stratification levels were used: grade 1, low risk (RV < 30, within normal limits); grade 2, low-intermediate risk (RV 31–60, hyperplasia); grade 3, intermediate risk (RV 61–85, atypical cells); grade 4, intermediate–high risk (RV 86–95, low-/high-grade dysplasia (HGD)); and grade 5, high risk (RV > 95, squamous cell carcinoma or adenocarcinoma).
Statistical analysis
Statistical Package for Social Sciences 26.0 software was used for all statistical analyses. Normally distributed continuous data are expressed as x ± s, whereas nonnormally distributed data are expressed as M (quartile (Q) 1, Q3). Categorical data are presented as frequencies and percentages.
Results
Clinical characteristics
Three patients with LSBE were included in this study. All patients were men, with a mean age of 67.3 ± 7.1 years. The average body mass index was 22.1 kg/m2. Two patients reported acid reflux and all three experienced heartburn. One patient each presented with belching, retrosternal pain, and abdominal distension. Of them, one reported dysphagia. No patients reported abdominal pain. Regarding lifestyle and dietary habits, one patient had a 20-year history of smoking. All patients had a history of alcohol consumption; of them, two had been consuming alcohol for more than 30 years. All patients preferred preserved foods and consumed hot foods. Two patients had missing teeth. All patients had completed education up to junior high school. One patient had a family history of esophageal disease (Table 1 and Figure 2). The reporting of this study conforms to Case Report (CARE) guidelines. 8
Clinical characteristics of three patients with LSBE.
BMI: body mass index; LSBE: long-segment Barrett’s esophagus.

White-light endoscopy, electronic chromoendoscopy, and histopathological findings in three patients with LSBE. Case 1. (a) WLI: circumferential orange–red Barrett’s epithelium is observed in the esophagus 20–35 cm from the incisors. (b) NBI: irregular/fused glands, absent glands in depression, reticular dilated vessels. (c) Metaplastic columnar epithelium (H&E staining, ×4). Case 2. (d) WLI: a localized erythematous mucosal depression is observed 30–40 cm from the incisors. (e) NBI: gland loss, twisted vessels. (f) Intestinal metaplastic epithelium with goblet cells (H&E staining, ×10). Case 3. (g) WLI: circumferential orange–red Barrett’s epithelium is identified in the esophagus 28–35 cm from the incisors. (h) FICE: tea-brown discoloration and (i) intestinal metaplastic epithelium with goblet cells (H&E staining, ×10).
Endoscopic characteristics
BE spanned the upper, middle, and lower segments in one patient, whereas it spanned the middle and lower segments in the remaining two. The C were 13 cm, 4 cm, and 6 cm. The M were 15 cm, 10 cm, and 7 cm. Morphologically, all cases were categorized as circumferential type. Three patients had reflux esophagitis. Two patients each had hiatal hernia, chronic atrophic gastritis, and Helicobacter pylori infection. Regarding pathological types, moderately differentiated, early intramucosal adenocarcinoma was identified in one patient (type 0–III, concave). The remaining two patients had intestinal metaplasia (Table 2).
The endoscopic findings of three patients with LSBE.
C: extent of circumferential metaplasia; GERD: gastroesophageal reflux disease; LSBE: long-segment Barrett’s esophagus; M: maximal extent of the metaplasia.
In case 1, magnifying endoscopy (ME) suggested orange-colored Barrett’s epithelium around the esophageal ring, extending up to 15 cm. A flat lesion was visible in the middle of the esophagus; it showed brown discoloration and irregular local glandular ducts of different sizes and fusions. This duct disappeared in the sunken area, along with thickened, twisted, and expanded microvessels showing a grid-like pattern (type B2). Chest computed tomography (CT) and X-ray of the upper digestive tract showed lower esophageal wall thickening. Endoscopic ultrasonography showed flat, sunken esophageal lesions, categorized as type 0–IIb + 0–IIc. These signs were suggestive of high-grade intraepithelial adenomatosis, with possible focal intramucosal carcinoma. Moreover, the infiltration depth was confined to the muscularis mucosa layer (Figure 3). Endoscopic submucosal dissection (ESD) was performed. Histopathology affirmed BE with intestinal metaplasia and cancerization. The findings confirmed moderately differentiated, early intramucosal adenocarcinoma (type 0–III). The tumor measured 1.2 × 0.6 × 0.4 cm, invading the muscularis mucosa without penetrating it. The peripheral and basal incisal margins were clear, without signs of intravascular cancer thrombus and nerve invasion. Follow-up via ME and chest CT over 9 months indicated no recurrence or metastasis.

Esophagogram, WLE, NBI-ME, EUS, and histopathological findings of case 1. (a) Middle to lower esophageal mucosal irregularity, cardial incompetence (chalasia), contrast medium reflux. (b) Localized depressed erosions and scattered white exudates. (c) Depressed areas demonstrate glandular atrophy, dilated and tortuous microvessels (predominantly B2 pattern) with reticular arrangement. (d) EUS showed the possibility of focal intramucosal Ca, infiltration depth of MM layer and (e) early intramucosal adenocarcinoma confined to muscularis mucosae (H&E staining, ×4). Ca: carcinoma; EUS: endoscopic ultrasound; H&E: hematoxylin and eosin; NBI-ME: narrow band imaging with magnifying endoscopy; WLE: white-light endoscopy.
In case 2, under WLE, a superficial indentation with an erythematous and rough surface was observed on the left lateral esophageal wall. On magnification, the background mucosa was brown, with dilated intrapapillary capillary loops, categorized as B1 type. Microglandular tubes were missing in the depression, with distinct boundaries as well as distorted and dilated microvessels. In case 3, WLE showed smooth mucosa with strips of hyperemia, erythema, and erosion. In both cases 2 and 3, histopathology confirmed intestinal metaplasia without EAC.
Esophageal cell sampling via sponge cytology testing
Sample 1 demonstrated significant DNA content abnormalities, with a DI of 3.100. Several cells exhibited abnormal nuclear DNA content. This sample was categorized as grade 3, indicating squamous or columnar epithelial cells with indeterminate morphology and unconfirmed neoplastic potential. Finally, they were assessed as indicating moderate risk of esophageal cancer. Sample 2 (DI = 2.611) and sample 3 (DI = 2.697) showed 12 and 14 cells, respectively, with nuclear DNA content abnormalities. Both were classified as grade 2, suggesting a moderate-to-low risk of esophageal cancer (Table 3).
Sponge cytology findings from esophageal cell samples.
DI: DNA index; RV: risk value.
DI: Quantitative analysis of nuclear DNA content (reference ≤ 2.500).
Discussion
LSBE is a rare condition typically associated with classic gastroesophageal reflux disease (GERD) symptoms, 9 such as heartburn, acid regurgitation, and belching. The clinical manifestations observed in the present case series align with those reported in the literature. Endoscopically, LSBE is characterized by salmon-pink columnar epithelium replacing the healthy squamous mucosa and extending ≥3 cm above the gastroesophageal junction. Histopathology confirmation involves the identification of intestinal metaplasia. LSBE predominantly involves the distal esophagus, often extending toward the mid-esophagus. Morphologically, it is classified as circumferential, tongue-like, or island-type; however, island-like patterns are commonly observed in SSBE. In this case series, all three patients exhibited circumferential involvement of the middle and lower esophagus.
Geographic variations exist in the prevalence and progression of BE. LSBE predominates in Western populations, 10 whereas SSBE predominates in Asia, where the EAC incidence remains lower. Established risk factors for BE include chronic GERD, age >50 years, male sex, obesity, smoking habit, alcohol consumption, consumption of pickled or hot foods, low education level, and a family history of esophageal disease. All three patients reported alcohol consumption, a preference for pickled and hot foods, and junior high school education. Only one patient had a family history of esophageal cancer.
From a diagnostic perspective, WLE remains the mainstay for the initial assessment of LSBE. It facilitates the visualization of lesion extent, macroscopic morphology, and concurrent pathologies, such as reflux esophagitis, hiatal hernia, strictures, and ulcerations. When combined with electronic chromoendoscopy and ME, it enables the improved characterization of mucosal patterns. Intestinal metaplasia exhibits chestnut-brown villous or cerebriform surface structures with uniform reticular or coil-shaped microvasculature. In contrast, dysplasia and early-stage EAC lesions disrupt this microarchitecture, presenting as absent/disorganized glandular openings and abnormal microvascular features, including dilation, tortuosity, and irregular morphology. 11 This multimodal approach enhances the detection of intestinal metaplasia and dysplasia by meticulously analyzing mucosal and vascular patterns, guiding targeted biopsies. The integration of endoscopic findings with histopathological evaluation enables comprehensive risk stratification for malignant transformation, thereby optimizing surveillance protocols and therapeutic decision-making. However, the implementation of population-level endoscopic screening remains constrained by multiple factors such as the protracted timeline of BE carcinogenesis, substantial procedural costs, invasive nature, and suboptimal patient compliance. For example, a study conducted in the US that evaluated nonendoscopic cell collection devices demonstrated high sample adequacy (95.7%) and good patient acceptability (91.3%) for detecting BE. Therefore, these tools serve as promising diagnostic alternatives and warrant further development. 12 In the present case series, histopathological analysis confirmed early intramucosal adenocarcinoma only in case 1, whereas cytology detected atypical cells. There was complete concordance between cytological and histological results in the other two cases. This diagnostic discrepancy in case 1 may reflect technical limitations of the sponge capsule device, potentially related to insufficient cellular yield or statistical constraints resulting from the small sample size. Given our small, observational sample, future work requires standardized multi-point sampling protocols and large-scale validation studies for enhanced diagnostic accuracy and reliability.
A Chinese meta-analysis and systematic review suggested an inverse association between H. pylori positivity and LSBE development, indicating its protective role against dysplasia progression in Barrett’s mucosa. However, no significant correlation was observed between H. pylori infection and SSBE. 13 This phenomenon may be attributed to the strong association between H. pylori infection and chronic gastritis, particularly chronic atrophic gastritis, which reduces gastric acid secretion. Diminished acid output decreases gastroesophageal reflux, thereby lowering GERD incidence and reducing the risk of BE. 14 Interestingly, case 1 exhibited the longest esophageal segment involvement; however, it did not show evidence of chronic atrophic gastritis, aligning with previous reports.
BE is a premalignant condition characterized by a stepwise neoplastic progression through sequential histological alterations, including low-grade dysplasia, HGD, intramucosal carcinoma, and finally invasive adenocarcinoma. 15 Although esophageal squamous cell carcinoma (ESCC) remains predominant in China, epidemiological data suggest a rising incidence of EAC nationally, mirroring trends in Western populations where EAC has surpassed ESCC as the most common esophageal malignancy. 16 The carcinogenic transition from healthy esophageal epithelium to EAC demonstrates bidirectional developmental instability. 17 The trajectory of EAC progression is substantially influenced by prolonged exposure to modifiable risk factors and therapeutic interventions. Environmental determinants—particularly GERD, obesity, and tobacco consumption—are predominant risk factors that warrant heightened public-health attention.18,19
Patients with LSBE experience elevated risks of EAC progression, underscoring the importance of early detection and effective management of dysplasia in halting neoplastic advancement. 20 A Japanese multicenter cohort study demonstrated an annual EAC incidence of 1.2% among patients with LSBE.21,22 Furthermore, a U.S. systematic review and meta-analysis suggested significantly reduced neoplastic progression rates among patients with nondysplastic SSBE compared with patients with LSBE. For patients undergoing surveillance endoscopy, Barrett’s segment length serves as a practical biomarker for risk stratification, warranting tailored surveillance intervals based on the lesion length.23–25 Notably, BE with HGD poses a 7% cumulative risk of cancer progression (95% confidence interval 5%–8%), 26 emphasizing the imperative for early intervention, particularly for dysplasia.27,28 In the present cohort, only one patient with a BE segment with length 15 cm progressed to EAC, whereas the remaining two patients with BE segment length <10 cm segments remained stable, consistent with existing epidemiological patterns.
ESD has become the cornerstone for managing early Barrett’s-related mucosal lesions. 29 This technique offers distinct advantages, including feasibility of en bloc resection regardless of lesion size, reduced recurrence rates, and precise histopathological evaluation. 30 A meta-analysis of 524 patients with BE reported 93% en bloc resection rates, 74.5% complete resection rates, <2% complication rates (bleeding/perforation), and minimal recurrence after curative resection. 31 These characteristics confirmed the ability of ESD to achieve high complete remission rates in Barrett’s-related neoplasia. 32 Complementary therapeutic approaches include endoscopic radiofrequency ablation, which has demonstrated higher technical success rates and lower complication profiles in SSBE cases in the US. 33 These outcomes suggest that intensified surveillance protocols are a more pragmatic management strategy for LSBE, whereas ablative therapies remain particularly effective for cases with shorter segment involvement.
In summary, LSBE is a rare condition predominantly observed in elderly males with high-risk lifestyles (alcohol, pickled/spicy food) and comorbidities (hiatal hernia, H. pylori infection). Diagnosis relies on endoscopic and histopathological examination, with sponge cytology showing preliminary non-invasive screening potential. Integrated risk assessment and tailored surveillance for high-risk populations are suggested, requiring further multicenter validation.
Limitations
This study has certain limitations inherent to its retrospective nature, including (a) heterogeneity in the endoscopic equipment used; (b) a small sample size, which may have introduced selection bias; and (c) inaccessible complete follow-up data for a subset of the patients. These factors may have affected the generalizability of our findings.
Although cytosponge endoscopy proved technically feasible in these LSBE cases, it is crucial to note these are preliminary findings. The small sample size prevents meaningful statistical analysis and limits generalization to the broader LSBE population at this stage.
Prague C & M criteria weren’t systematically applied initially. Per the reviewers’ request, we added retrospective data via image review, with C & M confirmed using dual independent endoscopic reviews to ensure accuracy.
Footnotes
Acknowledgments
We sincerely thank the doctors of the Digestive Endoscopy Center for their assistance in data collection and analysis, as well as the reviewers for their constructive comments. Additionally, we used Deepseek for language polishing, although all academic content and conclusions remain the sole responsibility of the authors.
Author contributions
Ling Sun: Writing—original draft and funding acquisition
Wen J Ao: Writing—original draft
Hao Q Zhi: Data curation
Wuri N Bai: Investigation
Fan Yu: Methodology
Hui F Pang: Writing—review & editing, endoscopic procedures and surgery, funding support
Quan Man: Writing—review & editing
Consent to participate
All patients provided written informed consent to participate in the study.
Consent for publication
All patients agreed to the publication of these data and images.
Data availability statement
All the data from this study are freely available for use.
Declaration of conflicting interest
The authors declare that they have no conflicts of interest.
Ethical considerations
This study involves human participants and was approved by Tongliao People’s Hospital Ethics Committee (IRB:TYS-2025-34).
Funding
This study was supported by grants from the Inner Mongolia Autonomous Region Postgraduate Research Innovation Project (no. KC2024052S) and Inner Mongolia Medical Doctor Association Clinical Research and New Technology Promotion Project (no.YSXH2024KYF103).
