Impact of surgical vs medical management on histologic outcomes in Barrett’s esophagus: A meta-analysis

Abstract

BACKGROUND

Barrett’s esophagus (BE) is a premalignant condition associated with esophageal adenocarcinoma, yet its optimal management remains controversial. Proton pump inhibitors (PPIs) are widely used, whereas antireflux surgery may provide more effective reflux control and potentially influence histologic outcomes. However, comparative evidence regarding BE regression and progression remains inconsistent. We hypothesized that surgical fundoplication yields superior histologic outcomes compared with medical therapy.

AIM

To compare histologic regression and progression of BE following PPI therapy vs surgical fundoplication.

METHODS

We systematically searched PubMed, EMBASE, LILACS, Scopus, Web of Science, and the Cochrane Library through December 2023. Cohort studies comparing PPI monotherapy with fundoplication in histologically confirmed BE with ≥ 1-year endoscopic follow-up were included. A random-effects meta-analysis was performed. This review was registered in PROSPERO (CRD420251006124).

RESULTS

Of 4472 records identified, six cohort studies involving 1433 patients (912 medical, 521 surgical) were included, with a weighted mean follow-up of 66.1 months. Nissen fundoplication accounted for 94.9% of procedures. Surgery was associated with significantly higher BE regression than PPI therapy [odds ratio (OR), 0.24; 95% confidence interval (CI): 0.16-0.34]. Medical therapy was associated with a higher risk of progression to high-grade dysplasia or adenocarcinoma (OR = 2.58; 95%CI: 1.20-5.52). Overall progression showed a nonsignificant trend favoring surgery (OR = 3.28; 95%CI: 0.98-10.97).

CONCLUSION

Limited observational evidence suggests that fundoplication may improve histologic regression and reduce progression risk in BE; however, these findings should be interpreted cautiously.

Key Words: Gastroesophageal reflux disease; Esophagus; Barrett’s esophagus; Adenocarcinoma; Fundoplication; Antireflux surgery; Nissen; Proton pump inhibitor

Core Tip: Barrett’s esophagus is a premalignant condition for which the optimal strategy to prevent disease progression remains uncertain. This systematic review and meta-analysis directly compared surgical fundoplication with proton pump inhibitor therapy. Fundoplication was associated with higher rates of histologic regression and a reduced risk of progression to high-grade dysplasia or esophageal adenocarcinoma. By focusing exclusively on these two treatment strategies, this study provides clinically meaningful comparative evidence to inform therapeutic decision-making and long-term management in this high-risk population.

INTRODUCTION

Barrett’s esophagus (BE) is defined as intestinal metaplasia of the esophageal mucosa in which the normal squamous epithelium is replaced by a columnar epithelium resembling that of the gastric cardia[1-3]. It results from chronic exposure of the esophageal lining to gastric contents[4,5]. Approximately 6%-14% of individuals with gastroesophageal reflux disease (GERD) develop BE, and among these, 0.2%-0.5% progress to adenocarcinoma[6,7]. BE increases the risk of esophageal adenocarcinoma (EAC) by approximately 30- to 125-fold through the metaplasia-dysplasia-adenocarcinoma sequence[2-5,7,8]. Longer BE segments are also associated with a greater malignant potential[1,6,9].

Adenocarcinoma is currently the most common type of esophageal cancer in the United States[10], and its incidence continues to rise, likely reflecting the growing prevalence of obesity and GERD[2,6]. It is characterized by high mortality and poor 5-year survival rates (15%-20%)[7,11], ranking second only to pancreatic cancer in cancer-related lethality. Early detection enables surgical treatment and may improve survival to as high as 90%[6].

The primary objective of BE management is control of reflux, the principal modifiable factor in the metaplasia-adenocarcinoma sequence[3-5,12]. Effective therapy should promote mucosal healing and regression, and prevent progression to dysplasia or carcinoma[1,3,12,13]. Proton pump inhibitors (PPIs) are the first-line medical therapy because they provide superior acid suppression, symptom relief, and mucosal healing compared with H₂ receptor antagonists[14-16]. However, although PPIs suppress gastric acid production, they do not prevent reflux itself.

Both medical and surgical approaches are effective for reflux management. GERD was historically treated with H₂ receptor blockers, but PPIs have transformed therapy by achieving superior acid suppression, symptom relief, and mucosal healing in up to 90% of cases[14-16]. PPIs are recommended as first-line therapy for GERD and BE and are associated with an approximately 71% reduction in the risk of progression to high-grade dysplasia (HGD) or EAC, despite their inability to prevent reflux[15,16]. In contrast, surgical fundoplication restores the gastroesophageal barrier, corrects anatomical defects such as hiatal hernia, and suppresses both acid and duodenal reflux, thereby preventing persistent mucosal injury and potentially halting disease progression[1,3-5,12,17-20].

This systematic review and meta-analysis evaluates, in patients with BE, the effects of surgical fundoplication compared with PPI therapy on histopathologic regression and progression to HGD or adenocarcinoma, incorporating evidence from cohort studies and comparative trials. Clarifying the impact of each treatment strategy on disease progression may support more individualized therapeutic decision-making.

MATERIALS AND METHODS

This systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines[21]. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the identification number CRD420251006124. Because this study was based exclusively on previously published data, institutional ethical approval and informed consent were not required.

Search strategy

A comprehensive literature search was conducted in collaboration with a reference librarian and applied to PubMed, EMBASE, LILACS, Scopus, Web of Science, and the Cochrane Library. Studies published through December 2023 were considered, without language restrictions. The search strategy combined controlled vocabulary with free-text keywords and MeSH terms, including GERD, esophagus, BE, adenocarcinoma, fundoplication, antireflux surgery, Nissen, and PPI.

Two investigators (Isbert BBM and Dias LO) independently screened titles and abstracts for eligibility. Full-text articles were retrieved for studies that met the inclusion criteria or were deemed potentially relevant. Discrepancies were resolved by a third reviewer (Campos VJ). Reference lists of included articles were manually screened to identify additional eligible publications.

Inclusion and exclusion criteria

Studies were eligible if they included two treatment arms (a medical group and a surgical group), provided detailed descriptions of the interventions, and reported a minimum follow-up period of 12 months. Only studies in which the medical arm exclusively received PPI monotherapy were included. Studies combining PPIs with other medications were considered only when subgroup analyses were restricted to PPI monotherapy.

Histopathologic confirmation of BE prior to intervention and at least one follow-up endoscopy was mandatory. Eligible study designs included clinical trials, prospective or retrospective cohort studies, and case-control studies involving adults aged ≥ 18 years. Systematic reviews, meta-analyses, case reports, letters to the editor, conference abstracts, animal studies, and studies without comparison groups were excluded. Studies involving additional interventions, such as radiofrequency ablation or endoscopic resection, in either treatment arm were also excluded.

Quality assessment

Two researchers independently evaluated the methodological quality (risk of bias) of each selected study using the Newcastle-Ottawa Scale[22]. Table 1 presents the quality assessment results. Study heterogeneity was evaluated using Cochran’s Q test and the I² statistic.

Table 1 Quality assessment of the included studies.

Ref.	Country	Type of study	Cases (patients)	Selection (1-4)	Comparability (5)	Outcomes (6-8)	Total score	Assessment
Gurski et al[24]	United States	Retrospective	91; 77 ST (Nissen 61, Collis 14, Toupet 2); 14 MT	4	1	2	7	High
Rossi et al[26]	Italy	Prospective	35; 16 ST (Nissen); 19 MT	4	1	2	7	High
Zaninotto et al[18]	Italy	Prospective	89; 45 ST (43 Nissen, 1 Collis, 1 Toupet); 44 MT	4	1	2	7	High
Tolone et al[27]	Italy	Prospective	62; 37 ST (Nissen); 25 MT	4	1	2	7	High
Markar et al[25]	England	Retrospective	786; 166 ST; 620 MT	4	2	3	9	High
Szachnowicz et al[5]	Brazil	Prospective	398; 190 ST (Nissen); 207 MT	4	2	2	8	High

Numbers indicate the Newcastle-Ottawa Scale items fulfilled by each study: 1-4 correspond to the selection domain, 5 to the comparability domain, and 6-8 to the outcome domain. Higher total scores indicate better methodological quality. MT: Medical therapy; ST: Surgical treatment.

Data extraction

Data were independently extracted by two authors (Isbert BBM and Dias LO) using a standardized form and recorded in Microsoft Excel (Microsoft Corporation, Redmond, WA, United States). Extracted variables included: (1) Study characteristics: First author, publication year, country, study title, study design, total number of participants and intervention groups, proportion of patients without dysplasia and with low-grade dysplasia (LGD), type of surgery, type of PPI, diagnostic assessments before and after intervention, and follow-up duration; (2) Patient characteristics: Age, sex, body weight/body mass index (BMI), smoking status, and comorbidities; and (3) Outcomes: Endoscopic and histopathologic findings before and after treatment. A detailed summary of the extracted study and patient characteristics is provided in Table 2.

Table 2 Data from included studies, n (%).

Ref.	Study design	EGD protocol	Patients (n)	PPI	Surgery	PPI and BD	Surg and BD	F/U (months)	EGD at F/U	PPI	Surgery	REG PPI	REG surgery (n)	PROG (overall) PPI	PROG (overall) surgery	PROG HGD/EAC PPI	PROG HGD/EAC surgery
Gurski et al[24]	Retrospective cohort	Seattle	91	-	Nissen (61), Toupet (2), Collis Belsey (14)	14 (13 ND/1 LGD)	77 (52 ND/25 LGD)	50.3	At least two, spaced 6 months apart	14	77	1	28	1	8	1	3
Markar et al[25]	Retrospective cohort	-	786	Esomeprazole/omeprazole/pantoprazole 40 mg or lansoprazole 30 mg daily, ≥ 1 year	-	6201	1661	69.6	-	620	166	N/A	N/A	18	3	18	3
Rossi et al[26]	Prospective cohort	Seattle	35	Omeprazole 20 mg, twice daily	Nissen	19 LGD	16 LGD	18	At 6 months and 18 months	19	16	12	15	N/A	N/A	N/A	N/A
Szachnowicz et al[5]	Prospective cohort	Seattle	370	Omeprazole 20-80 mg daily	Nissen	1902	1802	80	Every 24 months	190	180	64	122	80	24	14	4
Tolone et al[27]	Prospective cohort	Seattle	62	Esomeprazole 40 mg, twice daily	Nissen	25 (12 ND/13 LGD)	37 (17 ND/20 LGD)	34	First and last EGD	25	37	15	34	2	0	2	0
Zaninotto et al[18]	Prospective cohort	Seattle	89	Esomeprazole/pantoprazole 40 mg or lansoprazole 30 mg or rabeprazole/omeprazole 20 mg	Nissen (43), Toupet (1), Collis Nissen (1)	44 ND	45 ND	34	First and last EGD	44	25	4	8	N/A	N/A	N/A	N/A
Total								66.1		912	521	96 (32.8)	207 (58.3)	101 (11.8)	35 (7.6)	35 (4.12)	10 (2.17)

¹Did not detail the presence or absence of dysplasia in the initial evaluation.

²Patients with low-grade dysplasia not included in the initial evaluation.

EGD: Esophagogastroduodenoscopy; PPI: Proton pump inhibitor; BD: Baseline dysplasia; ND: Non-dysplastic; LGD: Low-grade dysplasia; HGD: High-grade dysplasia; EAC: Esophageal adenocarcinoma; F/U: Follow-up; REG: Regression; PROG: Progression; N/A: Not applicable.

Outcomes

Primary outcomes included regression and progression of BE. Given the heterogeneity in outcome definitions across studies, endpoints were harmonized by grouping similar definitions into predefined categories based on the closest correspondence among study-specific criteria: (1) Regression: Transition from LGD to intestinal metaplasia or native esophageal squamous epithelium, or from intestinal metaplasia to native esophageal squamous epithelium; (2) Overall progression: Transition from intestinal metaplasia to low- or HGD, adenocarcinoma, or increased segment length of intestinal metaplasia; and (3) Progression to advanced disease: Development of HGD or adenocarcinoma.

This approach was intended to improve comparability across studies; however, potential differences in histologic thresholds, surveillance intervals, and classification criteria were taken into account when interpreting the results.

Statistical analysis

Statistical analyses were performed using R version 4.4.3 (R Foundation for Statistical Computing, Vienna, Austria)[23]. Meta-analyses were conducted using the meta package, and publication bias was assessed using Metafor. The significance level was set at α = 0.05. Effect measures are expressed as odds ratios (OR) with 95% confidence intervals (CI) comparing surgical treatment with medical treatment using PPIs. Meta-analyses were conducted using a random-effects model to account for expected between-study heterogeneity, regardless of the heterogeneity level, owing to the clinical and methodological diversity among the studies.

Heterogeneity was assessed using Cochran’s Q test, the I² statistic (25%, 50%, and 75% representing low, moderate, and high heterogeneity, respectively), and τ² (between-study variance). Publication bias was evaluated using funnel plots and Egger’s regression test, with P < 0.05 considered suggestive of bias. The statistical methods used in this study were reviewed by a biomedical statistician before submission.

RESULTS

Literature search results

The search strategy identified 4472 potentially relevant studies. After removing duplicates, 2844 records underwent title and abstract screening, and 13 were selected for full-text review. Three studies were excluded because they combined H₂ receptor antagonists with PPIs without subgroup differentiation, and four were excluded because they did not report endoscopic or histopathologic outcomes related to regression or progression. Ultimately, six studies met the inclusion criteria and were included in the analysis. The selection process is summarized in the PRISMA flow diagram (Figure 1)[21].

Figure 1 PRISMA flow diagram.

Study characteristics

The six included studies comprised four prospective cohort studies and two retrospective cohort studies[5,18,24-27], totaling 1433 patients: 912 (63.3%) received PPI therapy and 521 (36.4%) underwent surgery. Patients in the surgical group were younger (mean age, 53.2 years) than those in the clinical group (mean age, 57 years), and the overall weighted mean follow-up was 66.1 months. Most participants were male. Only two studies reported data on BMI and/or obesity status, and only one reported smoking status and race. None of the studies included data on associated comorbidities such as hypertension or diabetes.

Among 355 patients with available surgical details, 94.9% (n = 337) underwent Nissen fundoplication, and 5.1% (n = 18) underwent partial or other fundoplication procedures (Collis-Nissen or Collis-Belsey). Clinical therapy involves omeprazole, esomeprazole, or other PPIs administered daily at ranging from 20 mg to 80 mg. All studies performed pre- and post-treatment upper gastrointestinal endoscopies, and five followed biopsy protocols based on the Seattle criteria. Functional esophageal testing was reported in four studies, most frequently in the surgical group.

Patients presenting with HGD or adenocarcinoma on initial or pre-intervention endoscopy were excluded. The presence of LGD on initial EGD was reported in three studies[24,26,27], with a higher propensity for LGD in the medical group (56.8%, n = 33) than in the surgical group (46.9%, n = 61). One study excluded patients with dysplasia at initial EGD.

Histopathologic outcomes

Five studies[5,18,24,26,27] evaluated the histologic regression of Barrett's epithelium and consistently reported higher regression rates after surgery than after clinical therapy (58.3% vs 32.8%). Four studies[5,18,24,27] reported regression of intestinal metaplasia to the native squamous esophageal epithelium, observed in 37% of patients in the surgical group (n = 109) and 20% in the clinical group (n = 53). Two of these studies[24,27] also reported LGD regression to the native squamous epithelium without metaplasia, with rates of 21.4% and 73% in clinical and surgical groups, respectively. One study[26] specifically analyzed the regression of LGD to BE with intestinal metaplasia in 63.2% of patients treated with PPIs and 93.8% of those undergoing fundoplication.

Progression to HGD or EAC was analyzed in four studies[5,24,25,27] and was more frequent in the clinical group (4.1% vs 2.2%). The overall progression rate (histologic progression) was higher in patients treated with PPIs (11.8% vs 7.6%).

Meta-analyses of regression and progression

Given the limited number of included studies and relatively small sample sizes, outcomes were grouped into three main categories for comparative analysis between PPI treatment and fundoplication: Histologic regression, overall disease progression, and specific progression to HGD or EAC. This strategy aimed to improve comparability across studies by harmonizing heterogeneous outcome definitions; however, potential differences in study-specific criteria were considered when interpreting the results.

Regression

Five studies (n = 647; 292 PPI-treated and 355 surgical patients) contributed to the regression meta-analysis. Patients receiving medical therapy had a 76% lower likelihood of histologic regression compared with those in the surgical group (OR = 0.24; 95%CI: 0.16-0.24; < 0.001). Heterogeneity was absent (I² = 0%) and no publication bias was detected (Egger’s test, P = 0.5507) (Figure 2).

Figure 2 Analysis of Barrett’s Esophagus regression. A: Forest plot of effect estimates; B: Funnel plot evaluating publication bias. OR: Odds ratio; CI: Confidence interval.

Overall progression

Three studies (n = 523; 229 clinical and 294 surgical patients) evaluated overall histologic progression. The pooled (OR = 3.28; 95%CI: 0.98-10.97), indicating that medically treated patients had approximately threefold higher odds of progression compared to those undergoing fundoplication; however, this difference was not statistically significant. Heterogeneity was moderate (I² = 37%), and no publication bias was detected (Egger’s test, P = 0.8668) (Figure 3).

Figure 3 Forest plot of Barrett’s Esophagus progression. OR: Odds ratio; CI: Confidence interval.

Progression to HGD/EAC

Four studies (n = 1309; 849 medical and 460 surgical patients) evaluated progression to HGD or EAC. The pooled (OR = 2.58; 95%CI: 1.20-5.52; P = 0.015), indicating that patients treated with PPIs had approximately 2.6-fold higher odds of progression to adenocarcinoma compared to those undergoing fundoplication. Heterogeneity was absent (I² = 0%), and no publication bias was observed (Egger’s test, P = 0.7205) (Figure 4).

Figure 4 Progression from Barrett’s esophagus to high-grade dysplasia/adenocarcinoma. A: Forest plot of effect estimates; B: Funnel plot evaluating publication bias. OR: Odds ratio; CI: Confidence interval.

DISCUSSION

To our knowledge, few studies have specifically compared PPIs with fundoplication in patients with BE while excluding other therapeutic modalities, and this systematic review and meta-analysis aims to address this gap. This approach enables a more precise assessment of histologic outcomes, as PPIs have demonstrated superiority over H₂ receptor antagonists in symptom control and mucosal protection. In 2014, Singh et al[16] reported a 71% reduction in the risk of progression to HGD or EAC with PPI use, whereas H₂ blockers showed no significant effect. This comparison is timely and clinically relevant, given the widespread use of PPIs as first-line therapy.

Our findings suggest that fundoplication may be associated with higher rates of histologic regression (metaplasia or LGD) and a lower risk of progression to HGD or EAC compared with PPI-based medical therapy. These results remained consistent in sensitivity analyses and did not show substantial heterogeneity across key outcomes. Although the overall analysis of disease progression did not reach statistical significance, a clear trend toward a lower risk was observed in the surgical group, suggesting potentially improved disease control with fundoplication. However, the magnitude of the observed effect sizes (OR = 0.24 for regression and OR = 2.58 for progression to HGD/EAC) should be interpreted with caution, as relatively strong associations in observational studies may be inflated by underlying biases, despite the generally high methodological quality of the included studies. Residual confounding, particularly confounding by indication, may have influenced these associations, as patients selected for surgical treatment were often younger and potentially healthier and may have had more favorable baseline characteristics. Therefore, these findings do not allow definitive conclusions regarding causal treatment effects.

Taken together, however, these results are consistent with those of previous studies. Wilson et al[4] reported that fundoplication increased the likelihood of histologic regression by 4.38-fold and significantly reduced the risk of progression (OR = 0.34; 95%CI: 0.12-0.96). Although that study included heterogeneous clinical and surgical approaches, it corroborates the advantage of surgical intervention in modifying the natural history of BE.

The pathophysiologic basis of this benefit reflects differences in the type and intensity of reflux controlled by each treatment approach. PPIs reduce gastric acidity but do not prevent reflux, particularly bile or mixed reflux (acid + bile), leading to persistent mucosal injury[28]. In contrast, fundoplication mechanically restores competence of the gastroesophageal junction, corrects anatomical abnormalities, and significantly reduces both acid and bile reflux, as demonstrated by postoperative pH-metry and impedance studies[1,3-5,12].

The relevance of controlling mixed reflux is further supported by Oh et al[20], who demonstrated a strong association between this pattern of reflux and the development of erosive esophagitis, BE, and esophageal shortening in a cohort of 402 patients with GERD symptoms. These findings highlight refluxate composition as a key determinant of histologic progression[20,27,29]. Similarly, in one of the few randomized trials comparing PPIs and surgery involving 101 patients, adequate reflux control was achieved predominantly in the surgical group, which was also the only group without progression to EAC during follow-up[12].

Fundoplication provides more durable reflux control, greater symptom relief, and improved histologic stabilization compared with PPI therapy alone[4,5]. It represents a consistent, long-term, effective, safe, and durable approach that may reduce the need for prolonged medication use and be cost-effective over time[1,3,4,12]. However, the weighted mean follow-up duration across included studies was approximately 66.1 months, which may be insufficient to capture late recurrence of Barrett’s epithelium or delayed malignant transformation, given its slow natural history. While current evidence suggests a potential protective association, longer-term studies are needed to assess the durability of histologic benefits and their impact on EAC incidence. Accordingly, surgery could be considered a therapeutic option, particularly for younger patients and those with favorable surgical risk profiles. As with any invasive treatment, risks of failure or adverse effects exist; however, when appropriately indicated and technically well performed, fundoplication can provide more sustained reflux control than medical therapy alone[12].

A systematic review by Maret-Ouda et al[11] further demonstrated a reduced risk of adenocarcinoma following antireflux surgery in patients with BE. Notably, this effect was not observed among patients with GERD without BE, possibly reflecting the selection of more advanced cases for surgery, in which irreversible genetic alterations may already be present. These findings further suggest that surgical intervention could be more effective before irreversible molecular changes occur, supporting consideration of earlier surgical referral in patients with confirmed BE[30].

Although some studies found no significant differences between treatment strategies, this likely reflects selection bias as surgical patients often present with different baseline disease characteristics[2,11,31]. Cancer detected in the early postoperative period likely reflects preexisting molecular alterations rather than treatment failure. Early surgical intervention appears to offer meaningful protection against neoplastic progression, particularly in patients without dysplasia[1]. Csendes et al[32] highlighted that while surgery reduces the risk of dysplasia and carcinoma, it does not eliminate it, underscoring the continued need for long-term endoscopic surveillance even after successful surgical treatment.

Reported rates of histologic regression vary widely (14%-55%) depending on the disease stage, follow-up duration, and technique[3]. Although complete regression is not always achievable, effective reflux control remains essential to minimize the risk of progression and ensure long-term safety.

Strength and limitations

Several limitations should be considered. First, the number of eligible studies was relatively small, with only six studies included overall and some outcomes-such as overall progression-based on as few as three studies. The resulting limited sample size may have reduced statistical power for certain outcomes, particularly overall progression, thereby limiting the robustness of the findings. In addition, the small number of studies constrains the reliability of publication bias assessments, as statistical tests such as Egger’s test are underpowered in this context and should be interpreted with caution.

Second, all included studies were observational cohort studies, with no randomized controlled trials available. Treatment allocation was based on clinical judgment, symptom severity, anatomical findings and patient preference, precluding standardized patient selection across studies. Consequently, the analysis is subject to confounding by indication and selection bias. Patients selected for surgery were generally younger and potentially healthier, which may have influenced histologic outcomes. Although the Newcastle-Ottawa Scale indicated generally high methodological quality, residual confounding cannot be excluded.

Third, although Nissen fundoplication accounted for most of the surgical procedures, other techniques, such as partial fundoplication, were also reported. Due to the small number of patients undergoing non-Nissen procedures and the lack of technique-specific outcome reporting in most studies, stratified analyses by surgical approach were not feasible. Therefore, potential differences in histologic outcomes between complete and partial fundoplication could not be formally assessed.

Additionally, histologic definitions of regression and progression were not fully uniform across studies. Although outcomes were grouped into predefined categories to improve comparability, this approach may have introduced misclassification bias, particularly given differences in biopsy protocols, baseline dysplasia distribution, histopathologic interpretation and outcome classification across studies. Important risk factors-including BMI, smoking, alcohol use, Barrett’s segment length, detailed endoscopic characteristics, and functional testing-were also inconsistently reported. These sources of variability may not be fully captured by statistical measures of heterogeneity, even though low heterogeneity was observed for the primary outcomes. Accordingly, the findings should be interpreted as associations, rather than as definitive evidence of causality.

CONCLUSION

Our findings suggest that fundoplication is associated with higher rates of histologic regression and a lower risk of progression to HGD or adenocarcinoma compared with PPI therapy in patients with BE. However, these results are derived from observational cohort studies with non-randomized treatment allocation and should therefore be interpreted as associative rather than causal. Moreover, the available data reflect a mean follow-up of approximately 4 years, which may be insufficient to fully determine the long-term impact of surgical vs medical therapy on malignant transformation.

Within these limitations, fundoplication may represent a valuable therapeutic option for carefully selected patients, particularly younger individuals with favorable surgical risk profiles or inadequate reflux control with medical therapy. Future well-designed randomized controlled trials with standardized histologic definitions, technique-specific analyses, and long-term follow-up are warranted to more precisely define the role of antireflux surgery in modifying the natural history of BE and preventing EAC.

ACKNOWLEDGEMENTS

The authors recognize and gratefully acknowledge the financial support for the article processing charge provided by Hospital de Clínicas de Porto Alegre (HCPA) (ROR: https://ror.org/010we4y38), through the program Financiamento e Incentivo à Pesquisa (Fipe/HCPA).