Concordant and Discordant Interrelationships of the GERD Triad of Symptoms, Endoscopy Findings, and Histopathological Changes Over Time after One Anastomosis Gastric Bypass

Obesity remains a global health challenge, and metabolic and bariatric surgery (MBS) is highly effective in managing obesity and related medical conditions [1]. Recently, One-Anastomosis Gastric Bypass (OAGB) has gained traction, primarily due to its favorable effectiveness and safety profiles [2‐4]. OAGB has been endorsed by the American Society for Metabolic and Bariatric Surgery (ASMBS) and The International Federation for the Surgery and Other Therapies for Obesity (IFSO), and has shown a surge in popularity according to the IFSO global registries [5‐7].

There is an ongoing discourse surrounding post-OAGB gastroesophageal reflux disease (GERD). Aspects such as the correlation between reflux symptoms and corresponding macro- or microscopic abnormalities remain contentious among OAGB patients. Evidence suggests that symptoms alone may not reliably diagnose GERD after OAGB; therefore, routine upper endoscopy (UE) and/or biopsy have been advocated for definitive diagnosis [8, 9].

A prospective mid-term study of OAGB outcomes revealed that even asymptomatic patients exhibited macroscopic and microscopic inflammatory changes in the gastrojejunostomy, gastric pouch, and distal esophagus during UE [10]. Similarly, other studies have reported discordant findings regarding symptoms and histological changes in OAGB patients [11‐13]. Despite these observations, no research has comprehensively evaluated the triad of reflux symptoms, UE findings, and histopathological changes longitudinally after OAGB.

The literature highlights several knowledge gaps. Many studies have relied solely on symptoms, observed clinically or through questionnaires, to identify reflux [14‐20]. Others utilized a combination of clinical symptoms and UE to detect reflux [9, 21‐26]. A common limitation has been the failure to longitudinally assess the interplay between symptomatology, UE findings, and histopathological changes after OAGB, which could yield crucial insights into their evolving relationships over time.Therefore, the current study aimed to address the temporal evolution of this GERD-related triad.

The prevalence of OAGB has surged over the last decade, positioning it as the third most common MBS [38]. Despite the concerns about the high incidence of long-term GERD following bypass procedures, the long gastric pouch and wide anastomosis characteristic of OAGB has been proposed to create a low-pressure environment that minimizes the retrograde flow of gastric contents into the esophagus [39, 40]. Nonetheless, post-OAGB reflux and related abnormalities remain contentious within the surgical community.

The temporal changes and interrelations between post-OAGB reflux symptoms, macroscopic, and microscopic findings have not been systematically evaluated across short- and mid-term intervals. Understanding the dynamics of reflux symptomatology and related macroscopic and microscopic changes over time is critical for building an evidence base that addresses the ongoing debates surrounding post-OAGB reflux and associated complications. This study is the first to systematically address these complex issues, primarily aimed to contribute to bridging that knowledge gap.

We noted a nearly two-fold increase in the proportion of symptomatic patients from year 1 to year 3, with significantly less increase in UE and histopathology abnormalities. This raises the concern of 'clinically silent' patients who, despite being asymptomatic, demonstrated UE and histopathology abnormalities, underscoring the importance of continuous monitoring and in-depth comprehension of the relationships within the GERD triad.

Notably, while symptomatic patients nearly doubled from 25.7% at year 1 to 55.6% at year 3, existing literature from Australia indicated that, in comparison to sleeve gastrectomy and Roux-en-Y gastric bypass, OAGB was the only procedure showing a statistically significant reduction in GerdQ scores six months post-operatively [30]. However, it remains unclear if their cohort included patients with preoperative GERD or symptoms, unlike our series, which exclusively consisted of asymptomatic, GERD-free patients at baseline.

The Lyon Consensus 2.0 reinforces that GERD symptoms alone are insufficient for diagnosis [41], emphasizing the need for objective parameters such as acid exposure time and baseline mucosal impedance. The increasing discordance between symptoms, endoscopic, and histopathological findings in our study aligns with this concept, suggesting that a subset of patients may exhibit pathological reflux despite the absence of overt symptoms.

Pertaining to the relationships between the GERD triad components, we classified the cases into concordant or discordant, which yielded pivotal insights. Discordant cases were consistently asymptomatic at year 1 and year 3, hindering their clinical detection despite abnormalities in one or more diagnostic tests. This discordance highlights the intricate dynamics of the symptoms-UE-histopathology relationship and emphasizes the limitations inherent in relying exclusively on symptomatic evaluations to identify and manage post-OAGB reflux. Previous research has corroborated the weak correlation between symptoms and objective findings, where 17%−28% of endoscopy-confirmed post-OAGB ulcers were asymptomatic [42‐44]. Furthermore, an endoscopic and histopathological evaluation conducted two years post-OAGB yielded a 10.3% incidence of marginal ulcers identified via UE, despite that only half the patients presented with symptoms [8]. Pertaining specifically to gastric and esophageal reflux, research integrating endoscopic, biochemical, and histological analyses of 28 patients undergoing OAGB or RYGB found a poor correlation between patient-reported symptoms and objective findings [45]. In addition, some bariatric patients might have preoperative asymptomatic/silent GERD which adds further challenge to the assessment of post-OAGB GERD and raises the attention to the importance of pre-op UE [46‐48].

These findings underscore a pressing need for bariatric teams to proactively inquire about reflux after OAGB, as symptoms should not solely direct the assessments for reflux. Our findings also suggest that traditional UE assessment alone may be inadequate in identifying true reflux pathology, reinforcing the need for histopathological analysis and the utilization of more histological markers in line with the Lyon Consensus 2.0 in post-OAGB GERD surveillance [41].

No published studies conducted a simultaneous and thorough analysis of the symptoms-UE-histopathology triad across different time points following OAGB using a sizable cohort. In Brazil, a limited cohort of 39 patients presented some 'relationships' concerning UE findings before surgery and two years after surgery, focusing exclusively on UE findings without comparable histopathological or symptom data [8]. Similarly, in Finland, an investigation into post-OAGB bile reflux among 40 patients assessed histological findings preoperatively and at only one post-operative milestone (six months), again lacking parallel evaluations of UE/macroscopic findings or symptoms throughout these time points [49]. While such published assessments provide valuable insights, they carry inherent limitations as the examination of a single postoperative point offers only a single snapshot of patient status, obscuring subsequent changes and leaving a potential 'blind spot'. In addition, the practice of matching only two components of the triad risks creating knowledge gaps. Such isolated approaches to analyzing the components of the symptoms-UE-histopathology triad deliver a limited perspective on the continuous processes and pathways underlying this complex interplay and fail to capture the interrelated nature of these components as they evolve in concert post-operatively. A more integrated analysis is essential for a comprehensive understanding of these dynamics to decipher and contextualize these relationships effectively.

In addressing the third objective related to patient subsets, it is evident that concordant patients, whether asymptomatic or symptomatic were generally less challenging to identify. Asymptomatic concordant patients present no immediate risk, as indicated by their negative UE and histopathology results; conversely, concordant symptomatic patients, present overt clinical signs that alert practitioners to potential underlying issues, facilitating timely intervention.

In contrast, discordant patients appear to be more potentially ‘deceptive’, particularly the asymptomatic discordant patients, as their symptoms do not align with their UE/histopathology findings, posing a high risk of being overlooked by practitioners not maintaining a high index of suspicion.

Regarding the fourth objective of patient characteristics, it remains impractical to accurately predict which post-OAGB patients are more likely to experience discordance. Current demographic and anthropometric metrics, including weight loss, BMI, TWL%, and EWL%, along with associated medical conditions and various laboratory biomarkers did not indicate the likelihood of discordance at either year 1 or year 3 after surgery. Our findings resonate with existing literature highlighting that the underlying reasons for variability in symptom severity and complications related to reflux among individuals are inadequately understood [50‐52]. Furthermore, they corroborate the challenges involved in identifying the ‘at-risk’ patients for post-OAGB reflux, underscoring the necessity for comprehensive detection strategies that expand beyond traditional clinical markers. To delineate the traits of post-OAGB patients predisposed to discordance, sustained longitudinal follow-up is essential. This aligns with the consensus that the long-term GERD after MBS poses significant diagnostic complexities [39].

On the question of the critical time points warranting heightened vigilance for post-OAGB reflux-related abnormalities, we noted that the year 1 follow-up mark demonstrated a three-fold increased likelihood of discordance within the symptoms-UE-histopathology triad when compared to the year 3 follow-up. Thus, the year 1 milestone represents a crucial follow-up time mark and a pivotal opportunity for clinicians to closely monitor post-OAGB patients to detect reflux and related abnormalities and actively seek out discordant patients. Notably, elevated hemoglobin levels correlated with an increased 1.38 odds of discordance. However, there is no available clinical evidence that support or oppose this finding.

Previous studies have documented the weak correlation between clinical symptoms and objective findings in post-OAGB reflux cases. For example, bile reflux often precipitates histological gastritis but does not consistently equate to adverse symptomatic presentations [53]. Similarly, in other bariatric procedures, asymptomatic BE was found in about 21% of post-sleeve gastrectomy patients [54]. While this recognition of poor correlation is noteworthy, it lacks actionable tools for practitioners. More nuanced prompts and evaluative cues are needed. The current study's exploration of the concept of discordance and concordance within the GERD triad is a novel notion in advancing our understanding of the patient experience post-OAGB by elucidating the complex interrelationships among these factors. With this enhanced awareness, bariatric teams may better monitor patients to prevent those at risk from being overlooked.

This study has limitations. It was conducted at a single center. In addition, subclassification based purely on symptoms may have led to underdiagnosis of clinically significant reflux disease, given the high discordance rate observed in our study. Implementing Lyon Consensus 2.0 criteria could help refine post-OAGB patient classification, ensuring that those with histological or endoscopic evidence of reflux-related injury receive appropriate long-term surveillance and intervention [41]. It would have been useful to use objective tools such as scintigraphy, pH-impedance, baseline mucosal impedance and manometry, which could enhance the assessment of reflux, particularly in asymptomatic or discordant patients, and differentiate between acid and biliary reflux. The Lyon Consensus 2.0 emphasizes that GERD classification should integrate objective parameters such as pH-impedance monitoring and histopathological markers [41]. Another limitation was that the post-operative use of acid suppression at the time of data collection was not held before UE. This could be responsible for the high rate of discordance between symptoms and endoscopic or histopathological findings. Whilst some authors advocate stopping PPI and H2 blockers two weeks before completing the questionnaire, and also before conducting UE in patients who were using these medications [19] to prevent masking of findings, however, two weeks might appear not to be sufficient for pathology to revert/develop. An extended follow-up period with further endoscopic routine surveillance would have been useful in providing more insights into the changes in the GERD triad over time. Given the dramatic change in the incidence of asymptomatic and discordant patients between year 1 and year 3 in this study, assessments beyond year 3 might reveal further changes. The ASMBS recommends that clinicians should consider a screening UE at 3 or more years even with absence of symptoms after certain bariatric procedures, and further EGD screening every 5 years thereafter [29].

Despite these limitations, the current study has remarkable strengths, particularly as it represents a pioneering effort to investigate the longitudinal outcomes of patients after OAGB in terms of subjective reflux symptoms and objective diagnostic abnormalities. The study analyzed the dynamic interplay within the GERD triad, across a substantial cohort at both short-term and mid-term intervals after OAGB. The characterization of patients through the lens of the GERD triad introduced a novel conceptual framework distinguishing between concordant and discordant cases, laying the groundwork for deeper insights into the complexities of post-OAGB reflux phenomena. Furthermore, the study analysed whether the distinguishing features of concordant versus discordant patients varied across a comprehensive array of variables, to identify at-risk patients early. The analysis also assessed potential correlations between specific patient characteristics and time points, pertaining to the likelihood of experiencing discordance.

While our findings provide critical insights, several aspects warrant further exploration. Future research should integrate Lyon Consensus 2.0 diagnostic thresholds to distinguish between physiological and pathological post-OAGB reflux [41], refining the postoperative surveillance strategies, and improving predictive models for long-term GERD-related complications.

In addition, longer-term studies are needed to assess whether histopathological changes progress, stabilize, or regress beyond three years, identifying potential risk factors for persistent or worsening reflux disease. Moreover, the impact of surgical variations, including limb length modifications should also be evaluated to determine their role in reflux severity and progression [55].

Given the high prevalence of discordant cases, future efforts should focus on developing personalized risk stratification models that integrate symptom profiles, endoscopic changes, histopathological changes, and objective reflux diagnostic tools. This approach would ultimately guide individualized precision treatment plans for patients with persistent reflux despite normal symptomatology, ensuring optimized long-term management.

The evolution of the symptoms-UE-histopathology triad post-OAGB demonstrates significant variability. The year 1 data revealed a significant one-third lower probability of symptom development compared to the year 3 findings; however, there was a threefold increase in the likelihood of discordance within the symptoms-UE-histopathology triad. This underscores the necessity for more vigilant monitoring of post-OAGB patients and extending the follow-up of such patients beyond three years.