ETM Experimental and Therapeutic Medicine 1792-0981 1792-1015 D.A. Spandidos ETM-26-1-12050 10.3892/etm.2023.12050 Articles Predicting reflux symptom recurrence: The impact of gastroesophageal junction indicators and body mass index among outpatients WangQing 1 * LuJunhui 1 * SuiYue 1 FanJing 1 RenJinnan 1 WangZhenzhen 2 ChenXing 3 Department of Gastroenterology, Shanxi Medical University, Taiyuan, Shanxi 030000, P.R. China Department of Gastroenterology, Shanxi Datong University Affiliated Cancer Hospital, Datong, Shanxi 037000, P.R. China Department of Gastroenterology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030000, P.R. China Correspondence to: Dr Xing Chen, Department of Gastroenterology, The First Hospital of Shanxi Medical University, 85 South Xinjian Road, Yingze, Taiyuan, Shanxi 030000, P.R. China chen0419xing@163.com chenkwspine@163.com

*Contributed equally

 07 2023 31 05 2023 26 1 351 20 12 2022 11 05 2023 Copyright: © Wang et al. 2020 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

The present study aimed to evaluate the efficacy of the prediction model in predicting reflux symptom recurrence among outpatients with reflux esophagitis (RE). A total of 261 outpatients diagnosed with RE complicated by anatomical alterations at the gastroesophageal junction and reflux symptoms were included in the study. Through follow-up, patients were divided into a General group (149 cases) and a Recurrent group (112 cases). Receiver operating characteristic curves of the related factors and prediction model were analyzed to compare the efficacy of each element in predicting reflux recurrence. A prediction model was constructed for predicting reflux recurrence using the axial length of the hiatal hernia (HH), the diameter of the esophageal hiatus, Hill classification, and body mass index (BMI) as risk factors. The cutoff values of the aforementioned factors for predicting reflux recurrence were: an axial length of HH >2 cm, esophageal hiatus diameter ≥3 cm, Hill grade >III, and BMI >25.1 kg/m2. The multivariate prediction model constructed using the aforementioned four indicators together with chronic atrophic gastritis and Helicobacter pylori infection had the area under the curve of 0.801 (95% confidence interval: 0.748-0.854), and the cutoff value of 46.8 had a sensitivity and specificity of 71.4% and 75.8%, respectively. The predictive model in the present study can be used for the primary assessment of reflux recurrence in patients with RE.

 gastroesophageal reflux disease esophagogastric junction hiatal hernia recurrence Funding: The present study was partially supported (grant no. 201903D321140) by Key Research and Development (R&D) Projects of Shanxi (China). Introduction

Reflux esophagitis (RE) is classified as an upper gastrointestinal disease that is characterized by symptoms of regurgitation, heartburn and esophageal mucosal injury. Most of these symptoms are caused by regurgitation of gastric or duodenal contents into the esophagus. RE is a type of gastroesophageal reflux disease (GERD) with high incidence and recurrence rates. The occurrence of RE is attributed to the interaction of multiple factors, including the impaired anti-reflux function of the gastroesophageal junction (GEJ), low motility state of the stomach and esophagus, and decreased clearing ability of the extra-esophageal organs to regurgitation. Among these factors, damage to the anatomical structure of the GEJ is the most critical causative factor for the occurrence of RE (1). Gastroscopy is the preferred examination in the diagnosis and treatment of GERD. Abnormalities of the GEJ, including the severity of the esophageal mucosa injury, axial length of the hiatal hernia (HH), degree of relaxation of the cardia, and morphological changes in the gastroesophageal flap valve (GEFV), can be observed directly through gastroscopy. Reflux symptoms can recur or persist in patients with GERD and an abnormal anatomical morphology of the GEJ (2,3). A previous review showed that 17 to 45% of 21,736 patients still experienced reflux symptoms after treatment with proton-pump inhibitors (PPIs) (4).

The GERD clinical guidelines of numerous countries point out that the objective of GERD treatment should primarily consider cost-effectiveness (5,6). The initial evaluation methods of GERD include a PPI test, questionnaire and gastroscopy evaluation. When further diagnosis and treatment are required, including clarifying the degree and nature of regurgitation, endoscopic treatment and preoperative evaluation, objective examinations including multichannel intraluminal impedance-pH testing (MII-pH), high-resolution esophageal manometry (HRM) are needed.

Numerous studies have analyzed the risk factors for RE. However, only a few studies have examined the predictive factors for reflux recurrence by observing the structural abnormalities of the GEJ during endoscopy. In the present study, reflux recurrence and the efficacy of PPI treatment were evaluated through a Reflux Disease Questionnaire (RDQ) and collected data on gastroscopic findings and general information of patients with different degrees of reflux symptom recurrence. The prediction model and receiver operating characteristic (ROC) curves were constructed to evaluate the clinical predictive values of reflux recurrence.

 Materials and methods <sec> <title>Patients

An analysis was performed on patients who were treated in four hospitals from September 2020 to December 2021 for RE with structural abnormalities of the GEJ and reflux symptoms including regurgitation, heartburn, noncardiogenic chest pain, and food reflux. The present study protocol was approved (approval no. T20211223001) by the Ethics Committee of Linfen People's Hospital affiliated to Shanxi Medical University (Taiyuan, China). Inclusion criteria: Patients who were diagnosed using painless gastroscopy and responded to a 6-week treatment of esomeprazole were included in the study. Exclusion criteria were as follows: i) Patients diagnosed with other digestive system diseases, including achalasia of the cardia, esophageal cardia laceration, nodular gastritis, bile reflux gastritis, peptic ulcer, Zollinger-Ellison syndrome, refractory RE, secondary RE, gastroesophageal varices, gastroesophageal carcinoma, upper gastrointestinal surgery history, and digestive tract malformation; ii) those with non-digestive system diseases, such as depression and other psychiatric illnesses, severe dysfunction of important organs; iii) those with other conditions that required drug intake that affect the gastrointestinal function during treatment, including non-steroidal anti-inflammatory drugs, hormonal drugs, calcium antagonists, and other drugs. Patients who did not receive the standard treatment or had incomplete case information were also excluded from the study. The screening process is illustrated in Fig. 1. Among all the patients (n=261) participating in this study, there were 158 men and 103 women, ranging in age from 21 to 83 years old.

 Treatment and grouping criteria

The treatment administered was in accordance with the Chinese GERD guidelines (7). Esomeprazole (20 mg) was administered twice daily (i.e., 30 min before breakfast and before bedtime) for 6 weeks as the initial treatment, and the maintenance treatment was esomeprazole 20 mg administered once, if necessary. Patients were evaluated using the RDQ before the initial treatment and at the first and third months after the initial treatment to determine whether the initial treatment was effective or if the symptoms recurred (Table SI) (8). Effective treatment or no recurrence was defined as a decrease in RDQ score of ≥50% before the initial treatment; otherwise, the treatment was considered invalid or recurrent (9,10). Patients who responded to the initial treatment were screened and divided into general and recurrent groups according to the RDQ score and GERD guidelines. On the third month after the initial treatment, patients with severity and frequency scores of ≤2 points for any reflux symptoms were assigned to the general group while patients who met one of the following conditions were assigned to the recurrent group: i) the frequency score was >2 points regardless of the severity of reflux symptoms; ii) severity score was >2 points. The follow-up time for all patients is regular, so there is no difference in the follow-up time between the two groups of patients. During the follow-up, no patients in the General group needed maintenance treatment. By contrast, 67 patients in the recurrent group reported receiving maintenance therapy with Esomeprazole 20 mg once a day for 1 to 10 days after the initial treatment, while 19 patients remained on Esomeprazole.

 Data collection

The general information of the patients, including sex, age, body mass index (BMI), Helicobacter pylori (H. pylori) infection, smoking and drinking history, was collected during the follow-up. Gastroscopic findings include RE grade, GEFV grade, axial length of HH, esophageal hiatus diameter, chronic superficial gastritis and chronic atrophic gastritis (CAG).

RE grade was assigned based on the Los Angeles classification (11), GEVF was evaluated using the Hill classification, CAG was graded based on the Kimura-Takemoto classification (12) and H. pylori infection was diagnosed by the urea breath test. The distance from the diaphragmatic hiatus to the incisors subtracted by the distance from the dentate line to the incisors was defined as the axial length of the HH (13,14). During gastroscopy, images were captured after observing the morphology of GEFV for at least 30 sec and the diameter of the esophageal hiatus was assessed on these images. Using the endoscope shaft (~1 cm) as the reference, the algebraic multiple relationship between the esophageal hiatus diameter and endoscope shaft was measured (15). The diameters of the esophageal hiatus of all patients were evaluated and recorded by the same researcher. Since the diameter of the esophageal hiatus cannot be measured directly, a scoring system was used to represent the range of esophageal hiatus diameters for statistical analysis. Based on the measurement results, 1 cm ≤ diameter <2 cm was defined as 1 point, 2 cm ≤ diameter <3 cm was defined as 2 points, 3 cm ≤ diameter <4 cm was defined as 3 points, 4 cm ≤ diameter <5 cm was defined as 4 points and diameter ≥5 cm was defined as 5 points. The endoscopic images of each score are shown in Fig. 2. Two types of gastroscope (GIF-H290, Olympus Corporation; and EG760, FUJIFILM Wako Pure Chemical Corporation) were used in these assessments.

 Statistical analysis

Data were analyzed using SPSS V25.0 (IBM Corp.). All the quantitative data were normally distributed. Quantitative data were expressed as the mean ± standard error and independent samples t-test was used for comparison. Qualitative data were expressed as rate (%) and chi-square test was used for comparison. Correlations between the continuous variables (i.e., axial length of the HH) and ordinal categorical variables (i.e., RE grade and recurrence) were analyzed using the Kendall correlation coefficients. The factors with P<0.2 in the univariate analysis were included in the logistic regression analysis. The ROC curves and nomogram were built using R version 4.2.2 (www.r-project.org). P<0.05 was considered to indicate a statistically significant difference.

 Results

Sex, BMI, axial length of HH, esophageal hiatus diameter score, RE classification, Hill classification, smoking history, and drinking history between the two groups were significantly different. The results of univariate analysis are shown in Table I. Univariate analysis revealed that sex, smoking and alcohol consumption were closely associated with reflux symptom recurrence (P<0.001); however, these three factors were not independent risk factors for reflux recurrence after excluding the interaction among the factors through logistic regression analysis.

The factors with P<0.2 in the univariate analysis were included in the logistic regression analysis. Axial length of HH, esophageal hiatus diameter score, Hill classification, and BMI were independent risk factors for reflux recurrence. The results are shown in Table II. A total of 148 patients were classified as grade III, including 41 (27.7%) cases in the recurrent group and 107 (72.2%) cases in the general group; 113 patients were classified as grade IV, including 71 (62.8%) patients in the recurrent group and 42 (37.1%) cases in the general group. The average BMI of the general and recurrent groups were 24.4±2.3 and 25.6±2.2 kg/m2, respectively.

The axial length of the HH, esophageal hiatus diameter score, Hill classification, and BMI were used as test variables, and recurrence was used as a classification variable to construct the ROC curves (Fig. 3). In Table III, the AUC values of each factor are summarized. The cut-off value of the esophageal hiatus diameter score was >2 points, corresponding to the esophageal hiatus diameter of ≥3 cm. The differences in the AUC between the prediction model and each factor were statistically significant (P<0.000). The prediction model showed a higher accuracy in predicting reflux recurrence than each factor alone.

The nomogram was developed based on clinical experience and a literature review using the four independent risk factors, CAG and H. pylori infection (Fig. 4). The higher total point value for the six indicators, the greater the probability of reflux recurrence. In multivariate prediction model, the reflux recurrence score of 0.468 showed the most accurate prediction. The cut-off value of 46.8 revealed accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 74.0, 71.4, 75.8, 69.0 and 77.9%, respectively (Table IV). The multivariate prediction model for reflux recurrence was established using the data from all patients and showed a ROC of 0.801 (95% confidence interval: 0.748-0.854) (Fig. 5). In addition, the AUC of the two prediction models was not significantly different (P=0.552). The calibration curve revealed favorable predictive accuracy between the predicted and actual reflux recurrence (mean absolute error=0.023) (Fig. 6).

 Discussion

The occurrence of RE is attributed to the interaction of multiple factors. The abnormal anatomical morphology of the GEJ weakens the anti-reflux function and the low motility state decreases the clearance ability of the esophagus and prolongs acid exposure time, which not only aggravate regurgitation, but also affects the efficacy of PPI treatment (6). Reflux symptoms can recur or persist in patients with GERD and an abnormal anatomical morphology of the GEJ (2). In the present study, the anatomical morphology of the GEJ of patients with different severity of regurgitation was analyzed. Previous studies have indicated that factors, including HH and abnormal GEFV affect the efficacy of PPI treatment for GERD (16,17), but BMI does not (18). In the present study, it appeared that patients with axial length HH >2 cm, esophageal hiatus diameter ≥3 cm, Hill grade IV, and BMI >25.1 kg/m2 at the same time are vulnerable to severe regurgitation and may require long-term maintenance treatment.

In the current study, the optimal cut-off value of BMI was >25.1 kg/m2 and patients with recurrent regurgitation accounted for 58.2% (78/134). Pandolfino et al (19) analyzed the relationship between obesity and pressure of the EGJ; it was revealed that patients with BMI >25 kg/m2 had significantly higher intragastric pressure than those with BMI <25 kg/m2. This finding indicated that the gastroesophageal pressure in the GEJ increases with BMI, causing the anti-reflux function to become unstable. Furthermore, patients with a BMI >30 kg/m2 were more likely to develop HH and GERD, further supporting the results of the present study.

The morphology of the gastric mucosal fold and its fit with the endoscopic shaft reflects the anti-reflux function of the GEJ. Hill et al classified GEFV into four grades based on the appearance of the GEJ; grades I and II were normal, while grades III and IV were abnormal (20). In a meta-analysis examining the predictive value of the Hill classification on GERD (21), 3,914 patients were included in seven studies, and the sensitivity and specificity of abnormal GEFV in the diagnosis of RE were 54.8 and 75.7%, respectively. The Hill classification provides diagnostic information on the morphology of the EGJ and quantifies the severity of GERD, which facilitates the selection of a therapeutic regimen and observation of prognosis.

The endoscopic evaluation of sliding HH includes the axial length of the HH and esophageal hiatus diameter; however, presently, there is no unified standard for its endoscopic diagnosis and classification (2,22). Schlottmann et al (23) measured the axial length of HH using barium radiography and divided the study population into three groups: HH <3, 3-5, and >5 cm. Regurgitation occurred more frequently and esophagitis and reflux symptoms were more severe in patients with longer axial length of HH; in the current study, the average axial lengths of HH in the general and recurrent groups were 1.97±0.51 and 2.40±0.54 cm, respectively. Additionally, the Kendall tau-β correlation coefficients between the axial length of HH and RE classification and recurrence were 0.198 and 0.366, respectively (P<0.001), which were similar to the study conducted by Schlottmann et al.

A previous research showed that the average axial length of HH and Hill classification in patients with GERD were greater than those in non-GERD patients (1.9 and 2.7 cm vs. 1.6 and 2.2 cm). There was no statistical difference between the Hill classification and axial length of HH; however, in clinical practice, the Hill classification was more accurate in measurement than that of axial length of HH (24). In the present study, there was no statistical significance in the AUC between the Hill classification and axial length of HH (P=0.880), which indicates that the Hill classification was not superior to axial length of HH in predicting reflux symptom recurrence. The combination of the axial length of HH, esophageal hiatus diameter, Hill classification, and BMI showed a higher accuracy in predicting reflux symptom recurrence than that of each individual factor (P<0.001).

The relationship between H. pylori infection and GERD has not yet been resolved (25). Gastric atrophy and hyposecretion of gastric acid often occur in patients with H. pylori infection. Therefore, it is mostly considered believe that H. pylori infection is negatively correlated with RE, which may protect vulnerable individuals from GERD (26). Similarly, the effect of CAG on gastric mucosa is analogous to that of H. pylori infection (27). To construct a reasonable and complete prediction model, combined with the authors' clinical experience and literature review, atrophic gastritis and H. pylori infection were included in the multivariate prediction model, even if they are not independent risk factors for reflux recurrence. Specifically, the results may be more definitive when the sample size increases. In a similar study, a prediction model with a sample size of 494 patients showed improved discriminative power (28).

Actually, MII-pH or HRM have not yet been popularized in all medical institutions of developing countries including China, but patients with GERD are very common (5,29). Without complicated symptoms, outpatients or physical examination patients with GERD alone, usually do not require to be subjected to other examinations than endoscopy from a cost-effective perspective. There were several limitations to the present study. Given the patients' condition in the present study, the data were measured using RDQ and gastroscopy without other objective examination, including MII-pH or HRM. The esophageal hiatus diameter was indirectly measured by directly comparing the esophageal hiatus diameter and endoscope shaft, scores were used to reflect the range of the esophageal hiatus diameter and perform statistical analysis. The sample size may not be sufficient due to the exclusion criteria and patient compliance. Certain patients discontinued their treatment voluntarily after a slight improvement in symptoms. Further study with a larger sample size and more objective examination is required to confirm the efficacy of the prediction model in the present study.

This prediction model is more suitable for primary clinical evaluation without imposing additional burdens on outpatients. Patients with an axial length of HH >2 cm, esophageal hiatus diameter ≥3 cm, Hill grade >III, and BMI >25.1 kg/m2 are prone to have reflux recurrence or require PPI maintenance treatment. In clinical practice, patients who present with H. pylori infection and CAG are relatively less likely to develop reflux recurrence. However, this feature was not represented in the prediction model of the present study. Meanwhile, a reference was provided for diagnosing refractory RE and screening high-risk populations with poor drug efficacy or recurrent reflux.

 Supplementary Material The scoring criteria of Reflux Disease Questionnaire. Acknowledgements

The authors would like to thank Dr Chaoxi Liu and Dr Xuchun Wang (Department of Public Health, Shanxi Medical University) for guiding the statistical analysis of the present study.

 Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

 Authors' contributions

XC, QW and JL conceived and designed the study. JL performed statistical analysis. QW and JL analyzed the data. QW, YS, JF, JR and ZW performed data collection. QW and JL confirm the authenticity of all the raw data. All authors contributed to the writing of the manuscript and reviewed, read and approved the final manuscript.

 Ethics approval and consent to participate

The present study was conducted in accordance with the tenets of the Declaration of Helsinki. The present study protocol was approved (approval no. T20211223001) by the Ethics Committee of Linfen People's Hospital affiliated to Shanxi Medical University (Taiyuan, China). According to the Shanxi Medical University Ethics Committee, the study patients were notified of the study and permitted the opportunity to refuse participation in the study.

 Patient consent for publication

With regard to the informed consent of participants, the Ethics Committee of Linfen People's Hospital affiliated to Shanxi Medical University made a decision based on the Ethical Guidelines for Medical and Health Research Involving Human Subjects, which states that non-intervention studies are deemed exempt from patients' consent and, instead, researchers must notify the study subjects about the information regarding study contents on a home page, and guarantee an opportunity when the study subjects could refuse consent. All patients participating in the present study received written informed consent.

 Competing interests

The authors declare that they have no competing interests.

 References FuchsKHDeMeesterTROtteFBroderickRCBreithauptWVargaGMusialFSeverity of GERD and disease progressionDis Esophagus34doab00620213357573910.1093/dote/doab006 LiLGaoHZhangCTuJGengXWangJZhouXPanWJingJDiagnostic value of X-ray, endoscopy, and high-resolution manometry for hiatal hernia: A systematic review and meta-analysisJ Gastroenterol Hepatol35131820203120678810.1111/jgh.14758 AsaokaDTakedaTSasakiHShimadaYMatsumotoKUeyamaHMatsumotoKIzumiKKomoriHAkazawaYEvaluation of symptomatic reflux esophagitis in proton pump inhibitor usersBiomed Rep1027728220193108666110.3892/br.2019.1206 El-SeragHBecherAJonesRSystematic review: Persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studiesAliment Pharmacol Ther3272073720102066277410.1111/j.1365-2036.2010.04406.x KatzPODunbarKBSchnoll-SussmanFHGreerKBYadlapatiRSpechlerSJACG clinical guideline for the diagnosis and management of gastroesophageal reflux diseaseAm J Gastroenterol117275620223480700710.14309/ajg.0000000000001538 GyawaliCPKahrilasPJSavarinoEZerbibFMionFSmoutAJPMVaeziMSifrimDFoxMRVelaMFModern diagnosis of GERD: The Lyon ConsensusGut671351136220182943791010.1136/gutjnl-2017-314722 Multidisciplinary Branch of Gastroesophageal Reflux of China International Exchange and Promotion Association for Medical and Healthcare. Consensus on multidisciplinary diagnosis and treatment of gastroesophageal reflux disease in ChinaChin J Gastroesophagol Reflux Dis (Electronic Edition)71282020(In Chinese) DentJVakilNJonesRBytzerPSchöningUHallingKJunghardOLindTAccuracy of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump inhibitor treatment: The Diamond StudyGut5971472120102055145410.1136/gut.2009.200063 Value of reflux diagnostic questionnaire in the diagnosis of gastroesophageal reflux diseaseChin J Dig Dis5515520041561265710.1111/j.1443-9573.2004.00155.x ShawMJTalleyNJBeebeTJRockwoodTCarlssonRAdlisSFendrickAMJonesRDentJBytzerPInitial validation of a diagnostic questionnaire for gastroesophageal reflux diseaseAm J Gastroenterol96525720011119728710.1111/j.1572-0241.2001.03451.x LundellLRDentJBennettJRBlumALArmstrongDGalmicheJPJohnsonFHongoMRichterJESpechlerSJEndoscopic assessment of oesophagitis: Clinical and functional correlates and further validation of the Los Angeles classificationGut4517218019991040372710.1136/gut.45.2.172 QuachDTHiyamaTAssessment of endoscopic gastric atrophy according to the kimura-takemoto classification and its potential application in daily practiceClin Endosc5232132720193132718210.5946/ce.2019.072 SgourosSNMpakosDRodiasMVassiliadesKKarakoidasCAndrikopoulosEStefanidisGMantidesAPrevalence and axial length of hiatus hernia in patients, with nonerosive reflux disease: A prospective studyJ Clin Gastroenterol4181481820071788192610.1097/01.mcg.0000225678.99346.65 WallnerBBjörOAndreassonAHellströmPMForsbergAMTalleyNJAgreusLIdentifying clinically relevant sliding hiatal hernias: A population-based endoscopy studyScand J Gastroenterol5365766020182961683110.1080/00365521.2018.1458896 KaneyamaHKaiseMArakawaHAraiYKanazawaKTajiriHGastroesophageal flap valve status distinguishes clinical phenotypes of large hiatal herniaWorld J Gastroenterol166010601520102115797810.3748/wjg.v16.i47.6010 PengSXiaoYLCuiYLinJKZhangNHuPJChenMHHigh-dose esomeprazole is required for intraesophageal acid control in gastroesophageal reflux disease patients with hiatus herniaJ Gastroenterol Hepatol2789389820122209838710.1111/j.1440-1746.2011.06969.x CheongJHKimGHLeeBEChoiMKMoonJYRyuDYKimDUSongGAEndoscopic grading of gastroesophageal flap valve helps predict proton pump inhibitor response in patients with gastroesophageal reflux diseaseScand J Gastroenterol4678979620112161522210.3109/00365521.2011.579154 WatanabeAIwakiriRYamaguchiDHiguchiTTsuruokaNMiyaharaKAkutagawaKSakataYFujiseTOdaYRisk factors for resistance to proton pump inhibitor maintenance therapy for reflux esophagitis in Japanese women over 60 yearsDigestion8632333120122312834410.1159/000342393 PandolfinoJEEl-SeragHBZhangQShahNGhoshSKKahrilasPJObesity: A challenge to esophagogastric junction integrityGastroenterology13063964920061653050410.1053/j.gastro.2005.12.016 HillLDKozarekRAKraemerSJAyeRWMercerCDLowDEPopeCE IIThe gastroesophageal flap valve: In vitro and in vivo observationsGastrointest Endosc445415471996893415910.1016/s0016-5107(96)70006-8 OsmanAAlbashirMMNandipatiKWaltersRWChandraSEsophagogastric junction morphology on Hill's classification predicts gastroesophageal reflux with good accuracy and consistencyDig Dis Sci6615115920213207808810.1007/s10620-020-06146-0 DuranceauAMassive hiatal hernia: A reviewDis Esophagus2935036620162578956310.1111/dote.12328 SchlottmannFAndolfiCHerbellaFARebecchiFAllaixMEPattiMGGERD: Presence and size of hiatal hernia influence clinical presentation, esophageal function, reflux profile, and degree of mucosal injuryAm Surg84978982201829981634 HansdotterIBjörOAndreassonAAgreusLHellströmPForsbergATalleyNJViethMWallnerBHill classification is superior to the axial length of a hiatal hernia for assessment of the mechanical anti-reflux barrier at the gastroesophageal junctionEndosc Int Open4E311E31720162700424910.1055/s-0042-101021 RichterJERubensteinJHPresentation and epidemiology of gastroesophageal reflux diseaseGastroenterology15426727620182878007210.1053/j.gastro.2017.07.045 EusebiLHRatnakumaranRYuanYSolaymani-DodaranMBazzoliFFordACGlobal prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: A meta-analysisGut6743044020182823247310.1136/gutjnl-2016-313589 HanYMChungSJYooSYangJIChoiJMLeeJKimJSInverse correlation between gastroesophageal reflux disease and atrophic gastritis assessed by endoscopy and serologyWorld J Gastroenterol2885386720223531709810.3748/wjg.v28.i8.853 KimJYShinISMinYWKimKLeeHMinBHLeeJHKimJJRheePLEndoscopic prediction for acid reflux in patients without Hiatus HerniaKorean J Gastroenterol7613414120203296936110.4166/kjg.2020.76.3.134 XiaoYLZhouLYHouXHLiYQZouDWChenMHChinese Society of GastroenterologyChinese expert consensus on gastroesophageal reflux disease in 2020J Dig Dis2237638920213410526310.1111/1751-2980.13028

Case screening process.

Endoscopic images of different degrees of esophageal hiatus diameter. (A) Normal cardia for 1 point. (B) The esophageal hiatus diameter is ~2 cm for 2 points. (C) ~3 cm for 3 points. (D) ~4 cm for 4 points. (E) ~5 cm for 5 points.

ROC curves of prediction model, the axial length of HH, esophageal hiatus diameter score, Hill classification and BMI. 1-specificy: false positive rate, which is equal to 1-specificity (%). HH, hiatal hernia; ROC, receiver operating characteristic curve; AUC, area under the curve.

Nomogram for the multivariate prediction model of reflux recurrence.

ROC curves of the multivariate prediction model of reflux recurrence. ROC, receiver operating characteristic curve; AUC, area under the curve.

Calibration curve of the multivariate prediction model in predicting reflux recurrence.

The factors included in the present study and the results of univariate analysis.

Factors General group (n=149) Recurrent group (n=112) t-value P-value
Sex     11.41 0.001
     Female (%) 72 (48.3%) 31 (27.7%)    
     Male (%) 77 (51.7%) 81 (72.3%)    
Age (years) 55.2±12.2 56.7±10.3 -0.24 0.275
Body mass index (kg/m2) 24.4±2.3 25.6±2.2 -3.83 <0.001
Reflux esophagitis        
     Grade A (%) 78 (52.2%) 42 (37.5%)    
     Grade B (%) 57 (38.3%) 45 (40.2%)    
     Grade C (%) 12 (8.1%) 15 (13.4%)    
     Grade D (%) 2 (1.3%) 10 (8.9%)    
Hill        
     Grade III (%) 107 (71.8%) 41 (36.6%) 32.28 <0.001
     Grade IV (%) 42 (28.1%) 71 (63.3%)    
The axial length of hiatal hernia (cm) 1.97±0.51 2.40±0.54 -6.09 <0.001
Esophageal hiatus diameter score 2.48±0.62 3.07±0.62 -6.74 <0.001
Superficial gastritis        
     No 60 (40.2%) 50 (44.5%) 0.50 0.479
     Yes 89 (59.7%) 62 (55.4%)    
Atrophic gastritis        
     No (%) 89 (59.7%) 62 (55.4%) 5.06 0.080
     C1/C2 (%) 50 (33.6%) 48 (42.9%)    
     C3/O1 (%) 10 (6.7%) 2 (1.8%)    
Drinking        
     No 122 (81.8%) 78 (69.6%) 5.35 0.021
     Yes 27 (18.1%) 34 (30.4%)    
Smoking        
     No        
     Yes        
Helicobacter Pylori infection        
     No 123 (82.6%) 99 (88.4%) 1.72 0.190
     Yes 26 (17.4%) 13 (11.6%)    

Results of Logistic regression analysis and risk factors for reflux symptoms recurrence.

Risk factors β SE Wald P-value OR (95% confidence interval)
Sex (man) 0.548 0.354 2.394 0.122 1.730 (0.864~3.462)
Hill grade IV 0.875 0.366 5.722 0.017 2.399 (1.171~4.912)
Reflux esophagitis classification     3.716 0.294  
Grade B -0.564 0.920 0.376 0.852 0.829 (0.114~6.014)
Grade C -0.945 0.892 1.122 0.540 0.569 (0.094~3.451)
Grade D -1.436 0.959 2.242 0.134 0.238 (0.036~1.559)
Chronic atrophic gastritis     0.356 0.837  
C1/C2 0.079 0.952 0.007 0.934 1.083 (0.168~6.991)
C3/O1 0.265 0.957 0.076 0.782 1.303 (0.200~8.504)
The axial length of hiatal hernia 0.970 0.347 7.810 0.005 2.638 (1.336~5.207)
Esophageal hiatus diameter score 0.984 0.293 11.264 0.001 3.676 (1.506~4.754)
Body mass index 0.160 0.069 5.402 0.020 1.173 (1.025~1.342)
Helicobacter Pylori infection (Yes) -0.906 0.486 3.474 0.062 0.404 (0.156~1.048)
Drinking 0.409 0.443 0.852 0.356 1.505 (0.632~3.584)
Smoking 0.210 0.502 0.175 0.676 1.234 (0.461~3.300)

The prediction model for predicting reflux symptom recurrence.

Predictors AUC 95% CI Cut-off value Sensitivity (%) Specificity (%) P-value
The axial length of HH (cm) 0.681 0.630~0.733 >2 39.29 88.59 P1<0.000
Esophageal hiatus diameter score 0.719 0.665~0.773 >2 83.93 48.99 P2<0.000
Hill classification 0.676 0.618~0.734 > grade III 63.39 71.81 P3<0.000
BMI (kg/m2) 0.639 0.571~0.706 >25.1 69.64 63.09 P4<0.000
Prediction model 0.797 0.734~0.851 >0.539 65.18 81.88  

Prediction model developed by axial length of HH, esophageal hiatus diameter, Hill grade and BMI. P1, P2, P3 and P4 respectively reflect the statistical differences between the AUC of prediction model and the AUC of the axial length of HH, esophageal hiatus diameter score, Hill classification and BMI. HH, hiatal hernia; ROC, receiver operating characteristic curve; AUC, area under the curve; 95% CI, 95% confidence interval; BMI, body mass index.

The efficacy of the multivariate prediction model in predicting reflux recurrence.

Cutoff Accuracy Sensitivity Specificity Positive predictive value Negative predictive value Positive by prediction model
63.8 0.709 0.482 0.879 0.750 0.693 72 (0.276)
56.1 0.743 0.616 0.839 0.742 0.744 93 (0.356)
46.8 0.740 0.714 0.758 0.690 0.779 116 (0.444)
39.1 0.732 0.759 0.711 0.664 0.797 128 (0.490)
26.9 0.648 0.839 0.503 0.560 0.807 168 (0.644)
26.4 0.655 0.857 0.503 0.565 0.824 170 (0.651)
15.1 0.579 0.964 0.289 0.505 0.915 214 (0.820)
12.0 0.548 0.973 0.228 0.487 0.919 224 (0.858)
10.3 0.540 0.991 0.201 0.483 0.968 230 (0.881)
7.2 0.494 0.991 0.121 0.459 0.947 242 (0.927)
6.3 0.475 0.991 0.087 0.449 0.929 247 (0.946)
4.2 0.464 1.000 0.060 0.444 1.000 252 (0.966)
2.4 0.448 1.000 0.034 0.438 1.000 256 (0.981)

Multivariate prediction model developed by axial length of HH, esophageal hiatus diameter, Hill grade, BMI, CAG, and H. pylori infection. HH, hiatal hernia; BMI, body mass index; CAG, chronic atrophic gastritis; H. Pylori, Helicobacter pylori.