The potential of reduction in LES relaxation pressure during endoscopy in three cases of Achalasia

The potential of reduction in LES relaxation pressure during endoscopy in three cases of Achalasia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report The potential of reduction in LES relaxation pressure during endoscopy in three cases of Achalasia Peiwen Dong, Zhilin Yang, Kaidi Sun, Feng Tang, Qiong Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8385858/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aim Current high-resolution manometry (HRM) guidelines specify that manometry should be performed following esophagogastroduodenoscopy (EGD) but do not define an optimal interval between procedures. To investigate whether the timing of HRM relative to EGD influences diagnostic metrics for achalasia. Methods We unexpectedly discovered and analyzed three cases of suspected achalasia where the initial HRM, performed shortly after EGD, failed to meet diagnostic criteria. All patients subsequently underwent a repeat HRM several days after the initial EGD. Results In all three patients, the follow-up HRM studies demonstrated a significant increase in integrated relaxation pressure (IRP), with values reaching the definitive diagnostic threshold for achalasia, which were not observed in the initial studies. Conclusions The timing of HRM after EGD can affect IRP measurements and potentially impact diagnostic accuracy for achalasia. We recommend a delay of at least 3 days between EGD and HRM when achalasia is suspected to improve diagnostic yield. High-resolution manometry achalasia EGD interval Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Esophageal achalasia is a primary esophageal motility disorder characterized by dysphagia, regurgitation, and aspiration. In this condition, both the peristaltic contractions in the smooth muscle portion of the esophageal body and the relaxation of the lower esophageal sphincter (LES) are impaired, with the tonic contraction of the LES persisting [ 1 ] . In early stages, achalasia may be misdiagnosed as gastroesophageal reflux disease (GERD) and approximately 45% of patients have been mistakenly treated with acid-suppressive therapy [ 2 ] . Esophageal manometry is considered the gold standard for the diagnosis of achalasia because it can detect both the failure of LES relaxation and abnormal peristalsis [ 3 ] . It can divide achalasia into 3 types to guide subsequent treatment and predict prognosis [ 4 , 5 ] . HRM can achieve a diagnostic sensitivity for achalasia of up to 89%–97% according to reports [ 6 ] . However, with routine use of HRM, we have observed that some patients show significant variability between consecutive measurements. We propose the hypothesis that IRP measured by HRM is affected by preceding EGD. This report describes three cases of esophageal achalasia in which patients underwent manometry on the day following EGD, with IRP values within normal limits; however, repeat manometry three days later revealed IRP values above the upper normal limit, thereby supporting our hypothesis. Methods This study is a retrospective case series analysis. We analyzed three cases of suspected achalasia where the initial HRM, performed shortly after EGD, failed to meet diagnostic criteria. All patients subsequently underwent a repeat HRM several days after the initial EGD. Written informed consent was obtained from all three patients for the use of their anonymized clinical data in scientific research and publication. Ethical committee approval was received by the Medical Ethics Committee of the Third People’s hospital of Chengdu. (Approval no: [2023]S-No.133, Date: 2023.12.13). Case 1: An 18‐year‐old male presented with a one‐year history of recurrent dysphagia with episodes of vomiting, with no significant past medical history and an Eckardt score of 9. On March 27, EGD revealed increased resistance at the esophagogastric junction (EGJ). Endoscopic ultrasonography showed localized thickening of both the mucosal–muscularis propria layers at 39–40 cm from the incisors（3.56mm, Figure 1）, a narrowed lumen, and resistance at the EGJ, though passage was achieved after endoscopic dilation, raising suspicion for achalasia. On March 28, esophageal manometry demonstrated an LES resting pressure of 17.4 mmHg, and IRP of 9 mmHg (Figure 2a). All 10 swallows failed, two swallows exhibited PEP (pan-esophageal pressurization). According to the Chicago Classification 4.0, the findings were consistent only with absent peristalsis. 24h reflux monitoring showed an acid exposure time (AET) of 0.2 and a total reflux count of 20. The barium esophagogram did not reveal overt obstruction. But given the typical clinical symptoms, a repeat manometry was performed on March 31, which showed an LES resting pressure of 14.1 mmHg and IRP increased to 16.7 mmHg (Figure 2b), with 6 out of 10 swallows demonstrating PEP. These findings fulfilled the criteria for early-stage type II achalasia. Case 2: A 37‐year‐old male with a three‐year history of dysphagia, regurgitation, and vomiting, with no significant weight loss or past medical history (and a BMI of 20.5 kg/m²), initially underwent EGD in January 2018 at an outside institution, which was unremarkable; H-pylori testing was negative, and he received rabeprazole without symptomatic improvement. At a December 2020 evaluation at our center, the patient had a GERDQ score of 6 and an Eckardt score of 6. On December 27, our EGD showed no obvious abnormalities, but due to persistent dysphagia, a barium swallow was performed on December 28, which suggested severe achalasia with marked esophageal stasis and dilation. Consequently, manometry was performed on December 28, demonstrating an LES resting pressure of 13.4 mmHg, IRP of 10.1 mmHg (Figure 3a), and all 10 swallows failed; one swallow showed PEP. These findings were interpreted as absent peristalsis. Given the patient’s young age and after thorough discussion, treatment with sublingual isosorbide dinitrate was initiated for one month. However, with no significant improvement in symptoms and the emergence of adverse effects (e.g., dizziness), the medication was discontinued. As the symptoms persisted, the patient returned for evaluation six months later. On April 2021, repeat EGD revealed a dilated distal esophagus with slight liquid retention, and a tight EGJ that did not appear to open spontaneously, although gentle passage of the scope was possible, thus raising the suspicion of achalasia. Three days after this endoscopic evaluation, repeat manometry was performed and demonstrated PEP in all 10 swallows and IRP increased to 20 mmHg (Figure 3b), which allowed for a definitive diagnosis of type II achalasia. The patient subsequently underwent peroral endoscopic myotomy (POEM) with good postoperative recovery. Case 3: A 72‐year‐old male presented with a two-year history of reflux symptoms and occasional dysphagia when consuming solid food, along with intermittent vomiting and coughing. An initial EGD at a local hospital was unremarkable, and he was treated with proton pump inhibitors for presumed GERD without significant benefit. Three months prior to admission, following a COVID-19 infection, the patient experienced marked worsening of his dysphagia. His past medical history included hypothyroidism, hypertension, and benign prostatic hyperplasia, for which he was on sacubitril/valsartan and levothyroxine, respectively. On admission, his Eckardt score was 3 and his GERDQ score was 7. Laboratory studies—including thyroid function tests, tumor markers, BNP, cardiac enzymes, electrolytes, and an electrocardiogram—were unremarkable. Chest CT revealed esophageal dilation with significant intraluminal content. On May 16, 2023, our EGD with ultrasonography showed a narrowed EGJ, proximal esophageal dilation, and liquid retention. The distance from the incisors to the EGJ was 45 cm, and muscle layer thickening was observed from 42–45 cm, with a maximal thickness of approximately 3.32 mm(Figure 4), raising suspicion for achalasia. However, on May 17, manometry revealed an LES resting pressure of 15.7 mmHg and IRP of 4.6 mmHg (Figure 5a), precluding the diagnosis of an obstructive motility disorder. Given the prominent reflux symptoms, 24‐hour pH monitoring was performed, which revealed an AET of 1.3, a total reflux count of 16, and a negative SAP, thereby excluding GERD. Although the patient’s dysphagia was not prominent, the endoscopic and barium swallow findings continued to raise suspicion for achalasia. On May 20, a repeat manometry demonstrated an LES resting pressure of 19.8 mmHg, IRP elevated to 15.2 mmHg(Figure 5b), and PEP in 8 out of 10 swallows, confirming a diagnosis of type II achalasia. The patient subsequently underwent POEM with marked symptomatic improvement. Discussion In the three cases presented, all patients were highly suspected esophageal achalasia based on clinical symptoms and findings from EGD or barium studies. However, the initial HRM did not demonstrate a significantly elevated LES relaxation pressure. According to the Chicago Classification v4.0, a diagnosis of achalasia requires in the supine position, the median IRP needs to be higher than 15 mmHg when using the Medtronic manometry system [ 4 ] . Thus, the initial HRM findings did not meet the diagnostic criteria. Notably, repeat HRM studies in all three patients, performed several days after the initial assessment, demonstrated IRP values that reached diagnostic thresholds (Table 1 ). One possible explanation for these discrepancies is the natural variability in esophageal motility and the fact that HRM only captures the instantaneous pressure of the esophageal musculature, which may fluctuate over time as the disease progresses. Alternatively, our observations suggest another hypothesis: the timing of HRM relative to EGD might influence the measured IRP. All three patients underwent HRM 1–2 days after EGD. Current HRM guidelines specify that manometry should be performed following EGD to rule out structural abnormalities or malignancy, but do not define an optimal interval between procedures [ 7 ] . In routine practice, HRM is often scheduled the day after EGD to minimize the potential impact of topical anesthetics on the upper esophageal sphincter (UES) pressure. However, considering that pneumatic dilation—an established treatment for achalasia—induces muscle relaxation through forceful stretching of the LES [ 8 ] . However, the effectiveness of treatment decreases over time and requires repeated treatments [ 9 ] . For patients with achalasia, EGD shows that the cardia is tightly closed and the pressure increases when passing through the EGJ. It is conceivable that the expansion pressure generated by pushing the endoscope body and passing through the cardia when passing through the lower esophagus cause the IRP to decrease temporarily, thereby may resulting in failure to meet the diagnostic criteria during the HRM. Although daily post-EGD HRM assessments to track changes are impractical, our findings suggest that the transient reduction in LES pressure following EGD may lead to an underestimation of the true motility disorder if HRM is performed too soon. In all three cases, IRP increased to diagnostic levels 3–4 days after EGD. While we cannot confirm whether IRP returned to baseline, this pattern supports our hypothesis. Therefore, we recommend that in suspected achalasia, a resting period of at least 3 days following EGD may be necessary before performing HRM. Future studies will also strive to re-examine the HRM of patients with nondiagnostic IRP shortly after EGD to further verify and investigate this phenomenon. In summary, we recommend delaying HRM by at least 3 days after EGD in cases where achalasia is suspected. This adjustment in timing may improve diagnostic accuracy and better reflect the underlying esophageal motility disorder. Table 1 This chart clearly illustrates that, in all three cases, the initial HRM performed 1–2 days after EGD showed IRP values below the diagnostic threshold (IRP > 15 mmHg as per Chicago Classification v4.0), whereas the repeat HRM 3–4 days later showed elevated IRP values that met the criteria for esophageal achalasia. Case Timing of HRM (after EGD) IRP (mmHg) Case 1 1 day (Initial HRM) 9.0 4 days (Repeat HRM) 16.7 Case 2 1 day (Initial HRM) 10.1 3 days (Repeat HRM) 20.0 Case 3 1 day (Initial HRM) 4.6 4 days (Repeat HRM) 15.2 Declarations Ethics Approval Statement Ethical committee approval was received by the Medical Ethics Committee of the Third People’s hospital of Chengdu. (Approval no: [2023]S-No.133). Consent for publication Written informed consent was obtained from all three patients for the use of their anonymized clinical data in scientific research and publication. A copy of the written consent is available for review by the Editor of this journal. Availability of Data and Materials The data that support the findings of this study are not openly available due to reasons of patient privacy and data sensitivity and are available from the corresponding author upon reasonable request. All data are in the controlled access data storage of the Digestive Disease Database of Chengdu Third People's Hospital. Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding This work is supported by grants from The Bethune Charity Foundation (No. BCF-LX-XH-20221014-10), and The Third People's Hospital of Chengdu Intramural Research Project（No. CSY-YN-01-2023-042） Author Contributions Concept – PD, QW; Design – PD; Supervision – QW; Resources – ZY, FT; Data Collection – PD; Analysis– PD, KS; Literature Search – PD; Writing Manuscript – PD; Critical Review – QW References Gregersen, et al. “Pathophysiology and treatment of achalasia in a muscle mechanical perspective.” Annals of the New York Academy of Sciences vol. 1434,1 (2018): 173-184. doi:10.1111/nyas.13711 Pandolino JE, et al. High-resolution manometry In clinical practice: utilizing pressure topography to classify oesophageal motility abnormalities[J ]. Neurogastroenterol Motil,20021(8):796-806 Expert consensus on the diagnosis and treatment of achalasia in China (2020, Beijing) [J]. Chinese Journal of Digestive Endoscopy, 2021, 38(4): 256-275. DOI: 10.3760/cma.j.cn321463-20201208-00950. Yadlapati, Rena et al. “Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0©.” Neurogastroenterology and motility vol. 33,1 (2021): e14058. doi:10.1111/nmo.14058 Salvador R, et al. Manometric pattern progression in esophageal achalasia in the era of high-resolution manometry. Ann Transl Med. 2021 May;9(10):906. doi: 10.21037/atm.2020.03.149. Liu Xiaotong, et al. Diagnosis and treatment of achalasia[J]. Chinese Journal of Internal Medicine, 2022, 61(2): 214-218. DOI: 10.3760/cma.j.cn112138-20211214-00884. Committee of Gastroesophageal Reflux Disease，Chinese guideline for high resolution esophageal manometry in clinical practice[J].chin J Dig, 2020, 40(1):3-8. DOI:10.3760/cma.j.issn.0254-1432.2020.01.002 Borhan-Manesh F, et al. The efficacy of balloon dilation in achalasia is the result of stretching of the lower esophageal sphincter, not muscular disruption. Dis Esophagus. 2016 Apr;29(3):262-6. doi: 10.1111/dote.12314. Epub 2015 Mar 13. Mohammed, A. et al. (2022) ‘Pneumatic dilation for esophageal achalasia: patient selection and perspectives’, Scandinavian Journal of Gastroenterology, 57(6), pp. 650–659. doi: 10.1080/00365521.2022.2034940. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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3","display":"","copyAsset":false,"role":"figure","size":566116,"visible":true,"origin":"","legend":"\u003cp\u003e\u0026nbsp;Legend not included with this version.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8385858/v1/9ff9fb89f0ce5e5007ca4494.png"},{"id":100547017,"identity":"1d6d4887-dd9f-4b1f-a06a-28896fa22a6e","added_by":"auto","created_at":"2026-01-19 08:14:00","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":202304,"visible":true,"origin":"","legend":"\u003cp\u003e\u0026nbsp;Legend not included with this version.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8385858/v1/27b63efeac3ff473b4e43a07.png"},{"id":100546311,"identity":"792e749f-3a9e-4acb-bcc5-019f4252c035","added_by":"auto","created_at":"2026-01-19 08:05:36","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":438538,"visible":true,"origin":"","legend":"\u003cp\u003e\u0026nbsp;Legend not included with this version.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8385858/v1/c87b78fb31fa82693414c857.png"},{"id":102398307,"identity":"e84d3f8a-187c-4b61-a857-ec827c1a536d","added_by":"auto","created_at":"2026-02-11 10:22:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3698062,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8385858/v1/a243f24b-f45a-45fc-9bab-a8c05545729a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The potential of reduction in LES relaxation pressure during endoscopy in three cases of Achalasia","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEsophageal achalasia is a primary esophageal motility disorder characterized by dysphagia, regurgitation, and aspiration. In this condition, both the peristaltic contractions in the smooth muscle portion of the esophageal body and the relaxation of the lower esophageal sphincter (LES) are impaired, with the tonic contraction of the LES persisting \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. In early stages, achalasia may be misdiagnosed as gastroesophageal reflux disease (GERD) and approximately 45% of patients have been mistakenly treated with acid-suppressive therapy \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Esophageal manometry is considered the gold standard for the diagnosis of achalasia because it can detect both the failure of LES relaxation and abnormal peristalsis \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. It can divide achalasia into 3 types to guide subsequent treatment and predict prognosis\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. HRM can achieve a diagnostic sensitivity for achalasia of up to 89%\u0026ndash;97% according to reports \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. However, with routine use of HRM, we have observed that some patients show significant variability between consecutive measurements.\u003c/p\u003e \u003cp\u003eWe propose the hypothesis that IRP measured by HRM is affected by preceding EGD. This report describes three cases of esophageal achalasia in which patients underwent manometry on the day following EGD, with IRP values within normal limits; however, repeat manometry three days later revealed IRP values above the upper normal limit, thereby supporting our hypothesis.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study is a retrospective case series analysis. We analyzed three cases of suspected achalasia where the initial HRM, performed shortly after EGD, failed to meet diagnostic criteria. All patients subsequently underwent a repeat HRM several days after the initial EGD. Written informed consent was obtained from all three patients for the use of their anonymized clinical data in scientific research and publication. Ethical committee approval was received by the Medical Ethics Committee of the Third People\u0026rsquo;s hospital of Chengdu. (Approval no: [2023]S-No.133, Date: 2023.12.13).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase 1:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn 18‐year‐old male presented with a one‐year history of recurrent dysphagia with episodes of vomiting, with no significant past medical history and an Eckardt score of 9. On March 27, EGD revealed increased resistance at the esophagogastric junction (EGJ). Endoscopic ultrasonography showed localized thickening of both the mucosal\u0026ndash;muscularis propria layers at 39\u0026ndash;40 cm from the incisors（3.56mm, Figure 1）, a narrowed lumen, and resistance at the EGJ, though passage was achieved after endoscopic dilation, raising suspicion for achalasia. On March 28, esophageal manometry demonstrated an LES resting pressure of 17.4 mmHg, and IRP of 9 mmHg (Figure 2a). All 10 swallows failed, two swallows exhibited PEP (pan-esophageal pressurization). According to the Chicago Classification 4.0, the findings were consistent only with absent peristalsis. 24h reflux monitoring showed an acid exposure time (AET) of 0.2 and a total reflux count of 20. The barium esophagogram did not reveal overt obstruction. But given the typical clinical symptoms, a repeat manometry was performed on March 31, which showed an LES resting pressure of 14.1 mmHg and IRP increased to 16.7 mmHg (Figure 2b), with 6 out of 10 swallows demonstrating PEP. These findings fulfilled the criteria for early-stage type II achalasia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase 2:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 37‐year‐old male with a three‐year history of dysphagia, regurgitation, and vomiting, with no significant weight loss or past medical history (and a BMI of 20.5 kg/m\u0026sup2;), initially underwent EGD in January 2018 at an outside institution, which was unremarkable; H-pylori testing was negative, and he received rabeprazole without symptomatic improvement. At a December 2020 evaluation at our center, the patient had a GERDQ score of 6 and an Eckardt score of 6. On December 27, our EGD showed no obvious abnormalities, but due to persistent dysphagia, a barium swallow was performed on December 28, which suggested severe achalasia with marked esophageal stasis and dilation. Consequently, manometry was performed on December 28, demonstrating an LES resting pressure of 13.4 mmHg, IRP of 10.1 mmHg (Figure 3a), and all 10 swallows failed; one swallow showed PEP. These findings were interpreted as absent peristalsis. Given the patient\u0026rsquo;s young age and after thorough discussion, treatment with sublingual isosorbide dinitrate was initiated for one month. However, with no significant improvement in symptoms and the emergence of adverse effects (e.g., dizziness), the medication was discontinued. As the symptoms persisted, the patient returned for evaluation six months later. On April 2021, repeat EGD revealed a dilated distal esophagus with slight liquid retention, and a tight EGJ that did not appear to open spontaneously, although gentle passage of the scope was possible, thus raising the suspicion of achalasia. Three days after this endoscopic evaluation, repeat manometry was performed and demonstrated PEP in all 10 swallows and IRP increased to 20 mmHg (Figure 3b), which allowed for a definitive diagnosis of type II achalasia. The patient subsequently underwent peroral endoscopic myotomy (POEM) with good postoperative recovery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase 3:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 72‐year‐old male presented with a two-year history of reflux symptoms and occasional dysphagia when consuming solid food, along with intermittent vomiting and coughing. An initial EGD at a local hospital was unremarkable, and he was treated with proton pump inhibitors for presumed GERD without significant benefit. Three months prior to admission, following a COVID-19 infection, the patient experienced marked worsening of his dysphagia. His past medical history included hypothyroidism, hypertension, and benign prostatic hyperplasia, for which he was on sacubitril/valsartan and levothyroxine, respectively. On admission, his Eckardt score was 3 and his GERDQ score was 7. Laboratory studies\u0026mdash;including thyroid function tests, tumor markers, BNP, cardiac enzymes, electrolytes, and an electrocardiogram\u0026mdash;were unremarkable. Chest CT revealed esophageal dilation with significant intraluminal content. On May 16, 2023, our EGD with ultrasonography showed a narrowed EGJ, proximal esophageal dilation, and liquid retention. The distance from the incisors to the EGJ was 45 cm, and muscle layer thickening was observed from 42\u0026ndash;45 cm, with a maximal thickness of approximately 3.32 mm(Figure 4), raising suspicion for achalasia. However, on May 17, manometry revealed an LES resting pressure of 15.7 mmHg and IRP of 4.6 mmHg (Figure 5a), precluding the diagnosis of an obstructive motility disorder. Given the prominent reflux symptoms, 24‐hour pH monitoring was performed, which revealed an AET of 1.3, a total reflux count of 16, and a negative SAP, thereby excluding GERD. Although the patient\u0026rsquo;s dysphagia was not prominent, the endoscopic and barium swallow findings continued to raise suspicion for achalasia. On May 20, a repeat manometry demonstrated an LES resting pressure of 19.8 mmHg, IRP elevated to 15.2 mmHg(Figure 5b), and PEP in 8 out of 10 swallows, confirming a diagnosis of type II achalasia. The patient subsequently underwent POEM with marked symptomatic improvement.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the three cases presented, all patients were highly suspected esophageal achalasia based on clinical symptoms and findings from EGD or barium studies. However, the initial HRM did not demonstrate a significantly elevated LES relaxation pressure. According to the Chicago Classification v4.0, a diagnosis of achalasia requires in the supine position, the median IRP needs to be higher than 15 mmHg when using the Medtronic manometry system\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Thus, the initial HRM findings did not meet the diagnostic criteria. Notably, repeat HRM studies in all three patients, performed several days after the initial assessment, demonstrated IRP values that reached diagnostic thresholds (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). One possible explanation for these discrepancies is the natural variability in esophageal motility and the fact that HRM only captures the instantaneous pressure of the esophageal musculature, which may fluctuate over time as the disease progresses. Alternatively, our observations suggest another hypothesis: the timing of HRM relative to EGD might influence the measured IRP. All three patients underwent HRM 1\u0026ndash;2 days after EGD. Current HRM guidelines specify that manometry should be performed following EGD to rule out structural abnormalities or malignancy, but do not define an optimal interval between procedures\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. In routine practice, HRM is often scheduled the day after EGD to minimize the potential impact of topical anesthetics on the upper esophageal sphincter (UES) pressure.\u003c/p\u003e \u003cp\u003eHowever, considering that pneumatic dilation\u0026mdash;an established treatment for achalasia\u0026mdash;induces muscle relaxation through forceful stretching of the LES\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. However, the effectiveness of treatment decreases over time and requires repeated treatments\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. For patients with achalasia, EGD shows that the cardia is tightly closed and the pressure increases when passing through the EGJ. It is conceivable that the expansion pressure generated by pushing the endoscope body and passing through the cardia when passing through the lower esophagus cause the IRP to decrease temporarily, thereby may resulting in failure to meet the diagnostic criteria during the HRM. Although daily post-EGD HRM assessments to track changes are impractical, our findings suggest that the transient reduction in LES pressure following EGD may lead to an underestimation of the true motility disorder if HRM is performed too soon. In all three cases, IRP increased to diagnostic levels 3\u0026ndash;4 days after EGD. While we cannot confirm whether IRP returned to baseline, this pattern supports our hypothesis. Therefore, we recommend that in suspected achalasia, a resting period of at least 3 days following EGD may be necessary before performing HRM.\u003c/p\u003e \u003cp\u003eFuture studies will also strive to re-examine the HRM of patients with nondiagnostic IRP shortly after EGD to further verify and investigate this phenomenon.\u003c/p\u003e \u003cp\u003eIn summary, we recommend delaying HRM by at least 3 days after EGD in cases where achalasia is suspected. This adjustment in timing may improve diagnostic accuracy and better reflect the underlying esophageal motility disorder.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThis chart clearly illustrates that, in all three cases, the initial HRM performed 1\u0026ndash;2 days after EGD showed IRP values below the diagnostic threshold (IRP\u0026thinsp;\u0026gt;\u0026thinsp;15 mmHg as per Chicago Classification v4.0), whereas the repeat HRM 3\u0026ndash;4 days later showed elevated IRP values that met the criteria for esophageal achalasia.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTiming of HRM (after EGD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIRP (mmHg)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCase 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 day (Initial HRM)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 days (Repeat HRM)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCase 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 day (Initial HRM)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 days (Repeat HRM)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCase 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 day (Initial HRM)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 days (Repeat HRM)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical committee approval was received by the Medical Ethics Committee of the Third People\u0026rsquo;s hospital of Chengdu. (Approval no: [2023]S-No.133).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all three patients for the use of their anonymized clinical data in scientific research and publication. A copy of the written consent is available for review by the Editor of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are not openly available due to reasons of patient privacy and data sensitivity and are available from the corresponding author upon reasonable request. All data are in the controlled access data storage of the Digestive Disease Database of Chengdu Third People\u0026apos;s Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;This work is supported by grants from The Bethune Charity Foundation (No. BCF-LX-XH-20221014-10), and The Third People\u0026apos;s Hospital of Chengdu Intramural Research Project（No.\u0026nbsp;CSY-YN-01-2023-042）\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConcept \u0026ndash; PD, QW; Design \u0026ndash; PD; Supervision \u0026ndash; QW; Resources \u0026ndash; ZY, FT; Data Collection \u0026ndash; PD; Analysis\u0026ndash; PD, KS; Literature Search \u0026ndash; PD; Writing Manuscript \u0026ndash; PD; Critical Review \u0026ndash; QW\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGregersen, et al. \u0026ldquo;Pathophysiology and treatment of achalasia in a muscle mechanical perspective.\u0026rdquo; Annals of the New York Academy of Sciences vol. 1434,1 (2018): 173-184. doi:10.1111/nyas.13711\u003c/li\u003e\n\u003cli\u003ePandolino JE, et al. High-resolution manometry In clinical practice: utilizing pressure topography to classify oesophageal motility abnormalities[J ]. Neurogastroenterol Motil,20021(8):796-806\u003c/li\u003e\n\u003cli\u003eExpert consensus on the diagnosis and treatment of achalasia in China (2020, Beijing) [J]. Chinese Journal of Digestive Endoscopy, 2021, 38(4): 256-275. DOI: 10.3760/cma.j.cn321463-20201208-00950.\u003c/li\u003e\n\u003cli\u003eYadlapati, Rena et al. \u0026ldquo;Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0\u0026copy;.\u0026rdquo; Neurogastroenterology and motility vol. 33,1 (2021): e14058. doi:10.1111/nmo.14058 \u003c/li\u003e\n\u003cli\u003eSalvador R, et al. Manometric pattern progression in esophageal achalasia in the era of high-resolution manometry. Ann Transl Med. 2021 May;9(10):906. doi: 10.21037/atm.2020.03.149. \u003c/li\u003e\n\u003cli\u003eLiu Xiaotong, et al. Diagnosis and treatment of achalasia[J]. Chinese Journal of Internal Medicine, 2022, 61(2): 214-218. DOI: 10.3760/cma.j.cn112138-20211214-00884.\u003c/li\u003e\n\u003cli\u003eCommittee of Gastroesophageal Reflux Disease，Chinese guideline for high resolution esophageal manometry in clinical practice[J].chin J Dig, 2020, 40(1):3-8. DOI:10.3760/cma.j.issn.0254-1432.2020.01.002\u003c/li\u003e\n\u003cli\u003eBorhan-Manesh F, et al. The efficacy of balloon dilation in achalasia is the result of stretching of the lower esophageal sphincter, not muscular disruption. Dis Esophagus. 2016 Apr;29(3):262-6. doi: 10.1111/dote.12314. Epub 2015 Mar 13.\u003c/li\u003e\n\u003cli\u003eMohammed, A. et al. (2022) \u0026lsquo;Pneumatic dilation for esophageal achalasia: patient selection and perspectives\u0026rsquo;, Scandinavian Journal of Gastroenterology, 57(6), pp. 650\u0026ndash;659. doi: 10.1080/00365521.2022.2034940.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"High-resolution manometry, achalasia, EGD interval","lastPublishedDoi":"10.21203/rs.3.rs-8385858/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8385858/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eAim\u003c/strong\u003e Current high-resolution manometry (HRM) guidelines specify that manometry should be performed following esophagogastroduodenoscopy (EGD) but do not define an optimal interval between procedures. To investigate whether the timing of HRM relative to EGD influences diagnostic metrics for achalasia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eWe unexpectedly discovered and analyzed three cases of suspected achalasia where the initial HRM, performed shortly after EGD, failed to meet diagnostic criteria. All patients subsequently underwent a repeat HRM several days after the initial EGD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003eIn all three patients, the follow-up HRM studies demonstrated a significant increase in integrated relaxation pressure (IRP), with values reaching the definitive diagnostic threshold for achalasia, which were not observed in the initial studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e The timing of HRM after EGD can affect IRP measurements and potentially impact diagnostic accuracy for achalasia. We recommend a delay of at least 3 days between EGD and HRM when achalasia is suspected to improve diagnostic yield.\u003c/p\u003e","manuscriptTitle":"The potential of reduction in LES relaxation pressure during endoscopy in three cases of Achalasia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-16 15:11:30","doi":"10.21203/rs.3.rs-8385858/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2d1cae8b-bfd9-44e6-b652-1cb71ef5a3e5","owner":[],"postedDate":"January 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-11T08:58:12+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-16 15:11:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8385858","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8385858","identity":"rs-8385858","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}