Assessing the diagnostic yield of achalasia using provocative testing in high‐resolution esophageal manometry: Serial diagnostic study

Chicago Classification v4.0 recommends that if achalasia is demonstrated with single water swallows (SWS); provocative testing is not required. We determine whether provocative testing in patients with suspected achalasia can change manometric findings and reproduce symptoms.


| INTRODUC TI ON
Current high-resolution manometry (HRM) guidelines recommend that the diagnosis of achalasia is based on ten single water swallows (SWS) of 5-10 mL, whereby peristalsis is failed in 100% of swallows and the median integrated relaxation pressure (IRP) is elevated above a threshold (set according to the HRM technology used). 1 Depending on the observed esophageal body pattern of dysmotility, achalasia can be further divided into three subtypes.
In Type I (TI) there is absent peristalsis, in Type II (TII) absent peristalsis is superimposed by panesophageal pressurization events, and in Type III (TIII) premature or spastic esophageal contractions predominate. 1 This combination of abnormalities are responsible for the common presenting symptoms; dysphagia, regurgitation, chest pain, and weight loss, which are the basis for calculating the Eckardt symptom score.
3][4] HRM patterns have been shown to differ when swallowing boluses with different consistencies and volumes in both healthy and symptomatic patients. 2,3,5][8][9][10] As a result, the inclusion of SM and/or free drinking have gained favor in routine investigation 11 such that provocative testing techniques have now become incorporated into the new iteration of CC4. 1 There is now recommendation that provocative testing be included in the assessment of all dysphagia, albeit with the caveat that if achalasia has been identified with SWS, then the diagnosis is secured and provocative testing is not required. 12e subtype of achalasia is important as, not only can outcome following therapy be prognosticated, 13,14 but it can influence therapeutic decision-making.For example, therapy favors peroral endoscopic myotomy (POEM) in TIII achalasia [15][16][17][18] while new evidence suggests that short myotomy can be used in TI or TII achalasia. 19,20rther, in a study published by our group previously, patients with absent peristalsis and normal IRP with SWS, demonstrate obstruction and raised IRP after provocative testing is included. 21Crucially, challenging the esophagus is likely to help reproduce symptoms, thus further underscoring the relevance of the dysmotility identified. 2 As such, we hypothesized that, compared to what is diagnosed with standard SWS, including provocative swallows during the assessment of patients with suspected achalasia might induce a change in the achalasia subtype in some, or reveal persistent/recurrent achalasia where the IRP is normal in SWS.Our secondary aim was to assess the prevalence of reproduced symptoms during provocative testing.
Routine clinical therapeutic decisions which include the manometry report based upon provocative test results and their outcomes were also provided.
where diagnosis is unclear.Further, it can reproduce symptoms.Such findings can personalize and guide effective therapeutic decisions.

K E Y W O R D S
achalasia, eosophago-gastro junction ouflow obstruction, gastroscopy, manometry, timed barium swallow

Evidence before this study
• Chicago Classification version 4.0 has been recently published.
• It recommends that achalasia should be diagnosed using single water swallows on esophageal manometry should only be.
• Typical symptoms are not always reproduced with single water swallows on esophageal manometry.
• Subtyping achalasia is important for clinical decision-making.

Added value of this study
• Numerical and morphological findings remain unchanged in patients diagnosed with Type III achalasia on single water swallows.
• Provocative testing can alter the achalasia subtype.
• Provocative testing can reveal persistent/recurrent achalasia in patients with aperistalsis on single water swallows.
• Typical symptoms were more likely to be reproduced during provocative testing.
• In patients with achalasia, provocative testing may help personalize and guide effective therapeutic decisions.

| Patients
A retrospective cohort study of 127 HRM studies undertaken in a single tertiary referral center in London with a diagnosis of achalasia between September 2016 and January 2022 were recruited.All patients who were eligible, provided consent for their data to be used for this research study.Demographic data, clinical symptoms, timed barium swallow, and endoscopy results were collated.Both patients who were naïve and those with previous achalasia therapy were included.

| High-resolution manometry
HRM was performed using a 36-channel, solid-state system (Manoscan Eso Z; Medtronic).In all patients, a standard protocol was performed whereby 5 mL SWS, rapid drink challenge (RDC), and 200 g of rice were given.Both the water and rice were provided to the patient at room temperature.Swallows were performed in the upright, seated position to replicate normal behavior as per previously published studies. 2,22After SWS, RDC was undertaken wherein patients drank 200mL of water steadily through a straw without stopping when possible.This was then followed by a 1min observation period.Finally, patients ate 200 g of basmati rice at their normal pace, while in some who preferred to avoid rice, at least five 1 × 1cm cubes of bread were swallowed in sequence as previously described. 3Any symptoms reported at the time of testing during all swallow modalities were recorded directly onto the HRM trace.Symptom association was defined as any abnormal motility occurring within ≤10 s of the patient reporting the symptom. 9y abnormalities in esophageal peristalsis were also recorded.ManoView v3.3 was used to analyze HRM data.Patients with elevated median IRP were defined as follows: TI achalasia when there was 100% failed peristalsis; as TII achalasia when ≥20% swallows with panesophageal pressurization; as TIII achalasia when premature/spastic contractions were recorded.In patients with absent peristalsis but a median IRP that was not raised during SWS, a diagnosis of achalasia was given when obstruction was demonstrated with provocative testing.
Impedance bolus height measurement was obtained using the method described for patients with achalasia. 23The average impedance nadir was measured at 3 cm proximal to the esophagogastric junction (EGJ) during the first three swallows of the 200 mL RDC using the impedance topography format.This nadir impedance value was then used as the lower limit for liquid presence in the color scale.The upper limit for liquid presence was then arbitrarily set at the nadir impedance plus 1 kΩ.This was evident by the loss of purple color.At 1 min during expiration and after the RDC, the height of the impedance bolus was then measured with the smart mouse tool from the proximal aspect of the EGJ highpressure zone to the top of the visible purple topographic signal (Appendix 1).
RDC-IRP and solid swallows were evaluated using techniques previously described. 2,22IRP was considered elevated when any of the following were present: median IRP ≥12 mmHg with SWS (CC4), 1 ≥12 mmHg during RDC, or 25 mmHg for at least two swallows during the solid swallows. 2,22,24LES basal pressures and other esophageal body metrics were also recorded in all patients.A change in achalasia subtype was demonstrated when there was consistent change in both numerical and morphological patterns.For example, if there was continuous evidence of panesophageal pressurization during the SM, then this may be suggestive of TII achalasia.

| Timed barium swallow
Timed barium swallow was undertaken in accordance with a standard protocol. 25Patients drank 150-200 mL of barium while standing, with images taken at 1, 2, and 5 min after ingestion.A barium column of ≥5 cm in height above the EGJ retained at 5 min was considered positive. 7,26

| Gastroscopy
Information with regards to the most recent gastroscopy was recorded, including all descriptions of EGJ morphology, anatomy, food residue as well as presence of any mucosal insult.

| Therapy
Total Eckardt score was recorded before and after therapy. 27All therapies were based on clinical information available with the final achalasia subtype being defined by the provocative test result of the HRM study which is the standard at our institution.The choice of therapy was a clinical decision reached by both clinician and patient after the risks and merits of all treatment options were presented; complex cases were discussed at the multidisciplinary team meetings.Therapeutic options included graded pneumatic dilatation at 30 then 35 mm, POEM, Heller myotomy with partial wrap, laparoscopic cardioplasty as well as botulinum toxin (Botox) into the EGJ and/or esophageal body where appropriate.Following therapy, clinical review was performed a median of 4 months [range 1-8 months] after initiation of definitive therapy.TBS was performed a median of 3 months [range 1-6 months] after therapy.

| Analysis
Statistical power to determine sample size was not calculated as the prevalence and change in achalasia subtype diagnosed with provocative testing is unknown.Two previous studies measured against a different primary outcome than this study. 2,24Therefore to control for confounding factors, a large case series of patients specifically referred for suspected achalasia undergoing esophageal manometry, was important to ensure clinical validity and account for any patient heterogeneity.The change in manometric findings was calculated between patients who were diagnosed with achalasia during SWS, RDC, and with SM.Descriptive statistics were used to characterize demographic and manometric findings.To compare which cohorts were more sensitive to provocative testing, patients were grouped based on their SWS diagnosis and again on their SM manometric findings.Parametric data were reported as mean ± SD (standard deviation), and nonparametric data as median [IQR] (Interquartile ratio).Wilcoxon test was used as appropriate to compare continuous variables.Additionally, comparisons between each pair of groups were made using the Mann-Whitney U test.
Chi-squared test was used for categorical data comparison.In all instances, a p value of <0.05 was required for statistical significance.
Pairwise deletion was used for missing data and those who were lost to follow-up.Data were analyzed using SPSS Statistics, v25.0 (IBM Corp).

| RE SULTS
From a total of 197 patients with achalasia during HRM testing, 70 were excluded (described in Figure 1), leaving 127 patients comprising the final study cohort; 50.1 ± 16.0 years of age and 69 (54.3%) male (Table 1).Of those, 116 (91.3%) were able to complete RDC (Figure 2).Overall, 80 patients were naïve and 47 had some form of achalasia therapy undertaken prior to referral.
HRM measurements during SWS and provocative testing are presented in Table 2. TII achalasia exhibited the greatest EGJ outflow obstruction measurements across all modalities (Table 2).

| Numerical and morphological change with rapid drink challenge
Eleven patients either refused or were unable to tolerate the RDC due to fear of symptoms of choking, dysphagia, or vomit.Of the remaining 116 patients who completed the RDC, 90 (77.6%) demonstrated obstruction (RDC-IRP > 12 mmHg), with 88 (75.9%) of these corroborating with SWS.Two out of 12 patients with aperistalsis and normal IRP during SWS exhibited a non-relaxing sphincter during RDC (Figure 2), thus revealing TI achalasia.All patients that did not exhibit obstruction during free drinking demonstrated a nonrelaxing LES with solids.
Impedance bolus height was calculated for patients who were able to tolerate the RDC and whom were diagnosed with achalasia on RDC and/or solids (n = 108; 93.1%).Seven patients did not have concomitant impedance recording during their manometry due to a technical issue with the equipment.For the impedance bolus height calculation during the RDC, the median nadir impedance value was 0.31 kΩ (IQR, 0.20-0.52).The median impedance bolus height at 1 min post-RDC was 10.6 cm (IQR, 6.7-16.0cm).There was an overall statistical difference between the type of achalasia presented during the SWS and the impedance bolus height (p < 0.01), with both TIII achalasia and normal IRP achalasia having lower impedance bolus heights, 6.1 and 7.7 cm, respectively (Figure 2).
Impedance bolus height was also calculated for the excluded patients with normal IRP on SWS, and continued aperistalsis/normal IRP on RDC and with the introduction of a SM (n = 21).This was done to determine whether impedance analysis could reveal further information on patients with continued normal IRP achalasia.In this group of patients, the median nadir impedance value was calculated at 0.41 kΩ (IQR, 0.24-0.89).The median impedance bolus height at 1 min post-RDC was 7.1 cm (IQR, 5.0-4.95).Patients who remained with normal IRP/aperistalsis during the SM, had a significantly higher nadir impedance (p = 0.019), but had no difference in bolus height following the RDC at 1 min (p = 0.15).

| Numerical and morphological manometric changes with solid meal
All 127 patients underwent a SM with either 200 g rice meal (n = 109, 85.8%) or at least five 1 cm cubes of bread (n = 18, 14.2%); the latter being due to patient preference.Overall, manometric findings had changed in 57 (44.9%) patients during the SM (p < 0.001) (Figure 2).Of these, 29 (64.4%) with TI achalasia during SWS demonstrated features of TII achalasia and 1 (2.2%) of TIII during the SM.Also, 11 (19.3%)patients with TII achalasia during SWS demonstrated features of TIII achalasia during the SM (Figure 2).Patients with TI achalasia during SWS were most likely to have a change in subtype with a SM (66.7%), followed by those with TII achalasia (26.3%).On the other hand, of the 13 patients found to have TIII achalasia during SWS, there was no change in manometric findings with the introduction of any form of provocative testing (RDC or solid swallows) (p = 1.0).Overall, only after the introduction of solid swallows did an additional 21 (16.5%)patients demonstrate features of TII achalasia, while 15 (11.8%) patients had manometric findings of TIII achalasia.
Separately, 12 patients with aperistalsis and normal IRP during SWS subsequently exhibited features of achalasia with the introduction of solids (Figure 2).Additional qualitative findings identified during the SM can be seen in Appendix 2, and representative examples of manometric changes in achalasia during the SM are shown in Figure 3.

| Previously treated versus naïve to therapy
In 42 (33.1%)patients, achalasia-directed therapy had been undertaken prior to the most recent manometry (Table 3).There was no difference in symptom presentation or burden between those who had previous therapy and those had not (Median Eckardt    Symptoms were often reproduced during the SM (56.7%), compared to RDC (26.7%) and SWS (6.3%) (Figure 4).Patients with TIII achalasia on SWS were more symptomatic during the SM than during the RDC or SWS (Figure 4) despite demonstrating the same manometric features.For SWS, patients reported an individual symptom, or a combination of dysphagia (n = 6, 4.7%), chest pain (n = 3, 2.4%), regurgitation (n = 1, 0.8%), and/or cough (n = 1, 0.8%).

| Symptoms
For RDC, patients reported either dysphagia (n = 13, 10.2%) and/ or regurgitation (n = 23, 18.1%).Just under half of patients with achalasia reported dysphagia during the SM (n = 58; 45.7%), followed by chest pain (n = 13; 10.0%), regurgitation (n = 10; 7.9%), and cough (n = 2; 1.5%).Gastroscopy, TBS and HRM are considered the standard workup for investigating patients with suspected achalasia 13 ; however no one test is all encompassing with caveats and shortcomings apparent for each modality.The basis of this study is to determine how to improve the diagnostic yield of HRM, which is considered to be the most sensitive and specific test to diagnose achalasia. 1Although initial studies define a high diagnostic yield of HRM based on SWS, and although CC4 concludes that this methodology is sufficient to secure the diagnosis, 1 our study shows that limiting the test to SWS alone can misidentify the achalasia phenotype in a significant proportion of patients.Furthermore, as has been shown when investigating other forms of dysmotility, the simple addition of provocative maneuvers to standard methodology can more accurately subtype achalasia, reveal persistent/recurrent achalasia where otherwise obstruction was not seen, induce symptoms where the significance of the diagnosis is uncertain, and in turn might influence therapeutic decision-making.

| Post-HRM therapy
Provocative testing is easy, cheap, and confirmed to be useful for defining other minor and major motility disorders. 2,3,8,24,28,29r study showed that overall, 44.9% of patients demonstrated different manometric features during the SM, compared to the standard SWS.1][32][33] In our study, RDC was found to be useful in reaffirming the obstruction seen during SWS or uncovering obstruction where IRP was normal (77.6%).The impedance bolus height calculated from RDC also showed reduced columns of fluid in patients with TIII and normal IRP achalasia.A higher nadir impedance was also seen in patients with continued aperistalsis, which can be expected from the poor bolus clearance despite there being no quantifiable obstruction at the OGJ.This is likely due to the lack of coordinated peristalsis that is seen in all types of achalasia.This reconfirms findings from our previous work which highlights how provocative testing can reveal persistent/recurring achalasia in a series of patients with normal IRP and aperistalsis with SWS 21 ; we previously describe how 23 patients with normal IRP but aperistalsis with SWS had achalasia uncovered with free drinking. 21The metrics obtained from the impedance bolus height calculations are also consistent with previously published literature. 23On the other hand, RDC was not as accurate as the SM in identifying all obstruction as 16.2% of the 105 patients with obstruction during SWS were not reproduced with RDC; however this was noted primarily where previous achalasia therapy was undertaken.Woodland et al.
found that RDC-IRP was significantly lower in previously treated patients, and there was little correlation between SWS and TBS results. 34 the other hand, during the SM, although 70 patients had SWS Note: For all the values in bold, the significance level is p 〈 0.05.Abbreviation: TBS, timed barium swallow.

Ang et al. described how achalasia subtype changed in five patients
after solids were introduced with spasm and hypercontractile patterns becoming apparent. 2 achalasia was the most likely to exhibit a change in achalasia subtype (66.7%), followed by TII achalasia (26.3%).On the other hand, patients who had TIII achalasia diagnosed on SWS did not lead

TA B L E 3
Comparison between 42 patients that underwent previous achalasia-directed therapy and 82 that were naïve to therapy.

F I G U R E 4
Frequency of symptoms reproduced with every swallow modality for each achalasia subtype based on the achalasia diagnosis obtained from the solid meal.Patients were more symptomatic during the solid meal.
that in this cohort, greater stimulus of a SM distends the esophageal lumen and activates remaining excitatory postganglionic function, thus exhibiting the pathognomonic TIII manometric pattern.
The most common subtype of achalasia detected during the SM that was missed during SWS was TII achalasia, with 21 (16.5%)additional cases of TII achalasia diagnosed during the SM.Salvador et al. 36 built on the aganglionosis theory described by Goldblum et 37 and speculated that the neuronal loss is progressive from TII to TI achalasia.
They describe that TI achalasia is the end result of an inhibitory neuron network which has been steadily disrupted beyond a critical threshold. 39  tients with TII achalasia compared to TI and TIII other than their higher predilection to weight loss. 41It is suggested that heightened symptoms noted in TII achalasia is likely to be due to its pressurized morphology 35 Patients who exhibited only aperistalsis with SWS but then revealed persistent/recurring obstruction with provocative testing can then have the opportunity for more definitive therapy not available to them had testing ended at SWS.This was described previously by our group in which 29 patients who exhibited only aperistalsis with SWS, had achalasia identified (all subtypes) with provocative testing.These patients underwent achalasia therapy and had similar outcomes to a contemporaneous group of patients in whom IRP was raised with standard SWS. 21is study has limitations.Forty-one patients were excluded as they were unable to complete the SM, and 11 were unable to complete the RDC.Furthermore, it was difficult to recruit normal IRP achalasia patients, as these patients only undergo a manometry if they are particularly symptomatic.However this is real-world clinical evidence, which is generalizable to other esophageal physiology centers.In those who are unable to tolerate provocative maneuvers, traditional forms of assessment remain the standard.
2,24 A control group was not included as previous studies have already clearly shown the effect of including provocative testing with free drinking and solids on minor and major motility disorders in all comers. 2,24Therapeutic decision-making was not blinded to SWS and then the SM.Rather, this was a retrospective assessment of real-time clinical practice, and not based on a randomized trial or blinding.The routine at our institution is to adhere to our previously published protocols such that provocative testing (RDC and solids) are undertaken for all patients, regardless of presentation, with the final HRM report summarizing results including the provocative maneuvers, with an emphasis on where motility patterns were abnormal and where symptoms were reproduced.Furthermore, data collection occurred at least a year after the patient recruitment, therefore minimizing recall bias.Being a tertiary referral center, patients were referred nationally, so posttherapy outcome acquisition was limited to short-term follow-up in some cases (median 4 months).Furthermore, unless symptomatic, patients do not normally consent to routine HRM testing after successful treatment; however, post-procedure Eckardt score and TBS is part of the routine protocol and were included where available within the follow-up (72% and 58%, respectively).
Future studies should prospectively evaluate outcomes in the longer term to affirm longevity of therapy.

| CON CLUS ION
In achalasia, inclusion of provocative testing during manometry, specifically a SM, can reproduce symptoms and can be correlated to manometric abnormalities that could be treatable.This is particularly applicable when IRP is normal during baseline SWS, which often occurs in those with recurrence following prior therapy.A change in achalasia subtype from SWS was demonstrated in more than half of patients following the SM.On the other hand, where TIII achalasia was diagnosed during SWS, provocative testing does not appear to alter achalasia phenotype; although provocative testing can help reaffirm this diagnosis.These findings support the hypothesis that provocative testing can reveal persistent/recurring achalasia where diagnosis is not clear, reproduce relevant symptoms, and correlate to a manometric abnormality, which ultimately helps guide personalized and effective therapeutic decisions.

AUTH O R CO NTR I B UTI O N S
RS and HD played a role in planning and conducting of the study.HD was involved in the acquisition of data.RS, HD, and JE had a role in collecting and/or interpreting data.All were involved in reviewing and amending this manuscript.

F I G U R E 1
Flowchart of patients who were excluded from the study, and those patients included in the solid meal analysis.Diagnosis under the blue dashed line indicates the diagnosis based on the solid meal.TA B L E 1 Demographic data at the time of manometry testing.

F I G U R E 2
In total, 103 out of 127 (81.1%) patients with a median baseline Eckardt score of 6.0 [4.0-9.0]underwent some form of endoscopic or surgical achalasia treatment.All therapies were based upon a mutual decision agreed between clinician and patient, and all were based on clinical information available with the final achalasia subtype being defined by the provocative test result of the HRM study which is the standard at our institution; 46 (44.6%) patients who had achalasia therapy undertaken demonstrated different manometric features with provocative testing.Appendix 3 provides the breakdown of treatments undertaken.Seventeen patients who had TII or TIII achalasia derived following provocative testing and 4 with normal IRP at baseline but obstruction during solids received POEM.Of the 29 remaining patients who exhibited changes in manometric features, 5 underwent Botox, 17 pneumatic dilatation, 6 had a Heller myotomy, and 1 had a laparoscopic cardioplasty.Overall, posttreatment Eckardt score decreased from a median of 6.0 [4.0-9.0] at baseline to 1.0 [0-2.0](p < 0.001) at follow-up (median 4 months [range 1-6 months]) after therapy.All treatments were effective, regardless the achalasia subtype; the decision for therapy was based upon the final achalasia subtype which was defined by the provocative test result of the HRM study.There was no difference in post-therapy Eckardt score outcome between those who exhibited a change in manometric features (0.0 ± 1.0) and those who did not (0.0 ± 1.0) (p = 0.5).Post-therapy TBS with ≥5 cm barium column height at 5 min decreased from a median of 12.7 [5.0-19.7]cm at baseline to 8.0 [0.4-14.7]cm at follow-up (median 2 months [range 1-3 months].There was no difference in post-therapy TBS height between those who exhibited a change in manometric features and those who did not (p = 0.15).Number of patients who demonstrated a change in diagnosis from single water swallows during free drinking (top) and solid meal (bottom), median nadir impedance and impedance bolus height of patients of each type of achalasia diagnosed on 5 mL water swallows (middle).Purple indicates no change in diagnosis.* denotes statistical significance at <0.01.
diagnosis reaffirmed, in 57 (44.9%) the diagnosis changed to a different phenotype of achalasia.Studies have repeatedly demonstrated that the inclusion of solids during HRM has the ability to change diagnosis, and therefore improve the diagnostic yield. 2,11,28,29TA B L E 2 Median, interquartile range (IQR) and p-values (Kruskall-Wallis and chi-squared) of manometric measurements between Type I, Type II, and Type III achalasia.on 5 mL water swallows (Median [IQR]) (mmHg) 25 [19.5-33.Timed barium swallow: patients with ≥5 cm barium column height at 5 min (

F I G U R E 3
Demonstrating representative cases showing the impact of including a solid meal in high-resolution esophageal testing.Three cases showing the impact of including a solid test meal in HRM studies.The upper panel shows (A) normal IRP achalasia with SWS (median IRP 5.2 mmHg) and, (B) in the same patient, Type II achalasia with repeated, prolonged episodes of panesophageal pressurization with max IRP of 36.3 mmHg during the solid test meal.Typical symptoms of dysphagia and chest pain were associated with panesophageal pressurization.The middle panel shows (C) Type I achalasia on SWS (median IRP of 38.5 mmHg) and, (D) in the same patient, Type II achalasia again with panesophageal pressurization with max IRP of 76.1 mmHg.The patient-reported symptoms of dysphagia during the solid test meal.The bottom panel shows (E) Type II achalasia on SWS (median IRP 42.8 mmHg) and, (F) in the same patient, Type III with max IRP of 43.7 mmHg and frequent episodes of hypercontractile peristalsis (max DCI of 29,435.8mmHg s cm) with esophageal shortening of 3-4 cm during the solid test meal.Distal latency was <4.5 seconds in these swallows.All three patients provided informed consent for their manometric images to be used for this research study.DCI, distal contractile integral; HRM, high-resolution manometry; IRP, integrated relaxation pressure; PIP, pressure inversion point; SWS, single water swallows.toany change in diagnosis during provocative testing, thus suggesting no apparent benefit by introducing RDC or SM.We theorize that this is due to preserved ganglionic cells in the myenteric plexus of the esophageal wall, suggesting that an element of peristaltic activity persists regardless of provocation in TIII achalasia.[35][36][37][38]Furthermore we demonstrated provocative testing can unmask TIII achalasia in a cohort of patients.In our study, with the inclusion of a SM, an additional 15 patients (11.8%) were diagnosed with TIII achalasia.We theorize at 5 min) (n, %)

About 56 .
7% of patients experienced their typical symptoms during their SM, therefore reconfirming how provocative testing in achalasia can help reproduce relevant symptoms.Patients with TII achalasia reproduced their typical symptoms more often during the SM manometry, despite there being no significant difference in baseline Eckardt score between TI, TII, and TIII achalasia.This is consistent with a study by Patel et al. who found that there were no differences in symptom presentation (dysphagia, regurgitation, or chest pain) in pa-

Diagnosis based on 5 mL water swallows Demographic data Type I Type II Type III Normal IRP Total
Abbreviations: IRP, integrated relaxation pressure; TBS, timed barium swallow.
Data are presented as frequency and percentage for categorical data, and median and IQR for continuous data.Kruskall-Wallis and chi-squared tests were used.For all the values in bold, the significance level is p 〈 0.05.
This might explain the discordance in diagnosis we find and sug- 35,40st apparent in TII achalasia.35,40Suchfindings underscores the importance of identifying the most appropriate achalasia subtype, as such information can help prognosticate outcome, counsel patients, and help make better therapeutic decisions.