Supplementary appendix

Transcription

1 Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Ang D, Misselwitz B, Hollenstein M, et al. Diagnostic yield of high-resolution manometry with a solid test meal for clinically relevant, symptomatic disorders: serial diagnostic study. Lancet Gastroenterol Hepatol 2017; published online July 3.

2 Supplemental Figures Figure S1: Diagnostic hierarchy for esophageal disorders. Similar to Chicago Classification v3.0, only abnormalities that occurred more than once were classified as a disorder. 1

3 Achalasia EGJ outflow Spasm Hypercontractile Absent Oesophageal Motility Hypertensive Normal Total Achalasia EGJ outflow Spasm Hypercontractile Absent Hypertensive Normal Total Figure S2: Diagnostic agreement between single water swallows (SWS) and solid test meal (STM) in the validation set. The prevalence of all major disorders, except absent peristalsis, was increased with STM. SWS: single water swallows; STM: solid test meal; EGJ: esophagogastric junction; IEM: ineffective Pink tabs: minor/normal HRM with SWS and major disorder on STM Green tabs: major disorder on SWS and minor/normal HRM findings with STM Blue tabs: minor/normal findings on both SWS and STM 2

4 Figure S3: Esophagogastric junction (EGJ) outflow with solid test meal (STM): A 67-year-old female with dysphagia and intermittent "vomiting" of undigested material. Endoscopy and radiology were normal. Acid suppression did not improve symptoms. Panel A shows normal esophageal contractility and normal EGJ function with SWS (IRP 13 mmhg). Panel B demonstrates EGJ outflow with IRP 29.9 mmhg during STM. Symptoms of dysphagia were associated with compartmentalized pressurization (IRP>50mmHg). 3

5 Figure S4: Peristalsis reserve in solid test meal (STM). A 73-year-old male referred for atypical chest pain distinct from his usual angina pain. Cardiac evaluation and endoscopy were normal. 24 hour ph study showed normal acid exposure and negative symptom correlation. Panel A shows ineffective/weak peristalsis with single water swallows (SWS). Panel B demonstrates normal peristalsis with effective clearance during STM indicating preserved physiological reserve. 4

6 Figure S5: Distal esophageal spasm with solid test meal (STM): A 46-year-old female with persistent heartburn with poor response to acid suppression. Endoscopy was normal. 24 hour ph study showed normal esophageal acid exposure. Panel A shows normal, well-coordinated persistalsis and normal EGJ function with SWS (Distal latency DL s). Panel B shows symptomatic spasm with STM. 5

7 Figure S6: Hypercontractile oesophagus with solid test meal (STM): A 49-year-old male with intermittent chest pain after meals, as well as intermittent "vomiting". Endoscopy and radiology were normal. Acid suppression did not improve symptoms. Panel A shows normal peristalsis with single water swallows (SWS). Panel B shows hypercontractile " Jackhammer" esophagus during STM with DCI>8000 mmhg.cm.s 6

8 Figure S7: Esophagogastric junction (EGJ) outflow with solid test meal (STM):A 48-year-old female with progressive dysphagia and chest pain following placement of a gastric band 4 years earlier. Symptoms did not improve despite deflation of the band. Endoscopy and radiology showed normal postoperative findings. Panel A shows normal with single water swallows (SWS). Panel B shows symptomatic at the level of the gastric band 5cm distal to the EGJ. At operation, symptoms were attributed to extensive fibrous reaction to the gastric band. 7

9 Supplementary Table 1. Comparison of HRM metrics used to define abnormal esophageal by the Chicago Classification version 3.0 (CCv3.0) for single water swallows and the modified Chicago Classification for Solid Swallows (CC-S) for the solid test meal. Achalasia Type 1 Achalasia Type 2 Achalasia Type 3 EGJ outflow Spasm Hypercontractile (Jackhammer) Aperistalsis CC-S standard softcooked CC v3.0 ten 5ml single water swallows 6 rice test meal 22 Mean IRP>15mmHg, 100% failed peristalsis 2 swallows with IRP>25mmHg, 1 effective Premature (spastic) contractions with swallow, otherwise unchanged DCI<450mmHg s cm are failed peristalsis Mean IRP > 15 mmhg, no normal peristalsis, panesophageal 2 swallows with IRP > 25 mmhg, 1 effective pressurization (POP) with 20% swallows swallow, otherwise unchanged Mean IRP >15mmHg, no normal peristalsis, premature 2 swallows with IRP >25mmHg, 1 effective (spastic) contractions with 20% wet swallows, may be swallow, otherwise unchanged mixed with POP Mean IRP>15 mmhg, not meeting criteria for achalasia 2 swallows with IRP>25mmHg, not meeting criteria for achalasia Normal mean IRP, 20% premature contractions 2 swallows with DL <4.5s (distal latency <4.5s) two esophageal contractions with unchanged DCI>8000mmHg.s.cm. Hypercontractility may involve or be localized to EGJEGJ Normal mean IRP, 100% swallows with failed unchanged peristalsis DCI <100mmHg.cm.s Esophageal Motility (Weak or fragmented peristalsis **) Mean IRP<15 mmhg and >50% contractions with DCI <450mmHg.cm.s or >5cm breaks in the 20 mmhg isobaric contour. Mean IRP <25mmHg and >80% pharyngeal swallows associated with ineffective esophageal contractions during STM defined by DCI <1000mmH.cm.s or >3cm breaks in the 25mmHg isobaric contour. Hypertensive * (Nutcracker) Esophageal contraction with mean DCI>5000mmHg.s.cm not meeting criteria for hypercontractile esophagus unchanged * based on Chicago Classification version 2 (diagnosis removed from version 3) ** Definition of ineffective esophageal in this study includes both weak and fragmented in this study based on evidence that these two conditions exist together, both have similar effects on bolus transport and both have similar clinical presentation and outcome. 8

10 Supplementary Table 2: Demographic parameters and HRM diagnoses with SWS and STM in all patients in the prospective validation study. The diagnostic yield of major disorders was increased by STM compared to SWS (p=0.010). Group 1 Dysphagia (n=98) Group 2 Reflux symptoms (n=123) Total (n=221) Male/Female (% male) 40/58 (44.9%) 57/66 (46.3%) 97/124 (43.9%) Age SD) (mean Prior surgery (n=5) Achalasia surgery (n=1) Post fundoplication (n=1) Post bariatric (n=1) Achalasia surgery (n=0) Post fundoplication (n=2) 5/221 (2.5%)* Any dys SWS 63(64.3) 65 (52.8) 128(57.9) Any dys STM 78(79.6) 62(50.4) 140 (63.3) Major dys SWS Major dys STM Minor dys SWS Minor dys STM 34 (34.7) 15 (12.2) 49 (22.2) 50(51.0) 23(18.7) 73(33.0) 29 (29.6) 50(40.7) 79(35.8) 28(28.6) 39 (31.7) 67(30.3) SWS: single water swallows; STM: solid test meal; SD: standard deviation * less post-surgical cases included in the validation cohort compared to developmental cohort (p<0.001) 9

11 Achalasia EGJ outflow Spasm Hypercontractile Absent Hypertensive Normal Total Supplementary Table 3. Diagnostic agreement between SWS and STM for patients with dysphagia (development set). Achalasia EGJ outflow Spasm Hypercontractile Absent motilty Hypertensive Normal Total SWS: single water swallows; STM: solid test meal; EGJ: esophago-gastric junction; IEM: ineffective disorder Pink tabs: Minor/normal HRM with SWS and Major Motility Disorder on STM Green tabs: Major disorder on SWS and minor/normal HRM findings with STM Blue tabs: Minor/normal findings on both SWS and STM. Yellow tabs: Similar HRM findings on SWS and STM. 10

12 Achalasia EGJ outflow Spasm Hypercontra ctile Absent Hypertensive Normal Total Achalasia EGJ outflow Spasm Hypercontrac tile Absent Hypertensive Normal Total Supplementary Table 4. Diagnostic agreement between SWS and STM in patients with dysphagia (validation set). Achalasia EGJ outflow Spasm Hypercontractile Absent Hypertensive Normal Total SWS: single water swallows; STM: solid test meal; EGJ: esophago-gastric junction; IEM: ineffective Pink tabs: Minor/normal HRM with SWS and Major Motility Disorder on STM Green tabs: Major disorder on SWS and minor/normal HRM findings with STM Blue tabs: Minor/normal findings on both SWS and STM. Yellow tabs: Similar HRM findings on SWS and STM. Supplementary Table 5. Diagnostic agreement between SWS and STM for patients with suspected reflux (development set). Achalasia EGJ outflow Spasm Hypercontractile Absent Hypertensive Normal Total SWS: single water swallows; STM: solid test meal; EGJ: esophago-gastric junction; IEM: ineffective Pink tabs: Minor/normal HRM with SWS and Major Motility Disorder on STM Green tabs: Major disorder on SWS and minor/normal HRM findings with STM Blue tabs: Minor/normal findings on both SWS and STM. Yellow tabs: Similar HRM findings on SWS and STM. 11

13 Achalasia EGJ outflow Spasm Hypercontractile Absent Hypertensive Normal Total Supplementary Table 6. Diagnostic agreement between SWS and STM in patients with suspected reflux (validation set). Achalasia EGJ outflow Spasm Hypercontractile Absent Hypertensive Normal Total SWS: single water swallows; STM: solid test meal; EGJ: esophago-gastric junction; IEM: ineffective Pink tabs: Minor/normal HRM with SWS and Major Motility Disorder on STM Green tabs: Major disorder on SWS and minor/normal HRM findings with STM Blue tabs: Minor/normal findings on both SWS and STM. Yellow tabs: Similar HRM findings on SWS and STM. 12

14 Achalasia EGJ outflow Spasm Hypercontratile Absent motlity Hypertensive Normal Total Supplementary Table 7. Diagnostic agreement between SWS and STM for group 3 patients with dyspeptic and other non-specific symptoms (development set) Achalasia EGJ outflow Spasm Hypercontractile Absent Hypertensive Normal Total SWS: single water swallows; STM: solid test meal; EGJ: esophago-gastric junction; IEM: ineffective Pink tabs: Minor/normal HRM with SWS and Major Motility Disorder on STM Green tabs: Major disorder on SWS and minor/normal HRM findings with STM Blue tabs: Minor/normal findings on both SWS and STM. Yellow tabs: Similar HRM findings on SWS and STM. 13

15 Supplementary Table 8. Frequency of symptom reporting in Group 1 patients with dysphagia during STM (development set) Diagnosis based on STM Symptoms during STM No symptoms Total no. of patients Major disorder Achalasia 30(71.4%) 12(28.6%) 42 Esophagogastric junction outflow (EGJOO) 127 (90.7%) 13 (9.3%) 140 Aperistalsis 11(100.0%) 0 (0.0%) 11 Spasm 36 (76.6%) 11(23.4%) 47 Hypercontractile 1(100.0%) 0(0.0%) 1 Total major disorder 205 (85.1%) 36 (14.9%) 241 Minor disorder Hypertensive 6(75.0%) 2(25.0%) 8 34(79.1%) 9(20.9%) 43 Total minor disorder 40 (83.3%) 8 (16.7%) 48 Normal 36 (52.9%) 32(47.1%) 68 Supplementary Table 9. Frequency of symptom reporting in Group 2 and 3 patients (combined) with reflux during STM (development set) Diagnosis based on STM Symptoms during STM No symptoms Total no. of patients Major disorder Achalasia 1(50.0%) 1(50%) 2 Esophagogastric junction outflow (EGJOO) 36 (78.2%) 10 (21.8%) 46 Aperistalsis 3 (60.0%) 2 (40.0%) 5 Spasm 17 (73.9%) 6 (26.1%) 25 Hypercontractile 3 (75.0%) 1 (25.0%) 4 Total major disorder 60 (75.0%) 20 (25.0%) 80 Minor disorder Hypertensive 7 (58.3%) 5 (41.7%) (67.4%) 29 (32.6%) 89 Total minor disorder 67 (60.3%) 34 (39.7%) 111 Normal 53 (25.4%) 156 (74.6%)