High Resolution Manometry: Optimal Technique and Diagnostic Insights University of Pennsylvania



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High Resolution Manometry: Optimal Technique and Diagnostic Insights University of Pennsylvania Functional Imaging of Esophageal Peristalsis MANOMETRY 4 4 John E. Pandolfino, MD, MSci Department of Medicine Feinberg School of Medicine rthwestern University Manometric port Manometric Sleeve 4 2 2. 4. 8. 8.8..6 7. 3. Functional Imaging of Esophageal Peristalsis HIGH-RESOLUTION MANOMETRY Functional Imaging of Esophageal Peristalsis ESOPHAGEAL PRESSURE TOPOGRAPHY Pressure Clouse Plot 9 4 7 3 Manometric port Manometric port - 2. 4. 8. 8.8..6 7. 3. 2. 4. 8. 8.8..6 7. 3.

What does it add More akin to an imaging modality Defines important anatomical landmarks and abnormalities. Refines measurement of important motor events EGJ relaxation Peristaltic velocity Contractile activity Defines intra-luminal pressurization patterns Esophageal Pressure Topography: The Method: Procedure Device- High-Resolution Manometry Catheter Spans from the pharynx to the stomach with sensor separation of no more than a centimeter within and around the sphincters. Greater than 32 pressure sensors Temporal frequency response matched to the zone of the esophagus The immediate advantages of HRM are: ) a simplified procedural set up with improved sphincter localization, 2) elimination of movement artifact 3) simplified data interpretation and 4) ability to perform more sophisticated analysis of esophageal function. Sierra Scientific Instruments Medical Measurement Systems Sandhill Scientific Inc. Each sensor has 2 pressure sensitive segments Esophageal Pressure Topography: The Method: Procedure Procedure Protocol Studies are done in a supine position and the manometric assembly is positioned transnasally with at least intragastric sensors to optimize EGJ and intragastric recording. The manometric protocol includes at least ten ml swallows and a - minute period to assess basal sphincter pressure in the supine position. Addition of upright and provocative swallows may be helpful in specific patients.» Eliminate vascular Artifact» Increase the yield of eliciting abnormalities not seen in the supine position Practicality Patient tolerance is excellent studies complete in less than 3 minutes Major risks are rare [sore throat, epistaxis] Performed by motility technician/nurse 2 3 EGJ Esophageal Pressure Topography: The Method: Data Analysis a stepwise EPT analysis algorithm is performed: -7 swallows many be adequate First Segment Second Segment UES proximal esophagus Third Segment Proximal trough distal esophagus Distal trough Fourth Segment 2 9 7 3-2

Length along esophagus (cm) The Chicago Classification absent peristalsis some instances of intact or weak peristalsis IRP is normal AND absent peristalsis OR reduced distal latency OR DCI > 8, -cm-s Achalasia Subtypes I,II,III EGJ Outflow Obstruction Achalasia variant versus mechanical obstruction Absent Peristalsis Diffuse esophageal spasm (DES) 2% of swallows with reduced DL(<4.s) Jackhammer esophagus 2% of swallows with DCI > 8, -scm and normal DL The Chicago classification IIIa 2 Step -EGJ Assess EGJ PIP EGJ Morphology Basal pressure 3 I IIIb 2 Rapid contraction 2% of swallows with rapid CFV (>9 cm/s) and normal DL RIP IRP is normal AND Minor Peristaltic Abnormalities *outside of normative range/clinical significance less clear Hypertensive Peristalsis 2% of swallows with DCI >, -s-cm and normal DL Weak Peristalsis 3% of swallows with small (2- cm) breaks in the 2- IBC 2% of swallows with large (> cm) breaks in the 2- IBC 3 3 rmal Frequent Failed Peristalsis 3% of absent swallows 3 6 9 2 time (sec) Pressure () time (sec) Neurogastroenterology and Motility, Vol 24; (Supplement ) March 2. In Press 2 3 4 The Chicago classification Step -EGJ EGJ Relaxation Pressure IRP EGJ relaxation measure HRM nadir 4s Integrated Relaxation Pressure Median [IQR] () 3.6 [.9.8] 7.9 [6.4.] 9th percentile (high) The Chicago classification Step 2 Assess Peristalsis Characterize Peristaltic Integrity Using the IBC set at 2» Intact» Weak» Small versus large» Failed Characterize Contractile Pattern Calculate DCI, Latency and CFV for each swallow» Jackhammer» Hypercontractile» Spasm» Rapid 3

The Chicago classification Step 3 Assess Pressurization Pattern Using the IBC set at 3 -Panesophageal versus Compartmentalized Figure 3 4 Measure: Integrated Relaxation Pressure Panesophageal Pressurization Compartmentalized Pressurization 3 2 2 Length along the esophagus (cm) - 3 - I E I E I E I E I 2 Seconds Validation of the IRP: Flow Permissive Time EGJ pressures during swallowing Videofluoroscopy + Endoclip High Resolution Manometry (HRM) 3D High Resolution Manometry (3D-HRM) Time:.3 s Measuring EGJ relaxation is complicated Must consider anatomy and peristalsis The 4 second IRP provides an integrated measurement of all of the components affecting bolus transit across the EGJ LES, Crural opening, IBP and axial position of LES Thresholds for abnormality are determined by mechanical forces of peristalsis SCJ Elevated Intrabolus pressure Provides important information regarding esophageal emptying > 3 mm Hg supports an outflow obstruction Ghosh SK et al.am J Physiol. 27 Oct;293(4):G878-8 Scherer JR et al. J Gastrointest Surg. 29 Dec;3(2):29-4

Clinical Evolution of Achalasia Assessing clinically relevant phenotypes Clinical Evolution of Achalasia Assessing clinically relevant phenotypes Type I Type II Type III 3 Early Type II or III Chronic Type II/III--I Late Type I Type I achalasia is associated with absent peristalsis and minimal esophageal body pressurization Type II achalasia is associated with pan-esophageal pressurization related to a compression effect. Type III achalasia has evidence of abnormal contractility (spastic) Pandolfino JE, et al. Gastroenterology 28 Response Rates of Achalasia Treatments Patients categorized by pressure topography subtype Refining the IRP Classification Regression Analysis Tree EPT with aperistalsis and an IRP of EndoFLIP with impaired EGJ opening Pandolfino JE, et al. Gastroenterology 28 Salvador R, et al. J Gastrointest Surg Pratap N, et al. J Neurogastroenterol Motil Rohof W, Gut ; 6 (Suppl 3) EPT studies from 22 consecutive patients were studied ( supine water swallows). Mean IRP values and EPT swallow patterns from each study based on Chicago Classification criteria were used as inputs to train a classification and regression tree (CART) model with a MATLAB program. The optimal IRP threshold for distinguishing type I achalasia from absent peristalsis is reduced to due to the low intrabolus pressure associated with absent peristalsis. The optimal IRP threshold for distinguishing type III achalasia from DES is increased ( 7 secondary to the effect of reduced latency on shortening the deglutitive relaxation window to less than 4. seconds. Will be presented-ddw 2

Pressure () Axial position (cm) Axial position (cm) Axial position (cm) Axial position (cm) Type III Achalasia: not all the same Impaired EGJR, 2% spastic contractions EGJ Outflow Obstruction IIIa: Premature contraction Reduced Distal Latency IIIb: Residual contraction rmal Distal Latency some instances of intact or weak peristalsis EGJ Outflow Obstruction Achalasia variant versus mechanical obstruction Distal latency = 3.9 s IBC Distal latency = 6 s IBC 7 IBC Distal latency = 3. 3 IBC Distal latency = s Neurogastroenterology and Motility, Vol 24; (Supplement ) March 2. In Press Increased IRP and IBP with EGJ Outflow Obstruction The Chicago classification 4 3 2 IRP-mean3 IBP-IRP3 IRP IBP-max3 Max-IBP Asymptomatic Control * * * Post-Fundoplication Symptomatic Post- Fundoplication * = p <. vs. asymptomatic control * * * Idiopathic Functional Obstruction absent peristalsis some instances of intact or weak peristalsis Achalasia Subtypes I,II,III EGJ Outflow Obstruction Achalasia variant versus mechanical obstruction Treatment Primarily focused on reducing EGJ outflow through disruption of the LES [Endoscopic/Surgical] Smooth muscle relaxants have minimal efficacy Special Considerations Type I- Absent peristalsis- requires complete obliteration of LES Type II- Panesophageal pressurization- best prognosis Type III- Spasm- will likely required adjunct treatment of spasm Treatment Requires further evaluation to distinguish cause as this could potentially be an achalasia variant or pseudoachalasia. EGD-Biopsies to rule out EoE Recommend EUS if biopsies are negative Special Considerations Possible achalasia variant [trial of medication- Botox] Consider Pneumatic dilation if no response Possible EoE- PPI/ Fluticasone/Diet Old peptic injury- empiric dilation with Balloon or Bougie Hiatus hernia- may require surgery Scherer JR et al. J Gastrointest Surg. 29 Aug 2. Neurogastroenterology and Motility, Vol 24; (Supplement ) March 2. In Press 6

Length along the esophagus (cm) EGJ Outflow Obstruction Measuring EGJ Relaxation Pressure Functional Obstruction due to Hiatal Hernia 2 7 3 EGJ - Pressure () 2 7 LES 3 3 CD - Pressure () Weak Peristalsis IRP. HTN Contraction, IRP 9 Pandolfino et al Surgery. Jan;47():7-64 Elevated CD Relaxation Pressure and Intrabolus Pressure Among HH-Dysphagia Patients Figure 2 Swallow Integrity of the Wavefront 4 4 UES IRP CD () 3 HH-GERD IBP IRP () 3 HH-Dysphagia HH-GERD HH-Dysphagia 2 3 EGJ EGJ relaxation P (transition zone) 3 isobaric contour D 3 s Pandolfino et al Surgery. Jan;47():7-64 7

Peristaltic Defect Gaps in the peristaltic wavefront Pill Esophagitis with Chest Pain Transition Zone Defect Fox M et al. Neurogastroenterol Motil. 24 Oct;6():33-42. Pohl D et al.am J Gastroenterol. 28 Oct;3():44-9 Ghosh SK. Neurogastroenterol Motil. 28 Dec;2(2):283-9 Combined HRM with MII Esophageal pressure Topography with Bolus Transit Large: >2% large breaks in the 2 isobaric contour (> cm in length) Small: >3% small breaks in the 2 isobaric contour (2- cm in length) Large: major 8. cm s IBT 2.2 cm s Small: minor 2.8 cm CBT IBT Impedance isocontour Bolus present Bolus absent 2 3 EGJ Measure: Contraction pattern [DCI] Length UES proximal esophagus Transition Zone Time Contractile Activity Above 2 IBC DCI = contractile activity above 2 X Time X length 9 7 3 - Hypotensive/ Weak Swallow A threshold DCI value of s-cm in EPT plot could be utilized to predict IES. DCI can also distinguish failed swallows using a threshold value of -s-cm Hypertensive/Hypercontractile Hypertensive DCI > -s-cm Hypercontractile- DCI > 8 -s-cm Figure 3 Roman et al. Am J Gastroenterol. Feb;6(2):349-6 2 8

Axial position (cm) Axial position (cm) Axial position (cm) Length along the esophagus (cm) Figure 9 Hypertensive-Hypercontractile Nutcracker heterogeneity Esophagus Based on DCI [ s cm] Contractile Vigor 2 A) rmal B) Hypertensive-Nutcracker C) Hypercontractile-Jackhammer DCI= 32 -s-cm DCI= 68 -s-cm DCI= 2,42 -s-cm 3 Weak peristalsis/ Hypotensive Transition Zone Defects Defined by defect size of first trough Distal (segments 2 and 3)- IEM A threshold DCI value of -s-cm in EPT plot could be utilized to predict IES. DCI can also distinguish failed swallows using a threshold value of The manometric correlate of IEM in EPT is a mixture of swallows with either failed peristalsis or IBC-breaks in the middle and distal pressure troughs. 3 s s s Hypertensive/Hypercontractile Hypertensive- DCI > Hypercontractile- DCI > 8 Figure 4b Measure: Define the CDP 4 Contractile Front Velocity-fast= 3.3 cm/s 2 Stripping wave 8 Contractile Front 6 Velocity-slow =. cm/s Emptying phase 4 3 CDP 2-2 3 Length along the esophagus (cm) Figure Measure: Contraction Pattern [Latency] 9 7 3 9 7 3 Latency measured with conventional manometry EPT: normal latency swallow EPT: short latency swallow 3 s s s s 2s Globular Formation Pandolfino et al. Neurogastroenterol Motil. 29 Dec 27. [Epub] 9

Figure 4 Rapid Contractions rmal Deglutitive Inhibition-rmal Latency Figure 9 Distal Esophageal Nutcracker heterogeneity Spasm Abnormal Deglutitive Inhibition-Abnormal Latency Intact Swallow D Weak Peristalsis Impedance C Spastic Achalasia Distal Esophageal Spasm D Bolus present CBT 3. cm IBT CFV= 3 cm/s CFV= 3 cm/s Bolus absent s s Behar and Biancani, Gastroenterology 993;: Pandolfino JE, et al.gastroenterology Figure 3 Phenotypes of Rapid Contraction A) Rapid Contraction B) Weak Contraction 3 cm/s. cm. cm cm/s cm/s - cm/s 2 cm/s 2.9 s 7. s 2 cm/s 3 3 C) Premature Rapid Contraction D) Premature Contraction Figure 4 Distal Esophageal Spasm Defining Relevant Phenotypes Premature Contractions (n=24) [Distal Latency < 4. sec] 6 7 consecutive patients with clinical EPT studies 9 Patients with rapid propagation Rapid Contractions (n= 67) [CFV > 9cm/sec, rmal Distal Latency] 4 7 2 Bolus Escape 7. cm 3. cm 4 cm/s 8 39 2 3 cm/s 2 6 cm/s 3 3. s 3 4.4 s Achalasia DES Functional EGJ Obstruction Weak peristalsis Weak peristalsis-segmental contraction Hypertensive peristalsis Otherwise rmal Pandolfino JE, et al.gastroenterology Pandolfino JE, et al.gastroenterology

Phenotypes of Rapid Contraction The Chicago Classification absent peristalsis Achalasia Subtypes I,II,III There is a difference between rapid contractions and spastic contractions. Does the contraction occur too early [latency]? Should consider whether contraction is altered by deglutitive inhibition. The effect of peristaltic defects should be considered. Revising criteria may improve treatment outcomes. some instances of intact or weak peristalsis IRP is normal AND absent peristalsis OR reduced distal latency OR DCI > 8, -cm-s EGJ Outflow Obstruction Achalasia variant versus mechanical obstruction Absent Peristalsis Diffuse esophageal spasm (DES) 2% of swallows with reduced DL(<4.s) Jackhammer esophagus 2% of swallows with DCI > 8, -scm and normal DL Rapid contraction 2% of swallows with rapid CFV (>9 cm/s) and normal DL IRP is normal AND Minor Peristaltic Abnormalities *outside of normative range/clinical significance less clear Hypertensive Peristalsis 2% of swallows with DCI >, -s-cm and normal DL Weak Peristalsis 3% of swallows with small (2- cm) breaks in the 2- IBC 2% of swallows with large (> cm) breaks in the 2- IBC Frequent Failed Peristalsis 3% of absent swallows rmal Neurogastroenterology and Motility, Vol 24; (Supplement ) March 2. In Press The Future of Evaluating PPI non-responders Simultaneous HRM-Impedance-pH UES LES relaxation 2 Length along the esophagus (cm) 3 EGJ opening

Peter J. Kahrilas, M.D. rthwestern University NU IRB 2

3