Editorials

Uncovering Hidden Information in Achalasia Using Esophageal

Pressure Topography
See Outcomes of treatment for achalasia depend on manometric subtype, by Rohof WO,
Salvador R, Annese V, et al, on page 718. Podcast interview: www.gastro.org/gastropodcast.
Also available on iTunes.

chalasia is the most well-defined esophageal motor

disorder in terms of its presentation, pathogenesis,
and treatment strategy. Patients typically present with
dysphagia, chest pain, and regurgitation; these symptoms
are a manifestation of the 2 main features of the disorder:
impaired lower esophageal sphincter (LES) relaxation and
aperistalsis. Given the fact that one of the main defects in
achalasia focuses on a physiologic obstruction at the LES,
therapy has simply centered on disrupting the sphincter.
The overall success rate for this approach depends on a
number of variables, of which the technique utilized to
reduce the obstruction is probably most important. Pneumatic dilation and surgical myotomy effectively disrupt
the LES and these therapies are comparable and much
more effective than management with botulinum toxin or
smooth muscle relaxants. A recent randomized, multicenter, European trial compared the 2 modalities by assessing the outcome of 200 patients randomized to myotomy with Dor fundoplication or pneumatic dilation.1
The success rates for these approaches after 2 years were
both approximately 90% if one allowed a maximum of 3
dilations to be the equivalent of a single myotomy.
Although the success rate during the European Achalasia Trial was quite high, the overall success rates will
likely be lower outside of a controlled trial. Thus, an
assessment of prognostic features in achalasia has always
been of great interest in the management of this disorder.
Previous studies have focused on a number of potential
candidates, but the main focus of these studies has always
targeted features of the LES. This emphasis is logical
because definitive therapies focus on disrupting this muscle. However, the data describing the prognostic value of
baseline LES pressure or nadir pressure during swallowing
are conflicting.25 Thus, these prognostic variables had
limited data to support clinical decisions and little
thought was given to the manometric variables beyond
the values, which determined the diagnosis.
This had been the status quo until the introduction of
esophageal pressure topography (EPT). This technique
created a paradigm shift where the emphasis moves away
from the sphincter and back toward the esophageal body.
In 2002, Clouse and Staiano6 presented their seminal

work introducing topographic analysis into the consciousness of clinical esophagologists. Their work was met
with lukewarm enthusiasm,7 and I have to admit that I
was not an early adopter of this technique. However, Ray
Clouse encouraged me to broaden my horizons and in
2004 our group obtained our first high-resolution manometry system. At first, this seemed to be an overwhelming challenge and I found myself almost completely ignoring the EPT plots and using the tracing format
exclusively. However, that changed when I recognized my
first type II pattern. As I opened the study, I was intrigued
by the patterns and I immediately thought of the old
adage a picture is worth a thousand words. However, in
my mind this adage was now converted to an EPT plot is
worth a thousand pressure tracings.
EPT allows one to focus on the interactions of pressure
gradients to visualize the mechanical dynamics of esophageal emptying. These visual patterns immediately led to
a better understanding of emptying dynamics in the
esophagus. This was highlighted by the elegant description of the pump gun hypothesis of esophageal emptying in achalasia8 and the subsequent commentary on the
potential role of longitudinal muscle contraction in achalasia.9 One could now visualize how contraction in the
esophagus could manipulate Boyles law to show how a
reduction of esophageal volume owing to contraction
causes a compensatory rise in esophageal pressurization.
Although this could be visualized as isobaric pressurization on tracings, this volumepressure relationship could
never fully be appreciated until EPT.
Building on these new insights, it was conceptualized
that achalasia could now be subtyped into 3 groups based
on obvious patterns of esophageal body pressure patterns.10 The 3 patterns were broadly defined as: Type I,
complete absence of peristaltic contractile activity and
minimal pressurization; type II, absence of peristaltic contractile activity with panesophageal pressurization to a
level 30 mmHg; and type III, evidence of spasm using
conventional criteria. Other results supported the conclusion that type II subtype had better outcomes compared
with the other subtypes and that the type III subtype
seemed to do poorly.1113 These observations made sense
mechanistically, but had limitations in that the study
design was retrospective and the outcome measure not
rigorous enough for more than moderate confidence.
In this issue of GASTROENTEROLOGY, Rohof et al14 present the best evidence that the subtype classification of
achalasia is an important determinant of treatment success. They performed a retrospective analysis of manometric and outcome data collected during the European
GASTROENTEROLOGY 2013;144:681 690

Editorials, continued
Achalasia Trial to determine whether the pre-intervention
subtype could predict outcome. The study utilized validated outcome measures within the framework of a prospective protocol using a large number of patients. Although they used conventional line tracings, their
methodology for defining the subtypes was based on the
findings originating from EPT and thus would not be
possible without this analysis technique.11 Their results
confirmed that after a minimum follow-up period of 2
years the outcomes were significantly better in type II
(96%) than type I (81%) and type III (66%) patients. These
findings are in line with previous work10 and with 3 other
retrospective studies suggesting that the subtypes matter.1113 However, their data do not support an initial
observation that surgical myotomy is associated with better outcomes in types I and III achalasia. This could be
related to the fact that the success rates of both techniques in the European Achalasia Trial were very high and

that the type I patients in this trial did not exhibit severe
dilatation, because this was an exclusion criteria mentioned by the authors.
However, another issue that should be considered is
that the subtype classification that was initially described
is not perfect. The initial classification of achalasia was
heavily dependent on measuring the integrated relaxation
pressure (IRP). This measurement is a surrogate for the
intrabolus pressure driving the esophagogastric junction
(EGJ) open during swallowing and EPT allowed us to
understand that the pressure signal through the EGJ was
much more complex than we could realize using pressure
tracings alone. Such a model ignores the esophageal body
in terms of assessing prognostic value of manometry and
focuses a value of 15 mmHg as the final arbiter of achalasia. This issue was subsequently revisited with the determination that the IRP value should be utilized with a
certain degree of latitude based on the pressure pattern

Figure 1. Characterization of
achalasia subtypes in 2013.
Given the fact that the achalasia
subtypes are defined by patterns
of pressure in the esophageal
body during swallowing, the
classification has evolved further
to focus on these patterns. The
IRP remains an important measurement in the Chicago Classification; however, it should not
be viewed as a dichotomous
value and thresholds can be
modified to compensate for
body function. The main issue in
achalasia is to determine that
a preferential flow gradient through the EGJ does not occur.
This can be supported by the
type II pattern alone or an IRP
15 mmHg in type I achalasia,
where severe dilatation or impaired esophageal body function may not allow sufficient
esophageal body pressurization to overcome the obstruction created by impaired LES
relaxation.
682

Editorials, continued
exhibited in the body of the esophagus.15 Using a classification regression analysis tree model, the IRP threshold
for achalasia could be lowered to a value of 10 mmHg in
patients with absent peristalsis, with the type II pattern
alone being diagnostic (Figure 1).15
Additionally, there are other issues that require further
study. The threshold value of 30 mmHg isobaric contour
for type II was chosen based on the historical relevance of
30 mmHg.16 However, this value likely has some latitude
and the cutoff for distinguishing some remaining esophageal function is likely 30 mmHg. Anecdotally, it seems
that patients with severe dilatation have much lower
esophageal pressures; therefore, the threshold may be lowered to focus on predicting severe dilatation and the
doomed myotomy.17 Another issue that requires some
clarification is focused on the description of the type III
subtype, because there has been confusion regarding the
distinction between type III achalasia and EGJ outflow
obstruction. The achalasia subtypes were initially conceived before the concept of latency was incorporated into
the Chicago classification. Originally, we used the conventional definition and now that we have differentiated
patterns of rapid contraction based on latency, the type III
pattern should be redefined to only include premature
swallows (distal latency, 4.5 seconds).18 Swallows with
rapid contractions and normal latency or swallows with
preserved peristalsis should be categorized as EGJ outflow
obstruction and, once again, may represent achalasia variants as suggested in a recent publication19 (Figure 1). This
is an important distinction, because it is likely that achalasia presenting with an EGJ outflow obstruction pattern
will have a better prognosis when compared with type III
achalasia.

Future Directions
The evolution of high-resolution manometry and
EPT analysis has been rapid and this has been largely
owing to the foundation that was developed using conventional tracing analysis. The Chicago classification was
a direct extension of the conventional classification created by Spechler and Castell,16 with modifications made
based on the fact that we could now measure and visualize
important physiologic and mechanical variables that were
buried between the pressure sensors of conventional manometry. The task at hand is to determine whether these
distinct categories truly matter in clinical practice. Certainly, it seems that the subtypes of achalasia do have
prognostic value. However, we do need outcome data to
determine whether subtypes can inform treatment options. In addition, we also need to explore how other
patterns defined by EPT can be exploited to focus on
disorders beyond 10 water swallows; careful manometric
interpretation of body pressure profiles may be important
in disorders beyond achalasia.

In the end, EPT is a major improvement in manometric

technique because it allows the expression of complex
data sets in a single image. The information presented is
much more helpful than arbitrary dichotomous cutoffs,
which may only confuse matters when the picture tells a
different story. Thus, manometric interpretation using
EPT has evolved more into an art than a strict algorithm
that ignores the big picture. Like any good piece of art,
time will be the judge of how EPT has changed our view
of esophageal motor diseases.

JOHN E. PANDOLFINO
Department of Medicine
Northwestern University
Feinberg School of Medicine
Chicago, Illinois
References
1. Boeckxstaens GE, Annese V, des Varannes SB, et al. Pneumatic
dilation versus laparoscopic Hellers myotomy for idiopathic achalasia. N Engl J Med 2011;364:18071816.
2. Arain MA, Peters JH, Tamhankar AP, et al. Preoperative lower
esophageal sphincter pressure affects outcome of laparoscopic
esophageal myotomy for achalasia. J Gastrointest Surg 2004;8:
328 334.
3. Khajanchee YS, Kanneganti S, Leatherwood AE, et al. Laparoscopic Heller myotomy with Toupet fundoplication: outcomes predictors in 121 consecutive patients. Arch Surg 2005;140:827
833.
4. Eckardt VF, Aignherr C, Bernhard G. Predictors of outcome in
patients with achalasia treated by pneumatic dilation. Gastroenterology 1992;103:17321738.
5. Farhoomand K, Connor JT, Richter JE, et al. Predictors of outcome
of pneumatic dilation in achalasia. Clin Gastroenterol Hepatol
2004;2:389 394.
6. Clouse RE, Staiano A, Alrakawi A, et al. Application of topographical methods to clinical esophageal manometry. Am J Gastroenterol 2000;95:2720 2730.
7. Holloway RH. Topographical clinical esophageal manometry: a
better mousetrap or manometric overkill? Am J Gastroenterol
2000;95:26772679.
8. Tutuian R, Pohl D, Castell DO, et al. Clearance mechanisms of the
aperistaltic oesophagus: the pump gun hypothesis. Gut 2006;
55:584 585.
9. Tipnis NA, Mittal RK. Does longitudinal muscle contraction of the
oesophagus hold important secrets? Gut 2006;55:1208.
10. Pandolfino JE, Kwiatek MA, Nealis T, et al. Achalasia: a new
clinically relevant classification by high-resolution manometry.
Gastroenterology 2008;135:1526 1533.
11. Salvador R, Costantini M, Zaninotto G, et al. The preoperative
manometric pattern predicts the outcome of surgical treatment
for esophageal achalasia. J Gastrointest Surg 2010;14:1635
1645.
12. Pratap N, Reddy DN. Can Achalasia subtyping by high-resolution
manometry predict the therapeutic outcome of pneumatic balloon
dilatation? Authors reply. J Neurogastroenterol Motil 2011;17:
205.
13. Min M, Peng LH, Yang YS, et al. Characteristics of achalasia
subtypes in untreated Chinese patients: a high-resolution manometry study. J Dig Dis 2012;13:504 509.
683

Editorials, continued
14. Rohof WO, Salvador R, Annese V, et al. Outcomes of treatment for
achalasia depend on manometric subtype. Gastroenterology
2013;144:718 725.
15. Lin Z, Kahrilas PJ, Roman S, et al. Refining the criterion for an
abnormal integrated relaxation pressure in esophageal pressure
topography based on the pattern of esophageal contractility using
a classification and regression tree model. Neurogastroenterol
Motil 2012;24:e356 363.
16. Spechler SJ, Castell DO. Classification of oesophageal motility
abnormalities. Gut 2001;49:145151.
17. Orringer MB, Stirling MC. Esophageal resection for achalasia:
indications and results. Ann Thorac Surg 1989;47:340
345.
18. Pandolfino JE, Roman S, Carlson D, et al. Distal esophageal
spasm in high-resolution esophageal pressure topography: defining clinical phenotypes. Gastroenterology 2011;141:469
475.
19. Galey KM, Wilshire CL, Niebisch S, et al. Atypical variants of
classic achalasia are common and currently under-recognized: a

study of prevalence and clinical features. J Am Coll Surg

2011;213:155161.

Reprint requests
Address requests for reprints to: John E. Pandolno, Northwestern
University, Feinberg School of Medicine, Department of Medicine,
676 St Clair St, Suite 1400, Chicago, Illinois 60611-2951. E-mail:
j-pandolno@northwestern.edu
Conicts of interest
This author discloses the following: Given Imaging, (Speaker,
Grant, Consultant), Sandhill Scientic (Consultant, Grant), Medical
Measurement Systems (Consultant).
2013 by the AGA Institute
0016-5085/$36.00
http://dx.doi.org/10.1053/j.gastro.2013.02.017

The Cheesecake Factory: Lessons for Expanding the Menu for Colorectal
Cancer Screening
See Magnetic resonance colonography for
detection of colorectal neoplasia in asymptomatic adults, by Graser A, Melzer A, Lindner E
et al, on page 743.

he last time I visited a Cheesecake Factory, I was

overwhelmed by the size of the menuliterally a
book with binder. I asked myself, Is it better to have a
small menu of limited options, or a large menu that
might fit any taste? Clearly, Cheesecake fans have voted,
and the franchise has many devoted patrons.
What about the menu for colorectal cancer (CRC)
screening? We have recommendations from the MultiSociety Task Force on Colorectal Cancer and the United
States Preventive Services Task Force.1,2 The menu is
based on 2 potential targets of screening: early-stage cancer and important cancer precursor lesions.

Tests That Mainly Detect Cancers

Fecal occult blood tests detect cancers and some
precancerous polyps. Randomized, controlled trials have
demonstrated that guaiac-based tests can identify cancers at
an early and curable stage and lead to both reduced mortality and over time, some cancer prevention.1 The guaiac-based
tests suffer from mediocre detection of cancer (50%), poor
detection of advanced neoplasia (11%), and poor specificity.
In recent years, this menu item has undergone some quality
improvement, with the development of the fecal immunochemical test (FIT), which detects components of human
hemoglobin. Using 1 stool sample, the sensitivity for cancer
is 68%78% and for advanced neoplasia, 26%35% with specificity of 95%.3,4 These operating characteristics are depen684

dent on the manufacturer, the cutoff values for a positive

test, and the number of samples.
Most experts believe that FIT is superior to guaiacbased tests. Most countries with organized screening programs have now adopted FIT, although there remains
some confusion about the appropriate cutoff value. Like
the guaiac test, it must be repeated every 12 years because
of the imperfect sensitivity for cancer; this requirement
for programmatic follow-up necessitates that the primary
care provider or medical system devise a recall plan to
optimize results, which is no simple task.5

Tests That Detect Both Early Cancer

and Cancer Precursors
The second type of CRC screening tests are structural examinations of the colon, which have good sensitivity for both early cancers and most cancer precursor
lesions. We have endoscopic and imaging options. Flexible
sigmoidoscopy has been rigorously studied with three
large randomized controlled trials,6 8 which demonstrate
mortality reduction (26% 43%) and incidence reduction
(21%33%) in the screened sample. However, the benefit
seems to be limited to the distal colon. Despite the evidence that sigmoidoscopy is effective, it has fallen out of
favor in the United States owing to patient preferences
given that sigmoidoscopy examines only part of the colon,
and to poor reimbursement.
Intuitively, colonoscopy should be more effective than
sigmoidoscopy, because it examines the entire colon. In
the absence of randomized trials, cohort and case-control
studies suggest that colonoscopy screening would reduce
mortality from CRC by 65%, with incidence reductions
of 45%77%. Recent studies have raised doubt about the