Title:Esophageal motor disorders are frequentduring pre and post lung transplantation.Can they influence lung rejection?

Authors:Constanza Ciriza de los Ríos, FernandoCanga Rodríguez-Valcárcel, Alicia de PabloGafas, Isabel Castel de Lucas, David LoraPablos, Gregorio Castellano Tortajada

DOI: 10.17235/reed.2018.5263/2017Link: PubMed (Epub ahead of print)

Please cite this article as:Ciriza de los Ríos Constanza, CangaRodríguez-Valcárcel Fernando, de PabloGafas Alicia, Castel de Lucas Isabel, LoraPablos David, Castellano Tortajada Gregorio.Esophageal motor disorders are frequentduring pre and post lung transplantation.Can they influence lung rejection? . Rev EspEnferm Dig 2018. doi:10.17235/reed.2018.5263/2017.

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OR 5263

Esophageal motor disorders are frequent during pre and post lung transplantation.

Can they influence lung rejection?

Constanza Ciriza-de-los-Ríos1, Fernando Canga-Rodríguez-Valcárcel1, Alicia de-Pablos-

Gafas1, Isabel Castel-de-Lucas1, David Lora-Pablos2 and Gregorio Castellano-Tortajada1

1Department of Gastroenterology. Hospital Universitario 12 de Octubre. Madrid, Spain.2Clinical Research Unit. IMAS12-CIBERESP. Hospital Universitario 12 de Octubre.

Madrid, Spain

Received: 21/09/2017

Accepted: 02/01/2018

Correspondence: Constanza Ciriza-de-los-Ríos. Department of Gastroenterology.

Hospital Universitario 12 de Octubre. Av. de Córdoba s/n. 28041 Madrid, Spain

e-mail: constanzacarpa@gmail.com

ABSTRACT

Background: lung transplantation (LTx) is a viable option for most patients with end-

stage lung diseases. Esophageal motor disorders (EMD) are frequent in candidates for

LTx, but there is very little data about changes in esophageal motility post-LTx.

Aim: the aim of our study was to assess esophageal motor disorders by high resolution

manometry (HRM) both pre-LTx and six months post-LTx in patients with and without

organ rejection.

Study: HRM (Manoscan®) was performed in 57 patients both pre-LTx and six months

post-LTx. HRM plots were analyzed according to the Chicago classification 3.0.

Results: EMD were found in 33.3% and in 49.1% of patients pre-LTx and post-LTx,

respectively, and abnormal peristalsis was more frequently found post-LTx (p = 0.018).

Hypercontractile esophagus was frequently found post-LTx (1.8% and 19.3% pre-LTx

and post-LTx, respectively). Esophagogastric junction (EGJ) morphology changed

significantly pre-LTx and post-LTx; type I (normal) was more frequent post-LTx (63-2%

and 82.5% respectively, p = 0.007). EMD were more frequent post-LTx in both the non-

rejection and rejection group, although particularly in the rejection group (43.2% and

69.2% respectively, p = 0.09). EMD such as distal spasm, hypercontractile esophagus

and EGJ outflow obstruction were also observed more frequently post-LTx in the

rejection group.

Conclusion: significant changes in esophageal motility were observed pre-LTx and

particularly post-LTx; hypercontractile esophagus was a frequent EMD found post-LTx.

EMD were more frequent in the group of patients that experienced organ rejection

compared to the non-rejection group. EMD leading to an impaired esophageal

clearance should be considered as an additional factor that contributes to LTx failure.

Key words: Esophageal motility disorders. High resolution manometry. Lung

transplantation. Hypercontractile esophagus. Lung rejection.

INTRODUCTION

Lung transplantation (LTx) is a viable option for most patients with end-stage lung

diseases (1). Transplant failure is frequently caused by the development of

bronchiolitis obliterans syndrome (BOS), a devastating complication that accounts for

30% of all deaths within a three-year period post transplantation (1). Risk factors

associated with the development of BOS include cytomegalovirus infection and

positive antibodies to class I HLA. Gastroesophageal reflux disease (GERD) is associated

with other pulmonary diseases such as asthma, cystic and pulmonary fibrosis and

obstructive sleep apnea syndrome (2). Therefore, pH, bile acid and trypsin levels in

GERD have been studied as biomarkers for chronic allograft dysfunction (3). GERD is

also associated with esophageal motor disorders (EMD), although it is not clear if GERD

is the cause or the consequence of the esophageal motility impairment (4). Although

GERD has been extensively studied as a factor associated with LTx rejection, there are

some gaps with regard to the potential contribution to the abnormal motility of the

esophagus. Esophageal dysmotility can impair esophageal clearance and could favor

retrograde movement of the esophageal content to the pharyngeal area. Therefore,

the refluxate material is not necessarily the acid that comes from the stomach. In this

respect, experimental studies performed in rat lung transplant models (WKY-to-F344)

showed that both acid (pH 2.5) and neutralized acid pH (pH 7.4) caused lesions

consistent with obliterative bronchiolitis (5). Findings show that impaired esophageal

peristalsis and hypotensive lower esophageal sphincter (LES) are more prevalent in LTx

candidates with GERD (6) and hypercontractile motor disorders have been reported

post-LTx (7). Patients who have undergone a bilateral lung transplantation or a re-

transplantation have a more pronounced delay in gastric emptying, impaired

esophageal motility and delayed esophageal acid clearance as compared to patients

who had undergone a unilateral lung transplantation (8).

Esophageal high-resolution manometry (HRM) represents an unquestionable advance

in esophageal manometry and allows a better characterization of EMD and

esophagogastric junction (EGJ) morphology (9). The Chicago classifications include the

new data that HRM provides for the study of EMD (10).

The aim of the study was to assess esophageal motor disorders by high resolution

manometry (HRM) both pre-LTx and six months post-LTx, in patients with and without

organ rejection.

MATERIAL AND METHODS

Patients

This was a single-center retrospective analysis of a prospectively-collected database of

57 consecutive patients over 18 years of age referred to our esophageal motility

laboratory both pre-LTx and six months post-LTx, between October 2009 and

November 2016. Inclusion criteria were: a) signed informed consent; 2) a minimum

age of 18 years; and 3) indication for LTx. The exclusion criteria was: a) patients who

refused to sign the informed consent.

Gastrointestinal (GI) symptoms were evaluated both pre and six months post-LTx using

the modified DeMeester Questionnaire that evaluated heartburn, regurgitation and

dysphagia. These were scored between 0-3 (0: none; 1: mild; 2: moderate; 3: very

severe) (11).

Acute rejection was defined as a clinical, radiological or functional episode that was

compatible with a histological demonstration according to the international

classification of the Lung Rejection Study Group, or without histological demonstration

but with a response to the specific treatment for rejection (12). Chronic rejection was

defined according to the international guidelines. This was defined as a drop in forced

expiratory volume in one second (FEV1) < 80% of the maximum volume achieved after

transplant. This was on the condition that other etiologies such as infections, airway

stenosis or native lung complications in single-lung transplant recipients were excluded

(12). Chronic rejection can present at any time after the transplant.

The study was performed following the protocol proposed by the Lung Transplant

Program approved by the Hospital Universitario 12 de Octubre.

HRM protocol

HRM was performed both pre-LTx and six months post-LTx in all patients according to

the protocol established at our hospital. HRM was performed using a solid-state

manometric assembly with 36 circumferential sensors with an outer diameter of 4.2

mm spaced at 1-cm intervals (Given Scientific Instruments Inc., Los Angeles, CA, USA).

The transducers were calibrated at 0 and 300 mmHg by applying an external pressure

prior to recording. The previously described standard protocol was used (13). All

subjects were studied following an overnight fast and after discontinuing medication

within 48 hours (except for immunosuppressant therapy post-LTx) that could affect the

examination results. However, all patients received a double dose of proton pump

inhibitors (PPI) post-LTx as per protocol and when the HRM was performed six months

post-LTx. After calibrating the equipment, the recording probe was introduced nasally

with the patient in the supine position (14). Subsequently, the recording was started

with a 30 second basal period (landmark) with no deglutitions in order to obtain the

sphincter pressures, followed by ten deglutitions of 5 ml every 20 seconds. If the first

landmark were not satisfactory, a second landmark was performed at the end of the

study. Furthermore, if the patient swallowed twice or the interval between swallows

was under 20 seconds, these deglutitions were not considered as valid for the analysis.

The final analysis required ten valid deglutitions (15).

24h pH-monitoring protocol

Twenty-four hours ambulatory pH-monitoring without PPI was carried out pre-LTx. The

sensor was placed 5 cm above the upper limit of the lower esophageal sphincter (LES)

determined by HRM. The study catheter was attached to an ambulatory recorder

(Matla Systems Inc, Madrid, Spain). Post-LTx, pH-monitoring was performed with a

double dose of PPI as per protocol (Lung Transplantation Unit). The proximal sensor

was placed 5 cm above the upper limit of the LES and the distal sensor on the stomach.

Patients were encouraged to carry out their normal diet and daily activities.

Data analysis

Manometric data were analyzed using the Mano ViewTM analysis software version 2.1

(Given Scientific Instruments Inc. Los Angeles, CA, USA) and reanalyzed with the new

version 3.3. Two experienced researchers performed HRM and reviewed manually all

the deglutitions of each patient. Finally, a manometric diagnosis was reached using the

analysis algorithm recommended by the Chicago Classification. Esophageal motor

function (10) was evaluated according to the Chicago Classification v. 3.0 (10).

Subsequently, the EMD were classified into the following subtypes: normal, achalasia,

hypercontractile esophagus, distal esophageal spasm, absent and ineffective peristalsis

(16).

The following manometric measurements were analyzed: basal pressure of the LES

(normal values: 10-35 mmHg; minimum pressure obtained with the sleeve device)

(17), integrated relaxation pressure (IRP) (four seconds IRP normal values [IRP4s]: < 15

mmHg) (10), pressurization presence or absence (9), distal contractile integral (DCI)

(normal values: 450-8,000 mmHgm.s.cm) (10), and distal latency (DL) (normal values: >

4.5 s) (10).

The normal values (thresholds) applied were based on the Chicago Classification,

except for the cut-offs for LES resting pressure, as this was not considered in this

classification. LES was considered as normal (basal pressure was between 10 and 35

mmHg and IRP-4s < 15 mmHg), hypotensive (basal LES pressure was < 10 mmHg and

IRP < 15 mmHg) and hypertensive (basal pressure ≥ 35 and IRP < 15 mmHg).

HRM diagnosis was divided into the following groups: normal, ineffective peristalsis (≥

50% weak and failed contractions; DCI < 450 mmHg.cm.s and DCI < 100 mmHg.cm.s

respectively), absent peristalsis (100% failed contraction and IRP < 15 mmHg), EGJ

outflow obstruction (EGJOO) (IRP-4s ≥ 15 mmHg), achalasia (100% of failed

contractions and IRP ≥ 15 mmHg), distal esophageal spasm (≥ 20% of premature

contractions; distal latency < 4.5 s) and hypercontractile esophagus (≥ 20% of

hypercontractile contractions; DCI ≥ 8000 mmHg.cm.s) (10).

EGJ morphology was classified depending on the distance between the LES and crural

diaphragm (CD) as follows: type I (normal), for distances < 1 cm; type II, for distances

between 1-2 cm; and type III (hiatal hernia), for distances over 2 cm (10,18).

Patients were classified as having GERD when the total time at pH < 4 was over 4.5%

according to the DeMeester reference values when the procedure was performed

without PPI (19) and 1.6% when performed with PPI (20). The association with reflux

symptoms was not used in the final diagnosis for GERD as most patients were

asymptomatic. pH data were not compared pre-LTx and post-LTx.

Statistical analysis

HRM quantitative data were described using the mean and confidence intervals (CI) for

parametric variables and the median and interquartile range (IQR) for non-parametric

variables. Qualitative data were expressed as absolute frequencies. Acute and chronic

rejection patients were grouped for analysis purposes. Data were stratified for patients

as rejection and non-rejection and the distribution was compared with the Mann-

Whitney U test (non-normal distribution) or Chi-squared test (categorical variables) or

Fisher’s exact test, as appropriate. The statistical significance of paired differences

between pre-LTx and post-LTx HRM data was calculated using the Wilcoxon signed

rank test (non-normal distribution) or McNemar’s test (categorical variables). The data

analysis was generated using the IBM SPSS statistics 22 software.

RESULTS

Fifty-seven patients were included and analyzed both pre-LTx and post-LTx. Forty-four

(77.2%) did not experience a rejection, nine (15.8%) had acute rejection and four (7%),

chronic rejection. Most patients had obstructive type end-stage lung disease both in

the non-rejection and rejection groups (53.2% and 46.2%). GI symptoms were very

infrequent and the symptom score was similar in both the pre-LTx and post-LTx

groups. Overall, 17.5% and 15.8% of patients had symptoms pre-LTx and post-LTx,

respectively; heartburn and regurgitation were the most frequent. None of the

patients had dysphagia either pre-LTx or six months post-LTx. However, two patients

presented with dysphagia during follow up after the initial six month period. Patient

characteristics are shown in table 1.

Analyses (pre-LTx vs post-LTx)

HRM parameters and diagnosis are shown in table 2. EMD were found in 33.3% and

49.1% of patients pre-LTx and post-LTx respectively (p = 0.018); hypercontractile

esophagus was the most relevant EMD post-LTx (p = 0.018). Accordingly, DCI was

significantly higher post-LTx (p < 0.001) (Fig. 1). Of the eleven patients with

hypercontractile esophagus post-LTx, three (27.3%) had abnormal pH monitoring, two

(18.2%) had EGJOO and one (9%) had abnormal pH monitoring with EGJOO. There was

no evidence of other possible causes in the remaining five (45.5%) cases.

An EGJ morphology change was observed pre-LTx and post-LTx; type I (normal) was

more predominant post-LTx (63.2% and 82.5% respectively, p = 0.007). Accordingly,

EGJ length was shorter post-LTx due to a decrease in the intrathoracic length.

Hypotensive LES was more frequent pre-LTx than post-LTx (33.3% and 17.5%

respectively, p = 0.017) (Table 2). There were no differences in the frequency of EMD

according to the type of LTx (bilateral or unilateral); 19 (51.4%) patients had bilateral

LTx and ten (50%) patients with unilateral had normal peristalsis (NS).

Analysis rejection vs non-rejection group

EMD were more frequent post-LTx in both the non-rejection and rejection groups, but

particularly in the rejection group (43.2% and 69.2%, respectively; p = 0.09).

Hypercontractile esophagus was observed in 23% of the cases post-LTx in the rejection

group (Table 3). Accordingly, DCI tended to be higher in the rejection group (Fig. 2).

EGJ was more frequently classed as type I (normal) in the non-rejection compared to

the rejection group (86.4% vs 69.2% respectively, NS) (Table 3).

The HRM results were as follows in the nine patients with acute rejection, three cases

had no abnormalities, three had hypercontractile esophagus (one of them had also

EGJOO), one had EGJOO and two, distal spasm. The three patients with

hypercontractile esophagus still had the same disorder one year post-LTx. Two of these

patients presented with dysphagia during follow up after six months and were treated

with endoscopic botulinum toxin injection (Fig. 3). In addition, four patients had

chronic rejection, two had weak peristalsis and one had EGJOO.

DISCUSSION

Patients with end stage lung disease pre-LTx have a high prevalence of EMD and

hypotensive LES with a reported frequency of around 76.6% using HRM (1). We found

a similar frequency in our series of 66.6% (including EMD and hypotensive LES).

According to the Chicago Classification 3.0, the frequency of EMD pre-LTx in our series

was 33.3%, and these alterations increased post-LTx up to 49.1%. The most frequent

disorders found were ineffective peristalsis, hypercontractile esophagus and EGJOO.

Previous studies performed with water perfused manometry have reported dysmotility

post-LTx in up to 44% of the patients. Although the results are not strictly comparable

between conventional and HRM, the authors found similar findings, including

ineffective motility and nutcracker esophagus (21). In addition, we found significant

changes in EGJ morphology pre-LTx and post-LTx; more type I (normal) EGJ was

observed post-LTx, particularly in the non-rejection group. These changes could be

related to the surgical changes and the improvement of pulmonary function. However,

these findings were not present in the rejection group (Table 3).

There is some evidence that demonstrates a link between GERD and LTx rejection

(8,22,23) that can occur early post-LTx (21), but the potential implication of esophageal

dysmotility in LTx rejection has not yet been clarified. The importance of EGJOO for

chronic rejection has been recently reported (24). In our series, EGJOO was observed

pre-LTx in five patients, two related with abnormal acid reflux. The disorder persisted

post-LTx in the same five patients and only one had abnormal pH-monitoring. When

the data was analyzed considering the rejection vs non-rejection group, EGJOO was

more frequent in the rejection group. On the other hand, hypercontractile esophagus

was diagnosed more frequently than expected in the post-LTx group, which was 19.3%

(18.2% in the non-rejection and 23% in the rejection group).

The physiopathology of hypercontractile esophagus remains unclear and different

hypotheses have been suggested, including mechanical EGJOO, occurrence secondary

to reflux disease, primary esophageal muscle hypercontractility (25) and eosinophilic

infiltration into the muscularis propria (26). In this regard, EMD was observed in one

patient four weeks post-LTx, who nevertheless recovered without any specific

treatment besides PPI (7).

In our series, all the patients received double doses of PPI as per protocol post-LTx and

HRM was performed after six months. Therefore, the disorder was not corrected with

PPI use. Furthermore, the small group of patients with complications post-LTx and

EMD were followed up over six months and the disorder persisted in all cases.

Therefore, we do not consider this as a transient problem. It was not possible to clarify

the etiology of the disorder in 45.5% of the patients. In this respect, and according to

previous reports (25), the disorder could have been initiated by neuromuscular stress

induced by surgical trauma and perhaps, complicated by partial vagotomy during LTx

leading to esophageal dysmotility. Some medications such as azithromycin can

influence esophageal motility (27), but none of the patients were under the effects of

this medication during the procedure as this treatment was stopped at least 48 hours

previously.

The mechanism could be related to abnormal acid reflux or EGJOO in the remaining

54.5% of patients. An abnormal pH monitoring result was found in 27.3% of cases.

EGJOO was a possible mechanism in 18.2% of cases with hypercontractile esophagus,

and abnormal GERD was also found in one of these cases. Therefore, some of the

complications post-LTx could be related to GERD and others could be a consequence of

retained material in the esophagus due to an impaired esophageal clearance. A very

recent finding supports our theory, namely, that poor esophageal clearance is due to

an abnormal post-reflux swallow-induced peristaltic wave index associated with

obstructive chronic lung allograft dysfunction (24). PPI treatment is necessary in these

types of patients due to the high prevalence of GERD, although it would not be useful

to prevent the aspiration of esophageal content. Even though antireflux surgery has

been demonstrated to be safe post-LTx and leads to a stabilization of lung function in

patients with reflux, there is no definitive data supporting the hypothesis that it

improves the survival rate (28). On the other hand, antireflux surgery has not

prevented acute rejection episodes (28). Although some other factors can influence

rejection, it is important to appreciate that esophageal dysmotility which can impair

bolus transit, may also contribute to LTx failure.

The main limitation of our study is the small number of patients in the rejection group,

although we still observed significant changes pre-LTx and post-LTx and between the

rejection vs non-rejection group. Another limitation is the fact that HRiM and 24h

pH/impedance was not performed in all of the patients.

In conclusion, significant changes in esophageal motility can be observed pre-LTx and

particularly post-LTx; hypercontractile esophagus is a frequent EMD. EMD were more

frequent in the rejection group compared to the non-rejection group. Esophageal

motility alterations leading to impaired esophageal clearance should be considered as

another factor that might contribute to LTx failure.

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Table 1. Patient characteristics pre-LTx and post-LTx according to the rejection vs

non-rejection groups

Clinical data Non-rejection (n =

44)

Rejection (n =

13)

p-

value

Age (mean [CI 95%], yr)

Pre-LTx

Post-LTx

52.6 (41.7-63.5)

57.4 (46.4-68.3)

55.1 (50.2-59.8)

57.9 (53.1-62.8)

0.962

0.505

Male (n [%]) 28 (49.1%) 8 (61.5%) 0.890

BMI (mean; kg/m2)

Pre-LTx

Post-LTx

24.6 (22.1-27)

24.7 (21.5-27.8)

26.3 (23.9-28.6)

35.7 (23.5-27.9)

0.024

0.025

Abdominal perimeter (mean; cm)

Pre-LTx

Post-LTx

94.5 (88.7-100.2)

92.3 (82.9-101.5)

95.2 (89.6-

100.7)

94.8 (89.1-

100.6)

0.487

0.189

LTx indication (n [%])

Obstructive

COPD

Emphysema

Cystic fibrosis

Bronchiectasis

Fibro emphysema

Restrictive

Scleroderma

Idiopathic pulmonary fibrosis

Pulmonary hypertension

Others (histiocytosis X, etc.)

23 (52.3%)

5 (21.7%)

9 (39.1%)

5 (21.7%)

1 (4.4%)

3 (13%)

13 (29.5%)

1 (7.7)

12 (92.3%)

4 (9.1%)

4 (9.1%)

6 (46.2%)

6 (100%)

0

0

0

0

4 (30.8%)

4 (100%)

0

3 (23%)

0

0.414

DeMeester score (mean)

Pre-LTx 2.8 (0.9-4.5) Nd

Post-LTx 1.9 (0.1-3.6) Nd

GI and extraesophageal symptoms

pre-LTx

None

Heartburn

Heartburn and regurgitation

Hoarnesses

Chest pain

Cough

34 (77.3%)

4 (9.1)

3 (6.8%)

1 (2.3%)

1 (2.3%)

1(2.3%)

13 (100%)

0.611

GI and extraesophageal symptoms

post-LTx

None

Heartburn

Heartburn and regurgitation

Hoarnesses

Chest pain

Cough

36 (81.8%)

3 (6.8%)

2 (4.5%)

0

2 (4.5%)

1 (2.3%)

12 (92.3%)

0

0

0

0

1 (7.7%)

0.318

pH-monitoring pre-LTx*

Normal

Abnormal

Not performed

31 (70.5)

11 (25%)

2 (4.5%)

5 (38.5%)

8 (61.5%)

0

0.019

pH-monitoring post-LTx*

Normal

Abnormal

Not performed

31 (70.5%)

9 (20.5%)

4 (9%)

10 (76.9%)

3 (23.1%)

0

0.966

LTx type (n [%])

Bilateral

Right lung

Left lung

28 (63.6%)

12 (27.3%)

4 (9.1%)

9 (69.2%)

3 (23.1%)

1 (7.7%)

0.933

BMI: body mass index; LTx: lung transplantation; GI: Gastrointestinal; Nd: no data

(patients did not report symptoms). Statistical method: Mann-Whitney U, Chi-squared

test. *Double channel esophageal pH monitoring pre-LTx was performed without PPI

and double channel esophago-gastric pH monitoring post-LTx, with PPI as per protocol.

pH data pre-LTx and post-LTx were not compared.

Table 2. HRM parameters, EGJ morphology and EMD diagnosis pre-LTx and six

months post-LTx

HRM parameter Pre-LTx

Median (IQR)

Post-LTx

Median (IQR)

p-value

LES pressure (mmHg) 11.4 (6.9-18.9) 15.8 (10.7-26.3) < 0.001

IRP (mmHg) 6.9 (3.3-11.5) 7.4 (4.9-12.8) 0.324

EGJ total length (cm) 3.9 (3.4-4.2) 3.5 (3.3-4.1) 0.044

EGJ abdominal length (cm) 2.1 (1.8-2.5) 2.1 (1.9-2.7) 0.677

EGJ thoracic length (cm) 1.6 (1.3-2.3) 1.4 (1.1-1.7) 0.004

DCI (mmHg.cm.s) 1,503 (782.8-2,647.5) 2,559.8 (1,523.2-4,593) < 0.001

Distal latency (s) 6.3 (6-7.3) 7 (6-7.7) 0.029

Intrabolus pressure (mmHg) 15.4 (13-20.7) 17.8 (13.8-24.4) 0.155

LES basal pressure (n, %)

Normal

Hypotensive

Hypertensive

37 (65%)

19 (33.3%)

1 (1.7%)

42 (73.7%)

10 (17.5%)

5 (8.8%)

0.017

EGJ morphology (n, %)

Type I

Type II

Type III

36 (63.2%)

19 (33.3%)

2 (3.5%)

47 (82.5%)

10 (17.5%)

0

0.007

Diagnosis (n, %)

Normal

EMD

Ineffective peristalsis

Absent peristalsis

Hypercontractile

esophagus*

Distal spasm

EGJOO

Achalasia

38 (66.7%)

19 (33.3%)

6 (10.5%)

4 (7%)

1 (1.8%)

3 (5.3%)

5 (8.8%)

0

29 (50.9%)

28 (49.1%)

9 (15.8%)

0

11 (19.3%)

3 (5.3%)

5 (8.8%)

0

0.018

HRM: high-resolution manometry; LES: lower esophageal sphincter; IRP: integral

relaxation pressure; EGJ: esophagogastric junction; DCI: distal contractile integral;

EGJOO: esophagogastric junction outflow obstruction; IQR: interquartile range.

Statistical methods: Wilcoxon signed rank test and McNemar’s test. *Two patients

with hypercontractile esophagus also had EGJOO post-LTx.

Table 3. HRM results with regard to the rejection vs non-rejection group pre-LTx and

six months post-LTx

HRM results Non-rejection (n = 44) Rejection (n = 13)

Pre-LTx Post-LTx* Pre-LTx Post-LTx*

EGJ morphology (n, %)

Type I

Type II

Type III

27 (61.4%)

16 (36.4%)

1 (2.2%)

38 (86.4%)

6 (13.6%)

0

9 (69.2%)

3 (23.1%)

1 (7.7%)

9 (69.2%)

4 (30.8%)

0

Diagnosis (n, %)

Normal

EMD

29 (65.9%)

15 (34.1%)

25 (56.8%)*

19 (43.2%)

9 (69.2%)

4 (30.8%)

4 (30.8%)*

9 (69.2%)

Type of EMD

Ineffective peristalsis

Absent peristalsis

Hypercontractile esophagus

Distal spasm

EGJOO

Achalasia

6 (13.6%)

3 (6.8%)

0 (0%)

2 (4.5%)

4 (9.1%)

0

7 (15.9%)

0

8 (18.2%)

1 (2.3%)

3 (6.8%)

0

0

1 (7.7%)

1 (7.7%)

1 (7.7%)

1 (7.7%)

0

2 (15.4%)

0

3 (23%)

2 (15.4%)

2 (15.4%)

0

HRM: high-resolution manometry; EMD: esophageal motor disorder; EGJOO:

esophagogastric junction outflow obstruction. *Comparison of post-LTx between the

non-rejection and rejection group (normal vs EMD, p = 0.09). Statistical methods: Chi-

squared test or Fisher’s exact test, as appropriate.

Fig. 1. DCI pre-LTx and six months post-LTx.

Fig. 2. DCI pre-LTx and post-LTx in the rejection vs non-rejection groups.

Fig. 3. High resolution manometry (HRM) plot pre-LTx and six months post-LTx. High

resolution impedance manometry (HRiM) was performed three months later to follow

up the esophageal motor disorder (EMD) previously treated with botulinum toxin (at

the level of the esophagogastric junction [EGJ] and in the esophageal body) when the

patient presented dysphagia and also acute rejection. A. HRM plot pre-LTx. B. HRM

plot six months post-LTx with a diagnosis of hypercontractile esophagus and impaired

EGJ relaxation. C. HRiM performed three months later, after treatment with botulinum

toxin. Persistence of EMD and bolus retention can be observed.