- Email: [email protected]
Ultrasonography and Transmural Healing in Crohn’s Disease
Accepted Manuscript Ultrasonography and transmural healing in Crohn´s disease T. Ripollés, J.M. Paredes, E. Moreno-Osset
PII: DOI: Reference:
S1542-3565(15)00165-2 10.1016/j.cgh.2015.02.026 YJCGH 54185
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 17 February 2015 Please cite this article as: Ripollés T, Paredes J, Moreno-Osset E, Ultrasonography and transmural healing in Crohn´s disease, Clinical Gastroenterology and Hepatology (2015), doi: 10.1016/ j.cgh.2015.02.026. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. All studies published in Clinical Gastroenterology and Hepatology are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.
ACCEPTED MANUSCRIPT
Ultrasonography and transmural healing in Crohn´s disease. Ripollés T, Paredes JM, Moreno-Osset E.
RI PT
We do not have any conflict of interest and/or comercial incolvement Editor:
We have read with interest the study by Dr Zorzi and colleagues regarding the
SC
usefulness of a new sonographic quantitative index, sonographic lesion index
for Crohn´s disease (SLIC), to monitor transmural bowel damage in CD patients
M AN U
during anti-TNF therapy (1).
In this study, a significant improvement of SLIC score after induction of antiTNFs therapy (it seems that as monotherapy) was observed only in the responder group of patients. No changes or worsening were observed in the nonresponder group or in the control group (treated with mesalamine) of
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patients. In this study, there were no patients with complete resolution of lesions (transmural healing). In their series 62% of patients had a penetrating or stricturing behavior.
EP
In 2009, our group carried out a study using sonography to assess changes caused by biological therapy and its relationship with the clinical-biological
AC C
response. The sonographic examination performed at 12 weeks, after induction of treatment, showed a significant reduction of sonographic features (bowel wall thickness and color Doppler grade) in 65%, and transmural complications disappeared in 100 % of responder patients group. Complete resolution of sonographic lesions was observed in 29% of responder patients (20% of all patients), compared to none of the patients who did not respond to treatment. In our series there were no patients with stricturing behavior (2).
ACCEPTED MANUSCRIPT
Subsequently, three studies have been published, with Magnetic Resonance (MR) (3) or ultrasound (4, 5), evaluating the usefulness of imaging techniques to detect mucosal healing after anti-TNF and/or immunomodulators treatment, in
RI PT
which our group participated on 2 of them. All these 3 studies showed good correlation between endoscopic mucosal healing and the changes in imaging techniques (transmural healing) (Table 1). All studies included a small
SC
percentage of cases with complicated behavior (srticturing and/or fistulizing). In
the MR study a magnetic resonance index of activity lower than 50 at week 12
M AN U
(cutoff correlated with mucosal healing) occurred in 50% of patients (complicated pattern present only in 26% of the population). Ultrasonographic studies also showed good correlation between the normalization of thickness wall and endoscopic mucosal healing. Transmural healing (defined as thickness <3mm) occurred in 25% of the patients in the study of Castiglione et al
TE D
(complicated pattern in 18% of the population) (3) and in 50% in the study of Moreno et al (complicated pattern in 20%) (4). It is know that complicated behavior of the disease leads to greater structural lesion of the bowel and
EP
therefore, to a lower response to treatment (6), leading to higher probability of having fibrosis (stricturing pattern) (7). Therefore, we suggest that the absence
AC C
of patients with complete resolution of lesions in the Zorzi series may be due to the inclusion a high rate of patients with a complicated behavior. On the other hand, an important question that remains to be studied is whether imaging improvement and/or transmural healing has the same clinical meaning of endoscopic mucosal healing.
RI PT
ACCEPTED MANUSCRIPT
Behaviour
Technique
Imaging index
Endoscopic index
Results
MR
MaRIA
CDEIS
r = 0.51
n=48 Ordás I 2013
B2 6.3% B3 20.8% n=133
Castiglione F 2013
US
wall thickness
TE D
B2 12%
M AN U
Author/year
SC
Table 1: Main characteristics of the studies evaluating the usefulness of imaging techniques in the evaluation of treatment response and mucosal healing in patients with Crohn’s disease.
accuracy=84%
SES-CD
κ = 0.63
CDEIS
κ = 0.73
B3 6% n=30 Moreno N 2014
B2 0%
EP
B3 20%
US
wall thickness
accuracy=86%
AC C
B2= stricturing behavior; B3= penetrating behavior; MR= Magnetic Resonance; MaRIA= Magnetic Resonance Index of Activity; US = Ultrasonography; CDEIS= Crohn’s Disease Endoscopic Index of Severity; SES-CD= Simple Endoscopic Score for Crohn´s disease; r= Spearman rank correlation; κ= Kappa correlation.
References:
ACCEPTED MANUSCRIPT
1- Zorzi F, Stasi E, Gerolamo B, Scarozza P, Biancone L, Zuzzi S, Rossi C, Pallone F, Calabrese E. A sonographic lesion index for Crohn’s disease helps monitor changes in transmural damage during therapy. Clin
RI PT
Gastroenterol Hepatol 2014;2 (12):2071-77. 2- Paredes JM, Ripollés T, Cortés X, Martínez MJ, Barrachina M, Gómez F, Moreno-Osset E. Abdominal sonographic changes after antibody to
SC
tumor necrosis factor (anti-TNF) alpha therapy in Crohn´s disease. Dig Dis Sci 2010; 55:404-10.
M AN U
3- Ordás I, Rimola J, Rodríguez S, Paredes JM, Martínez-Pérez MJ, Blanc E, Arévalo JA, Aduna M, Andreu M, Radosevic A, Ramírez-Morros AM, Pinó S, Gallego M, Jauregui-Amezaga A, Ricart E, Panés J. Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn's disease. Gastroenterology.
TE D
2014 Feb;146(2):374-82.e1. doi: 10.1053/j.gastro.2013.10.055. 4- Castiglione F, Testa A, Rea M, De Palma GD, Diaferia M, Musto D, Sasso F, Caporaso N, Rispo A. Transmural healing evaluated by
EP
bowel sonography in patients with Crohn's disease on maintenance treatment with biologics. Inflamm Bowel Dis 2013;19:1928-34.
AC C
5- Moreno N, Ripollés T, Paredes JM, Ortiz I, Martínez MJ, López A, Delgado F, Moreno-Osset E. Usefulness of abdominal ultrasonography in the analysis of endoscopic activity in patients with Crohn's disease: changes following treatment with immunomodulators and/or anti-TNF antibodies.
J
Crohn’s
Colitis.
10.1016/j.crohns.2014.02.008.
2014
Sep
1;8(9):1079-87.
doi:
ACCEPTED MANUSCRIPT
6- Moran GW, Dubeau MF, Kaplan GG, Yang H, Seow CH, Fedorak RN, Dieleman LA, Barkema HW, Ghosh S, Panaccione R. Phenotypic features of Crohn's disease associated with failure of medical treatment. Gastroenterol
Hepatol
2014
10.1016/j.cgh.2013.08.026.
Mar;
12
(3):
434-42doi:
RI PT
Clin
7- Rieder F, Zimmermann EM, Remzi FH, WJ Sandborn. Crohn’s disease
1084 doi: 10.1136/gutjnl-2012-304353
M AN U
Ripollés T*, Paredes JM** and Moreno-Osset E**.
SC
complicated by strictures: a systematic review. Gut 2013; 62:1072-
*Servicios de Radiología y **Medicina Digestiva. Hospital Universitario Dr Peset. Universidad de Valencia. Valencia. Spain. Address for correspondence:
JM Paredes, MD, Departament of Gastroenterology
Avd. Gaspar Aguilar 90. 46017 Valencia Spain Tel: 34 676124514
AC C
EP
[email protected]
TE D
Hospital Universitario Dr. Peset
PII: DOI: Reference:
S1542-3565(15)00165-2 10.1016/j.cgh.2015.02.026 YJCGH 54185
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 17 February 2015 Please cite this article as: Ripollés T, Paredes J, Moreno-Osset E, Ultrasonography and transmural healing in Crohn´s disease, Clinical Gastroenterology and Hepatology (2015), doi: 10.1016/ j.cgh.2015.02.026. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. All studies published in Clinical Gastroenterology and Hepatology are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.
ACCEPTED MANUSCRIPT
Ultrasonography and transmural healing in Crohn´s disease. Ripollés T, Paredes JM, Moreno-Osset E.
RI PT
We do not have any conflict of interest and/or comercial incolvement Editor:
We have read with interest the study by Dr Zorzi and colleagues regarding the
SC
usefulness of a new sonographic quantitative index, sonographic lesion index
for Crohn´s disease (SLIC), to monitor transmural bowel damage in CD patients
M AN U
during anti-TNF therapy (1).
In this study, a significant improvement of SLIC score after induction of antiTNFs therapy (it seems that as monotherapy) was observed only in the responder group of patients. No changes or worsening were observed in the nonresponder group or in the control group (treated with mesalamine) of
TE D
patients. In this study, there were no patients with complete resolution of lesions (transmural healing). In their series 62% of patients had a penetrating or stricturing behavior.
EP
In 2009, our group carried out a study using sonography to assess changes caused by biological therapy and its relationship with the clinical-biological
AC C
response. The sonographic examination performed at 12 weeks, after induction of treatment, showed a significant reduction of sonographic features (bowel wall thickness and color Doppler grade) in 65%, and transmural complications disappeared in 100 % of responder patients group. Complete resolution of sonographic lesions was observed in 29% of responder patients (20% of all patients), compared to none of the patients who did not respond to treatment. In our series there were no patients with stricturing behavior (2).
ACCEPTED MANUSCRIPT
Subsequently, three studies have been published, with Magnetic Resonance (MR) (3) or ultrasound (4, 5), evaluating the usefulness of imaging techniques to detect mucosal healing after anti-TNF and/or immunomodulators treatment, in
RI PT
which our group participated on 2 of them. All these 3 studies showed good correlation between endoscopic mucosal healing and the changes in imaging techniques (transmural healing) (Table 1). All studies included a small
SC
percentage of cases with complicated behavior (srticturing and/or fistulizing). In
the MR study a magnetic resonance index of activity lower than 50 at week 12
M AN U
(cutoff correlated with mucosal healing) occurred in 50% of patients (complicated pattern present only in 26% of the population). Ultrasonographic studies also showed good correlation between the normalization of thickness wall and endoscopic mucosal healing. Transmural healing (defined as thickness <3mm) occurred in 25% of the patients in the study of Castiglione et al
TE D
(complicated pattern in 18% of the population) (3) and in 50% in the study of Moreno et al (complicated pattern in 20%) (4). It is know that complicated behavior of the disease leads to greater structural lesion of the bowel and
EP
therefore, to a lower response to treatment (6), leading to higher probability of having fibrosis (stricturing pattern) (7). Therefore, we suggest that the absence
AC C
of patients with complete resolution of lesions in the Zorzi series may be due to the inclusion a high rate of patients with a complicated behavior. On the other hand, an important question that remains to be studied is whether imaging improvement and/or transmural healing has the same clinical meaning of endoscopic mucosal healing.
RI PT
ACCEPTED MANUSCRIPT
Behaviour
Technique
Imaging index
Endoscopic index
Results
MR
MaRIA
CDEIS
r = 0.51
n=48 Ordás I 2013
B2 6.3% B3 20.8% n=133
Castiglione F 2013
US
wall thickness
TE D
B2 12%
M AN U
Author/year
SC
Table 1: Main characteristics of the studies evaluating the usefulness of imaging techniques in the evaluation of treatment response and mucosal healing in patients with Crohn’s disease.
accuracy=84%
SES-CD
κ = 0.63
CDEIS
κ = 0.73
B3 6% n=30 Moreno N 2014
B2 0%
EP
B3 20%
US
wall thickness
accuracy=86%
AC C
B2= stricturing behavior; B3= penetrating behavior; MR= Magnetic Resonance; MaRIA= Magnetic Resonance Index of Activity; US = Ultrasonography; CDEIS= Crohn’s Disease Endoscopic Index of Severity; SES-CD= Simple Endoscopic Score for Crohn´s disease; r= Spearman rank correlation; κ= Kappa correlation.
References:
ACCEPTED MANUSCRIPT
1- Zorzi F, Stasi E, Gerolamo B, Scarozza P, Biancone L, Zuzzi S, Rossi C, Pallone F, Calabrese E. A sonographic lesion index for Crohn’s disease helps monitor changes in transmural damage during therapy. Clin
RI PT
Gastroenterol Hepatol 2014;2 (12):2071-77. 2- Paredes JM, Ripollés T, Cortés X, Martínez MJ, Barrachina M, Gómez F, Moreno-Osset E. Abdominal sonographic changes after antibody to
SC
tumor necrosis factor (anti-TNF) alpha therapy in Crohn´s disease. Dig Dis Sci 2010; 55:404-10.
M AN U
3- Ordás I, Rimola J, Rodríguez S, Paredes JM, Martínez-Pérez MJ, Blanc E, Arévalo JA, Aduna M, Andreu M, Radosevic A, Ramírez-Morros AM, Pinó S, Gallego M, Jauregui-Amezaga A, Ricart E, Panés J. Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn's disease. Gastroenterology.
TE D
2014 Feb;146(2):374-82.e1. doi: 10.1053/j.gastro.2013.10.055. 4- Castiglione F, Testa A, Rea M, De Palma GD, Diaferia M, Musto D, Sasso F, Caporaso N, Rispo A. Transmural healing evaluated by
EP
bowel sonography in patients with Crohn's disease on maintenance treatment with biologics. Inflamm Bowel Dis 2013;19:1928-34.
AC C
5- Moreno N, Ripollés T, Paredes JM, Ortiz I, Martínez MJ, López A, Delgado F, Moreno-Osset E. Usefulness of abdominal ultrasonography in the analysis of endoscopic activity in patients with Crohn's disease: changes following treatment with immunomodulators and/or anti-TNF antibodies.
J
Crohn’s
Colitis.
10.1016/j.crohns.2014.02.008.
2014
Sep
1;8(9):1079-87.
doi:
ACCEPTED MANUSCRIPT
6- Moran GW, Dubeau MF, Kaplan GG, Yang H, Seow CH, Fedorak RN, Dieleman LA, Barkema HW, Ghosh S, Panaccione R. Phenotypic features of Crohn's disease associated with failure of medical treatment. Gastroenterol
Hepatol
2014
10.1016/j.cgh.2013.08.026.
Mar;
12
(3):
434-42doi:
RI PT
Clin
7- Rieder F, Zimmermann EM, Remzi FH, WJ Sandborn. Crohn’s disease
1084 doi: 10.1136/gutjnl-2012-304353
M AN U
Ripollés T*, Paredes JM** and Moreno-Osset E**.
SC
complicated by strictures: a systematic review. Gut 2013; 62:1072-
*Servicios de Radiología y **Medicina Digestiva. Hospital Universitario Dr Peset. Universidad de Valencia. Valencia. Spain. Address for correspondence:
JM Paredes, MD, Departament of Gastroenterology
Avd. Gaspar Aguilar 90. 46017 Valencia Spain Tel: 34 676124514
AC C
EP
[email protected]
TE D
Hospital Universitario Dr. Peset