INVITED COMMENTARIES
Is Colectomy Still an Option in the Infliximab Era? Daniela Knafelz and Fiammetta Bracci See ‘‘Does Infliximab Prevent Colectomy in Acute and Chronic Active Ulcerative Colitis?’’ by Dan-Nielsen et al on page 768.
Despite the limitation of being a retrospective design with heterogeneous population, this study confirms that IFX is a viable and safe treatment in both chronic active and acute UC in children before considering colectomy. Colectomy is a lifesaving procedure in patients with toxic megacolon or acute surgical abdomen but can lead to serious chronic complications such as pouchitis, faecal incontinence, anastomotic ulcers and stenosis, and female infertility. Therefore, IFX treatment should always be considered before colectomy. Further studies are needed with larger and more homogenous populations, and with a longer follow-up, to establish the efficacy and safety of the treatment in the long term.
REFERENCES
U
lcerative colitis (UC) is a chronic inflammatory bowel disease that can affect both children and adults. Goals of treatment are induction and maintenance of remission to preserve the colon and its functions while minimizing the risks of treatment morbidities. Nevertheless, sometimes colectomy remains the only treatment option, especially in acute attacks. In the first 60 years of the last century, the majority of patients underwent colectomy. The introduction of corticosteroids in the 1960s reduced the colectomy rate by 60%, and recently, the use of cyclosporine reduced it by 80% (1). Recently, it has been demonstrated that infliximab (IFX) is an effective treatment for moderate-to-severe UC, including acute severe colitis. The ACT 1 and ACT 2 randomized trials conducted in adult UC patients (2) showed a colectomy rate of 10% in the IFX-treated arm, versus 17% in the placebo arm. A paediatric multicentre study by Turner et al (3) showed that IFX is effective as salvage medical therapy in 70% to 80% of affected children, reducing short- and long-term colectomy rate. Consequently, IFX has been used as a possible last treatment option, before colectomy in adult and children and has been recommended as rescue therapy for paediatric patients, failing intravenous corticosteroids before colectomy (4). The study of Nielsen et al (5) in this issue of the Journal of Pediatric Gastroenterology and Nutrition is a long-term retrospective multicentre paediatric study on a relatively large cohort of children, with chronic active or acute UC treated with IFX. Primary endpoints of the study were clinical response, risk of surgery, risk of new course of steroids, and safety in IFX treatment. It shows a total response rate (full or partial remission) in 69% of patients and 1 year and 2 year cumulative risk of colectomy, after IFX treatment of 21% and 26%, respectively, with no difference between patients in full or partial remission. It showed a lower risk of colectomy compared with a recent study by Hyams et al (6) in which the 1- and 2-year colectomy rate was 28% and 39%, respectively. It also demonstrated a lower need of subsequent use of corticosteroids after starting IFX, as compared with the Hyams et al (6) study. Adverse effects were reported in 46% of patients, but only 7% discontinuation of the therapy was required; this is in line with previous reports. Received and accepted February 9, 2014. From the Hepatogastroenterology Unit, Bambino Gesu` Children Hospital, Rome, Italy. Address correspondence and reprint requests to Daniela Knafelz, Hepatogastroenterology Unit, Bambino Gesu` Children Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000339
1. Castro M, Papadatou B, Ceriati E, et al. Role of cyclosporin in preventing or delaying colectomy in children with severe ulcerative colitis. Langenbecks Arch Surg 2007;392:161–4. 2. Sandborn WJ, Rutgeerts P, Feagan BG, et al. Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology 2009;137:1250–60. 3. Turner D, Mack D, Leleiko N, et al. Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology 2010;138:2282–91. 4. Turner D, Travis SP, Griffiths AM, et al. Consensus for managing acute severe ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN. Am J Gastroenterol 2011;106:574–88. 5. Dan-Nielsen S, Wewer V, Paerregaard A, et al. Does infliximab prevent colectomy in acute and chronic active ulcerative colitis? J Pediatr Gastroenterol Nutr 2014;58:768–77. 6. Hyams J, Walters TD, Crandall W, et al. Outcome following infliximab therapy in children with ulcerative colitis. Am J Gastroenterol 2010;105869:1430–6.
Value of Endoscopic Mucosal Biopsies in Normal-Appearing Colonic Mucosa Harland Winter and Melvin Heyman See ‘‘Good Agreement Between Endoscopic Findings and Biopsy Reports Supports Limited Tissue Sampling During Pediatric Colonoscopy’’ by Manfredi et al on page 773.
I
n contrast to the practice in adult gastroenterology, obtaining biopsies at the time of an endoscopic procedure has been considered important for the endoscopic evaluation of infants Received March 8, 2014; accepted March 20, 2014. From the Massachusetts General Hospital, Boston, MA. Address correspondence and reprint requests to Harland S. Winter, MD, Massachusetts General Hospital, Boston, MA (e-mail: hwinter@ partners.org). The authors report no conflicts of interest. Copyright # 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000384
676 JPGN Volume 58, Number 6, June 2014 Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
JPGN
Volume 58, Number 6, June 2014
and children. Manfredi et al (1) question this practice in children having a colonoscopy by demonstrating a good correlation between endoscopic and histologic findings. In children with a normal-appearing mucosa, the likelihood of having a normal colonic biopsy is extremely high. Most of the discrepancy between visual and histologic findings occurred when the mucosa appeared to be abnormal, but the pathologist found normal histology. Patients who were immunosuppressed or who had or were suspected of having inflammatory bowel disease were more likely to be in the group with abnormal histology and normal-appearing mucosa. Earlier studies from our group identified intraepithelial eosinophils in the upper gastrointestinal tract in the esophagus of children with symptoms of reflux as an early marker of inflammation (2). Had mucosal biopsies not been obtained from normalappearing mucosa, this biomarker would not have been identified. This recent study raises the issue as to the relevance of colonic mucosal biopsies in children with a normal-appearing mucosa. Because approximately 90% of the subjects in this retrospective, but consecutively enrolled cohort were >20 kg, the observations apply primarily to children >5 years of age. Clinicians should be careful in extrapolating these data to younger children who may be more likely to have mucosal inflammation related to dietary protein intolerance without appreciable endoscopic changes. Mucosal biopsies in young children may also identify a lack of B cells or changes in T-cell subsets that support a diagnosis of an immunoregulatory defect. These conditions are often suspected based on a clinical history of recurrent infections or specific laboratory studies and represent a group in which mucosal biopsies may be diagnostic. For these reasons, additional data in children
Is Colectomy Still an Option in the Infliximab Era? Daniela Knafelz and Fiammetta Bracci See ‘‘Does Infliximab Prevent Colectomy in Acute and Chronic Active Ulcerative Colitis?’’ by Dan-Nielsen et al on page 768.
Despite the limitation of being a retrospective design with heterogeneous population, this study confirms that IFX is a viable and safe treatment in both chronic active and acute UC in children before considering colectomy. Colectomy is a lifesaving procedure in patients with toxic megacolon or acute surgical abdomen but can lead to serious chronic complications such as pouchitis, faecal incontinence, anastomotic ulcers and stenosis, and female infertility. Therefore, IFX treatment should always be considered before colectomy. Further studies are needed with larger and more homogenous populations, and with a longer follow-up, to establish the efficacy and safety of the treatment in the long term.
REFERENCES
U
lcerative colitis (UC) is a chronic inflammatory bowel disease that can affect both children and adults. Goals of treatment are induction and maintenance of remission to preserve the colon and its functions while minimizing the risks of treatment morbidities. Nevertheless, sometimes colectomy remains the only treatment option, especially in acute attacks. In the first 60 years of the last century, the majority of patients underwent colectomy. The introduction of corticosteroids in the 1960s reduced the colectomy rate by 60%, and recently, the use of cyclosporine reduced it by 80% (1). Recently, it has been demonstrated that infliximab (IFX) is an effective treatment for moderate-to-severe UC, including acute severe colitis. The ACT 1 and ACT 2 randomized trials conducted in adult UC patients (2) showed a colectomy rate of 10% in the IFX-treated arm, versus 17% in the placebo arm. A paediatric multicentre study by Turner et al (3) showed that IFX is effective as salvage medical therapy in 70% to 80% of affected children, reducing short- and long-term colectomy rate. Consequently, IFX has been used as a possible last treatment option, before colectomy in adult and children and has been recommended as rescue therapy for paediatric patients, failing intravenous corticosteroids before colectomy (4). The study of Nielsen et al (5) in this issue of the Journal of Pediatric Gastroenterology and Nutrition is a long-term retrospective multicentre paediatric study on a relatively large cohort of children, with chronic active or acute UC treated with IFX. Primary endpoints of the study were clinical response, risk of surgery, risk of new course of steroids, and safety in IFX treatment. It shows a total response rate (full or partial remission) in 69% of patients and 1 year and 2 year cumulative risk of colectomy, after IFX treatment of 21% and 26%, respectively, with no difference between patients in full or partial remission. It showed a lower risk of colectomy compared with a recent study by Hyams et al (6) in which the 1- and 2-year colectomy rate was 28% and 39%, respectively. It also demonstrated a lower need of subsequent use of corticosteroids after starting IFX, as compared with the Hyams et al (6) study. Adverse effects were reported in 46% of patients, but only 7% discontinuation of the therapy was required; this is in line with previous reports. Received and accepted February 9, 2014. From the Hepatogastroenterology Unit, Bambino Gesu` Children Hospital, Rome, Italy. Address correspondence and reprint requests to Daniela Knafelz, Hepatogastroenterology Unit, Bambino Gesu` Children Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000339
1. Castro M, Papadatou B, Ceriati E, et al. Role of cyclosporin in preventing or delaying colectomy in children with severe ulcerative colitis. Langenbecks Arch Surg 2007;392:161–4. 2. Sandborn WJ, Rutgeerts P, Feagan BG, et al. Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology 2009;137:1250–60. 3. Turner D, Mack D, Leleiko N, et al. Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology 2010;138:2282–91. 4. Turner D, Travis SP, Griffiths AM, et al. Consensus for managing acute severe ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN. Am J Gastroenterol 2011;106:574–88. 5. Dan-Nielsen S, Wewer V, Paerregaard A, et al. Does infliximab prevent colectomy in acute and chronic active ulcerative colitis? J Pediatr Gastroenterol Nutr 2014;58:768–77. 6. Hyams J, Walters TD, Crandall W, et al. Outcome following infliximab therapy in children with ulcerative colitis. Am J Gastroenterol 2010;105869:1430–6.
Value of Endoscopic Mucosal Biopsies in Normal-Appearing Colonic Mucosa Harland Winter and Melvin Heyman See ‘‘Good Agreement Between Endoscopic Findings and Biopsy Reports Supports Limited Tissue Sampling During Pediatric Colonoscopy’’ by Manfredi et al on page 773.
I
n contrast to the practice in adult gastroenterology, obtaining biopsies at the time of an endoscopic procedure has been considered important for the endoscopic evaluation of infants Received March 8, 2014; accepted March 20, 2014. From the Massachusetts General Hospital, Boston, MA. Address correspondence and reprint requests to Harland S. Winter, MD, Massachusetts General Hospital, Boston, MA (e-mail: hwinter@ partners.org). The authors report no conflicts of interest. Copyright # 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000384
676 JPGN Volume 58, Number 6, June 2014 Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
JPGN
Volume 58, Number 6, June 2014
and children. Manfredi et al (1) question this practice in children having a colonoscopy by demonstrating a good correlation between endoscopic and histologic findings. In children with a normal-appearing mucosa, the likelihood of having a normal colonic biopsy is extremely high. Most of the discrepancy between visual and histologic findings occurred when the mucosa appeared to be abnormal, but the pathologist found normal histology. Patients who were immunosuppressed or who had or were suspected of having inflammatory bowel disease were more likely to be in the group with abnormal histology and normal-appearing mucosa. Earlier studies from our group identified intraepithelial eosinophils in the upper gastrointestinal tract in the esophagus of children with symptoms of reflux as an early marker of inflammation (2). Had mucosal biopsies not been obtained from normalappearing mucosa, this biomarker would not have been identified. This recent study raises the issue as to the relevance of colonic mucosal biopsies in children with a normal-appearing mucosa. Because approximately 90% of the subjects in this retrospective, but consecutively enrolled cohort were >20 kg, the observations apply primarily to children >5 years of age. Clinicians should be careful in extrapolating these data to younger children who may be more likely to have mucosal inflammation related to dietary protein intolerance without appreciable endoscopic changes. Mucosal biopsies in young children may also identify a lack of B cells or changes in T-cell subsets that support a diagnosis of an immunoregulatory defect. These conditions are often suspected based on a clinical history of recurrent infections or specific laboratory studies and represent a group in which mucosal biopsies may be diagnostic. For these reasons, additional data in children
