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Erozkan K, Costedio MM, DeRoss AL. Operative Management of Inflammatory Bowel Disease in Children. Surg Clin North Am 2025; 105:329-356. [PMID: 40015820 DOI: 10.1016/j.suc.2024.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
Inflammatory bowel disease (IBD) encompasses a spectrum of chronic, idiopathic, and progressive inflammatory conditions of the gastrointestinal tract, with Crohn's disease and ulcerative colitis comprising the majority. Both conditions have distinct pathophysiological and clinical characteristics but share common immune-mediated mechanisms. Specific facets of IBD and its management in the pediatric population differ from adult parallels. This article explores the surgical treatments of pediatric IBD, focusing on indications for surgery and perioperative considerations.
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Affiliation(s)
- Kamil Erozkan
- Colorectal Division, Department of General Surgery, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Meagan M Costedio
- Division of Colorectal Surgery, Department of General Surgery, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Anthony L DeRoss
- Cleveland Clinic Children's, Section of Pediatric Surgery, 9500 Euclid Avenue, R3, Cleveland, OH 44195, USA.
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2
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Glenisson M, Bonnard A, Berrebi D, Belarbi N, Viala J, Martinez-Vinson C. Complications and Disease Recurrence After Ileocecal Resection in Pediatric Crohn's Disease: A Retrospective Study. Eur J Pediatr Surg 2024; 34:253-260. [PMID: 36882155 PMCID: PMC11076103 DOI: 10.1055/a-2048-7407] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 12/15/2022] [Indexed: 03/09/2023]
Abstract
OBJECTIVE The aim of this retrospective study was to describe the risk of postoperative recurrence (POR) after ileocecal resection, the occurrence of surgical complications, and identify predictors of these adverse postoperative outcomes in pediatric Crohn's disease (CD). PATIENTS AND METHODS All the children less than 18 years of age with a diagnosis of CD, who underwent primary ileocecal resection for CD between January 2006 and December 2016 in our tertiary center, were considered for inclusion. Factors related to POR were investigated. RESULTS A total of 377 children were followed for CD between 2006 and 2016. During this period, 45 (12%) children needed an ileocecal resection. POR was diagnosed in 16% (n = 7) at 1 year and 35% (n = 15) at the end of the follow-up, with a median follow-up of 2.3 years (Q1-Q3 1.8-3.3). Median duration of the postoperative clinical remission was 1.5 years (range 0.5-2). Multivariate Cox regression analysis identified only young age at diagnosis as a risk factor for POR.In total, 7 of the 43 patients (16%) developed severe postoperative complications, defined as requiring surgical, endoscopic, or radiological intervention. The only risk factor was intraoperative abscess. CONCLUSION Only young age at diagnosis was associated with POR. This information could be useful to develop targeted therapeutic strategies for young CD children. At the end of follow-up with a median follow-up of 2.3 years (Q1-Q3 1.8-3.3), there was no surgical POR: endoscopic dilatation for POR should be considered in order to delay or prevent surgery.
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Affiliation(s)
- M Glenisson
- Department of Pediatric Surgery, Hôpital Universitaire Robert Debré, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris, France
| | - A Bonnard
- Department of Pediatric Surgery, Hôpital Universitaire Robert Debré, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris, France
| | - D Berrebi
- Department of Pediatric Pathology, Hôpital Universitaire Robert Debré, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris, France
| | - N Belarbi
- Department of Pediatric Radiology, Hôpital Universitaire Robert Debré, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris, France
| | - J Viala
- Department of Pediatric Gastroenterology, Hôpital Universitaire Robert Debré, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris, France
| | - C Martinez-Vinson
- Department of Pediatric Gastroenterology, Hôpital Universitaire Robert Debré, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris, France
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3
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Kolho KL, Nikkonen A, Merras-Salmio L, Molander P. The need for surgery in pediatric patients with inflammatory bowel disease treated with biologicals. Int J Colorectal Dis 2024; 39:58. [PMID: 38661931 PMCID: PMC11045629 DOI: 10.1007/s00384-024-04634-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/19/2024] [Indexed: 04/26/2024]
Abstract
PURPOSE Inflammatory bowel disease (IBD) in childhood often presents with a more extensive and more aggressive disease course than adult-onset disease. We aimed to evaluate if biological treatment started in childhood decreases the need for intestinal surgery over time. METHODS This was a retrospective, single-center, cohort study. All pediatric patients with IBD initiated to biological therapy at the Children's Hospital, were included in the study and followed up to the first surgical procedure or re-operation in their adulthood or until 31.12.2021 when ≥ 18 of age. Data were collected from the pediatric registry of IBD patients with biologicals and medical charts. RESULTS A total of 207 pediatric IBD patients were identified [150 with Crohn´s disease (CD), 31 with ulcerative colitis (UC), 26 with IBD unclassified (IBDU)] of which 32.9% (n = 68; CD 49, UC 13, IBDU 6) underwent intestinal surgery. At the end of a median follow-up of 9.0 years (range 2.0-25.9), patients reached a median age of 21.4 years (range 18-36). Patients who had intestinal surgery in childhood were more likely to have IBD-related surgery also in early adulthood. The duration of the disease at induction of the first biological treatment emerged as the only risk factor, with a longer duration in the surgical group than in patients with no surgery. CONCLUSION Despite initiation of biological treatment, the risk of intestinal surgery remains high in pediatric IBD patients and often the need for surgery emerges after the transition to adult IBD clinics.
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Affiliation(s)
- Kaija-Leena Kolho
- Children's Hospital, Helsinki University Hospital HUS and Helsinki University, Helsinki, Finland.
| | - Anne Nikkonen
- Children's Hospital, Helsinki University Hospital HUS and Helsinki University, Helsinki, Finland
| | - Laura Merras-Salmio
- Children's Hospital, Helsinki University Hospital HUS and Helsinki University, Helsinki, Finland
| | - Pauliina Molander
- Abdominal Center, Gastroenterology, Helsinki University Hospital HUS and Helsinki University, Helsinki, Finland
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Carter M, Lim IIP. Surgical management of pediatric Crohn's disease. Semin Pediatr Surg 2024; 33:151401. [PMID: 38615423 DOI: 10.1016/j.sempedsurg.2024.151401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2024]
Abstract
Management of pediatric-onset Crohn's disease uniquely necessitates consideration of growth, pubertal development, psychosocial function and an increased risk for multiple future surgical interventions. Both medical and surgical management are rapidly advancing; therefore, it is increasingly important to define the role of surgery and the breadth of surgical options available for this complex patient population. Particularly, the introduction of biologics has altered the disease course; however, the ultimate need for surgical intervention has remained unchanged. This review defines and evaluates the surgical techniques available for management of the most common phenotypes of pediatric-onset Crohn's disease as well as identifies critical perioperative considerations for optimizing post-surgical outcomes.
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Affiliation(s)
- Michela Carter
- Department of Surgery, Division of General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Irene Isabel P Lim
- Department of Pediatric Surgery, Children's Mercy Hospital, University of Missouri-Kansas City School of Medicine, 2401 Gillham Road, Kansas City, MO 64108, United States.
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Shehada M, McMahon LE. Recurrent Crohn's disease. Semin Pediatr Surg 2024; 33:151403. [PMID: 38593515 DOI: 10.1016/j.sempedsurg.2024.151403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Abstract
Although surgical management of the ileocolic segment in pediatric Crohn's disease is not curative, the main goal of therapy is to allow for growth, adequate nutrition, and age-appropriate development. Recurrent disease at the site of anastomosis presents as a major morbidity. Several factors have been implicated in the development of surgical recurrence though data in the literature is scarce. This review explores the epidemiology of recurrent ileocolic disease following primary surgery, indications for surgical intervention, and techniques reported in the literature. Pediatric data is scarce, and therefore, much of it is extrapolated from adult literature.
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Affiliation(s)
- Mahmoud Shehada
- Department of Surgery, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03756, USA.
| | - Lisa E McMahon
- Division of Pediatric Surgery, Phoenix Children's Hospital, Phoenix, AZ, USA.
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Recurrence rates following ileo-colic resection in pediatric patients with Crohn's disease. Pediatr Surg Int 2023; 39:83. [PMID: 36645480 DOI: 10.1007/s00383-022-05346-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/14/2022] [Indexed: 01/17/2023]
Abstract
BACKGROUND Ileo-colic resection (ICR) is an important therapeutic option for Crohn's disease (CD) patients. There are limited updated data of clinical and endoscopic post-operative recurrence (POR) in pediatric patients with CD for the long run. We aimed to determine recurrence rates following ICR over an extended period of time and asses its risk factors. METHODS This is a single-center retrospective review of 35 patients with CD between the ages of 6 and 17.9 years who required ICR between 2003 and 2021 at Schneider Children Medical Center of Israel. Medical charts were reviewed at different time-points post-ICR. RESULTS Clinical recurrence following ICR was demonstrated in only 11.4% and 28.6% (n = 4, n = 10) in the first two and five years-much lower rates than what was reported so far. We found no specific risk factor that correlated with clinical recurrence, although patients that were treated with early prophylaxis of anti-TNF medications following ICR tend to have less recurrence. CONCLUSIONS We found lower POR following ICR, especially in the first years after surgery-which can be attributed to close surveillance and early medical treatment. Such surveillance seems to improve recurrence rates in the first years following ICR.
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Rintala RJ, Pakarinen MP. Inflammatory Bowel Disease. PEDIATRIC SURGERY 2023:1031-1050. [DOI: 10.1007/978-3-030-81488-5_76] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Spencer EA, Jarchin L, Rolfes P, Khaitov S, Greenstein A, Dubinsky MC. Outcomes of Primary Ileocolic Resection for Pediatric Crohn Disease in the Biologic Era. J Pediatr Gastroenterol Nutr 2021; 73:710-716. [PMID: 34292216 PMCID: PMC8604760 DOI: 10.1097/mpg.0000000000003241] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Current clinical algorithms position surgery as the last option in pediatric Crohn disease (CD). Studies suggest improved outcomes with earlier surgery, but pediatric postoperative outcomes data in the biologic era are limited. We aimed to describe the preoperative management and postoperative outcomes in a pediatric CD cohort who underwent ileocolic resection (ICR) at a tertiary care inflammatory bowel disease center over the last decade. METHODS Single-center, retrospective study of pediatric (<18 years) CD patients who underwent ICR between 2008 and 2019 with primary outcome of rate of endoscopic recurrence (Rutgeerts' >i2) at 2 years post-ICR. Key secondary outcomes included endoscopic remission (Rutgeerts' i0), frequency of 30-day postoperative complications, anthropometric changes, and histologic recurrence. Uni- and multivariable analyses examined associations of clinical/laboratory characteristics with endoscopic recurrence. Factors predictive of 30-day complications were also analyzed. RESULTS Seventy-eight children underwent ICR a median of 17.8 months (interquartile range [IQR] 2.6-53.9) from diagnosis. Median age at diagnosis and surgery was 13.8 (11.1-16.7) and 16.8 years (15.1-17.8), respectively. In the 41 patients with >1 post-operative endoscopy, the rate of endoscopic recurrence was 46% at 2 years (median time to recurrence: 10 [7-20] months). Histologic recurrence was present in 44% in endoscopic remission (κ = 0.11, P = 0.53). Endoscopic recurrence was associated with younger age at diagnosis and longer disease duration. 30-day complications occurred at a rate of 18%; only 1% experienced severe complications. All anthropometric measures significantly improved after surgery. CONCLUSIONS Given the inherent risk of postoperative recurrence associated with age and disease duration, children would benefit from postoperative surveillance and effective prophylaxis.
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Affiliation(s)
| | | | | | - Sergey Khaitov
- Department of Surgery, Mount Sinai Hospital and Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center, New York, NY
| | - Alexander Greenstein
- Department of Surgery, Mount Sinai Hospital and Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center, New York, NY
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9
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Dipasquale V, Antonelli E, Cannavò L, Cavatoi G, Romeo C, Trimarchi G, Navarra G, Romano C. Surgery-Related Quality of Life of Pediatric Patients With Crohn's Disease. Front Pediatr 2020; 8:608370. [PMID: 33392119 PMCID: PMC7773926 DOI: 10.3389/fped.2020.608370] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 11/23/2020] [Indexed: 12/29/2022] Open
Abstract
Objective: Up to 30% of pediatric patients with Crohn's disease (CD) require surgery. The aim of the study was to evaluate long-term health-related quality of life (HRQoL) outcome in children with CD who have had ileocolonic resection. Materials and methods: This was a retrospective cross-sectional study on all pediatric patients who had undergone surgery for CD between January 2015 and December 2017 in the Pediatric Surgery and Gastroenterology Units of the University Hospital of Messina. Surgical treatment was represented by laparoscopic ileocecal resection with latero-lateral anastomosis. Patients were asked to fill in a modified version of the IMPACT III questionnaire made up of 15 closed questions before and after surgery. The questionnaire was scored on a five-point scale with 5 reporting "not a problem" and 1 "a very severe problem." The total score ranged from 15 (worst HRQoL) to 75 (best HRQoL). Frequency of relapses, reoperations, complications during follow-up, and postoperative bowel function were also studied. Results: Data were obtained in 10 patients (9 males), who underwent surgery at a median age of 13.5 years (range 13-18), after a median post-diagnosis period of 2.5 years (range 0-8). Preoperative scores were low in all 4 domains of the questionnaire. Postoperatively, HRQoL measures improved significantly (p < 0.05) about symptoms, school attendance, social and emotional functioning. Overall, nearly all patients were completely satisfied with the surgical outcome. Conclusions: HRQoL is low in CD children referred for possible operation, and surgery may positively affect the overall HRQoL. Collecting HRQoL data provides insight into the impact of treatment on children health status.
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Affiliation(s)
- Valeria Dipasquale
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Enrica Antonelli
- Pediatric Surgery Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Laura Cannavò
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Giorgio Cavatoi
- Pediatric Surgery Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Carmelo Romeo
- Pediatric Surgery Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | | | - Giuseppe Navarra
- Surgical Oncology Division, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Claudio Romano
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
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10
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Wesson DE, Lopez ME, Vogel AM. Surgical Aspects of Inflammatory Bowel Disease in Children. ENCYCLOPEDIA OF GASTROENTEROLOGY 2020:593-601. [DOI: 10.1016/b978-0-12-801238-3.66039-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Abstract
The incidence of paediatric Crohn's disease (CD) and ulcerative colitis (UC) is increasing. Surgical intervention is required during childhood in approximately 25% of children diagnosed with CD, and for 10% of those diagnosed with UC. Although there is evidence that the rate of surgical intervention undertaken in children is decreasing since the introduction of biologic therapy, this may only represent a delay rather than true reversal of the risk of surgery. Surgery for CD is not curative and limited resection is the key principle thus preserving bowel length. For UC, subtotal colectomy is relatively curative; ileo-anal pouch anastomosis can be performed to restore bowel continuity.
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Affiliation(s)
- Arun Kelay
- Department of Paediatric Surgery, University Hospital Southampton, Southampton, UK
| | - Lucinda Tullie
- Department of Paediatric Surgery, University Hospital Southampton, Southampton, UK
| | - Michael Stanton
- Department of Paediatric Surgery, University Hospital Southampton, Southampton, UK
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12
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Zimmerman L, Bousvaros A. The pharmacotherapeutic management of pediatric Crohn's disease. Expert Opin Pharmacother 2019; 20:2161-2168. [PMID: 31574236 DOI: 10.1080/14656566.2019.1659778] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Introduction: Crohn's disease (CD) is a chronic inflammatory condition that can occur throughout the gastrointestinal tract. The aims of treatment of children with CD are to induce and maintain clinical remission of disease, optimize nutrition and growth, minimize adverse effects of therapies, and if possible, achieve mucosal healing.Areas covered: This review summarizes evidence for the various therapeutic options in the treatment of children with CD. Exclusive enteral nutrition, corticosteroids, and biologics may be used for induction of remission. Immunomodulators (thiopurines, methotrexate) and biologics (infliximab, adalimumab) may be employed for maintenance of remission to prevent flares of disease and avoid chronic steroid use. In cases of fibrotic disease, intestinal perforations, or medically refractory, surgery may be the best therapeutic option.Expert opinion: Exclusive enteral nutrition, corticosteroids, and biologics (including anti-TNF inhibitors) may be used for induction of remission in patients with active flare of their disease. Immunomodulators and TNF inhibitors may be used for maintenance of remission. Early use of anti-TNF inhibitors in patients with moderate to severe CD may improve efficacy and prevent penetrating complications of disease. While pediatric data is limited, newer biologics, such as vedolizumab and ustekinumab, are used off-label in anti-TNF refractory disease.
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Affiliation(s)
- Lori Zimmerman
- Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA.,Division of Gastroenterology, Hepatology, and Nutrition, Harvard Medical School, Boston, MA, USA
| | - Athos Bousvaros
- Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA.,Division of Gastroenterology, Hepatology, and Nutrition, Harvard Medical School, Boston, MA, USA
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13
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Quality of life and colorectal function in Crohn's disease patients that underwent ileocecal resection during childhood. Eur J Pediatr 2019; 178:1413-1421. [PMID: 31327075 PMCID: PMC6694081 DOI: 10.1007/s00431-019-03427-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 07/01/2019] [Accepted: 07/08/2019] [Indexed: 12/12/2022]
Abstract
Psychosocial and functional outcomes after intestinal resection in pediatric Crohn's disease (CD) are lacking. Therefore, we (I) assessed health-related quality of life (HRQOL), colorectal function, and satisfaction with surgery and (II) investigated their relationship with surgical outcomes, after ileocecal resection for CD. Crohn's patients that underwent ileocecal resection during childhood were included. HRQOL and colorectal function were assessed using SF-36 and COREFO, respectively, and compared with reference values. Satisfaction was scored on a 5-point Likert scale. In total, 80 patients (50% male, median age 23.0 years) were included. Physical HRQOL was impaired (SF-36 [mean]: CD, 47 vs. general, 54; p < 0.001), while mental HRQOL was similar to that in the general population. Overall colorectal function was impaired (COREFO [mean]: CD, 12.6 vs. normal, 7.2; p < 0.001). Worse colorectal function was associated with increasing clinical disease activity and longer interval since resection. Majority of patients was satisfied with surgery (81% satisfied/very satisfied, 11% neither satisfied nor dissatisfied, 8% dissatisfied/very dissatisfied). Decreased satisfaction with surgery was associated with increased clinical disease activity but not related to colorectal function.Conclusions: Physical HRQOL and colorectal function in CD patients who underwent ileocecal resection during childhood seem impaired and related to adverse surgical outcomes. This emphasizes the need for post-operative monitoring and prophylactic therapies. What is Known: • Up to 25% of pediatric-onset Crohn's disease (CD) patients undergo an intestinal resection within 5 years from diagnosis. • Many children and adults with CD experience disruption of their daily activities and health-related quality of life (HRQOL). What is New: • Physical HRQOL and colorectal function are impaired in patient with CD that underwent ileocecal resection during childhood. • Increasing clinical disease activity, a longer interval since surgery, severe complications related to surgery, and recurrent surgeries are all associated with worse colorectal function.
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14
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Ashton JJ, Mossotto E, Ennis S, Beattie RM. Personalising medicine in inflammatory bowel disease-current and future perspectives. Transl Pediatr 2019; 8:56-69. [PMID: 30881899 PMCID: PMC6382508 DOI: 10.21037/tp.2018.12.03] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Up to 25% of inflammatory bowel disease (IBD) presents during childhood, often with severe and extensive disease, leading to significant morbidity including delayed growth and nutritional impairment. The classical approach to management has centred on differentiation into Crohn's disease (CD) or ulcerative colitis (UC), with subsequent treatment based on symptoms, results and complications. However, IBD is a heterogeneous condition with substantial variation in phenotype, disease course and outcome, so whilst effective treatment exists one size does not fit all. The ability to predict disease course at diagnosis, alongside tailoring medications based on response gives the potential for a more 'personalised approach'. The move to a pre-emptive strategy to prevent IBD-related complications, whilst simultaneously minimising side effects and long-term toxicity from therapy, particularly in those with relatively indolent disease, has the potential to revolutionise care. In very early-onset IBD, personalised approaches to diagnosis and management have become the standard of treatment enabling clinicians to significantly alter the outcomes of the few children with monogenic disease. However, the promise of discoveries in genomics, microbiome and transcriptomics in paediatric IBD has not yet translated to clinical application for the vast majority of patients. Despite this, the opportunity presents itself to apply data gathered at diagnosis and follow-up to predict which patients are likely to progress to complicated disease, which will respond well and which will require additional therapy. Using complex mathematics and innovative, cutting-edge machine learning (ML) techniques gives the potential to use this data to develop personalised clinical care algorithms to treat patients more effectively, reduce toxicity and improve outcome. In this review, we will consider current management of paediatric IBD, discuss how precision medicine is making inroads into clinical practice already, examine the contemporary studies applying data to stratify patients and explore how future management may be revolutionised by personalisation with clinical, genomic and other multi-omic data.
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Affiliation(s)
- James J Ashton
- Department of Paediatric Gastroenterology, Southampton Children's Hospital, Southampton, UK.,Department of Human Genetics and Genomic Medicine, University of Southampton, Southampton, UK
| | - Enrico Mossotto
- Department of Human Genetics and Genomic Medicine, University of Southampton, Southampton, UK.,NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK
| | - Sarah Ennis
- Department of Human Genetics and Genomic Medicine, University of Southampton, Southampton, UK
| | - R Mark Beattie
- Department of Paediatric Gastroenterology, Southampton Children's Hospital, Southampton, UK
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15
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Afratis NA, Klepfish M, Karamanos NK, Sagi I. The apparent competitive action of ECM proteases and cross-linking enzymes during fibrosis: Applications to drug discovery. Adv Drug Deliv Rev 2018; 129:4-15. [PMID: 29627371 DOI: 10.1016/j.addr.2018.03.004] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 02/11/2018] [Accepted: 03/13/2018] [Indexed: 12/12/2022]
Abstract
Progressive loss of organ function in most organs is associated with fibrosis, a tissue state associated with abnormal matrix buildup. If highly progressive, the fibrotic process eventually leads to organ failure and death. Fibrosis is a basic connective tissue lesion defined by the increase in the amount of fibrillar extracellular matrix (ECM) components in a tissue or organ. In addition, intrinsic changes in important structural cells can induce the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix-producing myofibroblasts. ECM enzymes belonging to the family of matrix metalloproteinases (MMPs) and lysyl oxidases (LOXs) play a crucial role in ECM remodeling and regeneration. MMPs have a catalytic role in degradation of ECM, whereas LOX/LOXLs mediate ECM, especially collagen, cross-linking and stiffening. Importantly, enzymes from both families are elevated during the fibrotic response to tissue injury and its resolution. Yet, the apparent molecular competition or antagonistic activities of these enzyme families during the various stages of fibrosis is often overlooked. In this review, we discuss the diverse roles of MMPs and LOX/LOXL2 in chronic organ fibrosis. Finally, we review contemporary therapeutic strategies for fibrosis treatment, based on neutralization of MMP and LOX activity, as well as the development of novel drug delivery approaches.
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Affiliation(s)
- Nikolaos A Afratis
- Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - Mordehay Klepfish
- Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - Nikos K Karamanos
- Biochemistry, Biochemical Analysis & Matrix Pathobiology Res. Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras 26500, Greece
| | - Irit Sagi
- Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel.
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16
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Abstract
Pediatric Crohn disease is characterized by clinical and endoscopic relapses. The inflammatory process is considered to be progressive and may lead to strictures, fistulas, and penetrating disease that may require surgery. In addition, medically refractory disease may be treated by surgical resection of inflamed bowel in an effort to reverse growth failure. The need for surgery in childhood suggests severe disease and these patients have an increased risk for recurrent disease and potentially more surgery. Data show that up to 55% of patients had clinical recurrence in the first 2 years after initial surgery. The current clinical report on postoperative recurrence in pediatric Crohn disease reviews the risk factors for early surgery and postoperative recurrence, operative risk factors for recurrence, and prevention and monitoring strategies for postoperative recurrence. We also propose an algorithm for postoperative management in pediatric Crohn disease.
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17
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Ashton JJ, Ennis S, Beattie RM. Early-onset paediatric inflammatory bowel disease. THE LANCET CHILD & ADOLESCENT HEALTH 2017; 1:147-158. [PMID: 30169204 DOI: 10.1016/s2352-4642(17)30017-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2017] [Revised: 06/08/2017] [Accepted: 06/14/2017] [Indexed: 12/27/2022]
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Anti-TNFα Treatment After Surgical Resection for Crohn's Disease Is Effective Despite Previous Pharmacodynamic Failure. Inflamm Bowel Dis 2017; 23:791-797. [PMID: 28426458 DOI: 10.1097/mib.0000000000001050] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The outcome of patients with Crohn's disease who failed anti-tumor necrosis factor alpha (anti-TNFα) therapy despite adequate serum drug levels (pharmacodynamic failure) is unclear. We aimed to assess such pediatric patients who underwent intestinal resection and were re-treated with the same anti-TNFα agent postoperatively. METHODS Pediatric patients with Crohn's disease who underwent intestinal resection and were treated with anti-TNFα agents postoperatively were assessed retrospectively. Patients were stratified to those with preoperative anti-TNFα pharmacodynamic failure and those with no preoperative anti-TNFα treatment. RESULTS A total of 53 children were included, 18 with pharmacodynamic failure and 35 controls. Median age at intestinal resection was 14.8 years with 23 (43%) girls. The median time from intestinal resection to anti-TNFα initiation was 8 months (interquartile range 4-14 months). At the time of postoperative anti-TNFα initiation there were no differences in clinical, laboratory, and anthropometric measures between groups. Similar proportions of patients from both groups were in clinical remission on anti-TNFα treatment after 12 months and at the end of follow-up (1.8 years, interquartile range, 1-2.9 years): 89% versus 88.5% and 83% versus 80% for pharmacodynamic failure patients and controls, respectively; P = 0.9. No significant differences were observed at 14 weeks and 12 months of postoperative anti-TNFα treatment including endoscopic remission rate and fecal calprotectin. Both groups significantly improved all measures during postoperative anti-TNFα treatment. CONCLUSIONS Pediatric patients with Crohn's disease who failed anti-TNFα therapy despite adequate drug levels and underwent intestinal resection can be re-treated with the same agent for postoperative recurrence with high success rate similar to that of anti-TNFα naive patients.
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Amil-Dias J, Kolacek S, Turner D, Pærregaard A, Rintala R, Afzal NA, Karolewska-Bochenek K, Bronsky J, Chong S, Fell J, Hojsak I, Hugot JP, Koletzko S, Kumar D, Lazowska-Przeorek I, Lillehei C, Lionetti P, Martin-de-Carpi J, Pakarinen M, Ruemmele FM, Shaoul R, Spray C, Staiano A, Sugarman I, Wilson DC, Winter H, Kolho KL. Surgical Management of Crohn Disease in Children: Guidelines From the Paediatric IBD Porto Group of ESPGHAN. J Pediatr Gastroenterol Nutr 2017; 64:818-835. [PMID: 28267075 DOI: 10.1097/mpg.0000000000001562] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.
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Affiliation(s)
- Jorge Amil-Dias
- *Department of Pediatrics, Centro Hospitalar, S. João, Porto, Portugal †Children's Hospital Zagreb, Faculty of Medicine, Zagreb, Croatia ‡The Juliet Keidan Institute of Pediatric Gastroenterology & Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel §Department of Pediatrics, Hvidovre University Hospital, Hvidovre, Denmark ||Pediatric Surgery, Children's Hospital, University of Helsinki, Helsinki, Finland ¶Department of Pediatric Gastroenterology, University Hospital Southampton, Southampton, UK #Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw, Poland **Department of Pediatrics, University Hospital Motol, Prague, Czech Republic ††Queen Mary's Hospital for Children, Epsom and St Helier NHS Trust, Surrey ‡‡Chelsea and Westminster Hospital, London, UK §§Paris-Diderot Sorbonne-Paris-Cité University and Robert Debré Hospital, Paris, France ||||Pediatric Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, Ludwig Maximilians-University, Munich, Germany ¶¶St George's, University of London, London, UK ##Boston Children's Hospital and Harvard Medical School, Boston, MA ***Department NEUROFARBA, University of Florence - Meyer Hospital, Florence, Italy †††Unit for the Comprehensive Care of Pediatric Inflammatory Bowel Disease, Hospital Sant Joan de Déu, Barcelona, Spain ‡‡‡Department of Pediatric Gastroenterology, Necker Enfants Malades University Hospital, Sorbonne Paris Cité University, Paris Descartes University, Institut IMAGINE - INSERM U1163, Paris, France §§§Pediatric Gastroenterology Institute, Ruth Children's Hospital, Rambam Medical Center, Haifa, Israel ||||||Department of Pediatric Gastroenterology, Bristol Royal Hospital for Children, Bristol, UK ¶¶¶Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II," Naples, Italy ###Department of Pediatric Surgery, Leeds Children's Hospital, Leeds General Infirmary, Leeds, UK ****Child Life and Health, University of Edinburgh, Scotland, UK ††††MassGeneral Hospital for Children, Harvard Medical School, Boston, MA ‡‡‡‡Children's Hospital, University of Helsinki, Helsinki, Finland
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Hukkinen M, Pakarinen MP, Merras-Salmio L, Koivusalo A, Rintala R, Kolho KL. Fecal calprotectin in the prediction of postoperative recurrence of Crohn's disease in children and adolescents. J Pediatr Surg 2016; 51:1467-72. [PMID: 26891835 DOI: 10.1016/j.jpedsurg.2016.01.017] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Revised: 01/09/2016] [Accepted: 01/09/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Fecal calprotectin (FC) correlates with endoscopic recurrence of Crohn's disease (CD) in adults but has not been studied among children postoperatively. We aimed to analyze whether FC relates with postoperative CD recurrence in children. METHODS Altogether 51 postoperative endoscopies and FC measurements from 22 patients having undergone surgery for CD at age ≤18years were included. RESULTS Ileocecal resection (n=15), small bowel resection (n=6), or left hemicolectomy (n=1) was performed at median age of 15.1 (interquartile range 14.4-17.6) years. Following surgery, FC decreased significantly (659 vs. 103μg/g, p=0.001). During median follow-up of 5.7 (4.2-7.7) years, either endoscopic or histological recurrence occurred in 17 patients (77%). FC >139μg/g at time of endoscopy or FC increase of 79μg/g compared to first postoperative value was suggestive of endoscopic recurrence (Rutgeerts score i2-i4), while FC >101μg/g or increase of 21μg/g indicated histological recurrence. Best accuracy for prediction of recurrence was obtained by combining FC at endoscopy and the postoperative increase of FC. The corresponding AUROC values were 0.74 (95% 0.58-0.89) for endoscopic recurrence whereas 0.81 (95% CI 0.67-0.95) for histological recurrence. CONCLUSION FC is a useful surrogate marker of postoperative recurrence also in pediatric CD patients.
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Affiliation(s)
- Maria Hukkinen
- Pediatric Liver and Gut Research Group, Children's Hospital, University of Helsinki, Finland.
| | - Mikko P Pakarinen
- Pediatric Liver and Gut Research Group, Children's Hospital, University of Helsinki, Finland; Section of Pediatric Surgery, Children's Hospital, University of Helsinki, Finland
| | - Laura Merras-Salmio
- Pediatric Liver and Gut Research Group, Children's Hospital, University of Helsinki, Finland; Section of Pediatric Gastroenterology, Children's Hospital, University of Helsinki, Finland
| | - Antti Koivusalo
- Section of Pediatric Surgery, Children's Hospital, University of Helsinki, Finland
| | - Risto Rintala
- Section of Pediatric Surgery, Children's Hospital, University of Helsinki, Finland
| | - Kaija-Leena Kolho
- Section of Pediatric Gastroenterology, Children's Hospital, University of Helsinki, Finland
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Ross AR, Hall NJ, Ahmed SA, Kiely EM. The extramucosal interrupted end-to-end intestinal anastomosis in infants and children; a single surgeon 21year experience. J Pediatr Surg 2016; 51:1131-4. [PMID: 26743344 DOI: 10.1016/j.jpedsurg.2015.11.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Revised: 11/10/2015] [Accepted: 11/21/2015] [Indexed: 11/24/2022]
Abstract
BACKGROUND/PURPOSE To report outcomes of a standardised technique for intestinal anastomosis in infants and children. METHODS Data were prospectively collected on all paediatric intestinal anastomosis by a single surgeon over a 21year period. Anastomoses were constructed using an end-to-end extramucosal technique with interrupted polypropylene sutures. Demographic and clinical data were recorded. RESULTS Six-hundred and thirteen anastomoses were constructed in 550 patients. Median age at time of anastomosis was 6months (range 1day-226months). The most common reason for anastomosis was stoma closure (n=271, 49%). For those patients that required multiple anastomoses the most common pathology was acute NEC (n=22/41, 54%). One-hundred and one (18.4%) patients passed stool within 24hours of surgery, 175 (31.8%) between 24-48 hours and 95 (17.3%) between 48-72 hours. Anastomotic complications occurred in 7 patients (1.3%) including anastomotic leakage (n=5, 0.9%) and anastomotic stricture (n=2, 0.4%). The majority of anastomotic leakages (80%) followed resection of acute NEC. CONCLUSIONS The interrupted extramucosal anastomosis is safe and effective. The return of bowel function is rapid and the complication rate acceptable. We recommend this technique be used for all intestinal anastomoses in children and infants.
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Affiliation(s)
| | | | - S A Ahmed
- Great Ormond Street Hospital, London UK
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Lourenço R, Azevedo S, Lopes AI. Surgery in Pediatric Crohn Disease: Case Series from a Single Tertiary Referral Center. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2016; 23:191-196. [PMID: 28868459 PMCID: PMC5580150 DOI: 10.1016/j.jpge.2016.03.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 03/20/2016] [Indexed: 01/15/2023]
Abstract
Introduction There is a recognized increase of lifelong surgery risk in Crohn disease (CD). Outcome data concerning surgery in children, particularly in the biological era, are limited. Aim To characterize the clinical profile and the clinical outcome in children and adolescents with CD who underwent surgical intervention, in a single tertiary referral center. Methods Retrospective, cross-sectional study, including pediatric patients with CD undergoing intra-abdominal surgery in the last 11 years. Results Included eight of 50 CD total patients (16%); six female; median age at CD diagnosis of 12.0 years; Paris classification: (a) location: ileocolonic (5), colonic (1), upper disease (1), ileocolonic/upper disease (1); (b) behavior: stricturing (4), nonstricturing nonpenetrating (2), penetrating (1), both penetrating and stricturing disease (1); growth delay (2). Six children received thiopurines, five mesalazine, three corticosteroids and four anti-TNF therapy, preoperatively. Surgery followed diagnosis by a median of 2.9 years. Median PCDAI at the time of surgery was 35.0. Elective surgery was performed in six patients and emergency surgery in two, without major complications. Five children received anti-TNF and three thiopurines post-operatively. Within the follow-up period (median 1.7 years), relapse occurred in one child (3.2 years after intervention); the remaining seven patients persist in clinical remission. Median PCDAI in the last evaluation was 6.3. Weight and height recovery was observed in seven patients, at last follow-up. Conclusion Surgical treatment of CD is a valid alternative in selected cases, contributing to the resolution of acute complications and maintenance of remission, allowing disease-free interval and nutritional recovery.
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Affiliation(s)
- Rita Lourenço
- Pediatric Department, Hospital do Divino Espírito Santo de Ponta Delgada, Azores, Portugal
| | - Sara Azevedo
- Gastroenterology Unit, Pediatric Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Ana Isabel Lopes
- Gastroenterology Unit, Pediatric Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
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Hojsak I, Kolacek S, Hansen LF, Bronsky J, Piekkala M, Lionetti P, Skaba R, Kolho KL. Long-term outcomes after elective ileocecal resection in children with active localized Crohn's disease--a multicenter European study. J Pediatr Surg 2015; 50:1630-5. [PMID: 25913894 DOI: 10.1016/j.jpedsurg.2015.03.054] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Revised: 03/03/2015] [Accepted: 03/21/2015] [Indexed: 12/13/2022]
Abstract
PURPOSE The aim of this study was to investigate the therapeutic role of an elective ileocecal resection in children with active localized Crohn's disease. METHODS This was a retrospective multicenter study which included five European referral centers which included all children with Crohn's disease who underwent ileocecal surgery from 2000 to 2011 and had a minimum of 12 months follow-up. RESULTS Altogether 68 patients fulfilled inclusion criteria. Median age at diagnosis was 13.7 years (6.6-17.9 years) and at surgery 15.2 years (8.6-18.5 years). Median duration of postoperative clinical remission was 20 months (3-95 months). Overall 54 patients (79.4%) were in remission one year after surgery and 38 (55.9%) during the total postsurgical follow up (median 30 months; range 12-95 months). Z score height for age significantly improved postoperatively in children who were at the time of surgery younger than 16 years of age (mean difference 0.232 SD; p=0.029). Cox proportional hazard regression model failed to indicate risk factors associated with postsurgical relapse. CONCLUSION Elective ileocecal resection is a valid treatment option which should be considered in a subset of pediatric patients with localized Crohn's disease with the aim of achieving clinical remission and to improve growth.
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Affiliation(s)
- Iva Hojsak
- Children's Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
| | - Sanja Kolacek
- Children's Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia
| | | | - Jiri Bronsky
- Department of Paediatrics, University Hospital Motol, Prague, Czech Republic
| | - Maija Piekkala
- Children's Hospital, University of Helsinki, Helsinki, Finland
| | | | - Richard Skaba
- Department of Paediatric Surgery, University Hospital Motol, Prague, Czech Republic
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Abstract
OBJECTIVES The aim of this study was to describe surgery rates, complications, and risk of disease recurrence after surgery in paediatric Crohn disease (CD). METHODS Children <18 years with a diagnosis of CD and a least 1 intestinal resection from the period January 1, 1978 to December 31, 2007 were identified using the Danish National Patient Registry. Patient charts were used to extract data. RESULTS A total of 115 of 422 children with CD, who had surgery in 2 referral centres, were further studied. Disease extension according to the Montreal classification at the time of operation was available in 106/115 patients: B1, 39/106 (37%); B2, 59/106 (56%); and B3, 8/106 (7%). Before/after surgery 89%/36% of the patients received corticosteroids, 26%/61% azathioprine, and 15%/34% infliximab. Ileocoecal resection was performed in 54 (47%); 17 (15%) underwent ileal resection, 21 (18%) colectomy, 13 (11%) hemicolectomy, and 10 (9%) a combined colonic and ileal resection. Median time from diagnosis to surgery was 23 months (range 0-147). The median follow-up time after surgery was 121 months (16-226), and median time to disease recurrence was 12 months (3-160). The cumulative clinical recurrence rates at 1, 5, and 10 years were 50%, 73%, and 77%, respectively. More than 1 bowel resection was needed in 39%. Postoperative azathioprine treatment did not affect rate of recurrence after surgery. CONCLUSIONS In this large cohort of children with CD studied for >10 years postoperatively, we found a high postoperative recurrence rate of disease and a frequent need for >1 intestinal resection.
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Fu YTN, Hong T, Round A, Bressler B. Impact of medical therapy on patients with Crohn’s disease requiring surgical resection. World J Gastroenterol 2014; 20:11808-11814. [PMID: 25206286 PMCID: PMC4155372 DOI: 10.3748/wjg.v20.i33.11808] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Revised: 03/17/2014] [Accepted: 04/23/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the impact of medical therapy on Crohn’s disease patients undergoing their first surgical resection.
METHODS: We retrospectively evaluated all patients with Crohn’s disease undergoing their first surgical resection between years 1995 to 2000 and 2005 to 2010 at a tertiary academic hospital (St. Paul’s Hospital, Vancouver, Canada). Patients were identified from hospital administrative database using the International Classification of Diseases 9 codes. Patients’ hospital and available outpatient clinic records were independently reviewed and pertinent data were extracted. We explored relationships among time from disease diagnosis to surgery, patient phenotypes, medication usage, length of small bowel resected, surgical complications, and duration of hospital stay.
RESULTS: Total of 199 patients were included; 85 from years 1995 to 2000 (cohort A) and 114 from years 2005 to 2010 (cohort B). Compared to cohort A, cohort B had more patients on immunomodulators (cohort A vs cohort B: 21.4% vs 56.1%, P < 0.0001) and less patients on 5-aminosalysilic acid (53.6% vs 29.8%, P = 0.001). There was a shift from inflammatory to stricturing and penetrating phenotypes (B1/B2/B3 38.8% vs 12.3%, 31.8% vs 45.6%, 29.4% vs 42.1%, P < 0.0001). Both groups had similar median time to surgery. Within cohort B, 38 patients (33.3%) received anti-tumor necrosis factor (TNF) agent. No patient in cohort A was exposed to anti-TNF agent. Compared to patients not on anti-TNF agent, ones exposed were younger at diagnosis (anti-TNF vs without anti-TNF: A1/A2/A3 39.5% vs 11.8%, 50% vs 73.7%, 10.5% vs 14.5%, P = 0.003) and had longer median time to surgery (90 mo vs 48 mo, P = 0.02). Combination therapy further extended median time to surgery. Using time-dependent multivariate Cox proportional hazard model, patients who were treated with anti-TNF agents had a significantly higher risk to surgery (adjusted hazard ratio 3.57, 95%CI: 1.98-6.44, P < 0.0001) compared to those without while controlling for gender, disease phenotype, smoking status, and immunomodulator use.
CONCLUSION: Significant changes in patient phenotypes and medication exposures were observed between the two surgical cohorts separated by a decade.
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Blackburn SC, Wiskin AE, Barnes C, Dick K, Afzal NA, Griffiths DM, Beattie RM, Stanton MP. Surgery for children with Crohn's disease: indications, complications and outcome. Arch Dis Child 2014; 99:420-6. [PMID: 24395646 DOI: 10.1136/archdischild-2013-305214] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Outcome data for surgery in paediatric Crohn's disease are limited. We report 10 years' experience at a regional paediatric gastroenterology centre. METHODS Children undergoing surgery for Crohn's disease (January 2002-December 2012) were identified from an onsite patient register. Patients were followed until transition to adult services. Data were obtained from medical records and are expressed as median (range). RESULTS Sixty-nine children, aged 13.8 years (6.3-17.0) at diagnosis, were included. 42 were male (61%). Follow-up was 1.8 years (27 days-6 years). Surgery followed diagnosis by 9 months (0 days-7 years). 52 children (75%) received thiopurines and 5 (7%) anti-TNF (tumour necrosis factor) therapy preoperatively. 58 (84%) underwent intra-abdominal surgery (40 right hemicolectomy, 8 stoma formation, 2 subtotal colectomy, 2 small bowel resection, 6 other) and 10 (14%) underwent surgery for perianal disease. The commonest indications for intra-abdominal surgery were stricturing disease 35 (60%) and unresponsive luminal disease 13 (22%). There were 13 (22%) early, and 5 (8.6%) late, complications following intra-abdominal surgery. Nine children had disease relapse, five required further surgery. Height SD scores (SDS) did not increase between diagnosis; -0.5 (-3.4-2.1) and most recent follow up; -0.4 (-3.0-1.1). Body Mass Index (BMI) SDS increased from -1.0 (-6.3-1.5) to -0.3 (-3.3-2.0) (p<0.05). CONCLUSIONS Surgery was associated with a 22% early complication rate and a 15% risk of relapse. 21% of patients required a second unplanned intra-abdominal procedure. Surgical intervention was associated with an increase in BMI SDS, but not in height SDS.
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Affiliation(s)
- S C Blackburn
- Department of Paediatric Surgery, Southampton University Hospital NHS Trust, , Southampton, UK
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