Expert Rev Gastroenterol Hepatol. 2009;3(3):249-256. © 2009
Abstract and Introduction
Abstract
Crohn's disease is a chronic, relapsing–remitting inflammatory disease of the intestinal tract that commonly requires surgical treatment. Unfortunately, the majority of patients will ultimately develop postoperative disease recurrence and require subsequent surgery. A number of medications have been researched for the maintenance of postoperative remission. Of these, few have demonstrated consistent efficacy. A recently published randomized, controlled trial indicated that infliximab is effective in the maintenance of postoperative remission.
Introduction
Crohn's disease (CD) is a chronic, relapsing–remitting inflammatory disease that affects the entire GI tract. As many as 50–80% of CD patients will ultimately require surgery for complications such as fistulas, strictures, abscesses and perforations.[1–4] Surgery is often required early in the disease course, as demonstrated by Bernell et al., who found that 44% of patients underwent operations within the first year of diagnosis.[1]
Surgery does not cure CD and many patients suffer postoperative relapse at or just proximal to the surgical anastomosis. The behavior of CD recurrence, that is, whether the disease is stricturing or fistulizing, is usually the same as the primary indication for the initial surgery.[4–9]
At least 20% of patients who have undergone surgical resection will require a subsequent operation.[2,10] Data suggest that up to 50% of patients undergo reoperation after 20 years.[11–13] Efforts to reliably predict which patients will suffer recurrence have been only modestly successful; thus, researchers have tried to identify effective prophylaxis of relapse among postsurgical CD patients.[14]
Definition of Recurrence
Recurrence among CD patients has been defined in a variety of ways. Most commonly, postoperative recurrence is defined by the presence of radiographic, endoscopic or pathologic CD.[6,11] It is important to note that this definition is not predicated on the presence of clinical symptoms. Endoscopic recurrence at the ileocolonic anastomosis or neoterminal ileum has been quantified using a scoring system developed by Rutgeerts et al. (Box 1).[14,15] In addition to providing real-time recurrence assessment, the Rutgeerts score provides prognostic information: 80–85% of patients with a score of i-0 or i-1 will be asymptomatic 3 years after surgery compared with fewer than 10% of those with a score of i-3 or i-4.[2,14,15] Among those with a score of i-0 or i-1, the chance of clinical recurrence at 3 years is less than 5%, whereas endoscopic scores of i-2, i-3 and i-4 correlate with 3-year clinical recurrence rates of 15, 40 and 90%, respectively.[14] Endoscopic recurrence heralds clinical recurrence; therefore, many clinical trials consider recurrence as any score of i-2 or greater.[8,16,17]
Natural History of Postoperative CD Recurrence
Active CD can develop in the neoterminal ileum within a few weeks of surgical resection.[4,6,15] Olaison et al. have observed that the natural course of postoperative CD progresses from early aphthous ulcer formation to larger ulcers and then fistulas or strictures.[4–6] It is postulated that CD recurrence is triggered by a luminal factor that elicits inflammation and its sequelae.[6,18,19] Rutgeerts et al. found no new CD lesions among postoperative patients who had ileostomy and diversion of the fecal stream away from the distal ileocolonic anastomosis. When bowel continuity was reinstated, however, ulcers developed in the neoterminal ileum and CD progression ensued.[6,18,19] D'Haens et al. showed that intestinal contents elicited CD recurrence in the neoterminal ileum through both mucosal invasion by inflammatory cells and activation of lymphocytes.[20] The details of this process remain obscure. It is clear, however, that the subsequent disease course correlates to the severity of these early lesions.[4,15]
In a meta-analysis performed by Pascua et al., the 1-year postoperative pooled clinical recurrence rate was 56% and the endoscopic recurrence rate was 58%.[16] Other studies report 1-year postoperative endoscopic recurrence rates of between 73 and 93%, with clinical recurrence as low as 30%.[4,5,11,21] The need for repeat surgery 3 years after the initial intestinal resection ranged from 15 to 45% and was as high as 80% 20 years later.[8,13]
Postoperative Surveillance
Given the fact that postoperative endoscopic CD recurrence correlates with future clinical recurrence and the need for repeat surgery, there is increasing emphasis on endoscopic evaluation 6–12 months after surgery.[4,6,22]
Colonoscopy and wireless capsule endoscopy (WCE) are the two primary modalities to assess for mucosal recurrence. Bourreille et al. recently compared the effectiveness of WCE and ileocolonoscopy and found that ileocolonoscopy was more sensitive in detecting neoterminal lesions. However, efforts are underway to more formally assess small bowel CD and establish a scoring system for WCE.[4,14,23] A recent publication by Gralnek et al. offers such a scoring system that looks at three different parameters: villous edema, ulcers and stenosis.[24] Capsule retention is an additional concern in the use of WCE to monitor postoperative CD patients. While WCE is generally safe, capsule retention necessitating surgical extraction occurs in 10–13% of CD patients. At present, colonoscopy with inspection of the ileocolonic anastomosis and neoterminal ileum is the test of choice for the evaluation of postoperative CD. WCE should be reserved for patients with mid-small bowel surgical anastomosis or anastomosis at other sites outside of the reach of the standard colonoscope.
Abstract and Introduction
Abstract
Crohn's disease is a chronic, relapsing–remitting inflammatory disease of the intestinal tract that commonly requires surgical treatment. Unfortunately, the majority of patients will ultimately develop postoperative disease recurrence and require subsequent surgery. A number of medications have been researched for the maintenance of postoperative remission. Of these, few have demonstrated consistent efficacy. A recently published randomized, controlled trial indicated that infliximab is effective in the maintenance of postoperative remission.
Introduction
Crohn's disease (CD) is a chronic, relapsing–remitting inflammatory disease that affects the entire GI tract. As many as 50–80% of CD patients will ultimately require surgery for complications such as fistulas, strictures, abscesses and perforations.[1–4] Surgery is often required early in the disease course, as demonstrated by Bernell et al., who found that 44% of patients underwent operations within the first year of diagnosis.[1]
Surgery does not cure CD and many patients suffer postoperative relapse at or just proximal to the surgical anastomosis. The behavior of CD recurrence, that is, whether the disease is stricturing or fistulizing, is usually the same as the primary indication for the initial surgery.[4–9]
At least 20% of patients who have undergone surgical resection will require a subsequent operation.[2,10] Data suggest that up to 50% of patients undergo reoperation after 20 years.[11–13] Efforts to reliably predict which patients will suffer recurrence have been only modestly successful; thus, researchers have tried to identify effective prophylaxis of relapse among postsurgical CD patients.[14]
Definition of Recurrence
Recurrence among CD patients has been defined in a variety of ways. Most commonly, postoperative recurrence is defined by the presence of radiographic, endoscopic or pathologic CD.[6,11] It is important to note that this definition is not predicated on the presence of clinical symptoms. Endoscopic recurrence at the ileocolonic anastomosis or neoterminal ileum has been quantified using a scoring system developed by Rutgeerts et al. (Box 1).[14,15] In addition to providing real-time recurrence assessment, the Rutgeerts score provides prognostic information: 80–85% of patients with a score of i-0 or i-1 will be asymptomatic 3 years after surgery compared with fewer than 10% of those with a score of i-3 or i-4.[2,14,15] Among those with a score of i-0 or i-1, the chance of clinical recurrence at 3 years is less than 5%, whereas endoscopic scores of i-2, i-3 and i-4 correlate with 3-year clinical recurrence rates of 15, 40 and 90%, respectively.[14] Endoscopic recurrence heralds clinical recurrence; therefore, many clinical trials consider recurrence as any score of i-2 or greater.[8,16,17]
Natural History of Postoperative CD Recurrence
Active CD can develop in the neoterminal ileum within a few weeks of surgical resection.[4,6,15] Olaison et al. have observed that the natural course of postoperative CD progresses from early aphthous ulcer formation to larger ulcers and then fistulas or strictures.[4–6] It is postulated that CD recurrence is triggered by a luminal factor that elicits inflammation and its sequelae.[6,18,19] Rutgeerts et al. found no new CD lesions among postoperative patients who had ileostomy and diversion of the fecal stream away from the distal ileocolonic anastomosis. When bowel continuity was reinstated, however, ulcers developed in the neoterminal ileum and CD progression ensued.[6,18,19] D'Haens et al. showed that intestinal contents elicited CD recurrence in the neoterminal ileum through both mucosal invasion by inflammatory cells and activation of lymphocytes.[20] The details of this process remain obscure. It is clear, however, that the subsequent disease course correlates to the severity of these early lesions.[4,15]
In a meta-analysis performed by Pascua et al., the 1-year postoperative pooled clinical recurrence rate was 56% and the endoscopic recurrence rate was 58%.[16] Other studies report 1-year postoperative endoscopic recurrence rates of between 73 and 93%, with clinical recurrence as low as 30%.[4,5,11,21] The need for repeat surgery 3 years after the initial intestinal resection ranged from 15 to 45% and was as high as 80% 20 years later.[8,13]
Postoperative Surveillance
Given the fact that postoperative endoscopic CD recurrence correlates with future clinical recurrence and the need for repeat surgery, there is increasing emphasis on endoscopic evaluation 6–12 months after surgery.[4,6,22]
Colonoscopy and wireless capsule endoscopy (WCE) are the two primary modalities to assess for mucosal recurrence. Bourreille et al. recently compared the effectiveness of WCE and ileocolonoscopy and found that ileocolonoscopy was more sensitive in detecting neoterminal lesions. However, efforts are underway to more formally assess small bowel CD and establish a scoring system for WCE.[4,14,23] A recent publication by Gralnek et al. offers such a scoring system that looks at three different parameters: villous edema, ulcers and stenosis.[24] Capsule retention is an additional concern in the use of WCE to monitor postoperative CD patients. While WCE is generally safe, capsule retention necessitating surgical extraction occurs in 10–13% of CD patients. At present, colonoscopy with inspection of the ileocolonic anastomosis and neoterminal ileum is the test of choice for the evaluation of postoperative CD. WCE should be reserved for patients with mid-small bowel surgical anastomosis or anastomosis at other sites outside of the reach of the standard colonoscope.
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