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Fichera et al provide a comprehensive review of the surgical approach to Crohn's disease from indications for surgery to the surgical approaches to the management of the various patterns of disease.1 There are several areas that may benefit from expanded coverage so that the surgeon managing this difficult chronic disease can understand more regarding some of the current areas of controversy.

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The onset of Crohn's disease has consistently been blamed on a yet to be identified alteration in mucosal immune response, possible in response to an altered susceptibility to luminal bacteria or other environmental exposures.2,3 Interestingly, there has been greater recognition of the consistent histopathologic changes of mucosal exudation, submucosal edema, and extensive dilation of lacteals seen in Crohn's disease lymphatics.4 These findings have correlated with animal models of lymphatic sclerosing agents leading to similar findings of inflammatory bowel disease. The inflammatory response was reduced with administration of cyclooxygenase (COX) inhibitors suggesting an arachidonic acid role. It is believed that the early lymphatic obstruction blocks the transfer of inflammatory cells to regional lymph nodes and the process of lymphoid neogenesis that produces lymphoid aggregates in the mesentery. Trapping the activated B lymphocytes in the region, coupled with an ongoing pattern of neoangiogenesis of lymphatics in the intestinal wall may be causally related to the development of the disease. Further credence is given to the theory because the virtual pathognomonic finding of fat wrapping is the result of cytokine and tumor necrosis factor (TNF) release from adjacent lymphatic tissue. These response leads to hypertrophy of fat cells in the mesentery that may be related to the common finding of thickened mesentery in patients with Crohn's disease. Although considerably more work is required to fully understand the interaction of abnormal lymph drainage and mucosal inflammation, it is intriguing to hypothesis that early resection of the draining mesentery might be an effective surgical strategy prior to the onset of chronic disease and extensive mesenteric involvement.

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The availability of an increasing number of biologic agents capable of creating greater immunosuppression has led to the suggestion of a so called "top-down" strategy of more aggressive medical therapy at diagnosis. This is contradistinction to the more typical "bottom-up" approach of beginning with corticosteroids or even 5-aminosalicylic acid (5-ASA) preparations and escalating only after persistent symptoms. Markowitz et al reported an almost 90% remission rate in children using a strategy of corticosteroids and 6-mercaptopurine (6-MP) as induction therapy.5 Similar benefits have been described with the use of either certolizumab pegol therapy, where superior response was seen in patients with disease duration of shorter than 1 year compared to patients with longer than 5 years of disease (75 vs 52%).6 A prospective trial assessing patients naive to any immunomodulator reported both an improved clinical remission rate at 52 weeks (62 vs 42%) and longer time to relapse (329 vs 174 days) with a strategy of infliximab infusion and azathioprine/6-MP compared to ...

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