45 Diversion Colitis

45 Diversion colitis KONRAD H. SOERGEL Table 1. Possible etiologic mechanisms of diversion colitis Introduction [13] Diversion colitis is an inflammatory bowel disease Luminal short-chain fatty acid deficiency (IBD) that has attracted considerable clinical and Deficient short-chain fatty acid metabolism by colonocytes scientific interest during the past 15 years. Indeed, Pathogenic microorganisms - direct invasion or toxin elaboration the histologic features of this entity were recognized Stasis - bacterial overgrowth (similar to bypass enteritis) only 28 years ago [1] and in that time it has acquired Bile acid deficiency several names, including bypass colitis, exclusion colitis, and disuse colitis. Since its first clinical description in 1981 [2], a number of case reports and series have been published [2-30]. Certain observa tions have sparked the current curiosity: Pathophysiology/colonic SCFA 1. It is the only model of non-infectious 'experi mental' colitis in humans, with the possible ex metabolism ception of radiation colitis. It occurs in 50-100% While the clinical setting in which diversion colitis of cases following exclusion of the distal colo- develops is well estabhshed, little is known regarding rectum and is predictably reversible by surgical the etiologic mechanism. The sequence of events reanastomosis [2, 17, 18, 21]. following surgical bypass that culminates in inflam mation and clinical symptoms remains poorly under 2. It is caused by diversion of the fecal stream, most stood. Several theories have been proposed (Table 1). likely by deprivation of short-chain fatty acids Among these, only the virtual absence of SCFA from (SCFA) [13], the preferred metabolic substrate of the lumen of the bypassed segment is supported by the colonic epithelium [31-33]. substantial evidence. Thus, no pathogenic micro organisms or toxins have been discovered in the 3. This 'nutritional deficiency' leads to an inflam contents of the inflamed segments [13, 26, 38]. matory process similar to that of other colitides Quantitative bacteriologic studies revealed a [34-36]. decrease in anaerobic bacteria by two log units with frequent absence of Eubacteria and Bifidobacteria 4. The disease has recently been reproduced in strains as compared to normal feces [38]. A stasis laboratory animals [37]. colitis, similar to the bypass enteritis observed after jejunoileal bypass for obesity, is unlikely since saline Thus, diversion colitis presents an ideal opportu irrigations are ineffective in diversion colitis [13]. nity to study the pathophysiology of an IBD in Luminal 'casts' composed of cell detritus and mucus humans: its occurrence after surgical bypass of glycoproteins are also rare occurrences in this normal colon is frequent, characteristics of disease [30]. There are no data to support or refute inflammation may be studied as they develop, and the theory of luminal bile salt deficiency. However, successful treatment by either surgical or medical colitis is not a feature of biliary obstruction. Excess means can be monitored. bile acids rather than deficiency, in the colon, cause secretion and mild cellular injury. Decreased ability of the colonic epithelium to metabolize SCFA is contradicted by several observations: the near- Stephan R. Targan, Fergus Shanahan and Lor en C. Karp (eds.), Inflammatory Bowel Disease: From Bench to Bedside, 2nd Edition, 811-821. © 2003 Kluwer Academic Publishers. Printed in Great Britain 812 Diversion colitis absence of these acids in the contents of diverted 7. The crypt cell production rate is decreased after segments [13] and the heaUng of mucosal inflamma surgical diversion [53-55] and irrigation with an tion when they are supplied by irrigation or by SCFA solution restores the cell proliferation rate surgical reanastomosis. to normal [56]. The concentration of SCFA (acetate + propionate + n-butyrate) in the sparse, mucoid contents of 8. Decreased colonic SCFA concentrations during rectosigmoid segments affected by diversion colitis therapy with broad-spectrum antibiotics have is only <5 mmol/L, compared to 100-200 mmol/L been implicated in the pathogenesis of Clostri in normal stool [39-41]. This reduction is caused by dium difficile-nQg'diivQ antibiotic-associated the exclusion of contents from the proximal colon diarrhea [57]. where the bulk of anaerobic carbohydrate fermenta tion occurs, by the reduced number of anaerobic 9. All three major SCFA (n-butyrate, propionate, bacteria [38] and by the absence of fermentable acetate) potently inhibit colonic secretion exogenous carbohydrate. The reduced bacterial flora induced by cholera toxin and E-coli heat-stable of these inflamed bowel segments is incapable of enterotoxin [58]. fermenting glucose at a rate sufficient to cause a rise in breath H2 concentration [13]. The following obser Luminal deficiency of SCFA caused by surgical vations support the SCFA deficiency hypothesis of diversion of the fecal stream results in a state of diversion colitis: energy deficiency. Presumably, this leads to a 'wea kened' epithelium when the colonocyte is unable to 1. SCFA, especially n-butyrate, are the preferred satisfy its metabolic requirements with alternate metabolic substrate of the colonic epithelium substrates such as glucose, ketone bodies, and gluta- [31, 32, 42]. SCFA are abundantly produced by mine [32, 42]. Increased epithelial permeability anaerobic fermentation and are rapidly absorbed develops, allowing bacterial translocation resulting in the human ileum and colon by a combination in a local inffammatory response. The transition of a distinct anion exchange transport system and from weakened epithelium to inffammation is poorly non-ionic diff'usion [39-41, 43-49]. understood, but it may resemble so-called starvation colitis [33]. While SCFA deficiency is the key to the 2. The preference for SCFA as the source of meta development of diversion colitis, nutritional depriva bolic fuel increases aborally along the colon [32, tion may not be the only explanation. As Table 2 42]. Thus, from cecum to rectum an increasing demonstrates, these acids have several additional percentage of metabolic need is derived from effects on colonic function, any of which may con SCFA. Diversions involving proximal colonic tribute to maintaining the functional and morpho segments are less likely to develop colitis [36], logic integrity of the colonic epithelium. and the surgical creation of neobladders from the proximal or transverse colon does not result in inffammation [50]. Table 2. Physiologic functions of colonic short-chain fatty 3. Blood concentrations of SCFA (except acetate) acids are negligible, so they must enter the colonocyte Preferred metabolic fuel for colonocytes [31, 32, 42] from the colonic lumen. Enhance Na, CI, and water absorption [48, 79] Acid-base balance: HCO3 secretion [45, 46] Regulation of motility [62] 4. Deprivation of luminal contents following surgi Mucosal growth [53, 70, 80, 81 ] cal diversion results in colitis only in the diverted Increase cell differentiation [53, 54] segment [36]. Carbohydrate caloric salvage [40, 44, 48] Bacteriostatic properties 5. Treatment of the colitis with SCFA irrigations Increase colonic blood flow [56, 79] Increase colonic oxygen consumption [79] decreases the inffammation [13]. 6. Metabolic inhibition of colonocyte SCFA meta bolism produces experimental colitis in animals [51, 52]. KonradH. Soergel 813 li;|||||| The sparse, predominantly anaerobic bacterial flora may play a contributory role. Compared to 1111111 controls, patients with diversion colitis have an III ilililiii^ increased number of rectal nitrate-reducing bacteria iiiiiiiiiil liiiil which may have pathogenic potential via enhanced production of NO [59]. :::. !• Clinical presentation •.•iiiiili ililiiill The incidence of diversion colitis is difficult to assess, llllllli; for several reasons. Some reports include patients lllil ^^^m^^^. iliiiliiiiiiiliiiliiii with pre-existing inflammation of the rectosigmoid, iiiipiiii liiiiii ' JIBiiiii:iiliM^^^^ - mm::3mmimsm iiiiiiiiiiliiiiiiii^ while in others only symptomatic patients were iiiiii iiii i iiiiiiiliiliii i ;iii:iiiiii i i : iiii i mmm^mm iiiiiiipipiii i iii»iiii examined. No longitudinal studies are available, -^ "'^'^'^ liiipiiiliiiliiiiiiie although the disease has been found as early as 1 month after the surgical diversion procedure [30]. Based on endoscopic criteria the prevalence varies between 40-50% [7, 10, 11, 30, 38, 55] to 70% [5], 80% [26], and 90-100% [2, 4, 9, 17-19]. Histologic examination of mucosal biopsies revealed inflamma tory changes in 68% [12], 83% [30], and 100% [7] of cases. The true incidence of diversion colitis will probably approach 100% when patients are examined sequentially and when clinicians and pathologists become more familiar with this entity. The most common symptom is an increase in the frequency and amount of mucoid discharge from the Figure 1. Severe diversion col^ resembles anus or the mucus fistula. Bleeding, usually painless uicerative colitis w|^^^^^^^^^^^^^^^^ surface exudate, crypt [25], may be noticed, ranging from blood-tinged distortion/ crypt ite^ mixed Inflammatioi discharge to significant blood loss [4], which may infiltrate In the laW^^^ require resection of the diverted segment [23]. Pain iHllr ori#^^^^^^^ •.KOTO:rowski,M^^^^^ in the pelvic area, the left lower quadrant, or the rectum is another rare complaint. The pain may be duU or cramping and is occasionally associated with the presence of mucoliths in the lumen

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