45 Diversion

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 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 [10, 30]. One prior to planned surgical restitution of colorectal patient represented with copious mucoid discharge continuity; (c) a prospective search for diversion of 400 ml/day; histologic study, however, revealed no colitis [5]. These asymptomatic patients may exhibit inflammation but the presence of goblet cell hyper­ the entire spectrum from chronic inflammation, plasia [3]. Other reported complaints include low- apparent only on histologic study, to severe inflam­ grade fever, anal irritation by the mucoid discharge, mation easily recognized during endoscopy. Late and anal fissure. The reported frequency of any stricture formation and areas of stenosis [6] may symptom attributable to diversion colitis varies obviate plans for surgical reanastomosis. between zero [5, 20, 22, 60], 10-20% [6, 9, 61], 28- 33% [26, 62], and 50%o [7, 9, 11]. Furthermore, there is no correlation between the severity of inflamma­ tion and the presence and degree of symptoms [7]. Histopathology Asymptomatic cases tend to be recognized in one The histologic spectrum of diversion colitis has been of three settings: (a) endoscopic re-evaluation follow­ summarized [7, 14, 21]. The disease is largely limited ing a bypass operation for IBD when either new to the mucosa, although fibrosis of the lamina inflammation or, less likely, worsening of pre-exist­ propria [17] progressing to thickening of the muscu- ing disease is found [15-17]; (b) routine examination laris propria [1, 63] may develop over time. The 814 Diversion colitis morphologic appearance varies with the severity of Table 3. Histologic findings in diversion colitis [1, 7,12,14, the disease and its duration. Many of its features 21,23,63] (Table 3) overlap with those of idiopathic and Common infectious colitides. Mucosal edema Active diversion colitis mimics idiopathic ulcera­ Mucin depletion tive colitis (UC) in many respects (Fig. 1). The Reactive crypt epithelium Lymphocytic infiltrate picture is dominated by marked mucosal edema, Lymphoid follicles surface exudate, mucin depletion, a mixed inflam­ Crypt abscesses matory infiltrate, and crypt abscesses. The degree of Crypt distortion and atrophy edema, and the fact that the histologic changes may Neutrophilic infiltrate Mucosal ulceration be non-uniform [2, 17], differ from the usual appear­ Surface exudate ance of UC. Aphthous lesions are rarely identified in Rare tissue sections [7], although they are commonly Increased mucin production described by the endoscopist. While mucin granulo­ Goblet cell hyperplasia mas have been presented, true mucosal granulomas Mucin granulomas have been reported only once [21], and their presence Villous surface changes should raise the question of Crohn's colitis [64]. Pseudomembranes Aphthous lesions Villous changes of the surface epithelium have been described [14]. Subacute or healing diversion colitis Never True granulomas (Fig. 2) is characterized by a persistent chronic inflammatory infiltrate, distortion of the colonic crypt, and the appearance of numerous lymphoid follicles [4, 12] which may appear as small polypoid

^%^,^ ^".^

4 * , •f.A

,* * * V -.

Figure l.ltversioncolitls-::iK^^^^ Konrad H. Soergel 815

Figure 3. Long-standJng diversion colitis on maintenance tiierapy with short-chain fatty acid irrigations. There is marked crypt atrophy with persisting mild chronic inflammation (H&E, original magnification x 7C). (Courtesy of Richard A. Komorowski, MD, Milwaukee, Wl.)

excrescences on gross inspection. Lymphoid follicu­ tions (Figs. 1 and 2) and of surgical reanastomosis. lar hyperplasia within the lamina propria, featuring By contrast, the response of distal UC to topical a high percentage of germinal centers, is nearly SCFA therapy is less predictable and less complete universal in diversion colitis. This is not a specific [66-68]. According to some reports, patients with finding, however, as it may also be present in chronic Crohn's disease (CD) showing acute inflammation UC and in lymphoid follicular proctitis [63]. The in their excluded rectosigmoid appear to suffer from chronic inactive stage (Fig. 3) presents with a striking diversion colitis rather than reactivation of their reduction in the number and depth of the colonic underlying disease [13, 15-17, 35]. By contrast, crypts [53], mild chronic inflammation, and persis­ chronic radiation proctitis may respond clinically tence of the nodular lymphoid hyperplasia. The and histologically to topical SCFA therapy [69] but appearance is that of atrophy involving the mucosa the distinction between diversion and radiation proctitis is clinically non-problematic. [22], but not the muscularis propria and myenteric plexus [65]. In summary, there is an evolving concept of the pathology of diversion colitis involving a continuum The clinically important distinction of diversion of minimal non-specific inflammation progressing to colitis from other types of colonic inflammation can acute inflammation, then chronic inflammatory rarely be made on the basis of a single set of mucosal changes, eventually resulting in fibrosis and mucosal biopsies. A histologic appearance compatible with atrophy. This continuum exhibits wide variability this diagnosis during the active phase of the disease, with regard to time of onset following diversion, the followed by resolution of mucosal edema, superficial severity of inflammation, and the rate of evolution. ulcerations, and neutrophilic infiltration with ther­ apy, strongly supports the diagnosis. The two effec­ tive therapeutic modalities consist of SCFA irriga­ 816 Diversion colitis Diagnosis In a patient with a surgical colonic bypass and preoperative documentation of normal rectosigmoid mucosa the diagnosis of diversion colitis is straight­ forward. The inflammation should involve the entire diverted segment, albeit non-uniformly, both in the longitudinal and circumferential axes [7]. The distal rectum tends to be most severely affected [30] while the blind end of Hartmann's pouch, or the area near a mucus fistula, may only show edema with loss of vascularity. Furthermore, the colonic segment in continuity with fecal stream should be free of inflam­ mation. Marked erythema, edema, friability, granu­ larity, and erosions covered by exudate are found in the acute stage (Fig. 4). Moderately active or healing disease is indicated by mild edema, erythema, and irregularly shaped erosions (Fig. 5). The inactive or healing stage can be recognized by edema, reduced Figure 4. Severe diversion colitis. Marked friability with vascular markings, and gradual narrowing of the spontaneous bleeding, exudate, and superficial ulceration lumen [6, 7] (Fig. 6). Diff'use mucosal modularity dominate the endoscopic appearance. caused by aggregates of enlarged lymph follicles has been observed [2, 17], and masses of inspissated cell detritus and mucus may be present [30]. Contrast radiographs confirm the findings of mucosal modularity [18, 70] and difl'use luminal narrowing [6, 22]. An indium'^'-labeled leukocyte scan was positive in a single patient [71]. Fistulas and abscess formation have not been reported as complications of diversion colitis. The major problem in differential diagnosis is idiopathic IBD. Patients with CD frequently undergo colonic bypass procedures and the surgeon is reluc­ tant to re-establish anatomic continuity in the pre­ sence of active inflammation in the bypassed seg­ ment. There exist several observations to suggest that reanastomosis may safely proceed in this situation [35]. 1. CD activity generally requires the presence of intestinal or colonic contents [72] and it subsides after these contents have been diverted. 2. A total of nine patients [16, 17, 19] (also personal observations) experienced healing of the inflam­ Figure 5. Moderate diversion colitis. Typical endoscopic mation after the bypassed segment had been findings include edema with loss of vascular markings, reconnected to the fecal stream. granularity and irregular areas of exudation, and superficial ulceration. 3. Ten patients with CD were treated with instilla­ tion of an SCFA solution and all responded within 6 weeks [15 (also personal observations). Although topical SCFA therapy of Crohn's coli­ tis has not yet been investigated, there is little reason to expect that it would be effective. Konrad H. Soergel 817

with a planned reanastomosis without the need for preoperative medical therapy. Diversion colitis dis­ appeared completely in all patients after colonic continuity had been re-estabhshed [2, 10, 16, 18, 21, 30, 55]. Second is the patient with symptomatic diversion colitis where reanastomosis or resection of the bypassed segment is contraindicated and which represents an indication for medical treatment. Third there are patients with asymptomatic diversion coli­ tis who are not candidates for reanastomosis. The decision for medical treatment rests on the question of whether progressive stenosis and the uncertain risk of neoplasia developing in the diverted segment (see 'Prognosis') justify chronic topical therapy. No recommendations can be given at this time because there are no observations on the efficacy of medical therapy in preventing these complications. Fourth is the patient with an inflamed segment and pre-exist­ Figure 6. Diversion colitis after 4 weeks of short-chain fatty ing IBD. Here a diagnosis of diversion coUtis will acid irrigation. Friability and ulceration have disappeared and favor a planned reanastomosis while active CD or vascular markings are noticeable, although mucosal edema UC would militate against it. As discussed earlier, remains (same patient as in Fig. 4). patients with known CD had a uniformly favorable outcome after continuity of the fecal stream had been re-estabhshed. In addition, three such patients were Only an occasional patient with UC will undergo treated by the authors with SCFA irrigations; the colectomy with plans for a later ileorectal anastomo­ inflammation subsided and did not reappear after sis. Persistent inflammation of the isolated rectum surgical reanastomosis. One may conclude, tenta­ usually represents diversion coUtis rather than UC, tively, that an inflamed diverted colorectal segment particularly if lymphoid follicular hyperplasia and in a patient with CD represents diversion colitis. surface exudates are present on histologic examina­ While the same reasoning may also apply to UC, a tion [73]. A therapeutic trial with instillations of favorable response to topical SCFA therapy does not neutral isotonic SCFA solution cannot distinguish distinguish between ulcerative and diversion colitis, between diversion colitis and persistent distal idio­ as discussed earlier. pathic UC because some patients with ulcerative proctosigmoiditis will improve [66-68]. The differen­ tial diagnosis should also include antibiotic-asso­ ciated colitis; while this is a theoretical possibility, it iVIisceiianeous ttierapy has not yet been reported. Finally, there may be mild The experience with medications known to be effec­ focal 'colitis' associated with diverticulitis in the tive in other IBD is largely anecdotal. Two patients bypassed colon, but this entity does not involve the with diversion colitis responded to 5-aminosalicylate entire excluded segment [10]. (Rowasa) [60, 74], while one did not [24]; one other failed to improve with Azulfidine suppositories [17]. Treatment with enemas caused improvement in six patients [2, 4, 11, 60], while six Treatment other patients did not respond [17, 23, 24]. Indications Decisions regarding the management of diversion colitis arise in different clinical settings: First there is Topicai SCFA tlierapy the patient with endoscopic and histologic findings The rationale for this therapy is to supply a mixture compatible with diversion colitis and documented of the three SCFA predominant in stool water by absence of mucosal disease prior to the surgical slow instillation into the diverted segment, either per diversion procedure. The surgeon should proceed rectum or through a mucus fistula. The composition Diversion colitis

Table 4. Short-chain fatty acid solution for treatnfient of diversion colitis [13]*

Acetic acid 7.206 g Propionic acid 4.448 g n-Butyric acid 7.049 g

Add 500-600 ml of deionized water; titrate with 1 N NaOH to pH7.0. Add NaCI, 2.500 g. Add water to total volume of 2.0 L. Osmolality: 285-290 mOsm/kg. Composition: acetate, 60 mmol/L; propionate, 30 mmol/L; n-butyrate, 40 mmol/L; Na, 152 mEq/L. May be kept in a screw-topped plastic container. Stable for 3 months, if refrigerated.

*This solution is not commercially available. Its use has not been reviewed by the US Food and Drug Administration.

of the solution used by the author is shown in Table 4. Sixty milliliters is instilled twice daily with a syringe, Prognosis either through a soft tip or an inflated Foley The prognosis of diversion colitis is good, although catheter. The patient remains supine for at least 30 prospective evaluations of patient groups over long min in order to avoid premature leakage. The initial periods of time are not available. Progressive luminal four patients so treated experienced resolution of narrowing and stricture formation have been symptoms, normalization of endoscopic appearance, observed repeatedly [1,6] and may begin as early as and disappearance of histologic evidence of acute 9 months following the diversion procedure [30]. inflammation [13]. Improvement generally is noted Surgical reanastomosis is not advisable in the pre­ at 2 weeks, but complete healing requires a treatment sence of a narrowed or strictured rectosigmoid seg­ period of 4-6 weeks. The authors have since treated ment. There are no data to document whether main­ tenance treatment with SCFA or corticosteroid six additional patients with identical favorable irrigations will stop the progression to a distal results [75]. Two children with diversion colitis also 'microcolon,' although this may be expected to occur. responded [12]. After healing has been achieved, There is no evidence of an increased risk of relapse will occur within 1-4 weeks if treatment is neoplasia in the disused segment. On theoretical discontinued. Remission can be maintained by redu­ grounds the decreased epithelial proliferation rate in cing the frequency of the instillations progressively to diversion colitis [53-55] supports this view, but the one daily for 1-2 months, then to three instillations/ differentiating effect of SCFA, especially n-butyrate, week. Instillations of the patient's own colostomy on various cell lines [53, 54] raises some concern in effluent into the diverted segment have been sug­ this regard. In one series of 45 patients with a gested [29]. This would avoid the need and cost of Hartmann's pouch, polyps were found in four and preparing the malodorous SCFA solution in the carcinoma in seven patients. However, these patients pharmacy or research laboratory, but this logical all had pre-existing conditions that placed them at idea has not yet been tested. No improvement was increased risk for colorectal neoplasia [11]. Patients reported in a placebo-controlled study of diversion with ureterosigmoidostomies and an intact fecal colitis, but the duration of observation was only 2 stream are at high risk of developing carcinoma of weeks, which may have been too little [8]. Negative the sigmoid, but this complication has not been results with SCFA enemas were obtained in a 3-week described in patients who underwent isolation of crossover trial of patients with underlying IBD [76], colonic segments for the creation of neobladders as well as in a 12-week study in which 14 of 21 [50, 78]. Certainly, patients who underwent colonic patients had IBD [77]. By contrast, in a 12-week resection for carcinoma with colostomy and a rectal study of seven patients with CD and an excluded Hartmann's pouch may develop metachronous car­ distal colorectum, marked improvement was noted cinomas [9, 10] and should therefore undergo regular beginning at 2 weeks of treatment [15]. In summary, endoscopic surveillance regardless of the presence of the effect of topical SCFA therapy on diversion diversion colitis. colitis continues to be debated. It appears, however, Concern has been expressed regarding bacterial that most patients receiving this therapy for at least 4 invasion of the 'weakened' epithelium in the diverted weeks, without underlying IBD and without the use segment, especially in patients with central venous of a solution preservative [76] will respond favorably. catheters who are prone to septicemia [26]. Konrad H. Soergel 819

In summary, the only definite risk of long-term 6. Flesh P. Wurbs D, Krueger P. Die Diversionskolitis. Dtsch MedVV^ochenschr 1986; 111: 1566-9. diversion colitis is progressive narrowing of the 7. Geraghty JM, Talbot IC. Diversion colitis: histological involved segment, which may preclude planned sur­ features in the colon and rectum after defunctioning colost­ gical reanastomosis. omy. Gut 1991; 32: 1020-3. 8. Guillemot F, Colombel F, Neut C et al. Treatment of diversion colitis by short-chain fatty acids: prospective and double-bhnd study Dis Colon Rectum 1991; 34: 861-3. 9. Haas PA, Haas GP. A critical evaluation of the Hartmann's Future directions procedure. Am Surg 1988; 54: 330-85. 10. Haas PA, Fox TA Jr, Szilagy EJ. Endoscopic examination of Research in diversion colitis will continue to focus on the colon and rectum distal to a colostomy. Am J Gastro­ the pathophysiology of this disease and its treatment. enterol 1990; 85: 850-4. There is considerable interest in the overlap between 11. Haas PA, Fox TA Jr. The fate of the forgotten rectal pouch after Hartmann's procedure without reconstruction. Am J idiopathic UC and diversion colitis, since both con­ Surg 1990; 159: 106-11. ditions share many histologic features as well as a 12. Haque S, West AB, Nioyer NIS. Correlation of clinical and favorable response to topical SCFA therapy [67]. pathologic features in pediatric patients with diversion Scientific inquiry into this disease is complicated by colitis. Gastroenterology 1991; 100: A215 [Abstract]. 13. Harig JM, Soergel KH, Komorowski RA et al. Treatment of the limited number of surgical diversions performed diversion colitis with short-chain fatty acid irrigation. N at any one medical center. An animal model of this Engl J Med 1989; 320: 23-8. disease has recently been described [37], but has not 14. Komorowski RA. Histologic spectrum of diversion colitis. Am J Surg Pathol 1990; 14: 548-54. yet been evaluated as to its applicability to humans. 15. Korber J, Soudah B, Schmidt FW. Effects of short-chain Specific areas of promising research directions fatty acids irrigation on excluded inflamed segments of the include the following questions: colon in Crohn's disease. Gastroenterology 1992; 102: A648 [Abstract]. 16. Korelitz BI, Cheskin LJ, Sohn N et al. Proctitis after fecal 1. What events are involved in the apparent link diversion in Crohn's disease and its elimination with reanas­ tomosis: implications for surgical management. Report of between metabolic starvation of the colonic four cases. Gastroenterology 1984; 87: 710-13. epithelium and the subsequent initiation of im­ 17. Korelitz BI, Cheskin LJ, Sohn N et al. The fate of the rectal mune/inflammatory responses? segment after diversion of the fecal stream in Crohn's disease: its implications for surgical management. J Clin Gastroenterol 1985; 7: 37-43. 2. Are diverted segments at increased risk of malig­ 18. Lechner CL, Frank W, Jantsch H et al. Lvmphoid follicular nant transformation? hyperplasia in excluded colonic segments: a radiologic sign of diversion colitis. Radiology 1990; 17: 135-6. 19. Lohr HF, Mayet WJ, Singe CC et al. Diversionskolitis bei 3. How do SCFA irrigations reverse diversion coli­ Morbus Crohn. Z Gastroenterol 1989; 27: 221-4. tis - direct replacement of a critical, obligate 20. Lusk LB, Reichen J, Levine JS. Aphthous ulceration in diversion colitis: clinical implications. Gastroenterology substrate, merely a nutritional adjuvant to help 1984; 87: 1171-3. heal inflamed tissue, or local vasodilatory effects? 21. Ma CK, Gottlieb C, Haas PA. Diversion colitis: a clinico- pathologic study of 21 cases. Hum Pathol 1990; 21: 429-36. 22. Mingazzini PL, Guiliana A, Caporale A et al. Defunctioned 4. 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