RECURRENCE AND ITS PREVENTION

Recurrence in Crohn's disease

ADRIAN J GREENSTEIN, MD, FACS, FRCS

AJ GREENSTEIN. Recurrence in Crohn's disease. Can J Gastroenterol 1993; 7(2):211-214. Although in 1932 Crohn, Ginzburg and Oppenheimer noted recurrence in two of their 14 patients, they did not appreciate the remarkable propensity of this disease to recur following resection of all macroscopically diseased bowel. It was only later that the true panenteric nature of the disease was appreciated. Dunng the following three decades many believed that 'radical resection' wmild cure the disease, but subsequent studies showed that this was fallacious. Three types of recurrent Crohn's disease may be Jefined: symptomatic, recurrence recognized by pathological, radiological or endoscopic techniques ( true recurrences); and operative. On! y recurrences confinned by endoscopy, and gross and microscopic pathology should be accepted as true recurrent disease. Many factors influence postoperative recurrence rates. All series studied ac­tuarially show a steady increase in calculated recurrence rates with time (which is the major and dominant factor). Other factors which increase recurrence rares are anatomic localization (ilea! or ileocolonic), type of operation performed (bypass versus resection), and multiple resections. Factors which probably in­fluence races arc long segment disease, second reoperation, perforating disease, and young age at onset. Factors which possibly influence rates are overt disease at the resection margins and female sex. The presence of microscopic or macro­scopic disease at the resection margins, and the amount of normal-appearing howel removed do not appear to affect rates of recurrence. Following stric­tureplasty recurrence rates arc at least as high as following resection.

Key Words: Crohn's disease, Recurrence, Recurrence rates, Posroperative recur­rence, Stricmreplasry

Recurrence de la maladie de Crohn

RESUME: Bien qu'en 1932 Crohn, Ginzburg et Oppenheimer aient note une recurrence chez deux de leurs 4uarorze patients, ils n'ont pas mesurc la rcmarqua­ble propension de cette maladie a recidiver suite a la resection de toutes les portions d'intestin affectees macroscopiqucmcnt. Ce n'cst que plus tard que la veritable nature panenterique de la maladie a ere appreciec a sa juste valeur. Au cours des trois decennies suivantes, plusieurs ont cru que la resection radicale serait la solution, mais des etudes subsequences ont infirme cette hypothese. T rois types de maladie de Crohn recidivantcs sont definis: syrnptomatique, c'esr-a-dire quc les rccidives sont reconnues par des techniques anatomo-pathologiques, radiologiques ou endoscopiques (recurrences vraies); et par la chirurgie. Seules les recurrences confinnees par endoscopie et par l'anatomo-pathologie macro-

Profe5sor of Surger:v, The Moun( Sinai School of Medicine of the City Unit•L>r.my of New York, New York, New York, USA

Comis/>ondence and reprinL1: Dr N Green.1Cem, Muun( Smai Medical Center, Department of Surgery. One Gustat•e L Lev)• Place, Neu, York, NY /0029, USA

CAN] GASTROENTERL)L VOL 7 No 2 FEBRUARY 1993

CROI IN ET AL (I) IN T l IEIR INITIAL

paper in 1932 on regional ileitis, noted that recurrent disease occurred in two of their L 4 patients. In the years that followeJ it became evident that the most common postoperative sequel of Crohn 's disease was recurrent ileitis, most frequently affecting the neoter­minal ileum just proximal to or at the anastomosis. Many factors influence postoperative recurrence rares. impor­tant among the surgical considerations are anatomic localization, type of operation performeJ (bypass versus resection, or complete versus staged procedures), the length of bowel in­volved, presence of microscopic or macroscopic disease at the resection margins, and amount of normal­appearing bowel removed.

It is generally accepted that the rate of postoperative recurrence is high in Crohn's Jisease involving only or mainly the small bowel. The question of recurrence in Crohn's colitis in which the disease is confined to the large bowel remains controversial. There is considerable variation, how­ever, in reported recurrence rates for all types of inflammacory bowel disease (lBD) , reflecting the differences in patient populations, referral patterns, ways of defining recurrent disease, methods of calculating recurrence rates, operative procedures and lengths of follow-up.

The diagnosis of primary and recur­rent Crohn's Jisease in the sympto­matic patient has classically been established by radiological methods (2) but thickened narrow bowel can also he

Z 11

GREEN~TEIN

scopique et microscopique Jevraienc etre acceptees comme signcs d'une recurrence reelle de la maladie. Plusieurs facteurs influent sur les raux de recurrence post-operaroire. Toutes les series etudiees par metho<le actuarielle font etat d'une augmentation conscante des taux calcules de recurrence avec le temps (qui est le facteur principal et dominant). Parmi les autres facteurs qui contribuent a la hausse au taux de recurrence, notons le siege anatomique (ilea I ou ileocolique), le type d'operation effectuee (deviation versus resection) et les resections multiples. Les facteurs qui influent cgalement sur ces taux sont l'ctcnduc Jes lesions, la re-operation, la maladie perforame et le jeune age au debut de la maladie. Les facteurs qui influencent possiblement les taux sont la maladie avercc aux margcs des resections ct le fair d'etre de sexe feminin. La presence de maladie microscopiquc ou macroscopique aux marges de resection et la portion d'intestin d'apparence normale n~sequec ne scmblcnt pas influer sur !es taux de recidives. Suite a la plastic des portions retrccies, !es taux de recurrence sont au moins aussi clevcs que suite a la resection.

apprecinte<l on computed tomography scan. Sites of recurrence may he seen endoscopically, provided I hey arc with­in reach of the colonoscnpc from he low or the gasrroduodenoscope or entcro­scope from above (3,4). W1ch these in­struments, macroscopic changes (such as aphthous or frank ulcers) can be ob­served, biopsies can he taken nnd, on rare occasions, granulomas dcmonstra­led, confi rming the presence of active Crohn's disease.

DEFINITION OF RECURRENT DISEASE

Lennard-Jones and Scalder (5) divided recurrences into recurrence uf clinical symptoms without evidence of new disease; recurrent symptoms wilh radiological and/or histological (endo­scopic should be added today) proof of disease; and recurrent disease requiring further surgery. Rutgeerrs ct al ( 4) defining a high incidence of endoscop1-cally recognizable recurrence (73% ar one year, of which only 20% were sympromauc), suggcstc<l that the ulti­mate course of the disease may be predicted by the severity of the early postoperative lcsiom ( 4 ).

METHODS OF ESTIMATING RECURRENCE

Many of the early discrepancies re­poncd in the literature reflect the fact that the earliesl repons est imatcJ over­a ll recurrence rates in a crude fashicm, simply noting the numher of recurren­ces occurring in the total group studied. In 196 7, Lennard-Jones and Stalder ( 5)

useJ actuarial methods incorporating the data obtamcd with progressive pas­sage of time into an actuaria l life-table. In 1975, the current authors (6) ex­amincJ several different factors influ­encing actuarially calculated recur­rence rates and confirmed many of the earlier findings. Sachar ct al (7), using multivariate analysis, observed that the critical question is not only which fac­tors influence recurrence rates, but which factors dn so in<lependently of other confounding influences.

FACTORS INFLUENCING RECURRENCE

DcDombal ct al (8) suggested that there were two types ofCrohn 's disease: an aggressive sort and a more slowly progressive type. We have studied a series of 770 patiems, among whom there appeared to he rwo different forms of Jiseasc. The perforating type appeared to he more aggressive anJ recurred sooner, while the nonperforat­ing type recurred later (9).

A ll series studied actuarially show a steady increase in calculated recur­rence rates with time which is the major and dominant factor in these rates. Ocher factors which influence: recurrence rares are ilea! or ilcocolonic disease, bypass and multiple resec­tions. Factors which probably influence rates arc long segment disease, second reoperation, perforating disease and young age m ornet. Factors which pos­sibly influence rares are overt disease at the resection margins and female sex.

Age appears w have an influence on

the 1endency en recur. In almost all reports on the subject, the recurrence rntc has hecn consistently greater 111

younger age groups. This 111/luence oi age remains valid even when actuarial methods are used to correct for varrn­tions m follnw-up inrerval. Most authors find no difference in recurrence rates hetwcen men and women, al­though a considcrnhly poorer prognosis in women has heen noted (8).

The anatomic site of 111volvemenr helps to determine the likelihood of recurrence. High recurrence rates, hoth crude and actuarial, have been reponcJ for most ~cries of patients with regional ileitis following resection ( recurrence rates ranging from 42 to 86% at 15 years). Even higher rates follow bypas\ and there is liule controversy regarding recurrence in small btYwel disease. The question of recurrence in Crohn's colitis, in which the disease is initially confined to the colon, however, has engendered argument. Most observer, believe that patienn, with disease con­fined to the colon have a lower rme of recurrence than tht)Se in whom the ter­minal ileum is involved, although some have found no difference (10). There is agreement that recurrence following subtotal colc:c tomy and ilcorectal or ileos1gmo1d re-anastomosis 1s high.

The propensity of the proximal and distal segments of the gut to develop evidence of disease after an operative procedure has bearing on the problem of postoperative recurrence. Most authors report recurrences in rhe neo­tcrminal ileum just proximal to the su­ture line in patients with anastomosis or in the most disrnl ileum following ileostomy. Koch ct a l ( 11) found that the site of recurrence was determined hy the site of primary disease. In ileitis, 100% of recurrences involved the proximal gut, 30% were both proximal and distal, anJ none was exclusively distal. Recurrences in ileocolitis patients developed proximally in 19%, distally in 19%, anJ both proximally and Jisrally in 62%. Thus, disease mi­tial ly confined to the terminal ileum may suhsequently progress to involve the colon following re~cction and rc­ana~tomosis.

Of 68 surgical ly treated cases of IBD

212 CAN J GA~TROENTEROL Vn1 7 Nt) 2 FERRUARY 1993

sparing the rectum, Korel1cz (1 2) found distal spread to the rectum in 4 3 (39°,,{,), proximal spread in 39 (35%), prox imal and dista l spread in 16 (14%) and no spread in 16 04'}6 ). In ileocolins or colitis, therefore, distal recurren ce is as common a~ proximal recurre nce, whereas in ile itis, proxima l recurren ce is considerably more common . A l­though a number of studies suggcsL an inverse relationship between recur­rence a nd preoperati ve durnrinn of dis­ease - the shorte r the duration , the highe r the recurre nce ra te - t his has not bee n confirmed.

In an outstanding study hy Rutgecrts et al ( 4) on 89 pau ents studied pre­opera tively and examined e ndoscop1-cally in t he postoperative pe riod, the ultima te course of the disease was best predic ted by the early postoperative lesion s observed at ileoscopy. C linical factors which influen ced outcome were preoperative disease activity, surgical indication , and number of surgical resections.

RECURRENCE FOLLOWING STRICTUREPLASTY

There h as been considerable dif­fe rence of opinion among surgeons regarding resection of apparently nor­mal bowe l beyond the obviously d1s­caseJ segment. Lengths of variable extem h ave heen suggested. However, the findings of a study by Pennington c t al ( 13 ) did no t support the concept of radical howe l resection . These oh-

REFERENCES I. Cmhn BB, G inzhurg L, Oppenheimer

GD. Regional ilettis; a pathologic and clinical enLily. JAMA I 932;99: l323-9.

2. Marshak RI I, Lmdner AE. Ra<liology of the Small Incest im', 2nd cdn. Philadelphia: WB Saunders Co. 1976: 179-300.

3. Waye JD. Endoscopy in mflammatnry bowel disease. C lin Gasrroemerol l 980;9:279-96.

4. Rucgeerts P, Gehoes K. Vanrrappen G, Beyls R, Kcrremans R, Hicle M. Pred ictabd uy of the postoperative course of Crohn's disease. Ga~troenterolngy J 990;99:956-6 >.

5. Lennard-Jones JE, Stalder GA. Prognosis after resectinn of chrome regiomi l ileitis. Gut 1967;8:332-6.

6. G rcen~1ein AJ, S;ichar DB, Pastemak BS, Janowicz HD. Reopenition and

servers found no difference in recur­ren ce rates whether there was d isease at t he rescctilm margin. Lee ct a l ( 14) al~o re ported that there was no ~1gnificant diffe rence in the ttmcs o r frequenc ies of recurrence a mong 24 patients with ac­tive inflammat ion ur Lo the limit of resection and a s imilar number studied with no disease at the resection ma rgin. The ir reCt)mmcndation was, therefore, to carry out 'cnteroplasty' witho ut resection on r a t1ents with multiple areas of d isease. They cla imed satisfac­to ry results, wnh preservation ot as muc h bowe l as possihle using these nonresect iona l techniques. A recent 10 year fo llow-up from Oxford by Dehn ct al (l 5) supports the ir early posit ive re po rts; they found a reoperation rate of 16%, four of 24 patients requiring a furthe r 13 stric turcplastics. Sayfan ct a l (16) found that the s ite-specific opera­tion -free inte rval~ 111 41 pat iem s of 75% at five years were no t significantly differe n t from an equa l number treated by sma ll bowel resection . However they used strictureplasty and n ot patients as the den ommator in the former group. In a series of 27 strictureplasty patients subjected to 126 strictureplasties car­ried out by this author e igh t required reoperation (two were for cancer, three for new stric tures, and three for per­forating complicat ions). Actua rially calculated reoperation rates were at least as high as for sma ll bowel resec­tion. A mo1,t i.ntercsting aspect of this type of surgery is t he relatively infre-

7.

8.

9.

IO.

recurrence m Crohn's coli tis and ileocoli11s: Crude and cumulalive rares. N Engl J Med J 975;293:685-90. Sachar DB, Wolfson OM, Greenstein AJ, GnldbergJ, Styczynski R, J,mown: HD. Risk factors for postoperative recurrence of Crohn 's disease. Gastrocnterology I 983;85:9 L 7-2 1. DeDomhal FT, Burton IL, Goligher JC. Recurrence of Crnhn's d15ease ;iftcr pnmary excisional surgery. C ut 197!;12:519-27. Greenstein AJ, Lachman P, Sachar DB, et al. Perfornrmg and nonperforaring ind1cau,ins for repeated ,,perat inns in Cmhn's d1sea,c: Ev1Jence for tw0 clinical fmms. n ut L 988;29:588-92. H11na l HS, Bell1veaup. Prngnnsi~ niter surgical treatment for granul0matous entcm1s and colit is. Am J Surg

CAN J GASTROFNTERm VOL 7 No 2 FrnRUARY J 993

Recurrence in Crohn's disease

q ue nt occurrence of recurrent st rictures at origina l st ricturcplasty sites, occur­nng in approx imately 2°1<, ( three of 127) of reported striLture plastics ( 17).

A lthough Ritchie and Lockha rt­Mummery ( 18 ) re po rted an inc reased recurrence rate in patie nts with staged operative procedures, this find mg is dis­puted hy S te inberg c t a l ( I 9) who found no suc h differen ce.

Cooke ct a l (20) found that the n umher of operations was greate r in

patien ts who received steroids. How­ever, patien ts who have required and received steroid therapy arc not , in most respects, cl inically comparable to those who have nor.

The ul t ima te o biective of treat­me n t of Crohn's disease 1s a phys10-log1cally we ll pa tient , wh o is a ble to

lead a norma l life , work regularly, a nd inte rac t 1,oc.ially in his o r her ordina ry environme nt. S tudies fro m Leeds, Birmingha m and New Yo rk, have fo und favorable results in over 90% of pa tie nts (2 l -23).

T he decision to intervene surgically in recurrent Crohn 's disease is one of the most cha lle nging problems in clini­cal medic ine. It should be a jo int decis ion made by surgeon and gastro­enternlog1st. When made at an appro­pnate time following fa ilure of medical thcrnpy to con trol the disease, ~urgical intervention will lead to a be tter quality of li fe, reduce morbidity and minimize morrnl1ty 111 this chronic, in­c urable intestinal affliction.

Jl)8 J ;142:347-9. I !. Koch TR, Cave DR, K1rsncr JB.

Anatomical pauerm of po,t surgical recurrence of Crnhn \ deius rmd ileocoltw,. Gastrocntcmlogy 1980;78: 11 97. (Abst)

12. Koreli u Bl. C lin ical course, late results, and pathological nawre of inflammatory dtse::ise of the colon m1w11ly sparing lhe rectum. Gut J 980;8:28 l-90.

J 3. Pennmgton L. l lamilwn SR, Bayless TM, Cameron JL. Surgical man.igemen1 of Crohn 's disease. I ntlucnce of disease at margin of resect ion. Ann Surg 1980;192: 31 1-8.

14. Lee ECG, Papaioannou N. Recurrence, following surgery for Crohn 's disease. Chn Ga~rrocnterol I 980;9:4 I 9- 38.

15. Dehn TCB, Ke ttlewell MGW,

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GREENSTEIN

Mortenson NJMcC, the late Lee ECG Jewell DP. Ten year experience of stricrureplasty for obstructive J1sease. Br J Surg 1989; 76:339-41.

16. Sayfan J , Wi lson DAL, Andrews AAH, A lexanJer-WilliamsJ. Recur­rence after strictureplasty for Crohn's disease. Br J Surg. 1989;76:335-8.

17. Fazio VW, Galan<l iuk S, Jagelman DG, Lavery IC. Strictureplasty in Crohn\ disease. Ann Surg 1989:210:6Zl-5.

18. R1tch1e, JK, Lockhart-Mummery I IE. Non-reswrative surgery in the

214

treatment ol Crohn's disease of the large bowel. Gut 1973;14:263-9.

19. Steinberg, DM, Allan RN, Thompson H, Brooke BN, AlexanJer-WilliamsJ, Cooke VVT. Excimmal surgery with ileostcimy for Cmhn's coli tis with particular reference to factors affecting recurrence. Gue 1974; 15:845-'i I.

20. Cooke VVT, Mallas E, Prior R, Allan RN. Crohn\ disease: Course, treatment and long-term prognosis. QJ Med 1980;195:363-84.

2 l. Goligher JC. In: Surgery of rhe Anus,

Rectum and Colon, 4th edn. Springfield: Charles C Thomas, 1980:745.

22. Allan R, Srcmberg DM. WilliamsJA, Cooke WT. Crohn's disease involving the colon: An audit of clm1cal management. Gastroem erology 1977;73:7723-32.

23 Meyers S, Walfish JS, Sachar DB, Grecnsrcin AJ, Hill AG, Janowm HD. Quality of life afrcr ,urgery for Cnihn's <lisease. A psychosocial survey. Gast rucnrerology 1980; 78: 1-6.

CAN] GASTROENTEROL VOL 7 N0 2 FERRUARY 1993

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