Toxic megacolon — unusual complication of pseudomembranous colitis

Thomas Hoogland, M.D. Avram M. Cooperman, M.D.

Department of General Surgery

Richard G. Farmer, M.D Department of Gastroenterology

Victor W. Fazio, M.D.

Department of Colon and Rectal Surgery

Pseudomembranous colitis (PMC) is a severe inflammatory disease process that affects the gastrointestinal tract. It was first described as a postoperative complication by Finney1 in 1893. T h e name is derived f rom a thick tenacious membrane that coats the lumen of the bowel and consists of fibrin, leukocytes, and microor-ganisms. The severity of the illness varies f rom mild and clinically undetected to fulminating and fatal.

Rarely will PMC have presenting symptoms or simulate toxic megacolon. An experience with two fatal postoperative cases has prompted this report and a review of previously published cases (Table).

Case reports Case 1. A 69-year-old woman with a rectosigmoid

tumor was admitted to the Cleveland Clinic Hospital on September 3, 1975. The preoperative proctoscopic biopsy specimen of this lesion revealed atypical cells. Results of physical examination and all laboratory tests (complete blood count, SMA-12, SMA-6, ECG, chest roentgenogram, spirometry, and arterial blood gases) were normal. At surgery a Meckel's diverticu-lum and benign sessile polypoid lesion of the colon were excised. Postoperatively, her progress was satis-factory until a symptomatic urinary tract infection (enterococcus, 100,000 colonies/ml) developed on the sixth postoperative day; the infection was treated with ampicillin, 500 mg orally, four times a day for 6 days.

149

150 Cleveland Clinic Quarterly Vol. 44, No. 3 '

Table. Summary of the five published cases of toxic megacolon complicating PMC

Antibiotic used before Underlying condi- onset of toxic dilata- Treatment at stage of

Authors tion tion megacolon Outcome

Brown et al23 Otitis med ia

Ecker et al5 Sinusitis 1970

Wells et al24 No t stated

Tet racycl ine , no-vobiocin, chlor-amphen ico l , cepha lo th in

Lincomycin

Cl indamycin

Lactobacil lus g r anu l e s , digi-talis, s teroids, methici l l in

D o n o r feces ene-mas , A C T H , cardio tonics , vancomycin

Not s ta ted

Satisfactory a f t e r 1 m o

Satisfactory a f t e r several m o n t h s

Fatal

H o o g l a n d e t al Postoperat ive , Kanomycin , am- "Blowhole" t rans- Fatal Case 1 resection of picillin verse colostomy

colonic polyp a n d loop ileos-tomy , methicil-lin, ch lo ram-phen ico l , cardi-otonic d rugs , s teroids

H o o g l a n d et al Postoperat ive , Lincomycin A s c e n d i n g a n d Fatal Case 2 total h i p re- t r ansverse co-

p lacement Ion "blowhole" colos tomy, van-comycin , ceph-a lo th in , cardi-otonics

On the 12th postoperative day, loose, watery green stools were passed, a rectal temperature of 101F and white blood cell count (WBC) of 21,600 mm3 were re-corded. Ampicillin was discontinued. A Gram stain and stool culture for aerobic and anaerobic bacteria revealed normal flora. Treatment was symptomatic and consisted of diphenoxylate (Lomotil) tab-lets and yogurt. The clinical course was stable for the next 4 days although the diarrhea continued. On the 17th postop-erative day she became lethargic. At this time a distended abdomen was noted. Laboratory data, previously normal, now revealed hemoconcentration (hematocrit 52%), an elevated blood urea nitrogen (BUN) of 62 mg/dl (normal 15 mg/dl), and a creatinine of 3.1 mg/dl. An abdom-inal roentgenogram revealed a dilated and gas-filled colon and rectum. The

patient became hypotensive, and Ringer's lactate (5 liters) and colloid (100 g albu-min) administered intravenously restored a depleted central volume. Proctoscopic examination revealed a diffuse, thick confluent pseudomembrane adherent to the rectal mucosa. A repeat abdominal roentgenogram revealed colonic dilata-tion to 12 cm (Fig. 1). Methicillin, 1 g; Chloromycetin, 250 mg; and methylpred-nisone, 300 mg, were each given intrave-nously every 6 hours. Eighteen hours later the abdomen became more dis-tended. Tachypnea and dyspnea as well as hypotension developed. The patient underwent a decompressive "blow hole" transverse colostomy and "loop ileos-tomy" in the hope of decompressing the colon and reducing the sepsis.

Postoperatively she became anuric, and metabolic acidosis and septic shock

Winter 1977 Toxic megacolon 151

Fig. 1. R o e n t g e n o g r a m shows di lated cecum a n d t ransverse co lon .

d e v e l o p e d . T h e W B C r o s e t o 5 5 , 0 0 0 m m 3 . H y p o t e n s i o n , b r a d y c a r d i a , a n d p r e m a t u r e v e n t r i c u l a r c o n t r a c t i o n s d e -v e l o p e d , a n d s h e d i d n o t r e s p o n d t o i n t r a v e n o u s fluids a n d c a r d i o t o n i c d r u g s . S h e d i e d 15 h o u r s a f t e r o p e r a t i o n .

A t a u t o p s y t h e e n t i r e c o l o n r e v e a l e d a d i f f u s e c o n f l u e n t p s e u d o m e m b r a n e t h a t w a s a d h e r e n t t o t h e c o l o n i c wal l . T h e p s e u d o m e m b r a n e s h o w e d l e u k o c y t e s , g o b l e t ce l l s , g r a m - p o s i t i v e cocc i a n d g r a m - n e g a t i v e r o d s . T h e p r o c e s s e x -t e n d e d i n t o t h e s u b m u c o s a a n d d i d n o t i n v o l v e t h e d e e p e r l a y e r s . T h e r e was n o i n v o l v e m e n t o f t h e s m a l l b o w e l o r o t h e r a b d o m i n a l o r g a n s .

C a s e 2 . A 6 2 - y e a r - o l d m a n w i t h o s -t e o a r t h r i t i s o f t h e r i g h t h i p w a s a d m i t t e d t o t h e C l e v e l a n d C l in i c H o s p i t a l o n N o -v e m b e r 17, 1974, f o r a r i g h t t o t a l h i p r e p l a c e m e n t . H e h a d a h i s t o r y o f e p i -s o d e s o f m i l d g o u t , h y p e r t e n s i o n , o b e s i t y , a n d a n a l l e r g y t o p e n i c i l l i n . A n a n a l fis-s u r e h a d b e e n e x c i s e d in 1960.

O n N o v e m b e r 18, 1974, h e r e c e i v e d a C h a r n l e y - M i i l l e r r i g h t t o t a l h i p p r o s -t h e s i s . P r o p h y l a c t i c p o s t o p e r a t i v e a n t i -b io t i c s c o n s i s t e d o f l i n c o m y c i n , 600 m g

i n t r a v e n o u s l y e v e r y 6 h o u r s f o r 3 d a y s a n d t h e n o r a l l y , 500 m g f o u r t i m e s a d a y f o r 3 d a y s . O n t h e first p o s t o p e r a t i v e d a y t h e t e m p e r a t u r e w a s 103F a n d t h e c h e s t r o e n t g e n o g r a m , W B C , a n d b l o o d c u l -t u r e s w e r e n o r m a l . F o r t h e n e x t 2 d a y s t h e t e m p e r a t u r e w a s n o r m a l . O n t h e fifth a n d s i x t h p o s t o p e r a t i v e d a y s t w o l i q u i d s too l s w e r e p a s s e d . T h e r e c t a l t e m p e r a -t u r e w a s 100F.

O n t h e e v e n i n g o f t h e s i x t h p o s t o p e r a -t ive d a y , h y p o t e n s i o n , a b d o m i n a l d i s t e n -s i o n , a n d d e h y d r a t i o n w e r e a p p a r e n t . A n a b d o m i n a l r o e n t g e n o g r a m s h o w e d m a r k e d g a s e o u s d i s t e n s i o n o f t h e e n t i r e c o l o n t o 14 c m (Fig. 2). P r o c t o s c o p i c e x a m i n a t i o n r e v e a l e d a n e r y t h e m a t o u s r e c t a l m u c o s a w i t h a t h i c k ye l l ow m e m -b r a n e c o a t i n g t h e e n t i r e r e c t u m .

A d i a g n o s i s o f P M C w i t h m e g a c o l o n w a s m a d e . A G r a m s t a i n o f t h e s t o o l s h o w e d n o r m a l flora. S t o o l c u l t u r e s w e r e n e g a t i v e f o r Staphylococcus a n d Salmonella b u t p o s i t i v e f o r t w o s t r a i n s o f Escherichia coli. B o t h s t r a i n s w e r e r e s i s t a n t t o all t e s t e d a n t i b i o t i c s . T h e c u l t u r e s a l s o r e -v e a l e d Klebsiella pneumoniae s e n s i t i v e t o c l i n d a m y c i n a n d e n t e r o c o c c i r e s i s t a n t t o c l i n d a m y c i n .

B l o o d c u l t u r e s r e v e a l e d E. coli r e s i s t a n t t o all t e s t e d a n t i b i o t i c s . T h e W B C w a s e l e v a t e d a t 3 6 , 0 0 0 / m m 3 . T h e B U N w a s 96 m g / d l . T h e s e r u m c r e a t i n i n e w a s 5 . 6 m g / d l . T h e s e v a l u e s h a d b e e n n o r m a l 3 d a y s e a r l i e r . S ix l i t e r s o f c o l l o i d a n d R i n g e r ' s l a c t a t e w e r e g i v e n i n t r a v e n o u s l y a n d t h e c e n t r a l v e n o u s p r e s s u r e w a s m a i n t a i n e d a t 10 c m H 2 ( ) . T h r o u g h a L e v i n t u b e , 1 g v a n c o m y c i n w a s g i v e n e v e r y 4 h o u r s , a n d c e p h a l o t h i n ( K e f l i n ) , 2 g i n t r a v e n o u s l y e v e r y 4 h o u r s . D u r i n g t h e n e x t 12 h o u r s t h e a b d o m e n b e c a m e m o r e d i s t e n d e d , t h e W B C r o s e t o 5 2 , 0 0 0 m m 3 , a n d t h e a b d o m i n a l r o e n t g e n o g r a m s h o w e d p r o g r e s s i v e d i s t e n s i o n o f t h e e n -t i r e c o l o n . T h e p a t i e n t w a s b r o u g h t t o s u r g e r y a n d u n d e r loca l a n e s t h e s i a a n a s c e n d i n g a n d t r a n s v e r s e " b l o w h o l e " co -l o s t o m y w a s m a d e . A p p r o x i m a t e l y 2 0 0 0 cc o f p u r u l e n t , m a l o d o r o u s m a t e r i a l w a s d r a i n e d , a n d a b i o p s y s p e c i m e n o f t h e

152 Cleveland Clinic Quarter ly Vol. 44, No. 3 '

Fig . 2. Severe dilatat ion of c ecum out l ined by a r rows .

c o l o n wal l s h o w e d P M C . P o s t o p e r a t i v e l y t h e p a t i e n t ' s c o n d i t i o n

d e t e r i o r a t e d . A r i g h t p l e u r a l e f f u s i o n w a s d r a i n e d a n d 1900 cc o f s e r o u s f l u i d w a s o b t a i n e d . I n t u b a t i o n w a s n e c e s s a r y a n d a n u r i a d e v e l o p e d . T h e W B C r o s e t o 8 2 , 5 0 0 m m 3 . S u b s e q u e n t l y h y p o t e n s i o n a n d b r a d y c a r d i a d e v e l o p e d w h i c h r e -m a i n e d r e f r a c t o r y t o c a r d i o t o n i c d r u g s . T h e p a t i e n t d i e d 72 h o u r s a f t e r s u r g e r y .

A n a u t o p s y r e v e a l e d s e v e r e P M C o f t h e e n t i r e c o l o n i n c l u d i n g a 2- x 2 - c m h a m a r t o m a t o u s p o l y p in t h e m i d - c o l o n . T h e p u r u l e n t , c r u s t y , y e l l o w - t a n p s e u d o -m e m b r a n e w a s f i r m l y a d h e r e n t t o t h e c o l o n wa l l . T h e c o l o n wal l w a s m i l d l y t h i c k e n e d a n d e d e m a t o u s . N o a r e a s o f f r i a b i l i t y o r o b v i o u s n e c r o s i s w i t h i n t h e b o w e l wa l l o r m e s e n t e r y w e r e p r e s e n t . T h e r e w a s n o i n v o l v e m e n t o f s m a l l i n t e s -t i n e o r o t h e r a b d o m i n a l o r g a n s .

M i c r o s c o p i c a l l y t h e p s e u d o m e m b r a n e s h o w e d m a n y l e u k o c y t e s , n e c r o t i c d e b r i s , f i b r i n , g o b l e t ce l l s , a n d m a n y g r a m - p o s i -t ive a n d g r a m - n e g a t i v e b a c t e r i a (Fig. 3).

Discussion

A l t h o u g h P M C h a s b e e n r e c o g -

Fig. 3. P s e u d o m e m b r a n e and polypoid le-sions on the gross spec imen at necropsy .

nized for 84 years, there has been no agreement regard ing its pathogen-esis, incidence, and t rea tment . Fac-tors predisposing to this process in-clude postoperative states,2 , 3 intes-tinal obstruction, colon surgery,3 sep-sis, cardiac disease,4 staphylococcal overgrowth of the bowel, and anti-biotics.5 Rarely will PMC develop in the absence of any of these factors.6

In the past few years nearly all re-

Winter 1977

ported instances have followed the use of antibiotics. T h e antibiotics in-cluded ampicillin, tetracycline, chlor-amphenicol, lincomycin and its chlo-rodeoxy analogue, clindamycin.7-13

Despite the numerous reports in-criminating antibiotics, it is difficult to prove that antibiotics alone are responsible for the development of PMC, since infection and other fac-tors that dictate the need for antibiot-ics may themselves be factors in the development of this process.

For example, Pettet et al14 com-pared the incidence of postoperative PMC at the Mayo Clinic in two 14-year periods. The incidence of PMC was similar before (1925-1938) and after (1938-1952) antibiotics were in-troduced. During the latter period an increased awareness of the entity led to a correct premortem diagnosis in 14 of 26 cases.

As antibiotics became more widely used, particularly in bowel prepara-tion, a number of reports showed that staphylococcal overgrowth was responsible for "enterocolitis."15 Even then, despite vigorous supportive treatment, a mortality rate of 91% was not uncommon in severely ill patients.16 As antibiotic preparation of the bowel became modified so that shorter preparations were used, en-terocolitis became less common.

Although diarrhea follows the use of antibiotics in 10% to 50% of cases, PMC develops much less frequently.17

In one prospective study, a procto-scopic picture compatible with PMC developed in 10% of patients receiv-ing clindamycin.17

When lincomycin and clindamycin were studied in experimental ani-mals, a consistent change in cecal bacterial flora was noted.18 These changes were dose related. This re-lationship between duration of usage,

Toxic megacolon 153

dose, and change in flora has not been as direct in the few human studies.

The clinical picture of PMC is fairly typical, beginning with diar-rhea, which may abate spontaneously when the d rug is stopped, or may progress to produce electrolyte ab-normalities and dehydration. It is im-portant that the diagnosis be made early, before these complications de-velop. This is because morbidity and mortality increase as the disease pro-gresses.17 An unusual feature of our two cases was the abrupt and explo-sive onset of symptoms. In one pa-tient hypotension and massive diar-rhea were the presenting symptoms. Whether this is unusual or represents a more aggressive onset in sup-pressed postoperative patients is un-known.

In many instances cessation of the antibiotics alone will result in relief of symptoms and reversal of the proctoscopic findings. Some investi-gators have observed that yogurt, do-nor fecal enemas,19 steroids,20 vanco-mycin21 or cholestyramine may has-ten resolution, but these reports are anecdotal and uncontrolled. In a few instances PMC may progress and simulate a toxic megacolon similar to that seen in inflammatory bowel dis-ease, Chagas' disease or amebiasis.

Kleckner et al22 in 1952 and Pettet et al3 in 1954 observed dilatation of the colon with PMC in autopsy stud-ies. However, it was Brown et al23 in 1968 who first described toxic dilata-tion of the colon complicating PMC. Since then other cases have been re-ported, although more have likely been encountered.5 , 2 4

Two important diagnostic tests that establish the diagnosis are procto-scopic examination and plain roent-genograms of the abdomen. Procto-

154 Cleveland Clinic Quarterly Vol. 44, No. 3 '

scopic examination will reveal a thick yellow membrane that coats the rectal mucosa. It consists of fibrin, cell de-bris, leukocytes, and viable bacteria which may lie between the pseudo-membrane and the mucosa.

Plain roentgenograms of the abdo-men will reveal dilatation of the colon in cases with megacolon. The diame-ter of the colon will vary; in our two cases the colons measured 12 and 14 cm at their widest diameter. The pic-ture is easily confused with a toxic megacolon of ulcerative or granu-lomatous colitis, amebiasis or Chagas' disease. Although dilatation of the colon per se may be encountered after operation, it is not associated with fulminating diarrhea. The need for barium studies in these acutely ill patients is in question and may be contraindicated.

After diagnosis is made antibiotic therapy should be stopped. In some patients, however, this may not halt the diarrhea and clinical course. For these patients, the number of pub-lished cases is too few to make any definitive statement regarding treat-ment.25

The principles of treatment com-mon to all critically ill patients should be applied to "PMC megacolon" pa-tients as well. A normal intravascular and extracellular volume should be established using colloid, salt and plasma solutions and, if necessary, blood. A nasogastric tube should be passed to decompress the stomach and prevent aerophagia. Since bacte-ria may proliferate beneath the mem-brane, a Gram stain and culture of the rectal mucosa, pseudomem-brane, and stool are done. If the clinical course progresses and sepsis develops, then antibiotics should be resumed. Our policy has been to in-

stitute gentamycin and Cleocin pend-ing culture reports. Beyond this, treatment is speculative.

Despite these measures, the clinical course of our two postoperative pa-tients progressed and deteriorated, and a decompressive transverse co-lostomy and ileostomy were done to vent the colon and reduce the sys-temic toxicity. Although successful in treating the toxic megacolon of ulcer-ative colitis and Crohn's disease,26

this surgical procedure did not alter the fatal outcome in our two cases. Whether this was because viable bac-teria remained beneath the pseudo-membrane and potentiated the septic course or whether the disease is more fulminant in postoperative patients is not known.

Success with ileostomy and colos-tomy, subtotal colectomy with ileos-tomy and a mucus fistula provides hope. Certainly early diagnosis and awareness of the disease offer more hope than either of these surgical alternatives.

Summary

PMC is an uncommon inflamma-tory condition that may involve the small and large intestines. Although described nearly 100 years ago, long before antibiotics were introduced, today the disease is associated with the use of antibiotics, particularly lin-comycin and clindamycin. In one prospective study, a proctoscopic pic-ture compatible with PMC developed in 10% of patients taking lincomycin. T h e severity of this disease varies f rom mild and not clinically sympto-matic to fulminating with a fatal out-come. Two cases are summarized. In the postoperative period (following insertion of a total hip prosthesis in one patient and excision of a sessile

Winter 1977

polypoid colonic lesion in the sec-ond), progressive abdominal disten-tion, diarrhea, and shock developed. One patient was taking ampicillin and the second lincomycin. In both, PMC was diagnosed. A loop ileos-tomy and transverse colostomy were done in both patients, but they died. The current literature is reviewed.

References 1. Finney J M : G a s t r o e n t e r o s t o m y fo r cica-

t r iz ing ulcers of the py lorus . J o h n s H o p -kins H o s p Bull 4: 53-55, 1893.

2. H u l t b o r n KA: Acu t e pos topera t ive en te r -ocolitis; r e p o r t of 7 cases a n d review of the l i t e ra tu re . Acta Ch i r Scand 111: 29-44, 1956.

3. Pet te t J D , Baggens toss A H , D e a r i n g W H , et al: Pos topera t ive p s e u d o m e m b r a n o u s enterocoli t is . S u r g Gynecol Obste t 98: 546-552, 1954.

4. T e d e s c o FJ, Stanley RJ , Alpers D H : Diag-nostic f ea tu re s of cl indamycin-associated p s e u d o m e m b r a n o u s colitis. N Engl J Med 290: 841-843, 1974.

5. Ecker J A , Williams RG, McKittrick J E , et al: P s e u d o m e m b r a n o u s enterocoli t is —an unwe lcome gastrointes t inal complicat ion of antibiotic t h e r a p y . A m J Gas t roen te ro l 54: 214-228, 1970.

6. Bai rd WL J r , Musser A W , Miller RL: Staphylococcal p s e u d o m e m b r a n o u s en te r -ocolitis. N C Med J 24: 508-510, 1963.

7. B e n n e r EJ, T e l l m a n W H : P s e u d o m e m -b r a n o u s colitis as a sequel to ora l l incomy-cin t h e r a p y . A m J Gas t roen te ro l 54: 55-58, 1970.

8. C o h e n LE, McNeill CJ , Wells RF: Cl inda-mycin-associated colitis. J A M A 223: 1379-1380, 1973.

9. P i t tman FE, P i t tman J C , H u m p h r e y CD: Colitis fol lowing ora l l incomycin t h e r a p y . Arch I n t e r n M e d 134: 368-372, 1974.

10. P i t tman FE, P i t tman J C , H u m p h r e y CD: Lincomycin a n d p s e u d o m e m b r a n o u s coli-tis. Lance t 1: 451-452, 1974.

11. Scott AJ, Nicholson G I , Ke r r AR: Linco-mycin as a cause of p s e u d o m e m b r a n o u s colitis. Lance t 2: 1232-1234, 1973.

12. S t roehle in J R , Sedlack RE, H o f f m a n H N , et al: Cl indamycin-associa ted colitis. Mayo

Toxic megacolon 155

Clin Proc 49: 240-243, 1974. 13. Viteri AL, H o w a r d P H , Dyck WP: T h e

s p e c t r u m of l incomycin-cl indamycin coli-tis. Gas t roen te ro logy 66: 1137-1144, 1974.

14. Pet te t J D , Baggenstoss A H , J u d d ED J r , et al: Genera l ized pos topera t ive p seudo-m e m b r a n o u s enterocoli t is . Proc Staff Meet Mayo Clin 29: 342-349, 1954.

15. T u r n b u l l RB J r : Clinical recogni t ion of pos topera t ive micrococcic (staphylococcic) enter i t i s . J A M A 164: 756-761, 1951.

16. Dixon CF, W e i s m a n n RE: Acute p s e u d o -m e m b r a n o u s enter i t is o r enterocoli t is ; compl ica t ion fol lowing intestinal su rge ry . S u r g Clin N o r t h A m 28: 999-1023, 1948.

17. T e d e s c o FJ, Ba r ton R W , Alpers D H : Clin-damyc in associated colitis; a prospect ive s tudy . A n n I n t e r n Med 81: 424-433, 1974.

18. Small J D : Fatal enterocol i t is in h a m s t e r s given l incomycin hyd roch lo r ide . Lab A n i m C a r e 13: 411-420, 1968.

19. Collins DC: P s e u d o m e m b r a n o u s en te ro -colitis; f u r t h e r observat ions on the value of d o n o r fecal e n e m a t a as an a d j u n c t in the t r e a t m e n t of p s e u d o m e m b r a n o u s en-terocolit is . A m J Proctol 11: 389-391, 1960.

20. P rohaska J V , L o n g E T , Nelsen T S : Pseu-d o m e m b r a n o u s enterocoli t is; its etiology and the m e c h a n i s m of the disease process . A r c h S u r g 72: 977-983, 1956.

21. K h a n MY, Hall W H : Staphylococcal en t e r -ocol i t i s—trea tment with oral vancomycin . A n n I n t e r n Med 65: 1 -8 , 1966.

22. Kleckner MS J r , B a r g e n J A , Baggenstoss A: P s e u d o m e m b r a n o u s enterocoli t is : clin-icopathologic s tudy of 14 cases in which disease was not p r e c e d e d by o p e r a t i o n . Gas t roen te ro logy 21: 212-222, 1952.

23. B r o w n C H , F e r r a n t e WA, Davis W D J r : Tox ic di la tat ion of the colon compl ica t ing p s e u d o m e m b r a n o u s enterocoli t is . A m J Dig Dis 13: 813-821, 1968.

24. Wells RF, C o h e n LE, McNeill CJ : Cl inda-mycin a n d p s e u d o m e m b r a n o u s colitis. Lance t 1: 66, 1974.

25. Stanley RJ , Melson GL, T e d e s c o FJ: T h e s p e c t r u m of r ad iog raph i c f ind ings in anti-biot ic-related p s e u d o m e m b r a n o u s colitis. Radiology 111: 519-524, 1974.

26. T u r n b u l l RB J r , Hawk W A , Weakley FL: Surgical t r e a t m e n t of toxic megacolon ; il-eos tomy a n d colostomy to p r e p a r e pa t ien ts f o r colec tomy. A m J Su rg 122: 325-331, 1971.