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ULCERATIVE COLITIS AND^ CROHN'S DISEASE
Lecture delivered at the Royal College of Surgeons of England on 5th October, 1952 by Charles Wells, F.R.C.S. Department of Surgery, University of Liverpool
Introduction IT IS ONLY in recent years, if indeed at all, that the need for surgical treatment in ulcerative colitis has^ gained general^ acceptance:^ and^ now that surgeons are more^ experienced they^ are^ finding^ that^ certain^ cases fail to conform to the general pattern both in their pathology and in their response to^ treatment.^ At the^ same^ time,^ there is^ an^ increasing^ awareness
that not all the cases submitted to operation for the relief of regional
ileitis have done as well as was expected. There is anxiety about the
ileal involvement often found in ulcerative colitis and there is uncertainty
about the colonic involvement found in^ regional ileitis. Until this con-
fusion is resolved progress cannot be made. If the (^) aetiology of Crohn's disease and ulcerative colitis were known, a rational classification^ would be^ simple.^ Since^ we^ have^ no^ certain
knowledge about causes,^ we^ can^ only^ hope^ to^ group^ the^ cases^ on^ a^ basis
of descriptive pathology. It is surely here that we must make a fresh
start and^ revise^ our^ definitions^ which have become^ so^ nebulous that the
nomenclature conveys no precise meaning.
I suggest that we^ should for^ practical purposes and^ for convenience
adopt the^ following definitions.
Definitions
- Idiopathic ulcerative colitis
I suggest that the clinical entity "^ idiopathic ulcerative colitis "^ should
be restricted to ulcerative states involving always and^ in^ continuity the
rectum and pelvic colon and usually extending in^ continuity as far as the
ileo-caecal valve. (Fig. 1.) This lesion occasionally involves the terminal
ileum. Crohn has vividly described this extension^ as^ due^ to^ "^ wash-back
from the caecum into the pool of the^ terminal^ ileum."^ Rarely, this involve-
ment of the small intestine may be^ found^ in^ virtually its^ entire^ length.
Such cases end fatally. These extensions of^ ulcerative colitis^ may be
termed "^ idiopathic ulcerative^ coloileitis," or^ "^ colo-ileo-jejunitis."
These rather clumsy terms^ are^ properly descriptive.
- Crohn's Disease
Crohn's disease I would define as a granulomatous lesion of unknown
aetiology characterised^ by great thickening of the^ bowel^ wall,^ involving
C. WELLS
(By courtesy of Prof. Sheehan)
Fig. 1. Crohn's disease.^ Whole section of terminal ileum^ stained with H and^ E. Note the occasional deep fissuring of^ the mucosa,^ and the^ enormous^ thickening of the submucosa. The^ latter shows^ (area^ ringed)^ non-specific granulation^ tissue.^ The change from normal segment to diseased^ segment is^ characteristically^ abrupt.
Fig. 2.^ Ulcerative colitis.^ Infra-red^ photograph.^ Double-barrelled^ side ileostomy with free portal-systemic anastomosis of veins^ due to^ cirrhosis^ of the^ liver.^ Secondary spout ileostomy (terminal) in^ more^ proximal^ segment^ of ileum.^ Observe^ robust whole-thickness skin covering upper surface of^ spout.^ A^ bag^ is^ worn^ with comfort and without leakage. Splenectomy^ and^ spleno-renal^ anastomosis^ relieved the^ venous congestion around the original ileostomy which^ had^ tended^ to^ bleed freely^ when touched. Partial^ gastrectomy was^ also^ done for^ multiple^ bleeding^ gastric^ ulcers. The patient, a young woman, is^ very^ well and^ recently^ was^ married.
C. WELLS
Fig. 4. Crohn's disease.^ Specimen of^ terminal^ ileitis^ removed from^ the^ patient whose X-ray is shown in Fig. 3. Fourteen inches of ileum are grossly involved, beginning abruptly and^ terminating at^ the^ caecum^ which, together with^ the^ appendix, is healthy.
not sanction this extension^ of the^ entity^ to^ which^ we^ give^ his^ name.
I am therefore content^ to^ describe^ it^ as a^ separate^ entity.
Whether or^ not^ segmental colitis^ is^ a^ variation^ of Crohn's^ disease^ it,
in my opinion, most certainly is not a variant of ulcerative colitis with
which it is^ often identified^ or^ confused.^ I^ believe^ it^ most^ important
to distinguish between the two. The observed differences between
them are described later.
Discussion
In drawing distinctions and comparisons between^ these three^ entities
we may profitably glance at^ the theories^ concerning their^ origins and
causes. We should then^ compare them^ on^ grounds of^ pathology,
clinical features and response to^ treatment.^ Throughout this^ discussion
we shall have in^ mind the^ known^ causes^ of intestinal^ granulomata^ and
specific intestinal inflammation.^ It^ is^ of interest^ that, in^ this^ country
at least, the^ idiopathic granulomata we^ have^ named^ far^ exceed^ in^ number
those of known aetiology, such as chronic bacillary dysentery, tuber-
culosis, bilharzia, amoebiasis and^ lymphogranuloma venereum.
Aetiology
First we must discuss the open question of the aetiological significance
of bacillary dysentery.
ULCERATIVE COLITIS AND CROHN'S (^) DISEASE
Bacilary dysentery may^ be^ caused by the bacilli of Flexner, Sonne, Shiga, and others. It is associated with^ insanitary conditions, is highly infectious, and occurs both^ sporadically and in epidemics, especially among troops under difficult service (^) conditions. The acute inflamma- tion attacks the whole length of the colon and (^) may, rarely, extend into the terminal ileum as well. It thus coincides with the distribution of ulcerative colitis. In the 1914-1918 war there were many severe cases of dysentery from among whom a small number of chronic infections persisted. In these there was continuing inflammation and the causal organism was
still present. This was, however, quite unusual and it is not likely to
occur today because of the specific effect of sulphonamide therapy.
A much greater number of sufferers continued to have changed bowel habit with variably increased frequency of stools. Such cases occur
also to-day. They are^ attributable to^ change in the mucosal covering
of (^) areas of the large bowel. There (^) is patchy fibrosis in the (^) bowel wall and islands of modified mucous membrane (^) may hypertrophy and become
polypoid in the later stages. Eventually carcinoma may arise.
Whilst some degree of permanent damage is almost certain to follow
a really severe attack of dysentery and lead to altered bowel habit for
life, it is remarkable that in the more severe chronic cases, diagnosed as
post-bacillary ulcerative colitis, the antecedent history is usually vague or presumptive. Thus the patients may have lived amongst dysentery but may have had no really clear-cut illness themselves. The dividing line between severe presumed post-dysenteric colitis and true chronic ulcerative colitis cannot be drawn. Aetiologically,
as has been said, a clear history is often unobtainable. It has been
held by Felsen, who studied an outbreak of dysentery in New Jersey,
that the original bacillary infection may be sub-clinical and that it may
be spread very readily from individual to individual even some time after
the original attack. Thus, he claims a high incidence of conjugal spread
(between husband and wife). The greater part of Felsen's evidence is
serological and turns on the question of diagnostic agglutination titres
against specific strains of B. dysenteriae. He speaks of a 10 per cent. incidence of chronic ulcerative colitis or Crohn's disease among 122 patients and contacts whom he followed after the epidemic. He also
claims diagnostic agglutination in 95 per cent. of these cases whereas,
in (^300) controls, the titres were (^) at a similar level in (^) less than 5 per cent. I have found this a (^) fascinating piece of work and (^) so many of (^) Felsen's
straws seem to blow in the same direction that one is tempted to believe
that bacillary dysentery is, indeed, the prime factor in chronic ulcerative
colitis. Unfortunately, however, agglutination tests for the shigellae
are far from specific and, unless the titre is (^) very high indeed, they are not regarded as significant by experienced bacteriologists. Similarly,
the finding of bacteriophage in the stool is non-specific. The dysentery
ULCERATIVE COLITIS AND CROHN S DISEASE
It is of some interest that all the aetiological implications so far dis- cussed apply (in so far as they apply at all !) with equal force to both Crohn's disease and ulcerative colitis. Vagotomy. It is known that in dogs, bilateral lumbar sympathectomy causes ulcerative changes in the bowel. It is suggested that this is due to excessive spasm and uninhibited contractions. Vagotomy corrects or prevents these changes from occurring. In man, in chronic ulcerative colitis, vagotomy relieves the symptoms in a significant proportion of^ cases, although very little^ change can be
seen on sigmoidoscopy or^ in^ radiological pictures and the stool is
unchanged in character. The average rate^ of^ passage of^ food^ through
the small gut is slowed by only four hours^ from^ 14!^ to^ 18-^ hours.^ The
rate of passage through the colon is^ unchanged. The^ frequency of bowel action is lowered^ by the^ combined^ effect^ of^ slowed^ rate^ of passage and diminished tone.^ The effect^ appears to be^ mainly^ in the^ small intestine, which is^ not^ surprising^ since^ most^ of^ the^ large^ bowel^ is^ not
supplied by the^ vagus. These^ findings suggest that^ exaggerated^ con-
traction and spasm of the intestine may play some part in aetiology.
Eddy (1951), who^ was^ associated^ with^ Clarence^ Dennis^ under Wangansteen at Minneapolis, found an average reduction to 1-2 from
5-15 stools daily in 42 vagotomised patients observed for a number of
years.
Only early^ and^ relatively^ mild^ cases^ are^ thought^ to^ be^ suitable^ for
vagotomy. One reason for refusing the later cases is that 15 per cent.
of all sufferers from chronic ulcerative colitis develop carcinoma of the
colon or rectum. This is regarded as a clear indication for colectomy
in cases of long standing, even in patients already relieved of their
symptoms by vagotomy.
The psycho-somatic concept
Finally, in this aetiological survey, we^ must^ include the^ concept of the
psycho-somatic origin of ulcerative^ colitis.^ This^ has for^ long been
accepted by many as an obvious truth. My own^ view is that^ nothing
was ever further from the truth. These patients are^ among the^ most
stout-hearted of all those with whom^ we^ have^ to^ deal.^ One^ man, who
gets long periods of relief from rest^ and retention^ enemata, accepted a
job as a steeple-jack. When^ forbidden^ this^ by his^ physician he^ went
to the other extreme^ and^ began to^ work^ down^ a^ coal mine.^ A^ young
woman patient of^ my own^ after^ two^ ileostomies, colectomy in^ two^ stages,
partial gastrectomy for^ bleeding gastric ulcers^ which^ threatened^ her^ life,
and, finally, splenectomy with^ spleno-renal anastomosis^ for^ portal
hypertension due^ to^ cirrhosis, recently^ became^ engaged^ and^ was^ married
two months ago. (Fig. 2.)
A third patient, again a young woman, was regarded as a^ psycho-
neurotic for two years because of her habit of^ biting her^ nails and^ an
unfortunate, wartime, bigamous marriage with a free-French sailor.
9-
C. WELLS
She was ultimately found to have regional ileitis and was completely
relieved by resection. Among those who do not get better there is a high percentage with strength of character enough to take their own lives.
Pathology and clinical features of the three lesions Crohn's disease. Turning now to^ the^ pathology of^ Crohn's disease, we may first discuss its^ typical^ form, terminal^ ileitis.^ Three^ stages^ are described in terms which relate pathological and clinical attributes, namely: (i) The early, acute, which simulates appendicitis. (ii) The irritative, in which diarrhoea is common. (iii) The stenotic which leads to obstruction. In this last the prognosis after operation is the most favourable. Cases in the early acute stage are most often picked up in children. The affected ileum is thickened, red and oedematous. The illness may be quite sharp and the abdomen is usually opened for supposed acute
appendicitis. The records suggest that the wisest procedure is to close
the abdomen. Twenty-five per cent. of^ cases recover^ completely.
Seventy-five per cent.^ progress and call^ for further^ surgery^ months^ or
years later when^ they are^ better able^ to^ stand^ the^ operation. In the irritative phase, in which diarrhoea is common, the main changes
are seen in the submucous layer and there is a strong tendency to spread
either (^) by continuity or by skips. The features of this phase of the
disease are intermittent diarrhoea, mild fever and general illness with
loss of weight and other constitutional changes of a " toxic" nature. A mass may be palpable in the region of the terminal ileum. The irritative phase may persist for months or years, during which the
true diagnosis may go unsuspected. Once suspected, confirmation may
be obtained by X-ray. The characteristic appearance is the string sign of Kantor. The obstructive lesion is late in the natural history of the lesion and may be found in a matter of months or years after the onset of symptoms.
As time passes, the affected loop of bowel becomes increasingly rigid
and thick, to resemble, externally, a length of garden hose. The lumen
becomes smaller as the submucous granulation tissue becomes more and more tough and bulky. Fibrosis is not conspicuous. The mucosa itself becomes split up into islets and has a cobble-stone appearance. Ulceration occurs as longitudinal fissures. This is a late phenomenon which leads to quiet perforation with the formation of abscesses^ and
fistulae, especially between the layers of the mesentery.
Sooner or later the regional glands become enlarged and^ rubbery.
Caseation is never seen.
Skip lesions are common and may involve contiguous parts of bowel.
I have, in different cases, seen involvement of "^ touching" parts^ of^ the
ileum and ascending colon and of ileum and pelvic colon;^ the^ colonic
C. WELLS
Fig. 6. Segmental colitis of ascending colon with skip lesion to pelvic colon. There was no ileal lesion.
less sub-mucosal thickening than is seen in the small intestine but more fibrosis. The mucosa shows a change similar to that found in the ileum except
that the fissures run^ irregularly rather than longitudinally, giving a
lace-like effect. The whole affected loop is much tougher than in chronic
ulcerative colitis; skip lesions are^ common, and slow perforation, with
fistula or sinus (^) formation, may occur.
Ulcerative colitis. In ulcerative colitis, by contrast, the bowel is
oedematous and friable and adhesions between loops are conspicuous
by their absence. Sinus formation does not occur. Skip or contact
lesions are never seen. The inflammation is purulent with fluctuating
attacks of pain, fever and diarrhoea, with purulent and often bloody
stools. Perforation is exceedingly rare and, when it occurs, leaks freely
ULCERATIVE COLITIS AND CROHN'S DISEASE
Fig. 7. Sections from non-specific intestinal granulomata showing (a) Granulation tissue with giant cells and (b) a typical "^ tubercle" with epithelial^ and^ giant cells.^ There^ is no^ caseation and the condition is not tuberculous.
without localisation into the general peritoneal cavity with^ the^ production
of general septic peritonitis. Segmental colitis is a non-specific granulomatous lesion^ affecting^ the colon without any associated ileitis. In all other respects, including the cobble-stone change in the mucosa, it closely resembles^ the^ colonic extensions seen in Crohn's disease. The^ bowel^ wall is^ moderately thickened, tough and fibrous with visceral^ peritoneal^ condensations. Adhesions and even fistulae are^ common^ as^ also^ are^ skip lesions^ by contact. As in Crohn's disease, the symptoms may^ be^ irritative,^ with^ diarrhoea, simulating ulcerative colitis,^ or^ obstructive,^ simulating^ some^ other obstructive granuloma or^ carcinoma. Microscopically, a non-specific granulomatous^ change is^ common^ to all these three lesions.^ Giant^ cells^ may be^ seen^ with^ or^ without^ epithe- lioid formations. Sometimes the giant-cell and epithelioid systems are so (^) perfectly formed as to simulate tuberculosis very closely. Caseation is, however, not seen and all these changes are characteristic of and attributable to a foreign body reaction. This type of reaction can be seen in relation to mucosal lesions of the colon, rectum and anus, no matter what their origin or nature. Crohn and his associates have made the most exhaustive attempts to detect tubercle bacilli by staining and by making emulsions of tissue for
ULCERATIVE COLITIS AND CROHN S^ DISEASE
more upon the degree of virulence of the disease than upon the precise operation performed. Until we know more of its true nature and aetiology we shall not be able to compile a satisfactory code of rules for
treatment and prognosis.
My advice is (i) to explore the abdomen widely enough to see all the lesions clearly. (ii) to consider all the possibilities carefully before embarking on a definitive procedure. (iii) where excision, even of two widely separated foci calling for two
separate resections, is easy and likely to prove complete-to resect;
(iv) otherwise to do a short-circuit with exclusion. (v) to resect at a second stage, after exclusion, in the event of persistent or recurrent irritative symptoms (diarrhoea-fever-weight-loss). The prognosis is never certain and relapse may occur even after years and even after apparently complete resection. The reasons for this are not apparent. In planning treatment in chronic^ ulcerative^ colitis it is helpful to think of three grades of severity:- (i) The mild case, amenable to medical treatment, blood transfusion, rest, diet, and retention enemata. (ii) The fulminating case in which ileostomy can be life-saving and should be done (^) early. (iii) The average moderately severe case with exacerbations and re-
missions. The operation is planned during an attack but is done
in a remission. One-stage ileostomy and colectomy is the best procedure. At Johns Hopkins, a one-stage operation is completed by bringing the
ileum to the anus. Apparently a fair degree of continenc^e is usual,
but I^ should like to see some of the patients myself before advocating the (^) procedure.
My own preference is for a spout ileostomy partly covered with a
skin flap and partly with a split skin graft. (British Journal of Surgery
-in the press.) This procedure not only enables a bag to be worn in comfort but also excludes the risk of prolapse of the ileostomy. This
is, otherwise, a troublesome complication.
End ileostomy with the Rutzen bag is a method of which I have no personal experience. It is undoubtedly excellent. After making the spout ileostomy the skin of the abdominal wall and
thigh is protected by nursing the patient in^ a semi-prone position on the
right side over split mattresses. The^ ileal^ content^ thus falls cleanly away into a receiver until the spout is strong enough to receive the bag.
Segmental colitis. It is important to distinguish this condition from
chronic ulcerative colitis, first because there is usually no need for ileostomy. The affected segments of bowel can be resected with end-to-end
anastomosis, or short circuit with exclusion may be practised with or
C. WELLS
without secondary resection. Extension and recurrence are not uncommon, but the rectum is unlikely to become involved. One is tempted to believe that it was on the basis of segmental colitis rather than chronic ulcerative colitis that the plan of operation advocated by Sir Hugh Devine was based. In it a double-barrelled ileo-colostomy is constructed with a view to subsequent ileo-sigmoid or ileo-rectal anastomosis. Certainly this procedure is not suitable in the average cases of chronic ulcerative colitis as we^ know it, where^ the rectum^ is invariably diseased. Other granulomata, etc. Certain other lesions (^) may need to be (^) dis- tinguished in diagnosis or (^) may throw some (^) light upon the (^) aetiology of the three idiopathic conditions (^) just described. These are: (^) amoebiasis, lymphogranuloma inguinale, tuberculosis and endometriosis. Amoebiasis may lead to the appearance of a rectal or recto-sigmoid or other colonic granuloma most closely simulating carcinoma. Cysts or ova should be looked for; sigmoidoscopy and biopsy should be done;
the therapeutic test may prove the condition within a matter of days.
Lympho-granuloma venereum (syn. L. inguinale) is a virus disease which responds to treatment with chloramphenicol. In the early stages the proctitis resembles that of chronic ulcerative colitis and the resulting strictures also resemble this condition. Multiple peri-anal abscesses or sinuses are common ; the venereal character of the infection is to be borne in mind ; Frei's test is confirmatory as also is the response to therapy.
Efforts to relate chronic ulcerative colitis to this virus infection have
so far failed.
Non-specific lesions resembling lymphogranuloma may arise, and I
have one such case under observation now. The Frei test is negative and the response to antibiotics is nil. Such cases suggest that chronic ulcerative (^) colitis may begin as a virus proctitis. A biopsy from this particular case is of interest. It closely resembles
all the other sections so far discussed. This merely suggests that the
appearances are all non-specific and that the foreign body granuloma is a secondary effect due to gross contamination with faeces.
Tuberculosis differs from the lesions under discussion both macro-
scopically, microscopically, and biologically. The lesions have a spread-
ing quality within the peritoneal cavity. Tubercles are visible to both
the naked eye and the microscopist. Caseation and cold abscess
formation are common. Oedema abounds and tissue planes disappear.
Resection is impossible and short-circuit with exclusion, often difficult. It may, on this account, need to be done at a spot far
removed from the site of the lesion. Organisms -can be seen or cultured
and emulsions of tissue are bacterially active.
The ground for aetiological confusion between tuberculosis and the three (^) granulomata seems slender indeed. Endometriosis has no (^) aetiological relation to chronic (^) colitis, but (^) may
C. WELLS
PALMER, W. L. (1948) Chronic ulcerative (^) colitis. Gastroenterology 10, 767. PRUDDEN, J. F., LANE, N. and MEYER, K. The effect of orally and intra-arterially administered lysozyme on the canine gastro-intestinal (^) mucosa. Amer. (^) J. med. Sci. 219, 291. RAVITCH ani HANDELSMAN (1951) One stage resection of entire colon (^) and rectum for ulcerative colitis and polypoid adenomatosis. Bull. J. Hop. Hos. 88, 59. RoSSER, C. (1945) Benign surgical lesions of the right colon. J. Amer. med. Ass. 127, 10, 568. SLOAN, W. P., BARGEN, J. A. and GAGE, R. P. (1950) Life histories of patients with chronic ulcerative colitis. Review of 2,000 cases. Gastroenterology 16, 25. STARR, A. (1948) (Editorial) Surg. Gyn. Obstet. 87, 351.
THE BUCKSTON BROWNE BENEFACTION
THE BUCKSTON BROWNE Benefaction was commemorated on Tuesday, 8th July. Professor David Slome, Bernhard Baron Professor, delivered a lecture at 5 p.m., in which he gave a most interesting account of the origin and development of the Buckston Browne Farm at Downe, and of the research work now in progress there. Later the same evening was held the Buckston Browne Dinner, the company of 130 being mainly composed of Fellows and Members in accordance with the donor's wish. The (^) toast of " The (^) College " (^) was proposed by Miss Patricia Hornsby- Smith, M.P., Parliamentary Secretary to the Ministry of Health, who opened with^ an^ amusing endeavour-and failure-to find common ground between the late (^) Sir Buckston Browne and herself. After referring to
the ancient traditions of the College, she praised the recent advances in
surgery, particularly that^ of the brain, heart and lung, and plastic surgery.
She thanked the College for cooperation and help given to the Ministry
of Health at all (^) times, and spoke of the increased number and better distribution of (^) Consultants since the operation of the National Health Service. She congratulated the (^) College on (^) moving with the times in
such matters as new examinations, the publication of the Annals, im-
perial connections, and all its activities as a scientific and (^) social centre -activities which would surely be greatly increased with the (^) rebuilding
and enlargement of the College.
The President (Sir Cecil Wakeley, Bt.) thanked Miss Hornsby-Smith for her compliments and replied on behalf of the College. " (^) To-day," he said, " (^) we commemorate the Buckston Browne Bene- faction, and turn our thoughts to the affectionate memory of that great-
hearted donor, George Buckston Browne. From 1874 to 1926 he was
a Member of this College, and from 1926 till his death in 1945 an elected Fellow. It was his ideal to bring together in a family party the Fellows and Members of the College and to that end he endowed this dinner. " (^) Buckston Browne we can no longer have with us in the flesh, but let us at least rejoice in the company of his son-in-law, Sir Hugh Lett, and congratulate him on the jubilee of his Fellowship which he attained last month.
