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Int J Colorect Dis (1990) 5:177-180

Coloi eeml
Disease
9 Springer-Verlag 1990

Original articles
Prognostic indicators and clinical course in proctosigmoiditis
L . D . Juby 1, D . E . Long 1, M . E Dixon 2 and A.T.R. Axon 1
1 Gastroenterology Unit and 2 University Department of Pathology, The General Infirmary, Leeds, UK
Accepted: 2 August 1990

Abstract. The progress and outcome ofproctosigmoiditis


(PS) varies from a benign self limited illness to severe or
continuous disease which may require major surgery.
This study identifies certain clinical features in the presenting attack which appear to influence the subsequent
course of the disease. Ninety-nine patients with PS were
referred to a colitis clinic between 1975 and 1985. Sixty
have been followed for at least five years or have required
surgery. They have been classified as follows. G r o u p A
asymptomatic after presenting attack (n = 14), group B symptoms after presenting attack for < 10% of follow-up
(n=25), group C symptoms for > 1 0 % of follow-up
( n = 11), group D - p a t i e n t s requiring surgical intervention (n = 10). Data obtained during the initial attack, including sex, age, length of history, disease extent, length
of first attack and therapy, were analysed. There was no
significant difference in the length of history or extent of
disease between groups. The mean ages in groups A - D
were 40, 45, 30 and 24 years respectively. The ages of
groups A and B were not significantly different, but differed from group C (p<0.05) and from group D
(p < 0.005). The length of the first attack was significantly
shorter (p < 0.01) in groups A and B (median 1.0 and 3.0
months respectively) than in groups C and D (median 5.0
and 6.0 months respectively).

Introduction
A number of studies have described the progress and
outcome of patients presenting with ulcerative colitis and
PS [1-7]. In general the prognosis of PS is considered to
be relatively benign [8-10], but the clinical course is variable and includes patients with a single attack, those with
a series of attacks and remission, some with continuous
unremitting disease, and occasional patients where the
condition extends to involve the whole of the colon [2, 11,
12]. Rarely major surgery is required, either for life
threatening disease or where symptoms such as tenesmus,
urgency or incontinence become intolerable [2, 12].

Previous studies have documented the clinical course


and prognosis of patients with PS, but have not studied
whether the clinical features of the presenting attack influence the longer term prognosis.
In this study a large series of patients with PS, attending a specialized inflammatory bowel disease clinic, were
studied over a five year period. Features of the presenting
attack in each case were noted and subsequently assessed
to determine whether any specific clinical, histopathological or radiological feature provided an indication of the
clinical course over the subsequent five years.

Methods
Patient selection
Between 1975 and 1985 all patients presenting to an inflammatory
bowel disease clinic were documented using a standard protocol.
Over this period 99 patients were referred with a first attack of
untreated PS. Diagnosis was based on clinical features, sigmoidoscopy, barium enema, and histology. Infectious colitides were
excluded by microbiological examination. Data was recorded in a
uniform manner. The records of these 99 patients were analysed in
two ways, firstly with particular reference to the clinical features of
the presenting attack and secondly according to the subsequent
course of the disease.
Data recorded at presentation included age, sex, length of history prior to presentation, symptoms leading to referral, extent of
disease on sigmoidoscopy and barium enema, and histological appearance with reference to activity and architectural disturbance.
Data recorded on follow-up included number and length of
subsequent attacks, duration of first attack after commencing therapy, any hospital admissions, presence of malignancy, systemic
manifestations, further disease extension and therapy over total
follow-up period.
Of the 99 patients, 60 had been followed up regularly for at least
five years following their initial attack or alternatively had required
surgery before this endpoint. The other 39 patients were excluded as
15 failed to attend follow-up, 23 had not reached the 5 year endpoint at the time of analysis, and 1 died of an unrelated cause.
Patients were divided into four groups depending on their clinical course. Group A had had no further symptoms after the initial
attack had resolved (n = 14). Group B were symptomatic for less
than 10% of the follow-up time (n = 25). Group C remained symp-

178
Table 1. Groups

Age (years) median


range

Sex M : F
Length of history prior to presentation (months)

Statistics

38
13-65

42
14-76

28
13 -46

21
14-44

A + B v C p<0.05
A + BvD p < 0.05
analysis of variance

0.75:1

0.67:1

1.75 : 1

1.5 : 1

NSD Chi squared

1
< 1-4

2
< 1-60

2
< 1-48

3
< 1-156

Bloody stools
Mucus per rectum
Bowel frequency
Weight, loss

71
54
71
15

100
52
64
28

91
82
64
27

100
80
80
10

Extent of disease on sigmoidoscopy

1:1

1.5:1

2.7:1

1.5:1

NSD
Fisher's exact text

Median
Range

1
1-15

3
1-8

5
2-18

6
1-18

A + B v C p<0.01
A + B v D p<0.01
Kruskall Wallis

Extension beyond
Sigmoid colon
During 5 years
(no. patients)

Median
Range

NSD
Kruskall Wallis

Symptoms at presentation (%)

<15 cm: >15cm

NSD
Fisher's exact test

Length of first attack (months)

tomatic for > 10% of the follow-up period (n=11) and group D
had required surgical intervention (n=10). The 36 patients in
groups B and C who had continuous symptoms or a series of acute
attacks were subdivided because follow-up showed that those with
symptoms for less than 10% of the time had a different clinical
course from those with symptoms for more than 10% of follow-up.
The figure of 10% was chosen because patients fell clearly to either
side of this.

Histological assessment
Five histological aspects were selected as possible predictors of
disease progression, (i) an overall assessment of the severity of the
inflammatory cell response (acute and chronic inflammatory cells),
(ii) density of lymphocytes in the lamina propria, (iii) lymphoid
follicle formation, (iv) alterations in crypt pattern (loss, distortion,
shortening), and (v) number of eosinophils. On this basis of assessments, the slides were ranked in ascending order of abnormality for
each aspect without knowledge of their clinical group. The rankings
for each group were subjected to a rank correlation test.

Su~e~
T h e m e a n time to surgical i n t e r v e n t i o n was 28.4 m o n t h s .
T h e o p e r a t i o n s p e r f o r m e d were m u c o s a l p r o c t e c t o m y
a n d c o l e c t o m y (7), s u b t o t a l c o l e c t o m y (1) a n d p r o c t o c o l e c t o m y (2). F o u r p a t i e n t s h a d e m e r g e n c y s u r g e r y
(subtotal colectomy) and later had a mucosal proctectomy. A l l s u r g e r y was p e r f o r m e d for failure o f m e d i c a l
t r e a t m e n t . T h e findings at o p e r a t i o n r e v e a l e d e x t e n s i o n
to involve the w h o l e c o l o n in 5 p a t i e n t s , to the h e p a t i c
flexure in 1, t r a n s v e r s e c o l o n 1, a n d splenic flexure 1. I n
two p a t i e n t s the disease r e m a i n e d c o n f i n e d to the s i g m o i d
c o l o n a n d rectum.

Hospital admission .for treatment


T h r e e p a t i e n t s in g r o u p s B a n d C r e q u i r e d i n - p a t i e n t
t r e a t m e n t w h e r e a s n o p a t i e n t s were a d m i t t e d in g r o u p A
a n d all p a t i e n t s in g r o u p D were a d m i t t e d b e f o r e surgical
intervention.

Results (see Table 1)


Barium enema

Neoplasia

T h e a p p e a r a n c e s o n b a r i u m e n e m a are listed in Table 2.

O n e p a t i e n t in g r o u p B h a d a n a d e n o m a t o u s p o l y p w i t h
high g r a d e d y s p l a s i a , b u t there was n o d y s p l a s i a elsew h e r e in the c o l o n o r r e c t u m . T h e lesion was c o n s i d e r e d
to be a c o i n c i d e n t a l s p o r a d i c a d e n o m a .

Histology
T h e r e was n o significant c o r r e l a t i o n b e t w e e n a n y o f the
h i s t o l o g i c a l p a r a m e t e r s e x a m i n e d a n d clinical g r o u p
(Rank correlation).

Therapy
Table 3 shows the n u m b e r o f p a t i e n t s w h o were given
each t y p e o f t h e r a p y over the five y e a r f o l l o w - u p p e r i o d .

179
Table 2. Barium enema

Not performed
Normal
Rectum only
Rectosigmoid

Group A

Group B

Group C

Group D

4
3
4
3

5
12
3
5

2
4
1
4

5
2
1
2

18, 211.

There is no significant difference between the groups

Table 3. Patients who required each type of therapy over the 5 years

Group A, n = 14
Group B, n=25
Group C, n = 11
Group D, n=10

As expected, the presenting symptoms were the same


in each group because it is the increased bowel frequency
and passage of blood and mucus per rectum which leads
to initial referral. This agrees with other studies [12, 17,

Local

SZP

Prednisolone
1st

Prednisolone
oral

12
23
11
10

12
19
11
10

1
6
5
5

1
10
7
10

Local = rectal suppository/enema of prednisolone/ASA/sala-zopyrin/hydrocortisone. SZP = oral salazopyrin. Prednisolone 1st = oral
prednisolone in first attack. Prednisolone oral = oral prednisolone
at any time over 5 years

There was no difference in the use of local therapy or oral


salazopyrin, but fewer patients in Groups A and B needed oral prednisolone to manage an acute attack.

Discussion
Ulcerative proctosigmoiditis is defined as an idiopathic
inflammatory process involving the rectosigmoid mucosa
with a clear upper border, but otherwise indistinguishable from diffuse ulcerative colitis (UC) [8]. Whereas the
incidence of U C has remained stable over twenty years
[13], the frequency of PS has increased. In recent series,
40 70% of patients with U C had an initial PS [5, 14-16].
In patients presenting with PS it would be helpful to be
able to predict which will have a good prognosis and
which will continue to relapse or undergo extension to
involve the whole colon.
While proctitis is usually regarded as a relatively 'benign' disease [8-10], only 23% of patients in this study
remained symptom free after treatment of the presenting
attack. The majority, 42%, had further symptoms for
< 10% of the follow up period: but 18% had symptoms
for > 1 0 % of the time and 17% eventually required
surgery. These figures show a more aggressive course
than for those of two other studies [17, 18]. In the 10
patients requiring surgery, 4 required an emergency operation which carries a higher mortality rate [19]. Seven
patients retained their anal sphincter, but three required
permanent ileostomy.
F r o m this data there is a 25% chance that no further
symptoms will occur, but conversely there is a 16%
chance that surgical intervention will be needed. The
rates for surgery in other centres were 3% [15], 4% [20],
5% [13], 8% [5, 18].

Patients with the most unfavourable course and those


requiring surgery presented at a younger age; similar results were obtained by Watts [22], and Farmer [23]. This
contrasts with UC where the outcome of first attacks is
worse in elderly patients [24].
Sinclair [5] showed that the rate of relapse following
initial diagnosis is not related to the severity or extent of
disease at presentation. This study confirms these findings.
The overall rate for proximal extension was 20%,
other studies vary from 6% [10, 17, 20] to 45% [25] depending on the method of assessment. Where the proportion showing extension is high, it could be that these
patients h a d more extensive disease initially. Proctosigmoiditis is part of the spectrum of U C and the activity is
known to wax and wane, therefore an erroneous macroscopic diagnosis of PS might be made in some cases if this
is the only inflamed area at the time of examination.
Patients in this study had barium enema/colonoscopic
examination only if a 'top limit' was not seen at initial
sigmoidoscopy and therefore may have included patients
with more extensive histological abnormality.
There was no difference in histological inflammatory
activity or architectural disturbance between the groups.
This confirms that patients with acute self-limiting colitis
were not misdiagnosed as early idiopathic inflammatory
bowel disease on initial rectal biopsy thereby being included in Group A. It might be surmised that marked
crypt destruction and more severe inflammatory cell infiltration (particularly by neutrophil polymorphs) are predictors of a more active, progressive disease. No such
relationship was found; nor was there a significant relationship between clinical group and the density of the
lymphocytic infiltrate and lymphoid follicle formation
(which might be indicators of a localized ~
lymphoid" proctitis) or increasing numbers of
eosinophils which have been claimed as predicting a "benign" course [26]. Our findings agree with those of Powell
Tuck who showed that no correlation existed between
histological assessment and outcome [27].
The time between referral and institution of therapy
made no difference to the outcome of the disease, but
those who settled quickly in the first attack did better in
the long term. Fewer patients in Groups A and B required oral prednisolone to achieve remission in the first
attack, and this trend in treatment continued over the
following 5 years.
This study shows that there are no reliable prognostic
indicators for PS at initial presentation, but generally
patients who are younger and those who take longer to
settle in the first attack have a less favourable prognosis.
A large multicentre study over a set period using a standard protocol of investigation is warranted.

180
References

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Gastroenterology 32: 983-1012
2. Lennard-Jones JE, Cooper GW, Newell AG, Wilson CWE,
Avery-Jones F (1962) Observations on idiopathic proctitis. Gut
3:201-206
3. Farmer RG, Brown CH (1966) Ulcerative proctitis course and
prognosis. Gastroenterology 51: 219-223
4. Both H, Torp-Pederson K, Kreiner S, Hendriksen C, Binder V
(1983) Clinical appearance at diagnosis of ulcerative colitis and
Crohn's disease in a regional patient group. Scand J Gastroenterol 18:987-991
5. Sinclair TS, Brunt PW, Ashley N, Mowat G (1983) Nonspecific
proctocolitis in Northeastern Scotland: A community study.
Gastroenterology 85: 1-11
6. Holdstock G, Savage D, Harman M, Wright R (1985) An investigation into the validity of the present classification of IBD. Q
J Med, New Series 54, No. 214:183-190
7. Stonnington GM, Phillips SF, Zinsmeister AR, Melton LJ
(1987) Prognosis of chronic ulcerative colitis in a community.
Gut 28:1261-1266
8. Farmer RG, Brown CH (1972) Emerging concepts of proctosigmoiditis. Dis Colon Rectum 15:142-146
9. Farmer RG, Brown CH (1971) Course and prognosis of ulcerative proctitis. Am J Gastroenterol 56:227-234
10. Freyberger H, Muller-Wieland K (1968) Proctosigmoiditis: a
special form of ulcerative colitis. Am J Proctol 19:270-277
11. Farmer RG (1979) Long term prognosis for patients with ulcerative proctitis. J Clin Gastroenterol 1:47
12. Nugent FW, Veidenheimer MC, Zuben S, Carabedian MM,
Pasrikh NK (1970) Clinical course of ulcerative proctosigmoiditis. Am J Dig Dis 15:321-326
13. Calkins BM, Lilienfeld AM, Garland CF, Mendeloff AI (1984)
Trends in the incidence rates of ulcerative colitis and Crohn's
disease. Dig Dis Sci 29:913 920
14. Ritchie JK, Powell-Tuck L Lennard-Jones JE (1978) Clinical
outcome of the first ten years of ulcerative colitis and proctitis.
Lancet ii: 1140-1143

15. Whitehead R (1985) Forms of Colitis - a review of recent


developments. Pathology 17:206-208
16. Wright JP, Marks IN, Jameson C, Garisch JAM, Burn SDG,
Kottler RE (1983) Inflammatory bowel disease in Cape Town
1975-1980 Part 1 Ulcerative colitis. S Afr Med J 63:223-226
17. Myers A, Humphreys DM, Cox EV (1976) A ten year follow up
of haemorrhagic proctitis. Postgrad Med J 52:224-228
18. Farmer RG, Brown CH (1967) Ulcerative colitis confined to
rectum and sigmoid flexure. Dis Colon Rectum 10:177-182
19. Hawley PR (1988) Emergency surgery for ulcerative colitis.
World J Surg 12:169-173
20. Powell-Tuck J, Ritchie JK, Lennard-Jones JE (1977) The prognosis of idiopathic proctitis. Scand J Gastroentero112: 727-732
21. Folley JH (1970) Clinical concepts of ulcerative proctitis. N
Engl J Med 282:1362-1364
22. Watts J McK, de Dombal FT, Watkinson G, Goligher JC (1966)
Long term prognosis of ulcerative proctitis. Br Med J 1:14471453
23. Farmer RG (1987) Nonspecific ulcerative proctitis. Gastroenterol Clin North Am 16:157-174
24. Watts J McK, deDombal FT, Watkinson G, Goligher JC (1966)
Early course of ulcerative colitis. Gut 7:16-31
25. Niv Y, Bat L, Ron E, Theodor E (1987) Change in the extent of
colonic involvement in ulcerative colitis: A colonoscopic study.
Am J Gastroenterology 82:1046-1051
26. Heatley RV, James PD (1979) Eosinophils in the rectal mucosa
- A simple method of predicting the outcome of ulcerative
proctocolitis? Gut 20:787-792
27. Powell-Tuck J, Day DW, Buckwell NA, Wadsworth J, LennardJones JE (1982) Correlations between defined sigmoidoscopic
appearances and measures of disease activity in ulcerative colitis. Dig Dis Sci 27:533-537

Dr. A. T. R. Axon
Gastroenterology Unit
The General Infirmary
Leeds, LS1 3EX
UK

Int J Colorect Dis (1990) 5:181-187

Col6i,eclal
Disease
9 Springer-Verlag 1990

Slow transit chronic constipation (Arbuthnot Lane's disease)


An immunohistochemical study of neuropeptide-containing nerves in resected specimens
from the large bowel
A. Dolk 1, G. Brod~n 1, B. Holmstr~m 1, C. Johansson i and M. Schultzberg 2
1 Department of Surgery, Karolinska Institute at Danderyd Hospital, Danderyd, Sweden
2 Department of Pathology, Karolinska Institute at Huddinge Hospital, Huddinge, Sweden
Accepted: 22 August 1990

Abstract. Seven patients (6 women, 1 man) with severe


idiopathic chronic constipation, who underwent surgery
with subtotal colectomy and ileorectal anastomosis, were
investigated for the occurrence and density of nerve
fibres, immunoreactive to different neuropeptides in the
mucosa, submucosa, ganglia and smooth muscle in fresh
specimens from the colon ascendens, the colon transversum and the colon descendens-sigmoideum. The following substances were studied: enkephalin, substance P,
somatostatin, neuropeptide Y, vasoactive intestinal polypeptide, calcitonin gene-related peptide, bombesin, motilin, tyrosine hydroxylase, dynorphin and galanin. Nerve
fibres immunoreactive to C G R P occurred in large numbers in the myenteric ganglia of the patients with severe
idiopathic chronic constipation, whereas in the myenteric
ganglia of the control cases they only occurred in low
numbers. In two patients there was no detectable motilin
immunoreactivity and in one patient only sparse in the
mucosa and the smooth muscle. The other neuropeptides
investigated occurred in the density and distribution previously reported in the normal gut. With the present technique there were indications that patients with severe
idiopathic chronic constipation have a significant difference in the occurrence of immunoreactive nerve fibres to
C G R P and motilin compared to control patients.

Introduction
The innervation of the mammalian gastrointestinal tract
has been studied extensively in the past, and Meissner [1]
in 1857 and Langley [2] in 1900 suggested that there is an
enteric nervous system. In addition to the "classical" neurotransmitters, noradrenaline and acetylcholine, a number of neuropeptides have been demonstrated to occur in
both intrinsic gut neurons as well as in nerves of extrinsic
origin innervating the gastrointestinal wall [3- 6].
Impaired colon motility is caused by aganglionosis,
as seen in Hirschsprung's and Chagas' diseases [7, 8].
Changes in content of acetylcholinesterase in mucosal

biopsies from patients with Hirschsprung's disease [9]


and ultrastructural changes in myenteric nerves [10] can
distinguish it from the normal large bowel. Increased
colonic motility is associated with irritable bowel syndrome [11] and diverticular disease [12, 13], but no
specific anatomical changes responsible for the motility
disturbances have been described.
Constipation is a common symptom due to many
different causes [14]. Idiopathic chronic constipation (Arbuthnot Lane's disease) [15-20] is a rare cause of severe
constipation occurring mostly in young women. It is diagnosed on the demonstration of delayed colon transit
time in a bowel of normal calibre [19]. Thus barium enema and other routine investigations are usually normal.
Severe idiopathic chronic constipation is often accompanied by pain, and the patients frequently depend on enemas for evacuation.
A distinctive abnormality in the myenteric plexus of
the colon with reduced numbers of, and morphologically
changed, argyrophilic neurons has been shown in these
patients [21, 22] but the pathophysiology is not completely understood. Earlier studies have shown that substance P (SP), bombesin and motilin have excitatory effects on colonic motility, whereas galanin, vasoactive intestinal polypeptide (VIP), somatostatin and enkephalin
are mainly inhibitory on intestinal motility [23 27].
We have investigated the occurrence and density of
neuropeptide-immunoreactive nerve fibres in the resected
colonic wall from patients with severe idiopathic chronic
constipation as compared with the resected colonic wall
of patients with colonic carcinoma and multiple colonic
polyps. Noradrenergic innervation was studied using an
antiserum against tyrosine hydroxylase (TH), the ratelimiting enzyme in catecholamine synthesis.

Materials and methods


Seven patients with severe idiopathic chronic constipation, verified
by a colon transit study [28], were investigated. The patients retained 48-100% of ingested markers after 5 days. There were six
women and one man with a mean age of 38.3 years (range 23-61).

Dynorphin, n = 3

Bowel part

Mucosa
Submucosa
Ganglia
Smooth muscle
Blood vessels

Peptide

0---~(+)
(+)~+ +
+--++ + +
+ + ~ + + +
0~ +

0-~(+)
(+)---~ + +
+ +---~+ + +
+ + --* + + +
0

Galanin, n = 3

o--~(+)

0
0

(+)-~+ +

+++~++++
+4++
+++
+++4++++
+4++++

o--, +

+-+++

+--,+ + +
o
++--~+++

0--~(+)
+ ---~+ +
+--*+ + +
+ + ~ + + +
0

D/S

o~(+)

0
0

o--,+ + +

D/S

+++4++++
+~++++
+++~++++
+++~++++
+4++++

D/S

o--~(+)

(+)-++ + +

+4+++
o--~(+)
++4+++

D/S

04+

++

04+ +
++-++++

(+)4++

Colon

TH, n = 3

0
0
0~+++
0
0

Colon

CGRP, n = 7

0-+++

o--~(+)
0-~+
(+)4+

Colon

+-~++

(+)-~+ +

+-~+ +
++-++++

o--~+ +

0
0
+~++
0~(+)
0

0--,(+)

o--~(+)
04(+)
o--q+)

Somatostatin, n = 7

04+ +
0--*+ +
++--.+++
+4++
0n++

D/S

04(+)

0~+++

0--4(+)

0 - + -}-

D/S

0-+++

o-~(+)
o-~+
(+)--~+

D/S

n = number of patients studied; A = colon ascendens; T = colon transversum; D/S = colon descendens-sigmoideum; ( + ) = only single fibres; + = low number of fibres; + + = moderate
number of fibres; + + + =large number of fibres; + + + + = d e n s e network of fibres

0
0
0-4(+)
0
0

Oo +
0
(+)~+
0-.(+)
0

Mucosa
Submucosa
Ganglia
Smooth muscle
Blood vessels

0--~(+)
0
0~(+)
0
0

o~(+)

0
o

(+)--,+ + +

+++~++++
+~+++
+++4++++
++~++++
++4++++

Bowel part

D/S

(+)--~+

(+)---~ +
0

+4++

D/S

++4+++
++
++4+++
++~++++
+4+++

D/S

+-+++

o--~ +

Colon

+-+++++

Colon

Colon

Peptide

Bombesin, n = 3

Submucosa
Ganglia
Smooth muscle
Blood vessels

+--~+ +

(+)4+++
+4+++
++4+++
+++
+4+++

Mucosa

Colon

Bowel part

+--~+ +

Motilin, n = 3

++
+4++
++4+++
++4+++
+4+++

Colon

0---~+ +
o-+(+)

NPY, n = 7

Peptide

+--~+ +

Colon

+-++++

o~(+)

+4+++

o--~(+)

0--++
o-+(+)

VIP, n = 7

(+)--~+ +
04(+)
(+)--~+ + +

(+)4++
o--~+
+4+++

Mucosa
Submucosa
Ganglia
Smoth muscle
Blood vessels

+4++
o--~(+)
++--~+++

Bowel part

o~++
o--~+
(+)--~+ + +

Colon

Colon
D/S

SP, n = 7

Peptide

Enkephalin, n = 7

Table 1. Slow transit constipation. Occurrence and density of neuropeptides in the different parts of the colon and in the different layers of the colonic wall

b~

0~(+)
0~+
+~+++
+~++
0

0~(+)
+~++
++~+++
+~+++
0

Motilin
n=l
A

Galanin
n=l
A
0
+
++
++
0

++
+
++
++
++

Bombesin

n=l
A

+ +
0
(+)
+
0

Dynorphin

n=l
A

+
0
(+)
(+ )
0

Mucosa
Submucosa
Ganglia
Smoothmuscle
Bloodvessels

Peptide

Bowel part

Mucosa
Submucosa
Ganglia
Smooth muscle
Blood vessels

Peptide

Bowel part

Mucosa
Submucosa
Ganglia
Smooth muscle
Blood vessels

Key as for Table 1

D/S

n=2
T

n=l
A

0
0
(+)
(+ )~ +
0

n=2
T

+ --++ + +
0--+ + +
+ --+ + +
+ ~ + +
0

n=2
T

+
+~++
++~+++
++~+++
+~+++

n=3
T

0
(+)
0
0
0

n=2
D/S

+ --+ + +
+
0--+(+)
+
0

n=2
D/S

++~+++
++
++~+++
++~++++
+~++

n=3
D/S

0
0
0
0
0

+++
+++
++++
+++
+++

0--*+ +
0
0
0~(+)
0

(+)--~+ +
0-~+ +

(+)~++
+~++

n=2

0~(+)

+--*+ +
++-++++

o--~(+)

+~++
+~++
+~+++

++
+
+++
++
+
0~++
0
0

n=2
D/S

0~(+)
o~(+)
0
0~(+)
0

n=3
D/S

n=2
T

0
0
0~+
0
0

n=3
T

+
0

(+)--~ +
(+)--~ +

0--++

n=3
D/S

n=l
A

TH

0
o
0
0
0

n=l
A

(+)
0

o-~(+)
o-~(+)

(+)

n=3
Y

n=2
D/S

+++~++++
+~+++
++~++++
++~++++
+++~++++

+++~++++
+~++
+++
++++
++~++++

n=2
T

n=3
D/S

n=3
T

+
0

+~+++
0

n=l
A

(+)
+

CGRP

+-+++

n=l
A

Somatostatin

o
++-~+++

Bowel part

(+)--+ +
0
++--++++
+ ~ + +
0--+(+)

+
0
+++
+
(+)

NPY

+ + + +
0--+(+)
+--,+ +
+ -~ + +
0~(+)

Peptide

+
0-+(+)
(+)--+ + +
+ ~ + + +
(+.)

+
(+)
++
+
0

n=3
D/S

Mucosa
Submucosa
Ganglia
Smooth muscle
Blood vessels

n=3
T

n=l
A

n=3
D/S

n=l
A

Bowel part

n=3
T

SP

Enkephalin

Peptide

Table 2. Controls. Occurrence and density of neuropeptides in the different parts of the colon and in the different layers of the colonic wall

u,U~

184

Fig. 1 A, B, Immunohistochemical micrographs


of sections of the human transverse colon after
incubation with antiserum to CGRP. The tissue
specimen was obtained from a patient with
severe idiophathic chronic constipation.
Varicose CGRP-immunoreactive fibres can be
seen in the myenteric plexus (arrows),
surrounding the ganglion cells. Magnification:
125 x (A) and 250 x (B)

Two of them had earlier undergone surgery for rectal prolapse and
all seven patients were subjected to subtotal colectomy and ileorectal anastomosis. Fresh colon tissue specimens were taken from
two different sites each in the middle part of the colon ascendens,
transversum and descendens-sigmoideum. The tissue samples were
analysed by immnnohistochemistry and routine histological staining. Two separate sections were studied and compared from each
region of the bowel and for each neuropeptide or TI-I, respectively.
Two patients with colonic carcinoma and one patient with multiple
colonic polyps who underwent colonic resection and subtotal colectomy, respectively, served as controls.
The tissues were immersed in a solution of 4% paraformaldehyde and 0.2% picric acid [29] in 0.1 M S6rensen phosphate buffer
(pH 6.9) at 4~ and 3 h later transferred to a solution of 10%
sucrose in S6rensen phosphate buffer (pH 7.4). Fourteen micrometer thick sections were taken on a cryostat (Dittes, Heidelberg) and
processed for indirect immunohistochemistry [30]. The sections
were incubated with primary antisera at 4~ overnight, rinsed in
0.01 M phosphate buffered saline (PBS), pH 7.2, for 2 x 10 min, and
incubated at 37~ for 30min with fluorescein isothiocyanate
(FITC)-conjugated goat anti-rabbit antibodies (1 : 15) (Boehringer/
Mannheim Scandinavia, Bromma, Sweden). After a final rinse in
PBS, the sections were mounted in a mixture of PBS and glycerol
containing p-phenylenediamine [31]. The primary antisera have previously been characterized and tested for cross-reactivity (see ref for
each antibody). The antisera were raised in rabbits against SP
(I :200) [32], neuropeptide Y (NPY) (1:200) (Cambridge Research
Biochemicals), VIP (1 : 150) (Dr. Stefan B. Svenson, Dept. of Vaccine Production, National Bacteriological Laboratory, Stockholm,
Sweden), somatostatin (1 : 100) [33] and (1:200) (Peninsula Laboratories Europe Ltd.; St. Helens, UK), TH (1:500) (Eugene Tech,
New Jersey), calcitonin gene-related peptide (CGRP) (1:400)
(Peninsula Laboratories Europe Ltd., St. Helens, UK), bombesin
(1:200) [34] and motilin (1:200) [35], dynorphin (l:400) [36],
galanin (1:400) (Peninsula Laboratories Europe Ltd., St. Hetens,
UK) and enkephalin (1:400) [37]. Control sera were obtained by
preadsorption of each antiserum with the respective antigen.
The sections were examined in a Nikon Optiphot microscope
and Tri-X black and white film (Kodak, Rochester) was used for
photography. No radioimmunoassay or other biochemical quantification of peptide content was performed.
In 4 patients with severe idiopathic chronic constipation and in
one control patient we investigated the occurrence of NPY, CGRP,
SP, enkephalin, V[P and somatostatin. In 3 patients and in 2 control
patients we also studied the occurrence of motilin, TH, galanin,
bombesin and dynorphin.

Results

The resected colon was n o r m a l with regard to m a c r o scopical appearance and bowel wall thickness in six patients. One patient had a slightly increased bowel wall
thickness and melanosis coli with histological signs o f
fibrosis in the s u b m u c o s a l layer. Routine histology did
n o t reveal changes in the n u m b e r or appearance o f the
ganglia in the bowel wall as estimated by an experienced
pathologist.
The results are presented in detail in Tables 1 and 2.
As there was no obvious difference in the occurrence o f
neuropeptide-containing nerve fibres between the longitudinal and circular muscle layer, they are presented together "as s m o o t h muscle layer" in the Tables.
Except for C G R P and motilin this study did n o t reveal significant differences c o m p a r e d with the localization and occurrence o f i m m u n o r e a c t i v e nerve fibres in the
h u m a n colon described earlier [26, 38 41]. Nerve fibres
i m m u n o r e a c t i v e to C G R P occurred in the myenteric ganglia o f the patients with severe idiopathic chronic constip a t i o n but n o t in the control cases (Tables 1, 2; Fig. 1).
Motilin was the only neuropeptide that could n o t be
d e m o n s t r a t e d in the ganglia at all, neither in the patients
with severe idiopathic chronic constipation n o r in the
control patients. Relatively large n u m b e r s o f enkephalin-, SP-, N P Y - , VIP-, T H - and galanin-positive fibres
were present in the myenteric ganglia o f all patients studied.
A few nerve fibres with somatostatin- and d y n o r p h i n like i m m u n o r e a c t i v i t y were also seen in the myenteric
ganglia o f all patients.
All o f the neuropeptides studied, except dynorphin,
could be seen in the s m o o t h muscle o f the colonic wall.
Nerve fibres i m m u n o r e a c t i v e to galanin [42], VIP, NPY,
enkephalin, SP and to T H were n u m e r o u s , whereas only
small n u m b e r s o f somatostatin-, C G R P - , bombesin- and
motilin-positive fibres were encountered in the s m o o t h
muscle layers o f the colonic wall.

185

Fig. 2. Immunohistochemical
micrograph of a section of human
sigmoid colon after incubation with
antiserum to VIP. The tissue specimen
was obtained from a patient with
severe idiopathic chronic constipation.
VIP-immunoreactive fibres are
abundant in the lamina propria (lp)
and lamina muscularis mucosae (lm) of
the intestinal mucosa. A few fibres can
be seen in the submucosa (s).
Magnification: 125 x

Motilin- and dynorphin-immunoreactive nerve fibres


were absent in the submucosal layer of the colon in both
patients and control cases. Nerve fibres immunoreactive
to CGRP, enkephalin, SP and somatostatin were few in
the submucosal layer. VIP- (Fig. 2), bombesin-, TH-,
galanin- and NPY-immunoreactive nerve fibres occurred
in moderate numbers but with clear differences between
individuals. NPY-, VIP-, SP- and TH-immunoreactive
nerve fibres occurred in close relation to blood vessels in
the submucosa whereas the other peptides studied did not.
There were no significant differences between the
three parts of the colon studied with regard to the number
of immunoreactive nerve fibres observed in smooth muscle and ganglia. Sections stained with control sera did not
show any of the immunoreactive fibres described in this
study.

Discussion

Although the patients with severe idiopathic chronic constipation have highly disturbed colonic motility, all of the
patients in this study had a normal occurrence of nerve
fibres and ganglia as observed by routine histological
examination. Only one patient had a slight increase of
bowel wall thickness and melanosis coli which were histologically verified. This differs clearly from patients with
Hirschsprung's and Chagas' disease, who have macroscopical changes in the colon and an absence of, or defects in, their ganglion cells as observed by routine histology [7, 8]. Patients with Hirschsprung's disease have
changes in the content of acetylcholinesterase in colonic
mucosa [9], and changes in the myenteric nerves observed
by electron microscopy [10].
We could demonstrate a difference in the amount of
nerve fibres immunoreactive to C G R P in the myenteric
ganglia between patients with severe idiopathic chronic
constripation and the control cases. We have not found
any similar observation in the literature. The physiological significance of this morphologic difference remains
open. Apart from the immunoreactive C G R P nerve
fibres we could neither demonstrate total absence nor a
highly increased amount of any type of immunoreactive

nerve fibres in the patients with severe idiopathic chronic


constipation that distinguished them from the control
patients. In contrast, the patients with Hirschsprung's
disease have clearly detectable changes in the content of
neuropeptides in the aganglionic and hypoganglionic
part of their colon [43]. A depletion of enkephalin and to
some extent VIP- [44] and SP-immunoreactive nerve
fibres has been observed together with an increase in
NPY-immunoreactive nerve fibres in Hirschsprung's disease [45].
In conclusion, this study shows a difference in the
content of immunoreactive nerve fibres to C G R P in the
ganglia of the large bowel wall, between patients with
severe idiopathic chronic constipation and the control
cases. No other significant changes in the number of certain neuropeptide-containing nerve fibres as compared to
the normal distribution of these nerves could be seen.
Degenerative changes in the plexus myentericus could
not be demonstrated. However, possible changes in neuropeptide content of the other neuropeptides may be too
low to be detected with the immunohistochemical technique, and a quantitative analysis with radioimmunoassay may reveal some changes. Changes in immunoreactivity have been demonstrated both in inflammatory bowel
disease [41, 46, 47] and with increasing age [48]. Since
colectomy in the same age group as the group of patients
with severe idiopathic chronic constipation is mostly
done because of inflammatory bowel disease or familial
adenomatous polyposis, this excludes them from serving
as ideal control cases. Patients with carcinoma of the
colon are often older, which may be a reason for variation in the amounts of regulatory peptides in the bowel
wall [48]. This could also be a reason why patients with
colonic carcinoma are not ideal controls in this study.
There are both electromyographical and motility
studies that suggest that the right and left colon have
different roles in colonic physiology [49]. The right colon
mainly transports and mixes the gut content and absorbs
water, whereas the left colon absorbs electrolytes. Regional colonic differences in concentrations of somatostatin and VIP have been demonstrated but only in mucosal specimens [50]. These physiological differences
make it difficult to investigate the pathophysiology of

186
disturbed colon motility. It has been shown, however,
that a right hemicolectomy is inadequate to cure slow
transit constipation, whereas subtotal colectomy offers a
cure in many cases.
Patients with severe idiopathic chronic constipation
have impaired motilin release in response to oral water
stimulation [24]. This observation may suggest that
motilin is involved in the pathophysiology of this disease.
Pharmacological studies in patients with chronic idiopathic constipation have shown lower fasting levels of
motilin as well as lower levels after meal stimulation [51].
Increased frequency o f bowel movements in patients with
metastatic carcinoid syndrome is correlated with elevated
plasma motilin concentrations and not with elevated 5H I A A levels [52]. This favours the theory that motilin is
involved in the regulation of intestinal motility. The lack
of change in the number of motilin-immunoreactive
fibres may be due to the small number of fibres seen with
this antiserum, at least in our hands.
Idiopathic chronic constipation has, in one study,
been associated with decreased content of VIP in the
muscularis externa of the colon descendens [53]. The
quantitation of VIP by radioimmunoassay may explain
the discrepancy with our results. Substance P levels determined by radioimmunoassay in mucosal biopsies from
patients with chronic severe constipation has been shown
to be significantly lower than in normal subjects [54]. This
is contrary to our results, but the biopsies did not involve
the deeper layers of the bowel wall, and the technique did
not determine the number of substance P immunoreactive nerve fibres in ganglia and smooth muscle, but measured the concentration of substance P.
In a previous study on patients with rectal prolapse or
internal rectal procidentia, there were no apparent
changes in the occurrence of 5-HT-, glicentin, peptide
YY- or somatostatin-containing cells in the rectal mucosa as compared to control patients [55]. N o specific
neural or muscular morphological defects were identified
in the colonic transmural sections in a patient with
chronic colonic pseudo-obstruction [56].
One possibility may be that the disturbance is at the
local receptor level, in the enteric interneurons which receive and transform the signals from the extrinsic nerves
[57, 58]. The severe idiopathic chronic constipation may
be a manifestation o f a systemic enteropathy [59], which
favours the theory of a general disturbance in bowel
motility in these patients. Evidence for this requires pharmacological studies with specific inhibitors of neuropeptides and/or classical neurotransmitters, and for most of
the peptides such inhibitors are not yet available.
In conclusion, the results from this study suggest that
there are no significant changes in the number of certain
neuropeptide-containing nerve fibres as compared to the
normal distribution of these nerves. Further investigation
of the pathophysiology of colon motility disturbances
may require other techniques, such as radioimmunoassay
for quantitative assessment, pharmacological studies including receptorautoradiography and inhibition studies
with specific antagonists [60].

Acknowledgements. The authors are grateful to Professor T. H6kfelt


(Department of Histology and Neurobiology, Karolinska Institute,

Stockholm) for generously providing space and material during the


initial part of this study, and for his advice and to the Department
of Clinical Pathology at Danderyd Hospital (Head, B. Sandstedt,
MD) for expert help with the routine histology of our large numbers
of colon specimens in this study. The authors wish to thank the
following for the generous provision of antibodies for this study:
Somatostatin (Dr. R. P. Elde, Minnesota University, Minnesota,
USA). Dynorphin+enkephalin (Dr. L. Terenius, University of
Uppsala, Uppsala, Sweden). Bombesin (Dr. G. J. Dockray, Liverpool University, Liverpool, UK). Substance P (Dr. E. Brodin,
Karolinska Institutet, Stockholm, Sweden). VIP (Dr. Stefan B.
Svenson, SBL, Stockholm, Sweden). Motilin (Dr. G. Nilaver, University School of Medicine, Portland, Oregon, USA). Ms. K. Andersson, Ms. C. Wickman and Ms. A. Wildte are gratefully acknowledged for expert technical assistance.
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Dr. A. Dolk
Department of Surgery
Karolinska Institute, Danderyd Hospital
S-182 88 Danderyd
Sweden

Int J Colorect Dis (1990) 5:188-194

Col6reetal
Disease

9 Springer-Verlag 1990

Ultrasonic endoluminal examination in the follow-up of colorectal cancer


Initial experience and results
K. Dresing and W. Stock
Surgical Department, Marien-Hospital Diisseldorf, Federal Republic of Germany
Accepted: 2 August 1990

Abstract. W e h a v e b e e n using e n d o l u m i n a l u l t r a s o n o g r a p h y since 1988 as p a r t o f the f o l l o w - u p p r o c e d u r e after


c o l o r e c t a l surgery. A t o t a l o f 106 p a t i e n t s w i t h a n t e r i o r
r e s e c t i o n o f the r e c t u m o r the sigrnoid c o l o n were inv o l v e d in 1988. T h e f o l l o w - u p p e r i o d for these p a t i e n t s
r a n g e d f r o m 1 to 56 m o n t h s after s u r g e r y (23.1_+ 15.1
m o n t h s after a n t e r i o r r e s e c t i o n o f the rectum; 25.7 + 22
m o n t h s after a n t e r i o r r e s e c t i o n o f the sigmoid). D u r i n g
the o b s e r v a t i o n p e r i o d 7 p a t i e n t s d e v e l o p e d r e c u r r e n c e
after a n t e r i o r r e s e c t i o n o f the r e c t u m a n d 5 after a n t e r i o r
r e s e c t i o n o f the s i g m o i d . T h e p r i m a r y stages for these
p a t i e n t s h a d b e e n 7 cases o f D u k e s ' B, 3 o f D u k e s ' C1 a n d
2 o f D u k e s ' D. R a i s e d s e r u m C E A levels were f o u n d in 5
cases. I n 3 o t h e r cases, we f o u n d p a t h o l o g i c a l c h a n g e s in
the a n a s t o m o t i c r e g i o n by m e a n s o f e n d o s c o p y . In these
the e n d o r e c t a l u l t r a s o n i c scan s h o w e d h y p o d e n s e m a s s e s
as a sign o f recurrence. I n 2 o f these 3 cases, the s e r u m
C E A level was n o r m a l . I n 4 cases e n d o l u m i n a l rectal
u l t r a s o n o g r a p h y a l o n e was suspicious. This led to f u r t h e r
d i a g n o s t i c p r o c e d u r e s a n d finally to r a d i c a l excision. A l l
s u s p i c i o u s u l t r a s o n i c i m a g e s were m o n i t o r e d 2 to 4 weeks
later. I n cases o f suspicion, e n d o s c o p i c , needle o r surgical
t r a n s r e c t a l b i o p s i e s were t a k e n f r o m all p a t i e n t s . I n all
cases, h i s t o l o g i c a l analysis c o n f i r m e d the u l t r a s o n i c d i a g nosis o f l o c a l recurrence.

Introduction
E n d o l u m i n a l u l t r a s o n i c scanning, in c o m b i n a t i o n w i t h
o t h e r ( m a n d a t o r y ) p a r a m e t e r s u s e d in the f o l l o w - u p o f
c o l o r e c t a l cancer, is a p o t e n t i a l m e a n s o f d e t e c t i n g r e c u r rence in the a s y m p t o m a t i c state [1, 2]. I t raises the possibility o f surgical r e - e x p l o r a t i o n , w i t h the u l t i m a t e a i m o f
a c h i e v i n g a cure.
F o l l o w - u p e x a m i n a t i o n after c o l o r e c t a l s u r g e r y seeks
to d e t e c t r e c u r r e n c e at a n e a r l y a s y m p t o m a t i c stage so
t h a t the p a t i e n t m a y be given r a d i c a l c u r a t i v e surgical
t r e a t m e n t . T h e efficiency o f f o l l o w - u p will d e t e r m i n e the
success o f s e c o n d a r y c u r a t i v e s u r g e r y [3].

P a t i e n t s with c o l o r e c t a l c a n c e r are m o n i t o r e d in a
carefully p l a n n e d f o l l o w - u p p r o g r a m m e . I t is k n o w n t h a t
a high p e r c e n t a g e o f recurrence occurs w i t h i n the first
18 m o n t h s after s u r g e r y [3, 4, 5, 6]. O u r a i m was to c o m p a r e the value o f e n d o l u m i n a l u l t r a s o n i c e x a m i n a t i o n
w i t h o t h e r e s t a b l i s h e d m e t h o d s for the f o l l o w - u p a n d
early d e t e c t i o n o f c o l o r e c t a l cancer.

Methods
Our patients with colorectal cancer were examined every 3 months
during the first year after surgery. During the second and third years
examinations were performed every 6 months and annually thereafter. The standard programme consists of recording the patient's
medical history, a physical examination including careful digital
rectal palpation, laboratory tests including CEA, an X-ray of the
lung and ultrasonic scanning of the liver and abdomen. Later, in
addition to routine rectoscopy, the patient is given a colonoscopy or
a barium enema of the colon. Computed tomography is reserved for
special problems such as extrarectal tumour growth.
Since January 1988, all patients who had anastomoses which
were palpable or could be visualized with a rectoscope were examined with endoluminal ultrasonography. The first ultrasonography
was performed 12 days after anterior resection during hospital
treatment. From July 1988, the first endoluminal sonography was
performed on an outpatient basis 4 to 6 weeks after surgery. We had
observed that the postoperative oedema of the anastomotic region
appearing as a spreading of the five ultrasonic interfaces of the
rectum wall - was no longer visible 4 to 6 weeks after surgery.
The ultrasonic probe we used is a 7.5 MHz transducer attached
to a Combison 310 unit made by Kretz (Austria). This bifocal
multiplane rectal transducer allows a 360 ~ panoramic scan and
sector scans at any angle of the longitudinal axis of the probe.
Before inserting the probe, a balloon is attached to its tip, then filled
with degassed water to inflate the rectum and to provide an acoustic
path for the ultrasonic waves. The probe was covered with acoustic
coupling gel, and inserted blindly after digital examination and
rectoscopy. The probe is designed with a palpable and visible scale
calibrated in cm, and may therefore be inserted up to regions of
interest. While turning the probe slowly, it was withdrawn to the
anus.
The ultrasonic images were recorded on VHS videotape and on
a videoprinter.
If the ultrasonic scan showed suspicious hypodense areas in the
rectum wall or in the perirectal tissue, the endoluminal ultrasonog-

189
[months]
60.

mo
50.

40.

30-

/.f~

20,

10.

0.

....
o.O..O-o- - -o-o-

.o..... ~ ' t - ~ H - ,
~..o.,~-e-

o-

'''H'"

.....

"

13

.......

_o.~o_o.e.~-o~-e~'~176
2

8 1012141618202224262830323436384042444648505254

T1NO

[patients]

Fig. 1. Follow-up times of 52 patients with anterior resection for


rectal cancer ( o - - o ) and 54 patients with anterior resection for
cancer of the sigmoid ( o - - o ) in 1988

T2NO

T3N0

T4N0

2
TIN1

T2NI

T3N1

T2N2

T3N2

T2N1M1 T3N2M1 T4N1M1

Fig. 3. TNM staging of 106 patients having anterior resection for


rectal or sigmoid cancer

20

[months]

45.

16
40

tz

35

30

20

15

3
i

I
Dukes A

I
Dukes B

I
Dukes C1

Dukes C2

10

11
12
[patients]

Fig. 4. Tumour recurrence as a function of time in months after


surgery (12/96 patients). [] Cancer of the rectum; [] cancer of the
sigmoid

10

Dukes D

2. Dukes' staging of 106 patients having anterior resection for


rectal or sigmoid cancer
Fig.

raphy was repeated 2 to 4 weeks later. In addition, the standard


ultrasonographic examinations gave continuing experience in the
interpretation of the ultrasonic structure of the rectal wall and the
perirectat tissue. If the control confirmed the image of a recurrence
or even showed growth of the tumorous mass, a biopsy was taken.
In cases of a recurrent tumour in the rectal wall, we proceeded to
take endoscopic biopsies with a punch; in cases of extrarectal
growth only, several needle biopsies were performed under general
anaesthesia. For these patients, we preferred to take the surgical
transrectal biopsy under general anaesthesia.
The results for patients in follow-up at the Marien-Hospital in
Diisseldorf during 1988 were evaluated with the Excel 1.51 spreadsheet program by Microsoft.

Results

Between January and December 1988, 422 patients with


colorectal cancer were monitored during follow-up in our
department. Of these, 106 patients had anterior resections - 52 for rectal cancer and 54 for cancer of the
sigmoid. Follow-up was between 1 and 56 months, patients with anterior resection of the rectum for an average
of 23.1 (SD + 15.1) months, patients with resection of the
sigmoid for an average of 25.7 (SD _+22) months. (Fig. 1).
The 56 female and 50 male patients had an average age of
68.5 (SD _+ 10.4) years. All anastomoses were carried out

with Auto Suture | staplers. Surgery was performed using


the principle of Turnbull's no-touch isolation technique.
After anterior resection of the sigmoid and anterior
resection of the rectum, the anastomoses were found at
8.5(SD + 3.8 cm) and 4.5 (SD __ 1.9 cm) above the dentate
line, respectively. The primary tumours were classified
using Dukes staging and the T N M classification o f / 9 8 7
(Fig. 2 and 3).
Twelve of 106 anterior resection patients developed
histologically proven recurrence of their tumours
(Fig. 4).
In 8 cases, we found local recurrence without metastases (Fig. 5 a), whereas in the remaining 4 cases the local
recurrence was accompanied by metastases (Fig. 5 b). N o
distant metastases occurred without local recurrence.
An increased level of carcino-embryonic antigen gave
a warning of tumour recurrence in only 5 cases. Endoscopic and physical examinations were also normal in
these patients. In 4 of these 5 cases, however, endorectal
ultrasonic scans showed tumorous masses in parallel with
the increase in CEA. In I case, the scan showed tumour
recurrence 4 weeks after the first C E A increase. In all five
cases, biospies confirmed the recurrence.
Four patients had striking findings at endorectal ultrasonography without any clinical or endoscopic signs
of recurrence. Their C E A levels were in the normal range.
Two of these patients showed hypodense areas in the
rectal wall without any enlarged lymph nodes. Four
weeks later, the ultrasonic check confirmed the suspicion

Rectal cancer
T3NOM0

Sigmoid
T3N2M0

Rectal cancer
T3NOM0

Sigmoid cancer
T4NIM1

Rectal cancer
T3NOM0

Rectal cancer
T3NOM0

Sigmoid cancer
T3N1M0

Rectal cancer
T3NIM0

Rectal cancer
T2NOM0

Sigmoid cancer
T3NOM0

Sigmoid cancer

10

11

12

9
9, 75

3
6
7

3
6

3
6
9
12

19

---

--

--

--

--

--

--

.
.

-.

--

.
-

--

17

4, 7, 10, 13

---

14

10

.
--

--

-.

+
--

3, 6
9
12

-.

+
+

3
6

3
4

----

15

0
3
6
9

14

.
--

Digital
exam
nation

.
---

Clinical
signs o f
recurrence

3, 6
9
12

3, 6
9

Follow-up
[months]

--, negative; + , uncertain; + , positive; A P E , a b d o m i n o p e r i n e a l

Rectal cancer
T3NOM0

Primary tumour
stage

Patient

excision

__%

_+

+
+

--

--

--

+
+
+
+

+
+

--

CEA

--

--

--

--

4-

.
_+

--

_+

.
---

+
+

-+

---

Retroscopy

+
+

---

-+

+
+

+
+
+

.
-+

.
+

Endoluminal
m a s s in
rectal wall

--

--

-+

+
+

--

----

--

--

--

Ultrasound
per
tumour

T a b l e 1. O u t c o m e o f 12 p a t i e n t s w i t h r e c u r r e n t c a n c e r f o l l o w i n g a n t e r i o r r e s e c t i o n o f t h e r e c t u m o r s i g m o i d

+
+

CT-scan

refused
+

Endoscopic
biopsy

+
+

Surgical
biopsy

APE

APE

Surgery refused
Radiation

Refused
Refused

APE

Refused APE
APE

Laparotomy: inoperable mass pararectal


and precoccygeal radiation and intraarterial chemotherapy

Radiation
Ileostomy

Drainage of abscess
Further treatment refused

Radiation

Refused
APE, radiation chemotherapy

APE

Treatment

191

Fig. 5. a Recurrent tumour without ultrasonic detection of local


metastasis. The hypodense mass is infiltrating into the perirectal
tissue (arrows). b Recurrent tumour associated with local metastasis
in lymph node (LK)

o f recurrence subsequently p r o v e n by biopsy and histological examination. Besides this local recurrence, the
other 2 patients had enlarged l y m p h nodes on ultrasound. C T scan confirmed this diagnosis in 1 case. Biopsies confirmed t u m o u r invasion in b o t h cases.
Two other patients complained o f pain during digital
examination o f the anastomosis. Endoscopically, we observed a n a s t o m o t i c erosions and ulcerations. The C E A
values were increased to 80 and 95 ng/ml. Endorectal
u l t r a s o n o g r a p h y showed the picture o f local t u m o u r
masses with enlarged l y m p h nodes, and surgical biopsies
were positive.
Only 1 patient complained o f perineal pain. All examinations, including the endoluminal ultrasonic scan were
abnormal.
Ten o f 12 patients with t u m o u r recurrence accepted
further treatment. In 6 cases we proceeded to a b d o m inoperineal a m p u t a t i o n o f the rectum (Table 1).
The staging o f the recurrent t u m o u r o f one patient
after anterior resection o f the rectum with p r i m a r y
p T 3 N O M 0 ( D u k e s ' B) was classified as T 1 N O M 0 (see
case report 1). Twice, the histological specimen showed a
T 4 N O M 0 stage. The rest o f these patients showed l y m p h
node involvement ( T 4 N 1 M 0 / M 1 ) after proctectomy.
Three patients were treated with radiation, 1 by combined treatment with radiation and intra-arterial chemotherapy.
One patient refused radical excision, and 1 rejected
any p r o p o s e d treatment.
In 24 o f the 94 patients w i t h o u t recurrence, ultrasonographic examination showed a b n o r m a l findings. Sixteen
patients had the picture o f local recurrence with a hypodense mass and a spreading o f the 5 interfaces o f the
n o r m a l rectum wall within the first 2 3 weeks. The interfaces themselves were never disrupted. C o n t r o l endosonographies 4 - 6 weeks after resection gave no hint o f
recurrence. O n 7 occasions we f o u n d extrarectal hypodense masses suggesting enlarged l y m p h nodes. Since
these findings could no longer be detected at follow-up,
we interpreted this as reactive l y m p h n o d e enlargement.
One patient h a d multiple h y p o d e n s e areas in the perirectal tissue 42 m o n t h s after resection. The histopatho-

Fig. 6. Hypodense mass in the rectal wall (black arrows) and enlarged lymph node (white arrows), the features of recurrent tumour
9 months after anterior resection of the rectum

logical sections revealed invasion with a n o n - H o d g k i n


lymphoma.
There were no complications f r o m endoluminal ultras o n o g r a p h y . The examination was well tolerated by all
patients.

Case report 1
A 67-year-old male patient underwent anterior resection of the
rectum (EEA) in November 1987. No problems occurred during the
postoperative period. The tumour was staged as pT3NOM0, Dukes'
B, G2. The follow-up at 3 and 6 months after surgery was unremarkable.
In August 1988, the patient had two small granulations - the
size of rice grains - at the anastomosis 9 months after surgery. The
histological analysis of these biopsies showed granulation tissue
without malignancy. The ultrasonic scan revealed disintegration of
the typical interfaces of the wall due to a hypodense mass (Fig. 6)
and one enlarged lymph node (uT2 with positive status of the lymph
nodes). The CEA was normal, with a value of 1.1 ng/ml. The second
transanal biopsy showed parts of an adenocarcinoma. Pathological
staging after procetectomy classified the recurrent tumour as
pTIN0 (Dukes' A). One enlarged lymph node was found in the
specimen with no evidence of malignancy but signs of inflammation.

Case report 2
A 56-year-old female patient underwent anterior resection of the
rectum in March 1987. The tumour was staged as pT3NOM0,
Dukes' B, G2 3. The follow-up at 3 and 6 months after surgery was
unremarkable (Fig. 7 a). Nine months after surgery, the CEA increased to 28 ng/ml. Other tests were normal. CT of the abdomen
and abdominal ultrasonography showed fatty liver infiltration. At
a 1-year follow-up, the CEA increased to 30 ng/ml. Digital, endoscopic and CT examinations showed no tumour recurrence. The
endorectal ultrasonic scan showed mainly hypodense masses in the
rectal wall (Fig. 7 b). Biopsy of the anastomosis showed no malignancy.
Two months later, the CEA level increased to 57 ng/ml. The
surgeon detected a mass at the anastomosis on digital examination.
Endosonography revealed enlarged hypodense masses in the rectal
wall (Figs. 7 c, d). A repeat biopsy revealed malignancy. The patient
refused proctectomy. Seventeen months after primary surgery, the
patient suffered perineal pain, and tumour at the anastomosis was

192

Fig. 7. a Normal endorectal ultrasonic image of the anastomosis


with 3 interfaces 6 months after surgery (arrows). b Hypodense mass
(arrows) 12 months after surgery, e, d 14 months after surgery:

enlarged hypodense mass visualized by a panoramic (c) and a sector


scan (d)

Fig. 8. a Case 3. Ultrasonic image 12 days after surgery: hypodense


infiltration of the perirectal tissue, b, e Three months after surgery:
hypodense mass (about 4 cm) infiltrating into the perirectal tissue

with hyperdense echoes in the central part of the mass. The diagnosis after re-operation: recurrent tumour and local abscess

easily palpable. The patient now agreed to proctectomy. During the


operation, we resected 40 cm of ileum attached to the tumour mass.
The pathologist reported a pT4N1M1 stage. The operation was
followed by radiation and intra-arterial perfusion of the pelvis. In
the following months, we saw this patient several times in our
emergency room with bowel obstructions caused by recurrence of
the enlarging tumour.

ing the operation we confirmed a recurrent cancer by biopsy, and


a local abscess was also drained. The patient refused further treatment - either surgery or radiation.

Case report 3
A 62-year-old male patient underwent anterior resection of the
rectum in July 1988 with a stapled anastomosis (EEA). The postoperative period was normal. The tumour was staged as pT3NOM0,
Dukes' B, G 2.
The first postoperative endorectal ultrasonic scan showed a
hypodense infiltration of the intestinal wall and the perirectal tissue.
The inner ultrasonic interface was intact (Fig. 8 a). The patient did
not accept a control sonography 4 weeks later.
Three months after resection, the patient was admitted to hospital with perineal pain and fever. Digital and endoscopic proctological examinations were very painful. Rectoscopic examination of
the rectum and anastomosis showed an intact mucosa. With the
ultrasonic scan, however, we saw a hypodense mass (about 4 cm)
infiltrating the perirectal tissue. The central part of the mass was
more inhomogeneous but was mainly hyperechoic (Fig. 8 b, c). Dur-

Discussion
F o l l o w - u p after surgery for colorectal cancer is a well
established p r o c e d u r e [3, 6 - 9 ] . Its a i m is to detect recurrence o f cancer at the earliest possible time, since p a t i e n t s
c a n u n d e r g o r e o p e r a t i o n with a p o t e n t i a l cure in 18 to
60% o f cases [3, 10, 11]. T h e effectiveness o f follow-up for
colorectal cancer a n d g o o d survival rates for p a t i e n t s
u n d e r g o i n g r e - e x p l o r a t i o n have been d e m o n s t r a t e d [3].
I n the first year following p o t e n t i a l l y curative resection, 30 to 50% o f t u m o u r recurrences are f o u n d - a
f u r t h e r 2 5 % b e i n g detected in the following 12 m o n t h s
[ 3 - 5 , 8]. Overall, the rate o f local recurrence varies f r o m
0 to 4 4 % [6, overview statistics 1 1 - 1 3 ] . The p r o g r a m m e
for follow-up is m a t c h e d with the t i m i n g of the r e c u r r e n t
t u m o u r . I n o u r follow-up for colorectal cancer we examined the p a t i e n t s every 3 m o n t h s d u r i n g the first p o s t o p erative year, a n d every 6 m o n t h s d u r i n g the second postoperative year.

193
The basic examinations in follow-up for colorectal
cancer are well established [7-9]. However, the sensitivity of each individual examination for detecting early recurrence varies greatly [5, 7, 14].
In follow-up after anterior resection for rectal and
sigmoid colon cancer, endoscopy m a y detect up to 55%
of recurrent tumours [5, 7].
The serial determination of the carcino-embryonic
antigen is an effective means of detecting local recurrence
and metastasis [7, 15, 16]. A rise in CEA is associated with
tumour recurrence with a 74.4 to 84% sensitivity [7, 15].
It has, however, been repeatedly shown that early
recurrence at the pT1NOM0 stage m a y be associated
with a normal C E A level [11, 16, 17]. In our own study,
4 of 12 patients with recurrent tumours had a normal
CEA. In addition, it has been shown that patients with
recurrence and a low C E A level have significantly better
results after second curative surgical procedures [16].
Computer-assisted t o m o g r a p h y is used in the followup of colorectal cancer in the event of C E A elevation,
when a tumour mass is palpable, or in any case of suspicion of perirectal recurrence [7].
Endorectal ultrasonography is a method with an established value in the preoperative staging of rectal cancer [7, 18-20]. Our own results, like those of others [1, 2,
20], show that endorectal ultrasonic scanning does improve the early detection of t u m o u r recurrence. In 4 of
our 12 patients with recurrence after anterior resection of
the rectum and sigmoid, we used endorectal ultrasonography as the principal indicator of recurrence. Hildebrandt et al. [2l] detected 6 of 22 recurrences with ultrasound alone. Beynon et al. diagnosed recurrence in 3 of
22 cases solely by endosonography [1].
In 5 of 12 patients in our series, we found an elevated
C E A level as an indication of t u m o u r recurrence. However, no other established method could detect the turnout.
This was achieved only by an endoluminal ultrasonic
scan. On the basis of these results, further tests were
performed followed by reoperation.
In comparisons of a digital examination, CT scans
and endorectal ultrasonography the last method has the
highest accuracy, sensitivity and specificity for the preoperative detection of turnouts [20, 22, 23, 24]. We found
similar results to those reported by others for postoperative follow-up [20, 23].
The ultrasonic image of recurrent rectal or sigmoid
cancer is the same as that of a primary cancer with interruption of the ultrasonic layers by a hypodense mass.
Perirectal invasion is even m o r e homogenous, but is difficult to differentiate from fibrosis or oedema [1, 2].
This is why we insist that 4 to 6 weeks after surgery the
first postoperative endosonographic examination is performed as a basis for the follow-up. Postoperative oedem a of the anastomotic region often occurs during the first
4 - 6 weeks when we have seen spreading of the ultrasonographic interfaces in the normal ultrasonic image of the
rectal wall. This m a y be misinterpreted as an early tum o u r recurrence. As the oedema decreases, we have noted that the interfaces converge. Inflamed lymph nodes
can no longer be found in control scans once the inflammation has gone.

I f we see a suspicious area at the anastomosis or in the


perirectal tissue, an ultrasonographic examination is repeated after 1 or 2 weeks. I f spreading of the ultrasonic
layers increases, local recurrence becomes more probable.
E n d o s o n o g r a p h y alone can never detect recurrence.
It will only identify abnormal areas in the rectum wall or
the perirectal tissue, and it cannot differentiate between
oedema, fibrosis and a tumour. It is not possible to diagnose a recurrent tumour on the basis of a single examination showing minor changes. Repeated endoluminal ultrasonic scans m a y detect recurrence, however [2]. Histopathological analysis is essential to confirm the diagnosis
of a recurrent tumour [1, 2, 23].
Our experience with endorectal ultrasonography
based on 106 patients for the follow-up of colorectal cancer after anterior resection in 1988 shows that it is a
method enabling the surgeon to detect early t u m o u r recurrence and to offer early, potentially curative re-operation. It is well tolerated, repeatable and without any exposure to X-rays. We have incorporated endosonography
into the routine follow-up of our patients with colorectal
cancer.

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194
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CEA-Testes ffir die Diagnostik und chirurgische Therapie des
rezidivierenden colorectalen Carcinoms. Chirurg 57:83-87
17. Mentges B (1988) Der EinfluB von seriellen CEA-Bestimmungen auf Diagnose, Therapie und Prognose des rezidivierenden
colorectalen Carcinoms. Langenbecks Arch Chir 373:227-234
18. Beynon J, Mortensen NJ McC, Foy DMA, Channer JL (1986)
Endorectal sonography: laboratory and clinical experience in
Bristol. Int J Colorect Dis 1:212 215
19. Badea R, Badea Gh, Philippi W, Dejica D, Bologa S (1988)
Weft und Grenzen der endorektalen Sonographie in der
pr/ioperativen Stadieneinteilung des Rektumkarzinoms. Ultraschall 9:265-269
20. Feifel G, Hildebrandt U, Dhom G (1985) Die endorectale
Sonographie beim Rectumcarcinom, Chirurg 56:398-408

21. Hildebrandt U, Feifel G, Schwar HP, Scherr O (1986) Endorectal ultrasound: instrumentation and clinical aspects. Int J
Colorectal Dis 1:203-207
22. Beynon J, Mortensen NJ McC, Foy DMA, Channer JL (1986)
Pre-operative assessment of local invasion in rectal cancer: digital examination, endoluminal sonography or computed tomography? Br J Surg 73:1015-1017
23. Romano G, de Rosa P, Vallone G, Rotondo A, Grassi R, Santangelo ML (1985) Intrarectal ultrasound and computed tomography in the pre- and postoperative assessment of patients
with rectal cancer. Br J Surg [Suppl]: $117-S119
24. Kramann B, Hildebrandt U (1986) Computed tomography versus endosonography in the staging of rectal carcinoma: a comparative study. Int J Colorect Dis 1:216-218

Dr. K. Dresing
Abteilung fiir Unfallchirurgie
UniversitfitsklinikumEssen
Hufelandstrasse 55
W-4300 Essen
Federal Republic of Germany

Int J Colorect Dis (1990) 5:195-199

Col6 ree|al
Disease

9 Springer-Verlag 1990

Surgical management of perforating diverticular disease in Austria


M. Hold, H. Denck and P. Bull
First Surgical Department, Krankenhaus Wien-Lainz, Vienna, Austria
Accepted: 2 August 1990

Abstract. Perforated diverticulitis is a much feared complication of diverticular disease and requires immediate
surgical therapy to limit the incipient peritonitis and its
sequelae. The ensuing surgical approach which could best
irradicate the septic focus as well as restore normal intestinal continuity with less morbidity and mortality has
been a matter of controversy. In the last ten years primary resection and colostomy has replaced the threestage procedure in most cases of peritonitis. Primary
anastomosis, when peritoneal involvement is well confined, has been shown to give excellent results. To assess
the surgical management of perforating diverticulitis in
Austria, a questionnaire was sent to leading hospitals
throughout the country and information of 241 patients
with perforating diverticulitis was compiled. The overall
peroperative mortality was 9%, and the highest rate of
complication (37.9%) was observed after primary resection and anastomosis with temporary defunctioning
proximal colostomy. The mortality, as expected, is directly proportional to the extent of peritonitis; it was
significantly greater among patients with generalised
peritonitis and lowest among cases of covered perforation.

Introduction
The treatment of perforated diverticulitis is still a matter
of controversy. The one-stage segmental resection with primary anastomosis in cases of uncomplicated diverticulitis
is the method of choice but this operative procedure has
also been advocated in the presence of advanced peritonitis and has gained acceptance on the grounds that it will
most effectively restore continuity with less disability [1,
2]. However, in the presence o f free perforation and faeculant peritonitis, this operation has not gained universal
acceptance. Some surgeons still prefer the three-stage
procedure initiated by Smithwick in 1942 [31. Other prefer the two-stage H a r t m a n n resection promoted by
Boyden in the nineteen fifties as it has been shown to
reduce complications [4-9]. Comparison between the dif-

ferent approaches is difficult as the extent of peritoneal


involvement at time of surgery is generally poorly
recorded [4].
The aim of this study was to learn more concerning
the results of management of perforated diverticulitis and
to compare the surgical procedures currently practised in
Austria. To do so a detailed questionnaire was sent to all
leading hospitals throughout the country relating to patients treated from 1985 to 1987.
Material and methods
A questionnaire seeking answers to 67 points pertinent to patients
with perforated diverticulitis was sent to the heads of department of
92 surgical services (Table 1). Information concerning age, sex, past
Table 1. Surgical departments involved in the survey
Patients
Amstetten Hospital
Eisenstadt Hospital (Barmherzige Brfider)
Dornbirn Hospital
Klagenfurt Hospital (Elisabethinen)
Linz Hospital (Elisabetbinen)
Feldbach Hospital
Feldkirch Hospital
Gmunden Hospital
Graz Hospital, Surgery II
Hanusch Hospital, Vienna
Innsbruck University Hospital, Surgery 1
Innsbruck University Hospital, Surgery II
Wien-Lainz Hospital, Surgery I
Neunkirchen Hospital
Kirchdorf an der Krems Hospital
Knittelfeld Hospital
Krems Hospital
Oberwart Hospital
Vienna Polyclinic
Steyr Hospital
Tulln Hospital
Villach Sanatorium
V6cklabruck Hospital
Wilhelminenspital, Vienna, Surgery II

8
3
31
3
24
3
5
7
8
7
12
15
13
15
8
3
9
11
8
15
2
3
7
21

196

Mortality
more than

20 cases
pertinent data
missing

24 h

29 cases
walled off
peritonitis

3.4%

10%

130 cases
localised
p e r itonitis

62 cases
diffuse
peritonitis

5.4%

Fig. 1. Mortality according to


stage of peritoneal involvement
and duration of disease (< or
>24 tl)

HARTMANN PROCEDURE

COLOSTOMY & DRAINAGE

RESECT.& ANAST.

RESECT.,ANAST. COLOST.

76

46

70

29

59%

lOO
41%

80
.......................................................
~ ....................
6 0 ...........................................................................................................................................................................................................................
I
4 0 .................................................................................................................................................................................................................

Complications

Death

Complications

Death

Complications

Death

Com~ications

d i f f u s e peritonitis

history, immunosuppression therapy, congenital disorders, method


of diagnosis, definition of peritoneal involvement, duration of
symptoms, surgical procedure was sought. Complications following
surgery, their treatment, the frequency of reconstitution of intestinal continuity were also assessed as was the duration of follow-up.
In all, duly completed questionnaires were returned by 24 departments. Eighteen others only communicated their general line of
approach and were therefore excluded from the study.
Peritoneal involvement at operation was classified into three
stages following the recommendation of Hinchey et al. [10]. These
included covered walled-offperforation (stage 1), localized (stage 2)
and diffuse peritonitis (stage 3). Diffuse peritonitis was not subdivided into purulent and faecal since it was thought that a clear
distinction was not possible to judge in most cases.
Statistical comparisons were made using the chi-square test.

Death

Fig. 2. Incidence of diffuse


peritonitis with complication
and mortality rates related to
surgical procedure

Results
F r o m 1985 to 1987, 241 patients u n d e r w e n t surgery for
perforated diverticulitis at the 24 hospitals. There were 99
m e n aged between 23 and 88 years (median 62.13 years)
and 142 w o m e n aged between 26 and 97 years (median
68.73 years). D u r i n g the initial treatment 22 patients died
(9%). These were aged between 52 and 97 years (median
78.54 years). The sigmoid colon was the site o f perforation in 95.2%, the right and transverse colon sharing
evenly in the remaining cases. N o case associated with
i m m u n e deficiency was reported.
Diagnostic procedures p e r f o r m e d included plain abd o m i n a l film in 63.4%, enema with water-soluble contrast media in 46.9%, c o l o n o s c o p y in 8.3% and c o m puted t o m o g r a p h y in 2%.

197

COLOSTOMY &
DRAINAGE

HARTMANN
PROCEDURE
67

[]

survivors

47 Restorations
62%
including 4 fistulas
I Death

[]

No further procedure
No date

RESECT., ANAST.
& COLOSTOMY
27

40 survTvors

14 Resections

.30%

4 Resections +
9%
colostomy closure
[ ~ 12 Colostomy
26%
closure only
No further procedure
[]

survivors

15 Colostomy
52%
closure
including 1 fistula
[~
No furfher procedure
[]~

No data

Fig. 3. Subsequent restoration of anal


function following surgical procedure with
corresponding complications and outcome

No data

Table 2. Extent of contamination, complication and mortality for each procedure


Hartmann

Cotostomy
& drainage

Prim. resec. +
anastomosis

Prim. resec. +
anastomosis
+ colostomy

Conservative

Drainage
alone

Total n

76

46

70

29

13

Diff. peritonitis (>24h)


Loc. peritonitis (>24 h)
Walled offperit. (>24h)

31 (19)
38 (33)
7 (3)

15 (10)
22 (19)
9 (2)

11 (4)
49 (42)
10 (4)

5 (3)
21 (18)
3

9
?
?

?
?
?

Complications n
Diff. peritonitis (> 24 h)
Loc. peritonitis (>24h)
Walled off perit. (> 24 h)

16
11 (8)
5 (1)
-

6
3 (2)
3 (2)
-

11
1
4 (2)
6 (4)

11
2
9 (t)

Death n
Diff. peritonitis (>24h)
Loc. peritonitis (>24 h)
Walled offperit. (>24 h)

9
6 (4)
2
I (1)

6
3 (2)
3 (1)

In 20 patients the Hinchey stage was not known. A


covered perforation was found in 29 patients (12.03%),
of w h o m 9 had had symptoms for longer than 24 h. A
localised peritonitis was present in 130 (53.9%), of w h o m
112 were more than 24 h duration. Sixty-two (25.7%)
had a generalised peritonitis with a duration of 24 h or
more in 36 cases.
The mortality was directly proportional to the stage
of the perforation as follows: stage 1, 3.44%; stage 2,
5.38% and stage 3, 19.44%. It was 10% in the cases with
incomplete data on the extent of perforation (Fig. 1).
The initial surgical treatment in 76 cases consisted of
a primary resection with end-colostomy ( H a r t m a n n procedure). In these cases, the prevalence of diffuse peritonitis was high at 40.7% (31 patients). Forty-six patients
were treated solely with a transverse colostomy. In these
generalised peritonitis was present in 32.6% (15 patients).
Primary resection and anastomosis without proximal

1 (1)
1 (1)

2
-

(2)
1

colostomy was carried out on 70 patients, of w h o m 11


(15.7%) had diffuse peritonitis. In 29 other cases including 5 (17.2%) with diffuse peritonitis a primary resection
and anastomosis was covered by a protective proximal
colostomy. Seven patients were managed conservatively
and 13 others were treated solely with drainage (Fig. 2,
Table 2).
In line with the high prevalence of generalised peritonitis, H a r t m a n n ' s procedure carried a higher mortality
of 11.8%. O f the 9 deaths 6 had a generalised peritonitis
(4 longer than 24 h) and 3 had local involvement (1 longer
than 24 h). O f these, 7 suffered from a postoperative diffuse peritonitis and one other from an ileus. The overall
morbidity of the H a r t m a n n ' s procedure (peritonitis,
ileus, colostomy infection) was 21.05% (16 cases)
(Fig. 2).
Morbidity following the 70 primary resections with
anastomosis occurred in 11 cases (15.7%). These in-

198
cluded anastomotic leakage (7), obstruction (2) and peritonitis (2), this latter cause being also responsible for one
of the two deaths (mortality 2.85%) (Table 2).
Following primary anastomosis with proximal transverse colostomy there were 11 cases (42.3%) with complications. These included anastomotic leakage (7), of which
two were fatal, obstruction (1), peritonitis (1) and infection at the colostomy site (2). The two deaths were caused
by generalised peritonitis.
Of the 46 cases treated by colostomy and drainage the
complication rate was 13 % (6 cases). All these cases died
owing to peritonitis which was generalised in three cases
and localised in three (Table 2).
Two out of the 7 patients treated conservatively died.
There was one death in the 13 patients treated by
drainage alone.
Restoration of continuity in the patients surviving
Hartmann's procedure was carried out on 47 of 67 survivors after an average interval of 4 months with one
death of non-surgical cause. This procedure was complicated by anastomotic leakage in 4 (11%) patients.
The colostomy was closed in 15 of the 27 cases treated
by primary resection with protective proximal colostomy. There was one leak in this group (Fig. 3).
Only 14 of the 40 surviving cases who had had a
simple colostomy underwent subsequent resection of the
inflamed segment with one case of anastomotic fistula. In
a further 12 patients the colostomy was closed without
resection.
Discussion

An estimation of the incidence of diverticular diseases in


the general population is difficult to obtain since information is scanty. The incidence of diverticular disease is
estimated to be about 5% of the general population but
in people over the age of 80, 75% are affected, according
to Rodkey and Welch [9]. Despite this high figure complications of the disease are remarkably low. The most serious is free perforation with faecal peritonitis (stage 4 of
the classification of Hinchey et al. [10]). The diagnosis
was confirmed in over 60% of our registered cases by
plain abdominal x-ray. This rate was higher than the 40%
reported by Nagorney et al. [4]. Bell et al. [5] in a retrospective study at the Vancouver General Hospital reported radiological evidence of free perforation in only
21.3% of patients with generalised peritonitis.
Primary resection with anastomosis is accepted as the
procedure of choice in the elective treatment of uncomplicated diverticulitis. However, there is no general agreement on the choice of procedure when peritoneal contamination is present. Nevertheless, in the past 10 years
the two-stage Hartrnann procedure has gained wide acceptance over the three-stage procedure since it has been
shown to yield a lower mortality and morbidity [4-9].
In the present series the highest incidence of complications (42.3%) occurred after resection and anastomosis
with temporary defunctioning transverse colostomy.
However, this operation was used in only 10% of cases
with diverticular perforation and Gregg [2], reviewing his
wide experience, reported the results of this procedure to

be superior to those of Hartmann's procedure used in


similar situations. Rodkey and Welch [9] reported 25
cases treated by resection with anastomosis protected by
temporary transverse colostomy without any mortality.
Hackford et al. [7], reviewing the Lahey Clinic experience
of resection with anastomosis with proximal colostomy,
reported no deaths and a morbidity rate of 22%. They
concluded, however, that the Hartmann operation was to
be preferred in the presence of generalised peritonitis.
The mortality rate of 13% of colostomy alone was
very similar to that following the Hartmann procedure in
our series. However, the degree of peritoneal contamination was different in the two groups with respective rates
of generatised peritonitis of 33 % and 41%. Furthermore,
there is a shorter period of disability following Hartmann's operation [4, 5]. Hackford et al. [7] determined
the duration of hospitalisation and average length of disability for each operative approach regardless of peritoneal involvement. They reported an average period of
hospitalisation of 21 days for primary resection and anastomosis which was similar to the finding in our study. For
patients having Hartmann's procedure they reported a
cumulative average hospitalisation of 39 days with 22
weeks of disability overall. In our experience the median
primary period of hospitalisation following Hartmann's
procedure was 16 days, which was shorter than after
colostomy and drainage, despite a greater degree of peritoneal involvement.
Nagorney et al. [4], reviewing their experience at the
Mayo Clinic, showed that in patients suffering from perforated sigmoid diverticulitis with generalised peritonitis,
proximal colostomy and resection or exteriorisation was
associated with a significantly lower mortality than proximal colostomy and drainage. Dawson et al. [11] reported
an 11% incidence of persistent intra-abdominal sepsis
after colostomy alone. This supports the concept that the
only satisfactory control of sepsis is through excision of
the perforated segment.
The lower morbidity and mortality rates found in the
present study after resection with primary anastomosis
compared with Hartmann's procedure are probably due
to the lower incidence of diffuse peritonitis in this group.
This supports the concept that in the presence of stage 1
and stage 2 peritoneal contamination, anastomosis subsequent to primary resection without proximal colostomy
can be safely recommended. This approach is associated
with the shortest period of disability [1, 2, 12, 13].
The results of this study indicate that in cases of extensive peritonitis (stage 3 and stage 4) Hartmann's procedure is to be preferred. Where, on the other hand, contamination is less (stage 1, stage 2) a resection and primary anastomosis should be undertaken. The use of
colostomy as the sole procedure, by leaving the inflamed
focus in place, increases the risk of persisting sepsis and
disability and may also complicate subsequent surgery.
References

1. Madden JL (1965) Primary resection and anastomosis in the


treatment of perforated lesions of the colon. Am Surg 31:781786

199
2. Gregg RO (1987) An ideal operation for diverticulitis of the
colon. Am J Surg 153:285-290
3. Classen JN, Bonardi R, O'Mara CS, Finney DCW, Sterioff S
(1976) Surgical treatment of acute diverticulitis by staged procedures. Ann Surg 184:582-586
4. Nagorney DM, Adson MA, Pemberton JH (1985) Sigmoid
diverticulitis with perforation and generalized peritonitis. Dis
Colon Rectum 28:71-75
5. Bell GA, Panton ONM (1984) Hartmann resection for perforated sigmoid diverticulitis: a retrospective study at the Vancouver General Hospital experience. Dis Colon Rectum 27: 253256
6. Eisenstat TE, Rubin RJ, Salvati EP (1983) Surgical management of diverticulitis: the role of the Hartmann procedure. Dis
Colon Rectum 26:429-432
7. Hackford AW, Schoetz DJ, Collar JA, Veidenheimer MC (1985)
Surgical management of complicated diverticulitis. Dis Colon
Rectum 28:317 321
8. Berman I, Hale H, Castro AF, Gallagher DM, Salvati EP
(1981) Surgical management of diverticulitis. Dis Colon Rectum 24:65-89

9. Rodkey GC, Welch CE (1984) Changing patterns in the surgical


treatment of diverticular disease. Ann Surg 200:466-477
10. Hinchey EJ, Schaal GH, Richards MB (1978) Treatment of
perforated diverticulitis of the colon. Adv Surg 12:85-105
11. Dawson JL, Hanon I, Roxburgh RA (1965) Diverticulitis coli
complicated by diffuse peritonitis. Br J Surg 52:359-365
12. Ryan P (1983) Changing concepts in diverticular disease. Dis
Rectum Colon 26:12-18
13. Dandekar NV, McCann WJ (1969) Primary resection and anastomosis in the management of perforation of diverticulitis of
the sigmoid flexure and diffuse peritonitis. Dis Colon Rectum
12:172 175

Dr. M. Hold
1. Abteilung ffir Chirurgie
Krankenhaus Wien-Lainz
Wolkersbergenstrage 1
A- 1130 Wien
Austria

Int J Colorect Dis (1990) 5:200 202

Col6reclal
Disease

9 Springer-Verlag 1990

Treatment of pilonidal sinus by excision and rhomboid flap


C. Jim~nez Romero 1, M. Alcalde 2, E Martin 2, A. Pulido 2 and P. Rico 1
1 Service of General and Digestive Surgery, Hospital 12 de Octubre, Madrid, Spain
z Service of General and Digestive Surgery, Hospital de Pozoblanco, Cordoba, Spain
Accepted: 5 September 1990

Abstract. A series o f 23 p a t i e n t s w i t h c h r o n i c p i l o n i d a l
disease h a v e been t r e a t e d b y excision a n d t r a n s p o s i t i o n
r h o m b o i d flap. F u l l p r i m a r y h e a l i n g was o b t a i n e d in all
p a t i e n t s , w i t h o n l y two cases o f w o u n d s e r o m a . T h e average h o s p i t a l stay was 9 days. T h e m e a n f o l l o w - u p p e r i o d
was 12 m o n t h s , a n d no late recurrences h a v e o c c u r r e d .

Introduction

of systemic cefoxitin (the first, 1 h before operation, and the other


two at 8 h intervals) were given as prophylaxis against infection.
The buttocks were retracted laterally with adhesive tape. The buttocks and sacrococcygeal area were shaved and washed with povidone-iodine solution. A rhombus CDEF including the pilonidal
sinus was marked (Fig. 1 b) with the major diagonal 7.5-13 cm long
(mean 9.6 cm), the minor diagonal 4 - 8 cm (mean 6.1 cm), and the
side 4.5-8 cm (mean 6 cm) long. The flap was delineated by prolongation of the minor diagonal EC and the side FC, crossing these
lines to form the angle ~. The line CB of equal length to the side of
the rhombus bisected the angle ~, and the equal line BA was drawn
perpendicular to the minor diagonal. The rhombus CDEF, including all fistulous tracts, skin and subcutaneous tissue down to the

P i l o n i d a l sinus is a c o m m o n disease t h a t still r e m a i n s


c o n t r o v e r s i a l in origin. It affects y o u n g p e o p l e c a u s i n g
c h r o n i c d i s c o m f o r t a n d loss o f c a p a c i t y to w o r k .
M a n y surgical t r e a t m e n t s h a v e been tried, i n c l u d i n g
incision a n d d r a i n a g e for a c u t e p i l o n i d a l abscess; excision
a n d h e a l i n g b y o p e n s e c o n d a r y i n t e n t i o n ; excision a n d
p a r t i a l c l o s u r e ( m a r s u p i a l i z a t i o n ) ; excision a n d p r i m a r y
closure, a n d excision a n d r e p a r a t i o n b y p l a s t i c p r o c e dures.
I n a n a t t e m p t to d e c r e a s e the failure a n d r e c u r r e n c e
rates, we h a v e u s e d the t r a n s p o s i t i o n r h o m b o i d flap first
d e s c r i b e d b y D u f o u r m e n t e l [1], a n d f u r t h e r e m p l o y e d b y
A z a b et al. [2] in the t r e a t m e n t o f p i l o n i d a l sinus.

Material and methods


Between February and December, 1988, 23 consecutive patients, all
men with chronic pilonidal disease, were treated by excision and
transposition rhomboid flap. The age of the patients ranged from 17
to 34 years (mean 25 years). The length of history ranged from 3
months to 13 years (mean 2.6 years). Hirsutism was present in all
patients, and moderate obesity in five. Before admission all had had
previous infections. These included abscess treated by surgical
drainage in 11 (twice in 3 of these); spontaneous drainage of abscess
in 7, and chronic emission of sero-purulent liquid in 5.

Operative technique (Fig.

1)

The operation was performed under general anaesthesia in 20 patients and epidural in 3. All were in the prone position. Three doses

Fig. 1. Schematic design of the different steps of the excision and


transposition rhomboid flap as treatment of chronic pilonidal disease

201
sacral fascia medially and to the glueal fascia laterally was resected.
In five patients a small triangular flap CIJ (Fig. I b) was mobilized
to avoid tension. Next, the line ABC was incised through skin and
subcutaneous tissue to the gluteal fascia (Figs. 1 b and c). The flap
AGHF was transposed (Fig. 1 d), so that point G approximated to
point D, H to E, and A to C (Fig. 1 e), thus covering the defect left
by the resected rhombus CDEF, and flattening the natal cleft.
Haemostasis was achieved with electrocoagulation. The wound was
closed in two layers. The subcutaneous tissue was approximated
with polyglactin or polyglycolic acid sutures to include a bite of
glueal fascia. The skin was closed using 000 silk interrupted mattress
stitches. A suction drain was placed deeply into the wound and
brought out above point B.

Postoperative management
The suction drain was removed when the daily drainage of serosanguineous liquid was less than 4 ml. This usually occurred between
the third and sixth postoperative days. The patients were nursed in
the lateral or prone position until the drain was removed. Thereafter, patients were allowed to walk and to sit on soft surfaces. After
the 15th to 18th days sitting on a hard surface was also allowed.
Half of the skin stitches were removed on the eight postoperative
day and the rest on the ninth.

Follow-up
All patients were seen after hospital discharge in the outpatient
clinic at 1 week and at 1, 3 and 9 months.

Results
The average hospital stay was 9 days (range 5 to 14 days).
Healing was uneventful in 21 patients (91%). Only two
patients (9%) suffered a w o u n d seroma (negative culture). This m a y have been due to excessive mobilisation
and blockage o f the drain, resulting in drainage t h r o u g h
the superior angle o f the wound. All patients returned to
n o r m a l acitivity three weeks after operation. Over a follow-up period o f 9 to 19 m o n t h s (mean 12 m o n t h s ) no
case o f recurrence was seen. Only one patient m e n t i o n e d
slight discomfort on sitting for long periods o f time, the
rest were a s y m p t o m a t i c , and n o n e complained o f a loss o f
skin sensation.

Discussion
The simplest treatments for pilonidal sinus often require
a p r o l o n g e d healing period and time-consuming w o u n d
care. The failure and recurrence rates are often high. Simple laying open has a reported recurrence rate o f between
8 and 24% [3, 4], with a median healing time o f 6 weeks
[3]. Likewise, excision with healing by secondary intention fails in f r o m 9 to 27.7% [5-7]. Recurrence following excision and marsupialization occurs in 4 to 9 % o f
cases [8, 9]. These o p e n techniques have the d r a w b a c k s o f
prolonged hospitalization and outpatient care o f 1 to 3
m o n t h s before healing is complete [10-12].
Excision and p r i m a r y suture might be t h o u g h t to be
the m o s t effective treatment. However, tension on the
suture line and the f o r m a t i o n o f a serosanguineous col-

lection in the subcutaneous layer frequently lead to infection and b r e a k d o w n o f the w o u n d [13], with a reported
incidence o f between 0 and 47% [5, 7, 14, 15], and an
average rate o f a r o u n d 10% [12]. F o r this reason, other
procedures have been devised to improve these results.
M o n r o and M c D e r m o t t [16] pointed o u t the i m p o r t a n c e
o f the obliteration o f the natal cleft, flattening it with a
Z-plasty. This technique minimizes friction and moisture
between the buttocks and avoids a dead space, thus reducing the potential for. serum or blood to collect. H o w ever, complications including necrosis, w o u n d infection,
skin numbness, pruritus and h a e m a t o m a [17], and a recurrence o f up to 10% have been reported [5, 17-19].
Excision and a m o r e complex W-plasty closure has been
used in a series o f 12 patients with recurrence in one case
(8.3%) [20]. A n o t h e r plastic surgical repair, the so-called
" D " excision, has been recently described with a 20%
recurrence rate in 30 cases [21].
In the Z-plasty technique the acute angles ( < 60 ~
occasionally result in ischaemic necrosis o f the flap corners [17]. In contrast, the r h o m b o i d flap avoids tension
on the suture lines, covering and flattening the natal cleft
with angles o f 60 ~ to 90 ~ allowing an excellent b l o o d
supply, as d e m o n s t r a t e d in this and another series [2].
The excision and transposition r h o m b o i d flap is our
treatment o f choice in all cases o f chronic pilonidal disease because it flattens the natal cleft, avoids dead space
and has a g o o d b l o o d supply. In addition, healing time is
short, m o r b i d i t y is low, recurrence is absent with 1 year
o f follow-up, and the technique can be easily performed
by a general surgeon.
References
1. Dufourmentel C (1963) An L-shaped flap for lozenge-shaped
defects. In: Transactions of the third international congress of
plastic surgery. Excerpta Medica Foundation, Amsterdam,
p 722
2. Azab ASG, Kamal MS, Saad RA, Abou al Atta KA, Ali NA
(1984) Radical cure of pilonidal sinus by a transposition rhomboid flap. Br J Surg 71:154-155
3. Edwards MH (1977) Pilonidal sinus: a 5-year appraisal of the
Millar-Lord treatment. Br J Surg 64:867-868
4. Bascom J (1983) Pilonidal disease: long-term results of follicle
removal. Dis Colon Rectum 26:800-807
5. Sood SC, Green JR, Perni R (1975) Results of various operations for sacrococcygeal pilonidal disease. Plast Reconstr Surg
56:559-566
6. McLaren CA (1984) Partial closure and other techniques in
pilonidal surgery: an assessment of 157 cases. Br J Surg 71:561
562
7. Kronborg O, Christensen K, Zimmerman-Nielsen C (1985)
Chronic pilonidal disease: a randomized trial with a complete
3-year follow-up. Br J Surg 72:303-304
8. Cavanagh CR, Schnug GE, Girvin GW, McGonigle DJ (1979)
Definitive marsupialization of the acute pilonidal abscess. Am
Surg 36:650 651
9. Duchateau J, De Mol J, Bostoen H, Allegaert W (1985) Pilonidal sinus. Excision - marsupialization phenolization? Acta Chir Belg 85:325 328
10. Palumbo LT, Larimore OM, Katz IA (195/) Pilonidal cysts and
sinuses; a statistical review. Arch Surg 63:852-857
11. Notaras MJ (1970) A review of three popular methods of treatment of postanal (pilonidal) sinus disease. Br J Surg 57: 886890

202
12. Allen-Mersh TG (1990) Pilonidal sinus: finding the right track
for treatment. Br J Surg 77:123-132
13. Fishbein RH, Handelsman JC (1979) A method for primary
reconstruction following radical excision of sacrococcygeal pilonidal disease. Ann Surg 190:231-235
14. Bentivegna SS, Procario P (1977) Primary closure of pilonidal
cysts and sinuses. Am Surg 43:214-216
15. Goligher JC (1984) Surgery of the anus, rectum and colon, 5th
edn. Bailliere Tindall, London, pp 221-236
16. Monro RS, McDermott FT (1965) Elimination of causal factors in pilonidal sinus treated by Z-plasty. Br J Surg 177-179
17. Bose B, Candy J (1970) Radical cure of pilonidal sinus by
Z-plasty. Am J Surg 120:783-786
18. McDermott FT (1967) Pilonidal sinus treated by Z-plasty. Aust
N Z J Surg 37:64-69

19. Middleton MD (1968) Treatment of pilonidal sinus by Z-plasty.


Br J Surg 55:516-518
20. Roth RF, Moorman WL (1977) Treatment of pilonidal sinus
and cyst by conservative excision and W-plasty closure. Plast
Reconst Surg 60:412- 415
21. Mann CV, Springall R (1987) "D" excision for sacrococcygeal
pilonidal disease. J R Soc Med 80:292-295
Dr. C. Jim6nez Romero
Servicio de Cirurgia General y Ap. Digestivo
4" planta
Hospital 12 de Octubre
Ctra. Andalucia, km 5.5
E-28003 Madrid
Spain

Int J Colorect Dis (1990) 5:203-206

Col6ree/al
Disease

9 Springer-Verlag 1990

Fertility and pregnancy in women with familial adenomatous polyposis


C. Johansen 1 M. Bitsch 1 and S. Billow 2'3
Department of Surgical Gastroenterology, 1Bispebjerg Hospital and 2 Hvidovre Hospital, University of Copenhagen,
3Danish Polyposis Register, Copenhagen, Denmark
Accepeted: 10 September 1990

Abstract. A q u e s t i o n n a i r e s t u d y was c a r r i e d o u t a m o n g
58 D a n i s h w o m e n w i t h familial a d e n o m a t o u s p o l y p o s i s
c o n c e r n i n g fertility, p r e g n a n c i e s , a b o r t i o n s a n d deliveries. F u r t h e r d a t a were o b t a i n e d f r o m o b s t e t r i c r e c o r d s
a n d g e n e r a l p r a c t i t i o n e r s . T h e fertility a n d the c o u r s e o f
the p r e g n a n c y o f w o m e n w i t h p o l y p o s i s , f r e q u e n c y o f
m i s c a r r i a g e s , legal a b o r t i o n s , m a t u r e a n d p r e m a t u r e infants c o r r e s p o n d s to the f r e q u e n c y a m o n g the o b s t e t r i c
p o p u l a t i o n in D e n m a r k . O f the 73 infants, eight ( 1 1 % )
were delivered b y c a e s a r e a n section. O f the 16 w o m e n
w h o gave b i r t h after an o p e r a t i o n for familial a d e n o m a t o u s p o l y p o s i s , 5 ( 3 1 % ) h a d a c a e s a r e a n section. O f the
seven infants w h o died, two h a d lethal c o n g e n i t a l m a l f o r m a t i o n s a n d three infants were very p r e m a t u r e .

tion from obstetrical and gynaecological departments as well as


information from their general practitioner concerning pregnancies,
abortions and deliveries. Furthermore, after informed consent
copies of death certificates and autopsy reports concerning dead
infants were obtained. The data were compared with the available
information on fertility, abortion rate and the course of deliveries
of Danish women in the general population [3, 4]. Abortion is
defined as a miscarriage or a legal abortion, and only when it has
been possible to verify this through records, has abortion been
included.
Sixty-four women in the Danish Polyposis Register fulfilled the
inclusion criterion, of whom 58 (90%) filled in the questionnaire.
The 6 women who did not consent to the collection of information
stated that they had had pregnancies and had delivered a total of 9
liveborn infants. It was only possible to obtain death certificates and
autopsy reports concerning 3 (41%) out of 7 dead infants.

Results
Introduction
P a t i e n t s suffering f r o m the a u t o s o m a l d o m i n a n t a n d prem a l i g n a n t disease familial a d e n o m a t o u s p o l y p o s i s ( F A P )
were p r e v i o u s l y t r e a t e d with p r o c t o c o l e c t o m y a n d
i l e o s t o m y (PCI), b u t are n o w m o s t often t r e a t e d w i t h
c o l e c t o m y a n d ileo-rectal a n a s t o m o s i s ( I R A ) , o r in selected cases w i t h r e s t o r a t i v e p r o c t o c o l e c t o m y a n d
i l e o a n a l a n a s t o m o s i s [1, 2].
T h e m e d i c a l c o u n s e l l i n g c o n c e r n i n g the a b i l i t y to bec o m e p r e g n a n t a n d the e x p e c t e d course o f a p r e g n a n c y
has been b a s e d solely o n the c o n v i c t i o n o f the i n d i v i d u a l
surgeon, as there are n o studies o f fertility a n d the course
o f a p r e g n a n c y o f w o m e n w i t h F A P . T h e a i m o f this s t u d y
was to e v a l u a t e the fertility a n d c o u r s e o f the p r e g n a n c i e s
as well as the deliveries o f D a n i s h w o m e n with F A P .

Patients and method


All women in the Danish Polyposis Register who were 18 years or
over on 1st November 1988 were contacted in writing and asked to
fill in a questionnaire on their pregnancies, legal and spontaneous
abortions, infertility and the course of their deliveries. At the same
time, the women were asked to consent to the collection of informa-

D a t a c o n c e r n i n g the 58 w o m e n are s h o w n in Table 1. A t


the time o f the investigation, 2 w o m e n were p r e g n a n t in
the 20th a n d 36th week, respectively. T h e y h a d b o t h h a d
a c o l e c t o m y w i t h ileorectal a n a s t o m o s i s . T h e i r p r e g n a n cies have n o t been i n c l u d e d in the survey.
T h i r t y - s e v e n ( 6 4 % ) o f the 58 w o m e n h a d been pregn a n t 89 times a n d 33 h a d delivered. T h e 89 p r e g n a n c i e s

Table 1. The study population


No. of women
Not operated upon
PCI
PCI and Kock continent ileostomy
IRA
IAA
Rectosigmoid excision
In total

6
17
4
27
3 (1 J-pouch, 2 S-pouch)
i
58

One or several pregnancies


Never pregnant

37
21 (Fertility investigation 4)

In total

58

204
Table 2. Fertility, pregnancy and method of delivery of 58 women
with FAP

Pregnancies
Confirmed miscarriages
Legal abortions
Vaginal delivery
Caesarean section

Total

No. of
pregnancies
before surgery

No. of
pregnancies
after surgery

89
4
12
65
8

65
3
5
54
3

24
1

7
11
5

Table 3. Infants delivered by women with FAP

Number of
mature infants

Total

No. of
infants before
surgery

No. of
infants after
surgery

69

54

15

Premature infants
(< 37. weeks)

Table 4. State of maturity and way of delivery among infants delivered by women after colectomy

Women with PCI


Women with IRA
Women with IAA
Total

Vaginal Caesarean
delivery section

Mature

Premature

3
8
11

5
10

1 (died)
-

15

3
2
5

Table 5. Data concerning 7 dead infants


Infant Method of
Age at
no.
delivery/week death
of gestation
(in days)

Autopsy

Diagnosis

Vaginal/40

120

Acute airway
obstruction

Vaginal/28

RDS

Vaginal/40

Multiple congenital malformations

Section/32

--

RDS
RDS
Hypertrophy of the
ventricle of the
heart, small VSD

Vaginal/28

--

Vaginal/40

Vaginal/40

One w o m a n delivered twins vaginally. Seven women


gave birth to one child, 25 women to two children, 10
women of three children, 3 women to four children, and
I w o m a n gave birth to five children. Eleven per cent of
the deliveries were by caesarean section.
Twenty-four (27%) of the pregnancies occurred after
the women had been operated on either by proctocolectomy with ileostomy (PCI) or colectomy with ileorectal
anastomosis (IRA) and 5 (31%) deliveries out of J 6 took
place after caesarean section. Ten women who had been
operated on by I R A delivered, and 2 of these by
caesarean section. A m o n g women operated on by PCI,
three deliveries out of six were by caesarean section. Only
one infant was premature and died in the perinatal period
(Table 4). Four women (7%) out of 58 had experienced
infertility, and they had all sought medical advice. In only
one w o m a n was an explanation found; a sactosalpinx
demonstrated through a laparotomy.
Seventeen (29%) women out of 58 had not wanted to
become pregnant or had not yet had sexual intercourse.
Thus, 4 (10%) women out of 41 had an unfullfilled desire
to become pregnant.
Of the 4 confirmed miscarriages, 3 occurred among
women before they had been operated on, whereas the
fourth woman had been operated on 3 years before the
pregnancy. This took place in the 22nd week of pregnancy due to a suspicion of intestinal obstruction and
spontaneous abortion occurred a few days postoperatively. Another woman, who developed intestinal obstruction in the first trimester, was operated on and had
an ileal resection. She gave birth to a normal, mature
infant at term. Only one w o m a n was operated on postpartum. Three days after caesarean section there were
clinical and radiological signs of intestinal obstruction,
which was however not confirmed at operation. She had
given birth to a liveborn child.
In 2 (3 %) of 73 liveborn infants there were congenital
malformations which were both lethal. Only in 3 of the 7
infants, who died either perinatally or neonatally, was a
postmortem performed. The infants had cardiac malformations, pyloric stenosis and unspecified multiple malformations, respectively.
In Table 5 the data concerning the dead infants are
compiled. Infant no. 1 was operated on aged 2 months
for pyloric stenosis and died aged 4 months due to an
acute airway obstruction for unknown reasons.

Discussion

RDS

The data concerning infants no. 3, 4, 5 and 7 originate from the


tentative cause of death as stated in the obstetric records
RDS, respiratory distress syndrome; VSD, ventricular septal defect
of the heart
resulted in 73 infants, of w h o m 4 were premature, 4 confirmed miscarriages and 12 legal abortions. Sixty-five
deliveries were vaginal and 8 women had a caesarean
section. The data on the pregnancies appears in Tables 2
and 3.

It is difficult to calculate fertility in a small patient series


and to compare it with the general population. We have
therefore chosen to compare the fertility of women with
FAP with the accumulated rate of deliveries from 1987
a m o n g women born in 1945 [4]. This rate was 90%, which
means that 90% of Danish women born before 1945 had
given birth to at least one child in 1987. The advantage of
applying the accumulated rate of the incidence of deliveries is that the desire for more children is not included in
the estimate and thereby a useful historical estimate of

205
fertility is obtained. The disadvantage of the estimate is
that reduced fertility, indicated by fewer children in the
study group than in the general obstetric population, is
not reflected in the estimate. Furthermore, no information is obtained about the age at which women give birth
to their first child.
Our data show that 10% of the Danish women with
polyposis had an unfulfilled desire to become pregnant.
Others have found no difference in fertility of women
operated on with PCI or an ileo-anal reservoir compared
with the general obstetric population [5-10]. However, in
each of these studies the examined populations have been
small.
Exact information about infertility in Denmark is unknown. In the light of the official statistics stated here
concerning pregnancies (births, legal abortions and miscarriages), it is estimated that approximately every 10th
couple has an unfullfilled desire to become parents [3, 4].
This is similar to our data regarding Danish women with
polyposis.
It is not known to what extent knowledge of the
hereditary nature of polyposis has an influence on the
patients' desire to have children. However, it is our general impression that this plays a minor role. Recent developments in cytogenetics including the identification of a
specific FAP gene will eventually in the future lead to the
possible prenatal diagnosis of the disease. Genetic counselling on the basis of a preclinical or even a prenatal
diagnosis will raise the controversial ethical question arising from therapeutic abortion [5]. This may have substantial impact on the future disease prevalence.
A pregnancy can be successful after abdominal
surgery [4, 10, 11]. Complications during pregnancy do
occur, but they do not seem different from the complications occurring in the general obstetric population, apart
from a change in the frequency of defaecation of women
who have had a pouch operation and the occurrence of
problems related to the ileostomy in proctocolectomy
patients [6, 10, 11]. In a study of 71 women who had a
proctocolectomy for ulcerative colitis or Crohn's disease,
fertility was significantly reduced after surgery [12].
A miscarriage was confirmed in 4 women but has
probably occurred in more cases. Of the around 80000
conceptions registered in 1983 in Denmark, only 527
(0.6%) cases of miscarriage were registered, but this small
number is probably due to insufficient registration [3]. In
the largest series of ostomates who completed a pregnancy, 3 miscarriages out of 89 pregnancies were reported [13]. Others have reported a similar occurrence of
miscarriages [10, 11].
Today most women can be brought safely through
pregnancy without major risk to themselves or the child.
It is very difficult to say if the prevalence of polyposis will
change, although combined obstetric, cardiac and anaesthetic expertise is available.
The frequency of caesarean sections performed in the
polyposis patients of 11% corresponds to the frequency
of caesarean section in the obstetric population in Denmark (12.8%) [3]. A study including 21 women with ilealpouch-anal anastomosis shows that 47% of the pregnancies ended with a caesarean section [6, 8]. In another

study of 71 women with an ileostomy the frequency of


caesarean section was 29 % of deliveries [12]. None of the
patients treated with restorative proctocolectomy in our
study have been pregnant. In our material, a caesarean
section has been performed on 3 women who had had a
conventional proctocolectomy. The indication for this
was both obstetric and related to the previous operation.
In one patient the indication was the perineal scar caused
by the rectal excision, in another patient prematurity and
in the third patient, placenta praevia and fetopelvic disproportion. Among women after colectomy a caesarean
section was performed twice on the same woman, and the
indication at both deliveries was a fear that vaginal delivery could cause destruction of the ileo-rectal anastomosis.
The indication for caesarean section among women
operated on for chronic inflammatory bowel disease is in
agreement with the indications in polyposis, i.e., to protect the ileostomy or pouch or purely for obstetric conditions [6, 8, 10-13].
Lethal malformations occurred in our material in 2
(3%) out of 73 of liveborn infants. In Denmark 1.6% of
liveborn infants and 9.5% of stillborn infants are reported to have congenital malformations. Other studies
have not shown congenital malformations in infants born
of mothers operated on for polyposis [6, 8, 10, 11, 13].
Studies of chronic inflammatory bowel diseases have also
not shown any increased frequency of congenital malformations [14].
Of the 73 liveborn infants 7 (10%) died, of whom 6
died in the perinatal period. This is an unusually high
number. Six of the dead infants were born of mothers
who had not yet been operated for polyposis. Of 21 infants operated on with pouch-anal anastomosis, 1 died of
hyaline membrane disease [5, 7]. Only one perinatal death
occurred in a child born of a mother operated on by
proctocolectomy with ileostomy [10]. The deaths of infants among the polyposis population were fairly evenly
distributed throughout the entire study period, and thus
the deaths cannot be explained by the improvements in
general perinatal care.
In conclusion, we find that the fertility of Danish
women with FAP is 90%, the same as in the general
obstetric population in Denmark. The risk of a miscarriage is not higher than that of the obstetric population in
Denmark. The total risk of women with FAP of having to
deliver by caesarean section is 11%. The frequency of
caesarean section among affected women operated on by
PCI or IRA was higher (30%) than among the obstetric
population in Denmark.
In the present patient series, the frequency of congenital malformations among liveborn infants was as expected. The rate of inexplicable deaths of infants born of
women with polyposis is 10%.
Further studies among national series of woman with
polyposis concerning fertility, pregnancies and outcome
are necessary before any final conclusions can be made
about a follow-up programme during pregnancy. Until
then we suggest that pregnant polyposis patients are
offered the possibility of ultrasonographic scanning and
amniocentesis during pregnancy.

206

References
1. Dozois RR (1986) Restorative proctocolectomy and ileal reservoir. Mayo Clin Proc 61:283-286
2. Billow S (1987) Familial polyposis coli. A clinical and epidemiological study (Thesis). Dan Med Bull 34:1-15
3. Medical Birth Statistics and Congenital Malformation Statistics (1986) Vital statistics (1988) 1:23. The National Board of
Health, Denmark
4. Befolkningens Bevaegelser (1989) Vital Statistics 1987. Denmark Statistical Department, Denmark
5. Billow S (1989) Familial adenomatous polyposis. Ann Med
21 : 299-307
6. Nelson H, Dozois RR, Kelly KAS, Malkasian GD, Wolff BG,
Ilstrup DM (1989) The effect of pregnancy and delivery on the
ileal pouch-anal anastomosis functions. Dis Colon Rectum
32:384-388
7. Barwin BN, Harley JG, Wilson W (1974) Ileostomy and pregnancy. Br J Clin Pract 28:256-258
8. Pezim ME (1984) Successful childbirth after restorative proctocolectomy with pelvic ileal reservoir. Br J Surg 71:292

9. Metcalf AM, Dozois RR, Beart RW Jr, Wolff BG (1985) Pregnancy following ileal pouch-anal anastomosis. Dis Colon Rectum 28:859-861
10. Gopal K, Amshel AL, Shonberg IL, Levinson BA, VanWert M,
VanWert J (1985) Ostomy and pregnancy. Dis Colon Rectum
28:912-916
11. Metcalf AM, Dozois RR, Kelly KA (1986) Sexual function
after proctocolectomy. Ann Surg 204:624-627
12. Wikland M, Jansson I, Aszt61y M, Palselius I, Svaninger G,
Magnusson O, Hult6n L (1990) Gynecological problems related
to anatomical changes after conventional proctocolectomy and
ileostomy. Int J Colorect Dis 5:49-52
13. Hudson CN (1972) Ileostomy in pregnancy. J R Soc Med
65:281-283
14. Damgaard B, Orholm M (1984) Chronic inflammatory intestinal disease and pregnancy. Ugeskr Laeger 146:1701-1704
Dr. C. Johansen
Department of Surgical Gastroenterology
Bispebjerg Hospital
DK-2400 Copenhagen
Denmark

Int J Colorect Dis (1990) 5:207-208

C,ol6i eeial
Disease

9 Springer-Verlag 1990

The effect of age on pelvic floor dynamics


M. Pinho, K. Yoshioka, J. Ortiz, M. Oya and M. R. B. Keighley
Queen Elizabeth Hospital, Birmingham, UK
Accepted: 5 September 1990

Abstract. Anorectal function is known to be influenced


by age but there is only scanty information a b o u t the
effect of ageing on pelvic floor dynamics. Pelvic floor
movements were assessed by videoproctography in two
groups of ten control females (mean age of 30.5 and 60.7
years, respectively). A significantly lower pelvic floor position was found at rest in the older group (p = 0.02), but
younger controls showed an increased pelvic floor descent during straining (p=0.01). These results suggest
that the pelvic floor is affected by progressive denervation but descent during straining tends to decrease with
advancing age.

Introduction
Anorectal function is influenced by age [1-3]. Disorders
of defaecation such as anal incontinence and rectal prolapse are predominantly found in advanced age, whilst
most cases of severe constipation are usually observed in
the second or third decades. Although electrophysiological and manometric studies have been performed to assess changes in the external sphincter with age [1, 2, 4]
there is only scanty information on the effect of age on
pelvic floor function [3]. The aim of this study has been
to observe the effect of ageing on pelvic floor dynamics in
normal subjects.

any variation from the rest position during contraction (ascent) or


attempted defaecation (descent).
Statistical analysis was performed using the Wilcoxon ranksum test for comparison and the Spearman rank test. Unless otherwise stated, values are given as mean and range.

Results
The pelvic floor was found to be at a significantly higher
position at rest in group A (2.4cm; 0.5-3.9) than in
group B (3.7 cm; 1.0-7.5) ( p = 0 . 0 2 ) (Fig. 2). Significantly greater pelvic floor descent was observed during
straining in group A (3.9 cm; 0 - 6 . 8 ) than in group B
(2.0 cm; 0 - 3 . 3 ) ( p = 0 . 0 1 ) (Fig. 3). N o significant difference was found in the extent of m o v e m e n t during pelvic
floor contraction between the groups (group A: 0.7 cm,
group B: 1.1 cm) (p=0.2). A significant correlation was
found between age and pelvic floor descent during straining (r = 0.46; p < 0.05) (Fig. 4). A significant correlation
was also found between the pelvic floor position at rest
and the descent observed during straining (r=0.55;
p < 0.05) (Fig. 5).

Methods
Videoproctography was performed in 20 control females having
herniorraphy, cholecystectomy or mastectomy with no colorectal or
anal symptoms. They were divided in two age groups. In the younger group (group A) the mean age was 30.5 years and in the older
group (group B) the mean age was 60.7 years. No patient with
disordered defaecation was included.
Videoproctography was performed using previously described
techniques [5]. Pelvic floor position at rest was defined as the distance from the pubococcygeal line to the anorectal junction (Fig. 1).
Assessment of pelvic floor movement was obtained by measuring

Pelvic Floor Position

"--

""

Fig. 1. Measurement of pelvic floor position

208
Cm (from
pubocococygeal
line)

Pelvicfloor
descent

(cm)

r=-.46
p<0.05

p=0.02
2

Group A

Group B

10

20

30

40
50
Age (years)

60

70

80

Fig. 2. Pelvic floor position at rest in relation to the pubococcygeal


line

Fig. 4. Correlation between age and pelvic floor descent during


straining

Cm (from
pubocococygeal
line)

Pelvicfloor 8
descent

(cm)
6

r=-.55
p<0.05

4 ~
p=0.01
o ~

2
0
Group A

Group B

O9

'

'

Fig. 3. Pelvic floor position during straining in relation to the pubococcygeal line

4
6
8
Rest (cm)
Fig. 5. Correlation between age and the difference between the
pelvic floor position at rest and straining

Discussion

References

The results obtained from this study suggest that pelvic


floor function is influenced by age. However, we did not
extend our studies to include measurement of fibre density or pudendal nerve terminal motor latency. The lower
rest position observed in older patients is probably explained by the progressive denervation of the pelvic floor
in these patients, even though clinical symptoms may
never occur [6]. However, this denervation does not seem
to affect the amount of pelvic floor descent during straining as suggested by Parks et al. [7]. Indeed, descent during
straining was found to decrease with advancing age.
These observations suggest that intra-abdominal pressure may play a role in determining the amplitude of
pelvic floor descent.
The higher pelvic floor position at rest and increased
pelvic floor descent during straining found in younger
subjects indicate that there is far greater potential for the
pelvic floor position to change in youth. Conversely, the
lower rest position and reduced descent observed in elderly controls suggests that pelvic floor movements are
reduced in the elderly despite the absence of clinical
symptoms.

1. Read NW, Harford WV, Schmulen AC, Read MG, Santa Ana C,
Fordtran JS (1979) A clinical study of patients with faecal incontinence and diarrhoea. Gastroenterology 76:747-756
2. Matheson DM, Keighley MRB (1981) Manometric evaluation
of rectal prolapse and faecal incontinence. Gut 22:126-129
3. Bannister JJ, Abouzekry L, Read NW (1987) Effect of aging on
anorectal function. Gut 28:353-357
4. Bartolo DCC, Jarratt JA, Read MG, Donnelly TC, Read NE
(1983) The role of partial denervation of the puborectalis in
idiopathic faecal incontinence. Br J Surg 70:664-667
5. Yoshioka K, Hyland G, Keighley MRB (1988) Physiological
changes after postanal repair and parameters predicting outcome. Br J Surg 75:1220-1224
6. Percy JP, Neill ME, Kandiah TK, Swash M (1982) A neurologic
factor in faecal incontinence in the elderly. Age Ageing 11:175179
7. Parks AG, Porter NH, Hardeastle J (1966) The syndrome of the
descending perineum. Proc R Soe Med 59:477-482

Prof. M. R. B. Keightley
Department of Surgery
Queen Elizabeth Hospital
Birmingham BI5 2TH
UK

Int J Cotorect Dis (1990) 5:209-212

Col6rec/al
Disease

9 Springer-Verlag 1990

Emergency resection and primary anastomosis for sigmoid volvulus


in an African population
A. Keller and P. Aeberhard
Department of Surgery, Kantonsspital, Aarau, Switzerland
Accepted: 2 August 1990

Abstract. We report 30 patients who underwent operation


for sigmoid volvulus during a two year period at the St.
Francis Hospital, Tanzania. Five patients were managed
initially by non-operative reduction. They all underwent
elective resection of the sigmoid during the same hospitalisation with one operative death. Twenty-five patients
underwent emergency laparotomy, 12 of them having
gangrenous bowel. Resection was carried out in 21 patients, 18 of whom had a primary anastomosis without
protective colostomy. In spite o f the high incidence of
gangrenous bowel (57%), there was only one operative
death (5%) in the 18 patients. Initial management of
sigmoid volvulus should consist of non-operative attempts at reduction provided that the bowel is viable.
Elective resection should be performed during the same
hospitalisation. Where non-operative therapy fails or
bowel gangrene is present, emergency laparotomy has to
be carried out. In the authors' experience resection of the
sigmoid and primary anastomosis can be performed safely in this situation.

Introduction
Sigmoid volvulus is uncommon in western countries,
whereas in eastern Europe, India and some parts of
Africa it is one of the major causes of large bowel obstruction [1-4]. The mortality rate from sigmoid volvulus is
high. In 1889 Senn [5] pointed out the importance o f early
diagnosis and prompt surgical treatment. Since the publication by Bruusgaard [6] in 1947, nonoperative reduction
of sigmoid volvulus by sigmoidoscopy and tube deflation
has been increasingly used. However, there is now general
agreement that an initial attempt at nonoperative reduction is indicated in patients who have no signs of peritonitis or gangrene [7-12]. Non-operative reduction may
avoid emergency surgery in a poorly prepared patient. It
is, however, not a definitive treatment and recurrences
with a significant risk of death have been reported in
more than 40% of cases [8, 12, 13]. Furthermore, after

nonoperative reduction there always remains the uncertainty of bowel viability, In some regions of Africa double
volvulus (a knot of ileum and sigmoid colon twisted together) occurs frequently. In this condition any attempt
at nonsurgical reduction is contraindicated [14, 15].
The strategy for surgical treatment of sigmoid
volvulus still remains controversial. As detorsion alone is
followed by a high recurrence rate, only resection can be
considered definitive treatment [4]. There has been much
discussion on the timing o f resection but there is good
evidence that elective resection following nonoperative
reduction should be performed during the same hospitalisation [8-11]. Gangrenous colon requires immediate resection. Resection of the underlying megacolon using a
Hartmann-type procedure or the Paul-Mikulicz technique with intestinal continuity being re-established
about three months later has long been considered the
safest treatment. However, some authors recommend a
primary anastomosis with or without protective colostomy [3, 16, 17].
In this paper we report our personal experience of a
comparably large number of cases of sigmoid volvulus
treated over a two year period at Saint Francis Hospital,
Tanzania. Special consideration is given to the results of
primary resection, and the recent literature on management of sigmoid volvulus has been reviewed.

Patients and methods


In a 24 months period between December 1986 and November
1988, 30 patients with sigmoid volvulus underwent surgical treatment at Saint Francis Hospital, a teaching hospital in Tanzania,
which serves a predominantly rural population. This number includes only patients who were consequently operated on. The diagnosis was made in all of them before operation from the presenting
features. The average age was 50.9 years with a range between 19
and 76 years. The male to female ratio was 5 : 1.
The operative technique of primary anastomosis was standardized. To avoid perforation the distended colon was usually decompressed at laporatomy by needle suction before untwisting. Stool
evacuation was completed by introduction of a wide rectal tube per
anum by an assistant and guided into the sigmoid by the surgeon.

210
Table

1. Seasonal occurrence of sigmoid volvulus at SFH from 1980-1988


1980

81

82

1
2
1
1
2
1

4
1
1
1
2

1
4
2
-

1
3
-

1
1
.
-

1
1
1

12

11

83

84

85

2
-

2
1
1
2
2

1
2
4
1
1
1

1
1

1
-

1
1
1
.
2

10

86

87

88

Total

Rainy season

January
February
March
April
May
June

10
7

3
4
2
I

4
3
1
1

16
15
9
8

15

15

92

65

Dry season

July
August
September
October
November
December

2. Hospitalisation time and mortality following 30 operative


procedures for sigmoid volvulus at SFH
Table

Procedure

NumBowel
ber of
ganpatients greme

Mean
Hospital
hospital- mortality
isation
days

Nonoperative detorsion
(rectoscopy + deflation)
+ elective resection

26

Operative derotation
(_+ elective resection)

36.5

Emergency resection with


- primary anastomosis
- Mikulicz resection
- Hartmann procedure

18
2
1

9
2
1

11.6
38
45

1 (20%)

(5%)

Care was taken to avoid any faecal contamination during resection.


Anastomosis was performed using a single layer technique with
interrupted sutures and resorbable material. Sphincter dilatation
was done routinely and antibiotics given at the start of the operation.

Results

T h e m e a n d u r a t i o n o f a c u t e s y m p t o m s p r i o r to h o s p i t a l
a d m i s s i o n was 3.4 days. A l l p a t i e n t s c o m p l a i n e d o f a b d o m i n a l pain. A b s e n c e o f w i n d a n d stool was f o u n d in all
p a t i e n t s e x c e p t two w h o h a d h a d a s m a l l a m o u n t o f w a tery d i a r r h o e a . V o m i t i n g was r e p o r t e d b y 24 p a t i e n t s
(80%). T h e m o s t c o m m o n clinical f i n d i n g w a s a b d o m i n a l
d i s t e n s i o n , b e i n g p r e s e n t in all o f the p a t i e n t s . Often, the
a b d o m e n was g r o s s l y d i s t e n d e d . Signs o f p e r i t o n i t i s were
f o u n d in 13 p a t i e n t s , a s s o c i a t e d w i t h the presence o f
g a n g r e n o u s bowel, w h i c h was f o u n d in 12 cases ( 4 0 % o f
the series). F e v e r was n o t a p r o m i n e n t sign, being p r e s e n t
in o n l y five p a t i e n t s . T h e p l a i n a b d o m i n a l x - r a y (availa b l e in 13 p a t i e n t s ) was a l w a y s typical. F r i m a n n - D a h l ' s

10

11

27

sign ( c o n v e r g e n c e o f the wall o f the d i l a t e d c o l o n in the


a r e a o f axial t o r s i o n in the left l o w e r q u a d r a n t [11]) was
p a t h o g n o m o n i c . F o u r t e e n p a t i e n t s (46.6 % ) h a d a h i s t o r y
o f p r e v i o u s volvulus l e a d i n g to h o s p i t a l i s a t i o n , 6 o f
w h o m h a d u n d e r g o n e a p r e v i o u s l a p a r o t o m y with s o m e
k i n d o f c o n s e r v a t i v e o p e r a t i o n w i t h o u t resection. A c o n c o m i t a n t n e u r o l o g i c a l d i s o r d e r was p r e s e n t in five p a tients, m o s t o f t h e m being epileptics. S t o o l analysis rev e a l e d the presence o f p a r a s i t e s in 57%.
T h e r e t r o s p e c t i v e s t u d y o f all p a t i e n t s o p e r a t e d for
s i g m o i d volvulus in S a i n t F r a n c i s H o s p i t a l since 1980
s h o w e d a clear s e a s o n a l p r e p o n d e r a n c e : M o s t o f the cases o c c u r r e d d u r i n g the r a i n y s e a s o n f r o m J a n u a r y - J u n e
(Table 1).
Table 2 lists the o p e r a t i v e p r o c e d u r e s c a r r i e d o u t on
30 patients. R e c t o - s i g m o i d o s c o p y was d o n e in 12 p a tients. D e f l a t i o n b y rectal t u b e was successful in 7 (58%).
Two o f these u n d e r w e n t i m m e d i a t e l a p a r o t o m y f o r
d o u b t f u l v i a b i l i t y o f the bowel. F i v e p a t i e n t s w h o h a d a
p r i m a r y successful n o n o p e r a t i v e d e c o m p r e s s i o n u n d e r w e n t elective r e s e c t i o n o f the s i g m o i d after a m e a n d e l a y
o f 8.6 days. O n e o f t h e m d i e d 5 d a y s after o p e r a t i o n due
to p o o r g e n e r a l c o n d i t i o n a n d m a l n u t r i t i o n . Twenty-five
patients underwent emergency operation. Derotation of
the volvulus alone was d o n e in f o u r patients, two o f w h o m
u n d e r w e n t elective r e s e c t i o n after a m e a n time i n t e r v a l o f
15 weeks. T h e o t h e r two refused a n y f u r t h e r o p e r a t i o n .
T w e n t y - o n e p a t i e n t s h a d an e m e r g e n c y r e s e c t i o n o f
the s i g m o i d c o l o n , a n d in 18 a p r i m a r y a n a s t o m o s i s witho u t p r o t e c t i v e c o l o s t o m y was c a r r i e d out. Two p a t i e n t s
were t r e a t e d b y a M i k u l i c z - t y p e r e s e c t i o n a n d one b y
H a r t m a n n ' s p r o c e d u r e . C o l o r e c t a l c o n t i n u i t y was res t o r e d in all 3 p a t i e n t s after a n a v e r a g e d e l a y o f 12 weeks.
Twelve p a t i e n t s ( 5 7 % ) in the g r o u p o f e m e r g e n c y resections h a d g a n g r e n o u s bowel. O n e p a t i e n t h a v i n g a p r i m a ry a n a s t o m o s i s (5 % ) d i e d o f p e r s i s t i n g s e p t i c a e m i a 3 d a y s
after o p e r a t i o n for c o m b i n e d g a n g r e n e o f the s i g m o i d
c o l o n a n d c a e c u m . T h e r e was n o case o f a n a s t o m o t i c
l e a k a g e . M o r t a l i t y a n d d u r a t i o n o f h o s p i t a l i s a t i o n foll o w i n g the different p r o c e d u r e s a r e s h o w n in Table 2.

211
Discussion

Sigmoid volvulus is a frequent cause of intestinal obstruction in central and east Africa. Different aetiological factors seem to favour its occurrence [2, 18-20].
These include the anatomical combination of a narrow mesosigmoid parietal attachment and redundant colon found in nearly all patients with sigmoid volvulus.
Dietary factors may be important. A large bulky meal
with a high fibre content is commonly consumed once a
day (e.g. in the rainy season). There may be a genetic
factor as suggested by tribal and sex incidence in some
areas. Chronic constipation may be the reason for increased incidence of volvulus in patients with neurological and psychiatric disorders. Megacolon caused by
Chagas' disease is found in a high percentage of patients
with sigmoid volvulus in Brazil.
There are two types of megasigmoid implicated in
sigmoid volvulus in tropical countries [20, 21]. In the first
the pelvic colon is grossly enlarged and thickened. There
is complete lack of normal haustrations and a marked
thickening of the circular muscular coat. The blood supply is markedly increased. Volvulus secondary to this type
is usually slowly progressive and intestinal obstruction is
rarely complete before several days. The most important
signs are gross abdominal distension and fluid loss. In
spite of this, the patient's general condition is well-preserved for a long time.
The second is the so-called thin-walled type, which
corresponds to the type of megacolon seen in elderly caucasians. The colon and its mesentery are elongated and
the blood supply is not increased. This type of megacolon
is also found in compound volvulus and has an acute
fulminating course.
With some experience the diagnosis of sigmoid
volvulus can be made generally from the clinical appearance of the patient. In particular, the abdominal distension is striking, comparable to a large drum. The signs on
the plain abdominal film are typical and virtually diagnostic.
Since the publication by Bruusgaard [6], nonoperative
management of sigmoid volvulus by sigmoidoscopy and
deflation has been more and more used. The success of
this procedure in uncomplicated, selected cases varies between 70 and 90% [2, 7, 8, 12]. However, in many of these
publications the authors have not commented on why
rectoscopy was attempted in only a proportion of cases.
In our experience the failure rate of nonoperative reduction was relatively high, particularly when acute symptoms had been present for several days. Deflation was
achieved in 58% of all sigmoidoscopies. Seven patients
underwent laparotomy immediately after sigmoidoscopy
for failure of deflation or suspicion of bowel gangrene.
The clinical differentiation between viable and non-viable bowel is often uncertain. Furthermore, the suspicion
of an underlying compound volvulus (ileosigmoid knotting) prohibits any nonoperative management.
Incomplete reduction and persisting bowel atony may
be responsible for the prolonged recovery after nonoperative management, which can also be seen from the

prolonged hospitalisation time (26 days or more than


twice as much as after resection).
Nonoperative reduction may be used as a temporizing measure in selected cases, allowing the patient's condition to improve before definitive operative therapy.
However, owing to the high rate of recurrence after nonoperative reduction with significant mortality, resection
of the sigmoid as a definitive therapy should be advised.
Recurrence (e.g. a history of previous volvulus) in our
own series was nearly 50%, corresponding to similar figures in large published series. Elective resection provides
a greater chance of long term survival than expectant
observation [8]. Resection in nongangrenous cases is best
carried out after a short delay in 3 to 4 days following
endoscopic deflation. An important argument against
conservative management is that it may be very difficult
to convince poorly educated people of the necessity for a
later elective resection. Once recovered from the initial
attack, our patients usually refused a second operation.
Operative detorsion alone is insufficient treatment
with a high recurrence rate and mortality [22]. Sigmoid;
opexy and mesocolonoplasty [23] have been tried in different ways. However they seem to be followed by the
same recurrence rate as seen after simple detorsion [2, 3,
13]. Persisting atony of the remaining sigmoid may be
responsible for the prolonged recovery after detorsion
alone. A segment of colon with absent or ineffective peristalsis produces a functional obstruction. Megacolon is a
frequent finding in recurrent obstruction after sigmoid
volvulus [24]. In our own series the hospitalisation time
proved to be three times as long after operative derotation compared with primary resection. We believe that at
emergency laparotomy the sigmoid should be resected
whenever possible.
Comparison of hospital mortality in relation to the
operative procedures is difficult mainly for two reasons.
First, occurrence of sigmoid volvulus is rare in western
countries and, secondly, mortality depends mainly on the
presence of bowel gangrene which is not mentioned in
most of the published reports. Large series of sigmoid
volvulus throughout the world report an overall mortality rate of 20% [2]. Comparing the mortality in patients
with viable and non-viable bowel provides a much better
understanding of the actual risk of death. In an international survey of 43 series including 2228 patients, Ballantyne [2] found a mortality of 12.3% in patients with viable
colon compared with 52.9% when bowel gangrene was
present.
In an analysis of 25 American series in which 507
operative procedures were done in 635 patients with sigmoid volvulus, emergency resection was performed in
195 cases with an overall mortality of 32.8% [2].
Resection without restoration of continuity by a
Mikulicz or Hartmann procedure has previously been considered to be the safest procedure. However, it is interesting that in the review of Ballantyne [2], primary anastomosis had the lowest mortality by far (25%). A critical
evaluation of the literature shows that restoration of
bowel continuity after Hartmann resection is performed
in a small percentage of patients only [25]. There may be
technical difficulties with a significant risk, which is im-

212
p o r t a n t to c o n s i d e r in a d e v e l o p i n g c o u n t r y w h e r e
s u r g e r y is often d o n e b y p e o p l e w i t h l i m i t e d experience.
F u r t h e r m o r e , a c o l o s t o m y , even w h e n t e m p o r a r y , i n t r o duces a v a r i e t y o f p r o b l e m s in the tropics.
T h e r e are t h e r e f o r e s t r o n g a r g u m e n t s for d o i n g a prim a r y a n a s t o m o s i s in e m e r g e n c y resection. M i s h r a [17]
r e p o r t e d a 6 . 4 % m o r t a l i t y d u e to a n a s t o m o s i s l e a k a g e in
77 cases o f p r i m a r y a n a s t o m o s i s . A h s a n [4] r e p o r t e d a
m o r t a l i t y as l o w as 3 . 8 % in selected cases w i t h v i a b l e
bowel. S i m i l a r results were r e p o r t e d b y A s t i n i [3]. O u r
o w n experience in 18 p r i m a r y a n a s t o m o s e s w i t h o u t p r o tective c o l o s t o m y s h o w e d a 5 % m o r t a l i t y . I n this series
5 0 % o f the p a t i e n t s h a d g a n g r e n o u s bowel. N o n e o f the
p a t i e n t s h a d l e a k a g e o f the a n a s t o m o s i s a n d the m e a n
h o s p i t a l i s a t i o n time was o n l y 11.6 d a y s . I m p o r t a n t c o n d i t i o n s f o r the success o f a p r i m a r y a n a s t o m o s i s i n c l u d e
d e c o m p r e s s i o n o f the r e m a i n i n g c o l o n b y rectal t u b e foll o w e d b y o n - t a b l e lavage. G r o s s faecal c o n t a m i n a t i o n
s h o u l d be m e t i c u l o u s l y a v o i d e d . T h e r e s h o u l d be a g o o d
b l o o d s u p p l y a n d a b s e n c e o f t e n s i o n at the s u t u r e line a n d
the s u r g e o n s h o u l d be f a m i l i a r w i t h the p r i n c i p l e s o f col o n surgery. U n d e r these c i r c u m s t a n c e s p r i m a r y a n a s t o m o s i s w i t h o r w i t h o u t a p r o t e c t i v e c o l o s t o m y c a n be carried o u t successfully even in the p r e s e n c e o f g a n g r e n e .

References
1. Ballantyne GH, Brandner MD, Beart RW, Ilstrup DM (1985)
Volvulus of the colon. Ann Surg 202:83-92
2. Ballantyne GH (1982) Review of sigmoid volvulus. Dis Colon
Rectum 25:494-501, 823-830
3. Astini C, Falaschi CF, Mulugheta Mariam, Alemayehu Desta
(1988) The management of sigmoid volvulus: report of 39 cases.
Ital J Surg Sci 18:127-129
4. Ahsan J, Rahman H (/967) Volvulus of the sigmoid colon
among Pathans. Br Med J 1:29-30
5. Senn N (1989) The surgical treatment of volvulus. Med News
55: 590- 598
6. Bruusgard C (1947) Volvulus of the sigmoid colon and its treatment. Surg 22:466-478
7. Anderson JR, Lee D (1981) The management of acute sigmoid
volvulus. Br J Surg 68:117-120

8. Bak MP, Boley SJ (1986) Sigmoid volvulus in elderly patients.


Am J Surg 151:71-75
9. Le Neel JC, Farge A, Guiberteau B, Kohen M, Leborgne J
(1989) Volvulus du c61on sigmoide. Ann Chir 43:348-351
10. Mangiante EC, Croce MA, Fabian TC, Moore III OF, Britt LG
(1989) Sigmoid volvulus. A four-decade experience. Am Surg
55:41-44
11. Pahlmann L, Enblad P, Rudberg C, Krog M (1989) Volvulus of
the colon. A review of 93 cases and current aspects of treatment.
Acta Chir Scand 155:53-56
12. Welch GH, Anderson JR (1987) Acute volvulus of the sigmoid
colon. World J Surg 11:258-262
13. Shepherd JJ (1968) Treatment of volvulus of sigmoid colon: a
review of 425 cases. Br Med J 1:280-283
14. Cornet L, N'Guessan HA, Richard-Kadio, Dick KR, Bankole
R, Keli E (1988) Les volvulus doubles du sigmoide et du gr~le
(physiopathologie). J Chir (Paris) 125:279 282
15. Kakar A, Bhatnagar BNS (1981) Ileo-sigmoid knotting: a clinical study of 11 cases. Aust N Z J Surg 51:456-458
16. Madden JL (1965) Primary resection and anastomosis in the
treatment of perforated lesions of the colon. Am Surg 31: 781786
17. Mishra SB, Sahoo KP (1986) Primary resection and anastomosis for volvulus of sigmoid colon. J Indian M A 84:265-268
18. Northeast ADR, Dennison AR, Lee EG (1984) Sigmoid
volvulus: New thoughts on the epidemiology. Dis Colon Rectum 27:260-261
19. Schagen yon Leeuwen JH (1985) Sigmoid volvulus in a west
African population. Dis Colon Rectum 28:712-716
20. El Masri SH (/987) Volvulus. In: Adeloye A (ed) Davey's companion to surgery in Africa, 2nd edn. Churchill Livingstone,
Edinburgh, pp 337-338
21. Ryan P (1982) Sigmoid volvulus with and without megacolon.
Dis Colon Rectum 25:673-679
22. Gibney EJ (1989) Sigmoid volvulus in rural Ghana. Br J Surg
76:737
23. Chenebaux D, Bouillot JL, Dehni N, Alexandre JH (1988) La
m6socoloplastie pour volvulus sigmoidien. J Chir (Paris)
125:661-662
24. Strom PR, Stone HH, Fabian TC (1982) Colonic atony in
association with sigmoid volvulus: its role in recurrence of obstructive symptoms. South Med J 75:933-936
25. Haas PA, Haas GP (1988) A critical evaluation of the Hartmann's procedure. Am J Surg 54:380-385
Dr. A. Keller
Department of Surgery
Kantonsspital
CH-5001 Aarau
Switzerland

Int J Colorect Dis (1990) 5:213-218

Col6rec/al
Disease

9 Springer-Verlag 1990

Factors affecting anal continence after restorative proctocolectomy


M. Pescatori and C. Mattana
Institute of Clinical Surgery, Universita Cattotica, Roma, Italy
Accepted: 30 August 1990

F r o m the Italian Registry of the Ileoanal Reservoir:

Introduction

A. Bastagli, E. Contessini, L. Gennari, W. Montorsi, M.


Fincato (Milano); E. Berti Riboli (Genova); G. Castiglioni, F. Crucitti, G. Cucchiara, G. Fegiz, G, Ribotta,
V. Speranza (Roma); E. Cavina, F. Mosca (Pisa); U.
Conti, A. Saccomani (Finale e Pietra Ligure) ; D. D'Amico, M. Lise (Padova); M. Dellepiane, E. Masenti, A.
Paletto (Torino); R. Dionigi, C. Morone (Pavia); G.
Gozzetti (Bologna); E. Landi (Ancona); F. Mazzeo, A.
Renda (Napoli); U. Mercati (Perugia); A. Napolitano
(Chieti); E. Pasquali (Verona); E Prete (Bari); G, Stancanelli (Ravenna); E Tonelli (Firenze).

The goals of restorative proctocolectomy and ileoanal


reservoir in the management o f ulcerative colitis and familial adenomatous polyposis are to excise completely
the diseased large bowel and to preserve anal function.
Even in most specialized centres, some degree of postoperative soiling seems to be unavoidable. This has
ranged from 10% to 51% of cases [1-3]. In an attempt to
improve function various modifications of the original
technique have been suggested. These include avoidance
of endo-anal mucosectomy [4], stapling the ileoanal anastomosis [5], increasing the capacity of the reservoir [6]
and eliminating its efferent limb [7]. However, it is still
uncertain how these relate to continence [8]. A better
understanding of the factors affecting faecal continence
after pouch operations is needed to solve the problem of
postoperative leakage.
The aim of the present multicentre study, carried out
on behalf of the Italian Registry of the Ileoanal Reservoir, was to define the incidence o f disordered continence
with respect to various factors. These included diagnosis,
surgeon's experience, age of the patient, length of rectal
cuff, pouch design, staged operation, pelvic complications, duration of follow-up, bowel frequency and pouchitis.

Abstract. The aim of this multicentre study was to define


the incidence of disordered continence after restorative
proctocolectomy and ileoanal reservoir with respect to
some factors which may influence the postoperative soiling rate. Two hundred and seven patients underwent the
operation, 156 had their ileostomy closed and were all
available for a functional assessment. Minor leakage was
observed in 26.9% of cases, whereas 1.9% complained of
troublesome faecal soiling. None had gross faecal incontinence. Patients over 45 years had significantly more
soiling than those younger (45% vs 24%, p < 0.05). Soiling was more prevalent in those with ulcerative colitis
than with other diseases (35% vs 18% p < 0.05). The soiling rate decreased after the first postoperative year from
34% to 21% (p < 0.05). A bowel frequency higher than 5
evacuations/24 hours increased soiling from 20% to 48 %
(p < 0.01). Pouchitis doubled the soiling rate from 26% to
50% (p<0.05) without there being any difference in
sphincter function. Soiling was not significantly related
to staged procedure, J-pouch, perineal complications or
a long rectal cuff. Careful preoperative evaluation of the
anal sphincter should be performed in older patients operated on for colitis as they are likely to leak during the
first year following restorative proctocolectomy, especially in cases with diarrhoea or pouchitis.

Patients and methods


Patients
Two hundred and seven patients underwent restorative proctocolectomy and ileoanal reservoir between March 1980 and May 1989 in
26 departments of surgery taking part in the Italian Registry. One
hundred and twenty three operations (60%) were performed in five
centres; 111 cases were treated by surgeons who had performed
more than five and 96 by surgeons who had carried out less than 5
such procedures. Of the 207 patients, 141 had ulcerative colitis, 65
familial adenomatous polyposis and 1 intractable constipation.
There were 122 men and 85 women, with a male:female ratio of
1.4:1. The age ranged from 8 to 67 years (median 34 years). Of the
207 patients, 62 (30%) had had a three-stage procedure as defined

214
by an initial colectomy with ileostomy with preservation of the
rectum followed by restorative proctocolectomy and, finally, by
closure of the ileostomy. The patients of this group had a stoma for
a mean period of 1051 days, compared with a mean of 173 days
among the 145 patients who had had a two stage procedure, defined
by restorative proctocolectomy and closure of the ileostomy.
At the time of proctocolectomy a carcinoma of the large bowel
was detected in 20 patients (9.6%). In 17 (85%) of cases it was
located in the left colon and rectum. The carcinoma was of Dukes'
stage A in 7 cases, B in 8 and C in 5 cases. In 18 (90%) patients, the
cancer occurred in patients affected by familial adenomatous polyposis, and in only two was it associated with colitis.
Selection criteria for the pouch operation included a severely
diseased rectum and adequate anal sphincters assessed either clinically or by means of manometry. This was carried out in 131 patients using the station pullthrough technique by means of an intraluminal probe inserted into the anal canal and connected to a
polygraph via a pressure transducer.

Operation
A J-pouch [9] was employed in 131 patients (63%), an S-pouch [10]
with a short efferent limb in 59 (29%), a W-pouch [5] in 13 (6%) and
an L-pouch [11] in 4 (2%). A GIA stapler was used in 50 patients
having a J-pouch. Close dissection of the rectum was performed. A
long rectal cuff(over 6 cm) was left in 29 (14%) cases. In 121 (58%)
patients the cuff was shorter. The rectum was completely removed
in 57 (28%) patients to reduce the extent of mucosectomy and
decrease the risk of pelvic abscess formation, bleeding and damage
to the internal sphincter. The mucosa was removed from the rectal
stump down to the dentate line via a peranal approach. The pelvis
was always drained by a tube placed either through the perineum
along the intersphincteric plane or through the abdominal wall. In
all but two patients a temporary diverting ileostomy was established.

Analysis of records and follow-up


All the clinical data including those on the occurrence of postoperative soiling (faecal or mucous, permanent or occasional) were
recorded on registry forms as previously reported [12].
Clinical information was available on all of the 156 patients
(75% of the total series) who had the ileostomy closed. The average
time of follow-up from the closure of the ileostomy was 13.4-/- 16.5
months (range 1-78 months). The Chi-square and Fisher's exact
tests were used in the statistical analysis of the data. Values were
expressed as mean ___ standard deviation of the mean.

suture line dehiscence 0 4 cases). I n t e s t i n a l o b s t r u c t i o n


o c c u r r e d b o t h after p o u c h o p e r a t i o n a n d i l e o s t o m y closure. A l a p a r o t o m y was r e q u i r e d for v a r i o u s c o m p l i c a tions in 57 p a t i e n t s (23.9%).
A f t e r c l o s u r e o f the i l e o s t o m y the p o u c h was either
excised or d e f u n c t i o n e d a n d a p e r m a n e n t i l e o s t o m y cons t r u c t e d in 12 cases. T h e r e a s o n s i n c l u d e d m e n t a l illness,
i n t r a c t a b l e d i a r r h o e a , severe i n c o n t i n e n c e a n d extensive
pelvic sepsis. P o u c h i t i s o c c u r r e d in 11.5% o f the p a t i e n t s ;
its o c c u r r e n c e w a s n o t statistically related to the t y p e o f
r e s e r v o i r u s e d (13.2% J - p o u c h , 11.1% S - p o u c h , 8 . 3 %
W-pouch).

Function
O n e h u n d r e d a n d fifty six p a t i e n t s were a v a i l a b l e for
f u n c t i o n a l a s s e s s m e n t at a m e d i a n o f 10 m o n t h s ( r a n g e 1
to 78 m o n t h s ) f r o m closure o f the i l e o s t o m y . T h e results
are given in Table 1. T h e m e a n n u m b e r o f e v a c u a t i o n s in
24 h was 4.2 1.9. A l m o s t h a l f o f the p a t i e n t s ( 4 1 . 6 % )
r e p o r t e d h a v i n g n i g h t e v a c u a t i o n s . Bowel f r e q u e n c y v a r ied slightly a c c o r d i n g to the p o u c h design: 4.4 _ 1.9 a f t e r
J - p o u c h , 3.9 + 2. t after S - p o u c h , 3.8 _ 1.1 after W - p o u c h ,
b u t these differences were n o t statistically significant.
S t a p l e d J - p o u c h a n d h a n d - s u t u r e d J - p o u c h led to a similar b o w e l f r e q u e n c y o f 4.5_+2.3 a n d 4 . 8 + 1 . 6 p e r 2 4 h ,
respectively, in p a t i e n t s o p e r a t e d o n for u l c e r a t i v e colitis
a n d assessed one y e a r after surgery. N e a r l y all p a t i e n t s
(97.5%) h a d s p o n t a n e o u s e v a c u a t i o n ; the f o u r w h o neede d to c a t h e t e r i z e t h e p o u c h h a d a n S - r e s e r v o i r w i t h a l o n g
efferent limb.
Less t h a n 2 % o f p a t i e n t s r e p o r t e d t r o u b l e s o m e faecal
soiling a n d 2 6 . 9 % c o m p l a i n e d o f o c c a s i o n a l leakage.

Factors affecting anal continence


F i v e f a c t o r s were significantly r e l a t e d to p o s t o p e r a t i v e
soiling. T h e s e i n c l u d e d age, d i a g n o s i s , l e n g t h o f followTable 1. Function in 156 patients assessed at a median of 10 months
(range 1 to 78 months) after closure of the ileostomy

n
Results

Complications
T h r e e p a t i e n t s died, t w o f r o m h e a r t failure, a n d one foll o w i n g p o u c h necrosis, giving a n o p e r a t i v e m o r t a l i t y o f
1.4%. T h e o v e r a l l c o m p l i c a t i o n r a t e was 4 0 . 5 % . F a i l u r e
to close the i l e o s t o m y o c c u r r e d in 12 cases (5.8%). I t w a s
d u e to dehiscence o f the r e s e r v o i r a n d o f the i l e o a n a l
a n a s t o m o s i s f o l l o w e d b y severe pelvic sepsis in eight p a tients; severe p o u c h i t i s (1 case), r e c u r r e n t r e c t a l c a n c e r (1
case) a n d i s c h a e m i c necrosis o f the p o u c h (1 case). O n e
p a t i e n t refused to h a v e the i l e o s t o m y closed. T h e p o u c h
was r e m o v e d in 4 o f these 12 p a t i e n t s .
W o u n d sepsis (25 cases) was the m o s t f r e q u e n t c o m p l i c a t i o n , f o l l o w e d b y pelvic sepsis (18 cases) a n d p o u c h

Bowel frequency: 4.2+ 1.9 evacuations/24h


Night evacuation
65
Pouch catheterization
4
Antidiarrhoeal drugs
42
Perianal soreness
85

41.6
2.5
20.2
54.4

Disordered continence
Occasional soiling
Mucus
Faeces
Permanent soiling
Mucus
Faeces
Total minor leak
Total major leak

45
40
31
9
5
2
3
42
3

28.8
25.6
19.9
5.7
3.2
1.3
1.9
26.9
1.9

0
6

0
2.9

Urinary dysfunction
Sexual dysfunction a
Males

215
Table 2. Length of follow-up vs postoperative soiling in 156 pa120'

[]
[]
[]

100'

normal continence
mucous soiling
faecal soiling

tients
< 1 year
(n = 98)
n

-ff
80,

Soiling overall"

e~

Mucus b

"5
0

Faeces a
Normal continence
Anal manometry

60.

40"

> J year
(n = 58)
%

33
34
21
21
12
13
65
66
RT b 41 12
VC a 100__+36

12
21
12
21
0
0
46
79
43 -- 23
141+60

=:.::+::::::::::::+::+::::::::+::::+::::

20'

a p < 0 . 0 2 ; bn.s.
RT = resting tone (mm Hg) ; VC = voluntary contraction (ram Hg)

::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::
::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::

::::::::::::::::::::::::::,:::::::::::::::::::::::::::: :::::::::::::::::::::

iiiiTii!ii:ili!;!ilili!!i?;iiii!Tiii:~iiTiiii77i!iiiiiiiii:i!iiiii ............................. 30%


V / / / / / / / / / A 0%
~/://.~
15%
::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::
:::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::

< 45 years

> 45 years
(I 5133 patients)

(30/123 patients)

Table 3. Bowel frequency (evacuation/24 h) vs postoperative soil-

ing in 156 patients


< 5/24 h
(n = J08)

Age
Fig. l. Age vs postoperative soiling. Soiling *p<0.05

up, bowel frequency and pouchitis. Postoperatively, soiling was nearly twice as frequent in patients over 45 years
with soiling rates of 24% below and 45% above this age
(Fig. 1). O f 99 patients operated on for colitis, 35 (35%)
had soiling c o m p a r e d with 10 (18%) of 56 who had familial adenomatous polyposis (p < 0.005). The effect of follow-up of less or greater than one year from closure of the
ileostomy is shown in Table 2. This is particularly notable
in the case of faecal soiling which did not occur after one
year. Mucous leakage did not improve. There was also no
i m p r o v e m e n t in resting anal pressure although voluntary
contraction rose significantly. Most of the patients (80%)
were continent when bowel frequency was lower than five
evacuations/24 h, whereas nearly half of the patients
(48%) experienced soiling when more than five bowel
motions were reported (Table 3). This difference was not
related to sphincter function. Eighteen patients developed pouchitis. O f these 9 (50%) had some soiling. This
was significantly greater than the rate of 26% in the 138
patients without pouchitis. Again, there was no relationship between sphincter function and soiling in this analysis (Table 4).
With regard to surgeon's experience, staged procedure, pouch design, length of rectal cuff, and postoperative perineal complications, the results were as follows.
Centres where less than five pouches had been performed
had a postoperative soiling rate of 22% c o m p a r e d with
21% of departments with more than five cases. Disordered continence was not statistically more frequent with
a two loop reservoir (J or L) (33%) than with a three or
four loop reservoir (S or W) (21%). In patients having a
three-stage procedure postoperative soiling was reported
in 35%. This was not statistically different from the
two-stage procedure. N o difference in leakage was observed in patients with a short, long or absent rectal cuff
(30%, 31%, 28%, respectively). Ileoanal anastomotic
complications did not cause a significant increase in post-

_>5/24 h
(n = 48)

Soiling overall"
Mucus
Faeces

22
18
4

20
17
4

23
15
8

48
31
17

Normal continence

86

80

25

52

Anal manometry b

RT 47__+19
VC 120-1-57

42 16
103___36

a p<0.01 (Chi square 10.9); b n.s.


RT = resting tone (mm Hg) ; VC = voluntary contraction (mm Hg)

Table 4. Pouchitis vs postoperative soiling in 156 patients

Soiling overall a
Mucus
Faeces
Normal continence
Anal manometry b

Pouchitis
(n = 18)

No pouchitis
(n= 138)

9
5
4

50
28
22

36
28
8

26
21
6

50

102

74

RT 50 4-19
VC 120+_28

46 + 19
116-t-57

" p <0.05 (Chi square 4.03); b n.s.


RT = resting tone (ram Hg); VC = voluntary contraction (mm Hg)

operative soiling. However, disordered continence occurred in two patients of the four who developed an anastomotic stricture following an ileoanal dehiscence.

Discussion

Anal continence following restorative proctocolectomy


in the present series was satisfactory considering that major faecal soiling was reported by less than 2% of the

216
Table 5. Faecal continence after restorative proctocolectomy and ileoanal reservoir reported in the literature
Authors

Patients
(n)

Reservoir

Continent
%

Minor
soiling %

Major
soiling %

Mean follow-up
(months)

Pezim et al. [3]


Everett [13]
Johnston et al. [16]
Fazio [17]
Fleshman et al. [14]
Fasth et al. [18]
Nicholls et al. [~9]
Wexner et al. [15]
Keighley et al. [8]
Italian Registry Present study

447
48
36
310
102
55
123
114
30
156

J
W
S, J, L
J, S
J, S
S
W, S, J
S, J
J, W
J, S, W

52
50
58
n.s.
77
60
83
74
90
71

44
46
42
26
23
40
15
24
10
27

4
4
0
n.s.
0
0
2
2
0
2

35
30
3
n,s.
> 12
12
43
60
>4
13

n.s. =not stated

patients. Most authors [/3-15] report similar findings.


Only a few claim no major soiling at all and attribute this
to the use of stapled ileoanal anastomosis and the avoidance of a transanal mucosectomy [5, 8, /0]. However,
more than 25 % of our patients experience some degree of
minor seepage. Our findings compare favourably with
those reported by others (Table 5), the percentage of perfect postoperative continence ranging between 50% and
90% in specialized centres. Among the factors investigated which may possibly affect anal continence five, including age, diagnosis, length of follow-up, bowel frequency
and pouchitis, did reach levels of statistical significance.
Deteriorating anal sphincter function with age has been
documented and may well affect postoperative continence [20]. However, in the present study there was no
significant difference in anal sphincter function between
younger and older patients, but it should be noted that
manometry was performed in different institutions and,
therefore, its results are of limited value in this study as
they could have been affected by several local factors
such as different probes, instruments, interpretations etc.
The occurrence of soiling was double in those patients
operated on for ulcerative colitis compared with those
who had the pouch constructed for familial adenomatous
polyposis. This could be due to several factors. Ulcerative
colitis may be associated with a staged operation, prolonged intestinal defunctioning and deterioration of anal
sphincter function [12], a more difficult mucosectomy in
an inflamed fibrotic rectum with the sphincters overstretched by anal dilatation and an increased risk of pouchitis leading to reduced stool consistency and reservoir
compliance.
The improvement in continence with the passage of
time observed here has previously been reported. Wexner
et al. [15] found that function initially reached a plateau
after about a year and then slowly improved over the next
several years. Pemberton et al. [21] noted that nocturnal
leakage decreased from 51% at six months to 20% at
four years after surgery and that faecal incontinence decreased from 4% to 0. This change may be due to several
factors. The capacity of the reservoir is reported to increase with time and the function of the anal sphincter,
initially stretched by the transanal procedure, recovers. A

late increase of resting tone determined by anal manometry has been reported following early postoperative impairrnent [22].
High bowel frequency and pouchitis significantly affected postoperative faecal continence in our series. The
two factors are to some extent inter-related since diarrhoea is the main symptom of an inflamed reservoir.
Disordered continence in this case is unlikely to be due to
sphincter deficiency, as shown by the anal manometric
results in the Registry patients. A case of frequent leakage
associated with good sphincter tone and severe reservoir
ileitis is reported by Everett [13]. The frequent urgency
and the liquid stool may be responsible for the disordered
continence. The incidence of pouchitis varies between
1/% and 27% in different series [12, /3] and treatment
with steroids and antibiotics, together with irrigation of
the pouch and dietary restrictions is usually effective.
There was no relationship between the pouchitis rate and
type of reservoir. Some authors believe that a large capacity reservoir should decrease the risk of pouchitis by a
better emptying of the contents [/4], but no correlation
has been demonstrated between pouch design, emptying,
or bacterial overgrowth with pouchitis [23, 24].
The surgeon's experience might be expected to play a
role in determining the risk of postoperative complications. A significant reduction in sepsis and hospital stay
with increasing experience has been reported [13]. In the
report by Wexner et al. [15] most of the patients who
experienced nocturnal incontinence underwent pouch
construction during the first three years of the study,
indicating that increased experience may play a role in
minimizing the risk of disordered continence. It was not
possible to show this in the present study, probably owing
to the number of different surgeons involved.
The importance of pouch design in determining the
outcome of restorative proctocolectomy has been widely
discussed in the literature [/4]. Very few prospective randomized studies have been published on this controversial point. Nicholls has published evidence to suggest that
the large capacity W-pouch is associated with low bowel
frequency [6], whereas Keighley compared J and Wpouches and showed no difference [8]. The Toronto
group has reported better function with an S-pouch,

217
when c o m p a r e d with a J reconstruction during the first
year after surgery [14]. The shortening and then the c o m plete elimination o f the efferent limb has been a d v o c a t e d
in o u r previous studies to i m p r o v e e m p t y i n g and anal
function by preventing kinking o f the limb itself, fibrosis
o f the reservoir outlet and sphincter d a m a g e due to excessive straining [7, 25]. The previous report f r o m the Italian
Registry [12] showed that neither o f the two m o s t comm o n l y used reservoirs, the J and the S designs, showed
a n y significant difference o f bowel frequency and continence. A difference in favour o f larger capacity pouches
was suggested in the present study and in other reports [6,
26]. In our series anal continence was slightly better in
those patients w h o had a two-stage procedure. In the
earlier Italian Registry report [12], incontinence was
m o r e likely in patients whose ileostomy closure had been
delayed for m o r e than one year. A n initial colectomy
w o u l d therefore be a risk factor in this regard. In a recent
study, a lower rate o f n o r m a l continence for a given reservoir design was reported in patients w h o had a threestage c o m p a r e d with a two-stage procedure (71% vs 83%
for S-pouch, 88% vs 100% for W - p o u c h ) [19]. However,
neither o f these c o m p a r i s o n s reached levels o f statistical
significance.
The length o f the rectal cuff did n o t seem to influence
anal continence in the Registry patients. Chaussade et al.
d e m o n s t r a t e d that conservation o f a rectal muscular cuff
is n o t necessary for the achievement o f g o o d clinical results [27]. W h e n c o m p a r i n g anal sphincter function in
two groups o f patients, with or w i t h o u t rectal cuff, no
differences were f o u n d between pre- and postoperative
results in either group, except for a significant decrease in
the resting pressure in b o t h g r o u p s [28].
Ileoanal complications, particularly stricture, are generally t h o u g h t to be an i m p o r t a n t factor affecting anal
continence after restorative p r o c t o c o l e c t o m y and ileal
p o u c h [17]. In a report f r o m T o r o n t o [14] the m o s t important factor influencing the functional result was anal
stricture formation. D a m a g e to the internal sphincter responsible for postoperative soiling m a y be the consequence n o t only o f distension during the transanal procedure but also pelvic sepsis [2].

Acknowledgements. The authors are indebted to the following surgeons who kindly reported the data of their patients: L. Batignani
(Firenze); L. Bertario, C. Cavagna, G. Doldi (Milano); M. Bezzi,
E Caracciolo, M. Castagneto, S. Minervini, V. Perri, A. Pronio
(Roma); L. Bucci, L. Coppola (Napoli); B. Ceccopieri, A. Gaetini,
M. Pinna Pintor (Torino); M. Chiarugi (Pisa); P. Colombo (Pavia);
G. Dodi, A. Infantino, S. Tropea (Padova); E Falchero (Pietra
Ligure); C. Marmorale (Ancona); G. Pitto (Genova); G. Poggioli
(Bologna); E. Restino (Bari); P. Ribichini (Ravenna), R. Villani.

References
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3. Pezim ME, Pemberton JM, Beart RW, Wolff BG, Dozois RR,
Nivatvongs S, Devine R, Ilstrup D (1986) Outcome of"indeterminant" colitis following ileal pouch-anal anastomosis: a technique to avoid mucosal proctectomy in the ileal pouch operation. Br J Surg 73:653-658
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with ileal reservoir. Br J Surg 76:77 81
14. Fleshman JW, Cohen Z, McLeod RS, Stern H, Blair J (1988)
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31:10-16
15. Wexner SD, Jensen L, Rothenberger DA, Wong WD, Goldberg
SM (1989) Long term functional analysis of the ileoanal reservoir. Dis Colon Rectum 32:275-281
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JN, Womack N, Axon ATR (1987) Preservation of the entire
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without mucosal resection with mucosal proctectomy and
endo-anal anastomosis. Br J Surg 74:940-944
17. Fazio VW (personal communication) Stapled ileoanal anastomosis. Proceedings of the Int. Syrup. on new trends in pelvic
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18. Fasth S, Scaglia M, Nordgren S, Oresland T, Hult6n L (1986)
Restoration of intestinal continuity (pelvic pouch) after previous proctocolectomy with distal mucosal proctectomy. Int J
Colorect Dis 1:256-258
19. Nicholls RJ, Holt SDM, Lubowski DZ (1989) Restorative proctocolectomy with ileal reservoir: comparison of two-stage vs.
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Ilstrup DM (1987) Ileal pouch-anal anastomosis for chronic
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components of preserved continence after ileoanal reservoir.
Surg Gyn Obstet 158:517-521
23. Moskowitz RL, Shepherd NA, Nicholls RJ (1986) An assessment of inflammation in the reservoir after restorative proctocolectomy with ileoanal reservoir. Int J Colorect Dis 1: 167-174
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218
25. Pescatori M, Manhire A, Bartram CI (1983) Evacuation
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Dis Colon Rectum 26:365-368
26. Nasmyth DG, Williams NS, Johnston D (1986) Comparison of
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28. Slors JFM, Taat CW, Brummelkamp WH (1989) Ileal pouchanal anastomosis without rectal muscular cuff. Int J Colorect
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Dr. M. Pescatori
Clinica Chirurgica
UCSC Policlinico Gemelli
Largo A Gemelli 8
1-00168 Roma
Italy

Int J Colorect Dis (1990) 5:219 222

Col6ree/al
Disease
9 Springer-Verlag 1990

Clinical and pathological correlates of HPV type 16 DNA in anal cancer


J.H. Scholefield t, j.G. Palmer 2, N . A . Shepherd 3, S. Love 4, K.J. Miller 1 and J . M . A . Northover 1
1
2
3
4

1CRF Cotorectal Unit, St. Mark's Hospital, London


Cumberland Infirmary, Carlisle
Gloucestershire Royal Hospital, Gloucester
Department of Research Statistics, Imperial Cancer Research Fund, Lincoln's Inn Fields, London, UK

Accepted: 23 August 1990

Abstract. The aetiology o f anal s q u a m o u s cell c a r c i n o m a


(SCC) has recently been associated with a sexually transmissible agent - h u m a n papillomavirus (HPV) type 16. In
this study clinical and pathological data f r o m a prospective series o f 67 anal SCC collected over a three year
period were c o m p a r e d with the H P V type 16 D N A content o f these t u m o u r s to determine whether any o f the
clinical o r histological parameters m i g h t predict H P V
D N A content in a t u m o u r specimen. O f twelve clinicopathological variables examined n o n e was significantly
correlated with H P V D N A c o n t e n t at the p = 0.01 level.

Introduction
Evidence o f an association between certain types o f hum a n papillomavirus (HPV) and s q u a m o u s cell c a r c i n o m a
o f the uterine cervix is b e c o m i n g increasingly compelling
[1]. A t least nine types o f H P V have been identified in
association with genital neoplasia, o f which only four are
c o m m o n l y encountered in the U n i t e d K i n g d o m . H P V
types 6 and 11 are associated with genital warts and some
intra-epithelial neoplastic lesions o f the cervix and vulva
[2]. H P V types 16 and 18, on the other hand, are f o u n d in
association with intra-epithelial neoplasia and invasive
cervical, vulval and penile carcinomas [3, 4].
Epidemiological evidence has suggested that anal
cancer m a y be associated with a sexually transmissible
agent [5, 6]. In the m o s t detailed o f these studies [7] a
history o f receptive anal intercourse in males was f o u n d
to be associated with anal cancer, c o m p a r e d to controls
with colon cancer. This study also showed that cases o f
anal cancer o f either sex h a d an increased relative risk o f
being smokers and o f a previous history o f genital warts.
E m b r y o l o g i c a l parallels between the epithelium o f the
cervix and anal canal and the association between papillomaviruses and cervical carcinoma, suggest that H P V
type 16 D N A might be involved in the aetiology o f anal
s q u a m o u s cell c a r c i n o m a (SCC). This thesis has been
tested by examining a series o f anal s q u a m o u s cell car-

cinomas, low rectal carcinomas and n o r m a l anal epithelium using Southern blot analysis and in situ hybridisation [8]. A highly statistically significant association between the presence o f H P V type 16 D N A and anal
s q u a m o u s cell c a r c i n o m a was d e m o n s t r a t e d and a n u m ber o f parallels with H P V - a s s o c i a t e d cervical c a r c i n o m a
were shown. Several other authors have reported a similar finding in small n u m b e r s o f cases [9-12].
The present study reports a univariate and multivariate analysis o f clinical and histological parameters which
might predict the presence o f H P V D N A in these tum o u r s in a prospective series o f 67 perianal SCCs.

Materials and methods


Patients were recruited to this study from our own clinical practice
and from other surgeons around the UK who knew of our interest
in anal cancer. More recently a number of cases have been referred
from the UKCCCR Anal Cancer Trial. Clinical details of each
patient were collected retrospectively from the medical staff involved in the care of each patient. In addition to basic demographic
data including marital status, the following details were collected
for each case: presenting complaint, smoking, sexual orientation,
previous history of sexually transmissible diseases including genital
condylomata, parity, size and site of tumour, systemic spread and
operative procedure. Since so many variables were being correlated
the level of statistical significance was taken as p = <0.01. In
Table 1 the numbers of patients for whom each piece of clinical
information was available is recorded and may not necessarily include all the patients in the study.
Uniformity of clinical data was not always possible, particularly regarding previous sexually transmissible infections, as not all
clinicians were aware of the association between anal SCC and
human papillomavirus or its possible sexual transmission. It was
considered inappropriate to request that each patient or even a
selected group of patients should be HIV-tested as this currently
requires fully informed consent; this may be upsetting to the patient
and was not clinically indicated.
Fresh anal cancer tissue was obtained from 75 patients who
were being examined (either under anaesthetic or in the outpatient
department) as part of the diagnostic process. The mean mass of
tissue collected was approximately 2 g (range 0.25 mg to 10 g). All
tissue was immediately frozen and stored in liquid nitrogen until
required. A portion of the fresh tissue obtained from each tumour
specimen was formalin-fixed and paraffin-embedded for routine

220
Table 1. Clinical and pathological variables assessed for HPV DNA

Table 2. HPV DNA in 67 anal squamous carcinomas

status
HPV type

No. (%)
positive

Technique

6
11
16
18

62
62
67
65

0
0
40
2

Dot blot
Dot blot
Southern & dot
Southern & dot

Sex

Male

Female

(67 patients)
HPV /6 positive
)~2= 0.64; p=0.5

(n=37)
( n = 30)
20 (54%) 20 (67%)

Age

0 50

51-65

66+

(67 patients)
HPV 16 positive
Z2 =6.33; p = 0.04

(n = 5)

(n = 35)

(n = 27)

4 (80%)

21 (60%)

/2 (44%)

Main complaint

Lump

Pain

Bleeding

Pruritis

(67 patients)
HPV 16 positive
Z2 =2.37; p=0.5

(n = 6)
5 (67%)

(n = 25)
18 (72%)

(n = 20)
/0 (50%)

(n = 3)
2 (67%)

Sex orientation

Male hetero

Male homo

(37 male patients)


HPV 16 positive
Z2 =0.32; p=0.6

(n = 30)

(n = 7)

19 (63%)

3 (43%)

Smoking

Never

Previous

Now

(47 patients)
HPV 16 positive
~2 =0.5; p=0.8

(n = 4)
2 (50%)

(n = 25)
17 (68%)

(n = / 8)
12 (67%)

Dentate line

Above

Astride

Below

Indeterminate

(67 patients)
HPV 16 positive
Z2 =2.37; p=0.7

(n = 8)
6 (75%)

(n = 28)
17 (61%)

(n = 16)
8 (50%)

(n = 15)
9 (60%)

Differentiation

Well

Mod

Poor

(67 patients)
HPV 16 positive
Z2 =0.81; p=0.7

(n = 20)

(n = 39)

(n = 8)

11 (55%) 25 (64%)

4 (50%)

Keratinisation

Well

Mod

Poor

(67 patients)
HPV 16 positive
Z2 =6.5; p = 0.04

(n = 13)
4 (31%)

(n = 28)
17 (61%)

(n = 26)
19 (73%)

Cell size

Small

Med

Large

(67 patients)
HPV" 16 positive
Zz =0.21; p=0.9

(n = 12)

(n = 33)

(n = 22)

Tissues were o b t a i n e d f r o m 75 cases o f a n a l cancer. Hist o l o g i c a l e x a m i n a t i o n r e v e a l e d t h a t 67 o f these were i n v a sive s q u a m o u s cell c a r c i n o m a s (SCC). T h e o t h e r t u m o u r s
were c a r c i n o m a in situ w i t h o u t invasive c a n c e r (4), a d e n o c a r c i n o m a (3), a n d m a l i g n a n t m e l a n o m a (1); these
were n o t i n c l u d e d in the f u r t h e r analysis.
O f the sixty-seven cases o f invasive a n a l c a r c i n o m a
37/67 ( 5 5 % ) o c c u r r e d in w o m e n . T h e m e d i a n age at pres e n t a t i o n was 58 y e a r s ( r a n g e 2 6 - 9 7 ) . T h e m o s t c o m m o n
p r e s e n t i n g c o m p l a i n t was b l e e d i n g (37%). Seven o f the 67
t u m o u r s were i n c i d e n t a l findings a t excision o f o t h e r a n a l
lesions ( h a e m o r r h o i d s (2), c o n d y l o m a t a (3), skin tags

7 (58%)

19 (58%)

14 (64%)

(2)).

Basaloid features

Positive

Negative

(67 patients)
HPV 16 positive
Z2 =0.05; p=0.9

(n = 12)
8 (67%)

(n = 55)
32 (58%)

(0)
(0)
(60)
(3)

n =number of tumours examined

The techniques of DNA extraction and Southern blotting used


in this study have been described in a previous publication [8].
Briefly, DNA was extracted from frozen tissue by proteinase K
digestion and phenol chloroform extraction, followed by precipitation in absolute ethanol. Restriction digests were performed on
i0 gg of genomic DNA using Barn H1, PST and EcoR/. Gel electrophoresis was performed in a 0.8% agarose gel followed by
Southern transfer to a nylon membrane. Hybridisation and washing
were performed to high stringency (0.1 x SSC at 68~ using a
cloned HPV DNA probe which had been radio-labelled with
32pdCTP by random priming. Autoradiography was performed at
-70~ using Kodak XAR 5 film exposed for 24-72 h between intensifying screens. The HPV DNA content of the tumours was
interpreted visually from the autoradiographs by comparison with
signal from positive and negative controls and by the position of the
bands.
The amount of viral DNA present in each tumour cell was
assessed by visual comparison with the 50 pg loading of HPV type
/6 DNA (50 pg represents one copy of the HPV genome per cell in
10 gg DNA (approximately 1 million cells)) and by comparison
with the CaSki DNA (500 copies per cell).
Statistical analysis was performed using chi squared analysis of
variables and logistic regression analysis.

Results

histological assessment by one histopathologist (NAS). The histological examination of the specimen allowed confirmation of the
diagnosis of squamous cell carcinoma and also permitted relatively
consistent interpretation of histological features. Tumours were assessed for differentiation, keratinisation, cell size, basaloid features
and lymphocyte infiltration.

Seven o f 30 m e n in this series ( 2 3 % ) a d m i t t e d to


b e i n g h o m o s e x u a l . E i g h t m e n ( i n c l u d i n g six h o m o s e x u als) were o f single m a r i t a l status a t the time o f p r e s e n t a tion. I n c o n t r a s t o n l y 8 % (3/37) o f the w o m e n s t u d i e d
were single; n o n e was k n o w n to be h o m o s e x u a l .
Four women (11%) with anal SCC had previously
u n d e r g o n e h y s t e r e c t o m y for c a r c i n o m a o f the u t e r i n e
cervix. I n two o f these, this h a d b e e n p e r f o r m e d m o r e
t h a n ten y e a r s p r i o r to p r e s e n t a t i o n w i t h a n a l SCC, a n d
in the o t h e r two the d i a g n o s i s o f cervical n e o p l a s i a prec e d e d the d i a g n o s i s o f a n a l S C C b y five y e a r s a n d f o u r
years. O n e o f these w o m e n w a s c o n c u r r e n t l y b e i n g
t r e a t e d for c a r c i n o m a in situ o f the vulva.

221
In this study it was found to be impossible to determine whether a t u m o u r had originated in the anal canal
or at the anal margin in 14/67 (21%) cases as the tumour
involved both sites in continuity. In a further 22/67 (33 %)
there was some uncertainty as to whether the turnout
originated at the anal margin or in the anal canal; it was
decided, therefore, not to analyse canal or margin tumours as separate subgroups.
O f the 47 patients with a smoking history, 18/47
(38%) were current smokers and a further 25/47 (53%) of
the group had smoked within the previous 10 years.
Forty of the 67 (60%) anal SCC contained HPV16
while two contained H P V 18 D N A (Table 2). In all cases
the H P V D N A was integrated into the host genome, but
in 5/40 H P V 16-containing tumours there was also episoreal (non-integrated) viral D N A . The a m o u n t of viral
D N A present in the tumours ranged from around 500
copies per cell (similar to CaSki cell line); the others contained only 1 - 2 copies per cell.
The clinical and pathological parameters examined
were tabulated against H P V 16 D N A content and chi
squared values were calculated (Table 1). N o n e of the
variables examined reached statistical significance at the
p = 0.01 level. Two variables, age at presentation and keratinisation of the tumour, almost achieved statistical significance. Those patients presenting under the age of 50
were more likely to have H P V DNA-containing tumours
(p = 0.04). However, only 5/67 tumours occurred in patients under 50 years of age; 4/5 were H P V D N A positive.
The poorly keratinised tumours were more likely to be
H P V DNA-containing than moderately or heavily keratinised tumours (p =0.04).

Discussion
This study has demonstrated that the H P V D N A content
of an anal SCC is not statistically significantly associated
with any clinico-pathological variables. This series of 67
cases of anal SCC represents the largest prospective series
of anal cancers reported. The lack of any significant correlation between H P V D N A content and any clinicopathological variables suggests that HPV-associated anal
SCC are not a subset of anal SCC occurring in particular
patients, and does not detract f r o m the proposed aetiological role for H P V type 16 in anal SCC.
Anal condylomata are prevalent in male h o m o sexuals, and several studies have shown that male h o m o sexuals are at risk for anal cancer [6, 7]. This trend was
also found in the present study; there was a disproportionate n u m b e r of single men (26% single men compared
with 9% single women); 7/8 of the single men admitted
homosexuality.
In women, the metachronous occurrence of anal and
cervical cancers m a y reflect the susceptibilities of these
epithelia to c o m m o n oncogenic agents. The multifocal
nature of genital cancers and their association with H P V
types 16 and 18 are widely recognised [4]. These parallels
have recently been shown to apply to the anus [13].
The technique of Southern blot analysis was at the
inception of this study the "gold standard" for the detec-

tion of h u m a n papillomavirus D N A sequences, being


quantitative, informative (integrated, supercoiled or
episomal D N A configurations m a y be distinguished) and
extremely sensitive (detecting the equivalent of one viral
genome copy per cell from one million cells). In the
course of the last twelve months, a highly sensitive
method of D N A amplification, the polymerase chain reaction, has begun to be used to examine turnouts for
H P V D N A . This method m a y be able to detect a single
H P V D N A sequence from a single cell. Further studies to
determine whether any of the anal SCC contain low levels
of H P V D N A using this new technique are awaited.
The anatomical complexity of the anal region is reflected in the plethora of malignant epithelial tumours
which arise there [14-20]. Classification of anal tumours
as arising from the anal margin or anal canal is difficult
as authors have defined the anal canal and anal margin
differently. Difficulties in assessing where the tumour
originated in relation to the dentate line justify analysing
all the tumours as one group. Furthermore, since the
treatment of choice in most tumours is now non-surgical,
the distinction between anal canal and anal margin is
becoming irrelevant.

Acknowledgements. The authors are indebted to a large number of


surgeons around the country who allowed the investigators to attend their operating sessions or outpatient clinics to collect fresh
tissue samples from the anal turnouts occurring in patients under
their care during the period 1986-1989.

References
1. zur Hausen H (1989) Papillomavirus in human cancers. Mol
Carcinogenesis 1:147 150
2. Gross G, Hagedorn M, Ikenberg H, Rufli T, Dahlet C,
Grosshans E (1985) Bowenoid papulosis. Presence of human
papillomavirus (HPV) structural arttigens and of HPV 16 related DNA sequences. Arch Dermatol 121:858-863
3. McCance D J, Clarkson PK, Dyson JL, Walker PG, Singer A
(1985) Human papillomavirus types 6 and 16 in multifocal
intraepithelial neoplasias of the female lower genital tract. Br J
Obstet Gynecol 92:1093-1100
4. McCance DJ (1986) Human papillomaviruses and cancer.
Biochim Biophys Acta 823:195-205
5. Austin DF (1982) Etiological clues from descriptive epidemiology. Squamous carcinoma of rectum or anus. National Cancer
Institute Monographs 62:89-90
6. Peters R, Mack T, Bernstein L (1984) Parallels in the epidemiology of selected anogenital carcinomas. JNCI 72:609-615
7. Daling JR, Weiss NS, Hislop PHTG, Maden C, Coates R J,
Sherman KJ, Ashley RL, Beagrie M, Ryan JA, Corey L (1987)
Sexual practices, sexually transmitted diseases, and the incidence of anal cancer. N Engl J Med 317:973-977
8. Palmer JG, Scholefield JH, Coates PJ, Shepherd NA, Jass JR,
Crawford LV, Northover JMA (1989) Anal cancer and human
papillomaviruses. Dis Colon Rectum 32:1016-1022
9. Wells M, Griffiths S, Lewis F, Dixon MF (1987) Identification
of human papillomavirus in paraffin sections of anal condylomas and squamous carcinomas by in situ DNA hybridisation.
J Pathol 151:A64
10. Beckmann AM, Daling JR, McDougall JK (1985) Human papillomavirus DNA in anogenital carcinoma. J Cell Biochem
[Suppl] 9:68
11. Hill SA, Coghill SB (1986) Human papillomavirus in squamous
carcinoma of the anus. Lancet II: 1333

222
12. Scheurlen W, Stremlau A, Gissman L, Hohn D (1986) Rearranged human papillomavirus type 16 molecules in anal and a
laryngeal carcinoma. Int J Cancer 38:671-676
13. Scholefield JH, Sonnex C, Talbot IC, Palmer JG, Whatrup C,
Northover JMA (1989) Anal and cervical intra-epithelial neoplasia - possible parallels. Lancet II: 765-769
14. Berg JW, Lone F, Stearns MW (1960) Mucoepidermoid anal
cancer. Cancer 13:914 916
15. Morson BC (1960) The pathology and results of treatment of
squamous cell carcinoma of the anal canal and anal margin.
Proc R Soc Med 53:416-420
16. Morson BC, Volkstadt H (1963) Mucoepidermoid tumours of
the anal canal. J Clin Pathol 16:200-202
17. Klotz Jr RG, Pamukcoglu T, Souilliard DH (1967) Transitional
cloacogenic carcinoma of the anal canal. Cancer 20: 1727-1745

18. Morson BC, Pang LSC (1968) Pathology of anal cancer. Proc
R Soc Med 61:623-624
19. Grodsky L (1969) Current concepts on eloacogenic transitional
cell anorectal cancers. JAMA 207:2057-2061
20. Dougherty BG, Evans HL (1985) Carcinoma of the anal canal:
a study of 79 cases. Am J Clin Pathol 83:159-164

Mr. J. M. A. Northover
ICRF Colorectal Unit
St. Mark's Hospital
City Road
London ECIV 2PS
UK

Int J Colorect Dis (1990) 5:223-227

Col6i'ec/al
Disease
9 Springer-Verlag 1990

Flow cytometric analysis in colorectal carcinoma:


prognostic significance of cellular DNA content
A. Schillaci 1 D.D. Tirindelli 2 M. Ferri i L. Teodori 2, E Mauro 2, V. Nicolanti 1 and S. Stipa t
1[. Department of Surgery, University "La Sapienza" and 2 Division of Physics and Biomedical Sciences, ENEA, C.R.E.,
Casaccia, Rome, Italy
Accepted: 17 August 1990

Abstract. T h e p r o g n o s t i c value o f D N A p l o i d y status was


e v a l u a t e d p r o s p e c t i v e l y in 70 p a t i e n t s with c o l o r e c t a l carc i n o m a . C e l l u l a r D N A c o n t e n t was m e a s u r e d b y flow
c y t o m e t r y f r o m fresh specimens with m u l t i p l e site sampling. Seventy-five p e r c e n t o f cases e x h i b i t e d a D N A ane u p l o i d p a t t e r n . I n a u n i v a r i a t e analysis, D N A p l o i d y
status s h o w e d a statistically significant c o r r e l a t i o n w i t h
survival (p < 0.05), w e a k e r t h a n D u k e s ' stage (p < 0.001).
N o c o r r e l a t i o n was o b s e r v e d b e t w e e n survival a n d presence o f m u l t i p l e D N A stemlines. I n a m u l t i v a r i a t e a n a l y sis, D u k e s ' stage was the s t r o n g e s t p r o g n o s t i c i n d i c a t o r
(p = 0.01) while D N A p l o i d y status d i d n o t s h o w a n indep e n d e n t p r o g n o s t i c value. It is c o n c l u d e d t h a t D N A
p l o i d y status is a s s o c i a t e d w i t h p a t h o l o g i c a l features o f
aggressive m a l i g n a n c y , b u t it does n o t have a d e t e r m i n a n t role in p r e d i c t i n g survival.

Introduction
F l o w c y t o m e t r i c analysis o f t u m o u r tissue can be perf o r m e d easily a n d r e l i a b l y to d e t e r m i n e the presence o f
a b n o r m a l D N A c o n t e n t . By this technique, t u m o u r s w i t h
n o r m a l (diploid) D N A cell p o p u l a t i o n s can be distinguished f r o m those with a b n o r m a l D N A c o n t e n t (aneuploid). T u m o u r D N A c o n t e n t h a s been i n c r e a s i n g l y corr e l a t e d w i t h p a t i e n t p r o g n o s i s in v a r i o u s solid t u m o u r s
[1]. I n this s t u d y we p r e s e n t a series o f c o l o r e c t a l t u m o u r s
in w h i c h cellular D N A c o n t e n t was m e a s u r e d in o r d e r to
establish the real p r o g n o s t i c significance o f D N A p l o i d y
status a n d its r e l a t i o n s h i p with c o n v e n t i o n a l m o r p h o logic p a r a m e t e r s .

Patients and methods


Patients
Seventy-eight patients with carcinoma of the colon or rectum referred to our Department from January 1982 to March 1987 entered
the study. Eight patients were excluded subsequently for the follow-

ing reasons: one patient had a metachronus tumour, four patients


had a local recurrence of a previously resected carcinoma, one
patient underwent only exploratory surgery, and in two patients the
DNA histograms were uninterpretable. The study group therefore
consisted of 72 primary resected colorectal carcinomas from 70
patients. Two patients had synchronous tumours, and, for the purpose of the study, only the more advanced cancer was considered.
There were 40 men (57%) and 30 women (43%). The mean age was
65 years (range 20 to 84 years). Forty-two patients (60%) had
primary carcinoma of the colon while 28 patients (40%) had rectal
carcinoma. The type of resection is reported in Table 1. Fifty-five
patients (79%) underwent "curative" resection in which all macroscopic tumour was removed. In 15 patients (21%) the resection was
regarded as palliative because there were hepatic (13) or pulmonary
(1) metastases, or peritoneal seedings (1). Pathological staging was
assessed according to Dukes' system and histological grading was
defined by Broders' classification. Seventeen patients with rectal
carcinoma received postoperative adjuvant radiotherapy (5000 cGy)
and nine patients with metastastic disease received chemotherapy.
The 66 patients who survived resection were followed up using
laboratory, endoscopic, sonographic and CT scan investigations.
The outcome was unknown until December 1989, when 64 (91%)
patients had been followed for a minimum of three years. The
median length of follow-up was 55 months (range 33-84).

Flow cytometry
Flow cytometric measurement of cellular DNA content was performed on fresh surgical specimens and multiple site sampling (core,
periphery, and, if present, lymph node and distant metastases) was
obtained in the majority of the cases (Fig. 1). Samples from the
same specimen were always used for double-blind histopathologic
examination. Specimens were placed in RPMI 1640 culture medium

Table l. Type of resection


No. of
patients

Anterior resection of rectum


Left hemicolectomy
Right hemicolectomy
Abdomino-perineal excision of rectum
Miscellaneous

29
15
11
7
8

41
21
16
10
12

Total

70

100

224
supplemented with 5% fetal calf serum at 4~ Monocellular suspension of biopsy material was obtained by mechanical and enzymatic treatment. The tissue was minced with scissors, washed in a
saline solution, and treated with 0.5% pepsin for 5 - 1 0 rain (Serva,
Heidelberg, FRG). Tris-buffer was then added. Samples were centrifuged at 200 9 for 5 min, and the pellet was resuspended in trisbuffer. Twenty gl o f N o n i d e t P40 (Fluka, Buchs, Switzerland), I ml
of 10 g/ml ethidium bromide (Serva, Heidelberg, FRG), and 1 ml of
25 g/ml mithramycin (courtesy of Pfizer, Italy) were added to 0.2 ml
of cell suspension. The samples were then measured with an [CP
arc lamp pulse cytophotometer and more recently with a P A R T E C
PAS II (Arlesheim, Switzerland). An average of 10 000 cells per
histogram were analyzed. D N A content distribution was accumulated in a multichannel analyzer and data were analyzed by a computer (Nuclear Data ND620 - Shaumberg, IL). The coefficients of
variation for aneuploid peaks ranged from 2% to 7%. In all cases,
normal colonic mucosa from the same patient was used as the
internal diploid standard. The D N A index (DI) was calculated as
the ratio of the G 1/0 aneuploid peak modal channel to the G 1/0
diploid peak modal channel.

45"

00

35"
30"

2,526%

20o
Z

1513%

I0-

5I%

~-.ORE

CORE
PERIPHERY

CORE
PERIPHERY
NODES

CORE
PERIPHERY
NODES
METASTASES

Fig. 1. Biopsis sites within tumour in 45 patients

Statistics

35-

Correlation between D N A ploidy or multiclonality and pathological features were analyzed using the Z2 test. Survival curves were
constructed using the Kaplan-Meier method and statistical significance was calculated utilizing the Logrank test. The prognostic
value of pathological and flow cytometric variables was assessed by
stepwise logistic regression analysis (STATLIB 7A - IBM).

30-

-6%

(/] 2 5 tz
w 2o

h
O

Results

60%

40-

24%

1513%

~, 10-

'7%

Seventeen tumours (24%) showed a D N A diploid pattern and 53 (76%) had a D N A aneuploid pattern. Among
aneuploid tumours, 26 (49%) had multiple D N A stem
lines, manifested as two (22 cases) and three or more
(four cases) aneuploid peaks. Figure 2 shows the distribution of tumours into subsets according to D N A index.
No statistical differences were observed in D N A ploidy
pattern between tumours from right colon, left colon or
rectum (p = 0.5).

Fig. 2. Distribution of tumour subpopulations according to D N A


Index (D.I.: ratio between G 1/0 aneuploid and G 1/0 diploid peak
modal channel). <1: hypoploid; 1: diploid; 1-2: hyperploid; 2:
tetraploid; > 2 hypertetraploid. In some instances tumours exhibited more than one aneuploid subpopulation

Histopathological grading

Table 2. Histopathological grading

5I'

I I '-'-

<1

<!
1-2

All tumours were adenocarcinomas and seven (10%)


were mucoid. Three (4%) were well differentiated tumours, 44 (63%) moderately differentiated, and 22
(31%) poorly differentiated; in one patient tumour grading was unknown. The distribution of histological grading according to D N A ploidy pattern failed to show any
statistical difference (p = 0.38) (Table 2).

Well differentiated
Moderately differentiated
Poorly differentiated
Unknown

Dukes' staging

p=0.38

According to Dukes' classification, 13 patients (19%)


were stage A, 23 patients (33%) stage B and 19 patients
(27%) stage C. Fifteen patients (21%) who had received
a palliative resection were considered stage D. D N A
diploid rates for Dukes' A, B and C tumours were similar,
but all D tumours showed a D N A aneuploid pattern
(Table 3). This distribution almost reached statistical significance (p = 0.052). However, when palliative resections
were excluded, no correlation was found (p = 0.5). Moreover, there was no relationship between Dukes' classification and presence of multiple D N A stem lines (p = 0.34).

<1
1-2
>2

1-2

I-2
:.2

No. of
patients

3
44
22
1

>2

0.1.

Diploid

Aneuploid

pts

pts

1
10
6
0

33
23
27
-

2
34
16
1

67
77
73

Table 3. Stage of disease


Dukes

A
B
C
D

No. of
patients

13
23
19
15

A vs B vs C vs D, p = 0 . 0 5 2 ; A vs B

Diploid

Aneuploid

pts

pts

5
8
4
0

38
35
21
-

8
15
15
15

62
65
79
100

vs

C,p=0.5

225
Survival
Seventeen out of the 51 patients who underwent "curative" resection (four who died post-operatively were excluded) developed recurrent disease. N o statistical correlation was observed between D N A ploidy pattern and
recurrence of disease: there were 4 cases of recurrence
(4/15 = 27%) among patients with D N A diploid tumours
and 13 recurrences (13/36=36%) among those with
D N A aneuploid tumours (p =0.57).
Actuarial 5-year survival rate was 50% for all patients
surviving resection. Actuarial 5-year survival rate was
65% following "curative" resection while none who had
palliative resection survived more than 2 years.
Overall, D N A ploidy pattern was significantly related
to the prognosis: 5-year survival rate was 68% for patients with D N A diploid tumours but only 44% for those
with D N A aneuploid tumours (p < 0.05) (Fig. 3).
In the subgroup of patients who had a "curative"
resection, there was no statistical correlation between
D N A ploidy pattern and prognosis: 68 % of patients with
D N A diploid tumours survived 5 years compared with
63% of patients with D N A aneuploid tumours (p > 0.5)
(Fig. 4).
Five-year survival rate was not significantly influenced by tumour D N A content in Dukes' stage B cases:
64% of patients with D N A diploid tumours survived
5 years compared with 62% with D N A aneuploid tumours (p>0.1).
For Dukes' stage A and C the analysis of survival
according to D N A ploidy was not meaningful as too few
patients exhibited a D N A diploid pattern.
The presence of multiple D N A stemlines did not show
any statistical influence on 5-year survival ( p > 0.5).
Variables of individual prognostic significance were
pathological stage (p<0.001) and D N A ploidy pattern
(p<0.05) but not histological grading (p>0.1). However, when these factors were considered sequentially by
logistic regression only pathological staging remained as
an independent factor (multiple correlation coefficient = 0.536; p = 0.01) whereas, D N A ploidy pattern was
not significant.

Discussion

The prognostic value of D N A ploidy status in colorectal


tumours was first emphasized by Wolley et al. [2]. The
authors reported that 65% of patients with D N A diploid
tumours survived 5 years compared with only 7.5% of
those with D N A aneuploid tumours. Subsequently other
investigators observed a significant relationship between
D N A ploidy status and survival. Using a multivariate
analysis, Armitage et al. [3], Scott et al. [4] and Quirke
et al. [5] demonstrated that D N A ploidy pattern was an
independent prognostic factor, but weaker than Dukes'
stage. Kokal et al. [6] found that D N A content of the
tumour was the strongest prognostic variable in predicting survival, even more important than stage of disease.
Nevertheless, the role of D N A ploidy status as a prognostic factor is still debated. Melamed et al. [7] and Rognum

1.00-

"'I

--L__

.80-

.60 -

DIPLOID

I'N..~." - L . . . . .

p <0.05
%" "~"L ...........

.40 -

ANEUPLOID

.20-

;
PATIENTS

~
AT

,~ YEARS

RISK

DIPLOID

15

15

13

1t

11

ANEUPLOID

51

~9

29

24

12

Fig. 3. Overall 5-year survival according to DNA ploidy (p<0.05).


Three patients who died without evidence of recurrent disease were
censored at time of death

1.00
. . . . . L-I I
-t.. 3
3.

.80

DIPLOID
"-L . . . . . .

L..,..,
L ..........

.60-

ANEUPLOID
p>0.5

.40

.20

,5 YEARS

11
2:5

11
12

3
5

PATIENTS

DIPLOID
15
ANEUPLOID 36

1
AT

15
:53

RISK

1:5
27

Fig. 4. Five-year survival for "curative" resection according to

DNA ploidy (p > 0.5). Three patients who died without evidence of
recurrent disease were censored at time of death
et al. [8] found survival to be similar for near-diploid and
aneuploid tumours. More recently, Jones et al. [9] reported that D N A ploidy was of individual prognostic
significance but not of independent significance in a regression analysis model.
In the present study D N A aneuploidy was associated
with pathological features of aggressiveness, since all tumours with distant metastases exhibited a D N A aneuploid pattern. In a univariate analysis, D N A ploidy pattern showed a statistically significant correlation with
survival, but weaker than Dukes' stage. However, if patients with distant metastases were excluded and the analysis was limited to "curative" resections, this correlation
lost significance. Similarly, no statistical correlation was
observed between D N A ploidy pattern and recurrence of
disease in patients having "curative" resection. These results suggest that Dukes' staging system is a more important prognostic indicator than D N A ploidy pattern. Our
impression was confirmed by logistic regression analysis
which demonstrated that stage of disease was the most

226
Table 4. DNA ploidy status and survival in colorectal carcinoma

Series

No. of
patients

Aneuploidy
(%)

Follow-up
(years)

Survival (%)
Diploid

Aneuploid

Fresh
Banner 1985
Hiddemann 1986
Frankfurt 1986
Metamed 1986
Rognum 1986
Paraffin-embedded
Armitage 1985
Scott 1987
Quirke 1987
Jones 1988

[10]
[11]
[12]
[7]
[8]

56
88
91
33
100

71
82
68
55
63

3
5

53
59

67
43

[3]
[4]
[5]
[9]

134
121
125
123

54
50
54
67

5
15
5
3

43
40
57
64

19
20
35
34

powerful prognostic factor, while D N A ploidy pattern


was not as an independent prognostic factor.
Our findings are consistent with the report of Jones
et al. [9] but differ from those of some authors [3-6].
Several reasons might explain these differences, such as
small numbers of patients in some studies, the retrospective nature of some reports, differences in technique, and
lack of standardization and quality control procedures
a m o n g different laboratories. In particular, the use of
paraffin-embedded material rather than fresh specimens
seems to be associated with a lower aneuploidy rate and
a significant correlation between D N A ploidy pattern
and survival (Table 4). The analysis of paraffin-embedded tissue allows study of a larger n u m b e r of patients
with longer follow up. However, this method presents
some problems, such as p o o r histogram resolution because of excessive background, and wider peaks which
obscure the presence of a near-diploid p e a k [13].
Moreover, a paraffin-embedded specimen represents
only a portion o f the tumour. It has been reported that
colorectal cancer is heterogeneous in cellular D N A content, with different populations of t u m o u r cells in different parts of the t u m o u r [14]. As a consequence, a single
biopsy from a t u m o u r m a y not be representative of the
whole t u m o u r - multiple sampling is needed to assess the
degree of i n t r a t u m o u r D N A stem line heterogeneity [11].
Jones et al. [9] analyzed paraffin-embedded material and
reported a multiclonality rate of 4%. F r a n k f u r t et al. [12]
examined one specimen per t u m o u r f r o m fresh tissue and
found a 16% multiclonality rate. H i d d e m a n n et al. [11]
reported a 40% multiclonality rate, analyzing an average
of nine fresh specimens for each tumour. In the present
series, a D N A stem line heterogeneity was detected in
49% of aneuploid tumours. This high rate p r o b a b l y reflects the evaluation o f multiple samples f r o m the same
t u m o u r (mean 2.5; range 1 - 4 ) . In fact, we were able to
demonstrate different D.I. in one or m o r e samples taken
from multiple sites in a single individual in 21 out of 25
aneuploid cases. Furthermore, in 13 out of 53 aneuploid
cases a diploid pattern was observed in one sample. H o w ever, there was no evidence that heterogeneous tumours
exhibit m o r e aggressive behaviour, as no significant rela-

ns
ns
0.001
0.0024
<0.02
0.007

tionship was found between the presence of multiple


D N A stem lines and either Dukes' stage or survival.
In the present study patients were prospectively evaluated and data were obtained from the analysis of fresh
specimens with multiple site sampling for each tumour.
The results clearly show that D N A ploidy status is correlated with pathological features of aggressive malignancy, but there was no correlation with survival. Hence,
at present, D N A ploidy status is not a determinant prognostic variable in colorectal cancer, and its value is only
complementary to Dukes' staging, which remains the
most reliable prognostic indicator. Obviously, the results
of this study must be confirmed by a larger n u m b e r of
patients with a longer period o f follow-up. Further cytometric variables which can be inferred from cell cycle
analysis (Phase S, proliferative index) should be investigated and a standardization of C F M technique is mandatory.

References

1. Friedlander ML, Hedley WD, Taylor IW (1984) Clinical and


biological significance of aneuploidy in human tumors. J Clin
Pathol 37:961-974
2. WolleyRC, Schreiber K, Koss LG, Karas M, Sherman A (1982)
DNA distribution in human colon carcinomas and its relationship to clinical behavior. J Nat Cancer Inst 69:15-22
3. Armitage NC, Robins RA, Evans DF, Turner DR, Baldwin
RW, Hardcastle JD (1985) The influence of tumour cell DNA
abnormalities on survival in colorectal cancer. Br J Surg
72:828-830
4. Scott NA, Rainwater LM, Wieand HS, Weiland LH, Pemberton JH, Beart Jr RH, Lieber MM (1987) The relative prognostic
value of flow cytometric DNA analysis and conventional clinicopathologic criteria in patients with operable rectal carcinoma. Dis Col Rect 30:513-520
5. Quirke P, Dixon MF, Clayden AD, Durdey P, Dyson JED,
Williams NS, Bird CC (1987) Prognostic significance of DNA
aneuploidy and cell proliferation in rectal adenocarcinomas. J
Pathol 151:285-291
6. Kokal WA, Gardine RL, Sheibani K, Morris PL, Prager E, Zak
IV, Terz JJ (1989) Tumor DNA content in resectable, primary
colorectal carcinoma. Ann Surg 209:188-193

227
7. Melamed MR, Enker WE, Banner P, Janov AJ, Kessler G,
Darzynkiewicz Z (1986) Flow cytometry of colorectal carcinoma with three-year follow-up. Dis Col Rect 29:184 186
8. Rognum TO, Thoru E, Lund E (1986) Clinical behaviour in
large bowel carcinoma patients with different DNA ploidy pattern. 14th International Cancer Congress, Budapest, Abstract
2439
9. Jones DA, Moore M, Schofield PF (1988) Prognostic significance of DNA ptoidy in colorectal cancer: a prospective flow
cytometry study. Br J Surg 75:28-33
10. Banner BF, Tomas-De La Vega JE, Roseman DL, Coon JS
(1985) Should flow cytometric DNA analysis precede definitive
surgery for colon carcinoma? Ann Surg 202:740-744
11. Hiddemann W, von Bassewitz DB, Kleinemeier H J, SchulteBrochterbeck E, Hauss J, Lingemann B, Bfichner T, Grundmann E (1986) DNA stemtine heterogeneity in colorectal cancer. Cancer 58:258-263

12. Frankfurt OS, Arbuck SG, Chin JL, Greco WR, Pavelic ZP,
Slocum HK, Mittelman A, Piver SN, Pontes EJ, Rustum YM
(1986) Prognostic applications of DNA flow cytometry for human solid tumors. In: Andreeff M (ed) Clinical cytometry. Ann
NY Acad Sci 468:276 290
13. Hedley DW (1989) Flow cytometry using paraffin-embedded
tissue: five years on. Cytometry 10:229-241
14. Petersen SE, Bichet P, Lorentzen M (1978) Flow-cytometric
demonstration of tumor-cell subpopulations with different
DNA content in human colo-rectal carcinoma. Eur J Cancer
15:383-386
Prof. A. Schillaci
Via Cortina D'Ampezzo 241
1-00135 Roma
Italy

Int J Colorect Dis (1990) 5:228-231

Coloree|al
Disease

9 Springer-Verlag 1990

Effects of hysterectomy on bowel and bladder function


T. Taylor 1, A . N . Smith 2 and Mary Fulton 3
1 Gastrointestinal Unit, University of Edinburgh, Western General Hospital, Edinburgh
z University Department of Surgery, Western General Hospital, Edinburgh
a Department of Community Medicine, University of Edinburgh Medical School, Edinburgh, UK
Accepted: 2 August 1990

Abstract. A case control study c o m p a r e d the bowel habit


o f 91 post-hysterectomy w o m e n with paired controls from
the same family d o c t o r practice. M o r e cases had an abn o r m a l bowel frequency, a firmer stool consistency and
assessed themselves as having a b n o r m a l bowel function,
p r e d o m i n a n t l y constipation after hysterectomy, t h a n
controls. Significantly m o r e cases t h a n controls h a d consulted a d o c t o r because o f constipation but there was no
significant difference in laxative usage. There was a significant short-term association between decreased bowel
frequency a n d increased u r i n a r y frequency after hysterectomy. This b e c a m e highly significant in those patients
w h o developed chronic s y m p t o m s . O o p h o r e c t o m y , unilateral or bilateral, did n o t significantly affect bowel
habit other t h a n to intensify the change in stool consistency. The hypothesis is discussed that the post-hysterect o m y effects on bowel and bladder function m a y have a
c o m m o n aetiology in a degree o f a u t o n o m i c denervation
o f b o t h viscera.

Introduction
A n u m b e r o f female patients presenting with severe constipation date its onset f r o m a hysterectomy. T h i r t y - f o u r
such patients have been investigated by us in the past two
years as tertiary referrals for the assessment o f colo-rectal
function. Increasingly, they require surgical m a n a g e m e n t
by sub-total c o l e c t o m y w h e n medical measures have
failed.
L o n g - t e r m sequelae o f h y s t e r e c t o m y on bladder function, n o t a b l y frequency and incontinence, are well docum e n t e d [1, 2]. It is claimed that their severity increases
with the extent o f the pelvic p r o c e d u r e but possible effects
on bowel function have been studied less extensively
[3, 4].
Intractable constipation after h y s t e r e c t o m y could be
the severe end o f a spectrum o f m o r e general bowel disorder and it remains to be determined h o w m a n y supposedly unaffected h y s t e r e c t o m y patients have a c h a n g e d

bowel habit. G u r n a r i et al. [3], reviewing this subject in


108 female patients after gynaecological surgery, showed
that chronic constipation and urinary incontinence occurred m o r e frequently the m o r e radical the operation
performed. T h e y attributed the increased risk o f complications to surgical injury o f intrapelvic nerve fibres. We
have described in a preliminary report the frequency o f
p o s t h y s t e r e c t o m y constipation [4]. This study describes
in greater detail aspects o f the bowel disturbance and its
relationship to altered u r i n a r y function after hysterect o m y and examines whether o o p h o r e c t o m y d o n e at the
same time contributes to the effects on pelvic function.

Methods
One hundred women who had had a hysterectomy for benign disease 2-8 years previously were identified in two Edinburgh practices. An upper age limit of 65 at the time of entry to the study was
set. The plan of the study was to compare hysterectomy cases with
controls from the same area and hence social background. Each
case was age-sex matched by taking the next woman born in that
year from the practice list. Ninety-one pairs of cases and controls
agreed to participate in the study and returned a questionnaire given
to each member of the pair. Women with major abdominal surgery
were excluded from the control group as were those irritable bowel
syndrome.
The questionnaire which was a simple, self-administered one,
was devised to allow assessment of both bowel and urinary function. It included a brief section on past health and current medication as well as asking about frequency of defaecation, stool consistency, laxative use and had a self-assessment of bowel habit in which
the subjects were asked whether they considered themselves to be
normal, constipated or to have loose motions. They were also asked
if they had consulted a doctor about constipation, experienced any
urinary dysfunction or incontinence, and whether there was any
postoperative effect of hysterectomy on bowel and urinary frequency. The questionnaire was adapted from ones used in other studies
for assessing bowel and bladder function [5, 6].
Ten women chosen at random for direct interview showed no
significant difference in their responses from those in their postal
questionnaire. Ten other women with severe symptoms, when re-interviewed, showed 29% responses indicating more severe constipation than formerly, 5% with less severe symptoms and 66% identical responses to the questions formerly asked. A comparative group

229
of 20 women treated by D and C at a similar time to the hysterectomy group, stated that this procedure had had no effect on their
bowel function.

Table 1. Control group: bowel habit compared with Connell et al.


(1965) [5]
Bowel
Formed Total
Laxatives
frequency
stool
number more often
3 x daily to
using
than weekly
every 3rd day
laxatives

Statistical analysis
Statistical analysis was by a chi-squared test or a McNemar's test
for paired comparisons.

Present study
Connell et at.
(1965) [5]

92%
98%"

81%
90%

22%
34.4% b

4.5%
16.8%b

Results

Bowel habit of controls


The bowel habit of the control group was broadly comparable to that of the well known study of Connell et al.
[5] as indicated in Table 1, though the questions asked
and the composition o f the groups were slightly different.

Comparison of bowel function between post-hysterectomy


cases and controls
Table 1 established various criteria for normality, for example, a range of bowel frequency from three times per
day to a bowel m o v e m e n t every third day, the passage of
a formed stool and little recourse to laxatives. Matched
pairs of cases and controls were analysed in respect of
whether they fell into a ' n o r m a l ' or an ' a b n o r m a l ' category by the above criteria.
(a) Bowel frequency. Eighteen cases but only 7 controls
had an abnormal bowel frequency when their pair did not
(p < 0.05, M c N e m a r ' s test); the majority had a bowel frequency of every fourth day or less (14 cases, 6 controls).
(b) Stool consistency. Twenty-six cases but only 9 controls
reported abnormal stools when their pair did not
(p < 0.01, M c N e m a r ' s test).
(c) Laxative use. Fifteen cases used laxatives fortnightly
or more frequently but only six controls did so when their
matched pair did not. The differences were not statistically significant (p > 0.05, M c N e m a r ' s test).

Patients" own assessment of bowel function


Twenty-seven cases felt that they had an abnormal bowel
function after hysterectomy but only 10 controls, when
their pair had normal bowel function. This difference was
highly significant statistically (p < 0.01, M c N e m a r ' s test).
Furthermore, 20 of the 27 assessed themselves as constipated but only 8 of the 10 controls. Fifteen cases but only
4 controls assessed themselves as severely constipated because they had consulted a doctor because of constipation, when their pair had not, the difference being significant (p < 0.05, M c N e m a r ' s test).

Correlation of boweI and bladder dysfunction


Cases were asked if their bowel or urinary frequency had
been altered after hysterectomy (Table 2). Twenty-two

a Varied 3 times daily to 3 times weekly


Age 30-69
Table 2. Post-hysterectomy: correlation of short-term changes of
bowel and bladder function
Urinary frequency

Increased
Not increased
Total

Bowel frequency
Decreased

Not decreased

Total

15
7
22

22
41
63

37
48
85

0~2, p < 0.05)


Table 3. Post-hysterectomy: correlation of long-term changes of

bowel and bladder function


Urinary frequency

Increased
Not increased
Total

Bowel frequency
Decreased

Not decreased

Total

8
2
10

19
56
75

27
58
85

(,~2, p<0.01)

claimed that their bowel frequency had reduced and 37


out of 85 said that their urinary frequency had increased
in the short term after the operation, including 15 who
noticed both changes. There is a significant association
(p < 0.05, Chi-squared test) between decreased bowel and
increased urinary frequency. N o t all of these changes
persisted, however. Ten claimed that they had a permanent increase in urinary frequency (Table 3), including 8
who had noticed both changes. This association was
highly significant (p < 0.01, Chi-squared test).

Correlation of bowel function after oophorectomy


Bowel function was examined in hysterectomy patients,
56 of w h o m had had an abdominal hysterectomy alone
and compared with 33 patients who had had an
o o p h o r e c t o m y in addition to their hysterectomy. Two
patients who had had a vaginal hysterectomy were excluded from analysis in this section. Bowel frequency,
laxative use and self-assessment of bowel function

230
showed no statistically significant difference between the
two groups. Nevertheless, women who had had an
oophorectomy in addition to their hysterectomy were
more likely to have an abnormal, firmer stool consistency; 10 women had abnormal stools after oophorectomy
compared with 1 control when their pair had not
(p < 0.05, McNemar's test).
There was no significantly increased tendency to have
associated bowel and bladder changes in patients who
had had an oophorectomy and a hysterectomy compared
to hysterectomy alone. Unilateral and bilateral oophorectomy were compared for bladder and bowel disturbance and did not have any statistically significant differences but the numbers were small.

Other comparisons
There was no significant difference between the hysterectomy cases and controls when tested for parity, number
of difficult births using instruments or Caesarean section,
the presence of urinary stress incontinence or the use of
a high-fibre diet which might have altered the bowel features of one or other group. There was no significant age
difference between those who had abnormal bowel function with those who did not.

Discussion
Bowel function varies markedly between populations and
within a given population. The bowel habit of our control
group is similar to those previously reported [5], the largest difference being a reduction in the use of laxatives,
perhaps part of the general decline in their use and the
general popularity of high-fibre diets [7]. Our previously
recorded results showed that women who have had a
hysterectomy were more likely to have less frequent bowel actions than an age-matched control group with a
trend towards constipation [4]. The present survey suggests that women who have had a hysterectomy are more
likely to have an abnormal bowel function which extends
not only to an abnormal frequency of defaecation and
abnormal stools but to an increassed tendency to consult
a doctor about constipation. The bowel disturbance is
not, however, severe enough to require increased recourse to laxative use.
Bladder and bowel symptoms were associated in our
group of patients. The increased frequency ofmicturition
and decreased frequency of bowel action presenting after
operation but not before suggest a c o m m o n aetiology for
the two problems. The one considered most likely to explain this occurrence is an interference of the autonomic
innervation of both viscera at risk of trauma in the pelvis.
The recovery of some of the cases with an increased association of the two changes in the remainder with the
passage of time intensifies the suspicion of a possible link
through autonomic nerve disturbance at operation.
Other possible mechanisms to be considered are the
psychological disturbance of hysterectomy but recent

prospective studies have shown that women are not likely


to become depressed after hysterectomy [8] and are even
likely to be less depressed than pre-operatively [9].
Some women may initially take laxatives for post-operative constipation and precipitate a vicious circle of
laxative abuse causing bowel atony resulting in the socalled "cathartic colon'. If this were so more laxative use
by the cases would be expected [10].
For the cases who had had an oophorectomy, the
only statistically significant difference was that women
who have had one or more ovaries removed were likely to
have an abnormal stool consistency. This might be taken
as evidence towards a hormonal pathogenesis for
changed bowel function because of a slower intestinal
transit. Women with slow transit constipation have been
found to be more likely to have raised serum prolactin
and lower plasma oestradiol levels [11]. Against this, it
has been shown that women who have a hysterectomy
have an earlier menopause [12]. There was no difference
between the ages of hysterectomy cases and controls with
abnormal bowel function and hysterectomy cases and
controls with normal function. Cases and controls in this
study had a similar obstetric history with the consequence that obstetric difficulty did not contribute to any
difference in the clinical features.
A mechanism for a similar pelvic nerve disturbance to
the one we envisage has been described by Catchpole [13]
in relationship to lower anterior resection. After this operation he found evidence of a partial autonomic denervation of the lower bowel. Cases of intractable constipation after hysterectomy have been found to have a seriously disturbed motility in the left colon but with no
upset in pelvic floor or sphincter function [14].
The parasympathetic innervation of the urinary bladder and left colon is derived from the sacral segments $2,
3 and 4, via the pelvic nerves from the inferior hypogastric plexus, and nerve fibres run forwards to innervate the
bladder and lower rectum and also pass upwards out of
the pelvis to innervate the upper rectum and left colon.
These fibres carry sensory fibres from both viscera. It is
conceivable that damage to the autonomic innervation
during pelvic surgery can result in functional disorders of
the colon from possible damage to the inferior hypogastric (pelvic) plexus which, in the female, is placed on each
side of the rectum, uterine cervix, vaginal fornix and posterior aspect of the urinary bladder and extends into the
base of the broad ligaments of the uterus. Furthermore,
Christensen and Schulze-Delrieu describe intramural
pelvic nerves which enter the bowel wall in the pelvis and
ascend through as much as 80% of the length of the colon
[15]. They describe numerous ganglia within the pelvic
parasympathetic outflow, some lying down within the
pelvic nerves on the mucosal surface, even of the distal
colon and others distributed throughout the pelvic
plexus. The location and orientation of these intramural
pelvic nerves make them potentially subject to trauma.
Events like constipation and childbirth, they suggest,
could stretch them to produce a mechanical cause for a
neuropathy. We believe that a similar stretch mechanism
causing pelvic nerve damage may be responsible for the
bowel function changes after hysterectomy.

231

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Vesico-urethral dysfunction after simple hysterectomy. Neurol
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physiology. Am J Obstet Gynecol 138:374-382
3. Gurnari M, Mazziotti F, Corazziari E, Badiali D, Alessandrini
A, Carenza L, Torsoli A (1988) Chronic constipation after
gynaecological surgery: a retrospective study. Ital J Gastroeneterol 20: 183-186
4. Taylor T, Smith AN, Fulton PM (1989) Effect of hysterectomy
on bowel function. Br Med J 299:300-301
5. Connell AM, Hilton C, Irvine G, Lennard-Jones JE, Misiewicz
JJ (1965) Variation of bowel habit in two population samples.
Br Med J 2:1095-1099
6. Yarnell JWG, Voyle GJ, Richards CJ, Stephenson TP (1981)
The prevalence and severity of urinary incontinence of women.
J Epidemiol Community Health 35:71-74
7. Eastwood MA, Brydon WG, Baird JD, Elton RA, Helliwell S,
Smith JH, Pritchard JL (1984) Fecal weight and composition,
serum lipids and diet among subjects aged 18 to 80 years not
seeking health care. Am J Clin Nutr 40:628 634
8. Coppen A, Bishop M, Beard R J, Barnard G JR, Collins WP
(1981) Hysterectomy, hormones and behavionr: a prospective
study. Lancet i: 126-128

9. Gath D, Cooper P, Day A (1982) Hysterectomy and psychiatric


disorder: levels of psychiatric morbidity before and after hysterectomy. Br J Psychiatry 140:335-342
10. Rawson MD (1966) Cathartic colon. Lancet i: 1121-1124
11. Preston DM, Rees LH, Lennard-Jones JE (1983) Gynaecological disorders and hyperprolactinaemia in chronic constipation
Gut 24:A480
12. Siddle N, Sarrel P, Whitehead M (1987) The effects of hysterectomy on the age of ovarian faiture. Fertil Steril 47:94-100
13. Catchpole BN (1988) Motor pattern of left colon before and
after surgery for rectal cancer: possible implications in other
disorders. Gut 29:624-630
14. Smith AN, Varma JS, Binnie NR, Papachrysostomou M (1990)
Disordered colorectal motility in intractable constipation following hysterectomy. Br. J Surg (in press)
15. Christensen J, Schulze-Delrieu K (1985) Nerves in the colon:
discovery and rediscovery. Gastroenterology 89:222-223

Mr. A. N. Smith
University Department of Surgery
Western General Hospital
Edinburgh EH4 2XU
UK

Int J Colorect Dis (1990) 5:232 235

Col6ree|al
Disease

9 Springer-Verlag 1990

H o w I do it

The endorectal advancement flap procedure


J . M . Stone 1 and S . M . Goldberg 2

Section of Colon and Rectal Surgery, Stanford University, Stanford, California, USA
2 Division of Colon and Rectal Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
Accepted: 13 August 1990

The technique of sliding rectal advancement flap was first


described for the treatment of rectovaginal fistula by Noble in 1902 [1]. In his original description, Noble advocated " . . . splitting the rectovaginal septum, dissecting the
lower end of the rectum from the vagina and drawing the
anterior wall down through and external to the a n u s . . . " .
Forty years later, Laird described the advancement of a
partial thickness segment of rectal wall to the perineal
skin [2]. This technique did not require the extensive mobilization of the Noble operation, however, the blood
supply of the narrow-based flap was tenuous. In its current state of evolution, we advocate the creation of a
broad-based, trapezoid-shaped flap consisting of internal
sphincter and circular muscle with its overlying mucosa
[3]. The flap is advanced to an area one centimeter distal
to the fistula. Properly performed, this technique provides a well vascularized flap that can be advanced to the
anal margin without tension.
The endorectal flap advancement procedure is based
on the premise that the key to healing any type o f rectal
fistula is closure of the rectal (high pressure) side of the
communication. The technique accomplishes this by permitting a tension-free, two-layer closure of healthy rectal
wall at the fistula site. Endorectal flap advancement
should therefore not be performed in cases with large
(greater than 2.5 cm) defects, where suture-line tension
would be too great, or in situations where healthy tissues
can not be approximated (radiation or neoplastic fistula,
or active rectal Crohn's disease) (Table 1). Additionally,
the procedure should not be performed in the presence of
acute inflammation. We recommend a waiting period of
at least 90 days after the development of a fistula to allow
inflammation to resolve. Spontaneous healing of the fistula occasionally occurs during this period. The endorectal flap advancement procedure has been most commonly performed for the treatment of rectovaginal
fistulas, but it may also be used in the treatment of difficult fistula-in-ano, rectoprostatic fistula, and traumatic
rectoperineal fistula.
Rectovaginal fistulas may be classified as simple or
complex based on the etiology, size and location of the

fistula (Table 2) [4]. In our practice, endorectal advancement flap is the technique of choice for simple rectovaginal fistula (traumatic or infectious etiology, defect less
than 2.5 cm in diameter, lower two thirds of vagina).
There are several attractive features of the endorectal
advancement flap procedure in this setting. N o perineal
wound is created so there is minimal pain and healing is
rapid. No sphincter division is necessary so sphincter
function is not impaired, and contour defects of the anal
canal are avoided. If a pre-existing sphincter defect is
present, the procedure is easily combined with an overlapping sphincteroplasty. N o protecting colostomy is
necessary.
Rectovaginal fistulas occur spontaneously in approximately 10% of women with Crohn's disease [5]. Although a pessimistic attitude towards surgical repair has
prevailed in the past, recent reports indicate that in selected
patients surgical repair of a Crohn's rectovaginal fistula
Table 1. Contraindications to endorectal flap advancement
Acute Inflammation
Excessive suture line tension
Defects > 2.5 cm
Anastomosis in diseased tissue
Radiation fistula
Neoplastic fistula
Active rectal Crohn's disease
Table 2. Classification of rectovaginal fistula [4]
Simple
Low or mid vaginal septum
<2.5 cm in diameter
Traumatic or infectious etiology
Complex
High vaginal septum
>2.5 cm in diameter
Etiology: inflammatory bowel disease, irradiation or neoplastic
Multiple organ involvement
> 2 previous attempts at repair

233
has a good chance of success. The main contraindications to repair of a rectovaginal fistula in a patient with
Crohn's disease are active Crohn's disease of the rectum
and acute perianal suppuration. We also do not advocate
repair if symptoms from the fistula are minimal. Using
these criteria, successful results can be expected in approximately two thirds of patients with Crohn's rectovaginal fistula [5, 6]. When the alternative to repair will
be proctectomy, the rationale for attempting an advancement flap is even stronger.
Approximately one third of our patients with rectovaginal fistula have required a combined advancement
flap and sphincteroplasty. Our overall success rate (primary healing) with the endorectal flap advancement technique is 83 %. The success rate correlates with the number
of previous repairs. The initial attempt was successful in
88% of the patients. In patients with one previous repair
a success rate of 85% was still achieved, however, after
two failed repairs, the success rate was only 55% [4].
Therefore the history of a failed attempt to close the
fistula would not dissuade us from making a second attempt with the endorectal flap advancement technique.
We now feel that multiple recurrent fistulas are probably
associated with a decreased blood supply due to scarring.
In this situation a more complex repair designed to bring
in adequately vascularized tissue would be necessary.
Parks has shown that infection of the anal glands is
the usually cause of fistula-in-ano [7]. All modern treatments, therefore, are designed to (1) lay open or excise the
length of the fistula track and, (2) destroy any remaining
cryptoglandular epithelium. Fortunately, this is easily accomplished for the majority of fistulas, because they arise
at the dentate line and follow an intersphincteric or low
transsphincteric course to the perineum. A simple "laying
open" technique, which may involve transection of the
internal sphincter and the lower portion of the external
sphincter, will reliably cure the fistula without significantly altering continence. Difficulties in fistula surgery
arise when the fistula courses above the majority of the
external sphincter (high transsphincteric fistula) or above
the levator muscles (suprasphincteric fistula). In this situation, simply laying open the fistula cuts enough sphincter muscle that incontinence usually results. Other special
situations may arise where it is important to preserve
all possible sphincter function. Examples of this are
women with anterior fistula, where the relative paucity of
sphincter mass makes division of any external sphincter
a risky endeavor, and patients with marginal continence
prior to fistula surgery. A multitude of approaches have
been developed for dealing with these situations including: flstulotomy with immediate sphincter repair, re-routing the fistula, slow elastic transection with seton, staged
fistulotomy with seton, and fistula excision with closure
of the internal opening. Unfortunately, no method has
been more than modestly successful. The most commonly
used method, seton placement, is attractive because of its
technical ease. However, multiple staged procedures are
frequently necessary, and the risk of incontinence is still
in the range of 30% [8].
The endorectal advancement flap procedure is an appealing option in these situations because it does not

require the division of any sphincter muscle and it can be


completed in a single operation. Although experience
with the endorectal advancement flap procedure for fistula-in-ano is limited, early results have been encouraging. In four recent series of patients with complex fistulain-ano, all had primary healing rates of greater than 85%
for patients without Crohn's disease [10-13]. Primary
healing did occur in some patients with Crohn's disease;
however, failures were more common. As with rectovaginal fistula, the primary factor in selecting Crohn's patients for repair is the absence of active rectal Crohn's
disease. Other factors such as anal stenosis, fissure and
other perianal fistula must be considered, but are not of
themselves contraindications to repair. It is unfortunate
that no studies have been performed comparing the endorectal advancement flap procedure with other methods
of treatment for fistula-in-ano.

Technique
The endorectal flap advancement procedure should not
be undertaken until the local inflammatory reaction has
completely subsided. A standard mechanical and antibiotic bowel preparation is given. After the induction of
general or regional anesthesia, a urinary bladder catheter
is inserted, and the patient is positioned prone over a hip
roll with the buttocks spread by tape. Antiseptic perineal
skin and vaginal preparation is performed. A perianal
field block with 0.25% bupivacaine is given to relax the
sphincters and minimize trauma from sphincter stretch.
In addition to the field block, intramuscular injections of
a 1:200000 epinephrine solution are made along the
planned routes of dissection. Exposure is gained with a
bivalve anoscope and illumination is greatly aided by the
use of a headlight (Fig. 1 a). The exact anatomy of the
fistula is determined under anesthesia by gentle probing
and palpation of the track. The internal opening and
fistula track are thoroughly curretted and tissue from the
track is sent to pathology. For fistula-in-ano, this may
require incising the external opening and following the
granulation tissue until the track can be easily probed.
The rectal flap, which will be proximally based, and
will consist of mucosa, submucosa, and circular muscle is
then outlined around the fistula (Fig. 1 b). The base of the
flap should be at least two times the width of the apex to
ensure an adequate blood supply. Mobilization of the
flap begins at the apex, approximately one centimeter
distal to the fistula, and is carried to the base with sharp
dissection (Fig. 1 c). Hemostasis is achieved with electrocautery. Troublesome bleeding from vaginal veins implies
the plane of dissection is too deep. It is important to
mobilize the flap at least four centimeters cephalad to the
fistula to prevent tension on the suture line. The rectal
mucosa and submucosa are elevated laterally on each
side from the underlying internal sphincter muscle
(Fig. 1 d). The cut edges of the internal sphincter and
circular muscle may be approximated in either a longitudinal or transverse fashion with interrupted 2-0 polyglycolic acid sutures (Fig. 1 e).

234

t'
posterior

posterior

posterior
3:

Icosa
d
~rnal
qincter

)robe in
stula track

internal
sphincter
approximated
longitudinally

posterior

posterior

\
\

~--mJ

circular muscle; e repair of internal sphincter and circular muscle;


f internal sphincter approximated transversely

Fig. 1 a - f . Repair of rectovaginal fistula, a Appearance and speculum insterted; b line of incision for mucosa and internal sphincter;

e flap mobilised; d dissection of mucosa from internal sphincter and

ani

:!:.!
.::.!:~

mucosa
.

internal opening :
:::

.~ctalis

.X.:

external sphincter

i:."

*X:':

internal sphincter

":
:v..

track
a

Fig. 2 a - e . Fistula m ano. a Preoperative state; b elevation of flap and closure of internal opening; e advancement and suture of flap

If anal incontinence was an associated problem, a


plication sphincteroplasty may be performed at this
point. A curvilinear incision is placed on the perineum to
follow the outer edge of the external sphincter muscle.
The sphincter is widely dissected free from its bed, care
being taken to preserve the branches of the pudendal
nerve as they enter the muscle posterolaterally. Areas of
fibrosis at the transected ends of the sphincter are left in
place. The muscle ends are then overlapped and secured
in place with matress sutures of 2-0 polyglycolic acid.

The rectal flap of mucosa, submucosa, and circular


muscle is advanced over the repaired area of internal
sphincter and circular muscle. Excess flap including the
fistula opening is excised. The flap is sutured in place
along both sides and the apex with interrupted 3-0 polyglycolic acid sutures (Fig. I f). The vaginal mucosa is left
open for drainage. If a concomitant plication sphincteroplasty was performed the wound outside the sphincters is
partially closed, and the remainder packed with fine
gauze. In no case is rectal packing used.

235
In the case o f fistula-in-ano (Fig. 2a), the external
track is opened completely to the level o f the sphincters.
The p o r t i o n o f the track r u n n i n g t h r o u g h the sphincter is
t h o r o u g h l y curretted and the internal opening is closed
(Fig. 2 b). The external p o r t i o n m a y be marsupialized but
is left open for drainage. A small m u s h r o o m catheter
placed one centimeter f r o m the internal opening m a y be
a useful adjunct. The elevated flap is then a d v a n c e d and
sutured to the a n o d e r m well below the level o f the internal opening (Fig. 2 c).
The creation o f a diverting s t o m a is n o t necessary. I f
plication sphincteroplasty was performed, a low residue
diet is used for the first week. I f sphincteroplasty was n o t
performed, the patient is allowed to c o n s u m e a regular
diet with bulk laxatives to avoid constipation.

References
1. Noble GH (1902) A new operation for complete laceration of
the perineum designed for the purpose of eliminating danger of
infection from the rectum. Trans Am Gynecol Soc 27: 357-363
2. Laird DR (1948) Procedures used in the treatment of complicated fistulas. Amer J Surg 76:701-708
3. Rothenberger DA, Christiansen CE, Balcos EG, Schottler JL,
Nemer FD, Nivatvongs S, Goldberg SM (1982) Endorectal
advancement flap for treatment of simple rectovaginal fistula.
Dis Colon Rectum 25:297-300
4. Rothenberger DA, Goldberg SM (1983) The management of
rectovaginal fistulae. Surg Clin N A 63:61 79

5. Radcliffe AG, Ritchie JK, Hawley PR, Lennard-Jones JE,


Northover JMA (1988) Anovaginal and rectovaginal fistulas in
Crohn's disease. Dis Colon Rectum 31:94-99
6. Morrison JG, Gathright JB, Ray JF, Ferrari BT, Hicks TC,
Timmke AF (1989) Results of operation for rectovaginal fistula
in Crohn's disease. Dis Colon Rectum 32:497 499
7. Lowry AC, Thorson AG, Rothenberger DA, Goldberg S M
(1988) Repair of simple rectovaginal fistulas: Influence of previous repairs. Dis Colon Rectum 31:676-678
8. Parks AG (1961) Pathogenesis and treatment of fistula-in-ano.
Br Med J 1:463-499
9. Parks AG, Stitz RW (1976) The treatment of high fistula-inano. Dis Colon Rectum 19:487-499
10. Wedell J, Meier zu Eissen P, Banzahf G, Kleine L (1987) Sliding
flap advancement for the treatment of high level fistulae. Br J
Surg 74:390-391
11. Shemesh EI, Kodner IJ, Fry RD, Neufeld DM (1988) Endorectal sliding flap repair of complicated anterior anoperineal
fistulas. Dis Colon Recum. 31:22 24
12. Jones IT, Fazio VW, Jagelman DG (1987) The use of transanal
advancement flaps in the management of fistulas involving the
anorectum. Dis Colon Rectum, 30:919-923
13. Reznick RK, Bailey HR (1988) Closure of the internal opening
for treatment of complex fistula-in-ano. Dis Colon Rectum
31:116 118
S.M. Goldberg, M.D.
Department of Surgery
University of Minnesota
1731 Medical Arts Building
Minneapolis, MN 55 402
USA

Int J Colorect Dis (1990) 5:236-240

Colorec/al
Disease
9 Springer-Verlag 1990

Review

Infectious diarrhoea
C.P. Conlon and T. E. A. Peto
Infectious Diseases Unit, Nuffield Department of Medicine, John RadcliffeHospital, Oxford, UK
Accepted: 10 September 1990

Introduction
Gastroenteritis is the most common cause of morbidity
and mortality worldwide especially in children in developing countries, and remains a common cause of hospital
admission in the UK. Although patients will usually present to physicians, they may present to the surgeon either
with rectal bleeding in association with diarrhoea or with
an acute abdomen. In this review, we will discuss the
different types of infectious gastroenteritis, the common
causative pathogens and the approach to management.
Diarrhoea may occur when there is an imbalance between the absorptive and secretory capacity of the gastrointestinal tract brought about by the presence of microbial pathogens or when pathogens cause inflammation and damage. Gastric acid is a useful protection
against gastrointestinal infection and helps to maintain
sterility of the gastric contents. However, when this barrier does not exist, such as in patients with partial gastrectomy or those taking H2 blockers or antacids, the inoculum for a given pathogen needed to cause disease may be
dramatically lowered [1]. Likewise, intestinal motility
helps to maintain a normal distribution and flow of the
normal bowel flora. It is well known that stasis will lead
to bacterial Overgrowth and subsequent malabsorption
syndromes. Also, anti-diarrhoeal agents may reduce the
effectiveness of antibiotics and prolong fever and diarrhoea [2].
The normal intestinal flora is composed mainly of
anaerobic bacteria (> 90% of the total) and a relatively
small number of aerobic bacteria [3]. If the normal flora
is altered, for example by antibiotics, the susceptibility to
infection by gut pathogens is increased [4]. Finally, the
intestinal mucosa is well served by lymphocytes and
phagocytes, and specific humoral immunity involves
secretory IgA and probably some IgG and IgM leaking
from villus vessels.
The pathogenicity of micro-organisms depends on
their ability to adhere to and invade enterocytes but also
on their secretion of various enterotoxins and cytotoxins.
Organisms also differ in terms of the inoculum required
to cause disease; Shigella generally has a very low inoculum (< 102 organisms) whereas Vibrio cholerae may need
to be ingested in large amounts (> 10 s organisms). The

various mechanisms of pathogenesis determine the types


of diarrhoeal illnesses seen with infection. The syndromes
can be classified into three broad types, although there is
considerable overlap with some pathogens:
1. Non-inflammatory diarrhoea, usually caused by enterotoxins, involving the proximal small bowel.
2. Inflammatory diarrhoea, where the colon is infected
primarily, and where there may be bacterial invasion and
often cytotoxins are involved.
3. Penetrating infections affecting the distal small bowel
often with major systemic symptoms.

Non-inflammatory diarrhoea
Most of the time, infections of the proximal small bowel
produce a secretory watery diarrhoea, often in association with nausea and vomiting. There are usually no
leukocytes in the stools. In cases of '"food poisoning",
ingestion of bacteria or their toxins causes symptoms
with little damage to the intestinal mucosa. Acute nausea
and vomiting with some strains of Staphylococcus aureus
or Bacillus cereus is due to the ingestion of pre-formed
enterotoxins and these may act centrally to produce vomiting [5]. However, food poisoning of less abrupt onset is
due to the formation of toxins in vivo in the intestines, as
is the case with Clostridium perfringens and some Bacillus
cereus strains [6].
The classic example of non-inflammatory diarrhoea is
cholera, caused by the elaboration of a potent enterotoxin by the organism Vibrio cholerae. The toxin has a
direct effect on the intestinal mucosa causing net secretion. This is achieved by stimulating the activity of adenylate cyclase causing a rise in cyclic AMP which in turn
causes an isotonic fluid to be secreted into the lumen [7].
Some strains of Escherichia coli (enterotoxigenic E. coli
ETEC) produce a heat labile toxin (LT) very like cholera
toxin as well as a heat stable (ST) toxin. LT activates
adenylate cyclase while ST activates guanylate cyclase [8,
9]. Other bacteria such as Vibrio parahaemolyticus and
some Shigella and Salmonella species produce enterotoxins that may exacerbate the diarrhoea they cause through
other mechanisms.

237
Some viruses, notably rotavirus and Norwalk-like virus, though usually causing problems in infants, can affect adults [10]. The virus appears to disrupt the absorptive cells at the villus tip while secretory cells in the crypts
remain healthy [11]. The decrease in absorption plus
probable disruption of brush border micro-enzymes
leads to net secretion into the lumen with little in the way
of inflammation.
Some non-inflammatory diarrhoea may be acute in
onset but the symptoms may persist. This may be the case
with parasites such as Giardia lamblia or Cryptosporidium. Although these parasites adhere more readily to
enterocytes than to colonocytes, the pathogenesis of the
diarrhoea they cause is unclear. Various hypotheses include damage to brush border disaccharidases or adherent parasites causing a physical barrier to absorption [12,

13].
Another important type of secretory diarrhoea is socalled "traveller's diarrhoea" which many people experience during or after a holiday abroad, particularly in
developing countries. This normally takes the form of
acute diarrhoea which is usually self-limiting. The most
common cause is probably ETEC, or enterotoxigenic
E. coli. However, there are many other causes of which
Giardia, Shigella, and Salmonella are probably the most
frequent [14].
Inflammatory diarrhoea
Some organisms produce inflammatory changes largely
in the colonic mucosa, leading to a dysenteric illness.
There may also be small bowel involvement, as is often
the case with Campylobacter and Salmonella species.
There is often abdominal pain, there may be blood in the
diarrhoea, and the stool usually contains pus cells. The
severity of inflammation depends on the invasiveness of
the organisms but, in addition, some organisms produce
cytotoxins. Shigella species can cause acute bacillary
dysentery with fever, bloody diarrhoea, and systemic
symptoms such as headache and malaise. The incubation
period is usually two to three days but may be longer. The
most severe disease is caused by Shigella dysenteriae, but
Shigella sonnei and Shigella boydii are more common in
the United Kingdom. There is usually only superficial
mucosal damage and bacteraemia is relatively rare. Diarrhoea may be exacerbated by the production of cytotoxins [15].
Some strains of Escherichia coli (enterotoxigenic
E. coli, ETEC) produce large amounts of cytotoxins similar to that produced by Shigella [16]. It is now clear that
many strains of E. coli produce diarrhoea by a variety of
means, not all involving the elaboration of toxins [17]. Of
particular note is the enterohaemorrhagic E. coli (EHEC)
that has been the cause of outbreaks of bloody diarrhoea,
with one serotype, O157, being associated with haemolytic-uraemic syndrome [18].
Campylobacter jejuni infection is now recognised to
be one of the most common causes of infective diarrhoea
[19]. The diarrhoea may be bloody and is often accompanied by cramping abdominal pain and fever. A very sim-

ilar clinical picture is produced by salmonella enterocolitis. Many salmonella species are capable of causing these
symptoms but Salmonella enteritidis, phage type 4, infections have increased markedly over the past few years.
Both campylobacter and salmonella infections can mimic
acute inflammatory bowel disease with bleeding and ulceration on sigmoidoscopy. Both may cause severe symptoms enough to persuade the clinician there could be an
acute abdomen and both have the potential for developing toxic megacolon [20, 21].
Some parasites may produce a dysentery-like illness,
the best known being Entamoeba histolytica. The ingestion of cysts is followed by excystation in the small bowel
and the invasion of the colonic mucosa by the trophozoites. Although both cysts and trophozoites may be
identified in the stool, rectal biopsy may be a more sensitive means of diagnosis. Other parasites may also cause
inflammatory diarrhoea, although all would be rare presentations in travellers returning to temperate regions.
Initial infection with schistosomiasis, particularly S. japonicum and S. mansoni may lead to bloody diarrhoea for
a few weeks and at this stage numerous ova should be
found in the stools. Inflammatory colitis may occasionally result from acute infection with Trichinella spiralis or
Strongyloides stercoralis and even acute malaria may
present with bloody diarrhoea.
Venereal diseases may cause proctitis and diarrhoea,
particularly in homosexual men [22]. Rectal gonorrhoea,
Herpes simplex infection and chlamydia all need to be
considered. Secondary syphilis and lymphogranuloma
venereum can also lead to diarrhoea, so appropriate cultures and serological tests may need to be performed.

Pseudomembranous colitis
Many antibiotics have been associated with mild diarrhoea. The symptoms are usually short-lived and the
mechanism of the diarrhoea is poorly understood. Sometimes, however, a severe colitis results and is associated
with pseudomembrane "plaques" on the colonic mucosa.
These are not always apparent macroscopically but are
usually evident on histological examination of colonic
biopsies. It is now known that pseudomembraneous colitis is due to the effects of toxins secreted by Clostridium
difficile [23]. This organism, though normally present in
about 3% of healthy people, may overgrow in the presence of antibiotics to which it is resistant. Although originally associated with lincomycin and clindamycin, any
antibiotic may predispose to pseudomembraneous colitis. Clostridium difficile produces two cytotoxins, A and
B, which are involved in pathogenesis; one of which can
be detected for diagnostic purposes by tissue culture techniques or a less sensitive latex test [24].
Invasive infections
In some infections, abdominal pain and systemic illness
are more marked than the disturbance of bowel function,
although diarrhoea usually occurs at some stage. These

238
patients are often unwell and bacteraemic, so blood cultures should always be obtained. Infection with Salmonella typhi leads to an acute illness with fever, abdominal
pain and headache. Other features of enteric fever, or
typhoid, such as skin rash and splenomegaly may develop
later and mental confusion and cough are often reported.
Although constipation does occur, diarrhoea is more
common [25]. Enteric fever may also be due to Salmonella paratyphi A or B. In these cases diarrhoea is more
of a feature [26].
Sometimes other "non-typhoid" salmonella and
Carnpylobacterfetus can become invasive and produce an
enteric fever-like illness when diarrhoea is not the dominant symptom [27]. Included in the differential diagnosis
are yersinia infections. Both Yersinia enterocolitica and
Yersinia pseudotuberculosis may present with acute diarrhoea in addition to fever and abdominal pain [28].
Many patients with yersinia bacteraemia have been
found to have other underlying diseases, such as cirrhosis
and there is an association between severe disease and
iron overload [29, 30].

Intestinal tuberculosis
Abdominal tuberculosis usually involves the peritoneum
but may involve any part of the gastrointestinal tract.
Clinical presentations include the acute abdomen due to
perforation or obstruction, chronic malabsorption and
subacute or chronic diarrhoea [31]. There is often evidence of recent or past pulmonary tuberculosis. The diagnosis of intestinal TB is difficult and usually depends on
obtaining tissue for histology and culture.

Invasive parasites
Many parasites affect the gut and may lead to abdominal
discomfort and diarrhoea, either acute or chronic. If
there is a history of foreign travel or if the patient is found
to have eosinophilia then parasites such as Strongyloides
stercoralis, Toxacara canis, Ascaris lurnbricoides etc.
should be sought.

end of their lives. Often this causes swinging fevers, increased weight loss, and intermittent fever in addition to
diarrhoea [36]. Finally zidovudine, an anti-retroviral
agent used to treat HIV, may produce diarrhoea in some
patients.

Management of infections diarrhoea

When patients present with suspected infectious diarrhoea, the main differential diagnosis is usually inflammatory bowel disease. However, other differential diagnoses such as ischaemic colitis, diverticulitis, coeliac disease and endocrine cause of diarrhoea such as carcinoid
or VIPoma must be considered. A careful history and
clinical examination should help to reduce this differential. A history of suspect food intake may be important,
particularly if other people in the party have been affected. Clearly, foreign travel should be detailed and any
recent antibiotics should be noted. Whether or not the
diarrhoea is associated with nausea, vomiting or abdominal pain may be important as may the presence of fever.
The presence of blood in the stool suggests a colitis and
a past history or family history of inflammatory bowel
disease should be sought. Examination is really directed
towards the state of hydration of the patient and any
clinical signs suggesting septicaemia or extra-gastrointestinal manifestations of disease. There may be evidence of
peritonism. Initial investigations should include stool cultures and stool microscopy and, ideally, at least three
stools should be examined. It is helpful to discuss the
need for special cultures with an infectious diseases specialist or a microbiologist at an early stage. Blood cultures should be taken, particularly if the patient is febrile,
and abdominal films should be obtained in those with
severe symptoms. The role of sigmoidoscopy is debatable, particularly as it is often impossible to distinguish
between inflammatory bowel disease and infective colitis
with the naked eye, but this procedure should be performed in those suspected of having pseudomembranous
colitis. Rectal biopsies may be helpful but the results, of
course, are not available immediately [37].

General measures
Diarrhoea in HIV infection

In addition to enteric pathogens noted in homosexual


men before the AIDS epidemic, other infections are well
recognised in those immunosuppressed by HIV [32]. The
coccidan parasites, Cryptosporidium and Isospora belli,
predominantly affect the small bowel leading to profuse
watery, chronic diarrhoea [33]. Many patients with AIDS
develop chronic diarrhoea for which no causive agent is
found and it may be that HIV itself leads to the diarrhoea, either directly or indirectly [34]. More recently a
new enteric parasite has been recognised in AIDS patients; Microsporidiurn bieneusi [35]. It is not yet clear
whether this is a cause of diarrhoea in these patients.
Many AIDS patients develop infection with Mycobacteriurn aviurn-intracellulare complex (MAC) towards the

The mainstay of management of acute diarrhoea is adequate fluid and electrolyte replacement which can often
be done with oral electrolyte solutions. This treatment
alone is usually sufficient for most acute non-inflammatory gastroenteritides. There is controversy as to whether
antimotility drugs and opiates should be used in this setting. While there is a fear that these drugs will increase the
risk of invasion and hence bacteremia, and that they
might predispose to the development of toxic megacolon,
the evidence on which to base these fears is lacking. There
is only one study showing that antimotility agents may
prolong symptoms and excretion of Shigella [2]. In most
cases these drugs may help to slow the diarrhoea and
provide symptomatic relief. Prostaglandin synthetase inhibitors, such as indomethacin, may be useful in some

239
enterotoxin-induced diarrhoea. These drugs reverse the
effects of enterotoxin on the adenylate cyclase and
thereby reduce secretion into the bowel lumen [38].

Antibiotics
The role of antibiotics in infective diarrhoea is also controversial. For most salmonella and campylobacter infections rehydration is all that is required as infections are
usually self-limiting. In addition, many organisms, particularly if acquired abroad, are multiply resistant to antibiotics. Antibiotics may prolong symptoms and the excretion of the organisms [39, 40].
There are, however, some infections for which appropriate antibiotics are indicated. For example, cholera will
improve with glucose, fluid and electrolyte therapy but
tetracycline in addition will reduce the duration of the
illness, Typhoid fever should be treated with parenteral
antibiotics to which the S. typhi is sensitive; this will vary
depending on the geographic origin of the infection.
Yersinia infections will usually respond to co-trimoxazole
or to chloramphenicol, but again the choice of agent will
be governed by culture and sensitivity results. If diarrhoea is the only symptom due to yersinia, antibiotics
may have little effect on the illness. Moderate and severe
infections with Shigella species settle more quickly with
appropriate antibiotics [41]. Although most campylobacters are sensitive in vitro to erythromycin, this drug appears to have little clinical efficacy in gastroenteritis
caused by these organisms [42].
Parasitic infections, in particular giardiasis or amoebiasis, require specific therapy. Both of the above parasites will usually respond to oral metronidazole but as
Entamoeba histolytica cysts are not killed by this drug, a
drug active against the cysts, such as diloxanide furoate,
is often given as well. Clostridium difficile, the causative
agent in pseudomembranous colitis, is usually sensitive to
metronidazole and vancomycin and both are equally efficacious when given orally [43]. The large cost difference
favours metronidazole but vancomycin may be needed
for relapsed disease or the rare metronidazole-resistant
strains. Intravenous vancomycin is probably not effective
and if a patient is unable to take medication orally, then
intravenous metronidazole should be used. It is also
necessary to stop the offending antibiotic.
Ill patients with diarrhoea who may have invasive
disease and who may, therefore, be bacteraemic might
benefit from empiric antibiotic therapy after appropriate
specimens have been obtained. In these circumstances,
the newer quinolone antibiotics, such as ciprofloxacin
and norfloxacin, show promise, particularly as they do
not appear to alter the normal gut flora appreciably
[44, 45]. Unfortunately, there are already reports of
Salmonella species that are resistant to quinolones and it
appears that Campylobacter species have moderate resistance to these antimicrobial agents [46, 47]. Some other
bacterial and parasitic infections may need specific treatment and patients with HIV-related diarrhoea may have
complex problems, so advice should be sought from an
infectious diseases physician or from a microbiologist.

Su~e~
The role of surgery is ill-defined. Clearly, surgery is indicated if there is good evidence of perforation or generalised peritonitis. The problem is that severe dysentery,
regardless of aetiology, may produce symptoms and signs
very similar to peritonitis or even perforation and a clinical distinction may be impossible. Sometimes infections
such as salmonella colitis may lead to the development of
a megacolon, but because the bowel was previously normal compared to that seen in inflammatory bowel disease, surgery may not be required. It is with these difficult
cases that clinical skill is required and in which there
should be good communication between surgeon and
physician. Frequent review by experienced senior clinicians may prevent the patient with infectious diarrhoea
from undergoing unnecessary procedures.

Public health
Any patient admitted to hospital with proven or suspected infective diarrhoea should, ideally, be nursed in
side room with "enteric" precautions, i.e. excreta should
be handled wearing gloves and aprons and there should
be strict hand washing after dealing in any way with the
patient. This will minimise the risk of staff becoming
infected and the risk of nosocomial spread of gastroenteritis. Cases of food poisoning or gastroenteritis with a
proven pathogen should be notified to the local public
health official, as should any food handler or health care
worker who presents with gastroenteritis.

Conclusions

The majority of people with infective diarrhoea, i.e. those


with food poisoning or "traveller's diarrhoea", are relatively straightforward and will usually settle with rehydration and observation. The main problems in the field
of infectious diarrhoea are with differential diagnosis,
particularly from inflammatory bowel disease. Controversy surrounds the use of anti-diarrhoeal agents and the
role of empiric antibiotics has yet to be defined. Finally,
the place of the surgery in the management of these conditions can be very difficult but a conservative approach
to surgical intervention is probably the best option.
New pathogens as causative agents of diarrhoea are
found every few years. The demand for mass-produced
and quick-cook foods is increasing and the rules regarding the preparation and storage of food are often not
followed. Also, travel is becoming easier and many more
people are visiting developing countries. For these reasons and others it is likely that the problem of infective
diarrhoea will continue to increase in the future. In addition to elucidating the pathogenesis of various forms of
infective diarrhoea, future research will be directed towards prevention, earlier diagnosis and the development
of better medical therapies for this problem.

240
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(1986) Further evidence associating hemolytic uremic syndrome
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22. Quinn TC, Stature WE, Goodell SE, Mkrtichian E, Benedetti
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AB (1978) Antibiotic-associated pseudomembranous colitis
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26. Meals RA (1976) Paratyphoid fever: A report of 62 cases with


several unusual findings and a review of the literature. Arch
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of Campylobacterfetus infection: Report of 5 cases and review
of the literature. Q J Med 49:431-442
28. Cover TL, Aber RC (1989) Yersinia enteroeolitica. N Engl J
Med 321:16-22
29. Foburg U, Fryden A, Kihlstrom E, Perrson K, Wieland O
(1986) Yersinia enterocolitica septicaemia: clinical and microbiological aspects. Scand J Infect Dis 18:269-279
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with Yersinia enterocolitica in patients with iron overload. Br
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a retrospective review of 109 cases in a district general hospital.
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32. Laughton BE, Druckmann DA, Vernon A, Quinn TC, Polk BF,
Modlin JF, Yolken RH, Barttlett JG (1988) Prevalence of enteric pathogens in homosexual men and without acquired immunodeficiency syndrome. Gastroenterology 94:984-993
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35. Lucas SB, Papadaki L, Conlon C, Sewankambo N, Goodgame
R, Serwadda D (1989) Diagnosis of intestinal microsporidiosis
in patients with AIDS. J Clin Pathol 42:885-887
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with the acquired immunodeficiency syndrome: concepts regarding acquisition and pathogenehis. J Infect Dis 151:179-181
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acute self-limited colitis from idiopathic inflammatory bowel
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40. Saraglon G, Bisno AL (1978) Salmonella bacteremia and gastroenteritis after oral ampicillin therapy for gonorrhoea. So
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41. Levine MM (1986) Antimicrobial therapy for infectious diarrhoea. Rev Infect Dis 8:$207-$216
42. Anders B, Lauer BA, Paisley JW, Reller LB (1982) Doubleblind placebo-controlled trial of erythromycin for treatment of
campylobacter enteritis. Lancet 1:131 - 1 3 4
43. Teasley DG, Gerding DN, Olson MM, Peterson LR, Gebhard
RL, Schwartz MJ, Lee JT Jr (1983) Prospective randomised
trial of metronidazole versus vancomycin for Clostridium difficile-associated diarrhoea and colitis. Lancet 2:1043-1046
44. Reeves DS (1986) The effect of quinolone antibacterials on the
gastrointestinal flora compared with that of other antibacterials. J Antimicrob Chem 18 [Suppl D]: 89-102
45. Pichler H, Diridl G, Wolf D (1986) Ciprofloxacin in the treatment of acute bacterial diarrhoea: a double-blind study. Europ
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46. Piddock LJV, Whale K, Wise R (1990) Quinolone resistance in
salmonella: clinical experience. Lancet 335:1459
47. Endtz HP, Mouton RP, Van der Reyden T, Ruijs GJ, Biever M,
Van Klingeren B (1990) Fluoroquinolone resistance in Campylobacter spp isolated from human stools and poultry products.
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Dr. T. E.A. Peto
Infectious Diseases Unit
Nuffield Department of Medicine
John Radcliffe Hospital
Headington
Oxford OX3 9DU
UK

Int J Colorect Dis (1990) 5:241

Coloreclal
Disease
9 Springer-Verlag 1990

Acknowledgement to referees
The Editors wish to express their thanks to the referees of papers published in this volume.
Their time and trouble is much appreciated.
T. Allen-Mersh, London
N. Armitage, Nottingham
A. T. R. Axon, Leeds
D. C. C. Bartolo, Edinburgh
C. I. Bartram, London
T. Bates, Ashford, Kent
R. W. Beart Jr, Rochester
R. H. J. Begent, London
M. Betzler, Heidelberg
J. Beynon, Bristol
J. Bingley, London
W. V. Bogomoletz, Reims
S. G. Bown, London
J.-C. Brunetaud, Lille
J. Burn, Newcastle-upon-Tyne
N. D. Carr, Swansea
J. Christiansen, Copenhagen
B. Cola, Bologna
T. G. Cooke, Glasgow
J. P. Cruse, London
B. J. Cummings, Toronto
J. H. Cummings, Cambridge
A. Cuschieri, Dundee
R. Dozois, Rochester
M. A. Eastwood, Edinburgh
G. Ekelund, Malmo
M. S. Elliot, Cape Town
H. Ellis, Cambridge
W. Enker, New York
H. J. Espiner, Bristol
W. G. Everett, Cambridge
R. G. Farmer, Cleveland
P. Farrands, Brighton
M. J. G. Farthing, London
E. Farthmann, Freiburg
L. P. Fielding, Waterbury
P. Finan, Leeds
I. G. Finlay, Glasgow

P. Frileux, Paris
F. P. Gall, Erlangen
D. Galloway, Glasgow
J. R. Garrett, London
N. M. Gibbs, Guildford
H.-S. Goh, Singapore
S. M. Goldberg, Minneapolis
P. H. Gordon, Montreal
J. D. Hardcastle, Nottingham
A. L. Harris, Oxford
M. Harris, London
R. J. Heald, Basingstoke
G. Hellers, Stockholm
M. M. Henry, London
U. Hildebrandt, Homburg
C. Hoyle, London
L. Hult6n, Goteborg
D. G. Jagelman, Fort Lauderdale
J. R. Jass, Auckland
M. A. Kamm, London
S. Karran, Southampton
M. R. B. Keighley, Birmingham
K. Kelly, Rochester
I. Kodner, St Louis
O. Kronborg, Odense
J. H. C. Kuijpers, Nijmegen
D. Kumar, Birmingham
M. Lise, Padua
S. Love, London
M. Lowry, London
D. Z. Lubowski, Sydney
J. R. McGregor, Glasgow
M. J. McMahon, Leeds
R. S. McLeod, Toronto
P. H. G. Mahieu, Brussels
C. G. Marks, Guildford
M.-C. Marti, Geneva
D. M. Melville, London

C. Meyer, Strasbourg
R. Miller, Bristol
R. W. Motson, Colchester
J. Neoptolemos, Birmingham
A. H. W. Nias, London
B. Nordlinger, Paris
G. D. Oates, Birmingham
T. Oresland, Goteborg
J. D. Oriel, London
J. H. Pemberton, Rochester
F. Penninckx, Leuven
J. Pezim, Vancouver
R. K. S. Phillips, London
J. M. Polak, London
A. Polglase, Malvern, Australia
R. E. Pounder, London
P. Quirke, Leeds
N. W. Read, Sheffield
J. Rogers, London
D. A. Rothenberger, Minneapolis
J.-C. Sarles, Marseilles
P. Schofield, Manchester
N. Shepherd, Gloucester
D. Skipper, London
M. L. Slevin, London
A. N. Smith, Edinburgh
C. Spence-Jones, London
R. Springall, London
I. C. Talbot, London
H. Thompson, Birmingham
J. P. S. Thompson, London
A. T6rnqvist, Malmo
A. Vernava, St Louis
D. W. Warrell, Manchester
N. S. Williams, London
S. Winawer, New York
B. Wood, Liverpool
N. A. Wright, London

242

Book reviews
Pefia, A.: Atlas of Surgical Management of Anorectal Malformations. Berlin, Heidelberg, New York: Springer 1990. XIII, 104 pp.,
85 figs., hardcover. DM 168.00, ISBN 3-540-97067-3
Alberto Pena is a craftsman and has conveyed both this and his
immense experience with anorectal malformations in his book. His
early work with DeVries led to a modified description of the pelvic
musculature based on extensive dissections and added to by identifying muscle components directly by means of electric stimuli. The
resulting description is refreshingly clear and of considerable practical importance in the surgical treatment of anorectal abnormalities.
The book is beautifully illustrated with clear drawings which elegantly illustrate normal and abnormal anatomy. The first chapter
describes the normal anatomy in considerable detail. Malformations are grouped into categories which influence their management
and potential outcome. Stages in the management of all lesions are
clearly described in algorithms for both male and female patients.
The author indicates preference for a split colostomy in the left iliac
fossa and eloquently justifies this in preference to a transverse
colostomy. Emphasis is given to the importance of making the
colostomy as high as possible so as not to interfere with the length
of the sigrnoid colon and rectum available for subsequent pull
through. The definitive procedure is Posterior Sagittal Anorectoplasty. This single operation has been modified to deal with malformations of every degree of severity. The essence of the procedure is
a sagittal incision precisely in the midline which allows a clear and
safe demonstration of the anatomy and does not damage either the
blood or nerve supply to the pelvic muscles. The importance of
electro-stimulation to identify the correct plane is stressed and the
author has developed a reliable device for achieving this. All the
procedures are clearly described and illustrated. The author's vast
experience has allowed him to identify small points of technique and
potential pitfalls, often absent in less detailed accounts. The only
shortfall was in the description of vaginal reconstruction in complicated cloacal abnormalities. This difficult procedure was not described with the degree of clarity found elsewhere in the book.
Post-operative management is described precisely and stresses the

importance of regular dilatations of the new anus until the


colostomy is closed. There is an excellent chapter on the management of faecal incontinence, an all too frequent complication of
earlier operations for anoreetal abnormalities. It is a shame that
tongterm results are not reported but as an atlas the book is a very
important contribution to the understanding of these complicated
abnormalities.
K. Holmes (London)

Lev, R.: Adenomatous polyps of the colon. Pathological and clinical


features. Berlin, Heidelberg, New York: Springer 1990. XVII,
136 pp., 35 figs., hardcover. DM 146,00, ISBN 3-540-96985-3
The adenomatous polyp represents one of the few examples in
human carcinogenesis of a well-defined precursor lesion whose detection and removal could greatly reduce the incidence of a common
malignancy within a population. Robert Lev presents a well-reasoned and authoritative review of colo-rectal adenomas, the main
interest of which lies in his balanced discussion of several problematical and controversial aspects. Although already well-rehearsed,
the arguments in favour of the adenoma-carcinoma sequence
clearly outweigh those against, but other topics are more evenly
balanced. For example, the management of the malignant polyp is
not as straightforward as some authors have suggested when one
takes into account the confidence limits of previous studies which
claim an absence of residual disease. The subject of colonoscopic
screening and the manpower and cost considerations is another
aspect to which Lev brings a common-sense approach. The book
includes succinct coverage of cell biology and genetics in relation to
adenoma formation and transmission, but a more up-to-date consideration of oncogene expression could have been provided. The
interesting question of clonality is only briefly addressed. These
slight caveats apart, this book offers a useful and comprehensive
account of colorectal adenomas which will be of interest to all
concerned in their diagnosis and management.
M. E Dixon (Leeds)

Announcement
14-16 February 1991 - Ft. Lauderdale/
Florida]USA

Colorectal Disease in 1991


An International Exchange of Medical and Surgical Concepts
For further information contact: The Cleveland Clinic Foundation, Department of Continuing Education, 9500 Euclid Avenue, TT-31, Cleveland, OH 44195-5241, USA. Telephone: (216)444-5696 (local), 1-800-762-8173 (Other)

242

Book reviews
Pefia, A.: Atlas of Surgical Management of Anorectal Malformations. Berlin, Heidelberg, New York: Springer 1990. XIII, 104 pp.,
85 figs., hardcover. DM 168.00, ISBN 3-540-97067-3
Alberto Pena is a craftsman and has conveyed both this and his
immense experience with anorectal malformations in his book. His
early work with DeVries led to a modified description of the pelvic
musculature based on extensive dissections and added to by identifying muscle components directly by means of electric stimuli. The
resulting description is refreshingly clear and of considerable practical importance in the surgical treatment of anorectal abnormalities.
The book is beautifully illustrated with clear drawings which elegantly illustrate normal and abnormal anatomy. The first chapter
describes the normal anatomy in considerable detail. Malformations are grouped into categories which influence their management
and potential outcome. Stages in the management of all lesions are
clearly described in algorithms for both male and female patients.
The author indicates preference for a split colostomy in the left iliac
fossa and eloquently justifies this in preference to a transverse
colostomy. Emphasis is given to the importance of making the
colostomy as high as possible so as not to interfere with the length
of the sigrnoid colon and rectum available for subsequent pull
through. The definitive procedure is Posterior Sagittal Anorectoplasty. This single operation has been modified to deal with malformations of every degree of severity. The essence of the procedure is
a sagittal incision precisely in the midline which allows a clear and
safe demonstration of the anatomy and does not damage either the
blood or nerve supply to the pelvic muscles. The importance of
electro-stimulation to identify the correct plane is stressed and the
author has developed a reliable device for achieving this. All the
procedures are clearly described and illustrated. The author's vast
experience has allowed him to identify small points of technique and
potential pitfalls, often absent in less detailed accounts. The only
shortfall was in the description of vaginal reconstruction in complicated cloacal abnormalities. This difficult procedure was not described with the degree of clarity found elsewhere in the book.
Post-operative management is described precisely and stresses the

importance of regular dilatations of the new anus until the


colostomy is closed. There is an excellent chapter on the management of faecal incontinence, an all too frequent complication of
earlier operations for anoreetal abnormalities. It is a shame that
tongterm results are not reported but as an atlas the book is a very
important contribution to the understanding of these complicated
abnormalities.
K. Holmes (London)

Lev, R.: Adenomatous polyps of the colon. Pathological and clinical


features. Berlin, Heidelberg, New York: Springer 1990. XVII,
136 pp., 35 figs., hardcover. DM 146,00, ISBN 3-540-96985-3
The adenomatous polyp represents one of the few examples in
human carcinogenesis of a well-defined precursor lesion whose detection and removal could greatly reduce the incidence of a common
malignancy within a population. Robert Lev presents a well-reasoned and authoritative review of colo-rectal adenomas, the main
interest of which lies in his balanced discussion of several problematical and controversial aspects. Although already well-rehearsed,
the arguments in favour of the adenoma-carcinoma sequence
clearly outweigh those against, but other topics are more evenly
balanced. For example, the management of the malignant polyp is
not as straightforward as some authors have suggested when one
takes into account the confidence limits of previous studies which
claim an absence of residual disease. The subject of colonoscopic
screening and the manpower and cost considerations is another
aspect to which Lev brings a common-sense approach. The book
includes succinct coverage of cell biology and genetics in relation to
adenoma formation and transmission, but a more up-to-date consideration of oncogene expression could have been provided. The
interesting question of clonality is only briefly addressed. These
slight caveats apart, this book offers a useful and comprehensive
account of colorectal adenomas which will be of interest to all
concerned in their diagnosis and management.
M. E Dixon (Leeds)

Announcement
14-16 February 1991 - Ft. Lauderdale/
Florida]USA

Colorectal Disease in 1991


An International Exchange of Medical and Surgical Concepts
For further information contact: The Cleveland Clinic Foundation, Department of Continuing Education, 9500 Euclid Avenue, TT-31, Cleveland, OH 44195-5241, USA. Telephone: (216)444-5696 (local), 1-800-762-8173 (Other)