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Int J Colorect Dis (1998) 13: 5760
Springer-Verlag 1998
O R I G I N A L A RT I C L E
C.-A. Vasilevsky P. Belliveau J. L. Trudel

B. L. Stein P. H. Gordon
Fistulas complicating diverticulitis
Accepted: 21 November 1997
Abstract This study was undertaken to assess the appropriate management of patients with diverticulitis complicated by fistula formation. A retrospective chart review
was conducted on patients with symptoms of a fistula who
presented between 1975 to 1995. There were 42 patients
(32 women, 76%; 10 men, 24%) who ranged in age from
46 to 89 years (mean 69.89.8). Six patients had multiple
fistulas. The types of fistulas included colovesical (48%),
colovaginal (44%), colocutaneous (4%), colotubal (2%),
and coloenteric (2%). Operative procedures consisted of
resection and primary anastomosis in 38 patients and a
Hartmanns operation in one. Three patients were managed
conservatively with antibiotics (two due to poor performance status, the third due to resolution of symptoms).
There were no operative deaths. The postoperative course
was uncomplicated in 69%, while 12 patients (31%) experienced 19 complications (40%). These consisted of urinary tract infection (9.5%), atelectasis (7.1%), prolonged
ileus (4.8%), arrhythmias (4.8%) and renal failure, myocardial infarction, pseudomembranous colitis, peroneal
nerve palsy, unexplained fever, pulmonary edema (2.4%
each). There were no anastomotic leaks and no deaths. Hospital stay ranged from 6 to 31 days (mean 12.37.6). Fistulas due to diverticulitis were safely managed by resection and primary anastomosis without mortality and with
acceptable morbidity in this series. Patients deemed to be
poor operative risks can be managed with a course of nonoperative treatment.
frant de fistule traits entre 1975 et 1995 ont t revus. Le

collectif comporte 42 patients: 32 femmes (76%) et 10
hommes (24%) gs de 46 89 ans (moyenne = 69,8 ans).
Six patients ont des fistules multiples. Les fistules prsentes sont colo-vsicales (48%), colo-vaginales (44%), colocutanes (4%), colo-tubaires (2%) et colo-entriques (2%).
Le traitement chirurgical a consist en une rsection et une
anastomose primaire chez 36 patients et une opration de
Hartmann chez un sujet. Trois patients ont t traits de
manire conservatrice avec des antibiotiques (2 en raison
dun mauvais tat gnral, le troisime en raison dune rsolution de la symptomatologie). Aucune mortalit opratoire nest dplorer. La priode post-opratoire a t sans
complication chez 69% des patients alors que chez 12 patients (31%), on relve 19 complications (40%). Ces complications consistent en une infection urinaire (9,5%), une
atlectase (1%), un ilus prolong (4,8%), des arythmies
(4,8%) et une insuffisance rnale, un infarctus du myocarde, une colite pseudo-membraneuse, une paralysie du
nerf pronien, une fivre inexplique, un oedme pulmonaire (2,4%) pour chacune de ces complications. Il ny a
aucune fuite anastomotique ni aucune mortalit. La dure
des sjours va de 6 31 jours (moyenne 11,5 jours). Les
fistules dues la diverticulite peuvent tre traites de manire sre par rsection et anastomose primaire sans mortalit et avec une morbidit acceptable dans cette srie. Les
patients prsentant de mauvais risques opratoires peuvent
tre traits de manire non opratoire.
Key words Diverticular disease Fistula Surgery

Rsum Cette tude a t entreprise afin de dterminer
le traitement optimal des patients porteurs dune diverticulite complique de fistule. Les dossiers des patients souf-
C.-A. Vasilevsky () P. Belliveau J. L. Trudel B. L. Stein

P. H. Gordon
Division of Colorectal Surgery, Department of Surgery,
McGill University, 3755 Cote St Catherine Road, Montreal,
QC H3T 1E2, Canada
Introduction
Diverticular disease is a very common problem. Fistulas

complicating diverticulitis are the result of a localized perforation into adjacent viscera and represent one of the rarer
complications of acute diverticulitis in 4 23% of patients
hospitalized with diverticular disease [1]. Among patients
undergoing surgery for diverticular disease 20% are found
to have some type of fistula [2]. These fistulas were initially managed by staged approaches [3], but with a bet-
58
ter understanding of the disease process and the principles

of colon surgery as well as the advent of never antibiotics
and anesthetic techniques, the modern approach has shifted
to resection and primary anastomosis.
The aim of the current study was to review the treatment and outcome of fistulas associated with diverticular
disease.
Materials and methods

This was a retrospective chart review conducted on patients who presented to five colorectal surgeons at four McGill University teaching hospitals between 1975 ad 1995. The study group consisted of
42 patients, of whom 32 were women (76%) and 10 were men (24%).
They ranged in age from 46 to 89 years with a mean of 69.89.8
years. Data were obtained concerning presenting symptoms and
signs, fistula type, diagnostic investigations, management, and postoperative complications.
Results
The types of fistulas encountered consisted of colovesical

in 23 patients (48%), colovaginal in 21 (44%), and colocutaneous in 2 (4%). Of the two patients with colocutaneous fistulas one had undergone a previous sigmoid resection while the other had undergone a previous transverse
colostomy for perforated diverticulitis and presented with
simultaneous colocutaneous and colovesical fistulas.
Colotubal and coloenteric fistulas were found in one patient each (2%). Multiple fistulas were found in six patients
(12%): five with simultaneous colovaginal and colovesical fistulas and the previously mentioned patient with a
colovesical and colocutaneous fistula.
Pneumaturia and fecaluria constituted the most common presenting symptoms in patients with colovesical fistulas in 18 and 10 out of 23 patients, respectively, followed
by abdominal pain in 7, dysuria in 4, and weight loss, diarrhea, and urine per rectum in 1 each. All patients with
colovaginal fistulas presented with vaginal discharge while
five complained of abdominal pain and two of diarrhea.
The two patients with colocutaneous fistulas presented
with stool draining through the abdominal wall while the
patient with a coloenteric fistula complained of abdominal
pain. Vaginal discharge was the presenting symptom of the
patient with the colotubal fistula. Duration of the presenting symptoms prior to surgery ranged from 7 days to
4 years with a mean of 4.37.4 months. Patients presented
with few physical signs, including an abdominal mass in
four patients and left lower quadrant tenderness in five.
Diagnostic evaluations which confirmed the presence
of the underlying fistulas are listed in Table 1. Cystoscopy
was diagnostic in 47.8% with colovesical fistulas. Toward
the latter part of this study, computed tomography became
more readily available and was diagnostic in 30.4%. Barium enema demonstrated the presence of a colovaginal fistula in 38%. Vaginography which was used in the latter
part of the study demonstrated the fistula in the three pa-
Table 1 Diagnostic investigations
Cystoscopy
Barium Enema
CT Scan
Ultrasound
Vaginoscopy
Vaginography
a
Colovesical
Colovaginal
11/23
8/23
7/23
1/23
47.8
34.8
30.4
4.3
8/21
4/21
3/21
6/21
3/21
38.0
19.0
14.3 a
28.6
14.3
Endovaginal ultrasound
tients in whom it was utilized. Barium enema was diagnostic for both colocutaneous fistulas and the coloenteric fistula while no study was helpful with the diagnosis of a
colotubal fistula.
On further examination of the data on the 23 colovesical fistulas, 8 were men (34.8%). Of the 15 women 60%
had undergone previous hysterectomy. Of the 21 women
with colovaginal fistulas 20 (95%) had undergone previous hysterectomy.
At laparotomy, 35.7% demonstrated evidence of localized peritonitis. One patient had a small mesenteric abscess
containing approximately 20 cc of pus which was not suspected preoperatively.
Thirty-eight patients (91%) underwent resection and
primary anastomosis. One patient underwent a Hartmann
procedure because of a large phlegmon found at the time
of operation for a colovaginal fistula. With respect to
colovesical fistulas the edges of the bladder opening were
simply oversewn in two layers without the need to excise
the bladder wall. An in-dwelling Foley catheter was left
for at least 7 days. In the case of colovaginal fistulas no attempt was made to close the opening in the vagina once
the fistulous connection had been excised. For the coloenteric fistula the edges of the involved areas of terminal
ileum were freshened and the opening closed. The colocutaneous fistulas were divided from the colon and the abdominal wounds curetted, packed open, and left to heal by
secondary intention. The patient with the colotubal fistula
underwent left salpingo-oophorectomy concomitant with
the sigmoid resection. Whenever possible, omentum was
used to separate the anastomosis from the site of previous
fistulization.
Three patients (two with colovesical fistulas and one
with a colovaginal fistula) were treated conservatively. The
two patients with colovesical fistulas were deemed to be
poor surgical candidates because of life-threatening cardiac or respiratory conditions. The patient with the colovaginal fistula was treated with antibiotics and her symptoms eventually resolved both clinically and radiographically. She was the one patient who had not undergone a
previous hysterectomy.
Hospital stay for patients who underwent operative
management ranged from 6 to 31 days with a mean of
12.37.6 days. There were no operative deaths. The postoperative course was uncomplicated in 69% while 12 patient experienced 19 complications (40%). These consisted
59
of atelectasis (7.1%), prolonged ileus (4.8%), arrhythmias

(4.8%), and renal failure, myocardial infarction, pseudomembraneous colitis, peroneal nerve palsy, unexplained
fever, pulmonary edema in 2.4% each. Four patients (9.5%)
experienced urinary tract infections; however, these included two recorded urinary tract infections in two patients
operated on for colovesical fistulas. Follow-up ranged
from 1 to 120 months, with a mean of 30.831.4 months,
in 97% (38 of 39) of operated patients. No patient developed a recurrent fistula.
Discussion
It is estimated that approximately 20% of all patients with

diverticulitis require operative intervention [4]. In one
study [5] the primary indication for operation was fistula
formation in 12%.
Colovesical fistulas constitute the most common type
of spontaneously occurring fistulas associated with diverticular disease, accounting for 33 65% in reported series
[2, 3, 6]. In contrast to other studies in the literature in
which the preponderance of males to females ranges from
2 : 1 to 6 : 1 [3, 7], for colovesical fistulas the present study
ratio was 1 : 2. A precise explanation of this discrepancy is
unclear. It has been suggested that there is a higher incidence in males because the presence of the uterus affords
protection against the development of colovesical fistulas
in females. However, in the current study 60% of the
women with colovesical fistulas had undergone previous
hysterectomies. As to why there was a high incidence of
fistulas in women with uteri in place, one can only speculate that perhaps they were atrophic and did not confer the
usual protection.
The most sensitive diagnostic study of colovesical fistulas has been found to be computed tomography because
it provides intraluminal and extraluminal pathological findings helpful in planning a subsequent operation [8]. It will
easily demonstrate the fistula by the presence of air in the
bladder without prior history of instrumentation. It has been
reported to be diagnostic in 90 100% of cases [9]. Computed tomography was not available as a diagnostic modality for patients in the early part of this review. Although
cystoscopy was diagnostic in 47.8% of patients, results
from this examination may be disappointing since it is suggestive of a fistula in only 10 46% [2, 10], demonstrating
edema or erythema, without actually visualizing the fistula.
Colovaginal fistulas constituted the second most commonly encountered fistula. Most patients with colovaginal
fistulas had undergone previous hysterectomy [3, 11], and
this was the case in 95% of patients with colovaginal fistulas in the present report. The mechanism by which a colovaginal fistula develops is thought to be through inflammation and abscess of the sigmoid colon, which becomes
adherent to the vagina resulting in fistula formation [12].
Colcock and Stahmann [2] found that patients who had
undergone previous hysterectomy and developed a colovaginal fistula secondary to diverticular disease may have
no other symptoms other than fecal vaginal discharge, as

was evident in the present series.
Although barium enema successfully established the diagnosis in 38%, it has been found that this examination is
generally doomed to failure because the barium is too thick
and not enough pressure can be exerted to fill the channel
[11]. Overlapping loops of bowel may obscure visualization of the fistulous tract [14]. Nonetheless, barium enema
has been found to be diagnostic in 34 48% of reported series [3, 15]. Sigmoidoscopy and colonoscopy, although
useful in excluding other diagnoses such as malignancy,
usually fail to visualize the fistula [10]. The opening in the
vaginal vault has been found at or near the apex of the vagina by vaginoscopy and was present in 28.6% of our patients. A visible vaginal vault opening has been reported
in 75 87% in other series [3, 15]. Vaginography in which
a Foley catheter is inserted into the vagina and filled with
water soluble contrast can easily visualize the fistula and
the portion of bowel involved. It is useful in outlining multiple fistulas [11]. Advantages include simplicity, lack of
complications, easy entrance of contrast into narrow tracts,
and no problems with overlapping bowel loops obstructing visualization of a fistulous tract as is encountered with
barium enema. This was utilized successfully in three patients in the later years of the present study. Grissom and
Snyder [11] in a review of several series has reported 90%
accuracy compared to 49% with barium enema. A recent
study [16] reported a sensitivity of 79%. It was nonetheless recommended as the initial investigation of choice in
patients with clinically suspected vaginal fistulas. Simultaneous flexible fiberoptic vaginoscopy and colonoscopy
have been used successfully, in which a gastroscope is inserted into the vagina [11]. The colonoscope is passed peranally and is used to identify the light transmitted through
the fistula via the gastroscope.
Colocutaneous fistulas have been found to occur almost
exclusively as a complication of previous resection for diverticulitis in approximately 6% of patients [2, 17]. The
incidence is higher in patients in whom operation is performed in the presence of acute perforation or abscess.
Other factors reported to be associated with persistence of
fistulas include distal obstruction, sepsis, presence of unsuspected carcinoma, and Crohns disease [17]. Distal obstruction caused by anastomosis to a retained narrow-caliber distal sigmoid instead of the rectum has been found to
be responsible for persistent fistulas [17]. Colocutaneous
fistulas may also result from percutaneous drainage of diverticular abscesses without subsequent resection [10].
Signs or symptoms other than external drainage of feces
are absent in over 50% of patients [10].
With respect to coloenteric fistulas, Colcock and Stahmann [2] found that all patients had involvement of the terminal ileum, as occurred in this study. At the time of definitive colonic resection, five of six patients had symptoms referable to the fistula, and barium enema was positive in two of five patients. Simple closure of the opening
in the small bowel may be accomplished if the bowel lumen is not compromised [10]; otherwise limited resection
is required.
60
Colotubal fistulas are exceedingly uncommon and difficult to diagnose, as evidenced by the lack of positive findings on any of the employed diagnostic investigations. The
single example of a colotubal fistula in our series presented
with purulent vaginal discharge, and this is in keeping with
those previously reported in the literature [18]. Ingestion
of activated charcoal, however, may provide a simple noninvasive approach for diagnosis [18].
The present trend in management of internal fistulas associated with diverticulitis is primary resection and anastomosis, as originally reported by Woods et al. [3]. This
recommendation is supported by the present study. It is imperative to resect the entire sigmoid colon to ensure removal of the high-pressure zone and in many circumstances to mobilize the splenic flexure to ensure a tensionfree anastomosis [19], thus establishing an anastomosis
between the distal descending colon and proximal rectum.
Woods et al. [3] found a significant increase in the number of one-stage resections performed, with no change in
the complication rate over decades of observation.
Three of the patients in the present study were treated
nonoperatively with intravenous antibiotics. Previous experimental studies performed on animals suggest that
colovesical fistulas can be well tolerated except in the presence of distal urinary or gastrointestinal obstruction [20].
Amin et al. [21] treated 4 of 16 patients with antibiotics
and followed them for 3 14 years. No life-threatening episodes of bacteremia or significant renal insufficiency were
observed. It was concluded that nonsurgical treatment is a
viable option in selected patients who can be maintained
on antibiotics periodically, as was the case in three patients
in the present study.
Conclusion
Internal fistulas secondary to diverticular disease can be

treated successfully with acceptable morbidity and mortality by resection and primary anastomosis. In patients
deemed to be poor operative candidates a course of nonoperative treatment is an acceptable method of management. Repeated courses of antibiotics can usually prevent
ascending urosepsis.
Acknowledgement This research was, presented at the 65th Annual Meeting, Royal College of Physicians and Surgeons September
1996, Halifax, Nova Scotia.
References
1. Goligher J (1984) Surgery of the anus, rectum and colon, 5th
edn. Bailliere, Tindall and Cassel, London
2. Colcock PB, Stahmann FD (1972) Fistulas complicating diverticular disease of the sigmoid colon. Ann Surg 175: 838 846
3. Woods RT, Lavery IC, Fazio VW, Jagelman DG, Weakley FL
(1988) Internal fistulas in diverticular disease. Dis Colon Rectum 31: 591 596
4. Chappuis CW, Cohn I Jr (1988) Acute colonic diverticulitis. Surg
Clin N Am 68: 301 313
5. Auguste LJ, Wise L (1981) Surgical management of perforated
diverticulitis. Am J Surg 141: 122 127
6. Bacon HG, Shindo K (1971) Surgical management of pseudodiverticulitis of the colon. Surg Gynecol Obstet 132: 1049 1051
7. Steel M, Deveney C, Burchell M (1979) Diagnosis and management of colovesical fistulas. Dis Colon Rectum 22: 27 30
8. Jarrett TW, Vaughan ED (1995) Accuracy of computerized tomography in the diagnosis of colovesical fistula secondary to
diverticular disease. J Urol 153: 44 46
9. Morris J, Stellato TA, Haaga JR, Lieberman J et al (1986) The
utility of computed tomography in colonic diverticulitis. Ann
Surg 204: 128 132
10. Kurtz DI, Mazier WP (1990) Diverticular fistulas. Semin Colon
Rectal Surg 1: 93 96
11. Grissom R, Snyder TE (1991) Colovaginal fistula secondary to
diverticular disease. Dis Colon Rectum 34: 1043 1049
12. Small WP, Smith AW (1975) Fistula and conditions associated
with diverticular disease of the colon. Clin Gastroenterol 4: 171
199
13. Whiteway J, Morson BC (1985) Pathology of the aging: diverticular disease. Clin Gastroenterol 14: 829 846
14. Rothman D, Dedick P (1988) Case report: vaginography for
colovaginal fistula. N J Med 85: 227 228
15. Wychules AR, Pratt JH (1966) Sigmoidovaginal fistulas: a study
of 37 cases. Arch Surg 92: 520 524
16. Giordano P, Drew PJ, Taylor D, Duthie G, Lee PW, Monson JR
(1996) Vaginography investigation of choice for clinically suspected vaginal fistules. Dis Colon Rectum 39: 568 572
17. Fazio VW, Church JM, Jagelman DG, Weakley FL, Lavery IC,
Tarazi R, van Hillo M (1987) Colocutaneous fistulas complicating diverticulitis. Dis Colon Rectum 30: 89 94
18. Huettner PC, Finkler NJ, Welch WR (1992) Colouterine fistula
complicating diverticulitis. Charcoal challenge test aids in diagnosis. Obstet Gynecol 80: 550 552
19. Benn PL, Wolff BG, Ilstrup DM (1986) Level of anastomosis
with recurrent colonic diverticulitis. Am J Surg 151: 269 271
20. Heiskell CA, Ujiki GT, Beal JM (1985) Am J Surg 129: 316
318
21. Amin M, Nallinger R, Polk HC (1984) Conservative treatment
of selected patients with colovesical fistulas due to diverticulitis. Surg Gynecol Obstet 159: 442 444
T. Watanabe Y. Kubota T. Muto
Substance P containing nerve fibers in ulcerative colitis
Accepted: 15 August 1997
Abstract The distribution of and morphological changes

in substance P containing nerve fibers were examined immunohistochemically in the colonic mucosa of ulcerative
colitis (UC) patients. Quantitative and morphological
changes in substance P fibers were analyzed by digitized
morphometry. The linear density of substance P fibers
was significantly greater in the UC group (19.4 1.2 m/
1000 m2) than in the Crohns disease group (10.1 1.2 m;
P < 0.01) and the control group (8.4 0.8 m; P < 0.01).
Analysis of the UC group showed that the degree of inflammation affected the linear density of substance fibers,
with moderate cases presenting the highest linear density and severe cases the lowest. Substance P fibers were
thickened and coarse in UC; they were significantly wider
in the UC group (2.50.5 m) than in the Crohns disease
group (1.50.2 m; P < 0.01) and the control group
(1.2 0.1 m; P < 0.01). In conclusion, alterations in substance P containing nerve fibers, as evidenced by both the
linear density and morphology, may play some role in the
pathogenesis of UC.
Crohn et 8,4 0,8/1000 m2 dans le groupe contrle)

(P < 0.01). Une analyse du groupe de patients atteints de
recto-colite-ulcro-hmorragique montre que le degr
dinflammation affecte de manire linaire la densit en fibres Sub P: les biopsies provenant de patients atteints dune
colite modre prsentent la plus haute densit linaire
alors que ceux porteurs dune colite svre montrent la plus
faible densit linaire. Les fibres Sub P sont paissies en
cas de recto-colite et il y a une augmentation significative
dans la largeur des fibres Sub P dans le groupe de rectocolite 2,5 0,5: colite ulcro-hmorragique versus 1,5 0,2
dans le groupe Crohn et 1,2 0,1 m dans le groupe
contrle (P < 0,01, P < 0.01). En conclusion, les altrations
dans les fibres nerveuses contenant la substance P telles
que mises en vidence la fois par des altrations de la
densit linaire et de la morphologie peuvent jouer un rle
dans la pathognse de la recto-colite-ulcro-hmorragique.
Key words Human colon Neuropeptide Substance P

Ulcerative colitis Inflammatory bowel disease
Introduction
Rsum La distribution et les changements morphologiques dans des fibres nerveuses contenant la subsance P
(Sub P fibres) ont t examins de manire immuno-histochimique au niveau de la muqueuse colique de patients porteurs de recto-colite-ulcro-hmorragique. Afin dvaluer
les changements quantitatifs et morphologiques des fibres
Sub P, une analyse morphomtrique a t ralise. La
densit linare des fibres Sub P est significativement
augmente en cas de recto-colite-ulcro-hmorragique en
comparaison un groupe de patients atteints de maladie de
Crohn et dun groupe contrle (19,4 1,2 en cas de rectocolite-ulcro-hmorragique versus 10,1 1,2 en cas de
T. Watanabe ()1 Y. Kubota T. Muto
Department of Surgery, University of Tokyo, Tokyo, Japan
Present address:
1
3-15-5-620 Nishi-shinjuku, Shinjuku, Tokyo, Japan 160
The enteric nervous system is composed of a vast network

of neurons widely distributed throughout the gut [1]. The
interactions between these neurons are mediated by peptide or nonpeptide neurotransmitters. Among these neurotransmitters neuropeptides have received considerable attention in terms of their regulatory functions in the intestinal immune system [2 12]. A number of studies have revealed that neuropeptides modify both acute and delayed
inflammatory responses by modulating the activities of
various immunocytes. Disturbances in the enteric nervous
system are therefore considered to underlie the etiology
and pathogenesis of several inflammatory diseases.
Although the etiology remains to be clarified, it is believed that an abnormal immune response plays an important role in the pathogenesis of ulcerative colitis (UC) [13].
There is considerable evidence that both the concentrations
and the distributions of colonic neuropeptides are altered
in UC patients [2, 14 16]. However, most of these studies
62
have used radioimmunoassay as the quantitative method

of analysis, and results were not correlated with the amount
or distributions of neuropeptide containing nerve fibers in
the colonic mucosa.
To clarify the altered distribution of substance P (Sub P)
containing nerve fibers we applied digitized morphometric analysis to specimens immunostained for Sub P.
Sub P is the most extensively characterized neuropeptide
in relation to inflammatory diseases and has been studied
in great detail in the context of numerous disorders such
as arthritis and bronchitis. However, few studies have been
performed to identify Sub P containing nerve fibers in the
UC colon. To determine quantitative changes in nerve fibers we calculated the linear density of fibers, defined as
the total length of nerve fibers per unit area (m/1000 m2)
in the lamina propria. In addition, to evaluate morphological changes in Sub P containing nerve fibers in UC, the
width of nerve fibers was measured by digitized morphometry and compared between groups.
Table 1 Characteristics of patient population and surgical specimens

UC
No. of patients
20
Male/female
9/11
CD
Control
25
5/3
15/10
Age (years)
Mean
Range
28.1 3.4
11 44
38.1 4.1
20 51
54.1 4.4
16 81
Anatomical origin
No. of specimens
Ascending
Transverse
Descending
Sigmoid
Rectum
70
15
18
14
15
8
20
5
5
3
3
4
39
3
3
7
14
12
Slides were washed in MPBS and counterstained in hematoxylin for

10 s. The sections were dehydrated and finally mounted in synthetic medium. The specificity of the staining was confirmed by absorption test. Immunostaining of Sub P (Sigma) in nerve fibers was completely eliminated by previous absorption with Sub P.

Linear density of SP fibers
Tissue material
Fresh colonic specimens were obtained during surgery from 20 UC
patients. Specimens were also collected from 8 patients with Crohns
disease (CD) and 25 colorectal cancer patients as controls. In the UC
and the CD groups samples were collected from each segment of the
large bowel to obtain areas free of disease or with different degrees
of inflammation. From each patient in the control group a single specimen was obtained from each segment of the large bowel which was
free of malignancy.
Tissue fixative and processing
Each full-thickness colonic sample was immediately fixed in Hollandes fixative for 4 h. These were routinely processed and embedded in paraffin after fixation. Our preliminary study revealed that
fresh tissues and quick processing were essential to obtain consistent and reproducible, high-quality staining of enteric nerves. Sections of all tissues were routinely stained with hematoxylin and
eosin and were examined before digitized morphometric analysis.
Final diagnosis of the disease was made on the basis of histological
findings.
Immunohistochemistry
Immunohistochemistry was carried out by the avidin-biotin peroxidase complex (ABC) technique, using 5-m-thick sections. All dilutions of reagents were made in modified phosphate-buffered saline
(MPBS; NaCl 180 g/l, NaH2PO4 32 g/l, K2HPO4 188 mg/l with
20 mg/l merthiolate). The sections were saturated with nonimmune
goat serum diluted 1 : 10 in MPBS for 30 min to saturate nonspecific binding sites. Primary antibodies were then applied against Sub P
(rabbit IgG, antisubstance P; Eugene Tech International; 1 : 3000).
After the sections had been incubated overnight in a humidified
chamber, biotynilated affinity-purified goat anti-rabbit IgG (1 : 400;
Dakopatts) with 5% human serum was applied to the tissue section.
Incubation proceeded for 30 min, followed by washing in MPBS for
15 min. This was followed by incubation with freshly preformed
ABC (avidin DH-biotinylated peroxidase; Vector Laboratories) for
30 min and washing with three changes of MPBS for 15 min. The
ABC was made visible by the diaminobenzidine (Sigma) method.
The total length of Sub P fibers in the lamina propria was measured
in each visual field in which Sub P fibers were observed, and they
were cut perpendicular to the mucosal surface so that the whole of
the mucosa was visible. Digitized morphometry (Olympus SP500)
was used to measure five different visual fields in each specimen,
observers being blinded in respect with the patient group and mucosal site. To evaluate the variable densities of nerve fiber distribution
we calculated the linear density of Sub P fibers, defined as follows:
linear density of Sub P fibers (m/1000 m2) = (total length of Sub P
fibers in a visual field)/(area of lamina propria in which Sub P fibers
are observed). The linear density of Sub P fibers was calculated in
each specimen. However, since different numbers of specimens were
collected from each patient, the results may have been skewed by inclusion of a high number of specimens from a smaller number of patients. Therefore the average linear density of Sub P fibers per each
patient was calculated to confirm that the results were not biased because of selection of specimens from UC patients.
Width of Sub P fibers
As a parameter to evaluate morphological changes of nerve fibers,
the width of fibers was measured and compared between groups. In
each specimen the maximum width of a fiber was measured in ten
different fibers, and the average of these measurements was calculated.
Effects of site and inflammation in UC
The degree of inflammatory disease activity was assessed in a consistent manner by a single and blinded investigator. The degree of
inflammation was rated semiquantitatively as follows: (a) none, no
inflammatory changes present; (b) mild, slight to moderate increase
in the density of infiltrating cells; (c) moderate, increased inflammatory cells, presence of lymphoid aggregates in the lamina propria,
and a few crypt abscesses; and (d) severe, dense inflammatory infiltrates, frequent ulceration, and crypt abscesses. All surgical specimens of the large bowel were classified as ascending, transverse, descending, sigmoid colon, or rectum according to anatomical origin.
Table 1 shows the characteristics of the patient population and surgical specimens.
63
Fig. 1 Sub P containing fibers (arrows) in the lamina propria

Fig. 2 Sub P containing nerve fibers in the lamina propria in UC (a)
and control (b)
Statistical analysis
Statistical analysis was performed by one-way analysis of variance
and Duncans new multiple range tests were used, where appropriate. Data in the figures and tables are expressed as mean SEM.
Results
Sub P fibers were identified as long filaments in the lamina

propria, some of which contained small Sub P positive vesicles (Fig. 1).
Effect of disease
The linear density of SP fibers
Sub P fibers were observed more frequently in UC, and
there was a significant increase in the linear density of Sub
P fibers in the UC group (19.4 1.2, UC; 10.1 1.2, CD;
8.4 0.8 m/1000 m2, controls; each P < 0.01; Figs. 2, 3).
The average linear density of Sub P fibers per patient revealed the same result, with the UC group presenting the
highest density (18.1 1.2, UC; 9.6 0.9, CD; 8.4 0.6 m/
1000 m2, controls; each P < 0.01; Fig. 4).
Morphological changes in SP fibers
Morphological changes in Sub P fibers were evident in UC.
Sub P fibers were usually more tortuous and densely immunostained than fibers from control specimens (Fig. 5).
Fig. 3 The linear density of Sub P fibers (mean SEM). Data points,
specimens. Sub P fibers were significantly increased in UC (P < 0.01)
To evaluate these morphological changes of fibers the

width of Sub P fibers was measured. Figure 6 shows the
mean width of Sub P fibers (2.5 0.5, UC; 1.5 0.2, CD;
1.20.1 m, controls; each P < 0.01) They were significantly wider in the UC group than in other groups; however, the CD group they were also significantly wider than
in (P < 0.05).
64
Fig. 4 The average linear density of Sub P fibers of each patient

(mean SEM). Data points, patients. The average linear density of
Sub P fibers was significantly increased in UC (P < 0.01)
Fig. 6 Mean width of Sub P fibers. The UC group showed significantly greater width than CD and control groups (P < 0.01). CD group
also showed significantly greater width than the control group
(P < 0.05)
Fig. 7 The linear density of Sub P fibers in each segment according to anatomical origin (mean SEM). The UC group showed a
greater linear density in the distal colon and rectum, while no significant differences were observed in the control group. * Significantly different from ascending (P < 0.05)
Fig. 5 Morphological changes of Sub P fibers in UC. Fibers were

thick and more densely immunostained in UC
Effects of site and inflammation in UC

Effect of site
The linear density of Sub P fibers differed significantly according to the segment of the large bowel in the UC group
(14.51.1, ascending; 16.81.5, transverse; 23.4 1.1, de-
scending; 23.3 3.8, sigmoid; 24.4 5.6 m/1000 m2,

rectum). On the whole, the distal (descending and sigmoid)
colon and rectum had a tendency to greater linear densities
than the proximal (ascending and transverse) colon. However, the anatomical origin did not affect the distribution
of Sub P fibers in the control group. There were no significant differences in linear density between any two segments in the control group (7.63.5, ascending; 8.63.4,
transverse; 8.12.5, descending; 7.41.1, sigmoid; 9.2
1.4 m/1000 m2, rectum; Fig. 7).
65
Table 2 Variation in the degree of inflammation in each segment of
the colon and rectum (number of specimens; n =70)
Site
Degree of inflammation
None
Mild
Moderate
Severe
Ascending
Transverse
Descending
Sigmoid
6
1
1
0
6
6
3
3
3
10
9
4
10
1
Total
20
33
Effect of the degree of inflammation

The effects of the degree of inflammation on the linear density of Sub P fibers were evaluated in the UC group, with
70 specimens classified into four grades according to their
histological findings (none, 8 cases; mild, 20 cases; moderate, 33 cases; severe, 9 cases). Table 2 shows variations
in the degree of inflammation of the specimen in each segment of the colon and rectum. The distal colon and rectum
had a tendency to contain specimens with a higher degree
of inflammation than the proximal colon. All but one case
showing severe inflammation came from the distal colon
or rectum. The linear density of Sub P fibers showed the
highest value in moderate cases (18.2 1.4, none; 17.9
1.6, mild; 23.9 1.9, moderate; 6.6 2.2 m/1000 m2, severe; Fig. 8), while that severe cases was significantly
lower than in moderate cases (P < 0.01).
Discussion
It is believed that abnormal immune response plays an important role in the pathogenesis of UC [13]. With progress
in understanding their immunomodulatory functions, neuropeptides have received considerable attention in the
pathogenesis of UC. Previous investigations have reported
various changes in enteric neuropeptides in inflammatory
bowel disease patients [14 24]. However, the precise alteration of neuropeptides in UC still remains controversial.
These discrepancies may be due to technical problems associated with extracting neuropeptides from tissues. Most
previous studies have used radioimmunoassay as the
method of quantitative analysis, and with radioimmunoassay there exists the possibility of tissue extraction altering
neuropeptide content. Also, the specificity and sensitivity
of various radioimmunoassays for neuropeptides may vary,
yielding results which are not comparable.
To avoid these technical problems Kubota et al. [25, 26]
used digitized morphometric analysis, to quantify enteric
nerve fibers immunohistochemically stained for vasoactive intestinal peptide. Employing an immunohistochemical method, tissues are fixed immediately after resection,
thereby permitting satisfactory preservation of neuropeptides from fresh specimens. The immunohistochemical
method can also demonstrate both the distribution of and
morphological changes in nerve fibers. Quantitative anal-
Fig. 8 The linear density of Sub P fibers according to the degree of

inflammation (mean SEM). Moderate cases tended to show higher linear density, but difference was not statistically significant. There
was a significant decrease in severe cases (P < 0.01)
ysis of nerve fibers has been very difficult. Therefore most

past studies have conducted semiquantitative analysis of
nerve fibers. Digitized morphometric analysis, however,
provides a means of assessing nerve fibers quantitatively.
For these reasons we adopted an immunohistochemical
method with digitized morphometric analysis to evaluate
Sub P fibers in UC. Sub P has stimulatory effects on various immunocytes, characterizing both acute and delayed
inflammatory processes [27], and has been discussed in
various inflammatory diseases [28 36]. However, there
have been very few studies demonstrating the distribution
of Sub P fibers, assessing them quantitatively as well as
morphologically, in UC specimens.
Our results demonstrate that the linear density of SP fibers is significantly greater in UC than in CD and controls
(P < 0.01). This was also confirmed by calculating the average linear density of Sub P fibers per patient. In the UC
group this was significantly greater than in the CD or control group (P < 0.01). These results a similar to those reported by Keranen et al. [6]. Measuring substance P immunofluorescence intensity in the colonic wall of UC patients, Keranen et al. demonstrated that the number of
Sub P immunoreactive nerve fibers in the lamina propria
is markedly higher and their fluorescence intensity enhanced in UC. They therefore suggested the possibility of
Sub P being involved in the pathogenesis of UC through a
neurogenic mechanism [6].
In an analysis of Sub P fibers with respect to the anatomical site of the large bowel from which the specimens
were obtained, the increase was greater in the distal colon
than in the proximal colon. However, in control specimens
no site differences were observed in terms of the distribution of Sub P fibers. Therefore the site differences among
specimens did not seem per se to contribute to the increased
linear density of SP fibers in the distal colon and rectum
66
in the UC group. The degree of inflammation also affected

the linear density of Sub P fibers. The increase was especially prominent in moderate cases. In contrast, the linear
density decreased significantly in severe cases. In severe
cases inflammatory changes were very pronounced, with
formation of numerous ulcers, resulting in the destruction
of the lamina propria and also Sub P fibers in the lamina
propria. Therefore the decreased linear density of Sub P fibers in severe cases was considered to reflect the loss of
enteric nerve fibers in the lamina propria in response to inflammation.
A key question is why there was a significant difference
in the linear density of Sub P fibers between the proximal
colon vs. the distal colon and rectum in the UC group. One
possible answer to this question is as follows. The distal
colon and rectum included higher numbers of moderate
cases than the proximal colon (20 cases, 54.1%, distal colon and rectum; 13 cases, 39.9%, proximal colon). Therefore a high percentage of moderate cases, which presented
the highest linear density of Sub P fibers, may have contributed to the overall rise in the linear density observed in
the distal colon and rectum in the UC group.
Another important difference between UC and controls
was the morphological changes in Sub P fibers. In the UC
group Sub P fibers were thicken and irregular while in controls they were fine and smooth. Immunohistochemically
these thick, coarse fibers were more densely stained than
fibers in control group. The mean diameter of nerve fibers
in normal colonic specimens has been reported to be approximately 1 m [37]. In the present study the mean width
of Sub P fibers was 1.2 0.1 m in controls, presenting a
comparable result. However, Sub P fibers were thickened
two to three times their normal diameter in the UC group.
These morphological changes in neuropeptide-containing
nerve fibers have been reported particularly in the context
of CD [15, 16]. Bishop et al. [16] and OMorain et al. [38]
have suggested that these morphological changes in enteric
nerve fibers a primary changes in CD as they a observed
even noninvolved segments. However, the present study revealed the thickening of nerve fibers both in UC and CD.
Furthermore, our study has shown that these changes are
present in Sub P fibers, even though Sjolund [15] reported
that only vasoactive intestinal peptide containing fibers
were coarse in colonic tissues of CD. Therefore, taking into
account that these changes in fibers are specific neither to
the type of inflammatory disease nor to the type of neuropeptide, coarseness of nerve fibers is considered to be secondary to intestinal inflammation or fibrosis.
From all these results, the present study suggests that
the synthesis and/or accumulation of Sub P is increased in
the colonic mucosa of UC. In our previous reports we have
demonstrated decreased concentrations of vasoactive intestinal peptide and somatostatin in UC [25, 26, 39]. In
contrast to Sub P, these neuropeptides are known to have
inhibitory effects on inflammation [40 43]. Taken together, it is suggested that the distribution of neuropeptides
is disturbed in UC, and that this disorder affects the pathogenesis of UC. We cannot conclude that Sub P alterations
actually cause UC. However, taking into account that the
increase in Sub P per se may enhance inflammation, the

alteration in Sub P fibers might be modulating the pathogenetic processes of UC.
Acknowledgements The authors thank Ms. Masako Kuwahara and
Mr. Rokuro Miyazawa for their excellent technical assistance.
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P. Broens E. Van Limbergen F. Penninckx

R. Kerremans
Clinical and manometric effects of combined external beam irradiation

and brachytherapy for anal cancer
Abstract This study evaluates anorectal function after

combined tele- and brachytherapy for anal cancer using
manometric measurements and a standardized questionnaire. Eight patients received 44 3 Gy external beam
radiation followed by 20 4 Gy interstitial brachytherapy
with iridium-192. Patients were examined 43 months
(range 2583) after therapy. Maximum anal basal pressure,
squeeze pressure, and squeeze increment were significantly lower in patients (50, 163, 115 mmHg, respectively)
than in control subjects (75, 285, 180 mmHg, respectively). Decreased anal elasticity was not observed. Anal
prestretch normalized the contractility of the internal
and external sphincter. Thus damage to the anal epithelium
and hemorrhoidal cushions seems to be the most important
mechanism explaining reduced anal closing pressure values. The rectoanal inhibitory reflex was observed in all
but one patient. Rectal compliance was significantly reduced. Whereas all patients could retain a water filled
rectal balloon until the maximum tolerable sensation level
was reached, the rectal saline infusion test was strongly
abnormal. Four patients were perfectly continent. Four
patients were incontinent for gas and presented urgency
in case of liquid stools with limited soiling occurring
once weekly or less; three of them also had urgency for
solids. Defecation frequency was increased but regular in
most patients. Reduced anal closure together with reduced
rectal compliance are at the basis of stool frequency, urgency and partial incontinence with occasional soiling.
However, enough reserve sphincter function was maintained to preserve a clinically acceptable degree of anal
continence in our patients.
P. Broens F. Penninckx () R. Kerremans

Department of Abdominal Surgery,
University Clinics Gasthuisberg, Catholic University of Leuven,
Herestraat 49, B-3000 Leuven, Belgium
E. Van Limbergen
Department of Oncology, University Clinics Gasthuisberg,
Catholic University of Leuven,
Herestraat 49, B-3000 Leuven, Belgium
Key words Anal neoplasms Radiotherapy

Radiation effects Manometry Fecal incontinence
Rsum Cette tude vise valuer la fonction ano-rectale au moyen de mesures manomtriques et dun questionnaire standardis chez des patients traits par tl- et
brachythrapie pour un cancer de lanus. Huit patients ont
reu 44 3 Gy par irradiation externe suivis de 20 4 Gy
par brachythrapie interstitielle. Les patients ont t examins 43 mois (de 25 83 mois) aprs le traitement.
La pression basale maximale, la pression de contraction et
laugmentation de la pression de contraction sont significativement abaisses chez les patients (50, 163, 115 mmHg
respectivement) chez un groupe-contrle (75, 285, 180
mmHg respectivement). Une diminution de llasticit anale
na pas t observe. Une dilatation anale normalise la
contractilit des sphincters interne et externe. Une atteinte
de lpithlium anal et des coussinets hmorrodaires semble constituer le mcanisme le plus important expliquant
la diminution des pressions docclusion. Le rflexe rectoanal inhibiteur a pu tre dmontr chez tous les patients
lexception dun. La compliance rectale est significativement abaisse. Alors que tous les patients peuvent retenir
un ballonnet rectal rempli deau jusqu ce que le seuil de
sensation maximale tolrable soit atteint, le test dinfusion
de srum est fortement anormal. Quatre patients sont parfaitement continents. Quatre patients sont incontinents
pour les gaz et prsentent des urgencies en cas de selles liquides et un fecal soiling survenant une fois par semaine
ou moins; trois de ces patients ont aussi des urgences pour
les solides. La frquence des dfcations est augmente
mais rgulire chez la plupart des malades. Une diminution de la pression docclusion avec une diminution de la
compliance rectale est la base de la frquence des
exonrations, des urgences et de la continence partielle
avec fecal soiling occasionnel. Toutefois, une rserve fonctionnelle sphinctrienne suffisante a t maintenue pour
prserver un degr acceptable de continence anale chez nos
patients.
69
Introduction
Radiation therapy is increasingly used as a cancer treatment to avoid mutilating surgery. Nowadays the primary
treatment of anal cancer consists of radiotherapy with or
without chemotherapy. Radical surgical excision has been
limited to patients who are resistant to chemoradiation and
for recurrences [13]. The major advantage of radiotherapy is that 50100% of patients retain a functional anus,
depending on stage [47]. Both external beam radiation
therapy and interstitial brachytherapy alone have been used
in the treatment of anal cancer. The locoregional control
obtained by combined tele- and brachytherapy appears
superior to that of brachytherapy alone [8]. Also, the complication rate of combined radiation therapy is acceptable
and is less than after external therapy alone [1, 9].
Although tumor control and preservation of the anus are
obviously most relevant, the chronic effect of radiotherapy
for anal cancer has not been previously investigated using
anal manometry. Thus the aim of this study was to evaluate anorectal function after combined tele- an brachytherapy by using a standardized questionnaire and by anorectal manometric measurements.
was placed 58 cm above the anal verge. At the level of maximum

anal basal pressure a maximal internal anal sphincter relaxation was
induced by rectal balloon distension. The remaining pressure, called
the residual pressure (RP), can be attributed to striated sphincter tonic activity and to the expansion of the hemorrhoidal plexuses when
the smallest probe is used. However, when using probes of larger diameters, stretching of anal passive structural elements also contributes to the measured RP [10].
Rectal sensation was assessed in combination with the balloon
retention test as described previously [11]. Briefly, a condom is fixed
at the base of a catheter. An open-tip uretural catheter is inserted
through a soft rubber connection on the main catheter to the lower
limit of the condom for pressure recording. The bottom of the collapsed condom is placed just above the anal canal through a proctoscope. Then the patient is seated on a commode, with the hips flexed
at 90. The condom is filled at a constant rate at 60 ml/min with water at 37 C. The patient is instructed to retain the balloon as long as
possible and to report the following sensations: first sensation, i.e.,
the first transient sensation of rectal distension; constant sensation,
i.e., the sensation of constant rectal distension; and urge, i.e., the feeling of urgency to defecate. The test is stopped at the maximum tolerable volume, i.e., when rectal filling reaches the limits of tolerance. Infused volume and intraballoon pressure were measured at
each sensation level. The pressure due to balloon elasticity was always subtracted from the recorded pressure values. Compliance
measured in ml/mmHg is calculated at the maximum tolerable volume.
The rectal infusion test was performed as described [12]. In brief,
warmed saline solution is infused freely in the rectum at a constant
rate of 60 ml/min and stopped after 25 min. During the test the patient is seated on a commode, with the hips flexed at 90. The first
volume at which saline was lost and the total retained volume were
noted.
Methods
Patients
Analysis
Studies were carried out in eight patients after informed consent.

There were four males and four females with median age of 62 years
(range 3879). They presented squamous cell carcinoma (n = 4), mucoepidermoid adenocarcinoma (n = 2), and cloacogenic carcinoma
(n = 2) of the anal canal. Tumor stages were cT1 (n = 2), cT2 (n = 2),
and cT3 (n = 2). External beam radiation consisted of 44 3 Gy delivered in 21 2 fractions of 18 MeV to the pelvis, including the perianal region, perirectal, inguinal, and iliac lymph nodes. This was
followed by low dose rate interstitial brachytherapy with iridium192 to a dose of 20 4 Gy spread over 36 11 h. Two patients had
external radiation with concomitant chemotherapy: one 5-fluorouracil and mitomycin C (cT3), the other 5-fluorouracil only (cT2). Patients were examined 43 21 months (range 2583) after therapy.
The patient group was compared with 23 age-matched (median
60 years, range 3280) and sex-matched control subjects hospitalized for minor operations. All of them had normal anal function.
All manometric recordings were digitalized and stored on a computer (AT-CODAS Waveform recording system (DATAQ). Measurements were performed without knowledge of the clinical symptoms
of the patient. Median values with 95% lower and upper confidence
intervals are reported. The Mann-Whitney rank sum test was used
for the comparison of unpaired data. The exact two-tailed P values
are presented.
Clinical evaluation of anorectal function
After the manometry session the clinical degree of anal continence
was assessed using a standardized questionnaire [13].
Results
Anorectal manometry
Manometric measurements were performed after checking the emptiness of the rectal ampulla. Special bowel preparation was never required.
Standard anal manometry was performed in the left lateral
position using a conventional water-filled microballoon technique
(outer diameter 5 mm, length 7 mm) connected to a Gould P23XL
transducer and a Gould universal amplifier (model 13-4615-58). The
maximum anal basal pressure was recorded using the station pullthrough technique, performed in steps of 1 cm. Squeeze pressure was
recorded during a fast constant pull through.
Measurement of anal elasticity was also performed in the left lateral position, using microtransducers (Gaeltec, UK) in probes of 0.3,
1.0, and 2.0 cm diameter [10]. Anorectal pressure profiles at rest and
during maximal squeeze were recorded in the lateral direction that
did not contain tumor before treatment. A rectal distension balloon
Anorectal manometry
Using the classical microballoon technique, maximum anal
basal pressure, squeeze pressure, and squeeze increment
(squeeze basal) were found to be significantly lower in
patients than in control subjects (Table 1). The length of
the anal high-pressure zone was not significantly shortened.
The significant decrease in maximum anal basal pressure, squeeze pressure, and squeeze increment in irradiated patients was confirmed at manometry using a microtransducer on a 0.3-cm-diameter probe (Table 2). At larger
probe diameters no differences between the radiation and
70
Table 1 Results of standard anal manometry in controls and in the
irradiated group: mean values (95% lower and upper confidence
intervals); pressure data in mmHg
Control group
Maximum anal basal
pressure
Squeeze pressure
Squeeze increment a
Length of high-pressure
zone
a
75 (6795)
Radiation group P
50 (3065)
285 (219304) 163 (120235)

180 (136224) 115 (100185)
3 (2.43.4)
3 (2.23.1)
0.003
0.009
0.04
0.14
Squeeze max. anal basal pressure
Table 2 Results of anal manometry on probes of increasing diameter: median values (95% lower and upper confidence intervals);
pressure data in mmHg
Control group
Max. anal basal pressure
0.3 cm
50 (4860)
1 cm
70 (6278)
2 cm
90 (82104)
Radiation group P
25 (1439)
35 (2075)
75 (48115)
<0.001
0.06
0.32
Amplitude of max. internal sphincter relaxation

0.3 cm
30 (2537)
15 (428)
1 cm
35 (2941)
15 (240)
2 cm
30 (2640)
45 (2058)
0.03
0.05
0.35
Residual pressure
0.3 cm
1 cm
2 cm
20 (1829)
35 (3040)
55 (5169)
10 (421)
25 (450)
20 (077)
0.04
0.21
0.05
Squeeze
0.3 cm
1 cm
2 cm
110 (105157)
155 (154205)
240 (215255)
50 (3281)
125 (54261)
170 (84274)
0.001
0.37
0.14
Squeeze increment
0.3 cm
1 cm
2 cm
60 (55101)
90 (82125)
100 (85125)
25 (1149)
55 (0174)
95 (31165)
0.02
0.23
0.67
the control group were found, possibly due to the limited

number of patients. The results obtained after radiation
therapy indicate a shift to the right of the length (stretch)
tension (force) relationship, i.e., pressures recorded on
probes of 1 and 2 cm in irradiated patients are comparable
with pressure values recorded in controls on probes of 0.3
and 1 cm, respectively.
Analysis of the composition of the maximum anal basal pressure measured with probes of increasing diameters
revealed that both the internal sphincter and the residual
pressure (striated sphincter tonic activity, expansion of
haemorrhoidal plexuses, passive structural elements) were
almost equally affected by radiation therapy (Fig. 1). Indeed, the proportional composition of maximum anal basal pressure remained unchanged when assessed with
probes of 0.3 and 1 cm diameter, with a nonsignificant trend
towards a decreased contribution from the RP when using
a 2-cm-diameter probe.
Fig. 1 Composition of resting anal pressure as measured with

probes of increasing diameter (0.32 cm) in control subjects (CO)
and irradiated patients (RT). Mean pressure values from eight controls or patients were used. The residual pressure (RP) and the amplitude of a maximum internal anal sphincter relaxation (IAS) were
about 50% lower in the irradiated group than the control group when
measured with a 0.3 cm diameter probe. The shift to the right of the
length (stretch) tension (force) relationship is illustrated by the fact
that the absolute values and the composition of resting tone measured with a 1- and 2-cm-diameter probe in irradiated patients correspond well with the data obtained with a 0.3- and 1-cm-diameter
probe in the control group, respectively
Table 3 Volume and pressure data at consecutive levels of rectal

sensation: median values (95% lower and upper confidence intervals)
Control group
Radiation group P
First sensation
Volume (ml)
Pressure (mmHg)
73 (5994)
45 (3659)
53 (27101)
61 (4279)
0.23
0.13
Constant sensation
Volume (ml)
Pressure (mmHg)
118 (97136)
54 (4570)
70 (44139)
67 (5485)
0.11
0.12
Urge sensation
Volume (ml)
Pressure (mmHg)
155 (130207)
63 (4977)
100 (61185)
86 (7292)
0.10
0.06
Max. tolerable sensation

Volume (ml)
215 (185273)
Pressure (mmHg)
73 (6091)
138 (96229)
106 (87129)
0.05
0.03
Compliance (ml/mmHg)
2.9 (1.84.4)
1.5 (0.72.5)
0.01
Rectal sensation
All patients could retain the rectal balloon until the maximum tolerable sensation level was reached. The volume
needed to reach the maximum tolerable sensation level was
lower in irradiated patients than in controls. The pressure
recorded at maximum tolerable sensation, in contrast, was
higher after radiation. Volume and pressure values at the
other sensation levels were not significantly different but
showed the same trend (Table 3). This may be related to
71
the limited number of patients studied and/or to a somewhat variable effect of irradiation in different patients. The
rectal compliance at maximum tolerable distension was
significantly reduced after radiation therapy.
The rectal saline infusion test
In irradiated patients the first leak occurred at 127 ml
(range 10360; 95% confidence interval 40299) and only
300 ml could be retained (range 01000 ml; 95% confidence interval 25662). These findings are significantly
different from the 1.5 l retainable volume without leak
measured in control subjects.
Clinical results
Evaluation of anal continence using a standardized questionnaire revealed that continence was perfect in four patients. Four patients were incontinent for flatus and presented urgency in case of liquid stools. Limited soiling
occurred once weekly or less. Therefore, three patients permanently used a pad. One did so mainly by way of precaution, and another because he could not differentiate the nature of the rectal contents. The third patient lost a limited
quantity of stools about once weekly. She originally had a
T3 tumor and later a necrotic ulcer which had to be excised. She as well as two others had urgency for solids. No
patient was completely incontinent for solid stools.
Defecation was regular in six patients (3/day, range 25)
and irregular in two (min. frequency 1/day, max. 7/day).
No patient had to evacuate at night. Fecal consistency was
normal in six patients and semisolid in two (one using loperamide).
Discussion
This study demonstrates diminished anal basal and squeeze

closing pressures after combined 45 Gy teletherapy to the
whole anorectal canal and 20 Gy low dose rate brachytherapy to limited volumes in eight patients with anal cancer.
This is based on damage of the smooth and striated perianal musculature and to the passive structural elements.
This is to be expected since therapy was installed for anal
tumors occupying more than one-third of the canal in six
of the eight patients.
The decreased maximum anal basal pressure and the decreased amplitude of internal sphincter relaxation indicate
diminished internal anal sphincter function. Decreased
squeeze and squeeze increment pressure values indicate
disturbed striated anal sphincter function. Our study also
demonstrates reduced residual pressure. This can be explained by disturbed external anal sphincter resting activity but may also be due to shrinkage or destruction of the
hemorrhoidal plexuses or to a combination of the two.
The anal cushions normally fill the gap of 78 mm within
the internal sphincter ring [14]. Epithelial and hemorrhoidal destruction or shrinkage could explain the shift to
the right of the curve relating muscle force to muscle
stretch: all pressure values (residual pressure, amplitude of
the internal sphincter relaxation, maximum anal basal and
squeeze pressure, squeeze increment) measured with a
probe diameter of 1 and 2 cm in the irradiated group correspond perfectly with the pressure values measured in
control subjects using a probe diameter of 0.3 and 1 cm,
respectively. Thus increased anal prestretch seems to normalize the contractility of surrounding muscles. One
would also expect fibrosis of the anus and anal sphincters
after irradiation. Our pressure measurements on probes of
increasing diameter, however, do not reveal decreased elasticity. Thus damage to anal epithelial layer and anal cushions seems to be the mechanism which may explain the
manometric findings.
Objective assessment of anal continence can be performed by the rectal infusion test [12] and by the balloon
retention test [11]. Continence during rectal infusion of saline is maintained by the anal resting pressure, based
mainly on internal sphincter activity, and by the mucosal
plug formed by the anal cushions [12]. Continence for solids, in contrast, appears to be based mainly on striated perianal muscle function, activated only episodically to prevent fecal evacuation when intra-abdominal pressure rises,
or when urge sensation occurs, and the internal sphincter
is relaxed [15, 16]. Studies in incontinent patients, using
the same standard manometry equipment as in the present
study, have indicated that the sphincter requirements for
objective continence are a maximum basal pressure of
about 60 mmHg and a squeeze increment of another 60
mmHg to reach a global squeeze pressure of 120 mmHg
[16, 17]. The observations in our patients after tele- and
brachytherapy for anal cancer demonstrate a more pronounced reduction in resting pressure than of squeeze pressure values. This explains the patients inability to retain
a water enema, whereas their ability to retain simulated
solid stool, i.e., a rectal balloon filled with water, was much
less disturbed. Our findings correspond well with those in
patients presenting chronic radiation injury after 50-Gy
identical small field external beam radiotherapy for prostate carcinoma [18]. It therefore seems that the observed
effects must be related to the high radiation dose needed
and to the beneficial consequences of radiation therapy,
i.e., destruction of the anal cancer more or less involving
the anal cushions and the internal sphincter, as well as
the subsequent scar formation. Minimal, nonsignificant
differences in mean maximum squeeze and resting pressures, sphincter profile, minimum sensory threshold, and
rectoanal inhibitory reflex were found 4 weeks and 1442
months after 45-Gy preoperative external radiotherapy in
ten patients with rectal carcinoma [19, 20]. However, in
some of these patients the field of radiation did not include
the sphincter.
The rectoanal inhibitory reflex, i.e., internal sphincter
relaxation after rectal distension, has been reported to be
absent or decreased in patients with anorectal radiation injury [18, 21]. This may be related to neural damage but can
72
also be explained by the resting pressure in irradiated patients, which may be so low that it is difficult to demonstrate the rectoanal reflex when using a measuring system
of small diameter. In our set-up, stretching the sphincter
resulted in a higher basal tension and the reflex could easily be demonstrated in all but one patient. Thus we could
neither confirm nor reject possible nerve damage resulting
in a decreased conducting speed, as reported by others. The
rectoanal inhibitory reflex was present in all patients with
rectal cancer after 45-Gy preoperative external radiotherapy [20].
Our results confirm decreased rectal compliance, i.e.,
stiffening of the rectal wall, after irradiation. The volumes
needed to induce consecutive rectal sensation levels tended
to be diminished, as previously reported by others [21]. In
contrast, the pressure values at which patients experienced
consecutive sensation levels tended to be increased. Rectal sensation has been shown to be related mainly to the
balloon pressure and not to the balloon volume [22]. Since
50-Gy external beam radiation therapy for prostate carcinoma did not affect the balloon pressures recorded at each
sensation level [21], local anal destruction or damage due
to the higher local radiation dose seem to be responsible
for disturbing the receptors of anorectal filling sensation.
This is in agreement with the hypothesis that locates these
receptors at the anal level and not in or around the rectum
or in the puborectalis muscle [22].
There seems to be a contradiction or paradox between
our objective manometric data and the very good clinical
continence after anal irradiation. The gratitude of the patient may be one explanation. Another, equally valid explanation is that the decreased sphincter performance at
manometry remains subclinical because the patients fortunately have normal, not liquid stool.
In conclusion, anal function is clearly affected after
combined external irradiation and local iridium implantation in patients with anal cancer. Anal squeeze and resting
pressures are significantly reduced. Rectal capacity and
compliance are also reduced, while the pressure thresholds
needed for rectal sensation are increased. Nevertheless,
enough reserve sphincter function is preserved for most
patients to maintain a clinically acceptable degree of anal
continence provided anorectal function was normal before
treatment and provided stool consistency remains normal
after treatment. All patients undoubtedly prefer a natural
fecal transit to a stoma and tolerated well the minor defects
of anal function which in some cases can be identified only
by accurate, targeted questioning or manometrical studies.
References
1. Hintz BL, Charyulu KKN, Sudarsanam A (1978) Anal carcinoma: basic concepts and management. J Surg Oncol 10: 141
150
2. Cummings BJ, Thomas GM, Keane TJ, Harwood AR, Rider WD

(1928) Primary radiation therapy in the treatment of anal canal
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3. Tveit KM, Karlsen KO, Foss SD, Flokkmann A, Guldvog I,
Haffner J (1988) Primary treatment of carcinoma of the anus by
combined radiotherapy and chemotherapy. Scand J Gastroenterol 24: 12431247
4. Cummings BJ, Keane TJ, OSullivan B, Wong CS, Catton CN
(1991) Epidermoid anal cancer: treatment by radiation alone or
by radiation and 5-fluorouracil with and without mitomycin C.
Int J Radiat Oncol Biol Phys 21: 11151125
5. Allal A, Kurtz JM, Pipard G, Marti MC, Miralbell R, Popowski
Y, Egeli R (1993) Chemoradiotherapy versus radiotherapy alone
for anal cancer: a retrospective comparison. Int J Radiat Oncol
Biol Phys 27: 5966
6. Martenson JA, Gunderson LL (1993) External radiation therapy without chemotherapy in the management of anal cancer.
Cancer 71: 17361740
7. Kapp KS, Kapp DS, Stuecklschweiger G, Berger A, Geyer E
(1994) Interstitial hyperthermia and high dose rate brachytherapy in the treatment of anal cancer. Int J Radiat Oncol Biol Phys
28: 189199
8. Papillon J, Montbarbon JF, Chassard JC, Grard JP, Jaussand D
(1973) Place de la curiethrapie interstitielle, seule ou combine
la cobaltothrapie dans le traitement des cancers pidermoides
de lanus. J Radiol Electrol 54: 627633
9. Papillon J, Montbarbon JF (1987) Epidermoid carcinoma of
the anal canal, a series of 276 cases. Dis Colon Rectum 30: 324
333
10. Lestr B, Penninckx FM, Kerremans RP (1989) The composition of anal basal pressure. An in vivo and in vitro study in man.
Int J Colorect Dis 4: 118122
11. Penninckx FM, Lestr B, Kerremans RP (1989) A new balloonretaining rest for evaluation of anorectal function in incontinent
patients. Dis Colon Rectum 32: 202205
12. Read N, Haynes W, Bartolo D, Hall J, Read M, Donnelly T, Johnson A (1983) Use of anorectal manometry during rectal infusion
of saline to investigate sphincter function in incontinent patients.
Gastroenterology 85: 105113
13. Penninckx F (1987) Faecal incontinence. Int J Colorect Dis
2: 173186
14. Lestr B, Penninckx FM, Rigauts H, Kerremans RP (1992) The
internal anal sphincter can not close the anal canal completely.
Int J Colorect Dis 7: 159161
15. Read N, Bartolo D, Read M (1984) Differences in anal function
in patients with incontinence to solids and in patients with incontinence to liquids. Br J Surg 71: 3942
16. Penninckx F, Lestr B, Kerremans R (1995) Manometric
evaluation of incontinent patients. Acta Gastro-Enterol Belg
58: 5159
17. Penninckx F, Lestr B, Kerremans R (1992) The internal anal
sphincter: mechanisms of control and its role in maintaining anal
continence. Baillires Clin Gastroenterol 6: 193214
18. Varma JS, Smith AN, Busuttil A (1986) Function of the anal
sphincters after chronic radiation injury. Gut 27: 528533
19. Birnbaum EH, Dreznik Z, Meyerson RJ, Lacey DL, Fry RD,
Kodner IJ, Fleshman JW (1992) Early effect of external beam
radiation therapy on the anal sphincter: a study using anal
manometry and transrectal ultrasound. Dis Colon Rectum
35: 757761
20. Birnbaum EH, Myerson RJ, Fry RD, Kodner IJ, Fleshman JW
(1994) Chronic effects of pelvic radiation therapy on anorectal
function. Dis Colon Rectum 37: 909915
21. Varma JS, Smith AN, Busuttil A (1985) Correlation of clinical
and manometric abnormalities of rectal function following
chronic radiation injury. Br J Surg 72: 875878
22. Broens P, Penninckx F, Lestr B, Kerremans R (1994) The trigger for rectal filling sensation. Int J Colorect Dis 9: 14
G. D. Giebel R. Lefering H. Troidl H. Blchl
Prevalence of fecal incontinence: what can be expected?
Accepted: 29 October 1997
Abstract Fecal incontinence is a serious problem especially for the elderly. The epidemiology of incontinence is
not well described in the literature although it is often used
as an endpoint for treatment evaluation in clinical trials.
Complete continence is often assumed to be the normal
standard. The goals of this study were to establish detailed
prevalence rates for fecal incontinence in a standard population and to identify differences due to age and sex.
A questionnaire about fecal incontinence and its consequences with predefined answers was filled out anonymously by 500 volunteers. The study population was selected to meet the respective age and sex distribution of
the German adult population. The data indicated that 4.8%
of the persons were unable to control solid stools, while
19.6% had problems at least with one type of incontinence
(solid, pasty, or lipid stools, winds). Problems with pasty
or liquid stools are more frequent in women. The ability to
control wind is decreased in elderly persons. The time
needed to reach a toilet is shorter for women, and generally decreases in the elderly. Men more often describe
soiling the in underwear. Persons with signs of incontinence show decreased levels of social activities. A global
incontinence rate of 5% fits well with some previously published results. Soiling of the underwear is not well suited
for defining incontinence. The increased rate in women
may in part be explained by morphological differences.
The reduced time to hold stools especially in the elderly in
combination with a reduced mobility may result in a higher
rate of incontinence, which is correlated with reduced social activities.
G. D. Giebel () H. Troidl H. Blchl

Surgical Clinic, II Department of Surgery,
University of Cologne, Ostmerheimer Strasse 200,
D-51109 Cologne, Germany
R. Lefering
Biochemical and Experimental Division, II Department of Surgery,
University of Cologne, Ostmerheimer Strasse 200,
D-51109 Cologne, Germany
Key words Fecal incontinence Epidemiology

Soiling of the underwear Elderly persons
Suppression of stools
Rsum Lincontinence fcale est un problme srieux
particulirement chez les patients gs. Lpidiomologie
de lincontinence nest pas bien dcrite dans la littrature
bien quelle soit frquemment utilise comme valeur de
rfrence finale dans lvaluation dessais cliniques. Une
continence complte est souvent dfine comme tant le
standard normal. Objectif: Etablir les taux de prvalence
dtaills de lincontinence fcale dans une population standard et identifier les diffrences dues lge et au sexe.
Matriel et mthode: Un questionnaire propos de lincontinence fcale et de ses consquences au moyen de rponses pr-dfinies a t rempli de manire anonyme par
500 volontaires. La population tudie a t choisie afin
de correspondre la distribution de la population allemande adulte quant lge et au sexe. Rsultats: 4,8% de
la population est incapable de contrler les selles solides
alors que 19,6% avec au moins un des types dincontinence
(continence aux solides, aux selles molles, aux selles liquides et aux gaz). Les problmes avec des selles molles
ou des selles liquides surviennent plus frquemment chez
les femmes. La capacit de contrler les gaz diminue avec
lge de la population. Le temps ncessaire pour atteindre
des toilettes est plus bref chez les femmes et en gnral diminue avec lge de la population. Les hommes rapportent
plus souvent des souillures des sous-vtements. Les sujets
avec des signes dincontinence prsentent une diminution
des activits sociales. Discussion: Un taux global dincontinence de 5% correspond bien ceux dtudes publies
prcdemment. Des souillures des sous-vtements ne sont
pas un critre bien prcis pour dfinir lincontinence. Le
taux plus lev chez les femmes peut en partie tre d
des diffrences morphologiques. Le temps plus bref pendant lequel les selles peuvent tre retenues, en particulier
chez la population ge en combinaison avec une diminution de la mobilit, peut rsulter dans un taux plus lev
dincontinence qui correspond bien avec une diminution
des activits sociales.
74
Introduction
The epidemiology of fecal incontinence a serious problem especially for the elderly is not well described in the
literature. There exists no uniform definition of continence,
and many studies do not differ between urine and fecal incontinence. The findings also depend strongly on the selection of patients or volunteers. Reported prevelence rates
for incontinence range from 0% in elderly persons on admission to residential care [1] to 48% in a gerontopsychiatric survey [2]. Valid estimates for adults are rare. A survey of health insurance data in the United Kingdom showed
a prevelence of 0.19%. General practitioners in the United
Kingdom found 0.43% of their patients to be incontinent
[3, 4]. Other investigators report much higher rates in selected groups of students and hospital personal (5.3% [5])
or employees of a community department (5% [6]). A large
survey in the United States based on telephone interviews
showed a rate of 2.2% [7]. Selected groups of patients with
multiple sclerosis [8] or diarrhea [9] show prevelence rates
of incontinence of more than 50%.
Sex-specific differences of incontinence rates must also
be considered. A survey from New Zealand [10] on persons aged 65 years or above found higher prevelence rates
in men than in women. In general, however, women are
expected to be more prone to incontinence since their
external sphincter is smaller [11]. Some authors have found
the resting pressure measured in the anal canal to be lower
in women [12, 13], while others observe no difference
[14]. Sometimes delivery causes an injury of the nervous
pudendis [15, 16] or one or both of the sphincter muscles
[17] followed by a permanent reduction of continence [18].
The occurrence of anal incontinence is an important indicator of success for various operative procedures, such
as low anterior resection and pouch operations. It is often
used as an endpoint for treatment evaluation in clinical
trials. However, valid and detailed prevelence data regarding differences in sex and age are necessary to interpret
these trial results correctly.
The principal aim of this survey was to obtain age- and
sex-specific prevelence data for an average population in
a developed, Western country. A secondary goal was to investigate and document the influence of incontinence on
the activities of daily living.
Methods and materials

A questionnaire concerning anal incontinence and its consequences
was developed in 1993. Incontinence was determined separately for
solid, pasty, and liquid feces and for flatus. Most questions could be
answered on a four-point scale: always, often, seldom, or never. It
was explained to the interviewed person that always means daily,
often means at least once in 2 weeks, and seldom means less frequently. The questionnaire was self-explanatory and took about
10 min to read all questions and mark answers. Anonymity was guaranteed; no names were recorded.
A prospective survey of 500 patients was designed reflecting age
(six groups) and sex distribution in the German population. An ex-
pected prevalence rate of 5% can statistically be proven, with an

error of 2% (95% confidence interval). Patients under the age of
18 years were excluded, as were those with digestive diseases and
those with prior abdominal surgery (prior appendectomy was not an
exclusion criterion). The study population was composed of 275 consecutive patients from the Emergency Department of the Surgical
Clinic in Cologne-Merheim (without abdominal problems), 115 patients with diagnostic arthroscopies, 62 employees of the hospital,
and 48 relatives of the above groups of persons. The Merheim Clinic is located in the vicinity of Cologne, a city of 1 million inhabitants, the study population consisted of both an urban population and
inhabitants of small villages.
Statistical analysis was performed using the 2 test for contingency tables. Significant P values less than 0.05 are reported not to
verify hypotheses (multiple comparisons) but rather to serve as a
measure of association. Main results are given with 95% confidence
intervals (CI).
Results
The distribution of age and sex of the 500 persons included

in this survey is given in Table 1 together with the respective values of the German population based on 1993 statistics. Table 2 presents an overview of the most important
questions and the presence of sex or age specific differences.
Among the volunteers 90.4% classified their bowel behavior as normal, but one in ten did not (women twice as often
as men). Frequency of stools does not depend on age or sex.
Some 95% of all answers ranged between twice a day and
every 2 days. About one-third of the persons reported the
need to get up at night to pass a stool; this was especially
common among men. Women were less often able to suppress stools than men, but this was a very common complaint (29.4%). The time needed to reach a toilet decreases
with increasing age (Fig. 1); the median value was 30 min
for those aged under 60 years while most of those older must
reach a toilet within 5 min (possible answers were: 1, 5, 30,
or 60 min). There is also a difference due to sex; 60.9% of
men were able to hold stools for at least 30 min, while this
was true for only 45.3% of women (P<0.001).
The questionnaire contained different questions to assess the degree of incontinence. Table 3 summarizes five
different approaches to its definition. The responses of
4.8% (CI 2.9% 6.7%) were negative to the control of solid
stools (this question could be answered by yes or no
only), and 6.6% and 6.7% reported never to be able to control pasty or liquid stools, respectively. The ability to control liquid or solid stools was not age dependent. Women
reported more frequent problems with liquid stools. Control of wind was impossible for 5.5%. Fecal soiling, which
is sometimes used to define incontinence, was reported by
only 3.1%. Men more frequently reported signs of stool in
the underwear, but using the strong definition (often or
always) the numbers were too small to reach significance. Taken together, 98 persons (19.6%; CI 15.6 22.4)
reported at least one of the above types of incontinence,
but only 25 (5.0%, CI 3.1% 6.9%) had two or more of
these signs. With increasing age the control of flatus was
also less often reported (Tables 2, 3). This was also true
for uncontrolled flatus during micturition.
75
Table 1 Distribution of age and sex in the study population: corresponding percentage of the German population aged 18 years and above is given in parentheses
18 30
31 40
41 50
51 60
61 70
>70
Total
Women
52
10.4%
(10.9%)
43
8.6%
(9.4%)
37
7.4%
(7.7%)
43
8.6%
(8.6%)
35
7.0%
(6.9%)
42
8.4%
(8.8%)
252
50.4%
(51.3%)
Men
58
11.6%
(11.6%)
110
47
9.4%
(10.0%)
90
40
8.0%
(7.9%)
77
47
9.4%
(8.7%)
90
32
6.4%
(5.5%)
67
24
4.8%
(4.0%)
66
248
49.6%
(48.7%)
500
22.0%
(22.5%)
18.0%
(19.4%)
15.4%
(15.6%)
18.0%
(17.3%)
13.4%
(12.4%)
13.2%
(12.8%)
Total
100%
(100%)
Table 2 Main results of the questionnaire of 500 subjects; significant differences in prevalence (2 test) due to age or sex
Question
Prevalence
(%)
Significant differences
Abnormal defecation (subjective assessment)

Use of laxatives
Frequent stools due to stress
Poor ability to suppress stool
Stools at night
Frequent stools after meal
Pain in passing movement
Need to press during movement
No feeling of emptiness after defecation
Blood at the stool
Soiling of the underwear
Itching in the anal region
Poor control of winds
Frequently winds during micturition
10.6
19.5
44.8
29.4
33.5
20.1
32.5
14.8
18.5
13.4
35.1
48.6
24.4
56.5
More frequent in women **

More frequent in the elderly *** and in women **
More frequent in the elderly * and in women **

More frequent in men ***
More frequent in younger subjects *** and in women *
More frequent in the elderly ***
More frequent in the elderly * and in men *

More frequent in men ***
More frequent in men **
More frequent in the elderly *
* P < 0.05; ** P < 0.01; *** P < 0.001
Fig. 1 Percentage of persons

who need to reach a toilet within 5 min. Possible answers to
this question were: 1, 5, 30, or
60 min
76
Table 3 Prevalence of incontinence based on different definitions;
significant differences in prevalence (2 test) due to age or sex
Definition
Prevalence
Significant differences
Control of solid stool

Control of pasty stool
Control of liquid stool
Control of winds
Frequent soiling of the
underwear
4.8%
6.6%
6.7%
5.5%
3.1%
More frequent in women **

More frequent in women *
* P < 0.05; ** P < 0.01
Forty-two persons (8.5%) stated that they wear diapers

because of problems with incontinence. Of these persons,
men were significantly more disturbed by the fact. Concerning the limitations of daily activities due to continence
problems, those with at least one sign of incontinence
(n = 98) attended social events significantly less often, including theatre, concerts, and parties (60.8% vs 76.8%) and
traveled less regularly in vacation (51.0% vs. 68.2%).
The use of laxatives was reported by 19.5% of all people. This finding was strongly age dependent; 92.6% of
those aged 40 or under never used laxatives while 56% of
those aged 70 or above did so. In latter group 9% used laxatives every day. Furthermore, women used laxatives approximately twice as often as mean.
Discussion
Continence for solid and liquid feces is an important component of well-being and quality of life. It is often used as
the most important endpoint for indication or evaluation
of treatment in patients with anorectal diseases. In order to
ascertain the success of a specific therapy it is important
to have information about the prevelence of incontinence
in an average population. It is often assumed that the ability to control stool is a standard, and preoperative assessment is seldom carried out. Clinical studies, however, usually select specific groups of patients, and therefore it is
mandatory to have a pre- and posttreatment assessment of
continence.
Campell et al. [10] and Talley et al. [19] report rates of
3.1% and 3.7%, respectively, in patients aged 65 and above.
Drossman et al. [20] found 9.2% of persons aged 45 or
above to be incontinent. Nelson et al. [7] recently published a rate of 2.2%. Their survey was based on a random
telephone procedure to identify study subjects, but their
evaluation was based on a telephone interview including
not only the person directly talked to but all members of
the household. We think that a detailed questionnaire filled
out anonymously and accompanied by a personal communication to a physician yields more complete and candid
results.
The present investigation gives an impression about the
expected frequency of incontinence, stratified for age and
sex. The majority of our study population consisted of patients presenting themselves at our emergency department,
without serious problems that would limit their ability to
answer our questions and without any digestive disease.
This might bias our sample towards the more active part
of the population. However, the fact that all persons were
seen by a physician who explained the intention of the
questionnaire and guaranteed anonymity may have increased the candidness of answers and the validity of our
results.
Incontinence of solid stools was found in 4.8% of the
whole population, without any major differences due to age
or sex. This is only the worst form, however, disregarding
initial types of incontinence. Regarding the ability to control pasty or liquid stools or winds, there was a trend to increasing prevalence rates among the elderly and among
women.
The higher prevalence rate of fecal soiling of underwear
in men may be less a medical problem than the effect of
cleaning. Men usually have more hair in the anal region
than women. It has also been suggested that the longer
sphincter of men allows small amounts of residual stool to
be left in the anal canal which subsequently leak after a
bowel movement [21].
With increasing age persons are less able to delay defecation. This suggests that the problem of incontinence in
the elderly is caused at least in part by the increasing natural weakness of the anal sphincter muscle. The fact that
elderly persons are usually less agile may add to the problem, as well as the increased use of laxatives. However, the
frequency of stools is distributed uniformly among all age
groups and between men and women.
The slightly higher prevalence of incontinence among
women is correlated well with morphological findings. The
female anal sphincter is asymmetric [22, 23]; the neural
supply is reduced in elderly women which may result in
decreased contractility [24]. The possibility of sphincter
defects post partum have already been mentioned [3, 15,
16, 18].
Incontinence is a severe problem and its prevalence is
often underestimated. The present investigation may improve understanding as to what is normal and thus support the correct interpretation of clinical findings. For the
elderly the reduced time that stool can be held must be considered. Together with a reduced mobility this may have
an effect on social contacts.
References
1. Brocklehurst JC, Carty MH, Leeming JT, Robinson JM (1978)
Medical screening of old people accepted for residential care.
Lancet II: 141 142
2. Becker J (1988) Situation in der Alterspsychiatrie. Dtsch rztebl
85: 388
3. Thomas TM, Plymat KR, Blannin J, Meade TW (1980) Prevalence of urinary incontinence. BMJ 281: 1243 1245
4. Thomas TM, Egan M, Walgrove A, Meade TW (1984) The prevalence of faecal and double incontinence. Community Med
6: 216 220
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5. Drossmann DA, Sandler RS, Broom CM, McKee DC (1986) Urgency and faecal soiling in people with bowel dysfunction. Dig
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6. Enck P, Bielefeldt K, Rathmann W, Durrmann J, Tschpe D,
Erckenbrecht JF (1994) Epidemiology of faecal incontinence in
selected patient groups. Int J Colorect Dis 6: 143 146
7. Nelson R, Norton N, Cautley E, Furner S (1995) Communitybased prevalence of anal incontinence. JAMA 274: 559 561
8. Hinds JP, Eidelman BH, Wald A (1990) Prevalence of bowel
dysfunction in multiple sclerosis. Gastroenterology 98:
1538 1542
9. Leight RJ, Turnberg LA (1982) Faecal incontinence the unvoiced symptom. Lancet I: 1349 1352
10. Campell AJ, Reiken J, McCosh L (1985) Incontinence in the elderly: prevalence and prognosis. Age Ageing 14: 65 70
11. Stelzner F (1981) Die anorektalen Fisteln, 3rd edn. Springer,
Berlin Heidelberg New York
12. Loening-Baucke V, Anuras S (1985) Effects of age and sex on
anorectal manometry. Am J Gastroenterol 80: 50 53
13. McHugh SM, Diamant NE (1987) Effect of age, sex, and parity
on anal canal pressure: contribution of impaired anal sphincter
function to faecal incontinence. Dig Dis Sci 32: 726 736
14. Jameson JS, Chia YW, Kamm MA, Speakman CTM, Chye YH,
Henry MM (1994) Effect of age, sex and parity on anorectal
function. Br J Surg 81: 1689 1692
15. Snooks SJ, Setchell M, Swash M, Henry MM (1984) Injury to
the innervation of pelvic floor sphincter musculature in childbirth. Lancet II: 546 550
16. Sultan AN, Kamm MA, Hudson CN (1993) Obstetric related pudendal nerve damage can be asymmetrical, and can occur fol-
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lowing cesarian section: a prospective study. Gastroenterology

104: A588
Burnett SJ, Spence-Jones C, Speakman CT, Kamm MA, Hudson CN, Bertram CI (1991) Unsuspected sphincter damage following childbirth revealed by anal endosonography. Br J Radiol
64: 225 227
Snooks SJ, Swash M, Mathers SE, Henry MM (1990) Effect of
vaginal delivery on the pelvic floor: a 5-year follow-up. Br J
Surg 77: 1358 1360
Talley J, OKeefe EA, Zinsmeister AR, Melton III LJ (1992)
Prevalence of gastrointestinal symptoms in the elderly: A population-based study. Gastroenterology 102: 895 901
Drossman DA, Li Z, Andruzzi E, Temple RD, Talley NJ, Thompson WE, et al (1993) U. S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and
health impact. Dig Dis Sci 38: 1569 1580
Sentovich SM, Rivela LJ, Blatchford GJ, Christensen MA, Thorson AG (1995) Patterns of male fecal incontinence. Dis
Colon Rectum 38: 281 285
Stelzner F (1992) Anatomisch bedingte diagnostische und operationstechnische Probleme und Komplikationen in der Chirurgie am Anorektum. Zentralblt Chir 117: 111 114
Percy JP, Neill ME, Kandiah TK, Swash M (1982) A neurogenic factor in faecal incontinence in the elderly. Age Ageing
11: 175 179
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J. Benoit A. Meddahi N. Ayoub D. Barritault

A. Sezeur
New healing agent for colonic anastomosis
Abstract This study evaluated the healing property, on

colonic anastomoses, of a new compound termed RGTA11
(standing for regenerating agent, a dextran derivative
with heparin-like properties). Colonic anastomoses were
performed in 183 adult rats after dipping both ends of the
colon in solutions containing RGTA11. The anastomoses
were made end-to-end on a single plan, 8 sutures. Healing was evaluated mechanically by the bursting pressure
in 108 animals and histological analysis in 75. Results indicated that after 48 h RGTA11-treated animals presented
a twofold increased resistance to anastomoses breakage
(P < 0.01) over nontreated (saline buffer) animals. After
96 h and until day 7 there was no longer a difference between study and control animals. Although this difference
in breakage was not readily observed at histological level,
results suggest that RGTA11 could be used to aid colonic
anastomosis healing. RGTA11 is of potential clinical interest in this regard since complications that are known to
occur postoperatively result from early leakage.
La gurison a t value mcaniquement en mesurant la

pression de rupture chez 108 animaux et en procdant
une analyse histologique chez 75. Les rsultats indiquent
quaprs 48 heures, les animaux traits par RGTA11 prsentent une rsistance la rupture de lanastomose deux
fois suprieure (P < 0,01) comparativement aux animaux
non traits (solution saline). Aprs 96 heures et jusquau
7e jour, il ny a pas daugmentation de la diffrence entre
les sujets tudis et le groupe-contrle. Bien que la diffrence dans la fragilit nait pas t observe un niveau
histologique, nos rsultats suggrent que RGTA11 pourrait tre utilis pour favoriser la gurison des anastomoses
coliques. RGTA11 est donc potentiellement intressant
pour favoriser la gurison des anastomoses coliques tant
donn que les complications survenant dans la priode postopratoire rsultent de fuites anastomotiques prcoces.
Introduction
Key words Healing Colonic anastomosis RGTA

Heparin-like polymer Heparan
Rsum Afin dvaluer leffet sur la cicatrisation danastomose colique dune nouvelle substance nomme
RGTA11 (agent rgnrant, un driv du dextrane avec des
proprits de type hparinique), les expriences suivantes
ont t entreprises: Cent-quatre-vingt-trois anastomoses
coliques ont t ralises chez le rat aprs avoir immerg
les deux extrmits du clon dans une solution de RGTA11.
Des anastomoses ont t faites la main de manire termino-terminale en un seul temps avec 8 points de suture.
J. Benoit N. Ayoub A. Sezeur
Service de Chirurgie Gnrale et Digestive du Professeur Malafosse,
Hopital Rothschild, 33 Boulevard de Picpus, 75012 Paris, France
A. Meddahi D. Barritault ()
Laboratoire de Recherche sur la Croissance Cellulaire,
la Rparation et la Rgnration tissulaire (CRRET) UPRESA
CNRS7053, Universit Paris XII-Val de Marne,
Avenue du gnral de Gaulle, 94010 Creteil, France
e-mail: barritault@univ-paris12.fr
In previous work we have studied the healing properties of

a family of biopolymers named referred to as RGTA (for
regenerating agent) in various animal models including
skin [1], bone [2, 3], cornea [4], muscle, and nerve repair
[5]. These RGTA are obtained by controlled chemical substitution of dextran by carboxymethyl groups which are
then replaced by benzylamide groups followed by sulfonation as described in Mauzac et al. [6]. We have shown
[7] that some members of this family of biopolymers can
mimic heparin in its ability to interact with heparin-binding growth factors, stabilize, and protect these growth factors against proteolytic degradation. Furthermore, these
polymers were selected for their weak anticoagulant and
anticomplement activities [7].
From this in vitro data, we postulated that some RGTA
act in vivo by protecting the endogenously released heparin-binding growth factors at the site of the injury and
therefore favor tissue repair. We now extend our study on
tissue repair in a colonic anastomosis healing model using
a new member of the RGTA polymer family termed
79
RGTA11, since leakage from colonic anastomoses is a major complication in intestinal surgery.
Postoperative morbidity from colonic anastomoses varies between 10% and 30%, with a significant associated
mortality [8, 9]. Attempts to enhance anastomotic healing
have included the use of various surgical techniques and
materials (quality of suture threads, use of staples, control
of sepsis by specific bowel preparation before surgery, use
of parenteral nutrition, use of various sealants, etc.), but
none is sufficient to prevent the development of complications [10, 11]. More recently the use of growth factors
including fibroblast growth factor (FGF), platelet-derived
growth factor, transforming growth factor-, and epidermal growth factor has been reported, with some encouraging results, in intestinal wound healing [1214].
The aim of this work was to study a specific RGTA,
namely RGTA11, anastomotic healing, with the idea that
this compound could become a potential healing agent to
prevent early anastomotic leakage in large bowel surgery.
compound on the immersed colon tissue and was found sufficient for
maximal fixation.
The end to end colonic anastomoses were performed in a single
plan with eight separate suture points, using 6/0 polyglactin 910
thread (Vicryl, Ethicon, USA). Knots were made of six buckles. The
rats were separated into three groups of 12 animals. Each group corresponded to one of the three different solutions used to immerse the
anastomotic ends. All experiments were double-blinded using coded solutions (buffer, RGTA11, RGTA11/FGF-2) which were revealed after the bursting measure experiments and the histological
studies.
Measure of bursting pressure
For this study 108 rats were used. The quality of the anastomosis
was measured by recording the water pressure needed to induce leakage of anastomosis. The viscera were excised on days 2, 4, and 7,
cut 2 cm from the anastomosis, washed, and placed immediately in
saline buffer. One end of the cut colon was connected to an automated pushing syringe which injected water at a constant flow while the
other end was connected to a manometer. Pressure was recorded permanently, and leakage was detected immediately by loss of pressure.
Histological study
Material and methods

Synthesis of one RGTA
RGTA11 is carboxymethyl, benzylamide sulfonate derivative of
dextran synthetized as described [6] from a batch of dextran T40
MW 40,000 obtained from Pharmacia (Sweden). The batch of RGTA
(termed RGTA11) used in the study contained the following degree
of substitution: carboxymethyl, 110%; benzylamide, 2.6%; sulfonate
36.6% which were measured by microanalysis and infrared spectrophotometry [6]. By definition 100% is the maximal substitution possible for each free hydroxyl groups present on a single glucose
residue. The anticoagulant activity was measured as previously
described [6] and was 4.5 IU. In control experiments heparin
(bath H108, kindly provided by Maurice Petitou, Sanofi, France) was
173 IU.
Histological study was performed in 75 rats divided into groups treated in parallel to those above for the bursting pressure experiments.
All samples were collected. Colonic samples were also cut 2 cm from
the anastomosis and fixed in a 4% formaldehyde solution, dehydrated, and embedded in paraffin. Serial tissue sections of 5 m were
made and stained with hematoxylin and eosin. To compare the samples on days 2, 4, and 7 after surgery, we measured the length (in
millimeters), the loss of colonocyte epithelium covering the inside
of the colon, the thickness of the granulation tissue, and its cell content.
To test the statistical significance of differences between groups we
used Students t test (INSTAT 2.01).
RGTA11 protective action

In vitro characterization of RGTA11 protective activity against trypsin proteolysis was evaluated as described. Briefly, FGF-2 (provided by G. Mazue from Pharmacia, Italy) at 10 ng/ml was incubated
in the presence of trypsin (10 mg/ml) for 10 min at 37 C in the presence or the absence of 10 g/ml RGTA11. The incubation sample
(50 l) was then added to the culture medium (500 l) of CCL39
cells, and the biological activity of the FGF-2 was measured by its
capacity to stimulate thymidine incorporation in quiescent CCL39
cells. Heparin was used as control at 10 g/ml.
Colonic anastomosis formation
183 rats (Wistar, WI/WI, Ico, IFFA CREDO, France) between 200
and 225 g weight, were used in these experiments, in accordance with
the rules of the European Union for animal experimentation (rule no.
86/609/CEE). The operating protocol was as described by Van der
Hamm et al. [10]. Briefly, rats were anaesthetized by intraperitoneal
sodium pentothal injection (40 mg/kg), and a midline laparotomy
was performed. The sigmoid colon was cut 3 cm from the peritoneal
reflection. Both ends (5 mm depth) of the cut colon were immersed
for 2 min in a solution of RGTA11 (50 g/ml) or in a solution of
RGTA11/FGF-2 (50 g/ml, 100 ng/ml) or in physiological serum.
The incubation time of 2 min was previously established using iodinated FGF-2 and RGTA11 and by measuring the fixation of each
Results
In vitro protection assays of growth factors by RGTA11

Table 1 summarizes the results obtained for the measure
of the biological activitiy of FGF-2 after trypsin digestion
in the presence or absence of RGTA11. Values are reported
as a percentage of the initial biological activity. As indicated, RGTA11 was not as efficient as heparin for protecting FGF-2 against trypsin digestion since only 40% of
Table 1 Remaining biological FGF-2 activity
Incubation samples
Percentage of remaining
biological FGF-2 activity
FGF-2
FGF-2 + trypsin
FGF-2 + heparin
FGF-2 + heparin + trypsin
FGF-2 + RGTA11
FGF-2 + RGTA11 + trypsin
100 0.8
20 5.17
96 7.61
73 3.14
78 4.15
41 2.10
80
Table 2 Bursting pressure (mmHg) of colonic anastomoses after
2, 4, and 7 days (n = 12 per group)
Treatment
Bursting pressure
(mmHg)
Day 2
PBS (control)
RGTA11
RGTA11/FGF-2
40.08 28.90
87.50 46.73
69.50 40.65
Day 4
PBS (control)
RGTA 11
RGTA11/FGF-2
106.58 54.67
138.25 38.15
114.17 49.70
NS
NS
Day 7
PBS (control)
RGTA 11
RGTA11/FGF-2
184.83 41.93
182.17 38.40
184.33 48.04
NS
NS
< 0.01
NS
FGF-2 biological activity remained after RGTA11 protection versus 73% when heparin was added. However, the
low anticoagulant activity of RGTA11 was interesting for
in vivo use.
Healing of the anastomosis induced by RGTA11
Measurement of the bursting pressure of the anastomosis
after 2, 4, and 7 days is presented in Table 2. Both RGTA11
and RGTA11/FGF-2 treated anastomoses showed a greater
resistance to breakage in the first 48 h. Analysis indicated
that the twofold difference between pressures needed to induce leakage were significant compared to the nontreated
anastomoses (P < 0.01). On days 4 and 7, no differences
were detected between control and treated animals.
Histological studies
Histological studies performed on days 2, 4, and 7 showed
no significant differences between RGTA- or RGTA11treated animals and controls. On day 7 we observed the
formation of a dense vascularized conjunctive tissue.
Discussion
Our results indicate that a single administration of RGTA11

significantly strengthens an anastomosis in the first 48 h.
A twofold greater tensile strength was measured than in
control rats (P < 0.01). This difference ceased to be significant after 4 days, suggesting that RGTA11 was no longer
acting on the healing process of the anastomosis. After
7 days leakage pressure was the same between the three
solutions. The association of FGF-2 with RGTA11 showed
no advantage in strengthening the anastomosis compared
with the effects of RGTA11 alone, confirming other findings in which topical application of FGF-2 was ineffective
[12]. Although all samples were analyzed, no difference
was detected at the histological level between RGTA11,

RGTA11/FGF-2, and physiological serum treated anastomosis, even after 48 h when differences in breakage
forces were significant. The absence of differential effect
after 4 days between controls and RGTA11-treated animals
may be due solely to the diffusion of this compound. If this
hypothesis is correct, improvement of the wound healing
activity of RGTA11 should be obtained with the use of
slow-release devices at the site of the anastomosis.
The action of RGTA11 on anastomotic resistance to
breakage in the first few days must be compared to that of
RGTA11 and other RGTA in other wound healing models
[15]. In each of the cases the repair activity of RGTA was
explained by postulating that RGTA acts in vivo by trapping and protecting endogenously released FGFs or other
heparin-binding growth factors such as transforming
growth factor-, heparin-binding epidermal growth factor,
and platelet-derived growth factor.
In our search to understand the mechanism of RGTA11
in tissue repair we have more recently shown that
RGTA11 can inhibit plasmin [15] and elastase activity
[16] as efficiently as heparin and heparin sulfate [17].
Elastase is a secreted polymorphonuclear protease involved in collagen and other extracellular matrix protein
degradations. Hence RGTA11 can act both as a heparinbinding growth factor protector and as a heparin-binding
protease inhibitor.
Furthermore in vitro RGTA, as with heparin, modulates
collagen synthesis [18, 19], increasing collagen I synthesis and reducing type III collagen on smooth muscle cells
[19]. It can be proposed that in vivo a similar response explains the overall better resistance of the repair obtained
by RGTA treatment.
This study indicates that RGTA11 may represent a new
family of anastomotic sealing agents.
Acknowledgements The authors thank Prof. Norlindger for use
of the animal facilities of INSERM U402, Prof. Chatelet for all the
histological work and for helpful discussion, J. Josefonvicz and
D. Letourneur for directing A. M in the synthesis of RGTA11, and
R. Delelot for his advice in animal management. This work was
supported by research grant no. CRC932501 Assistance Publique
to A. S., by Inserm CJF 90014, by the Ministre de lEducation Nationale, by the CNRS, and by Naturalia et Biologica to D. B.
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JP, Josefonvicz J, Barritault D (1994) New approaches to tissue
regeneration and repair. Pathol Res Commun 190: 923928
2. Lafont J, Baroukh B, Meddahi A, Caruelle JP, Barritault D, Saffar JL (1994) Derivatized dextrans (RGTA) as promoters of bone
healing. Factors influencing their effectiveness. Cell Mater
4: 219230
3. Blanquaert F, Saffar JL, Colombier ML, Caruelle JP, Barritault
D (1995) Heparan like molecules induce the repair of skull trephine defects. Bone 17: 499506
4. Fredj Reygrobellet D, Hristova D, Ettaiche M, Meddahi A,
Jozefonvicz J, Barritault D (1994) RGTA11, functional analogue
of heparin sulfate as a new class of corneal ulcer healing agent.
Ophthalmic Res 26: 325331
81
5. Soulet L, Chevet E, Lemaitre G, Blanquaert F, Meddahi A,
Barritault D (1994) FGFs and their receptor, in vitro and in
vivo studies: new FGF receptor in the brain, FGF-1 in muscle,
and the use of functional analogues of low affinity heparin-binding growth factor receptor in tissue repair. Mol Reprod Dev
39: 4955
6. Mauzac M, Josefonvicz J (1988) Anticoagulant activities of dextran derivatives. I. Synthesis and characterisation. Biomaterials
5: 301304
7. Tardieu M, Gamby C, Avramoglou T, Josefonvicz J, Barritault
D (1992) Derivatized dextrans mimic heparin as stabilizers, potentiators, and protectors of acidic or basic FGF. J Cell Physiol
150: 194203
8. Goligher J, Moris C (1970) A controlled trial of inverting versus everting intestinal suture in clinical large bowel surgery. Br
J Surg 57: 817822
9. Fielding L, Stewart-Brown S, Blesovsky L, Kearny G (1980)
Anastomotic integrity after operations for a large bowel cancer:
a multicenter study BMJ 281: 411414
10. Van der Hamm A, Kort W, Weijama I, Van der Ingh M, Jeekel J
(1991) Effect of fibrin sealant on the healing colonic anastomosis in the rat. Br J Surg 78: 4953
11. Haukipuro K, Hulkko O, Alaivakko M, Laitinen S (1988) Sutureless colon anastomosis with fibrin glue in the rat. Dis Colon
Rectum 31: 601604
12. Slavin J, Nash J, Kingsnorth A (1992) Effect of transforming
growth factors B and basic fibroblast growth factor on steroidimpaired healing intestinal wounds. Br J Surg 79: 6972
13. Kingsnorth A, Vowles R, Nash J (1990) Epidermal growth factor increases tensile strength in intestinal wound in pigs. Br J
Surg 7: 409412
14. Mustoe TA, Andrew L, Cromack TD, Mistry D , Griffin A, Deuel
TF, Pierce GF (1990) Differential acceleration of healing of surgical incisions in the rabbit gastrointestinal tract by platelet-derived growth factor, type beta. Surgery 108: 324330
15. Meddahi A, Lemdjabar H, Caruelle JP, Barritault D, Hornebeck
W (1995) Inhibition by dextran derivatives of FGF-2 plasmin
mediated degradation. Biochimie 77: 703706
16. Meddahi A, Lemdjabar H, Caruelle JP, Barritault D, Hornebeck
W (1996) Inhibition of human neutrophil elastase by carboxymethyl benzylamide sulfonate dextran derivatives. Int J Biol
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17. Walsh RL, Dillon TJ, Scicchitano R, McLennan G (1991) Heparin and Heparan-sulphate are inhibitors of human leucocyte
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18. Asselot-Chapel C, Combacou L, Labat-Robert J, Kern P (1995)
Expression of fibronectin and interstitial collagen genes in
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19. Benazzoug Y, Logeart D, Labat-Robert, Robert L, Jozefonvicz
J, Kern P (1995) Derivatized dextrans modulate collagen synthesis in aortic smooth muscle cells. Biochem Pharmacol
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R. A. Awad J. Martin M. Cal y Major

J. L. Noguera R. Ramos C. Amezcua S. Camacho
R. Santiago J. L. Ramirez J. Castro
Transrectal ultrasonography: relationship with anorectal manometry,

electromyography and sensitivity tests in irritable bowel syndrome
Abstract Irritable bowel syndrome is the most frequently

diagnosed disorder in gastroenterology. It has been demonstrated with specialized motility studies that these patients compared to healthy subjects show changes in rectoanal electrical and mechanical activity and in rectoanal
sensitivity. However, until now no report has been published on morphological alterations in the rectum or the
internal anal sphincter. Twenty-five consecutive patients
with irritable bowel syndrome (mean age 32, range 17 47
years; 24 females) were evaluated prospectively by transrectal ultrasonography, rectal sensitivity studies, and recordings of both electrical and mechanical activity of the
distal rectum and internal anal sphincter during a 2-h interdigestive period. Ten healthy volunteers (mean age 34.5,
range 19 50 years) served as a control group. Paired and
non-paired Students two-tailed t test and linear regression
analysis were used. It was shown that muscle thickness of
the rectum during rest (4.7 0.1 mm) was correlated neither with its rectal spike amplitude (0.73 0.1 mV) nor with
rectal spike frequency (17.06 3.6 spike/2 h). In addition,
the diameter of the internal anal sphincter (1.2 0.1 mm)
was correlated neither with its resting pressure, nor with
frequency (17.1 3.2/2 h), duration (14.9 1.5 s), or amplitude (14.1 1.9 mmHg), of inhibition of the spontaneous
rectoanal inhibitory reflex. No correlation was found
between ultrasonographic parameters and rectal distension
variables (r =0.03). This study demonstrates for the first
time morphological anorectal changes in patients with irritable bowel syndrome compared to healthy subjects, in
addition to showing that morphological changes are independent of physiological ones. Therefore both transrectal
ultrasonography to determine anorectal morphology and
electromanometry to assess anorectal function are important measures in the evaluation of patients with irritable
bowel syndrome.
R. A. Awad () J. Martin M. Cal y Major J. L. Noguera
R. Ramos C. Amezcua S. Camacho R. Santiago J. L. Ramirez
J. Castro
Experimental Medicine and Motility Unit U-404-B,
Ministry of Health, Mexico City General Hospital,
D.F. 06726, Mexico
Key words Ultrasound Manometry Electromyography Rectum Anus Internal anal sphincter
Irritable bowel syndrome Rectal sensitivity
Rectoanal physiology
Rsum Le syndrome du clon irritable constitue le
trouble fonctionnel le plus frquemment diagnostiqu en
gastroentrologie. Des tudes spcialises de la motilit intestinale ont dmontr que ces patients, comparativement
des sujets sains, prsentent des modifications dans lactivit lectrique et mcanique recto-anale et dans la sensibilit anorectale. Jusqu prsent, aucune publication ne fait
mention daltrations morphologiques du rectum ou du
sphincter interne. Mthode: Vingt-cinq patients conscutifs
souffrant de clon irritable (ge moyen 32 ans, 14 47 ans;
24 femmes) ont t valus prospectivement avec une chographie transrectale des tudes de la sensibilit rectale et
des enregistrements la fois de lactivit lectrique et mcanique du rectum distal et du sphincter interne au cours
dune priode inter-digestif de deux heures. Dix volontaires sains (ge moyen 34,5 ans; 19 50 ans) ont servi de
groupes-contrles (moyenne dviation standard; test T de
Student bilatral appari ou non appari et une analyse de
rgression linaire). Rsultats: (1) Il a pu tre dmontr que
lpaisseur de la musculature rectale au repos (4,7 0,1 mm)
nest pas corrle avec lamplitude (0,73 0,1 mV) et la frquence (17,06 3,6 pics/2 heures) et que le diamtre du
sphincter interne (1,2 0,1 mm) nest pas corrl avec la
pression de repos, avec la frquence (17,1 3,2/2 heures),
la dure (14,9 1,5 sec.) et lamplitude (14,1 1,9 mmHg)
dinhibition du rflexe recto-anal inhibiteur spontan.
(2) Aucune corrlation na t trouve entre les paramtres
ultra-sonographiques et la distension rectale (r = 0,03).
Conclusion: Les rsultats de cette tude dmontrent pour
la premire fois les modifications dans la morphologie
ano-rectale survenant chez des patients porteurs dun clon
irritable en comparaison aux observations faites chez des
sujets sains en dehors du fait que ces modifications morphologiques sont indpendantes des donnes physiologiques. On en conclut que la fois lchographie transrectale
permettant dtudier la morphologie anorectale et llec-
83
tromanomtrie visant dterminer la fonction ano-rectale

sont des techniques importantes dans lvaluation des patients porteurs dun clon irritable.
Introduction
Irritable bowel syndrome (IBS) is the most frequently diagnosed disorder in gastroenterology [1, 2]. It usually leads
to a chronic condition that has a negative impact on the
patients quality of life. Although controversial [3], specialized motility studies have demonstrated changes in rectoanal electrical and mechanical activity [4 6] and sensitivity [6, 7] in patients with IBS. However, until now no
report has been published on morphological alterations of
the rectum or the internal anal sphincter.
Transrectal ultrasonography (TU) is currently the only
technique that provides clear and measurable images of
the rectal wall and the complete anal sphincter [8]. It is
quick and easy to carry out, causes little discomfort [9],
and emits no radiation. In addition, it is relatively inexpensive, easy to analyze by experienced personnel, and is
the most accessible radiological test [10]. TU is more reliable than computed tomography, which usually produces
poor-quality images of the rectoanal wall [11]. TU is currently employed to evaluate prostate disorders [12], rectal and perirectal pathology [13], staging [14], and detection of recurrent rectoanal cancer [15], pararectal fistules,
fissures, and abscesses in Crohns disease [9]. It is also
used in fecal incontinence [8], in the elderly [16], and in
constipation [17].
This report studied the rectoanal region by means of TU,
manometry, and electromyography in 25 consecutive patients with IBS and 10 healthy volunteers. We examined
the possible correlation between morphological and physiological findings, which could be useful in producing an
early diagnosis of IBS by means of a readily accessible
technique such as TU. This would obviate the need to
undergo rectoanal motility tests which are complicated [6,
18], not easily available [3], expensive, and time consuming to carry out and to analyze. This correlation would also
yield new knowledge on the physiopathology of this socalled functional disease, since there is little understanding about what functional means.
Subjects and study design

From August 1993 to February 1995 we examined 127 outpatients
consecutively referred to our tertiary unit. Among these there were
25 (mean age 32, range 17 47 years; 24 females) who were symptomatic for at least 2 years and fulfilled at least seven of the following ten criteria for IBS [19 21] (Rome criteria, 22): abdominal pain,
pain relieved by defecation, more frequent stools when pain begins,
looser stools when pain begins, abdominal distention, mucus per rectum, feeling of incomplete evacuation, altered stool frequency, altered stool form (hard or loose), and altered stool passage (straining,
urgency). Ten healthy volunteers (mean age 34.5, range 19 50 years;
4 females) served as a control group. Both sexes were included because although, almost all our patients were women, we do have male
patients [6, 23]. Subjects who had previously undergone abdominal
or anorectal surgery were excluded. None had taken any kind of drugs
for at least 7 days. None of the women were pregnant. For inclusion
in the protocol the IBS patients could have no concomitant disease,
including, for the women, previous obstetric injuries that would affect the appearance of the internal anal sphincter. All subjects underwent clinical history recording, standard laboratory tests, rectosigmoidoscopy (Welch Allyn 32823 sigmoidoscope, Skaneateles Falls,
NY, USA) and TU. IBS patients were also given manometric and
electromyographic tests of the distal rectum and the internal anal
sphincter.
The protocol was approved by the Ethics and Research Committee of the Ministry of Health, Mexico City General Hospital in August 1993. Signed informed consent was obtained from all subjects.
Transrectal ultrasonography
Examinations were carried out based on techniques described elsewhere [8, 9, 13, 21, 24, 25] using endorectal sonographic equipment
(model 1850 Bruel and Kjaer Copenhagen, Denmark) consisting of
a rigid device, 24 cm in length, with 7-Mhz radial transducer, 2 cm
in diameter, and a focal point of 2 5 cm. The transducer spins at a
frequency of two or three cycles and covers 360. It is covered by a
latex balloon that is itself covered with a latex condom for protection. The balloon is coated with gel and introduced into the patients
rectum while lying on the left side with knees at a 90 angle to the
body. The balloon is then filled with 60 ml water. The procedure
takes 15 min to carry out.
Images 8 cm from the anal margin were obtained in examining
the rectum [9, 13]. We measured the following layers: mucosa (hypoechoic layer nearest to the balloon), muscularis mucosae (second
hypoechoic layer), submucosa (third echogenic layer), and muscularis propria (outermost hypoechoic layer). To evaluate the internal
anal sphincter, the transducer was introduced 2.5 cm from the anal
margin [15]. Total and muscle thickness was measured, the latter taken as a hypoechoic layer next to the submucosa [10, 24 27].
Measurements of both rectum and internal anal sphincter were
taken three times in the area that provided maximum clarity, and by
electronic indicators built into the equipments program. Because the
equipment does not register measurements of less than 1 mm, minimum thickness was given a value of 0.5 mm. The dimensions were
measured in resting state, during defecation movement (straining),
and during voluntary contraction of the sphincter (squeezing).

Manometric and electromyographic recording technique
Setting
The study was conducted at the Experimental Medicine and Motility Unit, U-404-B, Ministry of Health, Mexico City General Hospital. This is a tertiary referred unit that carries out basic research with
clinical applications in motility, physiology, pharmacology, gastrointestinal hormones, and biofeedback. The study was also conducted
at the Ultrasound Department of the Radiology Service. The patients
studied were referred to our unit from the general hospital, which is
one of the largest in Latin America and receives patients from all
social strata and from all regions of Mexico.
Intraluminal pressure and electrical activity were recorded by means

of the same probe: (Honeywell MP-3 motility probe, Honeywell,
Denver, CO, USA), which contains three miniature pressure transducers within a surgical grade silicone rubber tube 5 mm in diameter. The transducers were staggered at 120 intervals around the
probe. Myoelectrical activity was recorded by means of two bipolar
AgAgCl ring electrodes positioned around the probe alongside the
pressure transducers.
One pressure transducer was positioned in the internal anal
sphincter. The second transducer and a ring electrode were positioned
84
Fig. 1 Muscle thickness of the internal anal sphincter at rest in a

healthy subject (TU)
Public Education, United States of Mxico (Awad Reyes R, Luna

Trillo VM, 1995, certificate # 68958).
Fig. 2 Muscle thickness of the internal anal sphincter during strain

in a healthy subject (TU)
Fig. 3 Muscle thickness of the internal anal sphincter at rest in an
irritable bowel syndrome patient (TU)
Results
Subjects
in the rectum 5 cm from the pressure transducer in the internal anal
sphincter, and the third transducer with a ring electrode was positioned a further 5 cm away. Care was always taken to ensure the proper position of the probe throughout the 2-h duration of the study; our
experience with this probe (>300 studies [6, 23, 28, 29, 30]) shows
that folding or movement from the high-pressure sphincter zone is
very rare and easily detectable. A period of 30 min was allowed for
the patient to become accustomed to the presence of the probe. The
study was performed with the subject in the left lateral position.
Pressure waves and electrical signals were recorded simultaneously on a Hewlett-Packard 8-channel polygraph model 4574A
(Waltham, MA, USA) with lower and upper cutoff frequencies
set at 5 30 Hz for electrical recordings, an amplifier gain of
12.5 mmHg/cm for motor recordings, and a paper speed of 0.5 mm/s.
A band pass filter of 5 30 Hz removed all slow wave activity and
allowed only spike activity to be recorded. Only spike potentials
greater than 0.02 mV were considered. A reference electrode was
fixed to the right leg skin with electrode paste.
Each transducer used a diaphragm-type sensor and was referenced to atmospheric pressure. Calibration was performed before and
after each experiment. Pressure changes of less than 5 mmHg and
identifiable artifacts were excluded from analysis. Two forms of mechanical activity were assessed: (a) basal anal pressure and (b) naturally occurring rectoanal inhibitory reflex. There was a 2-h basal
period, with the sensors static in the internal anal sphincter and the
rectum. The naturally occurring rectoanal inhibitory reflex can be
defined as the association of spontaneous increase in rectal pressure
associated with inhibition of the internal anal sphincter [6, 28, 29].
Rectal sensitivity was measured as described previously [6, 7, 29].
Of the 127 prospects interviewed, 45 fulfilled the necessary

requirements. Twenty declined to participate because they
refused to allow a TU study, and finally 25 were enrolled.
TU was carried out on IBS patients and healthy volunteers
alike. IBS patients were also given electromyography and
recto-anal manometry tests to compare procedures. All laboratory and rectosigmoidoscopic parameters were normal.
Transrectal ultrasonography
Rectal wall
In all studied subjects the four layers of the rectal wall were
identified and measured clearly. In healthy subjects the
thickness of the total rectal wall and submucosa was significantly reduced during strain and squeeze (P < 0.05),
while in patients with IBS the thickness of submucosa and
muscularis mucosae was significantly diminished during
strain (P < 0.05; Table 1). Total rectal thickness at rest was
less in IBS patients than in healthy subjects (4.7 0.1 vs.
6.1 0.1 mm; P < 0.001).
Internal anal sphincter
Data are presented as mean SEM. Statistical significance was assessed using paired and nonpaired Students two-tailed t test. Linear regression analysis was used to evaluate correlations between morphological and physiological rectoanal variables. An level of 0.05
was used. Sonography was performed by members of the radiological team experienced in the interpretation of ultrasound images who
were blinded to the results of manometric and myoelectrical evaluations. The copyright on the computer program used in the electromanometry for this study has been registered with the Ministry of
The internal anal sphincter was clearly defined and measured in both healthy volunteers and patients with IBS. In
healthy subjects both the total thickness of the anal sphincter and the muscle thickness of the internal anal sphincter at
rest (Fig. 1) were significantly diminished during strain and
squeeze (P < 0.05; Fig. 2, Table 1). In patients with IBS there
was the opposite, with total thickness at rest (Fig. 3) being
significantly increased during strain and squeeze (P < 0.05;
85
Table 1 Sonography: anal
sphincter and rectal thickness
(mm) in 10 healthy individuals
and 25 IBS patients
Internal sphincter
Rectum
Total wall
Total wall
Muscular
Mucosae
Muscularis Submucosae Muscularis

mucosae
propria
Healthy individuals
Rest
5.400.22
1.850.15
6.100.1
1.400.16 1.350.18
Strain
4.640.28 * 0.550.15 * 4.650.23 * 1.200.13 0.950.05
Squeeze 4.730.17 ** 0.550.05 ** 4.500.21** 1.150.15 1.100.06
1.800.20
1.150.10
1.400.16 * 1.100.12
1.350.15 ** 1.050.11
IBS patients
Rest
5.120.25
1.240.12
Strain
5.720.20 * 1.380.10
Squeeze 5.720.19 ** 1.560.22 *
4.700.19
4.680.26
4.560.24
1.120.08 0.860.06 1.160.09

1.080.11 0.700.05 * 0.940.07 *
1.060.10 0.740.07 0.980.08
1.080.07
1.040.10
1.080.10
* = P < 0.05, rest vs. strain

** = P < 0.05, rest vs. squeeze
Fig. 4 Muscle thickness of the internal anal sphincter during strain

in an irritable bowel syndrome patient (TU)
Fig. 4), and muscle thickness increased during squeeze

(P = 0.02; Table 1). Muscle thickness of the internal anal
sphincter at rest was less in IBS patients than in healthy subjects (1.2 0.1 vs 1.8 0.1 mm; P = 0.01); however, it increased during strain (P = 0.0001) and squeeze (P = 0.0001).
Rectal electrical activity
During the 2-h recording period there was no loss of electrical signal due to poor apposition between the electrodes
and the rectal wall. The IBS rectal spike frequency was
17.06 3.6 spike/2 h, and the amplitude was 0.73 0.1 mV
(Fig. 5).
Fig. 5 A recording at the distal rectum and internal anal sphincter

level in which the IBS patients rectal spike amplitude is accompanied by an increase in rectal mechanical activity and an inhibition of
internal anal sphincter mechanical activity (spontaneous rectoanal
inhibitory reflex)
the internal anal sphincter of 14.1 1.9 mmHg, and a duration of inhibition of the sphincter of 14.9 1.5 s (Fig. 5).
Rectoanal mechanical activity
Sonography and electromyography
In IBS patients basal anal pressure was 23.1 2.5 mmHg.

The naturally occurring rectoanal inhibitory reflex showed
a frequency of 17.1 3.2/2 h, an amplitude of inhibition of
In IBS patients total rectal thickness and that of each layer

were nonsignificantly correlated with the frequency and
amplitude of rectal spike (r = 0.02).
86
Sonography and manometry

Total and muscle thickness of the internal anal sphincter
were nonsignificantly correlated with basal anal pressure
(r = 0.11) and with frequency, amplitude, and duration of
internal anal sphincter inhibition during the naturally occurring rectoanal inhibitory reflex (r = 0.02).
Sonography and rectoanal sensitivity
The rectal sensitivity values found in this study were similar to those in our previous report on 80 IBS patients [6].
Patients felt a sensation with 15.3 1.3 ml and discomfort
with 55.9 8 ml, and the time to perceive the sensation was
4.5 0.9 s. No significant correlation was found with any
morphological, sonographic, or physiological parameters
(r = 0.02).
Discussion
These results demonstrate for the first time morphological

anorectal changes in patients with IBS compared to healthy
subjects. They also show that morphological changes are
independent of physiological ones.
In our IBS patients the total thickness of rectal wall at
rest was less than that in healthy subjects. The contrary has
been reported in inflammatory diseases such as Crohns
disease [9], where an increase in thickness of the rectal
wall has been observed by TU in 40% of all patients and
in 58% of those with active proctological lesions. Having
previously reported on excitatory rectal neurotransmission
in IBS [6, 22], we evaluated the possible correlation
between thickness of the rectal wall measured by TU and
excitatory and inhibitory neurotransmission measured by
rectal electromyography [6, 18]. However, since we did
not observe any significant correlation, it is suggested that
physiological changes in rectal spike activity are independent of rectal wall morphological ones. Therefore we can
assume that greater or lesser thickness of the wall is not
related to higher or lower electrical activity.
Muscle thickness of the internal anal sphincter at rest
in this study was 1.85 0.15 mm. This agrees with the
2.09 mm reported by Gantke et al. [26], the 2 mm reported
by Nielsen et al. [10], and the 2.2 mm registered by Papachrysostomou et al. [32]. Others have reported measurements in the range of 3 8 mm [9, 17, 25, 27]. The discrepancy in these figures could be explained by the variety of
methods used. At the moment there is no standard technique.
Muscle thickness of the internal anal sphincter was less
in patients with IBS at rest than in healthy subjects but became greater during strain and squeeze. We could find no
explanation for this because, to our knowledge, this is the
first report on the use of TU in patients with IBS. Nevertheless, a probable explanation is that IBS patients have
chronic rectoanal excitatory activity [6], the muscle at rest
having a reduced thickness because it undergoes greater

exercise. Once excited, while working harder, its thickness
increases during strain and squeeze.
Our values on basal anal pressure are lower than those
previously reported [26]. This is probably because most
researchers use a stationary pull-through for their measurements; this is not very accurate because a number of
variables can affect the data, such as movement and increase of spontaneous pressure when the patient feels the
device being removed. Our data were based on figures
taken over an average time span of 2 h.
We found no significant correlation between morphological data on the internal anal sphincter produced by TU
and physiological data produced by manometry and electromyography. This supports the findings of Nielsen et al.
[33] and Gantke et al. [26] who also found no correlation
between the internal anal sphincter diameter and pressure
at rest in healthy subjects. On the other hand, Law et al.
[8] reported a relationship between pressure at rest and
internal anal sphincter thickness in seven patients with neurogenic anal incontinence. Although there is a discrepancy,
which shows that there may or may not be a correlation,
Law et al. reported on a small number of patients in whom
a relationship was observed only in those with intact external anal sphincter. Therefore it seems that diameter
changes in the sphincter are not related to physiological
factors in IBS patients.
A technical limitation in this study was that the ultrasound equipment was not able to measure more exactly
than 1 mm. This problem, however, is not unusual, having
been reported previously [33]. Another possible limitation
is that we used a water-filled balloon rather than a plastic
cone for the anal ultrasound assessments. However, anal
endosonography was performed by the same team of radiologists throughout the study. Care was always taken to
use the same amount of water to prevent over inflation of
the balloon that could squash the internal anal sphincter
and give false images of the muscle thickness. Moreover,
the same technique is currently used by Nielsen et al. [33]
and by Tjandra et al. [25] who do not feel that the use of a
plastic cone is necessary and routinely perform anal endoluminal ultrasound in patients without it. Furthermore, the
internal anal sphincter was clearly defined and measured
in healthy volunteers and in patients with IBS, and our description is correlated with that of other groups of investigators [10, 26, 32].
In conclusion, these ultrasound data provide for the first
time valuable information about morphological rectoanal
changes in patients with IBS. These alterations are independent of rectoanal mechanical and electrical physiological changes. This suggests that there are different pathways of neurotransmission in the received stimulus and its
conscious integration into the nervous system, and the process carried out by the effector organ.
The two methods electromanometry to evaluate the
functioning of the rectum and the internal anal sphincter,
and TU to determine its morphology constitute important techniques in evaluating the rectoanal segment. This
information could well be useful in improving our under-
87
standing of the physiopathology of such a common and

complicated disorder as IBS. These findings will probably
also lead to improved and more scientifically based treatment.
Acknowledgements With appreciation for the collaboration of
J. G. de la Cruz, M. Castro, M. E. Martinez, M. C. Sandoval, and
John Hertzberg for the English revision of the manuscript. A portion
of this report was part of the postgraduate theses in radiology of
J. M., J. L. N., and R. R.
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P. A. Lehur P. Glemain S. Bruley des Varannes

J. M. Buzelin J. Leborgne
Outcome of patients with an implanted artificial anal sphincter

for severe faecal incontinence
A single institution report
Accepted: 2 December 1997
Abstract Implantation of an artificial sphincter is an alternative treatment for patients with severe faecal incontinence. This prospective study from one institution has
evaluated the results from 13. Preoperative and postoperative incontinence scores, anal manometry, and quality of
life were evaluated in 13 patients who had undergone implantation of an artificial sphincter over a 7-year period.
Two patients were definitive failures. One developed
acute total colitis after 5 years of satisfactory function,
and a second had discomfort and demanded removal of an
otherwise functioning device. After a median follow-up
of 30 (range 576) months, 11 patients had an activated
and functional device. These included 6 with a urinary
AMS 800 and 5 with the newly designed anal ABS. The
mean incontinence score decreased from 17 to 4, and quality of life improved markedly. Two of the 11 patients had
undergone successful reimplantation, one following rupture of the cuff and the second following ulceration of the
control pump through the labia. In no case was infection
or erosion of the anal canal a cause of failure. While the
cause of incontinence and age did not affect outcome, psychological reaction had a significant impact. The artificial
anal sphincter may have a role to play in severe faecal incontinence.
Supported by the Programme Hospitalier de Recherche clinique

1995 from the Ministre des Affaires Sociales, de la Sant et
de la Ville
Presented in part at the biennial meeting of the European Council
of Coloproctology, Edinburgh, June 1997
P. A. Lehur () J. Leborgne
Clinique Chirurgicale II, Htel-Dieu, 1 Place A Ricordeau,
F-44093 Nantes, France
P. Glemain J. M. Buzelin
Clinique Urologique, Htel-Dieu, 1 Place A Ricordeau,
S. Bruley des Varannes
Clinique dExplorations fonctionnelles digestives,
Htel-Dieu, 1 Place A Ricordeau,
Key words Faecal incontinence Artificial anal

sphincter Surgical technique Outcome
Rsum Limplantation dun sphincter artificiel constitue une alternative thrapeutique chez des patients porteurs dune incontinence fcale svre. Cette tude prospective issue dune institution value les rsultats de 13
patients. Lincontinence pr- et postopratoire, les rsultats
de la manomtrie et la qualit de vie ont t valus chez
13 patients qui ont subi limplantation dun sphincter articificiel au cours dune priode de 7 ans. Chez deux patients, lintervention sest solde par un chec dfinitif. Un
malade a dvelopp une pancolite aigu aprs cinq ans dun
rsultat fonctionnel satisfaisant et un second sest plaint
dun tel inconfort quil en est venu demander lablation
de la prothse bien quelle fonctionne de manire satisfaisante. Avec un suivi mdian de 30 mois (576), 11 patients
sont porteurs dune prothse active et fonctionnelle: il
sagit de 6 prothses urinaires de type AMS 800 et de 5
porteurs de la nouvelle prothse ABS. Le taux moyen du
score dincontinence a t abaiss de 17 4 et la qualit
de vie remarquablement amliore. Deux des 11 patients
ont subi une rimplantation avec succs, lun la suite
dune rupture du manchon et le second en raison dune
ulcration de la pompe de contrle dans la grande lvre.
En aucun cas, nous navons observ une infection ou une
rosion dans le canal anal comme cause dchec. Alors que
la cause de lincontinence et lage naffectent pas la qualit
du rsultat, les ractions psychologiques ont un impact important. Un sphincter artificiel peut donc avoir un rle important jouer dans le traitement de lincontinence fcale
svre.
Introduction
Severe faecal incontinence is distressing and can affect patients at any age. Results of conventional surgical sphincter repair are unpredictable [14] and subsequent management is controversial when sphincteroplasty is not indi-
89
Table 1 Basic details in 13 patients undergoing implantation
of artificial urinary or bowel
sphincter for faecal incontinence
Sex
Agea
(years)
Cause of
incontinence
Implantation
(model and date)
Stoma
Removal
(date)
1. Padb
2. Joyb
F
M
27
33
Anal agenesia
Anal agenesia
AMS 800 (09/98)

AMS 800 (03/91)
No
No
3. Soub
4. Irvb
5. Brob
6. Mar
7. Bou
8. Bon
9. Lar
10. Nie
M
F
M
F
M
F
F
F
22
32
28
48
27
60
52
52
Anal agenesia
Trauma
Trauma
Trauma
Anal agenesia
Neurogenic
Neurogenic
Trauma
AMS 800 (01/93)

AMS 800 (06/94)
AMS 800 (11/94)
AMS 800 (11/95)
AMS 800 (04/96)
AMS 800 (04/96)
AMS 800 (04/96)
ABS (05/96)
No
No
Yes
No
No
No
Yes
No
11. Let
12. Bra
13. Bou
F
F
F
60
42
48
Neurogenic
Neurogenic
Neurogenic
ABS (06/96)
ABS (04/97)
ABS (05/97)
Yes
No
No
Yes (02/94)
Yes
(reimplant ABS 10/96)
No
No
Yes (09/96)
No
No
No
No
Yes
(reimplant ABS 05/97)
No
No
No
Patient
a
b
At time of implantation
Patients previously reported with follow-up ending 09/95
cated or has failed [5, 6]. Two new procedures, dynamic

graciloplasty [7, 8] and artificial anal sphincter implantation [911] have recently emerged, both appear to be promising. However, their respective roles have not been clearly
defined to date, and careful evaluation of the comparative
benefits and drawbacks of these procedures is required to
determine the most effective treatment for patients in
whom conventional surgical management has failed. We
report the current findings of an ongoing prospective study
of the outcome of patients with end-stage faecal incontinence who have undergone implantation of an artificial
anal sphincter at our institution.
Patients and methods

Patients
Thirteen consecutive patients with end-stage faecal incontinence
[4 men and 9 women with a median age of 40 (range 2260) years]
underwent implantation of an artificial sphincter over a 7-year
period. Five have been previously reported with a shorter followup [10]. Two types of artificial sphincter were used: the AMS 800
urinary sphincter as previously described [9, 12], and the ABS
(Artificial Bowel Sphincter), both made by Pfizer-American
Medical Systems (P-AMS, Minneapolis, Minn, USA). The latter
model had been used in our institution since it became available in
May 1996. It was specifically designed for patients with faecal incontinence and incorporates several new features. Briefly, these include larger cuffs (2.9 cm in height and 12 cm in length) better
adapted to the normal anatomy; a reinforced cuff-closing system,
which is more resistant to straining efforts; a deactivation button on
the control pump, which allows the cuff to be left deflated for a prolonged period of time; an access port, located at the end of the pump
and which allows hydraulic fluid to be added to the system, if necessary, without additional surgery; and a prolonged time span before cuff reactivation to adapt to the time necessary for defecation.
All of the patients had had severe faecal incontinence for a median of 15 years (range 328 years) with an almost daily occurrence
of stool leakage. Four were markedly overweight. Thorough exam-
ination had excluded the possibility of local sphincter repair, and

creation of a stoma had been considered for each patient. Five patients had had between two and five previous attempts at repair. The
main details of the patients are shown in Table 1. Informed consent
was obtained prior to implantation.
Technique
Preoperative care included thorough bowel preparation and preparation of the skin using a iodinated disinfectant for a 48-h period.
Antibiotics were given at induction of general anasthesia. The skin
was shaved in the operating room immediately before the procedure.
The inflatable perianal cuff was implanted through a single anterior
anal incision, which allowed a rectovaginal or rectourethral separation large enough to accept the device. From this incision, a perianal
tunnel was created around the anal canal by blunt dissection. The optimal position of the cuff was at the level of the anorectal junction,
not too high, so that pressure was not applied on the rectum, and not
too low, so that the device did not protrude at the anal margin. Cuff
length was measured precisely to obtain the best fit using a specially designed template placed around the anal canal through the created wound. Pressure-regulating balloons, ranging from 80 to 100 cm
of water pressure, were implanted in the prevesical space, and the
control pump was inserted in the labia majora or scrotum through a
small horizontal abdominal incision. Mean duration of the procedure
was 130 min.
During the postoperative period, the patients were kept fasting
for 23 days to discourage early bowel movement. Ice packs were
applied in the region of the control pump to reduce edema. Frequent cleaning of the preanal incision was required. Laxatives and
small enemas were given to ease evacuation while the patient
adapted to the device. Mean postoperative hospital stay was 8
days. At approximately 8 weeks following surgery, the sphincter
was activated during a single-day hospital admission, and the patients were fully instructed in the manipulations required to open
the bowels.
The need for late reactivation or reoperation, as well as any factors observed during these procedures, were recorded. All of the implantations and subsequent readjustments or reoperations were performed by one surgeon (the first author). Incontinence scores were
recorded prior to the procedure and at each follow-up visit, using the
20-point Cleveland Clinic score [13]. Subjective assessment of quality of life and manometric evaluation [14] were performed annually.
90
Table 2 Manometric results
13 patients
mean FU:30 months
Definitive failures:
2 patients
1. intercurrent disease
2. psychological
Temporary failures,
reimplant: 2 patients
cuff rupture (1)
anal stenosis (1)
Preopera- After
After
tive
activation
activation
b
closed cuff open cuffb
Successful implant:
9 patients
Resting pressure (cmH2O)a

Anal canal length (cm)a
4110
1.9
727
2.1
4810
2.0
MeanSD
Results in 10 patients with device in function for more than
3 months (one patient refused postoperative manometry)
System in function:
11 patients
Fig. 1 Outcome of 13 patients implanted with anal artificial sphincter for severe faecal incontinence
Results
Of the 13 patients, two underwent subsequent reimplantation (Table 1). Therefore total of 9 unmodified artificial
urinary sphincters (AMS 800) and 6 artificial anal sphincters (ABS) were implanted. The median follow-up after
implantation was 30 (range 576) months. During the very
early stages of our experience, one postoperative infection
occurred in the abdominal incision of a patient with chronic
diarrhea and early return of bowel movement. It was successfully treated with debridement and antibiotics. Following this event, two other patients with diarrhea underwent
elective creation of a temporary stoma with closure at two
months after implantation. One obese patient underwent
surgery for an incisional hernia, which appeared on the
stoma site 1 year after implantation. There was no other
morbidity due to creation or closure of any stoma.
Four (30%) patients underwent removal of the device
(Fig. 1). Of these, two patients with an urinary sphincter
(AMS 800) failed definitively. One patient, after 5 years
of excellent results (during which time she married and had
two children), developed severe ulcerative colitis, which
was resistant to medical therapy, ultimately requiring a
proctocolectomy. The second, a male patient with iatrogenic traumatic incontinence was never satisfied with the
Fig. 2 Clinical score of incontinence before (white bars) and
after implantation of an artificial anal sphincter (black bars).
An AMS 800 was implanted in
patients no. 2 7; and an ABS
in patients no. 1, 8, 9, 10, and
11. The 20-point Cleveland Clinic score of incontinence has
been used for this evaluation
(normal continence: 0, max incontinence: 20)
device in spite of a good functional result. He asked for the

control pump to be repositioned in the scrotum three times.
Two years later, he opted for dynamic graciloplasty in another center, which also failed. He now has a stoma.
The other two patients underwent successful reimplantation. One, who had been implanted with an urinary
sphincter (AMS 800) in 1992, had had an unsatisfactory
functional result. Rupture of the cuff tab was identified
when the patient underwent reimplantation with an anal
sphincter (ABS). This latter device gave an excellent result following relocation of the cuff, which initially had
been too close to the anal margin. The second patient was
the first to undergo implantation of an ABS device. A toonarrow cuff led to faecal impaction 2 months after activation. The patient had compressed the pump repeatedly to
release the obstruction, which caused ulceration of the labia. Following removal of the device, the patient requested
reimplantation, since she had been very satisfied with the
initial outcome. Reimplantation with a larger cuff was successfully carried out 6 months later, and the device continues to give good results.
A further patient had to undergo reoperation to relocate
the pressure-regulating balloon because of chronic pain,
around it. In another patient, impaction occurred after an
8-day hospital stay for treatment of a cardiac problem. This
was resolved by deactivation of the sphincter and careful
evacuation of the fecaloma.
Eleven patients currently have had an activated artificial sphincter for more than 3 months. All have experienced a clear improvement in continence. Four have regained control of flatus. Two patients, one with an urinary
91
sphincter and one with an ABS, still have slight leakage of

liquid stool. The mean incontinence score decreased from
17 (range 1420) before the procedure to 4 (range 010)
at the last follow-up. Six patients report difficulties with
evacuation and regularly need small enemas, four of whom
also require oral laxatives. None of the patients are on a
special diet. One patient observed rapid closure of the cuff
without enough time to defecate. A change of the pump is
being considered in this case.
All patients reported a significant improvement in their
quality of life and psychological well-being. Two had had
normal pregnancies and delivered by cesarean section,
with special care taken not to cut the connecting tubes of
the device.
Manometric results are shown in Table 2. Variations
over time were minimal. Closing time of the cuff, which
restores anal pressure, ranged from 30 s (in the patient
needing to deactivate to be able to defecate) to 10 min with
a mean value of 6 min.
Discussion
There is increasing evidence that the artificial anal sphincter may be useful in treating severe faecal incontinence
[912]. The original fear that the device would not be tolerated, either because of postoperative infection or rejection, has so far not been borne out.
In this series, the infection rate was low and was never
a reason for removal. To achieve this, bowel preparation
and precise surgical technique are essential. The procedure
for implanting the anal device is straightforward, even in
obese patients. The use of two surgical teams, one abdominal and the other perineal, with a specially trained nurse
to prepare the device, are essential requirements. A diverting stoma is routinely required only in patients with chronic
diarrhea [12].
Careful patient selection may account for the good results obtained in this series. Patients with a very thin rectovaginal septum, excessive descending perineum, and severely scarred or irradiated perineum were excluded.
Follow-up also showed satisfactory long-term tolerance, as 11 patients have had the device for more than
1 year without any problem. Likewise, Wong et al. [11] reported similar findings at a mean of 58 months of followup. Urological experience has confirmed, on a larger scale
and for longer periods of time, that the artificial urinary
sphincter is well tolerated as a foreign body [15, 16]. The
infraperitoneal location of all the components may contribute to this satisfactory outcome. In previous reports [9, 11],
half of the failures were due to mechanical failure and the
other half to infection. Improvements in the latest device
accounted for the decreased incidence of mechanical failure in this series. Furthermore, mechanical failure was not
a cause of definitive failure, even if revisional surgery was
sometimes needed to rectify it. The patient must be clearly
informed preoperatively of possible problems which may
occur, as in any form of prosthetic surgery.
Like other authors [11], we were surprised by the quality of faecal continence obtained with the device. Patients
regained a high level of confidence and usually stopped
wearing a pad once they had become used to the device.
Although quality of life assessment was subjective, all of
the patients reported a marked improvement. Manometric
assessment showed that, while the deflated cuff creates a
small increase in resting anal pressure and a marked increase when the cuff is inflated, the pressure remains low
enough to avoid tissue ischaemia and erosion. Although it
may not be adequate to control profuse diarrhea, our patients indicated that they had enough time to reach the toilet with the activated device. Evacuation disorders appear
to be of greater concern [9, 10]. They were quite common
in our series, but usually settled with time after careful follow-up, involving patient education about the problems involved with constipation, regular telephone check-up, and
visits in the outpatient clinic during the first 6 months while
the patient adapted to the device. They were never a cause
of failure. However, restricted indications for use of an artificial anal sphincter include incontinence associated with
an evacuation disorder and excessive perineal descent with
straining, as the patients may be unable to overcome the
obstacle created by the cuff. Our experience indicates that
anal narrowing can be avoided by the use of a cuff with a
larger circumference, and precise adjustment of anal pressure can be achieved without surgery by increasing or decreasing the hydraulic pressure via the access-port on the
control pump.
Careful selection of patients, based on both clinical and
psychological factors, is mandatory before implantation of
an artificial anal sphincter. Our only device-related failure
occurred in a patient with psychological problems, a circumstance also observed by Wong et al [11]. Given our selection criteria, the cause of incontinence had no obvious
influence on the outcome of procedure. The result in patients with anal agenesis were especially gratifying, as the
patients were young and very demanding, and functional
results and tolerance were excellent.
The artificial anal sphincter is a possible option for treatment of end-stage, severe faecal incontinence not amenable to sphincter repair. The infection rate can be kept low
with adequate perioperative and intraoperative care and selective use of a diverting stoma, especially in patients with
diarrhea. There appears to be less risk of mechanical failure with the current model of the device. Further experience is needed to determine whether the same results can
be achieved with this new device and the procedure of dynamic graciloplasty [8].
References
1. Schener M, Kuijpers HC, Jacob PP (1989) Post-anal repair restores anatomy rather than function. Dis Colon Rectum 32:
960968
2. Setti Carraro P, Kamm MA, Nicholls RJ (1994) Long-term results of post-anal repair for neurogenic fecal incontinence. Br J
Surg 81: 140144
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3. Yoshioka K, Keighley MRB (1988) Clinical and manometric assessment of gracilis muscle transplant for fecal incontinence.
Dis Colon Rectum 31: 767769
4. Christiansen J, Ronholt Hansen C, Rasmussen O (1995) Bilateral gluteus maximus transposition for anal incontinence. Br J
Surg 82: 903905
5. Engel AF, Sultan AH, Kamm MA, Bartram CI, Nicholls RJ
(1994) Anterior sphincter repair for patients with obstetric trauma. Br J Surg 81: 12311234
6. Oliveira L, Pfeiffer J, Wexner SD (1996) Physiological and clinical outcome of anterior sphincteroplasty. Br J Surg 83:502505
7. Williams NS, Patel J, George BD, Hallen RI, Watkins ES (1991)
Development of an electrically stimulated neoanal sphincter.
Lancet 338:11661169
8. Baeten CG, Geerdes BP, Adang EM, Heineman E, Konsten J,
Engel GL, Kester AD, Spaans F, Soeters PB (1995) Anal dynamic graciloplasty in the treatment of intractable fecal incontinence. N Engl J Med 332:16001605
9. Christiansen J, Sparso B (1992) Treatment of anal incontinence
by an implantable prosthetic anal sphincter. Ann Surg 215:383386
10. Lehur PA, Michot F, Denis P, Grise P, Leborgne J, Teniere P, Buzelin JM (1996) Results of artificial sphincter in severe anal incontinence. Report of 14 consecutive implantations. Dis Colon
Rectum 39:13521355
11. Wong WD, Jensen LL, Bartolo DCC, Rothenberger DA (1996)
Artificial anal sphincter. Dis Colon Rectum 39:13451351
12. Michot F, Lehur PA, Forestier F (1997) Artificial anal sphincter. Semin Colon Rectal Surg 8:16
13. Jorge JMN, Wexner SD (1993) Etiology and management of fecal incontinence. Dis Colon Rectum 36:7797
14. Martelli H, Devroede G, Arhan P, Duguay C, Dornic C, Faverdin C (1978) Some parameters of large bowel motility in normal man. Gastroenterology 75: 612618
15. Litwiller SE, Kim KB, Foue PD, White RW, Stone AR (1996)
Post-prostatectomy incontinence and the artificial urinary
sphincter: a long-term study of patient satisfaction and criteria
for success. J Urol 156: 19751980
16. Montague DK (1992) The artificial urinary sphincter (AS 800):
experience in 166 consecutive patients. J Urol 147: 380382
A. Barrier S. Houry M. Huguier
The appropriate use of colonoscopy in the curative management

of colorectal cancer
Accepted: 10 February 1998
Abstract A total of 175 patients who underwent a curative resection for a colonic (n = 130) or a rectal cancer
(n = 45) between 1986 and 1992 were entered into a routine clonoscopy program. Colonoscopies were performed
1 year after the operation, and then at 2-year intervals. The
findings at colonoscopy, as well as those of preoperative
colonoscopy (when performed), were recorded. Eleven
anastomotic recurrences were diagnosed at an asymptomatic stage, at a mean follow-up of 14 months. All of them
were identified in patients with a stage B or C primary
rectosigmoid cancer. Eight patients underwent another
potentially curative re-operation. Only perioperative colonoscopy (preoperative colonoscopy; first postoperative colonoscopy in patients for whom the preoperative procedure
was incomplete or not performed) allowed diagnosis of
second cancers (n = 7) and adenomatous polyps greater
than 10 mm (n = 17). Further colonoscopies detected only
polyps less than 10 mm. Positive examination rates for successive follow-up colonoscopies were 15, 20 and 23%, respectively; they were significantly higher in patients who
had previously had adenomatous polyps than in patients
who had not: 30% versus 6% (P < 0.025), 46% vs 5%
(P < 0.005) and 38% vs 11% (P < 0.025), respectively. From
these data, the following recommendations are made: (1)
All colorectal cancer patients should have a total colonoscopy either before (whenever possible) or soon after operation; (2) Based on results of the perioperative colonoscopy, patients: should undergo their first follow-up colonoscopy only 3 yearly (presence of synchronous adenomatous polyps) or 5 yearly (absence of synchronous adenomatous polyps) after resection; (3) In patients with stage B
or C primary rectosigmoid cancer, a surveillance of the suture line by rigid proctosigmoidoscopy should be added
during the first 2 postoperative years: 6, 15 and 24 months
after the operation.
A. Barrier S. Houry M. Huguier ()

Department of General and Digestive Surgery, Hospital Tenon,
4, rue de la Chine, F-75020 Paris, France
Key words Colonoscopy Cancer Colorectal Surgery

Rsum 175 patients devant subir une rsection vise
curative pour un cancer colique (n = 130) ou rectal (n = 45)
entre 1986 et 1992 ont t inclus dans un programme de
colonoscopie de routine. Les colonoscopies ont t ralises une anne aprs opration, puis deux ans dintervalle. Les donnes des colonoscopies de mme que les
donnes des colonoscopies propratoires (lorsque ces dernires ont t ralises) ont t enregistres. 11 rcidives
anastomotiques ont t diagnostiques un stade asymptomatique, en moyenne 14 mois postopratoires. Ces dernires ont t diagnostiques chez des patients porteurs initialement dun cancer recto-sigmodien de stade B ou C.
Huit de ces malades ont t traits par une rintervention
potentionnellement curative. Seules des colonoscopies
priopratoires (colonoscopie propratoire ou premire
colonoscopie postopratoire chez des patients chez lesquels lexamen propratoire tait incomplet ou non ralis) ont permis un diagnostic de deuxime cancer (n = 7)
et de polypes adnomateux dune taille suprieure 10 mm
(n = 17). Les colonoscopies ultrieures nont dtect quun
seul polype de moins de 10 mm. Les constatations positives lors des colonoscopies de contrle successives ont t
respectivement de 15, 20 et 23%; les taux ont t significativement plus levs chez des patients qui avaient en
propratoire des polypes adnomateux que chez ceux qui
nen avaient pas: 30 vs 6% (P < 0.025); 46 vs 5% (P < 0.005)
et 38 vs 11% (P < 0.025). De ces rsultats, on peut tirer les
recommandations suivantes: 1) Tout patient porteur dun
cancer colo-rectal doit avoir une colonoscopie totale soit
avant lopration (si cela est possible) soit immdiatement
aprs. 2) En se basant sur les rsultats des colonoscopies
priopratoires, on peut conclure que les patients doivent
subir leur premire colonoscopie de contrle postopratoire seulement trois ans aprs lintervention (en cas de polypes adnomateux synchrones) ou cinq ans aprs lintervention (en cas dabsence de polypes adnomateux synchrones). 3) Chez des patients avec un stade B ou C de cancer recto-sigmodien primaire, une surveillance de la ligne
de suture au moyen dun proctosigmodoscope rigide doit
94
tre ralise durant les deux premires annes postopratoires: 6, 15 et 24 mois de lopration.
Introduction
The appropriate use of colonoscopy in the management of

colorectal cancer patients remains controversial, especially after operation. For many authors [1 3], colonoscopy should be performed regularly as a routine procedure.
The aim of such a follow-up is two-fold: early detection of
anastomotic recurrences, which improves the chance of a
new curative resection [1, 3, 4] and early diagnosis of metachronous cancers, but also their prevention by successive
interventions in the polyp-cancer sequence [5]. However,
this policy poses the problem of cost and patient acceptance. Moreover, its ability to alter the survival rates significantly is questionable [6, 7]. For these reasons, some
authors are reluctant to adopt it [8]; for them, routine colonoscopy should be confined to a single procedure, either
before or soon after operation, and further use of colonoscopy should be restricted to symptomatic patients.
The aim of this retrospective study was to assess the
usefulness of routine colonoscopy in the management of
colorectal cancer patients. We reviewed the results of preoperative and postoperative colonoscopies in a series of
175 consecutive patients who had been operated on curatively and were asymptomatic at the time of colonoscopy.
On the basis of our results and the literature available, a
colonoscopy program is proposed.

Between January 1986 and December 1992, 401 patients were admitted to our department with a diagnosis of colorectal cancer. Of
these, 305 (76%) underwent a potentially curative resection, defined
as the absence of apparent local or metastatic tumor at the end of the
operation and the absence of tumor at the margins of resection. Out
of the 305 patients, 91 did not undergo any postoperative colonoscopy because of age, associated disease, death within 18 months of
surgery, or refusal. Eight patients were lost to follow-up. In another
31 patients, colonoscopy was performed because of symptoms or an
increase in plasma carcinoembryonic antigen levels. The remaining
175 patients entered the present study. In these patients, one or more
postoperative total colonoscopies (i.e. examining the entire colon up
to the cecum or the ileocolonic anastomosis) were performed as a
routine procedure. There were 97 (55%) men and 78 (45%) women,
with a mean age of 66 years. Four patients were diagnosed with two
primary cancers. Thus, there were 179 carcinomas of the colon and
rectum diagnosed in these 175 patients. Site and pathologic stage
(according to the Astler-Coller classification [9]) of the primary cancers are given in Table 1.
In 98 patients, a total colonoscopy had been attempted prior to
operation. In 61 patients, the entire colon had been inspected; data
from these colonoscopies was recorded. In the remaining 37 patients,
the cecum could not be reached (failure rate = 38%) because of tumoral stenosis (29 patients), ineffective bowel preparation, or patient intolerance. In 38 other patients, the endoscopic evaluation had
been confined to a sigmoidoscopy. The remaining 39 patients had
not undergone any endoscopic examination, chiefly because they had
been operated on in an emergency. According to preoperative eval-
Table 1 Distribution of initial primary carcinomas by stage and site

Site
Ascending colon
Transverse colon
Descending colon
Sigmoid colon
Rectum
Total
Stage
A
B1
B2
C1
C2
Total
2
0
0
7
1
5
2
1
13
14
22
8
9
24
13
3
0
0
4
3
7
5
6
16
11
39
15
16
64
45
13
35
76
10
45
179
uation, patients were classified into two groups: patients who had
undergone a successful total colonoscopy (group 1: 66 known preoperative bowel status; n = 61) and patients who had not (group 2:
unknown preoperative bowel status; n = 114).
The postoperative schedule consisted of: (1) a first colonoscopy
12 6 months after the operation, irrespective of whether a preoperative colonoscopy had been performed, (2) a second colonoscopy
30 12 months after the operation, and (3) a third colonoscopy 54 12
months after the operation. Data from these colonoscopies was carefully recorded. A colonoscopy was considered as successful if: (1)
the entire colon up to the cecum or the ileocolonic anastomosis
had been seen, and (2) the bowel preparation had been effective. All
the polyps found were resected and evaluated pathologically. Only
adenomatous polyps were considered as positive findings; attention
was given to their size and location. An anastomotic recurrence was
defined as an intraluminal lesion occurring within 5 cm of surgical
anastomosis.
Findings from the first postoperative colonoscopy (12 6 months)
were compared in patients with unknown preoperative bowel status
(n = 114) and in patients with known preoperative bowel status
(n = 61), using the chi-squared test. P < 0.05 was considered significant.
Colonoscopies were divided into perioperative colonoscopies
and follow-up colonoscopies. Perioperative colonoscopies included
preoperative colonoscopies (when successful; n = 61) and first postoperative colonoscopies in patients with unknown preoperative bowel status (n = 114), whereas follow-up colonoscopies included first
postoperative colonoscopies in patients with known preoperative
bowel status (n = 61), second (n = 108) and third (n = 58) postoperative colonoscopies. For each follow-up colonoscopy, patients were
divided into two groups according to previous findings: absence or
presence of adenomatous polyps. The polyp occurrence rates were
calculated in these two groups and compared using the chi-squared
test. P<0.05 was considered significant.
Results
The findings from of 61 preoperative successful colonoscopies are given in Table 2. Four patients had synchronous
cancers. Forty-two adenomatous polyps were detected in
24 patients. They were distributed along the length of the
large bowel. Eleven polyps were greater than 10 mm.
Planned resection was altered by the results of preoperative colonoscopy in 6 patients (10%): 4 with synchronous
cancers, and 2 with adenomatous polyps greater than
20 mm.
A total of 341 postoperative colonoscopies were performed in the 175 patients: 175 at 12 6 months, 108 at
30 12 months and 58 at 54 12 months. Of these, 314 were
successful, giving a failure rate of 8%. The results are given
in Table 2. Eleven recurrences at the site of anastomosis
95
Table 2 Results of colonoscopy. Values in parentheses are percentages. (C colon)
Table 4 Adenomatous polyps: results of colonoscopy performed at

12 6 months in relation to results of preoperative colonoscopy
Timing of colonoscopy
First postoperative colonoscopy
Preop- 12 6
30 12
erative months months
54 12
months
Number of procedures
Successful procedures
Second cancers
98
61
4
175
163
3
58
52
0
Adenomatous polyps:
Number of patients
Number of polyps
Size (mm):<5
5 10
10 15
15 20
>20
24
42
17
14
6
2
3
44
88
60
22
4
1
1
20 (20) 12 (23)
38
25
34
20
4
5
0
0
0
0
0
0
9
5
7
15
6
29
10
25
15
9
14
5
7
7
5
9
11
3
1
1
Preoperative
colonoscopy
(n)
(n)
(%)
Polyps
Location:
Ascending C.
Transverse C.
Descending C.
Sigmoid C.
Rectum
Anastomotic recurrences
108
99
0
Table 3 Results of the first postoperative colonoscopy (126 months)

in relation to preoperative bowel status. Values in parentheses are
percentages
Preoperative bowel status
Anastomotic recurrences
Second cancers
Adenomatous polyps
Total number of polyps
Size (mm): <5
5 10
10 15
15 20
>20
Group 1 =
Known
(n = 61)
Group 2 =
Unknown
(n = 114)
4
0
9 (15)
17
15
2
0
0
0
5
3
35 (31)
71
45
20
4
1
1
were detected in asymptomatic patients, 9 at the 12 6

month colonoscopy and 2 at the 30 12 month colonoscopy. The mean time of diagnosis was 14 months (range:
7 and 26 months). All these recurrences were diagnosed in
patients with primary distal colon or upper rectal cancers.
Pathologic stage at the time of primary resection was B1
in 1 patient, B2 in 4 patients, C1 in 2 patients and C2 in 4
patients. Ten of these patients underwent re-operation, and
8 underwent a potentially curative resection (73%). Three
second cancers, all located in the ascending colon (cecum
and hepatic flexure), were diagnosed at the 12 6 month
colonoscopy (7, 8 and 11 months). These 3 patients underwent a curative re-operation. No second cancer was diagnosed after the 18th postoperative month. Adenomatous
polyps were found in 44 patients (25%) at the 12 6 months
colonoscopy, 20 patients (19%) at the 30 12 months colonoscopy and 12 patients (21%) at the 54 12 months colonoscopy. Their location and size are reported in Table 2.
Polyps
No polyps
24
37
7
2
(n)
(%)
No polyps
30
6
17
35
70
94
They were distributed along the length of the large bowel.

Six of the 88 adenomatous polyps detected at the 12 6
month colonoscopy were greater than 10 mm while all adenomatous polyps detected at further colonoscopies (38
and 25, respectively) were less than 10 mm.
Table 3 shows the results of the first postoperative colonoscopy in relation to the preoperative bowel status
(known or unknown). The three second cancers were
diagnosed in patients with unknown preoperative bowel
status. In these 3 patients, a total colonoscopy had been attempted prior to the operation, but the entire colon could
not be inspected because of a tumoral stenosis of the sigmoid colon. One of these patients had undergone a barium
enema, which had been reported as revealing no abnormality. Adenomatous polyps were found significantly more often in patients with unknown preoperative bowel status
(31%) than in others (15%); (2 = 5.36; P < 0.025). All the
adenomatous polyps found in patients with known preoperative bowel status were less than 10 mm. In contrast, 6
of the adenomatous polyps found in patients with unknown
preoperative bowel status were greater than 10 mm.
Perioperative colonoscopy (Table 2, column 1; Table 3,
column 2) allowed detection of a second cancer in 7 patients (4%) and of adenomatous polyps in 59 patients
(34%); 17 polyps were greater than 10 mm. Follow-up colonoscopies (Table 2, columns 3 and 4; Table 3, column 1)
did not allow detection of any second cancer. Forty-one
examinations were positive for adenomatous polyps: 9
(15%), 20 (20%) and 12 (23%), respectively. All the polyps
were less than 10 mm.
Table 4 shows the findings of colonoscopy performed
at 12 6 months (presence or absence of adenomatous
polyps) in relation to those of the preoperative procedure
(when successful). Among the 24 patients who had polyps
at preoperative colonoscopy, 7 were found to have new
polyps, giving a 1 year recurrence rate of 30%. Among the
37 patients who had negative preoperative colonoscopy,
2 were found to have polyps (6%). This difference is statistically significant ( 2 = 6.54; P < 0.025).
The first part of Table 5 shows the findings of colonoscopy performed at 30 12 months (presence or absence of
adenomatous polyps) in relation to previous findings.
Among the 39 patients with antecedent polyps. 18 were
found to have new ones, giving a 2-year recurrence rate of
46%. Among the 60 patients with no antecedent of polyps,
3 were found to have polyps (5%). This difference is statistically significant ( 2 = 23.97, P < 0.005). Similarly, the
second part of Table 5 shows the findings of colonoscopy
96
Table 5 Adenomatous polyps: results of colonoscopy performed at
3012 and 5412 months in relation to previous results. Values in
parentheses are percentages
Polyps
No polyps
30 12 months (n = 99)
54 12 months (n = 52)
Antecedent
of polyps
(n = 39)
No antecedent
of polyps
(n = 60)
Antecedent
of polyps
(n = 24)
No antecedent
of polyps
(n = 28)
18 (46)
21 (54)
3 (5)
57 (95)
9 (38)
15 (62)
3 (11)
25 (89)
performed at 54 12 months in relation to previous findings. Among the 24 patients with antecedent of polyps, 9
were found to have new ones (38%). Among the 28 patients with no antecedent of polyp, 3 were found to have
polyps (11%). This difference is also statistically significant (2 = 5.22; P < 0.025).
Discussion
Perioperative colonoscopy
Our experience confirmed the profitability of perioperative colonoscopy. Our observed synchronous cancer and
adenomatous polyps rates (4% and 34%, respectively) are
in agreement with the literature [10 14]. Seventeen adenomatous polyps were greater than 10 mm, thus of significant malignant potential [5]. Given the time intervals to
diagnosis of the three second cancers that were postoperatively detected (7, 8 and 11 months), it is almost certain
that they already existed at the time of operation, though
they were missed by operative palpation. One of these three
cancers was also not detected by preoperative barium enema. Similar cases of missed synchronous cancers have
been reported by others [10, 15]. This clearly suggests that
there is no alternative to a perioperative colonoscopy.
In fact, the only question is to determine whether perioperative colonoscopy is better performed before or soon
after operation When colonoscopy is performed prior to
the operation, inspection of the entire colon is often not
possible for reasons of tumoral stenosis, ineffective bowel
preparation, or patient intolerance. The reported failure
rate of preoperative colonoscopy varies from 21% to 58%
[10, 16, 17]; our observed failure rate (38%) falls within
this range. Given the necessity of a perioperative colonoscopy, the consequence of an unsuccessful preoperative procedure is to repeat the examination soon after operation.
For this reason, in order to avoid multiple invasive and expensive investigations, Barlow et al. [18] proposed performing colonoscopy only after surgery; at this time, colonoscopy is more often successful, with a reported failure rate of 10% (8% in our experience). This policy involves the risk of reoperation. In the series of Barlow et al.
[18], two patients required reoperation to remove adenomatous polyps that had been missed by preoperative barium
enema and operative palpation. In our experience, planned

resection was altered by preoperative colonoscopy in 6 of
61 patients (10%). Given the lack of sensitivity of operative palpation, it is probable that some of these 6 patients
would have required reoperation if preoperative colonoscopy had not been performed. In our opinion, these avoided
reoperations are a decisive argument for preoperative colonoscopy.
In patients with incomplete preoperative colonoscopy,
intraoperative colonoscopy has been proposed with good
results: a high percentage of complete examination, and
frequent alteration of the planned operation [19, 20]. We
have no experience of this policy, but is of interest because
of the reduction of the risk of: reoperation incurred. However, it cannot be applied everywhere because of the tight
cooperation between gastroenterologists and surgeons it
requires.
In our view, preoperative colonoscopy should be performed whenever possible. When colonoscopy is unsuccessful or not feasible (patients operated on in an
emergency), an early postoperative colonoscopy within
6 months of surgery (or an intraoperative colonoscopy,
where available) is mandatory. After curative resection and
perioperative total colonoscopy, the follow-up may begin
with a patient assumed to have a clear colon.
Follow-up colonoscopy
The appropriate postoperative use of colonoscopy remains
unclear; many programs as different as no routine colonoscopy in the early postoperative years, unless the entire
colon has not been inspected preoperatively [8] and annual routine colonoscopy for at least the first 6 postoperative years [2] have been proposed. The problem is to determine whether the profitability of routine colonoscopy
(positive examination rate, expected benefit) offsets its
cost. Indeed, a total colonoscopy costs approximately FF
4.000, including a 1-day hospitalization, fees of colonoscopy and anesthetic.
Approximately 10% of patients who have undergone a
potentially curative resection of a colorectal cancer will
develop an anastomotic recurrence [1, 3, 21]. Since successful resection of these recurrences in directly related to
early detection [4], intensive colonoscopic follow-up has
been advocated during this period. Many studies have been
carried out to assess the value of this policy with contradictory results and conclusions [1, 3, 8]. In the series of
Patchett et al. [8], all the patients with anastomotic recurrences were symptomatic at the time of diagnosis. Therefore, they concluded that, in the early postoperative years,
colonoscopy should be confined to symptomatic patients.
On the contrary, in the series of Buhler et al. [3] and Lautenbach et al. [1], asymptomatic anastomotic recurrences
were diagnosed as a result of routine colonoscopy and their
curative resection rate was higher than that of symptomatic
anastomotic recurrences. For these authors, colonoscopy
should be performed regularly as a routine procedure. Our
findings (11 asymptomatic anastomotic recurrences with
97
a curative resection rate of 73%) suggest that routine colonoscopy may actually detect anastomotic recurrences,
which are often amenable to potentially curative resection.
However, routine surveillance of the suture line seems useful only in selected patients and only for a limited time.
Anastomotic recurrences were only diagnosed in patients
with primary distal colon or upper rectal cancer. Similarly,
anastomotic recurrences were only found in patients with
stage B or C primary cancer. These findings are consistent
with other reports [1, 3, 21 23]. Therefore, routine surveillance of the anastomosis seems profitable only in patients with stage B or C primary rectosigmoid cancer.
Given the distance between anastomosis and anal verge in
these patients, this surveillance can be achieved by rigid
proctosigmoidoscopy, which is less invasive than colonoscopy. As is commonly reported in the literature [1, 3, 21,
22], most of our anastomotic recurrences (10 out of 11)
were diagnosed within 2 years of surgery. The latest one
was diagnosed during the 26th postoperative month. This
suggests that the duration of this surveillance may be safely
limited to the first 2 postoperative years. The following
schedule may be proposed: three rigid proctosigmoidoscopies during the 6th, 15th and 24th postoperative months.
A significant minority (1.5 3%) of patients surviving
after resection of a colorectal cancer will develop a second, metachronous, one [11, 15], while approximately 50%
will develop metachronous adenomatous polyps [13, 24].
These possibilities are the second reason advocated for a
colonoscopic follow-up. Routine colonoscopy is expected
to allow early detection of metachronous cancers, thereby
increasing the possibility of a new curative resection. It is
also expected to have a preventive role, as a result of removal of adenomatous polyps. This expectation is based
on the acceptance of the theory of the polyp-cancer sequence [5], which postulates that virtually all colorectal
cancers develop progressively and gradually from a benign
adenomatous precursor.
In the literature, it is often reported that routine colonoscopy may diagnose metachronous cancers in the first 2
or 3 postoperative years [1, 2]. This possibility should not
be interpreted as an argument for a colonoscopic surveillance. Indeed, as was suggested by the studies of Heald
et al. [25] and Kiefer et al. [15], two types of metachronous cancers must be distinguished: the early ones
(those detected in the early postoperative years) are in fact
missed synchronous cancers, whereas the late ones
represent true metachronous cancers, i.e. those which
have arisen after the primary resection. The reported mean
time for a real metachronous cancer to develop is about
10 years [1, 15, 25]. Hence, once the entire colon has been
perioperatively inspected with removal of all polyps found,
routine colonoscopy should not be expected to detect metachronous cancers in the early postoperative years; this was
confirmed by our experience. During this period, its potential findings are confined to adenomatous polyps. This
fact does not lead us to conclude that endoscopic surveillance is useless, since colonoscopic polypectomy has been
shown to result in a lower-than-expected incidence of
colorectal cancer [26, 27]. However, it clearly suggests that
the modalities of this surveillance must be guided by the

features of adenomatous polyps.
The adenomatous polyps that were detected at followup colonoscopies were distributed along the length of the
large bowel. The ascending colon was a common location.
These right-sided polyps would have been overlooked with
sigmoidoscopy. Therefore, we concur with other authors
who have recommended total colonoscopy, rather than sigmoidoscopy, for detection of metachronous adenomatous
polyps [28].
Concerning the appropriate frequency of examinations,
a few conclusions can be drawn from our experience. At
first sight, our colonoscopic program was profitable. At
each follow-up colonoscopy, adenomatous polyps were
found in 15 23% of patients; these positive examination
rates are consistent with other reports [2, 29]. However,
when analyzing size of detected polyps, this conclusion becomes doubtful. The malignant potential of adenomatous
polyps is known to be directly related to their size; it is
very low, less than 1%, for polyps less than 10 mm in diameter and only becomes significant for polyps greater
than 10 mm [5]. Therefore, our program only allowed detection of polyps of very low malignant potential. This suggests that our interventions in the polyp-cancer sequence
were too early. Time intervals between successive examinations should be adapted to the polyp growth rate. In the
present study, with 2-year intervals, all detected polyps
were less than 10 mm in diameter; most of them were even
less than 5 mm. Similar findings were reported by Wegener
et al. [30]: in their series, polyps of greater size than 10 mm
only appeared during the 3rd year after the index colonoscopy. This suggests that an adenomatous polyp needs more
than 2 years to reach the size of malignant potential. Therefore, a 3-year interval between successive examinations
seems appropriate: it allows the growth of polyps and their
removal when the real risk of malignancy has appeared.
The high 1-year recurrence rate of polyps is often the reason advocated for repeating colonoscopy 1 year after polypectomy [31, 32]. This polyp hunt, which does not respect the polyp growth rate, should be banished. It is a
source of considerable expense and unpleasant for patients.
Moreover, no benefit is provided as demonstrated in the
randomized study of Winawer et al. [33].
All patients do not have the same risk of metachronous
adenomatous polyps. In our series, patients with synchronous polyps developed metachronous ones significantly
more often than patients without. Similar results were reported by Kronborg et al. [14]: in their series, 27% of the
patients who had synchronous polyps developed metachronous ones, compared with 9% of those who did not have
synchronous polyps. This suggests that the colonoscopic
follow-up should not be the same for all patients. The
3-year interval between successive examinations should
only apply to patients at high risk of metachronous polyps
(those with synchronous polyps). For patients without synchronous polyps, given the high percentage of negative examinations, we propose to perform the first follow-up colonoscopy only 5 years after the perioperative procedure.
The theoretical risk of this 5-year interval is that a small
98
overlooked polyp may evolve into carcinoma during this

period. In fact, this risk is low since, as demonstrated by
Hofstad et al. [34], most adenomatous polyps go into spontaneous regression.
In conclusion, the following suggestions for a rational
use of colonoscopy in colorectal cancer can be made:
1. All colorectal patients must undergo a perioperative colonoscopy. This first procedure would be best performed
preoperatively.
2. Based on results of perioperative colonoscopy, patients
should undergo their first follow-up colonoscopy only
3 years (presence of synchronous adenomatous polyps) or
5 years (absence of synchronous polyps) after the initial
examination.
3. Patients with stage B or C primary rectosigmoid cancers represent special cases. They should have, in addition
to this program, regular examination of the anastomosis by
rigid proctosigmoidoscopy during the first 2 postoperative
years: at 6, 15 and 24 months.
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N. Y. Haboubi S. A. Abdalla S. Amini P. Clark

M. Dougal A. Dube P. Schofield
The novel combination of fat clearance

and immunohistochemistry improves prediction of the outcome
of patients with colorectal carcinomas: a preliminary study
Abstract To evaluate the significance of micrometastases in relation to survival rate, specimens from 48 colorectal carcinoma patients were analysed after fat clearance.
The number and size of the lymph nodes harbouring metastases and the significance of micrometastases for
patients survival were assessed. We found that although
the majority of metastatic lymph nodes (71.8%) were 5 mm
or less in diameter, their size had no effect on survival. Immunohistochemical staining of lymph nodes revealed that
15 of 25 patients with Dukes stage B diagnosed by routine staining had micrometastases, 86% of these lymph
nodes being less than 5 mm in diameter. The survival rate
of this subgroup was found to be considerably poorer than
that of Dukes stage B patients with no micrometastases.
None of the three patients with Dukes stage A carcinoma
had micrometastases. Since most of the metastases and micrometastases occur in lymph nodes of 5 mm and less and
can be easily missed by routine examination, we suggest
that fat clearance and routine immunohistochemical analysis of Dukes stage B improve the prediction of outcome
of colorectal cancer patients.
Key words Fat clearance Immunohistochemistry
Colorectal carcinoma Prognosis
Rsum Afin dvaluer la signification de micromtastases en relation avec le taux de survie, les pices opratoires de 48 patients porteurs dun cancer colorectal ont t
analyses aprs clearance de la graisse prirectale. Le nombre et la taille des ganglions lymphatiques contenant des
mtastases et la signification de ces micromtastases en
N. Y. Haboubi () S. A. Abdalla S. Amini P. Clark A. Dube
Department of Histopathology, Withington Hospital,
Nell Lane, Manchester M20 2LR, UK
M. Dougal
Department of Statistics, Christie Hospital,
Manchester, UK
P. Schofield
Department of Surgery, Withington Hospital,
Manchester, UK
relation avec la survie des patients ont t dtermins. Nous

avons trouv que la majorit des mtastases lymphatiques
(71.8%) avaient 5 mm ou moins de diamtre et que leur
taille navait pas deffet sur la survie. Des colorations immunohistochimiques des ganglions lymphatiques ont
rvl que 15 des 25 patients diagnostiqus comme prsentant un cancer au stade B de Dukes sur des colorations
de routine contenaient en fait des micromtastases et que
86% de celles-ci mesuraient moins de 5 mm de diamtre.
La survie de ce sous-groupe a t considrablement plus
mauvaise que celle de patients au stade B de Dukes sans
micromtastases. Aucun des trois patients un stade A de
Dukes ne prsentait de micromtastases. Etant donn que la
plupart des mtastases et micromtastases surviennent sur
des ganglions lymphatiques de 5 mm et moins et que ces
dernires peuvent aisment tre mconnues lors dexamens
de routine, nous proposons que la clearance de la graisse
prirectale et une analyse immunohistochimique de routine
des cancers au stade de Dukes B amliorent la prdiction de
survie des patients oprs dun cancer colorectal.
Introduction
Dukes classification for the staging of colorectal carcinoma

remains the most important prognostic parameter in assessing patients outcome [1]. It relies heavily on the accurate
detection of lymph node metastases. Failure of thorough
lymph node sampling may give rise to false staging and
therefore unrealistic prediction of survival. It is not possible
to detect macroscopically all lymph nodes which contain
metastases, and a significant proportion of metastases may
be present in lymph nodes less than 5 mm in diameter which
may be missed at routine cut-up [2, 3]. Some studies have
shown that the number of lymph nodes containing metastases influences prognosis more than tumour size or lymph
node site [4 6], but there are conflicting results as to the
significance of the volume of metastases [7 9].
The aim of this study was to assess the survival of patients with colorectal carcinomas whose colorectal resec-
100
tates were examined after fat clearance. Special emphasis

was placed on the frequency of metastasis in small (5 mm
or less) lymph nodes. The relation, if any, of the size of the
recovered lymph nodes containing metastases to survival
and the prognostic significance of micrometastases in
lymph nodes of Dukes A and B patients was investigated.

Specimens from 48 patients who had curative resections for colorectal carcinomas at the University Hospital of South Manchester
(between November 1989 and August 1992) were examined. All
specimens had undergone lymph node clearance, the details of which
have been previously described [10]. The pericolic and perirectal fat
was dehydrated in alcohol and left overnight in xylene, and the lymph
nodes were dissected out over a light box in a fume cupboard. All of
the lymph nodes obtained were routinely processed and 3-m sections were cut from the paraffin-embedded blocks before staining
with haematoxylin and eosin (H&E). The number and size of lymph
nodes with and without metastases was recorded. Nodules of tumour
deposits partially or totally surrounded by lymphocytes were regarded as metastatic deposits in lymph nodes and included in the analysis. All lymph nodes from patients with Dukes stages A and B were
stained for monoclonal cytokeratin (Cam 5.2, Becton and Dickenson) to check for micrometastases. The latter were defined as single
or small groups of malignant epithelial cells in lymph nodes that were
stained positively for cytokeratins and were not detected by H&E.
The survival data for the patients was obtained from the Cancer Registry. Statistical analysis was performed using the log rank test for
univariate analysis.
Results
Included in the investigation were 28 men and 20 women

with a mean age of 67.9 years (range 45.7 89.9 years).
The mean follow-up time was 55 months (range 3 91.7
months). In 39 cases the carcinomas were located in the
colon and nine were in the rectum. The tumours were
staged as Dukes stage A in three patients, Dukes stage B
in 25 patients Dukes stages C in 20 patients by routine
histopathology
A total of 2409 lymph nodes were cleared from the 48
specimens, of which 103 (4.3%) contained metastatic tumour (as assessed by routine H&E) and 2306 (95.7%) did
not, with means of 2.2 (range 0 50) and 48 (range 10 200)
lymph nodes respectively. The size and number of the
lymph nodes are presented in Table 1. Small lymph nodes
(5 mm or less in diameter) constituted 94% (n = 2271) of
all lymph nodes of which 74 nodes (3.25%) contained metastasis. Lymph nodes larger than 6 mm constituted 6%
(n = 138) and metastasis was found in 29 (21%). Of the 103
metastatic lymph nodes cleared 74 (71.8%) were 5 mm or
less.
None of the Dukes A patients (n = 3) had lymph nodes
metastases as determined by H&E and immunohistochemical staining and were alive at the time of the study. Analysis relating to survival rate was therefore limited to
Dukes stage B (n = 25) and Dukes stage C (n = 20) patients.
Table 1 Size and number of lymph nodes (LNs) obtained after xylene clearance in 48 colorectal cancer patients
Size
(mm)
Number of LNs
without metastases
Number of LNs
with metastases
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1097
563
311
145
81
51
25
16
6
1
4
3
2
1
0
14
13
19
13
15
5
8
6
5
2
2
0
0
0
1
Total
2306
103
Table 2 Changes in the staging of 25 Dukes B patients after cytokeratin (ck) immunostaining (LNs, lymph nodes)
Case no.
Number of ckpositive LNs
Dukes
stage
Survival
(months)
Outcome
1
2
3
7
9
10
12
13
14
16
4
5
6
8
11
15
17
18
19
20
21
22
23
24
25
0
0
0
0
0
0
0
0
0
0
7
2
2
2
2
1
1
1
1
2
1
6
2
2
3
B
B
B
B
B
B
B
B
B
B
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
84.8
84.6
84.3
45.8
79.4
79.5
77.9
62.6
68.8
56.2
49.6
96.0
82.4
17.3
78.9
54.6
55.5
24.1
55.2
54.2
54.0
53.6
91.8
37.4
20.4
Alive
Alive
Alive
Dead
Alive
Alive
Alive
Alive
Alive
Alive
Dead
Alive
Alive
Dead
Alive
Dead
Alive
Dead
Alive
Alive
Alive
Alive
Alive
Dead
Dead
Dukes B patients staged by routine H&E, as expected,

had a higher survival rate than Dukes C patients (P = 0.0193;
Fig. 1 a). According to the number of lymph nodes with metastases recovered, Dukes C patients were divided into two
groups containing either one to four or five or more metastatic lymph nodes. The survival rate of the first group of
patients was higher than that of the second group but did not
reach statistical significance (P = 0.4546). However, if the
survival of these two subsets of Dukes C groups was compared to the survival of Dukes B patients the difference in
the survival rate was significant (P = 0.0176; Fig. 1 b).
101
was slightly higher in the first group, the difference was

not significant.
All of the lymph nodes recovered from 25 Dukes B patients (n = 1266) were stained for cytokeratins. Thirty-five
lymph nodes (2%) in 15 patients were found to contain micrometastases (Table 2); 86% (n = 30) of these were small,
i. e. less than 5 mm in size. Six of these 15 patients died
of colorectal cancer within 55 months of surgery compared
with one of the 10 cytokeratin-negative patients
(P = 0.0652).
Discussion
Fig. 1 Survival of colorectal cancer patients stratified by (a) Dukes

stage and (b) number of metastases-positive lymph nodes recovered
after xylene clearance
Dukes C patients were then separated into two groups:

those with the largest metastatic lymph node/tumour deposit of less than 5 mm (i. e. 5 mm and less), and those with
at least one metastatic lymph node/tumour deposit 6 mm
or more in diameter, to compare the size of the metastatic
nodes with survival. Although the survival of the patients
The major prognostic factor in predicting survival of colorectal cancer patients is involvement of lymph nodes [11,
12]. This is usually based on the evaluation of the H&Estained sections of the lymph nodes recovered by routine
methods. It therefore becomes important to obtain the largest possible number of lymph nodes from the specimens.
The number of recovered lymph nodes varies from one laboratory or an others [13]. This may be due to the size of
the specimen, variation in the experience of the pathologist and the time spent to recover the nodes. To stabilise
some of these variables a number of techniques for fat
clearance have been used to allow lymph nodes to be easily identified [10, 13 15]. Xylene clearance is a simple
technique which allows the technician to take a greater part
and saving the pathologists time. This method allows detection of small lymph nodes (5 mm or less) which are often missed during routine dissection of specimens but
which may contain metastases [2, 3, 16]. This significant
increase in the yield of lymph nodes after fat clearance and
the prognostic value of this yield have been demonstrated
by many studies [3, 13, 15, 16].
Several investigators have addressed the relevance of
the number and size of metastases-containing lymph nodes
in colorectal cancer [3, 5, 9, 12, 17] and have recommended
a minimum number of lymph nodes to be recovered [18,
19]. Patients with one to four metastases-positive lymph
nodes have been reported to have a more favourable prognosis than those having more than five [3, 5, 6, 20]. Our
results are in agreement with Hida et al. [3] and indicate
that the presence or absence of lymph nodes with metastases is more important than their number in predicting
patients survival.
In our patients most of the lymph nodes with metastases (71.8%) are 5 mm or less in diameter. These findings
are in accordance with the results obtained by RodriguezBigas et al. [17]. Anticytokeratin antibodies were shown
to be capable of identifying micrometastases missed at routine H&E examination of lymph nodes [7, 8, 10].
Contradictory results have been reported in assessing
the significance of cytokeratin immunostaining for prognosis. Greenson et al. [7] reported a significant correlation
between the presence of cytokeratin-positive cells in
lymph nodes and poor prognosis, while Cutait et al. [8] and
Jeffers et al. [21] reported that the presence of cytokera-
102
tin-positive micrometastases had no effect on survival of

colorectal cancer patients. Fifteen out of our 25 (60%)
Dukes B patients were found to contain micrometastases,
86% of which were in small lymph nodes. Six of 15 cytokeratin-positive patients died within 5 years from colorectal carcinoma, while one out of 10 cytokeratin-negative patients died within the same period. Failure to recognise micrometastases may explain why a significant number of patients diagnosed as having Dukes stage B by the classical
methods resemble Dukes C patients. Our results confirm
the observations of Greenson et al. but differ from those
of Cutait et al. and Jeffers et al., possibly because other
prognostic factors such as differentiation, budding, lymphocytic infiltration and the extent through the wall, which
play a role in the overall outcome, were not taken into consideration.
We therefore recommend a combination of fat clearance
and immunohistochemical staining in Dukes stage B for
an accurate assessment of the lymph node status of colorectal carcinoma patients and to project a more realistic
prognosis.
References
1. Dukes CE (1932) The classification of cancer of the rectum.
J Pathol 35: 323 332
2. Herrera-Ornelas L, Justiniano J, Castillo N, Petrelli NJ, Stulc JP,
Mittleman A (1987) Metastases in small lymph nodes from colon cancer. Arch Surg 122: 1253 1256
3. Hida J, Mori N, Kubo R, Matsuda T, Morikawa E, Kitaoka M,
Sindoh K, Yasutomi M (1994) Metastases from carcinoma of the
colon and rectum detected in small lymph nodes by the clearing
method. J Am Coll Surg 178: 223 228
4. Hojo K, Koyoma Y, Moriya Y (1982) Lymphatic spread and its
prognostic value in patients with rectal cancer. Am J Surg 144:
350 354
5. Wolmark N, Fisher B, Wieand HS (1986) The prognostic value
of the modifications of the Dukes C class of colorectal cancer.
Ann Surg 203: 115 122
6. Hyder JW, Talbot TM, Maycroft TC (1990) A critical review of
chemical lymph node clearance and staging of colon and rectal
cancer at Ferguson Hospital 1972 to 1982. Dis Colon Rectum
33: 923 925
7. Greenson J, Isenhart C, Rice R, Mojzisik C, Houchens D, Martin E (1994) Identification of occult micrometastases in pericolic lymph nodes of Dukes B colorectal cancer patients using
monoclonal antibodies against cytokeratin and CC49. Cancer
73: 563 569
8. Cutait R, Alves V, Lopes L, Cutait D, Borges J, Singer J, et al
(1991) Restaging of colorectal cancer based on the identification of lymph node micrometastases through immunoperoxidase
staining of CEA and cytokeratins. Dis Colon Rectum 34:
917 922
9. Detry R, Kartheuser A, Lagneaux G, Rahier J (1996) Preoperative lymph node staging in colorectal cancer: a difficult challenge. Int J Colorect Dis 11: 217 221
10. Haboubi NY, Clark P, Kaftan SM, Schofield P (1992) The importance of combining xylene clearance and immunohistochemistry in the accurate staging of colorectal carcinoma. J R Soc
Med 85: 386 388
11. Shepherd N, Saraga E, Love S, Jass J (1989) Prognostic factors
in colonic cancer. Histopathology 14: 613 620
12. Fielding LP, Phillips R, Fry J, Hittinger R (1986) Prediction of
outcome after curative resection for large bowel cancer. Lancet
II: 904 907
13. Cawthorn SJ, Gibbs NM, Mark CG (1986) Clearance technique
for the detection of lymph nodes in colorectal cancer. Br J Surg
73: 58 60
14. Durkin, Haagensen (1980) An improved technique for the study
of lymph nodes in surgical specimens. Ann Surg 191: 419 429
15. Scott KW, Grace RH (1989) Detection of lymph node metastases in colorectal carcinoma before and after fat clearance. Br J
Surg 76: 1165 1167
16. Scott K, Grace R, Gibbons P (1994) Five-year follow-up study
of the fat clearance technique in colorectal carcinoma. Dis Colon Rectum 37: 126 128
17. Rodriguez-Bigas M, Maamoun S, Weber T, Penetrante R, Blumenson L, Petrelli N (1996) Clinical significance of colorectal
cancer: metastases in lymph nodes <5 mm in size. Ann Surg Oncol 3: 124 130
18. Goldstein N, Salford W, Coffey M, Layfield L (1996) Lymph
node recovery from colorectal resection specimens removed for
adenocarcinoma. Am J Clin Pathol 106: 209 216
19. Hernanz F, Revuelta S, Redondo C, Madrazo C, Castillo J, Gomez-Fleitas M (1994) Colorectal adenocarcinoma: quality of the
assessment of lymph node metastases. Dis Colon Rectum
37: 373 377
20. Gastrointestinal Tumour Study Group (1984) Adjuvant therapy
of colon cancers results of a prospectively randomised trial.
N Engl J Med 310: 737 743
21. Jeffers M, ODowd G, Mulcahy H, Stagg M, ODonoghue D,
Toner M (1994) The prognostic significance of immunohistochemically detected lymph node micrometastases in colorectal
carcinoma. J Pathol 172: 183 187
P. G. Setti Carraro I. C. Talbot J. R. Nicholls
Patterns of distribution of endoscopic and histological changes

in the ileal reservoir after restorative proctocolectomy for ulcerative colitis
A long-term follow-up study
Abstract Objective: This study was undertaken to assess

the long-term macroscopic appearance of the ileal reservoir after restorative proctocolectomy for ulcerative colitis, to determine whether there is any correlation between
macroscopic and histological changes and whether the distribution of these is homogeneous, focal or patchy. Background: No study has examined the macroscopic appearance of the ileal reservoir over a long period and it is still
unknown to what degree histological changes are diffuse
or patchy. Moreover, the relationship between macroscopic
and histological changes is poorly understood. Method:
Fifty-nine patients were examined by one clinician (PSC)
5.3 14.5 years (median 8.2 years) postoperatively. A rigid
sigmoidoscopy of the reservoir was performed. Four zones
in the posterior midline at 5-cm intervals from the ileoanal
anastomosis were inspected. At each level a macroscopic
score of severity of inflammation was given and a biopsy
taken. The degree of acute and chronic inflammation was
assessed using a histopathological scoring system. Results:
All reservoirs showed macroscopic abnormalities, which
were more marked distally in 14 (24%). There was no case
in which severity of inflammation was greater in proximal
than in distal zones. Endoscopy overall correlated with
both acute and chronic histological changes. On histological examination the patients could be divided into three
groups as follows: (1) all four biopsies were normal
(group 1, n = 8, 14%), (2) the score of acute and chronic inflammation decreased from distal to proximal zones
(group 2, n = 25, 42%) and (3) all four biopsies were abnormal with the same score (group 3, n = 26, 44%). The latter group significantly correlated with a present or past history of pouchitis. Conclusion: The study has shown that
when there is a gradation of inflammation within the ileal
P. G. Setti Carraro ()
Ospedale Maggiore, Istituto di Ricovero
e Cura a Carattere Scientifico,
Via F. Sforza 33, I-20122 Milan, Italy;
Tel.: +39(2)55033292; Fax: +39(2)5454379
I. C. Talbot J. R. Nicholls
Academic Institute, St. Marks Hospital, London, UK
reservoir this is more severe in distal than in proximal

zones.
Key words Restorative proctocolectomy
Ileo-anal anastomosis Ileal reservoir, Endoscopy
Histology Pouchitis Ulcerative colitis Surgery
Rsum But: Cette tude a t entreprise pour valuer
long terme lapparence macroscopique des rservoirs
ilaux aprs proctocolectomie restorative pour colite
ulcreuse et pour dterminer une corrlation entre les
changements macroscopiques et histologiques ainsi que
pour dterminer si la distribution de ces lsions tait homogne, focale ou ingale. Aucune tude na examin
lapparence macroscopique dun rservoir ilal sur un
long cours et on ne sait toujours pas quel degr les changements histologiques sont diffus ou ingaux. De plus, les
relations entre modifications macroscopiques et histochimiques sont mal comprises. 59 patients ont t examin
par un clinicien (PSC) de 5.3 14.5 ans postopratoires
(mdiane 8.2 ans). Une rectoscopie rigide du rservoir a
t ralise. Quatre zones sur la ligne mdiane postrieure
5 cm dintervalle partir de lanastomose ilo-anale ont
t examines. A chaque niveau, un score de svrit de
linflammation a t tabli sur la base des donnes macroscopiques et une biopsie a t prleve. Le degr dinflammation aigu et chronique a t tabli laide dun
score histopathologique. Rsultats: Tous les rservoirs
prsentaient des anomalies macroscopiques. Ces dernires taient plus prononces dans la partie distale du rservoir chez 14 patients (24%). Dans aucun des cas, linflammation tait plus svre dans la partie proximale que
dans la partie distale. Lendoscopie montre une bonne
corrlation avec, la fois, la partie aigu et la partie chronique de la lsion. Sur la base de lexamen histologique,
les patients peuvent tre diviss entre les trois groupes suivants: les quatre biopsies sont normales (groupe 1, n = 8,
14%), une diminution du score permettant de distinguer
linflammation aigu de linflammation chronique de la
partie distale en direction de la partie proximale (groupe
2, n = 25, 42%) et les quatre biopsies taient anormales
104
avec un mme score (groupe 3, n = 26, 44%). Ce dernier

groupe tait corrl de manire significative avec une histoire prsente ou passe de pouchite. Conclusion: Cette
tude a montr quil y a une gradation de linflammation
au sein du rservoir ilal et que linflammation est plus
svre dans la partie distale que dans la partie proximale
du rservoir.
Introduction
The macroscopic appearance of the ileal reservoir mucosa

after restorative proctocolectomy for ulcerative colitis has
been described in patients up to 5 years after closure of the
defunctioning ileostomy [1]. No study has examined this
over a longer period. There have, however, been many reports of the histological appearances [1 19], most of which
[1 12, 14 18] are based on a single or multiple biopsies
randomly taken at unspecified distances from the
ileoanal anastomosis (IAA). Thus, it is not known to what
degree histological changes are diffuse or patchy. Moreover, the relationship between macroscopic and histological changes is poorly understood. The first aim of this study
was to describe the long-term macroscopic appearance of
the reservoir and the second was to see whether a correlation exists between macroscopic and histological changes.
The third aim was to determine whether there is evidence
of longitudinal gradation of inflammation in the pouch.
Methods
Fifty-nine patients (37 men and 22 women), underwent restorative
proctocolectomy for ulcerative colitis at one hospital between November 1976 and December 1985. They were regularly followed up
for a mean of 8.7 years (median 8.2, range 5.3 14.5 years) and
formed a subgroup out of 110 patients operated on in the same period. The mean age at presentation was 33.4 years (median 31, range
14 60 years). A three-loop (S) reservoir was constructed in 19 patients, a two-loop (J) in 20 and a four-loop (W) in 18. Two patients
had an ileoanal Kock reservoir without the inverted nipple valve,
none had an anastomotic stricture.
All patients were consecutively seen in the outpatient clinic
during an 8-month period by one of the authors (PSC). A rigid sigmoidoscopy was performed and the presence or absence of the following features of inflammation was noted: loss of vascular pattern, granularity, oedema, mucosal haemorrhage, contact bleeding
and ulceration. Each feature was arbitrarily given a score of 1 to
yield a possible maximum score of 6. The entire reservoir and the
proximal ileal limb were examined, and four biopsies were taken
from the posterior wall starting at 5 cm from the ileoanal anastomosis and extending proximally and longitudinally at 5-cm intervals (Fig. 1). The specimens were orientated mucosa-uppermost
on a piece of cellulose acetate strip and fixed in buffered formalin (10%) for 24 h. They were then embedded in paraffin wax, cut
and stained with haematoxylin and eosin. All specimens were examined by one pathologist (ICT) unaware of the patients clinical
details. The severity of acute and chronic inflammation was recorded, based on histopathological criteria previously described
[1]. Acute (Ac) and chronic (Ch) inflammatory scores designated
Ac 0, 1, 2 etc. and Ch 0, 1, 2, etc. were given for each biopsy up
to a possible value of 6.
Fig. 1 Sites where biopsies were taken (centimetres from ileoanal

anastomosis)
A clinical diagnosis of pouchitis was made if a patient complained
of increased frequency of defaecation and the passage of watery
stools combined with acute inflammation (endoscopic score >3) seen
on rigid sigmoidoscopy and histological examination of a biopsy.
Unremitting pouchitis was diagnosed if severe inflammation and
symptoms persisted despite conventional treatment or recurred following treatment tapering. Patients were classified according to a
previous report [14] into one of three groups: A, never had pouchitis;
B, had isolated episode(s) of pouchitis; C, had chronic, unremitting
pouchitis.
The chi-square test was used to compare proportions for large samples and Fishers exact test was used for small samples. The relationship among scores was tested using Spearmans rank correlation
test and Kruskal-Wallis test. Normally distributed data were compared by Students t test and variance was tested using ANOVA test.
Differences were regarded as significant for a probability value of
less than 0.05.
Results
Macroscopic features
All reservoirs were macroscopically abnormal in some part
(Fig. 2). The commonest abnormality was loss of vascular
pattern, either alone (score = 1, n = 10) or with mild granularity (score = 2, n = 22), or with both of these and oedema
(score = 3, n = 16). More severe macroscopic inflammatory
changes (score >3) including ulceration occurred in 11
(19%) cases. Among these were two (3%) patients with
widespread mucosal ulceration (score = 6). In most cases
(45 out of 59, 76%) the macroscopic appearance and score
were the same throughout the pouch. A macroscopic gradient of severity of inflammation between the upper and
lower halves of the reservoir was found in 14 (24%) patients. In all of these cases the lower half exhibited the most
severe features (Fig. 2). There was no correlation between
macroscopic score and type of pouch, sex or interval from
ileostomy closure.
105
Fig. 2 The longitudinal distribution of severity of macroscopic inflammation in the ileal reservoir. Values given are median and range;
P<0.0001, Kruskal-Wallis test
Relationship between macroscopic appearance

and histology
The macroscopic score significantly correlated with both
acute and chronic histological score (Spearmans rank correlation test, r = 0.392, p = 0.002, r = 0.448, p<0.0001, respectively) generally throughout the pouch and at each
level sampled. In the 14 cases where endoscopic gradation
was seen, only 9 (64%) had corresponding histological gradation. Conversely, histological gradation was found in 16
other cases with a homogeneous macroscopic appearance.
Histology was normal in eight cases with homogeneous
macroscopic changes throughout the reservoir. In each of
these the macroscopic score included mucosal oedema
which itself was judged either by loss of vascular pattern,
oedema or granularity.
Microscopic features
Histological abnormalities were present in at least one biopsy from the reservoir in 51 (86%) patients. In eight (14%)
cases all biopsies showed normal small-bowel mucosa.
Acute inflammation was usually mild, not exceeding grade
Ac 1 in 49 (83%) cases. An acute score greater than grade
Ac 3 was never reported. The chronic inflammation grade
was usually greater, with scores of Ch 3 (n = 13, 22%),
Ch 4 (n = 13, 22%) and Ch 5 (n = 7, 12%) being reported.
An overall significant correlation between acute and
chronic inflammatory scores was observed (Spearmans
rank correlation test, r = 0.574, p = 0.0001).
When the four biopsies taken longitudinally in each patient were compared, combining acute and chronic scores,
three groups of patients could be identified (Fig. 3). In
group 1 (eight patients; 14%) the mucosa was histologically
normal in each of the four biopsies. In group 2
(25 patients; 42%) there was a highly significant gradient
of increasingly severe inflammation from proximal to distal zones (p<0.0001). In 15 of these cases the biopsies above
Fig. 3 The longitudinal distribution of severity of microscopic inflammation in the ileal reservoir. Values given are median and range.
Asterisk, significant difference in scores between biopsies taken at
different distances from IAA; P<0.0001
Table 1 The relationship between histological groups and pouchitis a. In group 1 all four biopsies were normal; in group 2 the score
of acute and chronic inflammation decreased from distal to proximal
zones; and in group 3 all four biopsies were abnormal with the same
score. Patients in group A never had pouchitis, those in group B had
isolated episode(s) of pouchitis and those in group C had chronic,
unremitting pouchitis [14]
Group 1
Group 2
Group 3
Total
a
Group A
Group B
Group C
Total
6
11
6
23
2
10
13
25
0
4
7
11
8
25
26
59
2 = 7.39297, df = 2, P = 0.024; A vs. B + C
15 cm were normal (Ac 0, Ch 0). In group 3 (26 patients;

44%) all biopsies were abnormal with the same degree of
inflammation in each. Most (21 out of 26) of these patients
were male (chi-square = 8.97, df = 2, p = 0.011). In group 2
the boundary between less and more inflamed mucosa was
roughly located at 5 cm in nine, 10 cm in nine and 15 cm
in seven patients. There was no correlation between the
presence of a histological gradient and pouch type (S, 4 out
of 19; J, 10 out of 20; W, 8 out of 18; p = 0.07), sex (p = 0.521)
or interval from ileostomy closure (p = 0.585).
Pouchitis
There was a highly significant correlation between severe
inflammation of the reservoir mucosa as detected macroscopically (score >3) and pouchitis or a history thereof
(p<0.000001). The relationship between the histological
groups and pouchitis is shown in Table 1. There was a
lower prevalence of chronic unremitting pouchitis or a history of previous pouchitis in group 1 than in groups 2 and
3 (p = 0.065). There was a significantly higher prevalence
of histologically normal mucosa among patients who never
had pouchitis. Those with previous or unremitting pouchitis were significantly more likely to be in group 3 than
in group 1 or 2 (p = 0.025). The presence of histological
106
Table 2 The relationship between histological score and pouchitis
in biopsies taken at 5 cm from IAA. a Patients in group A never had
pouchitis, those in group B had previous episode(s) of pouchitis and
those in group C had chronic, unremitting pouchitis
Cumulative (Ac + Ch) score
Group A
Group B
Group C
2 (0 7)
4 (0 5)
5 (4 8)
Values given are median (range); P<0.0001, Kruskal-Wallis test,

A vs B vs C [14]
gradation (group 2) did not correlate with pouchitis. Overall pouchitis was significantly related to the combined
score of acute and chronic inflammation in the biopsy taken
at 5 cm (Table 2).
Discussion
Early following ileostomy closure most asymptomatic patients have macroscopically normal mucosa [3, 5, 11, 20],
while symptomatic patients tend to have mild to moderate inflammation [3]. In a previous study using the same
scoring system [1] macroscopic abnormalities were observed in only a quarter of patients up to 5 years after
ileostomy closure. In the present study, by contrast, macroscopic abnormalities were seen in some part of the pouch
in all patients. This difference may be due to differences
in interpretation; however, also the longer follow-up time
with a minimum period of 5.3 years after closure of the ileostomy may be important since the follow-up time from
ileostomy closure is the main difference between these
studies. We cannot say whether the macroscopic changes
are progressive, or whether they mirror histological progression over time [8, 9, 15], as they occur soon after ileostomy closure and then tend to remain stable [11, 15].
Most macroscopic changes (i. e. loss of vascular pattern,
mild granularity, oedema) were mild and were interpreted
to indicate mucosal thickening, a change observed histologically by several authors in association with chronic inflammation [5 7, 21, 22]. This in turn is thought to be an
unavoidable response to faecal stasis [10]. In most patients
the macroscopic changes were evenly distributed throughout the entire pouch. This was always the case in the few
patients with acute pouchitis, in whom the macroscopic
changes consisted of diffuse erythema, contact and spontaneous bleeding and ulcers [1, 20, 21]. In a quarter, however, there was a difference in the macroscopic appearance
between the upper and lower part of the reservoir, whereby
the more severe changes were always seen distally. There
was not a single case with the reverse distribution.
As previously reported [1 4, 22] histological changes
included villous atrophy, crypt hyperplasia and inflammation and were unrelated to pouch design [2, 5, 6]. A significant relationship was found between macroscopic score
and both acute and chronic histological inflammatory
scores, confirming and extending the findings of Moskowitz et al. [1], who reported this relationship to be limited
to the acute inflammatory score. Despite the observed re-
lationship, in the presence of severe inflammation, endoscopy was less accurate and tended to overestimate the histological changes, as macroscopic scores up to 6 corresponded to acute histological scores which never exceeded
3. Similar findings have been previously reported [16, 17,
20] and might reflect the inaccuracy of the histological
scoring system, as recently pointed out by Goldberg et al.
[23], because there is no category for an indeterminate result. For instance, in a severely ulcerated specimen there
may be little or no residual epithelium, thus excluding the
contribution of acute polymorph mucosal infiltrate to the
score.
At the other extreme of the spectrum, endoscopy overestimated the severity of changes in the eight cases found
histologically to be normal. This may reflect the difficulty
in distinguishing between normal and mild macroscopic
abnormality (e. g. oedema, granularity or loss of vascular
pattern) in an otherwise histologically normal pouch. Alternatively it may be difficult histologically to identify mucosal oedema. Moreover, the sensitivity of endoscopy in
predicting the presence of a histological gradient was poor
(0.36), although it was reasonably specific (0.85) in excluding its presence. However, in no case did we underestimate macroscopic severity in patients with severe acute
changes seen histologically, as anecdotally reported by
McLeod et al. [16]. Thus in symptomatic patients, endoscopically severe acute features may not correlate with the
severity of histological changes; however, there is a good
correlation between histological and endoscopic findings
in cases where histological features show severe inflammation.
There is evidence from this study that a longitudinal
gradation of inflammation can occur within the reservoir.
Histology showed a diminution in severity of both acute
and chronic inflammation from proximal to distal zones in
almost half of the reservoirs (group 2). Whenever a gradation was found, it was always in this direction. It is unlikely that this was due to gradation along the same loop
of small intestine, since there was no relationship to the
type of reservoir. Histological gradation is unlikely to be
due to obstruction, as its prevalence was lowest in patients
with S pouches, most of whom (11 out of 19) used catheterisation to empty the reservoir. This observation might
well explain the heterogeneity of histological changes reported by others [24]. Four biopsies may not necessarily
be representative of the entire pouch mucosa; however, ethical considerations limit their number. We felt that four biopsies taken from set sites of the pouch would give a better representation of morphology than a single biopsy,
paired biopsies from the same site or multiple biopsies
taken at random sites [1 12, 14 18].
Shepherd et al. [13] reported the presence of a gradient
in the distribution of histological inflammatory scores
between biopsies taken at 10 and 5 cm from the ileoanal
anastomosis and between those taken from the anterior and
posterior wall at the same level (5 cm), suggesting that inflammatory changes may differ transversely. The latter was
recently confirmed by Veress et al. [19]. However, no information was available on the proximal part of the reser-
107
voir. Our data fill this gap since we demonstrated that in

almost half of the reservoirs a histological gradient does
exist and always increases in severity from proximal to distal zones. In patients with previous episodes of pouchitis
or with unremitting pouchitis, there was a tendency for an
even distribution throughout the entire pouch (Table 2).
This might suggest a generalised response of the reservoir
mucosa to a potential inflammatory agent rather than a local reaction due to direct contact. Similar observations and
conclusions were reported by Veress et al. [19]. It might
be that local contact by faeces can sensitise the mucosa in
some way to become generally inflamed. Moreover, extending previous observations [14], the present study has
confirmed that after an acute episode of pouchitis, the
pouch mucosa may return to normal, histologically, and
that, although uncommon, the entire pouch mucosa may
be histologically normal several years after ileostomy closure [14, 22].
In this study, a high combined acute and chronic score
for a biopsy taken at 5 cm appeared to be highly sensitive,
significantly correlating with a pouchitis in the past or
present. It suggests that a biopsy taken at this level might
be useful to identify patients in terms of their pouchitis risk
or as a marker of susceptibility to more extensive inflammation [13].
A significantly higher prevalence of pouchitis in males,
in particular of the unremitting variety, has been previously
reported [14, 25, 26], and recent studies [16, 18, 19] tend
to confirm this observation. The significance of this sex
difference has not been yet clarified.
In summary, after 5 years ileal pouches have macroscopic abnormalities which always involve the lower part
of the reservoir and in most cases its upper aspect. The abnormalities are usually diffuse and mild and are only occasionally severe. Endoscopy correlates with both acute
and chronic histological scores, but tends to overestimate
the underlying histological changes. A histological gradient, which is always more severe in distal than in proximal zones, can be detected in almost half of the reservoirs.
However, in patients with pouchitis or with a history of
pouchitis, histological changes are diffusely spread
throughout the pouch, suggesting the presence of an organ response to environmental factors.
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Silen W, Blair JE, Monahan-Earley R, Cisneros R, Cohen Z
(1994) Histological and microbiologic features of biopsy samples from patients with normal and inflamed pouches. Dis Colon Rectum 37: 26 31
17. Sandborn WJ, Tremaine WJ, Batts KP, Pemberton JH, Phillips
SF (1994) Pouchitis after ileal pouch-anal anastomosis: a pouchitis disease activity index. Mayo Clin Proc 69: 409 415
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19. Veress B, Reinholt FP, Lindquist K, Lofberg R (1995) Longterm histomorphological surveillance of the pelvic ileal pouch:
dysplasia develops in a subgroup of patients. Gastroenterology
109: 1090 1097
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of acute inflammation of the ileal reservoir after restorative ileoanal anastomosis. Gastrointest Endosc 36: 6 9
21. Tytgat GNJ (1989) The role of endoscopy in pouch monitoring
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210 213
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Ahren C (1980) Morphological and histochemical changes in
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does it reflect underlying Crohns disease? Gut 34: 1539 1542
P. A. Poletti A. Halfon M.-C. Marti
Papillomavirus and anal carcinoma
Abstract Human papilloma virus (HPV; 16 and 18) is

known to play an important etiologic role in cervical dysplasia, but its relationship with anal carcinoma is still unclear.
Surgical samples from 80 female patients treated for anal epidermoid carcinoma in the Policlinic of Surgery in Geneva
between 1976 and 1989 were retrospectively studied. Of
these, HPV detection was performed in 41 whose DNA was
preserved well enough to allow such an analysis. Seventeen
(42%) samples contained HPV, with a high percentage of
high risk HPV (15/41, 36%). Thirty-eight of the 80 patients
had a cervical smear, of which 18% revealed cervical carcinoma. When compared with epidemiological data, the results
of this study suggest that genital HPV infection predisposes
not only to cervical cancer, but also to anal carcinoma, possibly by means of contiguous contamination.
Key words Human papilloma virus HPV
Anal carcinoma Cervical dysplasia
Rsum Les virus HPV (16 et 18) sont connus pour jouer
un rle important dans ltiologie de la dysplasie cervicale,
mais les relations avec le cancer du canal anal demeurent
peu claires. Des prlvements chirurgicaux chez 80 femmes
traites pour un cancer pidermode du canal anal la
Policlinique de Chirurgie de Genve entre 1976 et 1989
ont t analyss rtrospectivement. La recherche du virus
HPV a t ralise chez 41 dentre elles dont le DNA a t
suffisamment prserv pour permettre une telle analyse.
17 prlvements (42%) contiennent du HPV avec un pourcentage lev de HPV de haut grade (15/41, 36%). 38 des
80 patientes ont galement subi des frottis du col utrin
dont 18% ont rvl la prsence dun carcinome cervical.
Les rsultats de cette tude ont t compars avec les
donnes pidmiologiques et suggrent quune infection
gnitale HPV prdispose non seulement au cancer du col,
mais galement au cancer du canal anal par contamination
de contigut.
P. A. Poletti A. Halfon M.-C. Marti ()
Policlinique de chirurgie, Hpital Cantonal Universitaire de Genve,
24 rue Micheli-du-Crest, CH-1211 Genve 4, Switzerland
Introduction
Anal carcinoma is rare, with an incidence in Switzerland

of about 0.6 cases/100 000 people per year. Elderly women
and homosexual males are more frequently affected. Epidemiological data suggest that a sexually transmitted factor plays an important role in its genesis.
Human papilloma viruses (HPVs) have been incriminated in epithelial neoplasia, particularly cervical dysplasia (condyloma, intraepithelial cervical neoplasia, carcinoma in situ, invasive carcinoma). Over 60 types of HPV
have been identified, but only a few (HPV 16, 18, 31, 33,
35) appear to be involved in genital intraepithelial invasive neoplasia or in low grade genital condyloma (HPV 6
and 11). However, the relationship between HPV and anal
carcinoma is still unclear. The available data are subject to
variation due to the techniques used for viral detection, including in situ hybridisation, southern blot analysis, and
polymerase chain reaction (PCR) with varying sensitivities
and specificities. Furthermore, the use of formaldehydefixed and paraffin-embedded tissues in retrospective studies has a deleterous effect on the DNA.
As stated above, anal carcinoma is much more frequent
in females than in males. This suggests the possibility that
cervical HPV infection spreads to the anal area from the
cervix, predisposing it for carcinoma. If such a contamination were to be demonstrated, antiviral treatment and
rectoscopic follow-up for women suffering from HPV cervical dysplasia might be justified.
In the present study, the relationship between anal carcinoma, HPV infection, and cervical dysplasia was analyzed. Using PCR, we retrospectively determined the prevalence of papillomavirus in fixed and embedded tissue sections of all patients treated for anal carcinoma in the surgical clinic of the Geneva Cantonal Hospital between 1976
and 1989. These data were then correlated with the prevalence of cervical dysplasia in the population studied.
109

Ninety-nine patients with available biopsy or surgical material treated for anal carcinoma in our hospital between 1976 and 1989 were
studied. These included 80 females and 19 males, of which the latter were excluded from the study.
HPV detection was performed for each tissue sample embedded
in paraffin according to the following method.
DNA extraction from paraffin embedded samples
The material was frozen for 30 min and cut into thin slices (510 m).
The paraffin was removed by leaving the slices in a xylol solution
for 20 min. The suspension was centrifugated for 15 min at 12 000 g
and, after decanting, the centrifugate was suspended in an ethanol
solution of progressively decreasing concentrations. After drying, the
material was resuspended in saline buffer. Proteinase K (400 g/ml)
was added and followed by 3-h incubation at 37 C. Proteinase was
inactivated by boiling for 10 min.
Determination of the presence of nucleic acids in the solution
Electrophoresis (minigel) of 10 l solution was carried out in an
ethidium bromide buffer solution, and analyzed by UV. Only DNAcontaining samples were used for further analysis. DNA quality was
studied by PCR, using a 100 (-gl 100) and 268 (-gl 268) bp -globin gene segment. Positive samples for -gl-100 or -gl-268 were
considered satisfactory for HPV detection-analysis by PCR. HPV
analysis of positive -globin samples by PCR used two different primers: PU-1M (Fujinaga 91) for high-risk HPV (16, 18, 31, 33, 52, 58)
and PU-31B (Fujinaga 91) for low-risk HPV (6 and 11). PCR solution was made with the following composition: 4 l DNA solution,
2 l PCR buffer, 1.6 l dNTPs (2.5 mM), 0.1 l TAQ (5 U/l),
0.4 l Primer (0.5 g/ml), 11.9 l Water for a total of 20 l solution.
30 amplification cycles were then performed each comprising denaturation (94 C, 30 s), annealing (53 C, 60 s), polymerization (72 C,
90 s). 12 l of this amplified solution was added to 2 l of bromophenol blue and placed on a 2% agarose gel. After electrophoretic migration, the samples were analyze in ultraviolet light.
Cervical smear analysis
Table 1 Females (n=33) with examinable anal biopsy. Incidence of

HPV DNA positivity
Case
Age
(years)
-Gl.
100
-Gl.
268
PU.IM
PU.31.B
2
4
7
8
11
13
16
26
27
30
32
37
38
41
44
50
53
54
55
57
65
66
68
70
75
77
81
82
83
86
90
94
96
65
68
54
86
56
69
68
68
65
35
71
84
47
79
53
61
82
42
78
73
81
79
55
73
71
72
70
84
68
83
66
57
53
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
66,2
22
15
12
Total
positives
33
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
All patients who had undergone gynaecological examination were

identified and available cervical smears were reexamined.
these 6 (42.8%) were HPV positive. All 6 patients were

furthermore in the group of 10 patients with a cervical lesion associated with HPV.
Results
Discussion
Each of the 80 paraffin-embedded samples was tested according to the method described above. Thirty-three samples were positive for -globulin and considered good
enough to be tested for HPV. The others were excluded
from further study.
HPV detection analysis was performed for these 33 patients (Table 1). Thirteen (39.4%) of 33 females were positive (12 high risk, 1 low risk). Of the 80 women, 38 had
undergone gynecologycal examination with can availably
cervical smear. Reexamination for atypia, carcinoma, condyloma, or other lesions in relation with HPV inclusion
(koilocytosis, dyskeratosis, parakeratosis) was undertaken. This identified 10 (26.3%) patients with a cervical
lesion associated with HPV (Table 2). Of the 38 patients,
14 (36.8%) were in the -globulin-positive group and of
HPV identification in formalin and paraffin-embedded

samples by PCR
Of the 80 samples analyzed in this study, only 33 had DNA
preserved well enough according to the criteria mentioned
above to allow analysis for HPV detection. This relatively
poor output (41.3%) is explained by DNA degradation by
fixing agents (formol and paraffin) and by our treatment
of fixed samples, which was necessary to allow analysis
of viral DNA. Formalin induces crosslinks between DNA
and environmental proteins and mechanical DNA fracture
is a major limitation in the extraction of DNA from embedded tissues. DNA degradation can be reduced by
cutting samples into very thin slices and by delicate manipulation of aqueous DNA-containing solutions. In spite
110
Table 2 Cervical smear analysis in 38 patients. Relationship between DNA positivity for anal HPV and cervical abnormality
Case
Age
(years)
1
2
7
8
14
15
16
20
21
27
30
35
39
40
45
46
50
51
64
65
66
67
68
76
78
80
82
85
86
88
90
91
92
94
95
97
99
69
65
54
86
48
71
68
52
34
65
35
81
66
61
69
42
61
79
80
81
79
62
55
86
59
73
84
50
83
77
66
85
26
57
75
65
60
Total
positives
38
63,4
-Gl. -Gl. PU.IM PU.31.B Cervical

100
268
smeara
+
+
N
N
N
C
N
N
N
N
C
N
CAM
N
N
N
N
N
CAM
SCC
P
SCC
N
N
N
N
N
N
N
N
AC
CAM
N
N
N
SCC
N
N
N
10
+
+
+
+
+
10
a
N normal, C condyloma, CAM microinvasive squamous cell carcinoma, SCC keratinizing squamous cell carcinoma, P parakeratosis,
AC adenocarcinoma
of all these precautions, a certain amount of DNA damage

is unavoidable.
Taq-DNA polymerase inhibitors are thought to be associated with the nucleic acids in paraffin-embedded tissues [1], causing false negative results. By eliminating
cases negative for -globin, the sensitivity of the method
used in our study was increased. Only three studies investigating anal material for the presence of HPV in anal cancer using PCR have been reported in the literature before
1993 [24]. The numbers of patients studied (13, 2, and
18) were smaller and selection criteria not specified. In the
study of Zaki et al. [4], DNA quality was verified using a
myeloxydase-specific primer, enabling amplification of a
genomic fragment of 359 bp. The test was positive for all
the samples studied. However, failure to specify the selection criteria of the 18 cases make if difficult to compare
these results with the present study. The well established

deleterious effect of paraffin and formalin on DNA analysis by PCR [59] makes it highly unlikely that 100% of the
embedded material to be analyzable by PCR. The effect of
fixation on the amplification of nucleic acids by PCR was
been studied [10], with evidence that the type of fixation
is important. Formaline is the most damaging agent for
DNA (3 (15%) cases positive out of 20 examined) and ethanol the least deleterious (13 (65%) positive out of 20).
The time interval between fixation and analysis by PCR
may also influence the sensitivity of the method [1113].
In our study, the mean delay for the 33 samples considered
analyzable was 9 years compared with 6.2 years (none over
9 years old) in the study of Zaki et al. [4].
Association between HPV infection and anal carcinoma
In our study, 13 (39.4%) of 33 patients with analyzable tissue contained HPV. These included 12 (36.4%) of high risk
(HPV 16, 18, 31, 52, or 58) and 1 (3%) of low risk (HPV
6 or 11). The prevalence of HPV in anal tissues without
neoplasia has varied in the literature between 0% [7] and
16,7% [4]. Our results reveal a prevalence 2.4 times higher
than the highest score described in the literature for nonneoplastic tissues using a similar method [4].
As previously described, was we found high-risk HPV
to be associated with anal carcinoma, in a high proportion
of cases [24, 1419]. This prevalence of HPV in anal carcinoma was lower in our study than in other studies using
a similar PCR method [24, 18]. For example, Zaki et al.
[4] detected HPV in 14 (77.8%) of 18 cases, including 7
(38.9%) high risk, 2 (11.1%) low risk, and 5 (27.7%) of
undetermined subtype. Palefski et al. [3] reported an overall prevalence of 11 (84.6%) of 13 cases, and Scholefield
et al. [17] of obtained a prevalence of 51%.
The lower prevalence of HPV in anal carcinoma in
present study could be explained by the definition of examinable tissues. We considered a tissue examinable if it
showed a positive response to either -globin-268 or globin-100 amplification. Zaki et al. [4] had amplified a
genomic fragment of 359 bp using a myeloxidase specific
primer. Long fragments being more difficult to amplify
than shorter ones [4] because of DNA degradation by fixation, their tissue DNA was probably less damaged than
ours. If the cases in our study showing no response to globin-268 amplification are removed the incidence of
HPV positivity of 13 (86.7%) of the remaining 15 cases is
very similar that reported by Zaki et al. [4]. It is important
to emphasize that the lack of response to -globin-268
(complication while positive for -globin-100 complication) does not indicate that it is impossible to detect HPV.
It only implies a decrease of the methods sensitivity [13].
Anal carcinoma and cervical dysplasia
In our patients with anal neoplasia, the incidence of cervical atypia of any form 26% was considerably higher than
111
the reported range of 212% in groups of asymptomatic

women [20, 21].
If in situ micro-invasive carcinoma is regarded as an invasive carcinoma, according to the Geneva tumour register, in our avaluable patients with anal neoplasia, 7 (18.4%)
women out of 38 had a cervical carcinoma, which is a significantly higher incidence in the general population.
These results indicate a close correlation between anal carcinoma and cervical dysplasia.
Many studies have shown that HPV plays an etiologic
role in cervical dysplasia. This may be in association with
co-factors, for example tobacco [17], HSV II, EBV [22],
CMV [6, 23, 24], HIV [25], sexual intercourse [26], and,
possibly, oral contraception [27]. Cervical HPV has been
found more frequently in association with uterine dysplasia than in histologically normal cervical smears [23, 28].
It may therefore be that once the virus has infected the genital tract, it invades the anal area by contiguity, predisposing to anal carcinoma. This could explain the high incidence of anal HPV in our study and the fact that anal carcinoma is much more frequent in females than in males.
Our findings are similar to those obtained by Scholefield et al. [18], who analyzed anal tissue from 152 patients
presenting with cervical carcinoma and from 50 patients
without cervical of similar age. Twenty-nine of the 152 patients (19%) were found to have anal dysplasia, compared
with none in the second group. Papilloma virus DNA was
found in 51% anal biopsies in the first group, and in 14%
in the second group. This could be correlated to the prevalence of anal dysplasia. In the present study, female patients with established anal carcinoma, a similar correlation with cervical dysplasia has been found.
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Int J Colorect Dis (1998) 13: 5760

C.-A. Vasilevsky P. Belliveau J. L. Trudel

Fistulas complicating diverticulitis

Accepted: 21 November 1997

frant de fistule traits entre 1975 et 1995 ont t revus. Le

Key words Diverticular disease Fistula Surgery

C.-A. Vasilevsky () P. Belliveau J. L. Trudel B. L. Stein

Diverticular disease is a very common problem. Fistulas

ter understanding of the disease process and the principles

Materials and methods

The types of fistulas encountered consisted of colovesical

Table 1 Diagnostic investigations

of atelectasis (7.1%), prolonged ileus (4.8%), arrhythmias

It is estimated that approximately 20% of all patients with

no other symptoms other than fecal vaginal discharge, as

Internal fistulas secondary to diverticular disease can be

Int J Colorect Dis (1998) 13: 6167

T. Watanabe Y. Kubota T. Muto

Substance P containing nerve fibers in ulcerative colitis

Accepted: 15 August 1997

Abstract The distribution of and morphological changes

Crohn et 8,4 0,8/1000 m2 dans le groupe contrle)

Key words Human colon Neuropeptide Substance P

The enteric nervous system is composed of a vast network

have used radioimmunoassay as the quantitative method

Table 1 Characteristics of patient population and surgical specimens

Slides were washed in MPBS and counterstained in hematoxylin for

Materials and methods

Fig. 1 Sub P containing fibers (arrows) in the lamina propria

Sub P fibers were identified as long filaments in the lamina

To evaluate these morphological changes of fibers the

Fig. 4 The average linear density of Sub P fibers of each patient

Fig. 5 Morphological changes of Sub P fibers in UC. Fibers were

Effects of site and inflammation in UC

scending; 23.3 3.8, sigmoid; 24.4 5.6 m/1000 m2,

Effect of the degree of inflammation

Fig. 8 The linear density of Sub P fibers according to the degree of

ysis of nerve fibers has been very difficult. Therefore most

in the UC group. The degree of inflammation also affected

increase in Sub P per se may enhance inflammation, the

33. Lotz M, Carson DA, Vaughan JH (1987) Substance P activation

Int J Colorect Dis (1998) 13: 6872

P. Broens E. Van Limbergen F. Penninckx

Clinical and manometric effects of combined external beam irradiation

Accepted: 21 November 1997

Abstract This study evaluates anorectal function after

P. Broens F. Penninckx () R. Kerremans

Key words Anal neoplasms Radiotherapy

was placed 58 cm above the anal verge. At the level of maximum

Studies were carried out in eight patients after informed consent.

285 (219304) 163 (120235)

Squeeze max. anal basal pressure

Amplitude of max. internal sphincter relaxation

the control group were found, possibly due to the limited

Fig. 1 Composition of resting anal pressure as measured with

Table 3 Volume and pressure data at consecutive levels of rectal

Max. tolerable sensation

This study demonstrates diminished anal basal and squeeze

2. Cummings BJ, Thomas GM, Keane TJ, Harwood AR, Rider WD

Int J Colorect Dis (1998) 13: 7377

G. D. Giebel R. Lefering H. Troidl H. Blchl

Prevalence of fecal incontinence: what can be expected?

Accepted: 29 October 1997

G. D. Giebel () H. Troidl H. Blchl

* P < 0.05; P < 0.01; * P < 0.001