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338 Wong et al.
tions are limited to 80 mEq/L, use of a supplemental line or oral administra-
tion may be required. Magnesium, an important electrolyte for energy-
requiring processes, is often overlooked [30]. Low levels of magnesium are
associated with large losses of gastrointestinal fluid and may make hypocal-
cemia resistant to treatment.
Enteral Nutrition
TPN has become the mainstay of nutritional therapy for patients with enter-
ocutaneous fistulas; however, enteral nutrition may also play a role. There
has recently been a renewed interest in enteral feeding for selected patients
with enterocutaneous fistula. Potential advantages of enteral nutrition in-
clude improvements in hepatic protein synthesis, gut mucosal integrity, and
immunological competence. Complete nutritional support with enteral feed-
ing is possible in selected patients. In most cases TPN is necessary initially
to stabilize the patient and establish positive nitrogen balance. In selected
cases TPN must be continued to maintain an anabolic state because only a
portion of the necessary calories can be given enterally.
Enteral nutrition in the form of low-residue diets has been shown ex-
perimentally [35] and clinically [36] to significantly decrease fistula output,
although to a lesser extent than TPN. Low-residue diets are relatively low
in cost, simple to administer, and require very little special equipment or
preparation. In addition, they help to preserve gut integrity [37]. Unfortu-
nately, low-residue diets have limited application in gastroduodenal and
upper small bowel fistulas unless the diet can be delivered to a point distal
to the fistula. With distal small bowel or colonic fistulas, low-residue diets
may be tolerated quite well, because an adequate length of small bowel will
affect complete absorption. At least 4 ft of functioning bowel must exist
between the ligament of Treitz and the fistula or between the fistula and
the ileocecal valve to allow adequate absorption.
Low-residue diets should not be used in patients with sepsis or perito-
nitis. Adynamic ileus, intra-abdominal abscess, and distal obstruction must
also be ruled out prior to the initiation of enteral feeding. The diet can be
administered through a nasogastric tube, a nasoduodenal tube, a feeding
jejunostomy, or a needle-catheter jejunostomy (elemental diets only). Tube
placement should always be checked either visually (at surgery) or radio-
graphically before feeding is started.
Elemental or low-residue diets are hyperosmolar and should be ad-
ministered by continuous infusion to minimize cramping and dumping. Ini-
tially the diet should be diluted to half strength and administered at a rate
of 50 mL/hr because the upper small bowel cannot tolerate hyperosmolar
infusion. When the small bowel is being used, the rate should be increased
before osmolarity. In some patients the small bowel may not tolerate more
than half-strength enteral feed and supplemental TPN will be required [37].
Very few series have involved the use of enteral nutrition exclusively.
Bury et al. [36] reported a 54% spontaneous closure rate and a 14–80%
Mangagement of Intestinal Fistulas 339
decrease in fistula output. Voitk et al. [38] reported a 75% rate of spontane-
ous closure and a fistula-related mortality rate of 16%. Recent studies eval-
uating “immune-enhanced” enteral formulas suggest a decrease in infec-
tious complications and may be indicated in a group of high-risk, complex
patients [31].
Somatostatin
Several studies have described the use of somatostatin to decrease fistula
output in patients with enterocutaneous fistulas [39–41]. The proposed
mechanism of action is a reduction in gastrointestinal secretions, primarily
through the inhibition of gastrin, gastric acid, biliary flow, pancreatic out-
put, and intestinal secretions. Somatostatin also is believed to inhibit gastro-
intestinal motility, thus increasing intestinal transit time [40]. The definitive
role of somatostatin in the treatment of patients with fistulas is unclear at
this time as no prospective studies have demonstrated an increased rate of
fistula closure with its use.
In a review of 175 patients treated with native somatostatin and TPN,
the overall spontaneous closure rate was 78%, with a mean closure time of
7 days [40]. However, side effects with native somatostatin are numerous;
they include hyperglycemia and rebound phenomena upon discontinuation
of the drug. Somatostatin analogue has demonstrated neither of these side
effects. Nubiola et al. [40] treated 27 patients with enterocutaneous fistulas
by using long-half-life somatostatin 201-995 analog. Within 24 hr of ad-
ministration, fistula output was dramatically reduced (mean reduction of
55%). Of 27 patients, 21 experienced spontaneous closure at a mean of 6
days (3–10 days). All six failures involved high-output fistulas; one patient
died of continued sepsis, and the remaining five had an anatomical reason
for nonclosure demonstrated at surgery (three complete anastomotic disrup-
tions and two distal obstructions). Mean spontaneous closure in a previous
group of patients treated with TPN alone was 3–5 weeks. The most encour-
aging results occurred with high-output small bowel fistulas in which the
addition of long-acting somatostatin analog increased the spontaneous clo-
sure rate from 50–90%.
Somatostatin analogue seems to be most effective in postoperative,
high-output fistulas. Its primary effect seems to be shortening of the time
to closure. It has no effect on fistulas that are anatomically incapable of
closure and does not appear to be effective in the treatment of fistulas re-
lated to intrinsic intestinal disease such as Crohn’s disease and ulcerative
colitis [42]. In fact, some authors do not recommend somatostatin and oc-
treotide in the treatment of intestinal fistulas outside of clinical trials [43].
Fibrin Glue
Many different substances have been injected into fistula tracts to obliterate
them. Cyanoacrylate glue, prolamine, and, most recently, fibrin glue all have
been used [44–46]. The most successful agent to date appears to be fibrin
glue. It is applied endoscopically if the internal origin can be visualized.
340 Wong et al.
The tract is irrigated clear and the patient is given pre- and postoperative
antibiotics. Aprotinin, a fibrinolysis inhibitor, is added to the solution to
reduce enzymatic breakdown. In 1990, Eleftheriadis et al. [46] reported on
seven patients with high-volume postoperative enterocutaneous fistulas
who were treated through endoscopic application of fibrin glue in the sec-
ond postoperative week. There were no complications, and an average of
2.4 sessions were required to close the fistulas. The mechanism of action
appears to center around the ability of fibrin to induce a cellular response
to injury and to assist in neovascularization and fibroblast proliferation.
When the intestinal opening cannot be identified, the tract can be visu-
alized percutaneously by using a flexible endoscope, as described by Lange
et al. [45] in 1990. Eighty-three patients were prepared with systemic anti-
biotics, and the fistula tracts were irrigated with streptokinase and strepto-
dornase. The endoscope or fistuloscope was advanced along the fistula
tract, and fibrin glue was injected to obliterate it. Of 48 patients who under-
went a gastroscopic or colonoscopic approach, 36 had successful occlusion
of their fistulas. An additional 16 of 35 patients had successful closure after
fistuloscopy and percutaneous obliteration. One patient died of air embo-
lism and another had pneumoperitoneum secondary to air insufflation. Air
insufflation is not currently performed because the tracts are usually mature
enough to remain open for visualization. Patients with an opening >2cm
in diameter or extensive necrotic masses were excluded from treatment.
Treatment failure occurred in fistulas <1 cm long, fistulas arising in irradi-
ated tissue, fistulas associated with active Crohn’s disease, and fistulas that
could not be completely obliterated with sealant.
Fistula obliteration with fibrin glue is a promising new option for the
nonoperative treatment of fistulas. Whether it should be used in conjunction
with other conservative therapy or reserved for high-risk patients who have
failed conservative therapy remains to be determined. The use of minimally
invasive techniques using occlusive agents to attempt fistula closure has
shown promising results. In a recent study, closure of abdominal-cutaneous
fistula tracts by occlusion with a modified VasoSeal collagen plug shows
promise in the management of low-volume fistulas refractory to catheter
drainage and other conservative approaches [47].
Outcome of Conservative Therapy
Overall, spontaneous closure can be anticipated in 60–70% of fistulas [3,
7,8,19], depending on anatomy, etiology, and concurrent sepsis. Simple
type 1 fistulas have the highest success rate, with reported closure rates
approximating 90% [3]. In contrast, complex type 2 fistulas have the lowest
rate of spontaneous closure, at less than 10% [2,3]. Fistulas arising second-
ary to intrinsic disease processes also have very low rates of spontaneous
closure when compared to postoperative fistulas. Reber et al. [7] reported
spontaneous closure rates of only 8, 26, and 14% in patients with Crohn’s
Mangagement of Intestinal Fistulas 341
disease, cancer, and radiation, respectively. Similar results were reported
by Rose et al. [19].
Fistulas occurring in patients with Crohn’s disease can be subdivided
into two types according to etiology [21]. Those fistulas secondary to spon-
taneous extension of active disease have a very low rate of spontaneous
closure (10%), whereas those occurring secondary to leakage of an anasto-
mosis usually close with conservative management (86%).
In a multivariate analysis to determine prognostic factors in gastroin-
testinal fistulas, Campos et al. [6] concluded that the likelihood of sponta-
neous fistula closure is higher for fistulas with surgical causes, low output,
and no complications. Mortality is higher in patients with complications
and with high-output fistulas.
Phase 4: Decision/Definitive Surgery
The decision to proceed with definitive surgical reconstruction should be
carried out only after the patient is stable, nutritionally replete, and free of
infection and an appropriate plan has been developed.
Indications and Timing of Definitive Surgery
Simple and Complex Type I Fistulas It cannot be overemphasized
that control of sepsis must be the number one priority in the management
of an enterocutaneous fistula. Control of sepsis must be undertaken as soon
as it is recognized during the course of management and must be sought
and treated in phase 1 and/or phase 2 of management. Definitive surgery
for the fistula should not be attempted at this time. Once sepsis has been
controlled, a persistently draining fistula in a sepsis-free environment for
6–8 weeks constitutes an indication for definitive surgical repair of simple
and/or complex type I fistulas as long as the patient is both metabolically
and nutritionally stable. Reber et al. [7] documented that 90% of fistulas
that close spontaneously will do so within 1 month of control of sepsis, but
less than 10% will do so in the second and third months after sepsis control.
Hence the investigators concluded that there is no reason to delay definitive
surgery beyond 3 months after control of sepsis. One possible exception is
the low-volume distal fistula with progressively diminishing output in a
patient who shows continuing clinical improvement. Therefore good clini-
cal judgment is important, and definitive surgical therapy must be individu-
alized for the patient’s circumstances. On the other hand, early surgical
intervention may be indicated in certain situations that make the fistula
unlikely to close. The two most commonly cited reasons are discontinuity
of the bowel ends and distal obstruction [5,7]. Active Crohn’s disease, ab-
dominal irradiation, malignancy, and a short tract (<2 cm) also constitute
reasons for earlier surgery [7,22].
Even when earlier surgical treatment is indicated, it is best to delay
surgery for a minimum of 6 weeks, because it has been well documented
342 Wong et al.
that obliterative peritonitis follows many major procedures, particularly
those associated with fistulization. This process is most likely to occur from
10–21 days after surgery and persists for 6–8 weeks [25]. The dense, woody
adhesions make dissection extremely hazardous and multiple enterotomies
frequently occur, which may compound the patient’s problem. Fazio et al.
[4] have reported that although the fistula cure rate did not change whether
the surgery was done after less than 10 days, 10–42 days, or more than 6
weeks, the mortality was significantly higher in the middle period (21%).
This rate was compared to a 13% mortality when surgery was done before
10 days and an 11% mortality when 6 weeks were allowed to pass. There-
fore definitive surgery should be delayed for at least 6 weeks. However,
there are instances in which very early surgical intervention (less than 10
days) is indicated, when the abdomen can be re-entered before sepsis be-
comes established and before the obliterative adhesive process develops [4].
The timing of surgical intervention may also be influenced by the
status of the abdominal wall. It is preferable to delay elective surgery until
the abdominal wall is soft, supple, and not inflamed. This situation gener-
ally can be appreciated by palpation and inspection.
The site may have some bearing on spontaneous closure and the indi-
cation and timing of the definitive surgery. MacFadyen et al. [9] reported
spontaneous closure in 100% of duodenal fistulas, 88% of jejunal fistulas,
79% of colonic fistulas, but only 40% of fistulas arising from the ileum.
Complex Type 2 Fistulas Guidelines to the indications for and the
timing of surgical treatment for simple or complex type 1 enterocutaneous
fistulas, as outlined earlier, should not be applied to the more complex
fistulas, in association with which mortality rates of 25–50% are commonly
reported [4,48]. Complex type 2 fistulas (those associated with large ab-
dominal wall defects) constitute a major challenge to the surgeon and the
management team. The indications for and the timing of definitive surgical
intervention differ from those associated with simple enterocutaneous fis-
tula because of the complexity in this seriously ill group. Whereas 30–80%
of simple and complex type 1 fistulas can be expected to heal spontane-
ously within 6 weeks, a complex type 2 fistula almost invariably requires
definitive surgery at some juncture.
Conter et al. [49] reported on a series of 51 patients with complex
enterocutaneous fistulas managed by delayed reconstructive surgery; they
noted a mortality of 4% and overall restoration of gastrointestinal continu-
ity in 94%. Conter et al. stressed that in their opinion “the single most
important factor is delaying of definitive surgery for an extended period of
time.” In this report, the mean time from fistula recognition to definitive
operation was 4.2 months (range of 10 weeks–13 months).
Guidelines for the timing of surgery for complex fistulas are not well
defined because few published reports address this important question. Nu-
Mangagement of Intestinal Fistulas 343
tritional and metabolic status should be normalized and immunocompetence
restored, and adequate time should be allowed for the obliterative peritoni-
tis to resolve. Since the majority of patients with complex fistulas have had
considerable peritoneal contamination and inflammation, a longer time is
generally required for this reaction to resolve. The abdominal wall should be
soft and pliable to palpation, in contrast to the woody induration suggestive
of an ongoing inflammatory process. Conter et al. [49] suggested digitalizing
any existing stoma, if available, in order to further clarify abdominal status.
By judicious individualized timing of appropriate surgery, successful recon-
struction with acceptable morbidity and mortality in these complex fistulas
can be achieved.
Definitive Surgery This discussion deals with definitive surgery and
treatment in patients who have persistent fistulas despite adequate conser-
vative measures. The optimum timing of such surgery has already been
addressed.
Simple Fistulas
SMALL BOWEL (JEJUNUM AND ILEUM)
Small bowel resection of the
fistula segment with primary anastomosis is the treatment of choice [7,25]
(Fig. 12). Success rates of 90% can be achieved [7]. Any temptation to try
direct suture repair should be avoided, because Reber et al. [7] have re-
ported that this method failed in 41% of 32 patients in whom it was tried.
In some instances, dissection of the entire length of the small bowel and
resection of the diseased segment is not safe, and a bypass or exclusion
procedure should be considered (see “Special Considerations,” below).
After induction of anesthesia, a Foley catheter is inserted and the ab-
domen is prepared. Every attempt should be made to exclude the draining
fistula site from the main operative wound. This exclusion can be accom-
plished by suture closure of the skin or by an exclusion barrier (e.g., Opsite
or Vidrape) or another similar method. The abdomen should be opened
through the old scar, but first it should be entered through an uninvolved
area in longitudinal continuity with the original scar. This area often is
located in the upper midline. Such entry minimizes the chances of small
bowel injury to the potentially densely adherent loops that are expected to
be present under the old scar. Once entry has been accomplished, Metzen-
baum scissors are used to dissect the small bowel from under the old inci-
sion, which is extended as the bowel is cleared. The intent should be to
divide all the adhesions and to free the small bowel in its entirety. This
process may be tedious and time-consuming, and extreme care should be
taken to avoid further injury to the small bowel.
Once the fistula site has been encountered, it is cut across at the level
of the abdominal wall. Spillage from the opening in the small bowel should
be controlled by temporary direct suture. A loop of small bowel is sought
for beginning the dissection to separate the loops and free the small bowel
344 Wong et al.
Figure 12 The operation of choice for a simple fistula is resection and primary
end-to-end anastomosis.
through its entire length. Resection of the segment of small bowel is then
performed back to soft, pliable intestine on either side of the fistula. At this
point distal obstruction should be ruled out. In many cases such obstruction
can be reasonably determined through inspection and palpation of the small
bowel. However, in those instances where doubt may exist, a Baker tube
can be used to aid in identifying an occult obstruction. Once the tube has
been passed distally, the balloon is inflated and the tube gradually with-
drawn, with any sites of narrowing noted. If such sites are found, the ob-
struction should be relieved by either strictureplasty or resection. In some
instances enteroscopy with a colonoscope passed transanally, cannulation
of the ileocecal valve, and examination of the small bowel directly may be
of value. This procedure necessitates that the patient be placed in the modi-
fied lithotomy position with the legs in the Allen stirrups at the outset. Once
distal obstruction has been ruled out, primary anastomosis of the small
Mangagement of Intestinal Fistulas 345
bowel can be accomplished. We prefer a one-layer 4–0 silk hand-sewn
anastomosis. Alternatively, a functional end-to-end stapled anastomosis can
be used.
In most cases an extensive dissection has been necessary and pro-
longed postoperative ileus occurs. Consideration should be given to per-
forming a Stamm gastrostomy to avoid prolonged nasogastric intubation
and patient discomfort. The abdominal cavity is irrigated with saline and
hemostasis is checked and secured. The abdominal wall fistula tract is de-
brided and usually left open. Alternatively, the internal aspect at the perito-
neal level can be sutured closed with 2–0 polyglycolic acid suture. The
abdominal wall is then closed in the usual manner.
TPN is continued during the postoperative period. Suction is main-
tained on the gastrostomy until flatus or stool is passed. At this point the
gastrostomy tube can be clamped and intermittently irrigated for patency.
Oral fluids can be started, and the patient’s diet can be advanced as toler-
ated. When sufficient oral nutrition can be maintained, TPN is discontinued.
It is best to retain the gastrostomy tube for at least 2 weeks after discharge
or until the patient is thriving without complication.
DUODENAL FISTULAS
Duodenal fistulas present a different manage-
ment problem. Anatomical considerations make simple resection and anas-
tomosis infeasible in most cases. Spontaneous closure rates vary from 37–
100% [7,9,50]. Overall mortality is 18–35% [7,50]. Two types of fistulas
occur: (1) end duodenal fistulas, which are almost invariably a complication
of duodenal stump leakage after a Billroth II anastomosis, or (2) lateral
duodenal fistulas of the second, third, or fourth part of the duodenum. End
duodenal fistulas usually have low output; with adequate drainage, they
should heal spontaneously [22]. Rarely, such fistulas may require a serosal
patch or Roux-en-Y duodenal jejunostomy. Lateral duodenal fistulas of the
second portion usually have high output and rarely close spontaneously.
They are associated with increased mortality and most require operative
management [22]. The operative treatment of choice is the application of a
serosal patch [25]. If one-half to two-thirds of the duodenal circumference
is intact, a Roux-en-Y jejunal patch is preferred by Malangoni et al. [51]
and Wolffman et al. [52]. If, however, less than one-half of the circumfer-
ence is present, a Roux-en-Y jejunal end-to-end or end-to-side anastomosis
is performed to avoid stenosis [52]. When a fistula arises from the third or
fourth portion of the duodenum, the segment can usually be mobilized and
resected and an end-to-end anastomosis in front of the superior mesenteric
artery achieved [25]. Very rarely, a Whipple pancreaticoduodenectomy is
needed for a complicated duodenal fistula [50].
Complex Type I Fistulas The general approach to definitive surgery
for a complex type 1 fistula (initially associated with intra-abdominal ab-
scess) is identical in most respects to that of a simple fistula. In fact, many
346 Wong et al.
complex type 1 fistulas have been converted to simple fistulas by earlier
control of sepsis, either by percutaneous drainage or by laparotomy drain-
age of the abscess and proximal diversion. The goal of surgical treatment
should be to resect the small bowel segment with primary reanastomosis
and closure of the proximal stoma when present. The same technique and
principles as previously outlined are followed. Dense adhesions of small
bowel loops are likely to be present at the site of the previously drained
abscess. If the timing of the surgery has been appropriate, these adhesions
can usually be separated with preservation of small bowel. Occasionally
small bowel is so adherent and indurated that an additional adjacent seg-
ment may require resection. Once distal obstruction has been ruled out, the
anastomosis can be performed. If all aspects of the procedure have been
uneventful, the proximal stoma, if present, can be safely closed at this time.
If, however, the circumstances of the primary anastomosis have been less
than ideal, the stoma can be left standing and can be closed at a later date
once healing has been ensured.
Complex Type 2 Fistulas Complex fistulas, particularly those as-
sociated with a large abdominal wall defect, rarely close spontaneously
(7–10%) [3,49]. They carry a mortality of 50–60% [3,15]. In a series by
Schein and Decker [15], the mortality was almost threefold that of the other
forms of fistulas. Sitges-Serra et al. [3] defined these more serious fistulas
as being associated with an abdominal wall defect >20 cm
2
. These complex
fistulas occur as a result of (1) major wound dehiscence secondary to un-
derlying intra-abdominal wall sepsis and intestinal leakage or (2) a laparos-
tomy as a planned procedure in order to control massive intraperitoneal
sepsis. Of 45 fistulas associated with a major abdominal wall defect, Schein
and Decker [l5] reported that 25 were caused by spontaneous dehiscence,
whereas 20 were the result of an open wound management policy.
A common pathophysiological mechanism is illustrated by the follow-
ing example. A patient sustains an anastomotic leak with massive peritoneal
contamination and then undergoes repeated laparotomies in an attempt to
control sepsis. The obliterative peritonitis is compounded by the repeat lap-
arotomies, and further small bowel injury often ensues. The abdominal wall
becomes edematous and often infected, and attempts at closure under ten-
sion result in wall necrosis. Increased intra-abdominal pressure secondary
to ileus and fluid accumulation further compounds the process. Draining
intestinal juices digest the anterior bowel wall. Eventually dehiscence oc-
curs, leaving the fistula and multiple loops of small bowel exposed. This
situation is the mark of a true surgical disaster. It is often the result of
injudicious management of intra-abdominal infection at the initial insult.
Those patients who have undergone a planned laparostomy usually
benefit from adequate control of sepsis, but the open method contributes to
the development of a type 2 fistula. Nevertheless, such patients may well
have been salvaged by this treatment method.
Mangagement of Intestinal Fistulas 347
Patients with complex type 2 fistulas present a demanding therapeutic
challenge to the surgeon and management team. Surgical management is de-
scribed here through a two-phase plan—initial control and late reconstruction.
INITIAL CONTROL
Proximal gastrointestinal diversion in an area re-
mote from the abdominal wall defect is the ideal initial surgical therapy,
but such diversion may be very difficult to achieve. Some authors have
advocated exteriorization of the ends of the fistulized bowel or exclusion
bypass. Although these approaches may be ideal if they can be achieved,
they are often not possible because the bowel is edematous and distended
and the mesentery is commonly foreshortened. Schein and Decker [l5] have
emphasized that multiple fistulas at the base of the defect may be better
left undisturbed rather than risking resection of an undefined mass. They
have stated that a proximal jejunostomy, even if done at a point just distal
to the ligament of Treitz, is tolerated reasonably well, and that the surgeon
should not rule out high proximal jejunal diversion for fear of unknown
consequences. If a fistula associated with a large abdominal wall defect is
close to the surface and properly walled off from the remainder of the
peritoneal cavity and sepsis is under control, such situations may not need
proximal diversion; a creative draining collection system may suffice to
control output until definitive restorative surgery can safely be performed.
When a large open wound defect is present, some authors advocate
initially covering the defect with mesh and later with a split-thickness skin
graft for definitive coverage [15]; others have advocated the use of pedicle
flaps [53]. In our experience, neither coverage method is routinely neces-
sary; most such wounds can be allowed to granulate and contract.
LATE RECONSTRUCTION
Once initial control of a fistula in association
with a dehisced or open wound has been achieved, definitive reconstructive
surgery should be delayed for several months and sometimes for as long as
1 year. This delay allows for adequate resolution of the extensive inflam-
matory process and improves the likelihood of successful reconstruction.
The 6-week guideline for simple or even complex type I fistulas is not appro-
priate for the more difficult problems posed by complex type 2 fistulas.
Conter et al. [49] reported on a series of 51 patients with complex
fistulas (15 patients, or 29%, had large abdominal wall defects; 36 patients,
or 71%, had either multiple or recurrent fistulas) managed by a policy of
delayed reconstructive surgery. The mean time to definitive surgery was
4.2 months. Spontaneous closure occurred in 5 of the 51 patients (10%);
46 patients, therefore, underwent reconstructive surgery, 38 by resection
and anastomosis (3 recurrences, 2 of which closed spontaneously), 5 by
simple diversion, and 3 by fistula takedown and repair (two of which re-
curred). Morbidity was 57%, fistula-related mortality was 4%, and gastro-
intestinal continuity was restored in 94%.
The authors attribute their excellent results to this delayed approach.
Fazio et al. [4] reported on four patients with multiple fistulas and severe