were able to achieve a 53% healing rate in a prospective study of 60 patients with complex cryptoglandular fistulas treated with fibrin glue with intraadhe-sive ceftazidime.63 The wide v
Trang 1more favorable outcomes, Zmora et al were able to achieve a 53%
healing rate in a prospective study of 60 patients with complex
cryptoglandular fistulas treated with fibrin glue with
intraadhe-sive ceftazidime.(63)
The wide variety of successful healing in studies looking at the
use of fibrin glue in the treatment of fistula-in-ano is multifactorial
Differences in the trials include patient selection, use of autologous
versus commercially prepared fibrin adhesive, etiology of the fistula
(cryptoglandular vs Crohn’s disease vs other causes), complexity
of the fistula, and length of follow-up While the application of the
tissue adhesive seems fairly straightforward, there are also assuredly
subtle differences in the application techniques of different
sur-geons The heterogeneity of the published trials makes direct
com-parisons very difficult While success rates vary over a wide range,
the advantages of attempting to treat high transsphincteric fistulas
with fibrin glue in terms of simplicity of technique, negligible
com-plication rate, and ease of reapcom-plication for failed treatments make
it an attractive option, at least initially Most surgeons seem willing
to accept a higher than expected failure rate in exchange for a low
complication rate, understanding that treatment failures will need
to be addressed in some other manner
Anal Fistula Plug
The topic that has perhaps generated the most discussion in recent
years is the use of the Surgisis® Anal Fistula Plug™ (AFP) (Cook
Surgical, Inc., Bloomington, IN) The AFP is a cone shaped
bio-prosthetic fashioned from Surgisis®, a bioabsorbable xenograft
made of lyophilized porcine intestinal submucosal Surgisis® has
been used extensively in abdominal and inguinal hernia repairs
(64–66) It is relatively resistant to infection, produces no foreign
body or giant cell reaction, and becomes repopulated with host
cell tissue within 3–6 months, providing mechanical integrity
while acting as a scaffold to guide tissue incorporation The AFP
is inserted into the fistula tract and secured at the level of the
pri-mary opening The principal effect is to close the pripri-mary fistula
opening, though incorporation of the AFP into the tract itself can
theoretically contribute to fistula closure The advantages of this
technique include negligible risk of incontinence postoperatively,
relative simplicity in placement of the AFP, less postoperative
patient discomfort, and the ability to repeat the procedure in cases
of failure without major consequences
Johnson et al (67) initially reported a small, nonrandomized,
prospective cohort study comparing the efficacy of fibrin glue
versus AFP in the treatment of high transsphincteric fistulas At a
mean follow-up of 14 weeks, in the fibrin glue cohort, healing was
seen in 40% (4 of 10), whereas in the AFP cohort, 13 of 15 (87%)
had healed (p < 0.05) The main advantage of the plug technique
compared with fibrin glue was felt to be the ability to securely close
the primary opening, which is felt to be a critical step in the
suc-cessful treatment of anal fistulas The drawback of fibrin glue is its
liquid nature, and its tendency to run out of the fistula tract, even
when both primary and secondary openings are sutured closed
Champagne et al (68) went on to report an overall healing
rate of 83% for cryptoglandular fistulas treated with an AFP in
a series of 46 patients followed for a mean of 12 months (range
6–24 months) The same authors reported a similar 80% success
rate for treatment of Crohn’s-related fistulas with an AFP in 20
patients at a median follow-up of 10 months.(69) Ellis (70) also reported success in a small group patients with transsphincteric
(n = 13) and rectovaginal fistulas (n = 5) with 88% complete
fis-tula closure at a median follow-up of 6 months
Other studies report inconsistent results Van Koperen et al reported a series of 17 patients treated with an AFP with only 41% success.(71) Patients with cryptoglandular disease and no history
of previous fistula surgery fared better than those with a history of previous surgical intervention In the small subsets of patients with
Crohn’s disease (n = 1) and HIV infection (n = 2), 100% healing
was seen, as opposed to 29% complete healing (4 of 14) in patients with cryptoglandular disease Schwandner et al (72) reported an overall success rate of 61% The subset of patients with Crohn’s fistulas related to Crohn’s disease showed higher closure rates than those with fistulas of cryptoglandular origin (85.7% vs 45.5%) More recent studies have varied widely in their results, reporting healing rates ranging from 24% to 71.4%.(73–76)
One of the largest prospective studies was reported by Ky et al
(77) The authors studied 45 patients with simple (n = 24) and complex (n = 20) anorectal fistulas treated with AFP’s An early
healing rate of 84% at 3 to 8 weeks postoperatively progressively declined to 54.6% at a mean follow-up of 6.5 months Healing rates were significantly higher in patients with simple rather
than complex fistulas (70.8% vs 35%, p < 0.02) and in patients
without Crohn’s disease compared to those with Crohn’s disease
(66.7% vs 26.6%, p < 0.02).
Despite a number of publications attesting to the safety and efficacy of the AFP, uniformity of opinion was lacking because
of contradictory reports in the literature as well as a lack of Level
I evidence showing any clear benefit Because of this, a consensus conference involving 15 surgeons with extensive experience with the AFP was held in May 2007 to make formal recommendations regarding inclusion/exclusion criteria, pre-, intra-, and postop-erative management, and definition of outcome failure.(78) Some technical notes regarding placement of the plug bear men-tioning It is essential that all sources of perineal sepsis are resolved prior to placement The use of pre- or postoperative antibiotics and preoperative bowel cleansing has not been studied in a prospec-tive, randomized fashion In most of the studies described herein, a preoperative dose of intravenous antibiotic was administered, and varying regimens of postoperative antibiotics were utilized The consensus panel did not make specific recommendations regard-ing preoperative bowel preparation; a sregard-ingle dose of preoperative systemic antibiotics was recommended without postoperative continuation.(78) Thorough cleansing of the fistula tract with hydrogen peroxide is generally recommended Mechanical cleans-ing via curettcleans-ing, debridement, or brushcleans-ing is not recommended due to disruption and enlargement of the tract The technique of fixation of the plug to the primary opening recommended by the manufacturer involves a figure of eight absorbable suture through the mucosa, submucosa, and internal anal sphincter that inverts the proximal end of the anal fistula plug beneath the mucosa, anchor-ing it to the tract while closanchor-ing the primary openanchor-ing over the plug (Figure 19.5) Earlier studies as well as the manufacturer’s recom-mendations suggested fixation of the distal end of the plug to the secondary fistula opening as an essential step in plug placement Most surgeons have abandoned this step, now simply trimming the
Trang 2distal end of the plug flush with the skin without fixation, as it has
been suggested that external fixation creates tension on the primary
fixation site with patient movement, predisposing to plug
extru-sion The consensus panel also recommended not fixing the distal
end of the plug to the secondary opening The majority of AFP
failures are due to plug extrusion, untreated or persistent source(s)
of perineal sepsis, or postoperative infectious complications
Ligation of Intersphincteric Fistula Tract
An interesting new concept in the surgical management of
fistula-in-ano has recently been described—ligation of the intersphincteric
fistula tract (LIFT).(79) In this method, intersphincteric
dissec-tion is performed and the fistula tract is identified and ligated in
this plane, leaving the sphincter muscles themselves undisturbed
The authors reported complete fistula healing in 17 of 18 patients
(94.4%), with a mean healing time of 4 weeks and no disturbances
in anal function While this study was small and observational in
nature, the simplicity of the technique and its negligible impact on sphincter function certainly warrant further investigation
aDDitiOnal iSSUeS Recurrence
Recurrence after incision and drainage of an anorectal abscess and anal fistula, should be considered as two entities True recur-rence after abscess drainage is typically due to inadequate drain-age or inadequate postoperative care What is more commonly seen is actually “persistent” disease as the abscess cavity matures into a fistula Vasilevsky and Gordon reported recurrent or per-sistent disease in 48% of patients (11% recurrent abscess, 37% fistula-in-ano) after undergoing incision and drainage of ano-rectal abscesses.(80) Results similar to these have been reported
by several authors, which argue against primary fistulotomy at the time of initial abscess drainage, as unnecessary fistulotomy
Figure 19.5 AFP product insert.
(D) (B)
Trang 3with potential altered fecal continence can be avoided in
approxi-mately 50% of patients
Common reasons for recurrent anorectal infection include missed
infection at the time of initial drainage in adjacent anatomic planes,
presence of an undiagnosed fistula at the time of initial abscess
drain-age, and failure to completely drain the abscess initially.(81) In a series
of 500 patients undergoing anorectal abscess drainage, Onaca et al
reported that 7.6% required reoperation within 10 days of the initial
procedure.(82) Factors leading to reoperation included incomplete
drainage (23%), missed loculations (15%), missed abscesses (4%),
and postoperative bleeding (3%) Horseshoe abscesses were
associ-ated with a 50% rate of operative failure.(82)
Similarly, recurrent fistula-in-ano is often seen after
surgi-cal management due to a failure to identify a primary opening
or recognize secondary extensions of a fistula Secondary tracts
accounted for early recurrences in 20% of patients studied by
Sangwan (83) Sygut et al reported a 14.3% recurrence rate after
surgical management of fistula-in-ano, though recurrence was
much more common after surgery for recurrent fistulas (51.7%)
than primary fistulas (5.4%).(84) In this same study, recurrence
was also more common in multi-tract fistulas (32.4%) than
single-tract fistulas (12%)
Recurrence rates after fistulotomy range from 0–18% (Table 19.1)
Premature closure of the fistulotomy wound is a clear risk factor for
recurrence; this can be prevented by creating an external wound
larger than the anal wound, ensuring that the internal wound will heal
first Meticulous postoperative care is essential to avoid bridging and
pocketing of the wound.(99, 100) Epithelialization of the tract may
also occur, leading to persistent fistula-in-ano.(101) Garcia-Aguilar
et al performed a retrospective study that reviewed the records of
624 patients undergoing surgery for fistula-in-ano in an effort to
determine factors associated with recurrence and incontinence.(98)
Recurrence was seen in 8% of patients; univariate and multivariate
regression analysis showed that factors associated with recurrence
included complex fistula type, horseshoe extension, lack of
identi-fication, or lateral location of the primary fistula opening, previous
fistula surgery, and the experience of the surgeon Recurrence rates
after staged fistula repairs using setons range from 0% to 9% (34, 98,
102–109), though the largest study with a 0% recurrence rate had
only 21 patients.(106)
Interestingly, the success rate of fistula surgery has been shown to
decrease with time In a study by van der Hagen et al (110),
recur-rence rates following fistulotomy at 12, 48, and 72 months were 7%,
26%, and 39%, respectively, with 33% of recurrences occurring in
the first 24 months after surgery A similar trend was seen following
the use of endorectal advancement flaps, with recurrence rates of
22%, 63%, and 63% seen at 12, 48, and 72 months respectively; 69%
of recurrences were seen within the first 24 months Van Koperen et
al (111) demonstrated recurrence rates at 3-year follow-up of 7%
for fistulotomy, and 21% for rectal advancement flaps
Mizrahi et al (112) described features associated with fistula
recurrence in a series of 106 consecutive endorectal advancement
flaps performed on 94 patients Recurrence was seen in 40.4% of
patients at a mean follow-up of 40.3 months Recurrence was
not associated with prior attempt at repair, type of fistula,
ori-gin of fistula, preoperative steroid use, postoperative bowel
con-finement, postoperative antibiotic use, or creation of a diverting
stoma Recurrence was significantly more common in patients
with Crohn’s disease (p < 0.04) Sonada et al reported a
simi-lar recurrence rate of 36.4% of patients undergoing endorec-tal advancement flap for repair of anorecendorec-tal and rectovaginal fistulas in a series of 105 patients.(42) Factors that negatively
impacted the healing rate were Crohn’s disease (p = 0.027) and a
diagnosis of rectovaginal as opposed to anorectal fistula (0.002) Patients on oral corticosteroid therapy showed a trend towards recurrence, though this did not reach statistical significance; no patients taking more than 20 mg/day of prednisone achieved long-term healing
Cigarette smoking has been shown to negatively impact fistula closure after endorectal advancement flap In a series of 105 patients undergoing endorectal advancement flap for anal fistulas not related to Crohn’s disease, Zimmerman et al reported successful fistula closure in 69%.(113) In patients who did not smoke ciga-rettes, healing was seen in 79%, compared with 60% in smokers
(p < 0.037) Furthermore, a significant correlation was seen between
the healing rate and the number of cigarettes smoked per day
(p = 0.003) Using intraoperative laser Doppler flowmetry, it has also
been shown that median bloodflow before endorectal advancement flap in nonsmokers was 35 volts, compared with 18 volts in smokers
(p = 0.018).(114) Thus, it seems likely that impaired wound
heal-ing due to diminished perfusion may be a contributheal-ing factor in the failure of endorectal advancement flaps in smokers Efforts to encourage smoking cessation preoperatively should be undertaken
to minimize postoperative morbidity
Incontinence
Fecal incontinence after abscess drainage should be relatively infrequent and is typically the result of iatrogenic damage to the sphincter mechanism Compromised continence may also be seen postoperatively if the external sphincter is damaged dur-ing incision and drainage in patient with borderline preopera-tive continence Inadvertent injury to the puborectalis during drainage of supralevator abscesses has also been reported.(115) Prolonged packing may prevent granulation tissue formation and promote generation of excessive scar tissue.(116) Primary fistulectomy at the time of incision and drainage has also been reported to cause disturbed fecal continence.(33)
On the other hand, incontinence rates following surgical management of fistula-in-ano vary widely The incidence of incontinence is related to the complexity of the fistula and the level of the primary fistula opening, with complex fistulas and those with posterior and high openings and fistula extensions at
a higher risk.(97) Posterior fistulotomy has a higher incidence
of recurrence due to a more circuitous route of the tract, result-ing in division of more sphincter muscle Drainage of extensions may damage small nerves and create scar tissue around the ano-rectum.(97) The incidence of incontinence is also related to the patient’s preoperative sphincter function and their would-heal-ing ability The incidence of impaired continence also increases with age and is more common in females.(98) Fecal seepage without true sphincter compromise can occur if the edges of a fistulotomy wound do not heal completely, preventing complete closure of the anus and allowing for leakage of fecal contents, and flatus
Trang 4In a large review of 844 patients undergoing surgery for anal
fistulas, Rosa et al (117) demonstrated a 6.9% incidence of altered
postoperative sphincter function Incontinence to flatus was seen
in 4.0%, liquid stool in 2.6%, and solid fecal material in 0.3%
The majority of patients in this series underwent fistulotomy or a
combined fistulotomy-fistulectomy method Sygut et al reported
postoperative gas and/or stool incontinence in 10.7% of patients
undergoing surgical management of anal fistulas, mainly in the
form of fistulotomy and cutting setons.(84) In this study, rates
of incontinence were higher following surgery for recurrent vs
primary fistulas (39.7% vs 3.7%) and after surgery for multitract
as opposed to singletract fistulas (29.4% vs 8.3%) In a review of
624 patients undergoing anal fistula surgery, Garcia-Aguilar et al
(98) showed that 45% of patients complained of some degree of
altered continence Factors associated with postoperative
inconti-nence included female sex, high fistula type, type of surgery, and
previous fistula surgery Incontinence after staged fistulotomy
using a seton ranges from 0% to 64%.(34, 97, 98, 102–109) Again,
all of the studies showing no recurrences were small, with the
largest being only 20 patients.(105)
In a study looking at long-term functional outcome, Van
Koperen et al (111) reported that after fistulotomy for low
cryp-toglandular fistulas, fecal soiling was seen in 41% of patients and
fecal incontinence was seen in 2.8% of patients at 3 year follow-up
Following rectal advancement flaps, soiling was seen in 43% and
incontinence was seen in 2.9% at 3 year follow-up None of
poten-tial risk factors examined (sex, age, prior fistula surgery,
smok-ing) were significant in both univariate and multivariate analysis
Schouten et al (39) showed that 35% of patients had deteriorated
continence postoperatively after endorectal advancement flap The
number of previous attempts at fistula repair did not adversely
affect continence
Zimmerman et al (46) reported deteriorated continence after
anocutaneous advancement flap in 30% of patients Aguilar et al
reported disturbances in continence to flatus in 7% and liquid stool in 6% in a series of 189 patients undergoing fistulectomy with endorectal advancement flap.(118) Kodner et al reported unchanged or improved continence in 98% of patients undergo-ing endorectal advancement flap for anorectal fistulas.(40) Other series have reported no alteration in postoperative continence after rectal advancement flaps.(45, 119)
Toyonaga et al performed an interesting study looking at pre- and postfistulotomy manometry studies.(120) They found that fistulotomy significantly decreased maximum resting pressure
(85.9 to 60.2 mmHg, p < 0.0001) and length of the high pressure zone (3.92 to 3.82 cm, p = 0.035), but did not affect voluntary contraction pressure (164.7 to 160.3 mmHg, p = 0.2792) Anal
sphincter dysfunction, in the form of soiling, incontinence to fla-tus, or incontinence to liquid stool, occurred in 20.3% of patients Multivariate analysis showed that while fistulotomy did not affect voluntary contraction pressure, those with lower preoperative voluntary contraction pressures were more likely to suffer from altered continence postoperatively, as were those who had under-gone multiple drainage procedures Age, sex, previous fistula sur-gery, duration of symptoms, and location and level of the primary opening did not significantly influence continence postoperatively The authors concluded that preoperative anal manometry may
be helpful in choosing the proper surgical procedure for patients with fistula-in-ano
Manometry studies following endorectal advancement flaps performed by Uribe et al (121) also showed significant reduc-tion in maximum resting pressure 3 months after surgery (83.6
vs 45.6 mmHg, p < 0.001), as well as significant reduction in maximum squeeze pressure (208.8 vs 169.5 mmHg, p < 0.001)
Disturbed anal continence was seen 21.4% of patients None of the variables looked at (age, sex, previous fistula surgery, Crohn’s disease) were predictive of postoperative incontinence In con-trast, manometry studies following endorectal advancement
Table 19.1 Results of fistula surgery.
* 3% solid stool, 17% liquid stool, 25% flatus.
** 0.7% solid stool, 2.0% liquid stool, 3.3% flatus.
*** 0 solid stool, 0.2% liquid stool, 0.5% flatus.
Trang 5flaps were performed by Kreis et al (122), showing no difference
in preoperative and postoperative maximum squeeze pressure
(100.0 vs 118.0 mmHg), maximum resting pressure (56.6 vs
52.8 mmHg), rectal compliance (4.4 vs 3.5 ml/mmHg), or any
other anorectal manometry parameter
Other studies evaluating preoperative manometric parameters
differ somewhat Chan and Lin (123) examined 45 patients with
intersphincteric fistulas and showed low preoperative resting
pres-sure to be the only independent factor predicting postoperative
incontinence In a prospective study by Perez et al (124) looking
at combined fistulotomy with primary sphincter reconstruction,
there were significant preoperative differences seen on
manom-etry between continent and incontinent patients that disappeared
after operation There were neither clinical nor manometric
dif-ferences between pre- and postoperative values in fully continent
patients, although three patients (12.5%) reported minor
altera-tions of continence
Crohn’s Disease
The overall incidence of anorectal fistulas associated with Crohn’s
dis-ease limited to the ileocecum is 20–25%; this rises to approximately
60% when Crohn’s disease affects the rectum.(125) Disease isolated
to the anorectum is seen in only 5% of patients.(126) Fistulizing
anorectal Crohn’s disease can be among the most frustrating
con-ditions surgeons are called upon to manage Surgical treatment is
fraught with the problems of poor wound healing, delayed wound
healing, and sphincter injury It is widely held that incontinence in
patients with anorectal Crohn’s disease is usually the result of
aggres-sive surgeons and not aggresaggres-sive disease.(127) Thus, a conservative
approach is practiced in most instances, taking extreme care to
pro-tect the sphincter When in doubt, one cannot be faulted for simply
draining the suppurative process by placing a draining seton
Any acute infectious process must be drained appropriately and
medical management of the disease should be optimized before
even considering surgical treatment For low-lying posterior
fistu-las, fistulotomy may be considered, especially if there is not rectal
disease Anterior fistulotomies in females should be avoided because
of the risk of postoperative incontinence Endorectal advancement
flaps are also a viable option, especially when there is no rectal
disease Joo et al (128) described 31 endorectal advancement flaps
performed in 26 patients, resulting in fistula eradication in 71% of
cases Success was more likely in the absence of concomitant small
bowel Crohn’s disease than in patients with concomitant small
bowel Crohn’s disease (87% vs 25%, p < 0.05) Other series have
shown that the presence of Crohn’s disease predisposes endorectal
advancement flaps to failure.(42, 112)
Data regarding the efficacy of the Surgisis© AFP is mixed As
mentioned earlier, O’Connor et al reported the AFP to be effective
in 80% of patients and 83% of fistula tracts in a series of 20 patients
with 36 fistula tracts Patients with single fistulas were more likely
to have success and success was not correlated with antitumor
necrosis factor therapy.(69) Schwander et al actually showed better
healing rates with AFP’s in patients with anal fistulas and Crohn’s
disease than in patients without Crohn’s (85.7% vs 45.5%) On the
other hand, Ky et al (77) reported complete fistula healing with an
AFP in 26.6% of patients with Crohn’s disease compared to 66.7%
of patients without Crohn’s (p < 0.02).
For patients with fulminant perineal sepsis due to fistulizing perineal Crohn’s, a low threshold for a diverting stoma must be entertained, especially since a large number of these patients will
go on to require proctectomy
Nonsurgical Management
For the most part, there is no role for nonoperative management
of anorectal abscesses Occasionally, an early inflammatory pro-cess, marked by pain and erythema or induration without fluc-tuance, may be prevented from progressing to an abscess with early initiation of antibiotic therapy However, once an abscess has formed, antibiotics alone are insufficient Failure to appropri-ately drain an anorectal abscess in a timely manner subjects the patient to the risk of progressive perineal sepsis, including opera-tive risks associated with surgery in the septic patient, technical complications associated with anorectal surgery in the face of severe inflammation (unclear anatomy, bleeding, risk of inadver-tent sphincter injury), and necrotizing perineal soft tissue infec-tion (Fournier’s gangrene) with associated mortality rates as high
as 67% (129–132), as described below
Nonoperative management of anal fistulas falls into two main categories – those related to cryptoglandular disease and those related to Crohn’s disease There is very little in the literature regarding nonoperative management of chronic cryptoglandular fistulas Obviously, acute suppurative processes must be drained, typically with a seton Draining setons may be left in place indef-initely, with little consequence other than patient discomfort As discussed later, in exceedingly rare cases, invasive carcinoma may develop in the setting of a chronic fistula
Conservative (nonoperative) therapy for anal fistulas in the set-ting of Crohn’s disease is the standard approach typically followed (331) Initial drainage of the acute suppurative process without division of the fistula tract is typically performed by placing drain-ing setons Long-term indwelldrain-ing draindrain-ing setons may be used as
an effective management modality for complex perianal Crohn’s fistulas, without a negative impact on continence.(134)
A number of medical therapies are utilized for the treatment
of anal fistulas related to Crohn’s disease Ciprofloxacin has been reported to improve symptoms in two small, uncontrolled trials (135, 136) Metronidazole had also been studied in a number of uncontrolled trials with varying rates of symptom relief and fistula healing.(137–140) Metronidazole must be used for maintenance
to be effective, as high recurrence rates are seen on discontinua-tion.(133) The combination of ciprofloxacin and metronidazole has also been shown to be effective in a small retrospective study
at reducing symptoms and healing fistulas; most patients in this series also regressed with cessation of treatment.(141)
A number of immunomodulators are also employed in the medical management of perianal Crohn’s fistulas Azathioprine and 6-mercaptopurine have been shown to induce complete fistula closure in 31–39% of patients, with even higher rates of symptom reduction without complete closure.(142–144) Again, recurrence occurred frequently with discontinuation of treat-ment Methotrexate and cyclosporine A have each been shown
to be efficacious in inducing remission on patients with Crohn’s disease (145, 146), though data regarding their effect specifically
on anal fistulas resulting from Crohn’s disease has been lacking
Trang 6Infliximab, a chimeric monoclonal antibody against tumor
necrosis factor-alpha (TNF-α), has revolutionized the medical
management of Crohn’s disease In mucosal biopsies of patients
with Crohn’s disease, enhanced secretion of TNF-α with failure
to release enhanced quantities of soluble TNF-α receptors is
seen Infliximab reduces disease activity by blocking the effects
of TNF-α and has been shown to be an effective maintenance
therapy in patients with Crohn’s disease with fistulas (147) and
without fistulas.(148) Despite a lack of convincing Level 1 data
proving the efficacy of infliximab specifically in the setting of
perianal Crohn’s fistulas, its use in this setting is becoming more
widespread
Long-term data regarding the efficacy of infliximab in
effect-ing perianal fistula closure is lackeffect-ing The combination of seton
drainage and infliximab infusion has been shown to be effective
as well, with healing rates ranging from 47–100%.(149–151) The
timing of seton removal in these patients is not clear If removed
too early, the patient is at risk of developing recurrent perianal
abscesses, and if they are not removed, complete fistula healing
will not occur Poritz et al (152) reported 44% complete anal
fistula healing when the seton(s) were removed between the
second and third infliximab infusions
As the use of infliximab escalates, patients who have failed
treat-ment are undergoing subsequent surgical intervention for
anorec-tal fistulas, raising concerns over whether preoperative infliximab
treatment has an adverse effect on anal fistula surgery Gaertner
et al (153) showed that patients with Crohn’s disease and anal
fistulas who were treated initially with infliximab and underwent
subsequent surgical treatment showed similar healing rates
com-pared with patients who did not undergo previous infliximab
treatment (60% vs 59%) Kraemer et al (154) reported that 9 of
11 patients with Crohn’s disease and anal fistulas who underwent
preoperative infliximab treatment followed by advancement flaps
demonstrated complete healing Thus, it seems feasible to proceed
with anal fistula surgery after failed infliximab treatment,
expect-ing to acceptable rates of wound healexpect-ing
HIV-positive patients
Patients with anorectal abscesses who are HIV-positive require
timely incision and drainage, as presentation is often delayed In
this population, the use of adjunct antibiotics is strongly
recom-mended Because these patients are at increased risk if of poor
wound healing (155), care should be taken to minimize the size
of surgical wounds while ensuring adequate drainage In one
study (155), serious septic complications or uncommon
pre-sentations of anorectal sepsis were seen in 13% of HIV-positive
patients who initially presented with anorectal suppuration In
another study (156), perianal sepsis in HIV-positive patients
was frequently associated with in situ neoplasia Interestingly,
immunosuppressive disease has not been found to contribute
to the need for early reoperation following initial abscess
drain-age.(82)
In a review by Munoz-Villasmil et al (157) of 83
immunocom-promised patients with perianal sepsis, 28% were HIV-positive In
this population, 91% of surgical wounds were healed in 8 weeks
Incontinence was seen in 6% of patients postoperatively, and
recurrence was seen in 7%
Carcinoma Associated with Fistula-In-Ano
In rare instances, patients with long-standing anal fistulas may
go on to develop invasive carcinoma Although this occurs more commonly in the setting of Crohn’s disease, carcinomas arising from anal fistulas have been reported in patients without Crohn’s disease.(158, 159) While Crohn’s disease is associated overall with
an approximately 6-fold increase in colorectal cancer compared
to the general population (160), the incidence of anal cancer aris-ing from an anal fistula in the settaris-ing a Crohn’s disease is signifi-cantly lower
In a series of over 1000 patients with anorectal manifestations of Crohn’s disease, Ky et al (125) reported seven patients (0.7%) who developed invasive carcinoma related to anorectal fistulas Four patients developed squamous cell carcinoma and three developed adenocarcinoma The average duration of Crohn’s disease before cancer diagnosis was 14 years and average age at diagnosis was
47 years Presenting symptoms included pain (n = 5), persistent fistula (n = 2), persistent anal ulcer (n = 1), and rectovaginal fistula (n = 1) In four patients, the diagnosis of carcinoma was
overlooked at initial examination, resulting in significant delay
in diagnosis All four patients with squamous cell carcinoma were treated with chemoradiation Two of these were success-fully treated with no evidence of residual disease One died of carcinoma 6 months after treatment The fourth patient required abdominoperineal resection due to persistent disease and died 1.5 years later One of the patients treated successfully with chemo-radiation developed a second primary squamous cell carcinoma
11 years later, which was successfully treated with wide local exci-sion All three patients with adenocarcinoma were treated with abdominoperineal resection One received preoperative chemo-radiation; this patient died 3.5 years later Of the remaining
2 patients, one died in the early postoperative period, and the second died of unrelated causes 5 years later
A number of other case reports in the literature describe patients with carcinoma arising from chronic fistulas and unhealed wounds
in a setting of Crohn’s disease.(161, 162) The take home message is that one must maintain a high degree of suspicion for carcinoma
in patients with persistent or complex anal fistulas, especially in the setting of long-standing Crohn’s disease In this setting, com-plex fistulas with associated anorectal strictures and/or severe anorectal pain mandate a thorough examination In cases where anorectal examination is limited or unequivocal, exam under anesthesia with biopsy or curettage of the fistula tract is essential Because lesions are typically diagnosed at a later stage of disease, prognosis is poor Timely diagnosis and institution of appropriate therapy is essential to improve survival rates
RefeRenCeS
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