Improved Outcomes in Colon and Rectal Surgery part 21 pptx

 improved outcomes in colon and rectal surgery more 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 reapplication 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 primary 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 single 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 curetting, debridement, or brushing 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 closing the primary opening 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 9 surgery and nonoperative therapy of perirectal abscesses and anal fistulas distal 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. (A) (C) (D)(B) 9 improved outcomes in colon and rectal surgery with 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 anorectal 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 contributing 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. 9 surgery and nonoperative therapy of perirectal abscesses and anal fistulas In 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. Author Year No. Patients Recurrence % Incontinence % Bennett (85) 1962 108 2.0 36.0 Hill (86) 1967 626 1.0 4.0 Lilius (87) 1968 150 5.5 13.5 Mazier (88) 1971 1000 3.9 0.001 Ani & Solanke (89) 1976 82 17.0 1.0 Marks & Ritchie (90) 1977 793 – 3, 17, 25* Ewerth et al. (91) 1978 143 2.8 3.5 Adams & Kovalcik (92) 1981 133 3.8 0.8 Kuijpers (93) 1982 51 4.0 10.0 Sainio & Husa (94) 1985 199 11.0 34.0 Vasilevsky & Gordon (95) 1985 160 6.3 0.7, 2.0, 3.3** Fucini (96) 1991 99 3.0 0, 0.2, 0.5*** Van Tets (97) 1994 19 – 33.0 Sangwan (83) 1994 461 6.5 2.8 Garcia-Aguilar et al. (98) 1996 293 7.0 42.0 * 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. 9 improved outcomes in colon and rectal surgery flaps 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 aggressive 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 indwelling draining 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. 9 surgery and nonoperative therapy of perirectal abscesses and anal fistulas Infliximab, 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 lacking. 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 healing. 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 setting 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 1. Parks AG. Pathogenesis and treatment of fistula-in-ano. Br Med J 1961; 1: 463–9. 2. Parks AG, Gordon PH, Hardcastle JD. 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Colorectal. 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. 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