Autologous fibrin glue in the treatment of rectovaginal and complex fistulas

This nonrandomized series reports the use of autologous fibrin glue to treat complex rectovaginal and anorectal fistulas. The use of an autologous source to prepare fibrin glue eliminates the risk of disease transmission. Ten patients, six women and four men, with complex fistulas were treated with autologous fibrin glue application. Five patients had rectovaginal fistulas; one of them had Crohn's disease. Five patients had complex anal fistulas; two of them had Crohn's disease, and one had a large postanal ulcer associated with HIV disease. All patients had outpatient preoperative mechanical bowel preparation and prophylactic parenteral antibiotics. Six of the ten patients (60 percent) reported complete healing of the fistulas. Follow-up ranged from three months to one year. Four of five rectovaginal fistulas healed. The two patients with Crohn's disease and complex anal fistulas and the patient with HIV disease did not heal, but all three reported significantly less drainage. Autologous fibrin glue is a viable alternative for the treatment of recurrent rectovaginal and complex abscess/fistulas.     

Rectovaginal fistula in Crohn's disease

Rectovaginal fistulas in the setting of Crohn's disease present a difficult management dilemma. Some patients with this problem require proctocolectomy, yet other patients with minimal symptoms never require an operation for treatment of the rectovaginal fistula. For a small percentage of patients, local surgical repair of the fistula may be warranted. Since 1980, this study has attempted local repair in seven patients with symptomatic rectovaginal fistulas from Crohn's disease. Five patients underwent staged repair of the fistula. Closure of the colostomy was eventually possible in three of these patients. Two of the three patients have had no evidence of recurrence at followup in excess of two years. The third patient required an ileostomy for intestinal disease and had no recurrence of the fistula. Two patients underwent primary repair of the rectovaginal fistula without fecal diversion; in one of these patients, the fistula recurred ten days after operation, necessitating a diverting ileostomy. The other patient remains cured 26 months after repair. The results of this review indicate that in the setting of quiescent rectal disease, an attempt to repair the fistula can be expected to have a reasonable chance of success. The presence of a rectovaginal fistula in a patient with Crohn's disease does not mandate removal of the rectum. Poster presentation at the meeting of the American Society of Colon and Rectal Surgeons, Anaheim. California, June 12 to 17, 1988.     

Results of operation for rectovaginal fistula in Crohn's disease

A retrospective review of patients with Crohn's disease treated at our institution from 1973 to 1986 revealed 12 patients operated on for rectovaginal fistula. Disease involved the large intestine in 10 patients. Primary fistula repair was performed in four patients and four others had staged repair with preliminary fecal diversion. Four patients with severe colonic and anorectal disease had proctocolectomy performed as the first procedure. Of eight patients who underwent fistula repair, complete healing occurred in six. One patient has a persistent fistula, which is minimally symptomatic, and the other required proctocolectomy after three unsuccessful repairs. Success of operation correlated with quiescent intestinal disease and absence of rectal involvement. In selected patients with symptomatic fistulas, surgical repair is indicated and healing can be anticipated. Read at the meeting of the American Society of Colon and Rectal Surgeons, Anaheim, California, June 12–17, 1988.     

Surgical repair of rectovaginal fistulas in patients with Crohn's disease: Transvaginal approach

The surgical management of rectovaginal fistulas complicating Crohn's disease has been associated with unacceptably high failure rates. We sought to modify the available surgical techniques to provide a solution to this challenging problem. Between December 1983 and January 1990, 14 patients with Crohn's disease underwent repair of a rectovaginal fistula. A modified transvaginal approach was employed by the authors. A diverting loop ileostomy was performed on all patients, either as the initial step in the staged management of intractable perianal disease or concurrent with the repair of the rectovaginal fistula. The fistula was completely eradicated in 13 of the 14 women and did not recur during the mean follow-up period of 55.0 months (range, 3–77 months). Intestinal continuity was reestablished in these 13 patients within 6 months after the initial fistula repair. One patient with a very low-lying fistula constituted our only failure. We have found the transvaginal method preferable to the transanal approach because of the relative ease in raising the vaginal flap as compared with a flap of fibrotic and inflamed anorectal mucosa. On the basis of this study, we conclude that a modified transvaginal approach is an effective method for repair of rectovaginal fistulas secondary to Crohn's disease.Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, April 29 to May 4, 1990.     

Remicade does not abolish the need for surgery in fistulizing Crohn's disease

PURPOSE: Tumor necrosis factor antagonist therapy in the form of infliximab has been shown to promote significant healing in fistulizing Crohn's disease and therefore is often considered as a possible alternative to surgery. Our aim was to evaluate the role of infliximab in supplanting surgery for fistulizing Crohn's disease. METHODS: We performed a retrospective chart review of all adult patients who received infliximab for fistulizing Crohn's disease at one institution between September 1998 and October 2000. RESULTS: Twenty-six patients (14 male; mean age, 38 years; range, 19-80 years) received a mean of three (range, one to six) doses of infliximab (5 mg/kg) with the intent to cure fistulizing Crohn's disease. Nine patients (35 percent) had perianal, 6 (23 percent) enterocutaneous, 3 (12 percent) rectovaginal, 4 (15 percent) peristomal, and 4 (15 percent) intra-abdominal fistulas. Nineteen (73 percent) of the patients had had prior surgery for Crohn' s disease. Six patients (23 percent) had a complete response to infliximab with fistula closure, 12 (46 percent) had a partial response, and 8 (31 percent) had no response to infliximab. Fourteen (54 percent) patients still required surgery for their fistulizing Crohn's disease after infliximab therapy (10 bowel resections, 4 perianal procedures), whereas half (6/12) of the patients treated with infliximab who still had open fistulas after treatment declined surgical intervention. Five of six patients with fistula closure on infliximab had perianal or rectovaginal fistulas. None of the patients with either enterocutaneous or peristomal fistulas were healed with infliximab. CONCLUSIONS: Although it was associated with a 61 percent complete or partial response rate, infliximab therapy did not supplant the need for surgical intervention in the majority of our patients with fistulizing Crohn's disease. Seventy-three percent of the patients either required surgery or still had open fistulas after infliximab therapy. Infliximab was much more effective in treating perianal disease than abdominal enterocutaneous disease.     

Complete remission of Crohn's disease after high-dose cyclophosphamide and autologous stem cell transplantation

In a 36-year-old male with ileocolic Crohn's disease (CD) no long-lasting remission was obtained by treatment with corticosteroids, mesalazine, azathioprine and antibiotics. Surgical interventions due to relapsing fistulae and abscesses resulted in the removal of >1.5 m of small bowel and left only 40 cm of large bowel. In July 2000, a new fistula and abscess developed. The combination of corticosteroids, mesalazine, ciprofloxacin, metronidazol, azathioprine, formula diet and anti-TNF-alpha antibody largely reduced clinical activity, and resection of fistula and abscess were successful. Despite clinical remission, histology showed activity in the small bowel and the colon. In March 2001, stem cell mobilization chemotherapy with cyclophosphamide was performed. It induced an endoscopic remission for 9 months, which was maintained on azathioprine and corticosteroids. After relapse, in March 2002, high-dose chemotherapy with cyclophosphamide and reinfusion of T-cell-depleted autologous peripheral CD34+ blood stem cells were performed. This led to a complete clinical, endoscopical and histological remission for 9 months without any treatment. Thereafter, endoscopy showed initial aphthous lesions with minimal histological signs of inflammation. The patient is asymptomatic, but low-dose prednisolone and methotrexate are prophylactically given. Immunoablative chemotherapy followed by autologous peripheral blood stem cell transplantation may be a beneficial therapeutic option in complicated refractory CD.     

Contemporary surgical management of rectovaginal fistula in Crohn's disease

Rectovaginal fistula is a disastrous complication of Crohn's disease(CD) that is exceedingly difficult to treat. It is a disabling condition that negatively impacts a women's quality of life. Successful management is possible only after accurate and complete assessment of the entire gastrointestinal tract has been performed. Current treatment algorithms range from observation to medical management to the need for surgical intervention. A wide variety of success rates have been reported for all management options. The choice of surgical repair methods depends on various fistula and patient characteristics. Before treatment is undertaken, establishing reasonable goals and expectations of therapy is essential for both the patient and surgeon. This article aims to highlight the various surgical techniques and their outcomes for repair of CD associated rectovaginal fistula.     

Infliximab- and azathioprine-related severe neutropenia and thrombocytopenia in a case with Crohn's disease

A 25-year-old female patient with Crohn's disease had been using azathioprine and metronidazole for an extended period because of recurrent perianal and rectovaginal fistulae. Infliximab was added to the treatment regimen following postoperative recurrence of a rectovaginal fistula. Upon the development of severe neutropenia and thrombocytopenia after the third dose of infliximab, azathioprine and infliximab were stopped. Neutropenia work-up did not reveal any other cause. Neutropenia was ameliorated with use of granulocyte colony-stimulating factor. Treatment was restarted with infliximab alone upon leakage from the rectovaginal fistula with no hematologic toxicity. This case was considered as a serious adverse effect of infliximab and azathioprine combination therapy.     

Embolization—An optional treatment for intractable hemorrhage from a malignant rectovaginal fistula

PURPOSE: Patients rarely have intractable hemorrhage from rectovaginal fistulas, which usually require surgical intervention. This report presents our experience with nonsurgical treatment of a high-risk patient with uncontrolled hemorrhage originating from a malignant rectovaginal fistula. METHODS: A 74-year-old female developed uncontrolled hemorrhage from a malignant rectovaginal fistula. Because of her poor physical condition, an embolization with metal clips of the right and left hypogastric arteries was performed, distal to the superior gluteal artery. RESULTS: Embolization was successful in controlling the rectovaginal bleeding, allowing the patient to live 12 months. She refused adjuvant radiotherapy or chemotherapy. CONCLUSIONS: Selective angiography and embolization is a worthwhile alternative in patients with uncontrolled bleeding from a malignant rectovaginal fistula who are poor candidates for surgical intervention.     

Gracilis Muscle Transposition for Fistulas Between the Rectum and Urethra or Vagina

Purpose This study was designed to assess the efficacy of gracilis muscle transposition in repairing rectovaginal and rectourethral fistulas. Methods Data were retrieved from a retrospective chart review of patients who underwent gracilis muscle transposition for fistulas between the rectum and urethra/vagina. All patients had fecal diversion as a preliminary or concurrent step to fistula repair. Follow-up data were gathered from outpatient clinic visits. Success was defined as a healed fistula after stoma closure. Results Six females and three males, aged 30 to 64 years, underwent gracilis muscle transpositions from 1999 to 2005. One pouch-vaginal, three rectourethral, and five rectovaginal fistulas were repaired. The etiologies were Crohn's disease (n = 2), iatrogenic injury to the rectum during radical prostatectomy (n = 2), previous pelvic irradiation for rectal cancer (n = 2) or for cervical cancer (n = 1), recurrent perianal abscesses with fistulas (n = 1), and obstetric tear (n = 1). Seven patients underwent previous medical and surgical repair attempts. There were no intraoperative complications. Postoperative complications included perineal wound infection (n = 1) and at the colostomy closure (n = 2). There were no long-term sequelae. At a median follow-up period of 14 (range, 1–66) months since stoma closure, the fistula healed in seven patients. One patient refused ileostomy closure. One patient with severe Crohn's proctitis has a persistent rectovaginal fistula. Conclusions Gracilis muscle transposition is a viable option for repairing fistulas between the urethra, vagina, and the rectum, especially after failed perineal or transanal repairs. It is associated with low morbidity and a good success rate. Underlying Crohn's disease and previous radiation are associated with poor prognosis. Presented at The Joint Meeting of the Israel Society of Colon and Rectal Surgery and the Israeli Society of Endoscopic Surgery, Eilat, Israel, December 16 to 18, 2004. Reprints are not available.     

Perianal fistulae following infliximab treatment: clinical and endosonographic outcome

BACKGROUND: Management of perianal and rectovaginal fistulae complicating Crohn's disease (CD) is unsatisfactory. Infliximab is effective in the treatment of fistulating CD. However, reopening of fistulae is frequent, suggesting the persistence of deep fistula tracts despite superficial healing. In this study, the clinical and endosonographic behavior of perianal fistulae were evaluated following infliximab infusions, as well as the role of anal endosonography (AE) in predicting their outcome. METHODS: Thirty CD patients presenting with perianal and/or rectovaginal fistulae received an infusion of infliximab at a dose of 5 mg/kg at weeks 0 (entry into the study), 2, and 6. Laboratory and clinical assessments were repeated at same intervals and at week 10. AE was performed at entry and at week 10. Thereafter, the perianal region was re-examined every 6 months, and patients were investigated regarding draining of the fistula in the previous months. RESULTS: Fifteen patients (53.6%) showed closure of the fistulae at week 10, but only 5 patients had the fistula tracts disappeared at AE. Clinical and AE closure of rectovaginal fistulae was less prevalent than that of perianal fistulae [14.3% versus 63.6% at week 6 (p = 0.035); 28.6% versus 59.1% at week 10 (p = 0.21); 14.3% versus 22.7% at AE (p = 1.00)]. The behavior of fistulae was not affected by their number and AE classification, presence of rectal disease, or setons. Twenty patients with perianal fistulae were followed for a median of 15.5 months. Patients with closed perianal fistulae at week 10 and disappearance of fistulae tract at AE showed a lower relapse rate than those with endosonographic persistence of fistula tract. CONCLUSIONS: Infliximab can heal perianal and rectovaginal fistulae in approximately 60% and 30% of patients, respectively. Despite closure, most fistula tracts are still detectable at AE. Persistence of the internal tract is a condition at higher risk of fistula recurrence.     

Oral tacrolimus (FK 506) in Crohn's disease complicated by fistulae of the perineum

We describe the cases of two patients with Crohn's disease affected by severe perineal fistulae resistant to conventional therapies, successfully treated with FK 506, a new immunomodulatory drug. It is well absorbed from diseased bowel and preliminary experiences have indicated its short-term use in complicated Crohn's disease. The first patient was a 24-year-old male with perineal fistula and severe skin ulceration (8 cm of external opening diameter). He had undergone colectomy and ileostomy because of severe pancolitis refractory to medical treatment and had been treated with azathioprine and metronidazole. Two months after starting FK 506, a dramatic improvement made further surgical operation unnecessary. Local and general benefit was observed during the following 26 months, until FK 506 was withdrawn. The second patient was a 28-year-old male with a diagnosis of ulcerative pancolitis changed to Crohn's disease two months after the onset of a perineal fistula, recurring despite drainage procedures, steroid therapy, and total parenteral nutrition. FK 506 was administered for two months with a complete healing of fistula. Successively, it was stopped and corticosteroids (associated to enteral nutrition) were given because of recurrent rectal bleeding. Our experience encourages the use of oral FK 506 in complicated Crohn's disease and suggests the possibility of a long-term primary therapy other than the use as a "bridge" to other treatments.     

Surgisis™ Mesh: A Novel Approach to Repair of a Recurrent Rectovaginal Fistula

PURPOSE: This study was designed to repair a recurrent rectovaginal fistula using a new surgical approach that incorporates a Surgisis mesh.METHODS: A 63-year-old female with a history of recurrent rectovaginal fistula, which was treated originally by a traditional mucosal advancement flap technique, underwent a surgical procedure in which a biocompatible mesh was incorporated into the repair.RESULTS: The patient was symptom-free one-year after the procedure.CONCLUSIONS: Surgery for recurrent rectovaginal fistula incorporating a Surgisis mesh can be used as an innovative option.     

Long-term treatment of rectovaginal fistulas in Crohn's disease: response to infliximab in the ACCENT II Study.

BACKGROUND & AIMS: The ACCENT II study (A Crohn's Disease Clinical Trial Evaluating Infiximab in a New Long-term Treatment Regimen in Patients With Fistulizing Crohn's Disease) evaluated the efficacy and safety of infliximab maintenance treatment in patients with fistulizing Crohn's disease. This post hoc analysis was conducted to determine the efficacy and safety of infliximab therapy in women with rectovaginal fistulas. METHODS: All patients received 5 mg/kg infliximab intravenously at weeks 0, 2, and 6. Patients who achieved response at weeks 10 and 14 then were randomized as responders if they had at least 50% of baseline fistulas closed, or as nonresponders, to receive placebo or infliximab 5 mg/kg every 8 weeks through week 54. RESULTS: Of 282 patients in the ACCENT II study, 25 of 138 (18.1%) women had a total of 27 draining rectovaginal fistulas at baseline. After infusions of infliximab at weeks 0, 2, and 6, 60.7% (17 of 28) and 44.8% (13 of 29) of rectovaginal fistulas were closed at weeks 10 and 14, respectively. Among responders, 72.2% (13 of 18) of rectovaginal fistulas were no longer draining at week 14. The duration of rectovaginal fistula closure was longer in the infliximab 5-mg/kg maintenance group (median, 46 wk) than in the placebo group (33 wk). CONCLUSIONS: Infliximab is effective in short-term closure of rectovaginal fistulas and maintenance treatment was more effective than placebo in prolonging rectovaginal fistula closure.     

Efficacy of cyclosporine in treatment of fistula of crohn's disease

Sixteen Crohn's disease patients with active fistula who had failed standard medical therapy were treated with intravenous cyclosporine. Ten patients had perirectal disease, four had enterocutaneous fistula, and two had rectovaginal fistula. Patients were initially treated with intravenous cyclosporine, 4 mg/kg/day, and then switched to oral cyclosporine, 6–8 mg/kg/day. Improvement was graded using the Present-Korelitz criteria, and success was defined as moderate to total closure of the fistula. Fourteen of 16 patients (88%) responded in the acute phase to parenteral cyclosporine. Closure of fistula occurred in seven (44%) with moderate improvement in the remaining seven (44%). Subsequently, five patients (36%) relapsed to some degree on oral cyclosporine (three severe and two mild relapses). Nine (64%) patients maintained their improvement in the chronic phase. Chronic steroids could be discontinued in 6/8 (75%) of patients. Mild side effects were common [paresthesias (75%) and hirsuitism (19%)]. A single patient had severe paresthesias requiring discontinuation of therapy. Mild hypertension was noted in four (25%) and one patient (6%) had to be withdrawn because of nephrotoxicity, which reversed after stopping cyclosporine. We conclude that intravenous cyclosporine is effective therapy for perianal, rectovaginal, and enterocutaneous fistula in Crohn's disease. Its future role awaits controlled trials as well as determination of the risk-benefit ratio.     

85例克罗恩病的临床研究

背景：克罗恩病（CD）是一种全胃肠道节段性、全壁层炎症性病变，其病因不明，临床表现多样。目的：探讨CD的临床特点、实验室指标和内科治疗进展，以期提高对CD的诊断和治疗水平。方法：对南京大学医学院附属鼓楼医院2000年1月。2005年8月住院病例中85例出院诊断为CD患者的临床表现、诊断方法和治疗进行总结和回顾性分析。结果：CD好发于男性，以青壮年为主，呈慢性病程。病变主要位于回结肠（52．9％），临床表现以腹痛（72。9％）、腹泻（56．5％）为主，结肠镜检查显示病变呈节段性，溃疡多见。简化CD活动指数（CDAI）评分与血沉（ESR）的相关系数为0．400（P〈0.01），与白细胞计数的相关系数为0．239（P〈0．05），与血小板计数的相关系数为0．454（P〈0.01），与血小板平均容积的相关系数为0．287（P〈0．01）。内科治疗对大多数病例有效，予5例复发性CD患者白体造血干细胞移植治疗，有4例缓解，1例术后6个月复发。结论：CD的发病率近年来逐年增高，诊断以临床表现结合结肠镜检查为主．ESR、白细胞计数、血小板计数和血小板平均容积可作为评估疾病活动度的参考指标。CD以内科治疗为主．顽固复发型CD患者可考虑行造血干细胞移植治疗。     

Die radiogene enterovaginale Fistel — Möglichkeiten der chirurgischen Versorgung

Between 1 Jan 1985 and 31 Dec 1996 more than 300 patients with rectovaginal fistula were operated in our clinic. Nineteen of these patients suffered from fistulas induced by irradiation because of gynecological carcinomas. In 18 cases we saw rectovaginal fistulas, in 1 case terminal ileum was involved in addition. Low-anterior resection with colo-anal sleeve-anastomosis and — mostly — additional diverting colostomy could be performed in 10 cases. In 8 patients only a colostomy could be performed because of poor general condition, progressive recurrent pelvic tumor or severe irradiation induced pelvic lesions. In 1 case local transperineal operation of the fistula was performed, followed by early postoperative dehiscence of the suture. Two patients died early postoperatively because of progressive tumor disease. In the patients with colo-anal sleeve-anastomosis procedures we saw partial dehiscences of the suture in 3 cases, but no further severe complications. At 28 Feb 1998 6 of the 10 patients with continence resections could be controlled. None of them suffered from incontinence or a recurrent fistula. We therefore believe that low-anterior resection with colo-anal sleeve-anastomosis — as recommended by Parks — should be the method of choice in surgical therapy of radiation induced rectovaginal fistula, good general condition of the patient and exclusion of recurrent tumor disease provided. A synchronous temporary colostomy seems to lead to a better healing of the anastomosis and therefore is recommendable.     

Association of NOD2/CARD15 mutations with previous surgical procedures in Crohn's disease.

OBJECTIVE: The aim of this study is to assess the importance of NOD2/CARD15 gene mutations as prognostic factors for surgical indications in Crohn's disease. PATIENTS AND EXPERIMENTAL DESIGN: A total of 165 Crohn s disease patients were studied, considering previous surgery related to Crohn's disease. We analyzed for previous surgery in global procedures as well as separately for the two main surgical indications: ileal resection and fistula treatment. The need for appendectomy was also studied. All patients were genotyped for the three CARD15 mutations, and association studies were developed using Chi-square statistics and Fisher's exact test whenever appropriate. RESULTS: Carriers of the G908R or 1007fs mutation needed surgery more frequently, both for ileal resection and fistula repair. In contrast, appendectomy was not associated with CARD15 mutations. CONCLUSIONS: As previously reported in this population, the R702W mutation does influence parameters of disease or need of surgery. The need for Crohn's disease-related surgery is higher in carriers of the G908R or 1007fs CARD15 mutation in the Galician population. Nevertheless, the frequency of these mutations does not allow their use to predict the course of disease.     

Seton management of complex anorectal fistulas in patients with Crohn's disease

Anorectal fistulas associated with Crohn's disease are difficult to manage, particularly when the rectum is diseased. Significant morbidity has been associated with both medical and surgical therapy. Although conventional therapy is acceptable in the management of simple fistulas in Crohn's disease, these approaches often exacerbate rather than ameliorate problems in patients with complex fistulas. The authors report ten cases of complex fistulas in patients with Crohn's disease managed with their technique of long-term, indwelling setons. These setons are placed through the fistula tract and tied loosely to maintain the patency of the fistula without cutting through the sphincters. At the time of insertion, although abscesses are incised and drained, no attempt is made to divide the superficial tissues or sphincter overlying the fistulous tract. The patients ranged in age from 23 to 81 years and had a history of Crohn's disease for 1 to 20 years. All cases resulted in excellent palliation. No patient required a proximal colostomy. These patients have been followed for four months to seven years. Despite severe proctitis in six of these patients at the initial operation, no patient has required a proctectomy. The authors believe this technique achieves adequate palliation and should be employed as the procedure of choice in patients with complex anal fistulas associated with Crohn's disease.