Local mesenchymal stem cell (MSC) therapy for complex perianal fistulas (PFs) has shown considerable promise. But, the long-term safety and efficacy of MSC therapy in complex PFs remain unknown.

To explore the long-term effectiveness and safety of local MSC therapy for complex PFs.

Sources included the PubMed, EMBASE, and Cochrane Library databases. A standard meta-analysis was performed using RevMan 5.3.

After screening, 6 studies met the inclusion criteria. MSC therapy was associated with an improved long-term healing rate (HR) compared with the control condition [odds ratio (OR) = 2.13; 95% confidence interval (95%CI): 1.34 to 3.38; P = 0.001]. Compared with fibrin glue (FG) therapy alone, MSC plus FG therapy was associated with an improved long-term HR (OR = 2.30; 95%CI: 1.21 to 4.36; P = 0.01). When magnetic resonance imaging was used to evaluate fistula healing, MSC therapy was found to achieve a higher long-term HR than the control treatment (OR = 2.79; 95%CI: 1.37 to 5.67; P = 0.005). There were no significant differences in long-term safety (OR = 0.77; 95%CI: 0.27 to 2.24; P = 0.64).

Our study indicated that local MSC therapy promotes long-term and sustained healing of complex PFs and that this method is safe.

Senescent cells and fibrosis are important components that impact the regenerative capacity of skin, particularly when considering chronic non-healing wounds. Anoderm and perianal fistulas in the setting of Crohn's disease are clinically pathophysiological extremes with consequently different healing processes which impact treatment modalities. This study describes the implications of potential senescence reversing techniques including autologous fat grafting and pharmacologic and immunomodulating agents. Given these findings, the authors propose a future direction of study involving exosomes loaded with senolytics as a method for potentially improving chronic wound healing. In conclusion, this manuscript explores the diversity of skin healing and healing outcomes which supports the future investigation of senotherapeutic agents promoting regenerative processes for non-healing wounds.

Acute or chronic anastomotic leak is a common complication after any gastrointestinal surgery in inflammatory bowel disease (IBD). The underlying disease of the bowel, comorbidities, malnutrition, anemia, and concurrent use of corticosteroids increase the risk for the development of anastomotic leaks. Anastomotic leak is traditionally managed with surgery. However, recent innovation has allowed the use of endoscopic methods in the management of some anastomotic leaks and their consequences. This article discusses a variety of endoscopic techniques that have either been established or are under current evaluation, for the management of anastomotic leaks in patients with IBD.

Perianal Crohn's disease is associated with decreased quality of life, high morbidity, and high health care use. Treatment goals are to provide infection control, stop fistula drainage, and heal fistula tracts while preserving the anorectal sphincter. Treatment includes a combination of medical and surgical intervention, but new techniques are using interventional endoscopy to act as either a bridge to surgery or to decrease the need for surgical intervention. The decision on which approach to pursue requires knowledge of prior surgery, altered anatomy, prior fistula treatment, and imaging and endoscopic evaluation of fistula complexity, mucosal involvement, and associated stricture or abscess.

Complex anal fistulas are difficult to treat. The main reasons for this are a higher recurrence rate and the risk of disrupting the continence mechanism because of sphincter involvement. Due to this, several sphincter-sparing procedures have been developed in the last two decades. Though moderately successful in simple fistulas (50%-75% healing rate), the healing rates in complex fistulas for most of these procedures has been dismal. Only two procedures, ligation of intersphincteric fistula tract and transanal opening of intersphincteric space have been shown to have good success rates in complex fistulas (60%-95%). Both of these procedures preserve continence while achieving high success rates. In this opinion review, I shall outline the history, compare the pros and cons, indications and contraindications and future application of both these procedures for the management of complex anal fistulas.

Crohn's disease is a chronic inflammatory bowel disease that affects various intestinal segments and can involve the perianal region. Although anti-tumor necrosis factor (TNF) agents have revolutionized the management of Crohn's disease and improved the prognosis for patients with perianal Crohn's disease (pCD), their long-term effectiveness is limited: over 60% of patients relapse after one year of maintenance therapy. In recent years, significant advances have been made in the treatment of complex perianal fistulas after anti-TNF failure. Concomitant treatment with antibiotics and immunosuppressants improves the effectiveness of anti-TNF agents. Therapeutic drug monitoring and dose adjustment of anti-TNF therapy (targeting a higher trough level) might also improve treatment response. Novel therapeutic strategies might provide new opportunities for pCD management; for example, ustekinumab might be effective after anti-TNF treatment failure, although more studies are needed. As suggested in recent international guidelines, mesenchymal stem cell injection might be an effective, safe treatment for complex pCD.

Crohn's anal fistula is a challenging condition, and may require multiple surgical procedures. To replicate successful procedures, these must be adequately reported in the literature. The aim of this study was to review the quality of reporting of components of surgical interventions for Crohn's anal fistula.

A systematic review was conducted. It was registered with PROSPERO (CRD:42019135157). The Medline and EMBASE databases were searched for studies reporting interventions intended to close fistula in patients with Crohn's disease, published between 1999 and August 2019. Abstracts and full texts were screened for inclusion by two reviewers. Dual extraction of data was performed to compare reporting to the TIDiER and Blencowe frameworks for reporting of interventions.

Initial searches identified 207 unique studies; 38 full texts were screened for inclusion and 33 were included. The most common study design was retrospective cohort (17/33), and the most frequently reported interventions were anal fistula plug (n = 8) and fibrin glue (n = 6). No studies showed coverage of all domains of TIDieR. Reporting was poor among domains related to who provided an intervention, where it was provided, and how it was tailored. Reporting of domains in the Blencowe framework was poor; the majority of studies did not report the component steps of procedures or efforts to standardise them.

This study demonstrates that reporting on technical aspects of interventions for Crohn's anal fistula is poor. Surgeons should aim to improve reporting to allow accurate reproduction of techniques both in clinical practice and in clinical trials.

Perianal Crohn's disease (CD) is a complex manifestation of CD that affects approximately 10% of patients. The spectrum of disease is quite variable, ranging from relatively mild disease to severe, aggressive manifestations that result in frequent hospitalizations, multiple surgeries, and poor quality of life. Despite significant recent advances in surgical and medical management, treatment remains challenging and frequently requires a multidisciplinary medical-surgical approach. The goal of this article is to review the current literature regarding the work-up, treatment, and future directions of therapy. Crucial features of effective management include the precise identification of manifestations, control of sepsis, limiting rectal inflammation, frequently with use of antitumor necrosis factor agents, and avoidance of extensive surgery.

Clinical trials have reported that flap repair (FR) can treat anal fistula (AF) effectively. However, no study systematically investigated its efficacy and safety for patients with AF. This study will systematically assess its efficacy and safety of AF.

We will retrieve MEDLINE, EMBASE, Cochrane Library, Elsevier, Springer, Web of Science, Scopus, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data from their inceptions to May 1, 2019 without any language limitations. The primary outcome is fistula cure rate. The secondary outcomes consist of fistula recurrence rate, fecal continence, quality of life, and complications. RevMan 5.3 software will be used for methodological quality assessment, data synthesis, subgroup analysis and sensitivity analysis.

The results of this study will summarize a high-quality synthesis of current evidence for the treatment of FR for patients with AF.

The findings of this proposed study will provide evidence for judging whether FR is an effective and safety intervention for AF or not.PROSPERO registration number: PROSPERO CRD42019135507.

Perianal diseases, common complications of Crohn's disease, are difficult to diagnose/manage. Patients with perianal Crohn's disease suffer from persistent pain and drainage, recurrent perianal sepsis, impaired quality of life, and financial burden. Conventional medical and surgical therapies carry risk of infection, myelosuppression, incontinence, disease recurrence. Although the phenotype of Crohn's disease has been extensively studied, reported outcomes are inconsistent. Endoanal ultrasonography is also becoming popular because of low cost and ability to acquire images in real time. Emerging management strategies for treatment including laser therapy, local injection of agents, use of hyperbaric oxygen, and stem cell therapy, have demonstrated efficacy.

Interventional (or therapeutic) inflammatory bowel disease (IBD) endoscopy has an expanding role in the treatment of disease and surgical adverse events. Endoscopic therapy has been explored and used in the management of strictures, fistulas/abscesses, colitis-associated neoplasia, postsurgical acute or chronic leaks, and obstructions. The endoscopic therapeutic modalities include balloon dilation, stricturotomy, stent placement, fistulotomy, fistula injection and clipping, sinusotomy, EMR, and endoscopic submucosal dissection. With a better understanding of the disease course of IBD, improved long-term impact of medical therapy, and advances in endoscopic technology, we can foresee interventional IBD becoming an integrated part of the multidisciplinary approach to patients with complex IBD.

There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology.

Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines.

All aspects of surgical care for IBD have been included along with 157 recommendations for management.

These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.

Prevalence of inflammatory bowel disease (IBD), ulcerative colitis and Crohn's disease has dramatically increased in Asian countries in the last three decades. In this period, many new medical therapies were introduced for the treatment of IBD, such as immunosuppressants, anti-tumor necrosis factor agents, leukocyte apheresis, anti-integrin antibody, and so on, which have contributed to induce remission and to reduce complications in IBD. As for surgical techniques for Crohn's disease, a stapled functional end-to-end anastomosis and conventional end-to-end anastomosis have similar perianastomotic recurrence rate and reoperation rate. Prospective randomized controlled studies which compare Kono-S anastomosis and stapled side-to-side anastomosis are ongoing. Variant two-stage ileal pouch anal anastomosis (IPAA) and transanal IPAA are new concepts for surgical treatment of ulcerative colitis. Various endoscopic procedures, such as balloon dilation for stenosis or stricture, endoscopic fistulotomy, injection of filling agents, and clipping for fistulas or perforations will be new options in the treatment of Crohn's disease. Adverse effects of preoperative treatments on postoperative complications should also be taken into account to improve surgical outcomes in IBD patients.

Fistulas in patients with inflammatory bowel disease (IBD) pose a key challenge in the management of these patients. We aimed to describe a novel endoscopic method to treat patients with IBD who have fistulas.

A cohort of 29 consecutive patients with fistulas and IBD were identified in the registry of our interventional IBD unit. An endoscopic fistulotomy with needle-knife was performed. The primary outcome was healing of the fistula without the need for surgical intervention.

A total of 29 patients underwent endoscopic fistulotomy; and the mean (± standard deviation) age of patients undergoing the procedure was 44.2 ± 14.6 years. Thirteen patients were male (44.8%), and 16 were female (55.2%). Twenty-six patients (89.6%) achieved complete resolution of the fistula as confirmed by endoscopy with a guidewire and/or cross-sectional abdominal imaging, with 10 patients (34.4%) requiring a single endoscopic treatment session. Three patients (10.3%) had a persistent fistula and required surgical intervention. One patient had postoperative bleeding requiring blood transfusion and hospitalization.

Endoscopic fistulotomy with a needle-knife appears to be safe and effective in treating IBD-related fistulas.

Perianal fistulae in patients with Crohn's disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two decades have seen significant advancements in the management of perianal fistulas in CD, which has evolved into a multidisciplinary approach that includes gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite the introduction of new medical therapies such as antitumour necrosis factor and novel models of care delivery, the best fistula healing rates reported with combined medical and surgical approaches are approximately 50%. More recently, newer biologics, cell-based therapies as well as novel endoscopic and surgical techniques have been introduced raising new hopes that outcomes can be improved upon. In this review, we describe the modern management and the most recent advances in the management of complex perianal fistulising CD, which will likely impact clinical practice. We will explore optimal use of both older and newer biological agents, as well as new data on cell-based therapies. In addition, new techniques in endoscopic and surgical approaches will be discussed.

Crohn's disease is increasingly thought to encompass multiple possible phenotypes. Perianal manifestations account for one such phenotype and represent an independent disease modifier. In its more severe form, perianal Crohn's disease confers a higher risk of a severe and disabling disease course, relapses, hospital admissions and operations. This, in turn, imposes a considerable burden and disability on patients. Identification of the precise manifestation is important, as management is nuanced, with both medical and surgical components, and is best undertaken in a multidisciplinary setting for both diagnosis and ongoing treatment. The introduction of biologic medication has heralded a significant addition to the management of fistulizing perianal Crohn's disease in particular, albeit with modest results. It remains a very challenging condition to treat and further work is required to optimize management in this group of patients.

Perianal localization of Crohn's disease involves significant morbidity, affects quality of life and results in an increased use of healthcare resources. Medical and surgical therapies contribute to its management. The objective of this review is to address the current understanding in the management of perianal Crohn's disease, with the main focus in reviewing pharmacological therapies, including stem cells. In complex fistulas, once local sepsis has been controlled by surgical drainage and/or antibiotics, anti-TNF drugs (infliximab, adalimumab) are the first-line therapy, with or without associated immunomodulators. Combining surgery and anti-TNF therapy has additional benefits for healing. However, response is inadequate in up to half of cases. A possible role of new biological drugs in this context (vedolizumab, ustekinumab) is an area of ongoing investigation, as is the local application of autologous or allogeneic mesenchymal stem cells. These are non-hematopoietic multipotent cells with anti-inflammatory and immunomodulatory properties, the use of which may successfully treat refractory patients, and seem to be a promising and safe alternative to achieving fistula healing in Crohn's disease, without known systemic effects.

Fistula and abscess represent penetrating disease phenotypes of Crohn's disease (CD) and can develop in patients with or without prior history of CD-related surgery. While CD fistula and abscess have been traditionally treated with medical and surgical therapy, the role of endoscopic therapy in this particular phenotype of CD is expanding recently, thanks to advanced endoscopic techniques and a better understanding of pathogenesis and natural history of the disease and principle of treatment. The success of endoscopic treatment for inflammatory bowel disease depends on comprehension and appreciation of principles, then techniques, followed by instrument and device. Attempts should be made to temporarily or permanently close the feeding side (or the primary) orifice at the gut, by various forms of clipping. Endoscopic fistulotomy is feasible, particularly for perianal fistula and surgery-associated distal bowel fistula. Perianal abscess can be treated with endoscopic incision and drainage and even seton placement. Endoscopic treatment for fistula and abscess as well as for stricture has become an important part of the multidisciplinary approach to complex CD.

Perianal fistulous disease is present in 10-15% of children with Crohn's disease (CD) and is frequently complex and refractory to treatment, with one-third of patients having recurrent lesions. We conducted a systematic review of the literature to examine the best surgical strategy or strategies for pediatric complex perianal fistulous disease (CPFD) in CD.

We searched CENTRAL, MEDLINE, EMBASE, and CINAHL for studies discussing at least one surgical strategy for the treatment of pediatric CPFD in CD. Reference lists of included studies were hand-searched. Two researchers screened all studies for inclusion, quality assessed each relevant study, and extracted data.

One non-randomized prospective and two retrospective studies met our inclusion criteria. Combined use of setons and infliximab therapy shows promise as a first-line treatment. A specific form of fistulectomy, "cone-like resection," also shows promise when combined with biologics. Endoscopic ultrasound to guide medical and surgical management is feasible in the pediatric population, though it is unclear if it improves outcomes.

There is a paucity of evidence regarding the treatment of CPFD in the pediatric population, and further research is required before recommendations can be made as to what, if any, surgical management is optimal.

Patients with Crohn's disease often develop perianal disease, successfully managed in most cases. However, its most aggressive form, complex perianal disease, is associated with high morbidity and a significant impairment in patients' quality of life. The aim of this review is to provide an updated approach to this condition, reviewing aspects of its epidemiology, diagnosis and therapeutic alternatives. Emerging treatment options are also discussed. A multidisciplinary assessment of these patients with a coordinated medical and surgical approach is crucial.

Several sphincter-preserving techniques have been described with extremely encouraging initial reports. However, more recent studies have failed to confirm the positive early results. We evaluate the adoption and success rates of advancement flap procedures (AFP), fibrin glue sealant (FGS), anal collagen plug (ACP) and ligation of intersphincteric fistula tract (LIFT) procedures based on their evolution in time for the management of anal fistula.

A PubMed search from 1992 to 2015. An assessment of adoption, duration of study and success rate was undertaken.

We found 133 studies (5604 patients): AFP (40 studies, 2333 patients), FGS (31 studies, 871 patients), LIFT (19 studies, 759 patients), ACP (43 studies, 1641 patients). Success rates ranged from 0% to 100%. Study duration was significantly associated with success rates in AFP (P = 0.01) and FGS (P = 0.02) but not in LIFT or ACP. The duration of use of individual procedures since first publication was associated with success rate only in AFP (P = 0.027). There were no statistically significant differences in success rates relative to the number of the patients included in each study.

Success and adoption rates tend to decrease with time. Differences in patient selection, duration of follow-up, length of availability of the individual procedure and heterogeneity of treatment protocols contribute to the diverse results in the literature. Differences in success rates over time were evident, suggesting that both international trials and global best practice consensus are desirable. Further prospective randomized controlled trials with homogeneity and clear objective parameters would be needed to substantiate these findings.

Treatment of perianal fistula has evolved with the introduction of new techniques and biologicals in Crohn's disease (CD). Several guidelines are available worldwide, but many recommendations are controversial or lack high-quality evidence. The aim of this work was to provide an overview of the current available national and international guidelines for perianal fistula and to analyse areas of consensus and areas of conflicting recommendations, thereby identifying topics and questions for future research.

MEDLINE, EMBASE and PubMed were systematically searched for guidelines on perianal fistula. Inclusion was limited to papers in English less than 10 years old. The included topics were classified as having consensus (unanimous recommendations in at least two-thirds of the guidelines) or controversy (fewer than three guidelines commenting on the topic or no consensus) between guidelines. The highest level of evidence was scored as sufficient (level 3a or higher of the Oxford Centre for Evidence-based Medicine Levels of Evidence 2009, http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/) or insufficient.

Twelve guidelines were included and topics with recommendations were compared. Overall, consensus was present in 15 topics, whereas six topics were rated as controversial. Evidence levels varied from strong to lack of evidence.

Evidence on the diagnosis and treatment of perianal fistulae (cryptoglandular or related to CD) ranged from nonexistent to strong, regardless of consensus. The most relevant research questions were identified and proposed as topics for future research.

Perianal fistulas in Crohn's disease are common and difficult to treat. Their aetiology is poorly understood. Assessment is clinical, endoscopic and radiological, and management is undertaken by a multidisciplinary team of gastroenterologists, surgeons and radiologists. Surgical drainage of the fistula tract system with the placement of loose setons precedes combined therapy with immunosuppressant and anti-TNFα agents in most patients. Proctitis should be rigorously eliminated where possible. Definitive surgical repair is sometimes possible and diversion or proctectomy are occasionally required. Combined medical and surgical management represents a promising avenue for the future.

Inflammatory bowel disease (IBD) comprises two distinct but related chronic relapsing inflammatory conditions affecting different parts of the gastrointestinal tract. Crohn's disease is characterised by a patchy transmural inflammation affecting both small and large bowel segments with several distinct phenotypic presentations. Ulcerative colitis classically presents as mucosal inflammation of the rectosigmoid (distal colitis), variably extending in a contiguous manner more proximally through the colon but not beyond the caecum (pancolitis). This article highlights aspects of the presentation, diagnosis, and management of IBD that have relevance for paediatric practice with particular emphasis on surgical considerations. Since 25% of IBD cases present in childhood or teenage years, the unique considerations and challenges of paediatric management should be widely appreciated. Conversely, we argue that the organizational separation of the paediatric and adult healthcare worlds has often resulted in late adoption of new approaches particularly in paediatric surgical practice.

The progression to fistula and strictures is part of the natural history of Crohn's disease (CD) and these complications negatively affect the quality of life of CD patients. Surgery is the traditional treatment of CD strictures. However, due the chronicity of the inflammatory process and the associated fibrosis, postoperative recurrence occurs frequently. The lack of specific drug to treat fibrotic strictures and their irreversible nature has drawn the attention to less invasive and bowel-sparing therapeutic modalities. Endoluminal therapies may provide effective option in relieving symptoms associated with CD complications and reduce the need for repeated surgery with substantial clinical benefit. This review will discuss the current use and efficacy of the endoscopic treatment of CD complications. New endoscopic modalities and recent advances will be also evaluated.

To develop a consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn's disease (pCD), based on best available evidence.

Based on a systematic literature review, statements were formed, discussed and approved in multiple rounds by the 20 working group participants. Consensus was defined as at least 80% agreement among voters. Evidence was assessed using the modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria.

Highest diagnostic accuracy can only be established if a combination of modalities is used. Drainage of sepsis is always first line therapy before initiating immunosuppressive treatment. Mucosal healing is the goal in the presence of proctitis. Whereas antibiotics and thiopurines have a role as adjunctive treatments in pCD, anti-tumour necrosis factor (anti-TNF) is the current gold standard. The efficacy of infliximab is best documented although adalimumab and certolizumab pegol are moderately effective. Oral tacrolimus could be used in patients failing anti-TNF therapy. Definite surgical repair is only of consideration in the absence of luminal inflammation.

Based on a multidisciplinary approach, items relevant for fistula management were identified and algorithms on diagnosis and treatment of pCD were developed.

Perianal symptoms are common in patients with Crohn's disease and cause considerable morbidity. The etiology of these symptoms include skin tags, ulcers, fissures, abscesses, fistulas or stenoses. Fistula is the most common perianal manifestation. Multiple treatment options exist although very few are evidence-based. The phases of treatment include: drainage of infection, assessment of Crohn's disease status and fistula tracts, medical therapy, and selective operative management. The impact of biological therapy on perianal Crohn's disease is uncertain given that outcomes are conflicting. Operative treatment to eradicate the fistula tract can be attempted once infection has resolved and Crohn's disease activity is controlled. The operative approach should be tailored according to the anatomy of the fistula tract. Definitive treatment is challenging with medical and operative treatment rarely leading to true healing with frequent complications and recurrence. Treatment success must be weighed against the risk of complications, specially anal sphincter injury. A full understanding of the etiology and all potential therapeutic options is critical for success. Multidisciplinary management of fistulizing perianal Crohn's disease is crucial to improve outcomes.

Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that includes both Crohn disease (CD) and ulcerative colitis. Abdominal pain, rectal bleeding, diarrhea, and weight loss characterize both CD and ulcerative colitis. The incidence of IBD in the United States is 70 to 150 cases per 100,000 individuals and, as with other autoimmune diseases, is on the rise. CD can affect any part of the gastrointestinal tract from the mouth to the anus and frequently will include perianal disease. The first description connecting regional enteritis with perianal disease was by Bissell et al in 1934, and since that time perianal disease has become a recognized entity and an important consideration in the diagnosis and treatment of CD. Perianal Crohn disease (PCD) is defined as inflammation at or near the anus, including tags, fissures, fistulae, abscesses, or stenosis. The symptoms of PCD include pain, itching, bleeding, purulent discharge, and incontinence of stool. In this report, we review and discuss the etiology, diagnosis, evaluation, and treatment of PCD.

Crohn disease involves the perineum and rectum in approximately one-third of patients. Symptoms can range from mild, including skin tags and hemorrhoids, to unremitting and severe, requiring a proctectomy in a small, but significant, portion. Fistula-in-ano and perineal sepsis are the most frequent manifestation seen on presentation. Careful diagnosis, including magnetic resonance imaging or endorectal ultrasound with examination under anesthesia and aggressive medical management, usually with a tumor necrosis factor-alpha, is critical to success. Several options for definitive surgical repair are discussed, including fistulotomy, fibrin glue, anal fistula plug, endorectal advancement flap, and ligation of intersphincteric fistula tract procedure. All suffer from decreased efficacy in patients with Crohn disease. In the presence of active proctitis or perineal disease, no surgical therapy other than drainage of abscesses and loose seton placement is recommended, as iatrogenic injury and poor wound healing are common in that scenario.

The two main diseases of inflammatory bowel disease are Crohn's disease and ulcerative colitis. The pathogenesis of inflammatory disease is that abnormal intestinal inflammations occur in genetically susceptible individuals according to various environmental factors. The consequent process results in inflammatory bowel disease. Medical treatment consists of the induction of remission in the acute phase of the disease and the maintenance of remission. Patients with Crohn's disease finally need surgical treatment in 70% of the cases. The main surgical options for Crohn's disease are divided into two surgical procedures. The first is strictureplasty, which can prevent short bowel syndrome. The second is resection of the involved intestinal segment. Simultaneous medico-surgical treatment can be a good treatment strategy. Ulcerative colitis is a diffuse nonspecific inflammatory disease that involves the colon and the rectum. Patients with ulcerative colitis need surgical treatment in 30% of the cases despite proper medical treatment. The reasons for surgical treatment are various, from life-threatening complications to growth retardation. The total proctocolectomy (TPC) with an ileal pouch anal anastomosis (IPAA) is the most common procedure for the surgical treatment of ulcerative colitis. Medical treatment for ulcerative colitis after a TPC with an IPAA is usually not necessary.

We aimed to analyze the feasibility and efficacy of a new transperineal access to treat anorectal sepsis (fistulae and abscesses) under endoanal ultrasonography guidance.

Twenty-five patients (80% Crohn disease) were included retrospectively. Twenty-one patients had fistulae (perianal, urethroanal, and anovaginal) treated by injection of heterologous fibrin glue and cyanoacrylate. Four patients with abscesses were treated by irrigation-injection of normal saline solution and an aminoglycoside antibiotic.

Twenty-five patients underwent 32 treatment sessions. At 4 weeks' evaluation, 19 patients (90.5%) with anal fistulae ultimately achieved a 4-week short-term success. Of these, 5 patients (26%) showed resolution of symptoms and persistent occlusion of the fistula track at long-term follow-up (>6 mo). At 4-week follow-up, the treatment of abscesses was successful in 3 of 4 cases. However, a relapse was observed in 2 cases after a mean period of 3 months. No serious adverse events were observed.

Endoanal ultrasonography-assisted percutaneous transperineal injection represents a sphincter-sparing alternative to the surgical route, with interesting outcomes and excellent tolerability for the treatment of anorectal sepsis.

Perianal fistulizing disease is a common complication of CD that requires a multidisciplinary collaboration between gastroenterology, surgery, and radiology professionals for successful assessment and treatment. Optimal success comes from a combined medical and surgical approach to treat the fistulizing disease (see Fig. 1). Unfortunately, even with a variety of surgical options, a subset of patients require permanent fecal diversion and/or proctectomy to successfully treat their disease. Further studies (likely requiring large, multicenter trials) of novel medical and surgical treatments are still warranted to formulate optimal management of this complex condition.

Perianal Crohn’s Disease (CD) is a significant cause of morbidity in CD patients. Accurate identification of perianal involvement requires advanced imaging techniques in addition to physical exam. Treatment of the disease is aimed at improving both the perianal and intestinal manifestations. Proper treatment depends upon the severity of the disease and combines current medical and surgical therapies to maximize response. The ability to improve perianal disease has grown significantly since the introduction of anti-TNF agents which are now a mainstay of treatment along with antibiotics and immunomodulators. New experimental therapies are limited by lack of research to support their use.

Fistulae or leakages of anastomotic junctions of the gastrointestinal tract used to be an indication for surgery. However, patients often are severely ill and endoscopic therapeutic options have been suggested to avoid surgical intervention.

This is a retrospective analysis of fibrin glue application in the treatment of gastrointestinal fistulae or anastomotic leakages.

The aim of this study was to investigate the value of fibrin glue in the treatment of gastrointestinal fistulae and leakages.

From September 1996 to November 2002, 52 patients with gastrointestinal fistulae or insufficiencies have been treated endoscopically including the use of fibrin glue (Tissucol Duo S®, Baxter, Unterschleissheim, Germany). Clinical data comprising concomitant therapies and results were analysed by chart review.

Twenty-six lesions were located in the oesophagus or gastroesophageal junction, 4 in the stomach, 7 in the small intestine, 13 colorectal and 2 in the pancreas. The duration of treatment ranged from 12 to 1,765 days. Two to 81 ml fibrin glue (median 8.5) was used in 1-40 sessions (median 4). All patients received antibiotics; additional endoscopic options were frequently applied. Endoscopic therapy cured 55.7% patients (n = 29); 36.5% (n = 19) were cured with fibrin glue as sole endoscopic option. In 23.1% (n = 12), surgical intervention became necessary. Patients without major infectious complications tended to have a higher cure rate without surgery (87.5% vs. 50%). Eleven patients died (21.1%).

Endoscopic therapy is a valuable option in the treatment of fistulae and anastomotic insufficiencies of the gastrointestinal tract. It usually is applied repeatedly. Fibrin glue is a mainstay of this procedure. Major infectious complications seem to define a subgroup of patients with poorer outcome.

Crohn's anal fistulas are common and cause considerable morbidity. Their management is often difficult; medical and surgical treatments rarely lead to true healing with frequent recurrence and complications.

To examine medical treatments previously and currently used, surgical techniques and the important role of optimal imaging.

We conducted a literature search in the Pub Med database using Crohn's, Anal Fistula, Surgery, Imaging and Medical Treatment as search terms.

Antibiotics and immunosuppressants have a role, but slow initial response, side effects and relatively low remission rates of up to around a third with frequent recurrence limit their value. Long-term infliximab produces clinical remission in 36-58% of patients with combined medical and surgical management achieving optimal outcomes. Traditional and newer surgical procedures often have a high rate of recurrence with a significant risk of temporary or, in up to 10% of cases, permanent stomas, incontinence and unhealed or slowly healing wounds in 30%.

Management of Crohn's anal fistulas remains challenging. Established principles are to drain infection, use setons as required, aggressively manage active proctitis, give antibiotics, immunosuppressants and employ anti-TNFα therapy, and they demand significant co-operation between gastroenterologists and surgeons.

In the last 5 years, significant advances have been made in the surgical approaches to, and medical management of, Crohn's disease (CD). This review summarizes these advances as they relate to the care of surgical patients with CD, with an emphasis on innovations in surgical techniques, specifically minimally invasive (laparoscopic) surgery, as well as on recent developments in biologic pharmacotherapies for CD that have important clinical implications for surgical patients. These include recent insights gained into the role of biologic therapy with infliximab and other newer agents in preoperative and postoperative therapy of CD patients. We will also review other recent developments relevant to the current and future surgical care of CD patients, including the treatment of less common forms of CD, such as duodenal and colonic CD, and the role of novel strategies such as fibrin glue, fistula plugs and stem cell therapy for the treatment of fistulizing anorectal CD.

Fibrin glue is a therapeutic for fistulas that activates thrombin to form a fibrin clot, which mechanically seals the fistula tract. We assessed the efficacy and safety of a heterologous fibrin glue that was injected into the fistula tracts of patients with Crohn's disease (ClinicalTrials.gov No. NCT00723047).

This multicenter, open-label, randomized controlled trial included patients with a Crohn's disease activity index < or =250 and fistulas between the anus (or low rectum) and perineum, vulva, or vagina, that drained for more than 2 months. Magnetic resonance imaging or endosonography was performed to assess fistula tracts and the absence of abscesses. Patients were stratified into groups with simple or complex fistulas and randomly assigned to receive fibrin glue injections (n = 36) or only observation (n = 41) after removal of setons. The primary end point was clinical remission at week 8, defined as the absence of draining, perianal pain, or abscesses. At week 8, a fibrin glue injection was offered to patients who were not in remission.

Clinical remission was observed in 13 of the 34 patients (38%) of the fibrin glue group compared with 6 of the 37 (16%) in the observation group; these findings demonstrate the benefit of fibrin glue (odds ratio, 3.2; 95% confidence interval: 1.1-9.8; P = .04). The benefit seemed to be greater in patients with simple fistulas. Four patients in the fibrin glue group and 6 in the observation group had adverse events.

Fibrin glue injection is a simple, effective, and well-tolerated therapeutic option for patients with Crohn's disease and perianal fistula tracts.

: affecting sphincter integrity and continence. Traditional surgical and medical approaches are not without their limitations and may result in either comorbidity, such as fecal incontinence, or incomplete healing of the fistulae. Over the last 2 decades these limitations have led to a paradigm shift toward the use of biomaterials, and more recently cell-based therapies, which have met with variable degrees of success. This review discusses the traditional and current methods of treatment, as well as emerging and possible alternative approaches that may improve fistula healing.

The current evidence for fibrin glue as a treatment for anal fistulae is mixed. This study reviews the experience of fibrin glue as a treatment for anal fistulae in a single tertiary referral centre and attempts to identify factors related to failure of therapy and the length of follow-up required.

Patients with fistulae in ano that were treated with fibrin glue between February 2004 and August 2008 were analysed. All procedures were performed by two colorectal consultants based at the Queens Medical Centre, Nottingham. All patients were followed-up to assess the outcome of this treatment.

Forty patients (21 male, 19 female) with a mean age of 46.5 years were studied. The mean duration of symptoms prior to presentation was 39 months (range 4-240 months). Presenting symptoms included perianal discharge (72.5%), perianal abscess (57.5%), pain (12.5%), PR bleeding (7.5%), itching (5%) and urgency (2.5%). Patients had a minimum of two follow-up appointments and the median follow-up period was 5.2 months (range 1-16 months). Following MRI and operative assessment, 28 (70%) of the 40 fistulae were considered complex (high trans-sphincteric, extra-sphincteric, pouch-vaginal). Patients who had inflammatory bowel disease were classified as simple tracts but all failed to heal (three patients). Twenty of the complex fistulae failed to heal. Three patients who had repeat application of glue for their complex fistulae failed to heal on follow-up. Of the remaining 12 patients who had simple fistulae in ano, five (41.7%) healed completely. There were no complications such as abscess, related to treatment. All patients who were asymptomatic at 3 months did not develop any further recurrence.

Fibrin glue is a simple treatment strategy, preserves sphincter function with minimal adverse side effects. It should therefore be considered as possible first line treatment in simple fistulae but it is less likely to be successful in complex or those fistulae associated with inflammatory bowel disease. Repeat gluing is unlikely to be successful. Fistulae that have failed to heal by 3 months will need further treatment.

Crohn's disease manifests with perianal or rectal symptoms in approximately one-third of patients, and is associated with a more aggressive natural history. Due to the chronic relapsing nature of the disease, surgery has been traditionally avoided. However, combined medical and surgical intervention when treating perianal fistulae has been shown to offer the best chance for success. Endoanal ultrasound examination or pelvic magnetic resonance imaging should be done in conjunction with an examination under anesthesia to characterize the disease. Any abscess should be drained and setons placed if there is active rectal inflammation or complex fistulae. Antibiotics and immunosuppressive therapy (especially with infliximab) should also be initiated. Simple fistulae can be treated surgically by fistulotomy or anal fistula plug. Complex fistulae can be closed with either an anal fistula plug or covered with flaps. Up to 20% of patients anorectal Crohn's disease require proctectomy for persistent and disabling disease.

Due to the considerable variety in the clinical presentation of anorectal and rectovaginal fistulas in Crohn's disease, data on treatment results for each type of fistula are limited. The aim of this study was to summarize the results after surgical treatment of such fistulas in a large consecutive series of patients.

All patients with anorectal or rectovaginal fistula due to Crohn's disease requiring surgery in our institution between 1991 and 2001 were extracted from a prospective database. A standardized telephone interview was conducted and patients were followed in our outpatient clinic, the department of internal medicine, or at their gastroenterologist. Type of fistula and interventions were classified and analyzed. Recurrence-free time intervals were estimated for each type of fistula and for the different surgical procedures. The influence of the surgical procedure, the number of operations performed, and the correlation to other localizations of the disease were analyzed in regard to the recurrence rate.

From 777 patients with Crohn's disease undergoing surgery between 1991 and 2001, 147 had anorectal or rectovaginal fistula (292 operations). Ninety-eight percent of them also had Crohn's disease in the colon or rectum compared to only 21% of patients without a fistula (p value <0.001). Over long-term follow-up, 29 patients (20%) required proctectomy. Submucosal fistulas needed major surgery in only 14% of cases compared to 56% of cases with rectovaginal fistulas. After 5 years, complex fistulas showed a strong trend towards a higher recurrence rate after surgery than simple submucosal fistulas (45.6% vs. 18.8%, p = 0.079). Whereas recurrences occurred over the whole observation period in the group of patients with complex fistulas, there was no further recurrence in patients with submucosal fistulas 13 months after surgery. In rectovaginal fistulas, additional levatorplasty showed no advantage over standard endorectal advancement flap.

Long-term follow-up demonstrates that recurrence rates after repair of complex fistulas for Crohn's disease are high and continuously increase over time. Submucosal fistulas have the best outcome; after 13 months without recurrence, definite cure can be expected.

Several techniques have been described for the management of fistula-in-ano, but all carry their own risks of recurrence and incontinence. Technology has evolved over the past 2 decades that may enable surgeons to deal with this troublesome issue with greater success. This review summarizes the history of fistula-in-ano management, the current techniques available, and describes new technologies.

Medline searches were performed using the PubMed, Ovid, Embase, Cochrane, and Google Scholar databases to identify articles reporting on fistula-in-ano management using surgery alone, fibrin glues, and fistula plugs. Forty-one articles reporting on the history of fistula-in-ano management and the use of new technologies were included.

Conventional fistula surgery techniques have their place, but new technologies such as fibrin glues and the anal fistula plugs offer an alternative approach, with initial studies reporting good success rates.

New technologies provide promising alternatives to traditional methods of management. There is, however, a real need for high-quality randomized control trials.

The advent of biological therapies has focused attention on the importance of healing luminal Crohn's disease, thereby modifying the disease course. Perianal fistulas are common in Crohn's disease and often have a poor prognosis, with permanent sphincter and perineal tissue destruction. The importance of healing these fistulas has been less well appreciated. Management still often is left in surgical hands alone, rather than the optimal combination of surgery, infection control, and immunosuppression. Drug therapy often is haphazard, and the means of assessing healing over a long time period has been characterized poorly. Recent studies have suggested that many of these patients can achieve fistula healing, at least in the medium term. We therefore call for more active intervention, with the goal of healing, in these sick patients. Perianal fistulas lead to substantial physical and emotional distress because of pain, discharge, incontinence, perineal and genital disfigurement, and slow resolution even with treatment. The advent of accurate anal imaging, improved knowledge of surgical outcomes, and potent biological therapies make it timely to reflect on current best-management strategies.

Infliximab is an effective treatment for active intestinal Crohn's disease; however, the efficacy of infliximab in perianal Crohn's disease is controversial. This study was designed to compare patients with Crohn's disease who underwent perianal fistula surgery with or without infliximab infusion.

A retrospective chart review of 226 consecutive patients with Crohn's disease who underwent operative treatment with or without infliximab (3-6 infusions of 5 mg/kg) from March 1991 through December 2005 was completed. Patients were classified as completely healed, minimally symptomatic (seton placement with minimal drainage and/or infliximab dependence), and failure (persistent or recurrent symptomatic fistula, diverting procedure, or proctectomy).

A total of 226 patients underwent operative treatment alone (n = 147) or in combination with infliximab infusion (n = 79). Age, gender, and preoperative history of intestinal and perianal Crohn's disease were similar between groups. Mean follow-up was 30 (range, 6-216) months. Operative treatment consisted of seton drainage (n = 112), conventional fistulotomy (n = 92), fibrin glue injection (n = 14), advancement flap (n = 5), collagen plug insertion (n = 2), and transperineal repair (n = 1). Eighty-eight patients (60 percent) healed completely with operative treatment alone, and 47 patients (59 percent) healed after operative treatment in combination with infliximab (P = not significant).

Operative treatment of perianal fistulas in patients with Crohn's disease resulted in complete healing in approximately 60 percent of patients. Preoperative infliximab infusion did not affect overall healing rates.