an anal fistula is a chronic phase of anorectal sepsis and is characterized by chronic purulent drainage or cyclical pain associated with abscess formation , followed by intermittent spontaneous decompression [ 1 , 2 ] .
the goals in the treatment of an anal fistula are to eliminate the primary fistula opening , any associated tracts , and any secondary openings without a change in continence .
most anal fistulae are simple and can be treated using a fistulotomy , which has a low recurrence rate and an acceptable rate of morbidity [ 3 - 6 ] .
however , the treatment of a complex anal fistula , which is defined as a fistula whose treatment poses an increased risk for a change in continence , still represent a challenge [ 7 - 9 ] .
the recurrence rate for a complex anal fistula managed with a cutting seton is reported to be 0 to 8% , with minor and major incontinence being reported in 34 to 63% and 2 to 26% of patients , respectively [ 10 - 14 ] .
advancement flap is still considered to be the gold standard of treatment for a complex anal fistula .
successful healing of the fistula has been demonstrated in 55 to 98% of patients [ 8 , 10 , 15 - 17 ] .
however , this procedure is technically demanding , and although the sphincter mechanism is not divided during advancement flap repair of the fistula , minor incontinence has been found in up to 31% patients and major incontinence in up to 12% of patients [ 10 , 18 , 19 ] . because of the risk of a change in continence with these conventional techniques , sphincter - preserving techniques for the management of complex anal fistulae have been evaluated .
glue was easy to apply , but probably not ideal for fistula treatment because of its liquid consistency . a failure of the formed glue clot in a properly sealed tract , the inability to securely fix the material within the tract and the uncertainty of tissue in growth into the glue may all explain the possible causes of the poor outcomes .
this article aims to review the literature and to identify the new sphincter - preserving techniques , such as the anal fistula plug , the ligation of intersphincteric fistula tract ( lift ) procedure and the cell therapy , used in the management of anal fistulae .
the small intestinal submucosa is a natural biomaterial harvested from porcine small intestine and fabricated into a biomedical product of various shapes and thickness .
the fact that it has been demonstrably useful as a bioprosthetic material in infected fields makes its application in fistula surgery quite reasonable .
1 ) . the idea is to bridge the defect of the fistula with a biocompatible material that would act as a scaffold for the patient 's own fibroblasts to come in and promote wound healing in the fistula tract [ 23 , 24 ] .
the technique of plug deployment is as follows : the tract is explored , probed , and irrigated gently with hydrogen peroxide .
then , the apex of the plug is tied to the probe from the internal opening , and the plug is dragged through to the external opening .
it is cut to fit and is secured in the internal opening by using a figure - of - eight suture , incorporating it with the mucosa of the anorectum to close the internal opening ( fig .
the anal fistula plug has been used in a number of cases with widely varying results ( table 1 ) [ 21 , 24 , 26 - 33 ] . in an early prospective series of 46 patients reported by champagne et al .
, after a median follow - up of 12 months ( range , 6 to 24 months ) , 17% of fistulae recurred .
johnson et al .   published a series comparing two prospective cohort groups of patients undergoing plug closure versus patients undergoing fibrin glue closure .
they reported an 87% closure rate for the plug group versus a 40% closure rate for the glue group .
others have had less favorable results with fistula recurrence rates as high as 80% [ 21 , 28 - 31 ] .
on review of these publications , possible explanations for this discrepancy include differences in patient selection and technical problems . in an attempt to standardize the indications for use of the bioprosthetic anal fistula plug and techniques for its placement ,
first , the group stressed that the use of the fistula plug could only be recommended for use in transsphincteric anal fistulae without acute inflammation or infection .
the group felt that dislodgement of the anal fistula plug was a problem related to issues in the technique of plug placement .
the group also stressed the importance of the external fistula opening being patent to allow for drainage .
although most fistula recurrences occur within the first 3 months after treatment , a significant number of recurrences are known to occur after this time .
a minimum one - year follow - up is generally accepted as being needed to justify the results of sphincter - preserving surgery .
reported that posterior fistula location , tobacco smoking , and a history of previous failure of the plug were independent predictors of plug failure .
the main limitation of application of the anal fistula plug in the treatment of anal fistulae in korea is the high cost . in korea ,
the cost of an anal fistula plug is not reimbursed by the national insurance system .
therefore , the cost of using a plug must be paid by the patients themselves .
it is interesting to note that the anal fistula plug procedure would probably be suitable for a low transsphincteric fistula . in a study from the university of minnesota ,
however , it was 65% for fistulae that involved less than one - third of the sphincter and 22% for those involving two - thirds or more .
recent reports from chulalongkorn university , bangkok , thailand , have described a novel technique called lift for the treatment of anal fistulae .
a success rate of 94.4% was reported in the treatment of 18 patients [ 34 , 35 ] .
this technique prevents the entry of fecal material into the fistula tract and eliminates the formation of a septic nidus in the intersphincteric space to allow healing of the anal fistula .
the location of internal opening is identified by injection of hydrogen peroxide or water through the external opening or by gently probing the fistula tract .
a 1.5 to 2.0 cm curvilinear incision is made at the intersphincteric groove overlying the fistula tract .
the dissection is kept close to the external sphincter to avoid cutting through the internal sphincter and breaching the anal mucosa .
after the intersphincteric tract has been identified and dissected out , the tract is ligated close to the internal sphincter .
. the tract next to the suture site is divided , and the rest of intersphincteric tract is excised .
after removal of the correct fistulous tract has been confirmed , infected granulation tissues in the rest of the tract and cavity are thoroughly removed with curettage .
the lift procedure has been used in five case series with promising early results ( table 2 ) [ 34 , 36 - 39 ] .
bleier et al .   reported that successful fistula closure was achieved in 57% of the 35 patients .
the advantages of the lift procedure may include preservation of the anal sphincter , minimal tissue injury , shorter healing time , and its being a procedure that is relatively easy to perform .
additionally , even if the fistula is not healed successfully , the lift procedure may convert a difficult - to - treat transsphincteric fistula into an easier - to - manage intersphincteric fistula .
first , the published results are the only case series of a heterogeneous population , and the good results may come from selection bias .
second , there were some variations in the manner in which the fistula was ligated and in the coring out or curettage of the external tract .
third , a longer and objective follow - up would be a better indicator of the durability , and no standardized questionnaires were used pre- or postoperatively with respect to fecal incontinence and quality of life .
additionally , as is the anal fistula plug , the indication for the lift procedure seems to be limited to the transsphincteric fistula .
interestingly , another intersphincteric approach for the treatment of a complex anal fistula has been described by matos et al . .
first , the ligation of the fistula tract is more secure than over sewing , and second , removal of infected granulation tissue by curettage is more practical and less time - consuming than total excision of the tract and primary repair .
apart from the difficulty in the lift procedure for a high transsphincteric or a suprasphincteric fistula , the identification of the intersphincteric tract through the intersphincteric approach seems to require more advanced technical skills than the removal of the intersphincteric tract and infected granulation tissue in a conventional technique does .
neal ellis   published outcomes with the biolift technique for the management of transsphincteric fistulae .
the biolift technique is a variation of the lift technique in which a bioprosthetic is placed in the intersphincteric plane to reinforce the closure of the fistula tract .
the bioprosthetic graft acts as a physical barrier in the intersphincteric space . actually , the biolift technique utilized a transection of the intersphincteric tract and closure of the fistula opening in the internal sphincter , which is similar to the procedure described by matos et al . , instead of ligating the intersphincteric tract . when compared to the lift , the biolift technique has two potential disadvantages .
first , it requires a more extensive dissection in the intersphincteric space because the bioprosthetic must overlap the closure of the fistula tract by at least 1 to 2 cm in all directions .
mesenchymal adult stem cells extracted from certain tissues , such as adipose tissue , can differentiate into various types of cell .
[ 43 , 44 ] chose adipose tissue as the source of stem cells because of their two biologic properties : their ability to suppress inflammation and their differentiation potential . moreover , enough fat can be obtained with liposuction , and the fat cells can be harvested with minimal adverse effects on the patient .
their phase i clinical trials show that adipose - derived stem cells are safe for the treatment of a fistula in crohn 's disease , and they published a phase ii multicenter , randomized controlled trial to further investigate the effectiveness and safety of ascs in the treatment of complex anal fistulae compared with the fibrin glue group .
the treatment procedures are as follows : 1 ) tract identification , with special emphasis on the identification of the internal opening ; 2 ) tract curettage , with special emphasis on the intersphincteric tract ; 3 ) closure of the internal opening ; 4 ) injection of a cell suspension through a long fine needle into the tract walls ; 5 ) sealing of the tract with fibrin glue .
they reported that fistula healing was observed in 71% of 24 patients who received ascs in addition of fibrin glue compared with 16% of 25 patients who received fibrin glue alone ( relative risk for healing , 4.43 ; confidence interval , 1.74 to 11.27 ; p < 0.001 ) .
the proportion of patients with healing was similar between the crohn 's and the non - crohn 's subgroups .
an advantage of using stem cells to treat an anal fistula is that , because tract resection is not required , the treatment does not injure the anal sphincter ( fig .
4 ) . there are , nonetheless , some limitations of the ascs - based therapy .
first , the cost of treatment with ascs is difficult to evaluate in detail at present .
second , technically , secure closure of the internal opening and complete injection of the cell suspension over the tract may be complicated procedures .
finally , as yet , there are no reports on the long - term effects of using ascs . in the meantime ,
a pilot study on autologous fibroblast - based therapy for the treatment of anal fistulae is in progress in the united kingdom . in brief
, the authors suggest that the addition of autologous fibroblasts to the filling material ( collage paste ) provides the best histologic healing .
to the colorectal surgeon , the complex anal fistula remains a challenging condition to manage despite the best of technologic advances .
therefore , the colorectal surgeon should become familiar with various new techniques for treating an anal fistula and remember that conventional fistula surgery , such as cutting seton and advancement flap , has an important role .
especially , the advancement flap is still the gold standard of treatment for complex anal fistulae .
definitive evidence of the advantage of the new sphincter - preserving techniques compared with the traditional intervention requires randomized control studies , which are now being conducted .
 surgery for an anal fistula may result in recurrence or impairment of continence . the ideal treatment for an anal fistula 
 should be associated with low recurrence rates , minimal incontinence and good quality of life . because of the risk of a change in continence with conventional techniques , 
 sphincter - preserving techniques for the management complex anal fistulae have been evaluated . 
 first , the anal fistula plug is made of lyophilized porcine intestinal submucosa . 
 the anal fistula plug is expected to provide a collagen scaffold to promote tissue in growth and fistula healing . 
 another addition to the sphincter - preserving options is the ligation of intersphincteric fistula tract procedure . 
 this technique is based on the concept of secure closure of the internal opening and concomitant removal of infected cryptoglandular tissue in the intersphincteric plane . 
 recently , cell therapy for an anal fistula has been described . 
 adipose - derived stem cells have two biologic properties , namely , ability to suppress inflammation and differentiation potential . 
 these properties are useful for the regeneration or the repair of damaged tissues . 
 this article discusses the rationales for , the estimated efficacies of , and the limitations of new sphincter - preserving techniques for the treatment of anal fistulae . 
INTRODUCTION
THE ANAL FISTULA PLUG
LIFT PROCEDURE
BIOLIFT PROCEDURE
EXPANDED ADIPOSE-DERIVED STEM CELLS (ASCs)
CONCLUSION