Alamshah S. M, Dorestan N, Kabiri A. Non-Surgical Treatment of Adult Fistula-in-Ano. Assessment of Curative Response to Intra-Tract Injections of Combined Sodium Tetra Decyl Sulphate, Ceftazidine and Metronidazol. Biomed Pharmacol J 2016;9(2).

---

Manuscript received on :February 10, 2016
Manuscript accepted on :April 05, 2016
Published online on: 12-08-2016

---

How to Citeclose    |   Publication History close

 Views: 

Visited 1,290 times, 1 visit(s) today

 

 PDF Downloads: 

753

Seyed Mansour Alamshah*, Nozar Dorestan and Alireza Kabiri

Department of surgery, Golestan Hospital. Ahwaz Jundishapou University of Medical Science. Ahwaz-Iran. *Corresponding Author E-mail: mansourseyedalam@gmail.com     

DOI : https://dx.doi.org/10.13005/bpj/979

Abstract

The standard treatment of fistula in-ano is surgical; however, considering recurrence and incontinence, non-surgical approach might be justified. The study was aimed to investigate application of combined antimicrobial drugs for cure the fistula as a primary treatment. 30 referral cases of perianal fistulas in three groups were enrolled during 15 months. Intermittent multiple intra-tract injections of combined Sodium Tetra Decyl Sulphate (STDS 1%), Metronidazol and Ceftazidine were performed and followed for ten months. 25 cases co-operated until the end of follow up. 16 cases (64%) were completely cured after 10 months of fallow up. 9 cases (36%) were recurred and referred for surgery. Metronidazol + Ceftazidine was shown 71.42% success; STDS + Metronidazol 70% success and STDS + Ceftazidine group 50% success. There were no significant differences between cured and recurrent fistulas considering demographic features, involvement duration, number of injections, length of tracts and distance of orifices from the anal verge. There was significant relation between recurrence and short tract length in anterior type of fistulas (P = 0.023). Conclusively, we suggest that direct injection of selective combined antibiotics, as premier Metronidazol, may cure perianal fistulas as the first step. Short tract anterior and cavitated active fistulas should not be considered.

Keywords

Perianal fistula; Non-surgical treatment; Combined antibiotic therapy;  Sodium Tetra Decyl Sulphate; Ceftazidine; Metronidazol

Introduction

Perianal fistulas may simply produce by ignorance of on time, careful and incorrect treatment of perianal infection and abscesses. Determination of the type and the pathway of this prevalent complication of cryptogenic perianal abscesses are necessary for selecting its wide range of treatment from simple fistulotomy toward mucosal flap advancement or even diversion of rectum. As surgery is the best treatment, both fistulotomy and fistulectomy are now commonly performed surgical procedures. However, in such procedures anal continence as the goal treatment and a full healing response may not be achieved [1- 4]. On the other hand, high, posterior curved, unilateral multi-orifice, bilateral multi-orifice (horseshoe) and recurrent fistulas are typically problematic and the sphincteric continence would be endangered by repeated surgeries. Complicated fistulas are currently best treated by different invasive and non-invasive combined medical-surgical procedures. Yet, as a general concept, all these procedures besides other new techniques may not provide the ultimate strategy for cure in all [3]. Nevertheless, they are accomplished, though as a rule, whenever the continence is being endangered the surgeon has to choose a certain alternative therapeutic strategy. Currently, there is no convincing accepted non-surgical procedure alone as an alternative. Application of local antibiotics, chemotherapeutic drugs into the fistulas with inflammatory bowel disease (IBD), Fibrin glue injection and mixed Seton or threads placement are examples of current popular non-invasive treatment options. The main advocated advantages of individualized non-surgical and minor non-invasive medical interventional treatments are preserving anal continence in spite of long-lasting healing processes compared to surgery. Their effectiveness varies and they are now being widely considered particularly in treatment of IBD producing anal fistulas. Therefore as a non-surgical treatment for fistula in-ano, this study aimed to investigate the therapeutic outcome, efficiency and credibility of intra-tract injection of combined selective antiseptics as the first therapeutic step for curative management.

Methods

This is a case series, interventional clinical study of 30 referral perianal fistulas to our surgical clinics affiliated to Jundishapour University of Medical Science, Ahwaz-Iran. During 15 months from August 2011 to November 2012, patients who referred for treatment of perianal discharges diagnosed as perianal fistulas by physical examination with their agreement and consent for this type of treatment were selected. Informed written consents was acquired for participation in the study based on ethical approval conform to the guidelines of 1975 declaration of Helsinki and approved research project of Jundishapour University of Medical Sciences institution and faculty registration. Thirty patients were recruited in three groups regardless of age, gender and the type of fistula and were followed 10 months for complete cure by the end of injections. Inclusion criteria were all referral patients for primary or relapsed anal fistulas. Exclusion criteria were short anterior epithelialized superficial fistulas (tract length ≤2 cm), active cavitated post drainage abscess and others with multiple orifices with underline disease (IBD). Firstly during admission, fistulas were probed by a fine blunt head semi-flexible plastic probe to find the direction, height and the length accompanied by injection of Povidin Iodine for determining the level of internal orifice during proctoscopy as upper or lower position related to dentate line. Three groups of antiseptic drugs were selected on the basis of colorectal bacterial colonization for randomly intra-tract injections: Sodium Tetra Decyl Sulphate (STDS) and Ceftazidine; STDS and Metronidazol; Ceftazidine and Metronidazol. We speculated that STDS has the ability to deteriorate new internal tract epithelialization and also could reinforce antibiotics to accelerate granulation and healing by its detergent property and PH. Injections were performed by dilution of Ceftazidine (1gm) with two ml of distilled water as suitable volume and concentration, Metronidazol (500 mg) drip injection from manufactured bag by the set and STDS (2 ml, 1%). All the materials were injected from the external orifice in the rate of one ml /5minutes very slowly through a fine blunt head injector needle to lodge the drug copiously into the tract. We begin the injection with STDS and then antibiotics in a manner of “every other day injection” intermittently, which after were followed weekly. Following weeks, injections were continued until external orifice was being closed and it’s over skin was completely healed and discharges were completely stopped (follow up was considered about three weeks to one month without discharge for next continues observation). No other intra venous or oral antibiotics were used. Patients were followed up for early and late recurrence after termination of discharges extended by monthly follow up until 3 months and every two months for 6 months respectively until 10 months were passed, unless any discharges were already reported. For recurrence, if the external orifice was active after injections, the second cycle was repeated until secondary closure. In cases that recovery was not achieved or the patient did not accept the second session,  patient was accounted as un-responsive and was referred for surgery. Cure was accepted as complete asymptomatic patient for at least over 10 months. The data were calculated and analyzed by independent sample test, T test, Spearman’s correlation, Chi-square test (Pearson, Fisher) where p<0.05 was considered statistically significant through the SPSS software.

Results

There were total 18 (72%) Male and 7 (28%) female from 30 (22 male,8 female) cases that completed follow up. 5 patients were omitted because of follow up rejection and irregular receiving injections. They had 28 – 63 (mean: 40.96) years old with 6 anterior and 19 posterior fistulas in which 15 were trans sphincteric and 10 Inter-sphincteric with short distance from anal verge (about:1.3 – 3.6 Cm, mean: 2.428)  without supra or extra-sphincteric or high type fistula . All were unitract with single orifice. Their internal orifices were juxta-dentate or below the dentate line mostly lateral and posterolateral. The length of tract was between 28 – 57 mm (mean: 42.04). Duration of involvement until referral was 2 – 27 (mean: 5.76) months. The numbers of injections were between 6 -14 (Mean: 8.92). There were no complication and all of the symptoms of pain, inflammation, and discharges were dramatically subsided until the termination of next injections and days before recurrence and patients were satisfied. 8 patients had intra tract injections of STDS + Ceftazidine in whom 4 cases were completely cured and 4 had recurrence after between1-3 months (50% success) and 2 missed follow up. In second group, 10 patients were injected with STDS + Metronidazol that 6 of them had cure by first session of injections in follow up, however, 4 patients relapsed after approximately 1-4 months. Two of recurred fistulas were received 5 and 8 re-injection respectively for second session due to very low discharges and one cured until followed up (70% success). Other 3, referred to surgery after 3 months for bulging and new symptoms. In the third group, 7 patients received Ceftazidine + Metronidazol injections. Five patients were cured and 2 were relapsed (71.42% success) (Table1). One patient was a case of previous fistulectomy with two recurrences and re operation by Seton placement during 20 months where the main tract was cured but has been referred again for an accessory tract in posterior side near the border of coccyx after 7 months. Overall, 16 (64%) patients were cured and had no symptom during 10 months of follow up and 9 (36%) relapsed. Of patients who had recurrence, relapse intervals were in between 3 to16 weeks from recovery. From those were relapsed 5 fistulas (55.5%) with the length of 29-40 mm were anterior type and 4 (44.4%) were posterior with the length of 37-50 mm. There were no complications or incontinence. 5 cases were excluded due to very late non-cooperative behavior and abruption to continue their complete ten months of follow up and poor compliance to the study protocol. Comparing the results, there were no significant differences between cured and recurrent fistulas considering gender, age, duration of involvement, number of injections, length of fistula and distance from anal verge (Table2). However, there was a significant relation between recurrence and anterior type of fistulas in the study (P = 0.023) and gender had no meaningful difference compared to recurrence and the type (Table3).

Table 1: Result of drug injections and the outcome of 10 months follow up.

* No response that was referred for surgery. ** Missed follow up, late rejections and follow up abruptions who were omitted. [*] Only one was cured.

Table 2: Comparing the means of variants related to recurrence and their P values.

SD (standard deviation), Sig (significance).

Table 3: Comparing the recurrence in anterior type of fistulas based on Goodsal Law and gender.  

Discussion

Treatment of fistula-in-ano has a fluctuated remedy, originated from multi factorial causes that directly affect the therapeutic outcome. Selective therapeutic protocols depend on fistula’s anatomy and patient’s habitual conditions. Long lasting constipation, high protein-fat diets and crypt bacterial reservoir are existing factors that facilitate resistance against healing. Having their predispositions be considered, therapeutic insight necessitates changing the glance more towards medical and non-surgical multi-modality interventional remedy for most fistulas, as they are complex. Since, ancient medicine had experienced the thought of using threads or Seton weltering to materials working as antiseptics for managing the fistula in ano, medical non-surgical interventions had been propounded (Ksharsootra by Indian physician Sushruta in the 600 BC) [1,5]. Although, nowadays, surgery alone is the promising ultimate cure in simple fistulas, however, saving the continence as a rule, has withdrawn it in the complex types. For instance, advancement flap is considered the gold standard for complex fistula; whereas it is associated with up to 31% post-operative minor incontinence and also more than 12% major incontinence [3]. The procedure fails in one of three patients [6], who are about 2-5 times more than fistulotomy – fistulectomy with or without Seton [7]. Seton placement alone has been substantially more effective in complex type with least incontinence [8]. Furthermore, sphincter saving procedures like plug placement, ligation of inter-sphincteric fistula tract (LIFT), Bio LIFT and stem cell injections are associated with technical disadvantages and were not trialed in details to be used with confidence as the standard methods [3,9,10]; although, advocated reports are available [11-13]. Application of alternative non-surgical interventional treatments has been also well introduced. Fibrin Glue injection postulated that possess safe and feasible usage in infants and children [14]; however, in adults have been shown that has led to unsatisfactory outcomes compared to staged mucosal flap surgery in complex and IBD base fistulas [15,16]. Moreover, the glue is accepted to be mostly promising in comparison to conventional surgery especially in simple fistulas [16,17] and even in using alone without accompanied procedures [18]. Its presented overall success was 83.3% [19] and 67.6% in high fistulas [20]. Yet, antibiotics are not clinically postulated to be directly curative alone in fistula but their effects were advocated for use, especially about Metronidazol and Silver phosphate [6,21]. As the etiology, bacterial colonization and active internal recto-perianal skin communication besides tract epithelialization are three well-known important causes for preventing the healing and closure of the fistula that were considered as the targets of our study. We were believed that if bacterial colonization and tract epithelialization were eliminated successively, internal mucosal orifice could rapidly be repaired and internal communication was cut. Therefore, the ground for granulation formation might be facilitated to progress and thus, the tract was obliterated and fibrosed. Based on our results, similarly, both STDS + Metronidazol group and Ceftazidine + Metronidazol were shown to be more effective in treatment of fistulas (70 & 71.4% success rate respectively) with less recurrence compared to STDS + Ceftazidine group. This can insist on the substantial role and direct effect of colonization control of Metronidazol as the premier compared to Ceftazidine and STDS. Since STDS was used to support antibiotics, here its effective role has not been completely become cleared. According to recurrence, the sum of relapses (5 recurrences of 6 anterior types) was strongly co-related to anterior type fistulas (P = 0.023) (table3). Presumably, as anterior type fistulas had lower range of tract length (29-40 mm) in the study, straight and short pathway covered by full epithelialization could perhaps cause therapeutic resistance. Overall, incontinence avoidance and mean treatment success rate of 64% in the results seem to be promising and acceptable consequence for the trial. Therefore, it can be suggested that combined selected antibiotics will be optimistically effective in the first step of treating fistula-in-ano among selective situations. However, since the patients expecting and persuading the surgeon for quick and full immediate recovery, they have to be explained for long lasting timeframe of multiple tract injections that need their patience. To avoid least complications, safe suggestion would be patient selection; step treatment and close follow up. Step treatment defines as non-surgical drug injections (selective antibiotics or alternatively fibrin glue), Seton placement (cutting [22] or simple), fistulotomy or fistulectomy “better with using manometry” respectively. For preventing recurrence or incontinence in complex fistulas: fistulotomy and simultaneously sphincter repair [23,24], LIFT, advancement flaps and plugs, based on surgeon’s experiences are suggested. In addition, we believe that our proposal and method may be a viable novel of primary approach in treatment of such simple and more probably multi-tract and recurrent complex fistulas. However this would require further studies to investigate in more population.

Acknowledgment

We would like to thanks Ms. M. Seyedtabib for her invaluable expertise in statistics and kindly support during this project.

References

1. Ramesh PB. Anal fistula with foot extension-treated by Kshara sutra (medicated seton) therapy: Arare case report. Int J Surg Case Rep. 2013 Apr 17;4(7):573-576. Doi: 10.1016/j.ijscr.2013.04.004.
2. Tobisch A, Stelzner S, Hellmich G, Jackisch T, Witzigmann H. Total fistulectomy with simple closure of the internal opening in the management of complex cryptoglandular fistulas: long term results and functional outcome. Dis Colon Rectum. 2012 Jul;55(7):750-5. Doi: 10.1097/DCR.0b013e3182569b29.
3. Kee Ho Song. New techniques for Treating an Anal fistula. J Korean Soc Coloproctol. 2012 February;28(1):7-12. Doi: 10.3393/jksc.2012.28.1.7 PMCID: PMC3296947
4. Toyonaga T, Matsushima M, Kiriu T, Sogawa N, Kanyama H, Matsumura N, Shimojima Y, Hatakeyama T, Tanaka Y, Suzuki K, Tanaka m. Factors affecting continence after fistulotomy for intersphincteric fistula-in-ano. Int J Colorectal Dis. 2007; 22(9):1071-5(ISSN:0179-1958).
5. Pasta V, Redler A, Amabile MI, Merola R, Monti M. Personal technique for treatment of perianal fistulas in outpatients. Ann Ital Chir. 2012 May-Jun;83(3):269-72.
6. van Onkelen RS, Mitalas LE, Gosselink MP, van Belkum A, Laman JD,Schouten WR. Assessment of microbiota and peptidoglycanin perianal fistula. Diagn Microbiol Dis.2013 Jan;75(1):50-4. Doi: 10.1016/j.diagmicrobio.2012.09.012.
7. Rosa G, Lolli P, Piccinelli D, Mazzola F, Bonomo S. Fistula in ano: anatomoclinical aspects, surgical therapy and results in 844 patients. Tech Coloproctol. 2006;10(3):215-21. (ISSN: 11234-6337)
8. Sileri P, Cadeddu F, D’Ugo S, Franceschilli L, Del Vecchio Blanco G, De Luca E, Calabrese E, Capperucci SM. Fiaschetti V, Milito G, Gaspari AL. Surgery for fistula-in-ano in a specialist colorectal unit: a critical appraisal. BMC Gastroentrol. 2011;11:120 (ISSN:1471-230X).
9. de la Portilla F, Rada R, Jimenez-Rodriguez R, Diaz-Pavon JM, Sanchez-Gil JM. Evaluation of a new synthetic plug in the treatment of anal fistula: results of a pilot study. Dis Colon Rectum. 2011 Nov;54(11):1419-22. Doi: 10.1097/DCR.0b013e31822c4d59.
10. Gupta PJ, Gupta SN, Heda PS. Which treatment for anal fistula? Cut or cover, Plug or paste, loop or lift. Acta Chir Iugosl. 2012;59(2):15-20.
11. Sirikurnpiboon S, Awapittaya B, Jivaoaisarnpong P. Ligation of intersphincteric fistula tract and its modification:Results from treatment of complex fistula. World J Gastrointest Surg. 2013 Apr 27;5(4):123-8. Doi: 10.4240/wjgs.v5.i4.123.
12. Han JG, Yi BQ, Wang ZJ, Zheng Y, Cui JJ, Yu XQ, Zhao BC, Yang XO. Ligation of the intersphincteric fistula tract plus a bioprosthetic anal fistula plug (LIFT-Plug): anew technique for fistula-in-ano. Colorectal Dis. 2013 May;15(5):582-6. Doi: 10.1111/codi.12062.
13. Mushaya C, Batlett L, Schulze B, Ho YH. Ligation of intersphincteric fistula tract compared with advancement flap for complex anorectal fistula requiring initial seton drainage. Am J Surg. 2012 Sep;204(3):283-9. Doi: 10.1016/j.amjsurg.2011.10.025
14. Osman MA, Elsharkawy MA, Othman MH. Repair of fistula in-ano in children using image guided Histoacryl injection after failure of conservative treatment. J Pediatr Surg. 2013 Mar;48(3):614-8. Doi: 10.1016/j.jpedsurg.2012.11.029.
15. van der Hagen SJ, Baeten CG, Soeters PB, van Gemert WG. Staged mucosal advancement Flap versus Staged Fibrin Sealant in the treatment of complex perianal fistula. Gastroenterol Res Pract. 2011;2011:186350. Doi: 10.1155/2011/186350.
16. Yeung JM, Simpson JA, Tang SW, Armitage NC, Maxwell-Armstrong C. Fibrin glue for the treatment of fistulae in ano—a method worth sticking to? Colorectal Dis. 2010;12(4):363-6 (ISSN1463-1318).
17. Cirocchi R, Santoro A, Trastulli S, Farinella E, Di Rocco G, Vendettuali D, Giannotti D, Redler A, Coccetta M, Gulla N, Boselli C, Avenia N, Sciannameo F, Basoli A. Meta-analysis of fibrin glue versus surgery for treatment of fistula-in-ano.
18. Singer M, Cintron J, Nelson R, Orsay C, Bastawrous A, Pearl R, Sone J, Abcarian H. Treatment of fistula-in-ano with fibrin sealant in combination with intra-adhesive antibiotics and/or surgical closure of the internal fistula opening. Dis Colon Rectum. 2005;48(4):799-808 (ISSN: 0012-3706).
19. Maralcan G, Baskon I, Aybasti N, Gokalp A. The use of fibrin glue in the treatment of fistula-in-ano: a prospective study.Surg Today. 2006;36(2):166-70 (ISSN:0941-1291).
20. Queralto M, Portier G, Bonnaud G, Chotard JP, Cabarrot P, Lazorthez F. Efficacy of synthetic glue treatment of high cryptoglandular fistula-in-ano. Gastroenterol Clin Biol. 2010;34(8-9):477-82 (ISSN:2210-7401).
21. Blaker JJ, Pratten J, Ready D, Knowles JC, Forbes A, Day RM. Assessment of antimicrobial microspheres as a prospective novel treatment targeted towards the repair of perianal fistulas. Aliment Pharmacol Ther. 2008;28(5):614-22.(ISSN:1365-2036).
22. Kamrava A, Collins JC. A decade of selective use of adjustable cutting seton combined with fistulotomy for anal fistula. Am Surg. 2011 Oct;77(10):1377-80.
23. Arroyo A, Perez-Legaz J, Moya P, Armananzas L, Lacueva J, Perez-Vicente F, Candela F. Fistulotomy and sphincter reconstruction in the treatment of complex fistula-in-ano: long-term clinical and manometric results. Ann Surg. 2012 May;255(5):935-9. Doi: 10.1097/SLA.0b013e31824e9112.
24. Ratto C, Litta F, Parello A, Zaccone G, Donisi L, De Simone V. Fistulotomy with end- to-end primary sphincteroplasty for anal fistula: results from prospective study. Dis Colon Rectum. 2013 Feb;56(2):226-33. Doi: 10.1097/DCR.0b013e31827aab72.