Pro-inflammatory cytokines in cryptoglandular anal fistulas.

BACKGROUND: Sphincter-preserving procedures for the treatment of transsphincteric fistulas fail in at least one out of every three patients. It has been suggested that failure is due to ongoing disease in the remaining fistula tract. Cytokines play an important role in inflammation. At present, biologicals targeting cytokines are available. Therefore, detection and identification of cytokines in anal fistulas might have implications for future treatment modalities. The objective of the present study was to assess local production of a selected panel of cytokines in anal fistulas, including pro-inflammatory interleukin (IL)-1ß and tumor necrosis factor α (TNF-α). METHODS: Fistula tract tissue was obtained from 27 patients with a transsphincteric fistula of cryptoglandular origin who underwent flap repair, ligation of the intersphincteric fistula tract or a combination of both procedures. Patients with a rectovaginal fistula or a fistula due to Crohn's disease were excluded. Frozen tissue samples were sectioned and stained using advanced immuno-enzyme staining methods for detection of selected cytokines, IL-1ß, IL-8, IL-10, IL-12p40, IL-17A, IL-18, IL-36 and TNF-α. The presence and frequencies of cytokine-producing cells in samples were quantitated. RESULTS: The key finding was abundant expression of IL-1ß in 93 % of the anal fistulas. Frequencies of IL-1ß-producing cells were highest (>50 positive stained cells) in 7 % of the anal fistulas. Also, cytokines IL-8, IL-12p40 and TNF-α were present in respectively 70, 33 and 30 % of the anal fistulas. CONCLUSIONS: IL-1ß is expressed in the large majority of cryptoglandular anal fistulas, as well as several other pro-inflammatory cytokines.

A multicenter experience with peri-rectal tumors: The risk of local recurrence.

BACKGROUND: Peri-rectal tumors are rare and their management is challenging, especially when presenting with local recurrence. The aim of the current study was to report a multicenter series of peri-rectal tumors, focusing on the risk of recurrence. MATERIAL AND METHODS: From 1994 to 2014, patients with peri-rectal tumors from three different centers were retrospectively analyzed. Sixty-two patients were identified and divided into two groups; Group 1: patients who presented with local recurrence at follow-up (n = 9, recurrence rate: 14.5%), and Group 2: patients without recurrence (n = 53). RESULTS: In Group 1, there were initially more patients with symptoms of a perineal mass (44.4% vs. 12.2%; p = 0.04), more malignant tumors (55.6% vs. 15.1%; p = 0.02), and larger lesions (+2.6 cm; p = 0.004). Incomplete resection was also more frequent in Group 1 (44.4% vs. 3.8%; p = 0.003). Eight patients with recurrence had further surgery, whilst one patient had radiological recurrence and was treated medically. Among the eight re-resections, five patients remain disease-free; two have had further recurrences and have had palliative treatment, whilst another has had a further resection and remains disease-free. CONCLUSIONS: Peri-rectal tumors are uncommon and there is no consensus on best management. Based on this large multicenter series, several risk factors seem to be associated with local recurrence, namely patient- (discovery of a perineal mass), tumor- (malignant and large lesion), and surgery-related (incomplete resection). Clinical follow-up should be adapted according to these factors.

Laparoscopic ventral rectopexy for faecal incontinence: equivalent benefit is seen in internal and external rectal prolapse.

AIM: An external rectal prolapse (ERP) is often associated with faecal incontinence, and surgery is the recommended therapy. It has been suggested that correction of a high grade internal rectal prolapse (HIRP) is also worthwhile for patients with faecal incontinence. The aim of the present study is to compare the results of laparoscopic ventral rectopexy (LVR) in patients with faecal incontinence associated with either an ERP or a HIRP. METHOD: Consecutive patients suffering from faecal incontinence, who underwent a LVR between June 2010 and October 2012, were identified from a prospective database. All patients underwent preoperative defaecating proctography, anorectal manometry and ultrasound. Symptoms were assessed preoperatively and at 1 year after operation using a standardized questionnaire incorporating the Faecal Incontinence Severity Index (FISI; range 0-61) and the Gastrointestinal Quality of Life Index (GIQLI). RESULTS: LVR was performed in 50 incontinent patients with a HIRP, and in 41 patients with an ERP. Preoperatively, the FISI was higher in patients with HIRP (HIRP 42 versus ERP 30, P < 0.01). The recurrence rate at 1 year was similar in both groups (HIRP 6 % versus ERP 2 %, P = 0.156). The FISI scores were significantly reduced in both groups (HIRP 48 % versus ERP 50 %, both P < 0.01). GIQLI was equally improved in both groups (HIRP 17 % versus ERP 18 %, both P < 0.01). CONCLUSION: Laparoscopic ventral rectopexy for the treatment of faecal incontinence achieves equivalent outcomes in both patients with an external rectal prolapse or high grade internal rectal prolapse.

Different characteristics of high and low transsphincteric fistulae.

AIM: Transsphincteric fistulae are classified as high or low. The aim of this observational study was to determine whether or not they have different characteristics. METHOD: A consecutive series of 300 patients with a transsphincteric fistula of cryptoglandular origin was studied. Two hundred patients with a high transsphincteric fistula underwent transanal advancement flap repair and 100 patients with a low transsphincteric fistula underwent fistulotomy or ligation of the intersphincteric fistula tract at the Division of Colon and Rectal Surgery, Erasmus MC, Rotterdam. Various patient and fistula characteristics were assessed. Data were analysed by means of logistic regression. RESULTS: Low transsphincteric fistulae occurred more frequently in females (43% low transsphincteric fistulae vs 30% high transsphincteric fistulae; P < 0.05). The internal opening of these fistulae was predominantly located anteriorly (76% vs 18% in high transsphincteric fistulae; P < 0.001). Mean age at surgery was lower in patients with a low transsphincteric fistula (42 vs 47 years; P < 0.001). In these patients an associated abscess was observed in 4% compared with 54% of those patients with a high transsphincteric fistula (P < 0.001). In multivariate analysis, the differences between high and low transsphincteric fistulae regarding location of their internal opening and the presence of associated abscesses remained significant (P < 0.001). CONCLUSION: Although not significant in multivariate analysis, low transsphincteric fistulae occur more frequently in younger patients and more often in females. These fistulae are predominantly located anteriorly and are rarely associated with an abscess. This was significant in univariate and multivariate analysis.

Ligation of the intersphincteric fistula tract in low transsphincteric fistulae: a new technique to avoid fistulotomy.

AIM: To date fistulotomy is still the treatment of choice for patients with a transsphincteric fistula passing through the lower third of the external anal sphincter, because it is a simple, effective and safe procedure with a minimal risk of incontinence. However, data suggest that the risk of impaired continence following division of the lower third of the external anal sphincter is not insignificant, especially in female patients with an anterior fistula and patients with diminished anal sphincter function. It has been shown that ligation of the intersphincteric fistula tract (LIFT) is a promising sphincter-preserving technique. Therefore, we questioned whether LIFT could replace fistulotomy in patients with a low transsphincteric fistula. METHOD: A consecutive series of 22 patients with a low transsphincteric fistula of cryptoglandular origin underwent LIFT. Continence scores were determined using the Rockwood Fecal Incontinence Severity Index. RESULTS: Median follow-up was 19.5months. Primary healing was observed in 18 (82%) patients. In the four patients without primary healing, the transsphincteric fistula was converted into an intersphincteric fistula. These patients underwent subsequent fistulotomy with preservation of the external anal sphincter. The overall healing rate was 100%. Six months after surgery, the median incontinence score was not changed significantly. CONCLUSION: Low transsphincteric fistulae can be treated successfully by LIFT, without affecting faecal continence. Division of the lower part of the external anal sphincter is no longer necessary in the treatment of low transsphincteric fistulae, which is essential for patients with compromised anal sphincters.

Assessment of microbiota and peptidoglycan in perianal fistulas.

Transanal advancement flap repair has been advocated as the treatment of choice for high transsphincteric perianal fistulas, but fails in 1 of every 3 patients. Persistence of the fistula after flap repair might be the result of ongoing disease in the remaining fistula tract. In 10 specimens of the distal part of the fistula, microbiota was assessed by means of conventional microbiological culture and 16S rRNA gene sequencing. Proinflammatory bacterial peptidoglycan and recognition proteins were assessed by immunohistochemistry. Bacterial species were bowel derived, skin derived, or a combination of both. No mycobacterium species were identified. 16S rRNA gene sequencing failed to identify bacteria in all but 1 specimen, most likely as a result of low numbers of organisms. Peptidoglycan was detected in 90% of the patients, and a host response to peptidoglycan in 60%. Therefore, we suggest that peptidoglycan might play a role in the ongoing inflammation in perianal fistulas.

Identification of epithelialization in high transsphincteric fistulas.

BACKGROUND: At present, transanal advancement flap repair (TAFR) is the treatment of choice for transsphincteric fistulas passing through the upper and middle third of the external anal sphincter. It has been suggested that epithelialization of the fistula tract contributes to the failure of the treatment. The aim of this study was to assess the prevalence of epithelialization of the fistula tract and to study its effect on the outcome of TAFR and TAFR combined with ligation of the intersphincteric fistula tract (LIFT). METHODS: Forty-four patients with a high transsphincteric fistula of cryptoglandular origin underwent TAFR. Nine of these patients underwent a combined procedure of TAFR with LIFT. In all patients the fistula tract was excised from the external opening up to the outer border of the external anal sphincter. In patients undergoing TAFR combined with LIFT an additional central part of the intersphincteric fistula tract was excised. A total of 53 specimens were submitted. Histopathological examination of the specimens was carried out by a pathologist, blinded for clinical data. RESULTS: Epithelialization of the distal and intersphincteric fistula tract was observed in only 25 and 22% of fistulas, respectively. There was no difference in outcome between fistulas with or without epithelialization. CONCLUSIONS: Epithelialization of high transsphincteric fistulas is rare and does not affect the outcome of TAFR and TAFR combined with LIFT.

Is it possible to improve the outcome of transanal advancement flap repair for high transsphincteric fistulas by additional ligation of the intersphincteric fistula tract?

BACKGROUND: Transanal advancement flap repair is successful in 2 of every 3 patients with a cryptoglandular fistula passing through the middle or upper third of the external anal sphincter. It has been suggested that ongoing disease in the remaining fistula tract contributes to failure. Ligation of the intersphincteric fistula tract might be a useful tool to eradicate this ongoing disease. OBJECTIVE: The aim of the present study was to evaluate the effect of an additional ligation of the fistula tract on the outcome of transanal advancement flap repair. DESIGN: This investigation was designed as a prospective clinical study. SETTINGS: The study took place in a university hospital. PATIENTS: A consecutive series of 41 patients with a high transsphincteric fistula of cryptoglandular origin were included. INTERVENTION: Ligation of the intersphincteric fistula tract was performed in addition to flap repair. MAIN OUTCOME MEASURES: Early and late complications were recorded. Continence scores were determined with the use of the Fecal Incontinence Severity Index. RESULTS: Median duration of follow-up was 15 months. Primary healing was observed in 21 patients (51%). Of the 20 patients with a failure, the original transsphincteric fistula persisted in 12 patients. In 8 patients, the transsphincteric fistula was converted into an intersphincteric fistula. These patients underwent subsequent fistulectomy, which was successful in all of them. The overall healing rate was 71%. LIMITATIONS: This was a preliminary observational study with no control group. CONCLUSIONS: : The ligation of the intersphincteric fistula tract procedure is prone to infection and does not enhance the outcome of flap repair.