Efficacy and safety of autologous adipose-derived stromal vascular fraction enriched with platelet-rich plasma in flap repair of transsphincteric cryptoglandular fistulas.

BACKGROUND: Transanal advancement flap repair of transsphincteric fistulas is a sphincter-preserving procedure, which frequently fails, probably due to ongoing inflammation in the remaining fistula tract. Adipose-derived stromal vascular fraction (SVF) has immunomodulatory properties promoting wound healing and suppressing inflammation. Platelet-rich plasma (PRP) reinforces this biological effect. The aim of this study was to evaluate the efficacy and safety of autologous adipose-derived SVF enriched with PRP in flap repair of transsphincteric cryptoglandular fistulas. METHODS: A prospective cohort study was conducted including consecutive patients with transsphincteric cryptoglandular fistula in a tertiary referral center. During flap repair, SVF was obtained by lipoharvesting and mechanical fractionation of adipose tissue and combined with PRP was injected around the internal opening and into the fistulous wall. Endpoints were fistula healing at clinical examination and fistula closure on postoperative magnetic resonance imaging (MRI). Adverse events were documented. RESULTS: Forty-five patients with transsphincteric cryptoglandular fistula were included (29 males, median age 44 years [range 36-53 years]). In the total study population, primary fistula healing was observed in 38 patients (84%). Among the 42 patients with intestinal continuity at time of surgery, primary fistula healing was observed in 35 patients (84%). In one patient, the fistula recurred, resulting in a long-term healing rate of 82%. MRI, performed in 37 patients, revealed complete closure of the fistula tract in 33 (89.2%). In the other patients, the tract was almost completely obliterated by scar tissue. During follow-up, none of these patients showed clinical signs of recurrence. The postoperative course was uneventful, except for three cases; venous thromboembolism in one patient and bleeding under the flap, necessitating intervention in two patients. CONCLUSIONS: Addition of autologous SVF enriched with PRP during flap repair is feasible, safe and might improve outcomes in patients with a transsphincteric cryptoglandular fistula. TRIAL REGISTRATION: Dutch Trial Register, Trial Number: NL8416, https://www.trialregister.nl/.

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.

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.

[Intersphincteric ligation of perianal fistula]. / Intersfincterische ligatie van perianale fistels.

Fistulotomy is inappropriate for patients with a high transsphincteric fistula, passing through the upper or middle third of the external anal sphincter, because this procedure requires division of a large part of the anal sphincter, with subsequent risk of fecal incontinence. Therefore, sphincter preserving procedures have been developed for the treatment of high transsphincteric fistulas, such as flap repair. In most hospitals, fistulotomy is still the treatment of choice for low transsphincteric fistula, passing through the lower third of the external anal sphincter. Although this procedure is considered simple and effective with a minimal risk of incontinence, data suggest that the risk of diminished fecal continence is not insignificant. Ligation of the intersphincteric fistula tract (LIFT) is a new sphincter preserving technique. This technique may be a sphincter preserving alternative for fistulotomy in low transsphincteric fistulas and for flap repair in high transsphincteric fistulas.

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.

Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients.

BACKGROUND: The optimal treatment of desmoid tumours is controversial. We evaluated desmoid management in Dutch familial adenomatous polyposis (FAP) patients. METHODS: Seventy-eight FAP patients with desmoids were identified from the Dutch Polyposis Registry. Data on desmoid morphology, management, and outcome were analysed retrospectively. Progression-free survival (PFS) rates and final outcome were compared for surgical vs non-surgical treatment, for intra-abdominal and extra-abdominal desmoids separately. Also, pharmacological treatment was evaluated for all desmoids. RESULTS: Median follow-up was 8 years. For intra-abdominal desmoids (n=62), PFS rates at 10 years of follow-up were comparable after surgical and non-surgical treatment (33% and 49%, respectively, P=0.163). None of these desmoids could be removed entirely. Eventually, one fifth died from desmoid disease. Most extra-abdominal and abdominal wall desmoids were treated surgically with a PFS rate of 63% and no deaths from desmoid disease. Comparison between NSAID and anti-estrogen treatment showed comparable outcomes. Four of the 10 patients who received chemotherapy had stabilisation of tumour growth, all after doxorubicin combination therapy. CONCLUSION: For intra-abdominal desmoids, a conservative approach and surgery showed comparable outcomes. For extra-abdominal and abdominal wall desmoids, surgery seemed appropriate. Different pharmacological therapies showed comparable outcomes. If chemotherapy was given for progressively growing intra-abdominal desmoids, most favourable outcomes occurred after combinations including doxorubicin.

Assessment of posterior compartment prolapse: a comparison of evacuation proctography and 3D transperineal ultrasound.

INTRODUCTION: Evacuation proctography (EP) is considered to be the gold standard investigation for the diagnosis of posterior compartment prolapse. 3D transperineal ultrasound (3DTPUS) imaging of the pelvic floor is a noninvasive investigation for detection of pelvic floor abnormalities. This study compared EP with 3DTPUS in diagnosing posterior compartment prolapse. METHOD: In a prospective observational study, patients with symptoms related to posterior compartment prolapse participated in a standardized interview, clinical examination, 3DTPUS and EP. Both examinations were analysed separately by two experienced investigators, blinded against the clinical data and against the results of the other imaging technique. After the examinations, all patients were asked to fill out a standardized questionnaire concerning their subjective experience. RESULTS: Between 2005 and 2007, 75 patients were included with a median age of 59 years (range 22-83). The Cohen's Kappa Index for enterocole was 0.65 (good) and for rectocele it was 0.55 (moderate). The level of correlation for intussusception was fair (kappa = 0.21). CONCLUSION: This study showed moderate to good agreement between 3DTPUS and EP for detecting enterocele and rectocele.

Rectal sleeve advancement for the treatment of persistent rectovaginal fistulas.

BACKGROUND: Different surgical procedures are available for rectovaginal fistula repair. Most of these procedures fail in a substantial number of women, especially in those with a persistent fistula after prior attempts at repair. In addition, these procedures have a potential risk of dyspareunia and impairment of continence. The question is whether rectal sleeve advancement could be a valuable option for women with such a persistent rectovaginal fistula. The present study was aimed to examine the feasibility of this new procedure. PATIENTS AND METHODS: Eight consecutive women (median age 41 years; range 28-53) with a persistent, low rectovaginal fistula underwent rectal sleeve advancement, six patients by a posterior "Kraske" approach and two patients by an abdominal approach. The aetiologies were obstetric trauma (n = 4), prior anal surgery (n = 2) and cryptoglandular fistulous disease (n = 2). RESULTS: Five patients had an uneventful postoperative course. Three patients encountered recurrent symptoms shortly after the procedure. In these three patients an additional transanal approach was performed to close the anal opening of the fistulous tract. This additional approach was successful in one patient. The median duration of follow-up was 12 months (range 3-17). The overall healing rate was 75%. None of the patients encountered de novo dyspareunia. One patient encountered involuntary loss of stool during the night postoperatively. CONCLUSION: Based on these early results, rectal sleeve advancement, either by a posterior "Kraske" approach, or by an abdominal approach, seems to be a valuable alternative for the treatment of persistent rectovaginal fistulas.

Required length of follow-up after transanal advancement flap repair of high transsphincteric fistulas.

OBJECTIVE: Repair of high perianal fistulas presents a major surgical challenge. Transanal advancement flap repair (TAFR) provides a useful tool in the treatment of these fistulas. Initially promising results have been reported. More recent studies indicate that TAFR fails in one out of three patients. The aim of the present study was to determine the appropriate length of follow-up needed to assess the healing rate after TAFR of high transsphincteric fistulas. METHOD: Between 1992 and 2000 a consecutive series of 80 patients with a high transsphincteric fistula of cryptoglandular origin underwent TAFR. Medical records of all patients were studied. The initial healing rate and the median healing time were assessed. The initial outcome was successful in 54 patients. The medical records revealed that only one of these patients presented with a recurrent fistula after 28 months. The other 53 patients were sent a questionnaire in 2006 aimed to determine whether they had any complaints or signs of a recurrent fistula. RESULTS: The initial healing rate was 68%. The median healing time was 3.6 months. The completed questionnaire was returned by 48 patients. None of these patients reported any complaints or signs of a recurrent fistula. Median duration of follow-up in these patients was 92 months. CONCLUSION: At a median time interval of 3.6 months fistula healing was observed in 54 patients (68%). Only one patient (2%) encountered a recurrence. The length of follow-up can be restricted to the healing time.

Obliteration of the fistulous tract with BioGlue adversely affects the outcome of transanal advancement flap repair.

BACKGROUND: Transanal advancement flap repair (TAFR) is useful in the treatment of high transsphincteric fistulas. Initially, promising results were reported. More recent studies have indicated that TAFR fails in one out of three patients. In almost all of our patients with a failure, we have observed healing of the flap except at the site of the original internal opening. A possible explanation for this remarkable finding might be persistent inflammation in the fistulous tract, finding a way out through the original internal opening. The question is whether obliteration of the fistulous tract by local installation at a surgical adhesive, can prevent persistent inflammation to break through the original opening. The aim of this pilot study was to investigate whether concomitant instillation of BioGlue could improve the healing rate following TAFR for high transsphincteric fistulas. METHODS: Between March 2006 and April 2006 a consecutive series of eight patients (four men, four women; median age 46 years) with a high transsphincteric fistula underwent TAFR after instillation of BioGlue in the fistulous tract. All patients were seen in the outpatient department for postoperative evaluation. RESULTS: Fistula healing was observed in only one patient (12.5%). All other patients experienced one or more of the following complications: prolonged severe pain (n=5), discharge of great amounts of purulent liquid from the external opening (n=3) and abscess formation (n=2), necessitating incision and drainage. Because of this unexpected outcome we decided to terminate the study prematurely. CONCLUSIONS: Our findings indicate that obliteration of the fistulous tract with BioGlue adversely affects the outcome of TAFR for high transsphincteric fistulas.

Rectocele repair by anterolateral rectopexy: long-term functional outcome.

INTRODUCTION: Rectoceles are frequently associated with feelings of pelvic discomfort and symptoms of obstructed defaecation (OD). Repair by a transvaginal or transanal approach might result in de novo dyspareunia in up to approximately 40% of the cases. This study was designed to investigate whether anterolateral rectopexy provides an adequate rectocele repair without dyspareunia as a side effect. METHOD: A consecutive series of 33 women (median age 55 years; range: 37-73) with a symptomatic rectocele (depth > 3 cm) underwent anterolateral rectopexy. Before the operation, all patients underwent evacuation proctography (EP), which was repeated 6 months after the repair in all but three patients. A standardized questionnaire concerning pelvic discomfort, OD and dyspareunia was used to assess the long-term effect of rectocele repair. The response rate was 91%. RESULTS: Six months after the procedure, EP revealed a recurrent or persistent rectocele in six patients (20%). However, in four of these six patients, the depth of the rectocele was < 3 cm. The median duration of follow-up was 74 months (range: 2-96). Among the patients with an adequate repair, signs of OD persisted in 55%. None of the patients encountered de novo dyspareunia after the procedure. CONCLUSION: Anterolateral rectopexy provides an effective tool for anatomical correction of rectoceles and does not result in dyspareunia as a side effect. However, despite adequate repair, OD persist in the majority of patients.

Impact of transanal endoscopic microsurgery on functional outcome and quality of life.

INTRODUCTION: Transanal endoscopic microsurgery (TEM) is a minimal invasive technique for local excision of rectal tumours. The procedure is performed via a rectoscope with a diametre of 4 cm. The aim of this prospective study was to assess both functional outcome and quality of life after TEM. PATIENTS AND METHODS: Between 2004 and 2006, 47 patients were studied prior to and at least 6 months after TEM. Demographics, operative details and post-operative complications were recorded. Functional outcome was determined using the Faecal Incontinence Severity Index (FISI). Quality of life was measured using the EuroQol EQ-5D questionnaire and the Faecal Incontinence Quality of Life (FIQL) score. RESULTS: Six months after surgery, median FISI score was found to be decreased (p<0.01), depicting an improvement in faecal continence. This improvement was most significant in tumours within 7 cm from the dentate line (p=0.01). From the patients' perspective, post-operative quality of life was found to be higher (p<0.02). A significant improvement was observed in two of the four FIQLS domains (embarrassment, p=0.03; lifestyle, p=0.05). The domains of lifestyle, coping and behaviour and embarrassment were correlated with the FISI (all p<0.05). CONCLUSION: This study indicates TEM has no deteriorating effect on faecal continence. Moreover, once the tumour has been excised using TEM, quality of life is improved.