Description of a new ultrasound sign to distinguish Crohn's anal fistula from cryptoglandular fistula: The rosary sign.

AIM: Endoanal and endorectal ultrasound are essential diagnostic tools for perianal fistula. Recent studies have examined ultrasound signs that help differentiate cryptoglandular anal fistula from perianal fistulizing Crohn's disease. The main aim of this work was to describe a new ultrasound sign for perianal fistula and to evaluate its ability to differentiate Crohn's disease from cryptoglandular anal fistula. METHOD: This study included 363 patients (113 women; mean age 46.5 ± 14.3 years). Overall, 287 (79.1%) patients had a cryptoglandular perianal fistula and 76 (20.9%) had fistulizing Crohn's disease. All patients underwent three-dimensional anal endosonography for perianal fistula. The reading was carried out by two observers. RESULTS: Observer 1, who was an experienced sonographer and colorectal surgeon, observed the ultrasound sign in 120 patients (33.1%), while observer 2, who was inexperienced, observed it in 129 patients (35.5%). The overall interobserver agreement was 67.22%. The Kappa coefficient measuring interobserver agreement was 0.273 (0.17-0.38). Among those patients with Crohn's disease, 48.68% had the sign and 16% did not (p = 0.001). A logistic regression study showed that the sign was a predictor of Crohn's disease (p = 0.001), with an odds ratio of 2.33 (1.39-3.91). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 38.68%, 71.08%, 30.83%, 83.95% and 66.39%, respectively. CONCLUSION: This study provides a new ultrasound sign for perianal fistula (the rosary sign) in patients with Crohn's disease. The sign can be used to differentiate Crohn's disease from other types of fistula. This is useful in the management of patients with anal fistula.

Surgical management of complex perianal fistula revisited in a systematic review: a critical view of available scientific evidence.

BACKGROUND: Treating complex perianal fistulas in Crohn's disease patients remains a challenge. Classical surgical treatments for Crohn's disease fistulas have been extrapolated from cryptoglandular fistulas treatment, which have different etiology, and this might interfere with its effectiveness, in addition, they increase fecal incontinence risk. Recently, new surgical techniques with support from biological approaches, like stem cells, have been developed to preserve the function of the sphincter. We have performed a systematic literature review to compare the results of these different techniques in the treatment of Crohn's or Cryptoglandular fistula. METHODS: PubMed, EMBASE, Database of Abstracts of Reviews of Effectiveness, Cochrane Central Register of Controlled Trials were searched systematically for relevant articles. We included randomized controlled trials and observational studies that referred to humans, were written in English, included adults 18+ years old, and were published during the 10-year period from 2/01/2010 to 2/29/2020. Evidence level was assigned as designated by the Scottish Intercollegiate Guidelines Network. RESULTS: Of the 577 citations screened, a total of 79 were ultimately included in our review. In Crohn's disease patients, classical techniques such as primarily seton, Ligation of Intersphincteric Fistula Tracks, or lay open, healing rates were approximately 50-60%, while in cryptoglandular fistula were around, 70-80% for setons or flaps. In Crohn's disease patients, new surgical techniques using derivatives of adipose tissue reported healing rates exceeding 70%, stem cells-treated patients achieved higher combined remission versus controls (56.3% vs 38.6%, p = 0.010), mesenchymal cells reported a healing rate of 80% at week 12. In patients with cryptoglandular fistulas, a healing rate of 70% using derivatives of adipose tissue or platelets was achieved, and a healing rate of 80% was achieved using laser technology. Fecal incontinence was improved after the use of autologous platelet growth factors and Nitinol Clips. CONCLUSION: New surgical techniques showed better healing rates in Crohn's disease patients than classical techniques, which have better results in cryptoglandular fistula than in Crohn's disease. Healing rates for complex cryptoglandular fistulas were similar between the classic and new techniques, being the new techniques less invasive; the incontinence rate improved with the current techniques.

Treatment of transsphincteric fistula-in-ano with growth factors from autologous platelets: results of a phase II clinical trial.

PURPOSE: The aim of this paper is to evaluate to the safety, feasibility and efficacy of a novel treatment for transsphincteric cryptoglandular fistula: injection of autologous plasma rich in growth factors (PRGF) into the fistula tract accompanied by sealing using a fibrin plug created from the activated platelet-poor fraction of the same plasma. METHOD: This article is a prospective, phase II clinical trial. The procedure was externally audited. Thirty-six patients diagnosed with transsphincteric fistula-in-ano were included. All patients underwent follow-up examinations at 1 week and again at 3, 6 and 12 months after discharge. Main outcome measures safety (number of adverse events), feasibility and effectiveness of the treatment. RESULTS: A total of 36 patients received the study treatment, with the procedure found to be feasible in all patients. A total of seven adverse events (AE) related to the injected product or surgical procedure were identified in 4 of 36 patients. At the end of the follow-up period (12 months), 33.3% of patients (12/36) had achieved complete fistula healing and 11.1% of patients (4/36) had achieved partial healing. In total, this amounted to 44.4% of patients (16/36) being asymptomatic at final follow-up. In successfully healed patients, a gradual reduction in pain was observed, as measured using a Visual Analog Scale (VAS) (p = 0.0278). Compared to baseline, a significant improvement in Wexner score was seen in patients achieving total or partial healing of the fistula (p = 0.0195). CONCLUSIONS: The study treatment was safe and feasible, with apparently modest efficacy rates. Continence and pain improvement following treatment may be considered predictive factors for healing.

Ultrasonographic evidence of Gatekeeper™ prosthesis migration in patients treated for faecal incontinence: a case series.

BACKGROUND: Faecal incontinence (FI) is both a medical and social problem, with an underestimated incidence. For patients with internal anal sphincter damage, implantation of biomaterial in the anal canal is a recognised treatment option. One such material, Gatekeeper™, has previously shown promising short- and medium-term results without any major complications, including displacement. The main aim of the present study is to assess the degree to which displacement of Gatekeeper prostheses may occur and to determine whether this is associated with patient outcomes. METHODS: Seven patients (six females) with a mean age of 55.6 years [50.5-57.2] and a mean FI duration of 6 ± 2 years were prospectively enrolled in the study. Each subject was anaesthetised and underwent implantation of six prostheses in the intersphincteric region, guided by endoanal 3D ultrasound (3D-EAU). Follow-up was performed at post-interventional months 1, 3, and 12 (median 12 ± 4 months), during which data were obtained from a defaecation diary, Wexner scale assessment, anorectal manometry (ARM), 3D-EAU, and a health status and quality of life questionnaire (FIQL). RESULTS: At 3-month follow-up, 3D-EAU revealed displacement of 24/42 prostheses in 5/7 patients. Of these, 15 had migrated to the lower portion and 9 to the upper portion of the anal canal and rectum. Despite this migration, treatment was considered successful in 3/7 patients. In one patient, it was necessary to remove a prosthesis due to spontaneous extrusion. CONCLUSIONS: We have shown that displacement of the Gatekeeper™ prosthesis occurs, but is not associated with poorer clinical outcomes.

Is the interval from surgery to ileostomy closure a risk factor for low anterior resection syndrome?

AIM: Low anterior resection syndrome (LARS) comprises a collection of symptoms affecting patients after restorative surgery for rectal cancer. The aim of the present study was to analyse the incidence of LARS in patients undergoing rectal cancer surgery with and without subsequent ileostomy and to determine whether the interval to ileostomy closure is a factor associated with its occurrence. METHOD: All patients undergoing curative anterior resection for rectal cancer from 2008 to 2012 in our institution were included in the study. They were divided into two groups according to whether or not a defunctioning ileostomy had been performed. Patients were assessed for LARS at a median interval of 23.60 ± 16.73 (12-48) months from anterior resection in those who did not have an ileostomy and at an interval of 11.31 ± 14.24 (12-60) months from closure of the ileostomy in those who did. They underwent a structured telephone interview based on a validated LARS score questionnaire. Univariate and multivariate analysis was carried out to assess possible associations between LARS and the variables studied. RESULTS: There were 150 patients (93 men) of whom 54.7% had no evidence of LARS, 17.3% had minor symptoms and 28% major symptoms of LARS. Univariate analysis showed that male gender, the presence of a temporary ileostomy and neoadjuvant therapy were predisposing factors for LARS. The interval from construction of the ileostomy to its closure did not appear to be a factor associated with LARS. In multivariate analysis, male gender and preoperative neoadjuvant therapy were significant predisposing factors for LARS. CONCLUSION: Male gender and preoperative neoadjuvant therapy are risk factors for LARS. The presence of ileostomy or time to ileostomy closure is not associated with the development of this syndrome.

Effectiveness of a three-dimensional anorectal ultrasound in perianal Crohn's disease: incompatibility with clinical and surgical examinations.

PURPOSE: We have correlated the 3D anorectal ultrasound (3D ARU) findings with clinical examination and the surgical findings and examined its capacity to provide ancillary information, which potentially alters patient management. PATIENTS AND METHODS: This is a prospective analysis conducted at a tertiary academic hospital. A total of 95 patients were included. We screened for sphincter defects and the presence of perianal Crohn's disease (PACD)-related lesions. RESULTS: We performed 150 3D ARUs. Exploratory ultrasound coincided with the rationale for diagnosis in 67.7% of cases, and fistulae were detected in 79% of cases where there was clinical suspicion. Fistulae were associated with abscesses in 29 cases, and isolated abscesses were identified in 19 cases (17.7%), only 12 of which (63.2%) were clinically suspected. Sphincter defects were observed in 15 cases with 7 cases (77.8%) presenting with clinical fecal incontinence. The operative findings coincided with ultrasonographic findings in 81.3% of the analyzed cases. The inter-observer variability of endosonographic classification resulted in a kappa score of 0.86. Ultrasonographic data altered the therapeutic plan of management in 73 cases (48.6%). CONCLUSIONS: Three-dimensional ARU is accurate in the diagnosis of fistula type in PACD and in the delineation of ancillary suspected and unsuspected abscess collections. Its use impacts therapeutic management in about half the cases examined. A new ultrasonographic-based PACD classification system is presented which has high inter-observer agreement but which requires future prospective validation in clinical PACD patients.

Percutaneous neuromodulation of the posterior tibial nerve for the treatment of faecal incontinence - mid-term results: is retreatment required?

AIM: Posterior tibial nerve stimulation (PTNS) has emerged in recent years as a therapy for faecal incontinence. Its long-term effectiveness is yet to be established, along with what the form of retreatment should be in the event of loss of effectiveness. The present study aimed to establish the mid-term results to identify the proportion of patients who may need further treatment, and if so when. METHOD: A prospective study including 30 patients was conducted at an academic hospital. The patients underwent 12 weekly outpatient treatment sessions, each lasting 30 min (first PTNS phase). Neuromodulation was discontinued in those patients who did not have a 40% decrease in their pretreatment Wexner score. Patients having a better than 40% response were offered another 12-week course of complete treatment (second PTNS phase), following which they received no further PTNS treatment (phase without PTNS) but were assessed at 6 months and 2 years. RESULTS: All patients finished the first phase and 22/30 patients continued to the second phase. During this phase 11 patients showed an improved Wexner score (baseline/first phase/second phase: 14.3 ± 4.2 vs 9.9 ± 5.4 vs 6.8 ± 5.4). After a 6-month period without any treatment, the score was still improved in 11/30 patients (9.1 ± 6.2). At 2 years there was improvement in 16/30 patients (8.8 ± 7.1). There was a significant improvement in three variables of the quality of life questionnaire: lifestyle, coping behaviour and embarrassment. CONCLUSION: The response to first and second phase PTNS was maintained for up to 2 years. Retreatment was not required in about half of patients, even when they had finished the treatment 6 months or 2 years previously.

Expanded allogeneic adipose-derived stem cells (eASCs) for the treatment of complex perianal fistula in Crohn's disease: results from a multicenter phase I/IIa clinical trial.

PURPOSE: The management of perianal fistula in patients with Crohn's disease is an extremely challenging medical problem as many fistulas do not respond to available treatments. The objectives were to assess the safety and efficacy of a suspension of expanded adipose-derived allogeneic mesenchymal stem cells (eASCs) for the treatment of complex perianal fistula in Crohn's disease METHODS: An open-label, single-arm clinical trial was conducted at six Spanish hospitals. Twenty-four patients were administered intralesionally with 20 million eASCs in one draining fistula tract. A subsequent administration of 40 million eASCs was performed if fistula closure was incomplete at week 12. Subjects were followed until week 24 after the initial administration. RESULTS: Treatment-related adverse events did not indicate any clinical safety concerns after 6 months follow-up. The full analysis of efficacy data at week 24 showed 69.2 % of the patients with a reduction in the number of draining fistulas, 56.3 % of the patients achieved complete closure of the treated fistula achieved, and 30 % of the cases presenting complete closure of all existing fistula tracts. Of note, closure was strictly defined as: absence of suppuration through the external orifice and complete re-epithelization, plus absence of collections measured by magnetic resonance image scan (MRI). Furthermore, MRI Score of Severity showed statistically significant differences at week 12 with a marked reduction at week 24. CONCLUSIONS: Locally injected eASCs appear to be a simple, safe, and beneficial therapy for perianal fistula in Crohn's disease patients. Additional studies are needed to further confirm the efficacy of the eASCs.

Long-term efficacy of dextranomer in stabilized hyaluronic acid (NASHA/Dx) for treatment of faecal incontinence.

AIM: Randomized, controlled trials have demonstrated the efficacy and safety of injectable bulking agents for the treatment of faecal incontinence (FI), although the long-term outcome has not been assessed. NASHA/Dx gel, a biocompatible, nonallergenic bulking agent consisting of nonanimal stabilized hyaluronic acid and dextranomer microspheres, has demonstrated efficacy and safety for up to 12 months after treatment. The objective of this study was to evaluate the long-term efficacy and safety of NASHA/Dx, assessed 24 months after treatment. METHOD: This study was a 24-month follow-up assessment of patients treated with NASHA/Dx under open-label conditions. Data on FI episodes and quality of life measures were collected from diaries over the 28-day period immediately preceding the 24-month assessment. Adverse events were collected. RESULTS: Eighty-three of 115 patients completed the 24-month follow-up assessment. At 24 months, 62.7% of patients were considered responders and experienced a ≥ 50% reduction in the total number of FI episodes. The median number of FI episodes declined by 68.8% (P < 0.001). Episodes of both solid and liquid stool incontinence decreased. The mean number of incontinence-free days increased from 14.6 at baseline to 21.7 at 24 months (P < 0.001). Incontinence scores and FI quality of life scores also showed significant improvements. The most common adverse events (AEs) were proctalgia (13.3%) and pyrexia (9.6%). The majority of AEs were mild to moderate, self-limited and resolved within 1 month of the injection. CONCLUSION: NASHA/Dx is safe, effective and durable over a 24-month period with a majority of patients experiencing significant improvement in multiple symptoms associated with FI.

Impact of a multidisciplinary medication reconciliation program on clinical outcomes: A pre-post intervention study in surgical patients.

BACKGROUND: Previous studies have evaluated the effects of medication reconciliation (MR) and suggest that it is effective in decreasing medication discrepancies. Nevertheless, a recent overview of systematic reviews concluded that there is no clear evidence in favor of MR in patient-related outcomes and healthcare utilization, and further research about it is needed. OBJECTIVE: To evaluate the impact of a multidisciplinary MR program on clinical outcomes in patients with colorectal cancer presenting other chronic diseases, undergoing elective colorectal surgery. METHODS: We performed a pre-post study. Adult patients scheduled for elective colorectal cancer surgery were included if they presented at least one "high-risk" criteria. The MR program was developed by internists, pharmacists and surgeons, and ended with the obtention of the patient's pre-admission medication list and follow-up care until discharge. The primary outcome was the length of stay (LOS). Secondly, we evaluated mortality, preventable surgery cancellations and risk factors for complications. RESULTS: Three hundred and eight patients were enrolled. Only one patient in the pre-intervention group suffered a preventable surgery cancellation (p = 0.317). The mean LOS was 13 ± 12 vs. 11 ± 5 days in the pre-intervention and the intervention cohort, respectively (p = 0.435). A difference in favor of the intervention group in patients with cardiovascular disease (p = 0.038) and those >75 years old (p = 0.043) was observed. No difference was detected in the mortality rate (p = 0.999) neither most of the indicators of risk factors for complications. However, the management of preoperative systolic blood pressure of hypertensive patients (p = 0.004) and insulin reconciliation in patients with treated diabetes (p = 0.003) were statistically better in the intervention group. CONCLUSIONS: No statistically significant change was observed in the mean global LOS. A statistically significant positive effect on LOS was observed in vulnerable populations: patients >75 years old and those with cardiovascular disease, who presented a 5-day reduction in the mean LOS.

Transanal rectocele repair using linear stapler and bioabsorbable staple line reinforcement material: short-term results of a prospective study.

PURPOSE: This study was designed to determine the short-term results of transanal rectocele repair with use of a linear stapler and Bioabsorbable Seamguard. METHODS: Ten women (median age, 56.1 y) with obstructed defecation syndrome were enrolled in the study. The preoperative study consisted of a medical history, physical examination, anoscopy, endoanal ultrasound, and defecography. All patients completed a severity score and a visual analog scale for global quality of life, and provided the postoperative dates of complications. RESULTS: Overall, the treatment significantly improved the obstructed defecation: the severity score improved from a median of 19.8 +/- 4.2 at baseline to 6.10 +/- 8.2 at one month (P < .005), 5.9 +/- 8.3 at 6 months (P < .005), and 6 +/- 8.3 at one year after the operation (P < .005). A significant improvement was observed in the visual analog scale, which improved from a median of 1.8 +/- 1.4 at baseline to 6 +/- 1.6 at one month (P < .005), 6.6 +/- 2.1 at 6 months (P < .004), and 7 +/- 2.5 at one year (P < .004). A significant improvement was also observed in various symptoms. Only 2 patients manifested urgent defecation. CONCLUSIONS: The present study demonstrates that rectocele repair using a linear stapler and Seamguard is a safe, easy procedure, with a very low rate of complications and good immediate outcome.

Autologous Platelet-Rich Plasma in the Treatment of Perianal Fistula in Crohn's Disease.

AIM: To assess clinical healing in patients with perianal Crohn's disease with local intrafistular injection of autologous platelet-rich plasma. METHOD: The pilot study was conducted at a single centre between January 2013 and December 2015. Autologous platelet-rich plasma was prepared in platelet-rich and platelet-poor fractions for local intrafistular injection in patients with proven, established perianal Crohn's disease. Patients were permitted biological therapies, and the Perianal Crohn's Disease Activity Index was recorded. Patients were followed for 48 weeks for clinical signs of healing (complete, partial or non-healing), monitoring fistula drainage, closure and epithelialization. RESULTS: The study included 29 patients (19 males; mean age 38 ± 12.8 years) with four exclusions in the operating room because surgery was not indicated and four lost to follow-up. Five adverse events were recorded, with two requiring the drainage of abscess collections. Of the 21 patients assessable at 24 weeks, there was complete healing, partial healing and non-healing in 7 (33.3%), 8 (38.1%) and 6 (28.6%) patients, respectively. By 48 weeks, there was complete healing, partial healing and non-healing in 6 (40%), 6 (40%) and 3 (20%) patients, respectively, with a reduction in the number of visible external fistula openings at both time points (P = 0.021). By the end of the study, there was a higher trend of healing if biological therapies were continued (85.7% with biologics vs. 75% without, P = 0.527), but there were no statistically significant differences and no differences in the Perianal Crohn's Disease Activity Index. CONCLUSION: Autologous platelet-rich plasma is safe in patients with perianal Crohn's disease, with an acceptable healing rate over a medium-term follow-up, particularly if biological therapies are used concomitantly.

Evaluation by three-dimensional anal endosonography of injectable silicone biomaterial (PTQ) implants to treat fecal incontinence: long-term localization and relation with the deterioration of the continence.

BACKGROUND: The purposes of the study were the long-term evaluation of silicone implants with three-dimensional (3D) anal endosonography and its correlation with anal incontinence. METHODS: Fifteen patients were injected with silicone because of anal incontinence and co-existing internal anal sphincter disruption (n = 8) or thinning (n = 7). The evaluation was performed with the Wexner score and 3D anal endosonographies. RESULTS: Forty-four implants were performed. The endosonography at 3 months detected that all the implants were properly located. At 24 months, it detected 37/44 implants of initially injected and 33/37 were properly located. Four of 37 implants had moved and 7/44 were neither in the anus nor in the rectum. A total of 8/15 patients had their implants correctly placed. Globally, silicone implants significantly improved fecal continence. CONCLUSIONS: The silicone implants might have moved or even be lost. The continence deterioration suffered by most patients after the first year of the injection has no relation with the localization and number of implants that the patients have.

Prospective multicentre clinical trial of stapled transanal rectal resection for obstructive defaecation syndrome.

BACKGROUND: This prospective multicentre study assessed the safety and effectiveness of stapled transanal rectal resection (STARR) for treatment of obstructive defaecation syndrome (ODS). METHODS: Between February 2001 and June 2006, 104 patients diagnosed with ODS were treated with STARR. Follow-up was scheduled for 1, 3 and 6 months after surgery, and annually thereafter. Variables related to the patient, surgical technique and outcome were analysed. RESULTS: Mean operating time was 46.7 min. Haemorrhage at the staple line occurred in 55 patients (52.9 per cent). Three patients required surgical revision in the first 48 h owing to persistent bleeding. The median postoperative pain score was 2.4 on a scale from 1 to 10. Mean hospital stay was 2.2 days. The mean constipation score improved from 13.5 before surgery to 5.1 at 1-year follow-up (P = 0.006). Twenty-three patients reported faecal incontinence at 4 weeks after surgery, but only nine still had minor residual incontinence by 1 year. At a median follow-up of 26 (range 12-72) months, ODS had recurred or persisted radiologically and/or clinically in 11 patients. CONCLUSION: STARR is associated with low morbidity and a short hospital stay, and is an effective alternative treatment for ODS.