Up-to-date meta-analysis of long-term evaluations of mesenchymal stem cell therapy for complex perianal fistula

BACKGROUND Local mesenchymal stem cell(MSC)therapy for complex perianal fistulas(PFs)has shown considerable promise.But,the long-term safety and efficacy of MSC therapy in complex PFs remain unknown.AIM To explore the long-term effectiveness and safety of local MSC therapy for complex PFs.METHODS Sources included the PubMed,EMBASE,and Cochrane Library databases.A standard meta-analysis was performed using RevMan 5.3.RESULTS After screening,6 studies met the inclusion criteria.MSC therapy was associated with an improved long-term healing rate(HR)compared with the control condition[odds ratio(OR)=2.13;95%confidence interval(95%CI):1.34 to 3.38;P=0.001].Compared with fibrin glue(FG)therapy alone,MSC plus FG therapy was associated with an improved long-term HR(OR=2.30;95%CI:1.21 to 4.36;P=0.01).When magnetic resonance imaging was used to evaluate fistula healing,MSC therapy was found to achieve a higher long-term HR than the control treatment(OR=2.79;95%CI:1.37 to 5.67;P=0.005).There were no significant differences in long-term safety(OR=0.77;95%CI:0.27 to 2.24;P=0.64).CONCLUSION Our study indicated that local MSC therapy promotes long-term and sustained healing of complex PFs and that this method is safe.

Multi-national observational study to assess quality of life and treatment preferences in patients with Crohn’s perianal fistulas

BACKGROUND Patients with Crohn’s disease(CD)are at risk of developing complications such as perianal fistulas.Patients with Crohn’s perianal fistulas(CPF)are affected by fecal incontinence(FI),bleeding,pain,swelling,and purulent perianal discharge,and METHODS This cross-sectional observational study was conducted in patients with CD aged 21-90 years via a web-enabled questionnaire in seven countries(April-August 2021).Patients were recruited into three cohorts:Cohort 1 included patients without perianal fistulas;cohort 2 included patients with perianal fistulas without fistula-related surgery;and cohort 3 included patients with perianal fistulas and fistula-related surgery.Validated patient-reported outcome measures were used to assess quality of life.Drivers of treatment preferences were measured using a discrete choice experiment(DCE).RESULTS In total,929 patients were recruited(cohort 1,n=620;cohort 2,n=174;cohort 3,n=135).Short Inflammatory Bowel Disease Questionnaire scores were worse for patients with CPF(cohorts 2 and 3)than for those with CD without CPF(cohort 1):Mean score 3.8 and 3.7 vs 4.1,respectively,(P<0.001).Similarly,mean Revised FI and FI Quality of Life scores were worse for patients with CPF than for those with CD without CPF.Quality of Life with Anal Fistula scores were similar in patients with CPF with or without CPF-related surgery(cohorts 2 and 3):Mean score 41 and 42,respectively.In the DCE,postoperative discomfort and fistula healing rate were the most important treatment attributes influencing treatment choice:Mean relative importance 35.7 and 24.7,respectively.CONCLUSION The burden of illness in CD is significantly higher for patients with CPF and patients rate lower postoperative discomfort and higher healing rates as the most desirable treatment attributes.

Emerging treatments for complex perianal fistula in Crohn's disease

Complex perianal fistulas have a negative impact on the quality of life of sufferers and should be treated.Correct diagnosis,characterization and classification of the fistulas are essential to optimize treatment.Nevertheless, in the case of patients whose fistulas are associated with Crohn's disease,complete closure is particularly difficult to achieve.Systemic medical treatments(antibiotics, thiopurines and other immunomodulatory agents,and, more recently,anti-tumor necrosis factor-αagents such as infliximab)have been tried with varying degrees of success.Combined medical(including infliximab)and less aggressive surgical therapy(drainage and seton placement)offer the best outcomes in complex Crohn's fistulas while more aggressive surgical procedures such as fistulotomy or fistulectomy may increase the risk of incontinence.This review will focus on emerging novel treatments for perianal disease in Crohn's patients. These include locally applied infliximab or tacrolimus, fistula plugs,instillation of fibrin glue and the use of adult expanded adipose-derived stem cell injection.More welldesigned controlled studies are required to confirm the effectiveness of these emerging treatments.

Can transcutaneous perianal ultrasonography be the first-line diagnostic instrument for evaluating pediatric perianal fistulas?

Background:Pediatric perianal fistula is a common disorder.It is more difficult to detect the fistula tract and internal opening(IO)in children than in adults.This study aimed to evaluate the clinical diagnostic value of transcutaneous perianal ultrasound for children with perianal fistula.Methods:A retrospective review was conducted by analysing the preoperative transcutaneous perianal ultrasound and intraoperative exploration results of 203 consecutive patients who were<3 years old and diagnosed with perianal fistula.Analyses were conducted to evaluate the accuracy and consistency of utilizing the transcutaneous perianal ultrasound in the diagnosis of the complexity and location of the IO of perianal fistulas.Results:Compared with intraoperative exploration,the preoperative transcutaneous perianal ultrasonography has almost perfect agreement(Kappa=0.881,P<0.001)in the diagnosis of fistula tract complexity and IO with a sensitivity of 92%and a specificity of 97%.In addition,both intraoperative exploration and transcutaneous perianal ultrasound diagnosis showed high consistency in the identification of the IO of perianal fistulas(QuadrantⅠKappa=0.831,QuadrantⅡKappa=0.773,QuadrantⅢKappa=0.735,QuadrantⅣKappa=0.802,all P<0.01).The IOs were mainly distributed in QuadrantsⅣandⅡin both simple and complex fistulas.Conclusions:Transcutaneous perianal ultrasound,as a non-invasive and simple imaging technique,showed high accuracy in the diagnosis and identification of the fistula classification and IO location.It could be considered a first-line diagnostic instrument for evaluating perianal fistulas among children.

Treatment of peri-anal fistula in Crohn's disease

Anal fistulas are a common manifestation of Crohn's disease(CD). The first manifestation of the disease is often in the peri-anal region, which can occur years before a diagnosis, particularly in CD affecting the colon and rectum. The treatment of peri-anal fistulas is difficult and always multidisciplinary. The European guidelines recommend combined surgical and medical treatment with biologic drugs to achieve best results. Several different surgical techniques are currently em-ployed. However, at the moment, none of these tech-niques appear superior to the others in terms of healing rate. Surgery is always indicated to treat symptomatic, simple, low intersphincteric fistulas refractory to medi-cal therapy and those causing disabling symptoms. Ut-most attention should be paid to correcting the balance between eradication of the fistula and the preservationof fecal continence.

Modern surgical strategies for perianal Crohn's disease

One of the most challenging phenotypes of Crohn’s disease is perianal fistulizing disease(PFCD).It occurs in up to 50%of the patients who also have symptoms in other parts of the gastrointestinal tract,and in 5%of the cases it occurs as the first manifestation.It is associated with severe symptoms,such as pain,fecal incontinence,and a significant reduction in quality of life.The presence of perianal disease in conjunction with Crohn’s disease portends a significantly worse disease course.These patients require close monitoring to identify those at risk of worsening disease,suboptimal biological drug levels,and signs of developing neoplasm.The last 2 decades have seen significant advancements in the management of PFCD.More recently,newer biologics,cell-based therapies,and novel surgical techniques have been introduced in the hope of improved outcomes.However,in refractory cases,many patients face the decision of having a stoma made and/or a proctectomy performed.In this review,we describe modern surgical management and the most recent advances in the management of complex PFCD,which will likely impact clinical practice.

Perianorectal abscesses and fistula due to ingested jujube pit in infant:Two case reports

BACKGROUND About 90%of perianal infection is caused by cryptoglandular infection.Only a few cases of peritonitis or intra-abdominal abscesses secondary to perforation of the digestive tract by an ingested foreign body have been reported.The most common sites of impaction and perforation include the appendix,cecum and the terminal ileum.The rectum is an unusual site of foreign body impaction.This report intends to highlight that ingested foreign body impacted in the rectum is an extremely rare cause of perianal abscess and subsequent fistula in infants.CASE SUMMARY Two cases of perianal abscess and fistula due to ingested jujube pit impacted in the rectum are reported.Both cases are infants with free previous medical history suffered from recurrent perianal infection.The caregivers of the two patients denied ingestion of a foreign body or any history of trauma.Physical examination combined with ultrasound or computed tomography scan established the diagnosis.Both of the patients underwent operation under general anesthesia.In case 1,a jujube pit with sharp ends was discovered embedded within a subcutaneous fistula.The jujube pit was then removed intact along with fistula resection.The wound was successfully laid open to allow healing by secondary intention.In case 2,a jujube pit was found with its sharp end puncturing the rectum,surrounded by pus and necrotic tissue.Subsequent incision and adequate drainage were performed.The whole jujube pit was then removed from the abscess cavity at the same time.Both patients received colonoscopy to rule out inflammatory bowel disease or other potential damages by the ingested jujube pit.The postoperative period was uneventful.At 1.5 year follow-up,no recurrent abscess or fistula were found in either patient.CONCLUSION An impacted foreign body must not be overlooked as an unusual cause of perianal abscess and fistula,especially in young children.

Long-term efficacy of infliximab maintenance therapy for perianal Crohn’s disease

AIM:To assess the long-term efficacy of seton drainage with infliximab maintenance therapy in treatment of stricture for perianal Crohn’s disease(CD). METHODS:Sixty-two patients with perianal CD who required surgical treatment with or without infliximab between September 2000 and April 2010 were identified from our clinic’s database.The activities of the perianal lesions were evaluated using the modified perianal CD activity index(mPDAI)score.The primary endpoint was a clinical response at 12-15 wk after surgery as a shortterm efficacy.Secondary endpoints were recurrence as reflected in the mPDAI score,defined as increased points in every major element.The clinical responses were classified as completely healed(mPDAI=0),partially improved(mPDAI score decreased more than 4 points),and failure or recurrence(mPDAI score increased or decreased less than 3 points). RESULTS:There were 43 males and 19 females,of whom 26 were consecutively treated with infliximab after surgery as maintenance therapy.Complete healing was not seen.Failure was seen in 10/36(27.8%) patients without infliximab and 4/26(15.4%)patients with infliximab(P=0.25).Partial improvement was seen in 26/36(72.2%)patients without infliximab and 22/26(88.5%)patients with infliximab(P=0.25). Short-term improvement was achieved in 48/62(77.4%) patients.Although the mPDAI score improved significantly with surgery regardless of infliximab,it decreased more from baseline in patients with infliximab(50.0%) than in those without infliximab(28.6%),(P=0.003). In the long-term,recurrence rates were low regardless of infliximab in patients without anorectal stricture.In patients with anorectal stricture,cumulative recurrence incidences increased gradually and exceeded 40%at 5 years regardless of infliximab.No efficacy of infliximab treatment was found(P=0.97).Although the cumulative rate of ostomy creation was also low in patients without stricture and high in patients with stricture,no protective efficacy was found with infliximab treatment(P =0.6 without stricture,P=0.22 with stricture). CONCLUSION:Infliximab treatment was demonstrated to have short-term efficacy for perianal lesions.Longterm benefit with infliximab was not proven,at least in patients with anorectal stricture.

Establishing a rabbit model of perianal fistulizing Crohn's disease

BACKGROUND Crohn’s disease(CD)is a chronic nonspecific intestinal inflammatory disease.The aetiology and pathogenesis of CD are still unclear.Anal fistula is the main complication of CD and is a difficult problem to solve at present.The main limitation of developing new therapies is bound up with the short of preclinical security and effectiveness data.Therefore,an ideal animal model is needed to establish persistent anal fistula and an inflamed rectal mucosa.AIM To improve the induction method of colitis and establish a reliable and reproducible perianal fistulizing Crohn’s disease animal model to evaluate new treatment strategies.METHODS Twenty male New Zealand rabbits underwent rectal enema with different doses of 2,4,6-trinitrobenzene sulfonic acid to induce proctitis.Group A was treated with an improved equal interval small dose increasing method.The dosage of group B was constant.Seven days later,the rabbits underwent surgical creation of a transsphincteric fistula.Then,three rabbits were randomly selected from each group every 7 d to remove the seton from the fistula.The rabbits were examined by endoscopy every 7 days,and biopsy forceps were used to obtain tissue samples from the obvious colon lesions for histological analysis.The disease activity index(DAI),colonoscopy and histological scores were recorded.Perianal endoscopic ultrasonography(EUS)was used to evaluate the healing of fistulas.RESULTS Except for the DAI score,the colonoscopy and histological scores in group A were significantly higher than those in group B(P<0.05).In the ideal model rabbit group,on the 7 th day after the removal of the seton,all animals had persistent lumens on EUS imaging,showing continuous fullthickness high signals.Histological inspection of the fistula showed acute and chronic inflammation,fibrosis,epithelialization and peripheral proctitis of the adjoining rectum.CONCLUSION The improved method of CD colitis induction successfully established a rabbit perianal fistula CD preclinical model,which was confirmed by endoscopy and pathology.

Loose Seton: A Misnomer of Cutting Seton

Purpose: The purpose of this study was to demonstrate loose silk seton actually acts as a slow cutting seton contrary to the idea of simply drainage. Besides, to show the effect of loose seton on patient’s incontinence is mostly proportional to the degree of division of the sphincter muscle. Design: Fifty patients with high transsphincteric fistulas were treated with loose seton technique. We measured the length of high sphincteric fistula tracts, pre- and postoperative anal sphincter pressures and incontinence scores. Results: Loose seton with heavy silk resulted in 72% percent of progressive migration of the fistula tract caudally. The more the progressive migration of the loose seton loop, the less the pressure drop in both resting and squeezing in manometric studies. This study is limited by its retrospective design in prospectively collected data and covers relatively small number of patients. Conclusion: Seton is still useful technique in high perianal fistula surgery. Defining this technique as simply “loose” seton is misnomer since it acts as a slowly cutting seton and results in progressive migration of the fistula tract caudally. The more the progressive migration of the loose seton loop, the less the pressure drop would be possible after postoperatively.

Evaluating the effectiveness of infliximab on perianal fistulizing Crohn’s disease by magnetic resonance imaging

Background and aim:Data on the radiologic evaluation of perianal fistulizing Crohn’s disease(PFCD)naive to anti-tumor necrosis factor therapy are scarce,especially in Asian populations.We assessed the effectiveness of infliximab(IFX)on PFCD and explored predictors of‘deep remission’based on clinical and radiologic assessments.Methods:Patients with Crohn’s disease and active anal fistulas attending our care center for IFX therapy were prospectively enrolled.Each patient underwent clinical examination according to the Fistula Drainage Assessment Index,endoscopy for assessment of Crohn’s Disease Activity Index(CDAI)and Perianal Crohn’s Disease Activity Index(PCDAI),magnetic resonance imaging(MRI)to determine Van Assche score and Ng score,and laboratory tests up to 2 weeks prior to the start of and up to 2 weeks after the sixth IFX therapy(Week 32).Results:Among 38 patients treated with IFX,52.6%achieved clinical remission based on the Fistula Drainage Assessment Index and 42.1%achieved deep remission based on Ng score.Van Assche score(from 14.5±4.26 to 7.36±7.53),CDAI(from 170±92 to 71±69)and PCDAI(from 7.45±2.65 to 2.44±3.20)decreased significantly after six IFX treatments.The only predictor of deep remission was simple fistula(P=0.004,odds ratio=3.802,95%confidence interval:1.541–9.383).Conclusions:IFX has been shown to have appreciable effectiveness in Chinese patients with PFCD.MRI is the gold standard for evaluating PFCD,but Van Assche score has some limitations.