Clinical characteristics and survival outcomes of perianal Paget’s disease:A SEER population-based study

Objective The aim of the study was to analyze the clinical features of patients with perianal Paget’s disease(PPD)and investigate prognosis risk factors.Methods The SEER*Stat software was used to identify 116 PPD patients from 1975 to 2015 in the SEER research database.The Kaplan-Meier method was used to conduct a univariate analysis for PPD patients.The differences in survival rates were evaluated using the log-rank test.The differences in the clinicopathological features of PPD patients with or without anorectal carcinoma were compared using the chi-square test.Results The median survival time of PPD patients was 44 months.The median age of onset was 73 years old.The 43.10%of the patients were alive at the end of follow up,and only 12.93%of the patients died of PPD.Elderly(age>70 years;χ^2=9.453,P=0.002),poor differentiation(χ^2=46.557,P=0.000)and abdominal perineal resection(APR;χ^2=46.557,P=0.000)were unfavorable risk factors of prognosis.Nearly 50%of PPD had combined with other malignancies,and over 22.41%of those had multiple primary neoplasms(3 or more).PPDs predisposed concurrent malignancy,and 48.21%of PPD patients with other malignancies combined with anorectal carcinoma in the study.Stage(χ^2=10.127,P=0.018),and surgical method(χ^2=12.245,P=0.007)were statistically significant in the PPD patients with or without anorectal carcinoma.The 16.07%of patients had multiple lesions of Paget’s.Conclusion Patients with PPD have a favorable survival,while the disease-specific mortality is low.Diagnosed age,differentiation,and surgical methods were the influence factors of prognosis in PPD patients.PPDs with anorectal carcinoma is of most important in further investigation.

Perianal Crohn’s disease:Still more questions than answers

In this editorial we comment on the article by Pacheco et al published in a recent issue of the World Journal of Gastroenterology.We focus specifically on the burden of illness associated with perianal fistulizing Crohn’s disease(PFCD)and the diagnostic and therapeutic challenges in the management of this condition.Evol-ving evidence has shifted the diagnostic framework for PFCD from anatomical classification systems,to one that is more nuanced and patient-focused to drive ongoing decision making.This editorial aims to reflect on these aspects to help clinicians face the challenge of PFCD in day-to-day clinical practice.

Navigating the complexities of perianal Crohn’s disease:Diagnostic strategies,treatment approaches,and future perspectives

This article discusses the literature review article by Pacheco et al published in July 2024;the authors provided good reviews of perianal Crohn’s disease(CD),and challenges faced by clinicians in the management.CD,characterized by its chronic and relapsing nature,is an idiopathic condition that can involve any segment of the gastrointestinal tract.Perianal disease impacts up to 40%of patients with CD,with perianal fistulas constituting up to 80%of perianal lesions.Perianal CD can be highly incapacitating and profoundly diminish the overall well-being of patients.The management focuses on controlling the perianal sepsis and treating luminal CD.Biologics are crucial to the treatment approach,and results have been encouraging.The surgery focuses on controlling the sepsis,with more definitive treatments being fistula surgery,fecal diversion,and proctectomy as the last resort.This manuscript briefly describes the burden of CD,the challenges posed by perianal CD,and the role of different treatment modalities from colorectal surgeon’s perspective.

Assessment of perianal fistulizing Crohn’s disease activity with endoanal ultrasound: A retrospective cohort study

BACKGROUND Perianal fistulas pose dual challenges to Crohn's disease(CD)patients.Low patient compliance due to the complexity of existing examination methods plagues the treatment and follow-up management of perianal CD.AIM To determine the accuracy of endoanal ultrasound(EUS)and shear wave elastography(SWE)for evaluating perianal fistulizing CD(PFCD)activity.METHODS This was a retrospective cohort study.A total of 67 patients from August 2022 to December 2023 diagnosed with CD were divided into three groups:Non-anal fistula group(n=23),low-activity perianal fistulas[n=19,perianal disease activity index(PDAI)≤4],high-activity perianal fistulas(n=25,PDAI>4)based on the PDAI.All patients underwent assessments including EUS+SWE,pelvic magnetic resonance[pelvic magnetic resonance imaging(MRI)],C-reactive protein,fecal calprotectin,CD activity index,PDAI.RESULTS The percentage of fistulas indicated by pelvic MRI and EUS was consistent at 82%,and there was good consistency in the classification of perianal fistulas(Kappa=0.752,P<0.001).Significant differences were observed in the blood flow Limberg score(χ^(2)=8.903,P<0.05)and shear wave velocity(t=2.467,P<0.05)between group 2 and 3.Shear wave velocity showed a strong negative correlation with magnetic resonance novel index for fistula imaging in CD(Magnifi-CD)score(r=-0.676,P<0.001),a weak negative correlation with the PDAI score(r=-0.386,P<0.05),and a weak correlation between the Limberg score and the PDAI score(r=0.368,P<0.05).CONCLUSION EUS combined with SWE offers a superior method for detecting and quantitating the activity of perianal fistulas in CD patients.It may be the ideal tool to assess PFCD activity objectively for management strategies.

Does shear wave elastography technology provide better value for the assessment of perianal fistulizing Crohn’s disease?

Magnetic resonance imaging is the gold standard compared other clinical fin-dings.But shear wave elastography technique combined with endoscopic ultra-sound can evaluate the degree of fibrosis of fistula tissue in Crohn’s disease patients.This topic is highly relevant to the current discourse,especially for It shows a certain degree of innovation and practicality and is worthy of study and popularization.

Retrospective analysis of perianal Paget's disease with underlying anorectal carcinoma

AIM:To analyze clinical and pathological characteristics of an aggressive subtype of perianal Paget's disease(PPD) and explore its rational treatment modalities.METHODS:PPD patients were retrospectively collected in the institutional colorectal database of the Fudan University Shanghai Cancer Center.Detailed patient histories of past medical condition,diagnosis,treatment,and pathological findings were reviewed.Surgical specimen from diagnosis and surgery were reviewed by two independent pathologists for confirmation of diagnoses.Follow up was accomplished by clinical interview by cellphone.RESULTS:In total,eight cases of PPD were analyzed.All patients had underlying anorectal adenocarcinoma,including seven with synchronous lesions and one with metachronous lesions.Moreover,all anorectal lesions had a mucin-producing component.The median age at diagnosis was 65(range 29-81 years),and the male/female ratio was 7:1.The Median follow-up time of all patients was 61.5 mo(range 10-204 mo).One patient treated with abdominoperineal resection(APR) died from lung metastases 10 mo after the APR operation.The other patients are still free of disease at the time of this analysis.CONCLUSION:PPD is a rare malignancy and is easily misdiagnosed.Underlying anorectal cancer was not unusual and was a significant prognostic factor.Rational treatment of both anorectal cancer and PPD lesion is essential for long-term survival.

Development a survival prediction model for patients with Paget disease of the breast based on the SEER database

Background:We explored the risk factors that affect the prognosis of patients with Paget disease of the breast(PD)and constructed a survival prediction model.Methods:The data of PD patients from 2004 to 2014 were collected through the SEER database.The factors affecting the prognosis of PD patients were analysed by a single factor,and the prediction model of the independent risk factor transformation model diagram that affected their 1-,3-,and 5-year survival rates was screened by multivariate Cox proportional hazard regression analysis coefficients.The consistency index was used to evaluate its predictive value,and its predictive performance was tested by the 1000 bootstrap method.Then,the calibration curve was used to verify the predictive performance of the model,and the receiver operating characteristic curve and decision curve analysis were used to assess the sensitivity and practicability of the model compared to the American Cancer Commission staging(AJCC)staging system.Results:The consistency index of the model was 0.795(95%confidence interval 0.773–0.818).The calibration curve shows good consistency,while the receiver operating characteristic curve shows the sensitivity of the model to predict the survival rate of PD at 1,3,and 5 years.Decision curve analysis confirmed that the nomogram can predict the survival rate of PD patients at 1,3,and 5 years instead of the traditional AJCC system.Conclusion:Regarding the independent prognostic factors of age,marital status,AJCC classification,surgery,radiotherapy,chemotherapy and marital status conversion in PD patients,the nomogram established in sequence has higher accuracy and clinical value than the traditional AJCC system.

Extramammary Paget’s Disease Manifested by Intraepithelial Adenocarcinoma of the Vulva and Anus Combined with Invasive Adenocarcinoma of the Ampullary Part of the Rectum

The Object of the Study: The author of the given paper describes an unusual combination of two diseases: extramammary Paget’s disease manifested by intraepithelial adenocarcinoma of the vulva and anus combined with invasive adenocarcinoma of the ampullary part of the rectum and describes the atypical manifestations of these diseases. The Content: The content of this research paper includes a description of the patient, an analysis of the clinical picture, diagnostic methods and therapeutic interventions used, a report of the following disease, and the result of the presented case. The Result of the Research Work: The result of the research work is the analysis of a clinical case with two different tumors, where such a combination of tumors is rarely described in the literature. Moreover, no large specific sample with this combination of diseases is available. Patient Characteristics: The given case report describes a patient of the Palliative Care Unit of the Gerontology Clinic with a primary diagnosis of C20-rectal adenocarcinoma in the background of the anal canal, perineal skin Paget’s disease, stage IV. The presented complications of the patient’s primary diagnosis are multiple metastases in the liver;status post palliative chemotherapy;hepatomegaly;metastases to abdominal lymph nodes, inguinal lymph nodes;metastases at Th12, L4 level;pain syndrome. The presented above combination of diagnosed diseases is very rare. Applied Diagnostics: In October 2021, it was performed diagnostic manipulation: biopsy and the pathologist have provided a microscopic description. The first tissue fragment had a pronounced electrothermal lesion and the epithelial structures were not valuable. The second skin tissue fragment was covered with hyperplastic and acanthotic epithelium;its basal and middle layers contained multiple large cells proliferates extending into the medial epidermis, and the cytoplasm of these cells reacted positively with PAS (Periodic Acid Schiff reaction). It needs to be noted that the patient had previously had several years of biopsies from the perineal and anal epidermis, where Paget’s disease had also been diagnosed. The performed immunohistochemistry showed these cells to be CK20 positive, CK7 rare positive and p16 negative. The following pathohistological findings were made: morphological and immunohistochemical picture is consistent with Paget’s disease. According to the ICD-10, the patient was diagnosed with C51 malignant neoplasm of the female external genitalia. Using imaging diagnostics, it became clear that the patient’s rectal adenocarcinoma had progressed to metastatic stage with distant liver metastases in the background of anal canal, perineal skin Paget’s disease. Therapeutic Plan of the Patient: Based on the patient’s main diagnoses, the complications of the principal diagnosis, the patient’s overall severe condition, pain syndrome, age and comorbidities, palliative chemotherapy was approved as a therapeutic option in council of doctors. Monitoring and Outcome of the Patient: The patient’s general condition was becoming worse over time, and she was diagnosed with exitus latalis in December 2022. At that time, the patient was discharged from hospital and was on palliative care at home under the control of her family physician.

Indications and surgical options for small bowel, large bowel and perianal Crohn's disease

Despite advancements in medical therapy of Crohn's disease(CD), majority of patients with CD will eventually require surgical intervention, with at least a third of patients requiring multiple surgeries. It is important to understand the role and timing of surgery, with the goals of therapy to reduce the need for surgery without increasing the odds of emergency surgery and its associated morbidity, as well as to limit surgical recurrence and avoid intestinal failure. The profile of CD patients requiring surgical intervention has changed over the decades with improvements in medical therapy with immunomodulators and biological agents. The most common indication for surgery is obstruction from stricturing disease, followed by abscesses and fistulae. The risk of gastrointestinal bleeding in CD is high but the likelihood of needing surgery for bleeding is low. Most major gastrointestinal bleeding episodes resolve spontaneously, albeit the risk of re-bleeding is high. The risk of colorectal cancer associated with CD is low. While current surgical guidelines recommend a total proctocolectomy for colorectal cancer associated with CD, subtotal colectomy or segmental colectomy with endoscopic surveillance may be a reasonable option. Approximately 20%-40% of CD patients will need perianal surgery during their lifetime. This review assesses the practice parameters and guidelines in the surgical management of CD, with a focus on the indications for surgery in CD(and when not to operate), and a critical evaluation of the timing and surgical options available to improve outcomes and reduce recurrence rates.

Management of perianal fistulas in Crohn's disease:An upto-date review

Perianal disease is one of the most disabling manifestations of Crohn's disease.A multidisciplinary approach of gastroenterologist,colorectal surgeon and radiologist is necessary for its management.A correct diagnosis,based on endoscopy,magnetic resonance imaging,endoanal ultrasound and examination under anesthesia,is crucial for perianal fistula treatment.Available medical and surgical therapies are discussedin this review,including new local treatment modalities that are under investigation.

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.

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.

Burden and outcomes for complex perianal fistulas in Crohn's disease:Systematic review

AIM To systematically review the literature on epidemiology,disease burden, and treatment outcomes for Crohn's disease(CD) patients with complex perianal fistulas.METHODS PubMed, Embase, and Cochrane were searched for relevant articles(published 2000-November 2016) and congress abstracts(published 2011-November 2016).RESULTS Of 535 records reviewed, 62 relevant sources were identified(mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14%(follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment(failure and relapse rates,respectively: medical, 12%-73% and 0%-41%; surgical:0%-100% and 11%.20%; combined medical/surgical:0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies(1 of infliximab; 3 of surgical interventions)have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD.CONCLUSION Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to antitumour necrosis factor-α agents, as evidenced by high failure and relapse rates.

Does capsule endoscopy have an added value in patients with perianal disease and a negative work up for Crohn's disease?

AIM:To investigate the role of capsule endoscopy in patients with persistent perianal disease and negative conventional work up for Crohn's disease(CD).METHODS:Patients with perianal disease(abscesses,fistulas,recurrent fissures) were evaluated for underlying CD.Patients who had a negative work up,defined as a negative colonoscopy with a normal ileoscopy or a normal small bowel series or a normal CT/MR enterography,underwent a Pillcam study of the small bowel after signing informed consent.Patients using nonsteroidal anti-inflammatory drugs or who had a history of inflammatory bowel disease or rheumatic disease were excluded.RESULTS:We recruited 26 patients aged 21-61 years(average 35.6 years),17 males and 9 females.One case could not be evaluated since the capsule did not leave the stomach.In 6 of 25(24%) patients with a negative standard work up for Crohn's disease,capsuleendoscopy(CE) findings were consistent with Crohn's disease of the small bowel.Family history of CD,white blood cell,hemoglobin,erythrocyte sedimentation rate or C-reactive protein did not predict a diagnosis of CD.Capsule endoscopy findings led to a change in treatment.CONCLUSION:In patients with perianal disease and a negative conventional work up to exclude CD,CE leads to incremental diagnostic yield of 24%.

Optimized timing of using infliximab in perianal fistulizing Crohn's disease

Infliximab(IFX),as a drug of first-line therapy,can alter the natural progression of Crohn’s disease(CD),promote mucosal healing and reduce complications,hospitalizations,and the incidence of surgery.Perianal fistulas are responsible for the refractoriness of CD and represent a more aggressive disease.IFX has been demonstrated as the most effective drug for the treatment of perianal fistulizing CD.Unfortunately,a significant proportion of patients only partially respond to IFX,and optimization of the therapeutic strategy may increase clinical remission.There is a significant association between serum drug concentrations and the rates of fistula healing.Higher IFX levels during induction are associated with a complete fistula response in these patients.Given the apparent relapse of perianal fistulizing CD,maintenance therapy with IFX over a longer period seems to be more beneficial.It appears that patients without deep remission are at an increased risk of relapse after stopping anti-tumor necrosis factor agents.Thus,only patients in prolonged clinical remission should be considered for withdrawal of IFX treatment when biomarker and endoscopic remission is demonstrated,especially when the hyperintense signals of fistulas on T2-weighed images have disappeared on magnetic resonance imaging.Fundamentally,the optimal timing of IFX use is highly individualized and should be determined by a multidisciplinary team.

Multidisciplinary and evidence-based management of fistulizing perianal Crohn's disease

Perianal symptoms are common in patients with Crohn's disease and cause considerable morbidity. The etiology of these symptoms include skin tags, ulcers, fissures, abscesses, fistulas or stenoses. Fistula is the most common perianal manifestation. Multiple treatment options exist although very few are evidence-based. The phases of treatment include: drainage of infection, assessment of Crohn's disease status and fistula tracts, medical therapy, and selective operative management. The impact of biological therapy on perianal Crohn's disease is uncertain given that outcomes are conflicting. Operative treatment to eradicate the fistula tract can be attempted once infection has resolved and Crohn's disease activity is controlled. The operative approach should be tailored according to the anatomy of the fistula tract. Definitive treatment is challenging with medical and operative treatment rarely leading to true healing with frequent complications and recurrence. Treatment success must be weighed against the risk of complications, specially anal sphincter injury. A full understanding of the etiology and all potential therapeutic options is critical for success. Multidisciplinary management of fistulizing perianal Crohn's disease is crucial toimprove outcomes.

Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn’s disease

BACKGROUND Tumor necrosis factor-alpha inhibitors,including infliximab and adalimumab,are effective medical treatments for perianal fistulising Crohn’s disease(CD),but not all patients achieve fistula healing.AIM To determine the correlation between perianal fistula healing and closure with infliximab and adalimumab trough levels.METHODS In this multicentre retrospective study conducted across four tertiary inflammatory bowel disease centres in Australia,we identified CD patients with perianal fistulae on maintenance infliximab or adalimumab who had a trough level within twelve weeks of clinical assessment.Data collected included demographics,serum infliximab and adalimumab trough levels(mg/L)within 12 wk before or after their most recent clinical assessment and concomitant medical or surgical therapy.The primary outcome was fistula healing,defined as cessation in fistula drainage.The secondary outcome was fistula closure,defined as healing and closure of all external fistula openings.Differences between patients who did or did not achieve fistula healing were compared using the chi-square test,t test or Mann-Whitney U test.RESULTS One hundred and fourteen patients(66 infliximab,48 adalimumab)were included.Forty-eight(72.7%)patients on maintenance infliximab achieved fistula healing and 18(27.3%)achieved fistula closure.Thirty-seven(77%)patients on maintenance adalimumab achieved fistula healing and 17(35.4%)achieved fistula closure.Patients who achieved fistula healing had significantly higher infliximab and adalimumab trough levels than patients who did not[infliximab:6.4(3.8-9.5)vs 3.0(0.3-6.2)mg/L,P=0.003;adalimumab:9.2(6.5-12.0)vs 5.4(2.5-8.3)mg/L,P=0.004].For patients on infliximab,fistula healing was associated with lower rates of detectable anti-infliximab antibodies and younger age.For patients on adalimumab,fistula healing was associated with higher rates of combination therapy with an immunomodulator.Serum trough levels for patients with and without fistula closure were not significantly different for infliximab[6.9(4.3-10.2)vs 5.5(2.5-8.3)mg/L,P=0.105]or adalimumab[10.0(6.6-12.0)vs 7.8(4.2-10.0)mg/L,P=0.083].CONCLUSION Higher maintenance infliximab and adalimumab trough levels are associated with perianal fistula healing in CD.

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.

Review of stem cells as promising therapy for perianal disease in inflammatory bowel disease

Those patients with perianal Crohn's disease or ul-cerative colitis experience a difficult to treat disease process with a delayed state and often inability to heal despite current therapies. The approaches currently used to treat these patients with corticosteroids,antibiotics,immunomodulators, anti-tumor necrosis factor-α drug, and surgical repair are limited in their healing ability. This review presents all current literature since emergence in the early 2000s of stem cell therapy for patients with perianal inflammatory bowel disease and analyzes the efficacy, outcomes and safety within these studies.

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.