Diagnosis and Management of Biliary Strictures after Deceased-Donor Liver Transplantation Based on Clinical Practice

Biliary complications are still the main complications for liver transplantation recipients. Biliary strictures comprise the major part of all biliary complications after deceased-donor liver transplantation (LT). Biliary strictures following LT are divided into anastomotic strictures (AS) and non-anastomotic strictures (NAS). A Limitation of current published researches is that most studies aren’t based on clinical practice. The aim of this review is to summarize risk factors, clinical presentation, diagnosis and management in post-LT biliary strictures.

Clinical approach to indeterminate biliary strictures:Clinical presentation,diagnosis,and workup

Despite advances in cross-sectional imaging and endoscopic technology,bile duct strictures remain a challenging clinical entity.It is crucial to make an early determination of benign or malignant nature of biliary strictures.Early diagnosis not only helps with further management but also minimizes mortality and morbidity associated with delayed diagnosis.Conventional imaging and endoscopic techniques,particularly endoscopic retrograde cholangiopancreatography(ERCP)and tissue sampling techniques play a key in establishing a diagnosis.Indeterminate biliary strictures(IDBSs)have no definite mass on imaging or absolute histopathological diagnosis and often warrant utilization of multiple diagnostics to ascertain an etiology.In this review,we discuss possible etiologies,clinical presentation,diagnosis,and management of IDBSs.Based on available data and expert opinion,we depict an evidence based diagnostic algorithm for management of IDBSs.Areas of focus include use of traditional tissue sampling techniques such as ERCP with brush cytology,intraductal biopsies,fluorescence in situ hybridization and flow cytometry.We also describe the role of endoscopic ultrasound(EUS)-guided fine needle aspiration and biopsies,cholangioscopy,confocal laser endomicroscopy,and intraductal EUS in management of IDBSs.

Still elusive: Developments in the accurate diagnosis of indeterminate biliary strictures

Indeterminate biliary strictures pose a significant diagnostic dilemma for gastroenterologists.Despite advances in endoscopic techniques and instruments,it is difficult to differentiate between benign and malignant pathology.A positive histological diagnosis is always preferred prior to high risk hepatobiliary surgery,or to inform other types of therapy.Endoscopic retrograde cholangiopancreato-graphy with brushings has low sensitivity and despite significant improvements in instruments there is still an unacceptably high false negative rate.Other methods such as endoscopic ultrasound and cholangioscopy have improved diagnostic quality.In this review we explore the techniques available to aid accurate diagnosis of indeterminate biliary strictures and obtain accurate hist-ology to facilitate clinical management.

Endoscopic management of benign biliary strictures:Looking for the best stent to place

Benign biliary strictures(BBS)might occur due to different pancreaticobiliary conditions.The etiology and location of biliary strictures are responsible of a wide array of clinical manifestations.The endoscopic approach endoscopic retrograde cholangiopancreatography represents the first-line treatment for BBS,considering interventional radiology and surgery when endoscopic treatment fails or it is not suitable.The purpose of this review is to provide an overview of possible endoscopic treatments for the optimal management of this subset of patients.

Management of urethral strictures and stenosis caused by the endo-urological treatment of benign prostatic hyperplasiad-a single-center experience

Objective:Urethral stricture disease after endo-urological treatment of benign prostatic hyperplasia(BPH)is a sparsely described complication.We describe management of five categories of these strictures in this retrospective observational case series.Methods:One hundred and twenty-one patients presenting with symptoms of bladder outflow obstruction after endo-urological intervention for BPH from February 2016 to March 2019 were evaluated.Among them,76 were eligible for this study and underwent reconstructive surgery.Preoperative and postoperative assessments were done with symptom scores,uroflowmetry,ultrasound for post-void residue,and urethrogram.Any intervention during follow-up was classed as a failure.The recurrence and 95%confidence interval for recurrence percentage were calculated.Results:The following five categories of patients were identified:Bulbo-membranous(33[43.4%]),navicular fossa(21[27.6%]),penile/peno-bulbar(8[10.5%]),bladder neck stenosis(6[7.9%]),and multiple locations(8[10.5%]).The average age was 69 years(range:60-84 years).Overall average symptom score,flow rate,and post-void residue changed from 21 to 7,6 mL/s to 19 mL/s,and 210 mL to 20 mL,respectively.The average follow-up was 34 months(range:12-58 months).Overall recurrence and complication rates were 10.5%and 9.2%,respectively.The recurrence in each category was seen in 3,1,2,1,and 1 patient,respectively.Overall 95% confidence interval for recurrence percentage was 4.66-19.69.Conclusion:Urethral stricture disease is a major long-term complication of endo-urological treatment of BPH.The bulbo-membranous strictures need continence preserving approach.Navicular fossa strictures require minimally invasive and cosmetic consideration.Peno-bulbar strictures require judicious use of grafts and flaps.Bladder neck stenosis in this cohort could be treated with endoscopic measures.Multiple locations need treatment based on their sites in single-stage as far as possible.

Double-face urethroplasty in patients with obliterative bulbar strictures post-transurethral resection of the prostate mid-term outcomes in high-volume referral center

Objective Incidences of post-transurethral resection of the prostate(post-TURP)strictures are between 2.2%and 9.8%.Stricture commonly occurs within the first 6 months.Our objective was to assess the outcomes of patients with obliterative strictures post-TURP that underwent a double-face urethroplasty.Methods This is a single-center prospective study of 17 patients with obliterative proximal bulbar stricture post-TURP who underwent double-face graft urethroplasty by two surgeons between January 2014 and January 2020.We defined post-TURP obliterative strictures as those patients who presented with complete or almost complete obstruction of the urethral lumen and who have had a history of acute urine retention.We have excluded patients with bladder neck contracture.Primary outcome was treatment success,defined as the no need for further treatments.Secondary outcome was post-urethroplasty continent rate.Results Seventeen patients were included in the study with median age of 66(interquartile range 40-77)years;median time of follow-up was 24(interquartile range 12-84)months;median stricture length was 4(interquartile range 2-6)cm.Of the 17 patients,15(88.2%)were successful.All patients were continent after urethroplasty.Conclusion With mid-term follow-up,treatment of obliterative proximal bulbar strictures with double-face buccal mucosa graft is a safe and effective procedure.Obliterative proximal bulbar strictures merit double-face urethroplasty with high-rate success and functional outcomes.

Direct Visual Internal Urethrotomy (DVIU) in the Management of Male Urethral Strictures. A Single Center Experience about 44 Patients

Introduction: Male urethral stricture is one of the oldest urological disorders. Many techniques have been proposed to treat them, including endoscopic internal urethrotomy (DVIU). Material and Methods: To evaluate the contribution of this technique in the treatment of urethra narrowing, a retrospective study on the records of patients with urethral stricture treated with endoscopic internal urethrotomy between January 2014 and December 2021 in the urology division of the Souro Sanou University Teaching Hospital. Results: A total of 44 male patients with urethral stricture were treated with this technique and 48 procedures were performed. The average age of the patients was 53.2 ± 18.2 years. The etiology of the stricture was dominated by iatrogenic, infectious, traumatic and idiopathic causes in 43.2% (n = 19), 27.3% (n = 12), 20.4 % (n = 9), and 9.1% (n = 4) respectively. The location of the stricture was bulbar in 72.7%, and the anterior penile urethra in 15.9%. The overall success rate was 72.7% with satisfactory urination without dysuria, evaluated after removal of the urinary catheter, at three months this rate fell to 69.1%, and at 6 months this rate was 67.5%. Five cases (5) of extravasation of blood or irrigation fluid into the scrotum were reported and managed conservatively as well as two (2) cases of false routes with postoperative oedema of the penis were observed. Conclusion: DVIU is a simple technique, free of major morbidity and requiring only short-term hospitalization. It can be proposed as a first-line treatment for urethral stricture.

Endoscopic incisional therapy for benign esophageal strictures: Technique and results

Benign esophageal strictures refractory to the conventional balloon or bougie dilatation may be subjected to various adjunctive modes of therapy, one of them being endoscopic incisional therapy(EIT). A proper delineation of the stricture anatomy is a prerequisite. A host of electrocautery and mechanical devices may be used, the most common being the use of needle knife, either standard or insulated tip. The technique entails radial incision and cutting off of the stenotic rim. Adjunctive therapies, to prevent re-stenosis, such as balloon dilatation, oral or intralesional steroids or argon plasma coagulation can be used. The common strictures where EIT has been successfully used are Schatzki's rings(SR) and anastomotic strictures(AS). Short segment strictures(< 1 cm) have been found to have the best outcome. When compared with routine balloon dilatation, EIT has equivalent results in treatment na?ve cases but better long term outcome in refractory cases. Anecdotal reports of its use in other types of strictures have been noted. Post procedure complications of EIT are mild and comparable to dilatation therapy. As of the current evidence, incisional therapy can be used for management of refractory AS and SR with relatively short stenosis(< 1 cm) with good safety profile and acceptable long term patency.

A brief review on anterior urethral strictures

The treatment of urethral strictures remains a challenging field in urology even though there are a variety of procedures to treat it at present,as no one approach is superior over another.This paper reviewed the surgical options for the management of different sites and types of anterior urethral stricture,providing a brief discussion of the controversies regarding this issue and suggesting possible future advancements.Among the existing procedures,simple dilation and direct vision internal urethrotomy are more commonly used for short urethral strictures(<1 cm,soft and no previous intervention).Currently,urethroplasty using buccal mucosa or penile skin is the most widely adopted clinical techniques and have proved successful.Nonetheless,complications such as donor site morbidity remain problem.Tissue engineering techniques are considered as a promising solution for urethral reconstruction,but require further investigation,as does stem cell therapy.

Endoscopic balloon dilation of crohn's disease stricturessafety,efficacy and clinical impact

AIM To evaluate the incidence of anastomotic strictures after intestinal resection in Crohn's disease(CD), demonstrate long-term efficacy and safety of endoscopic balloon dilation(EBD) in CD strictures and its impact on the diagnosis of subclinical postoperative endoscopic recurrence. METHODS Retrospective single tertiary center study based on prospectively collected data between 2010 and 2015including anastomotic and non-anastomotic strictures. RESULTS29% of 162 CD patients included developed an anastomotic stricture. 43 patients with anastomotic strictures and 37 with non-anastomotic strictures underwent EBD; technical success was 97.7% and 100%, respectively, however, 63% and 41% needed repeat dilation during the 4.4-year follow-up. Longer periods between surgery and index colonoscopy and higher lactoferrin levels were associated with the presence of stricture after surgery. Calprotectin levels > 83.35 μg/g and current or past history of smoking were associated with a shorter time until need for dilation(HR = 3.877, 95%CI: 1.480-10.152 and HR = 3.041, 95%CI: 1.213-7.627). Anastomotic strictures had a greater need for repeat dilation(63% vs 41%, P = 0.047). No differences were found between asymptomatic and symptomatic cohorts. Disease recurrence diagnosis was only possible after EBD in a third of patients. CONCLUSION EBD is an effective and safe alternative to surgery, with a good short and long-term outcome, postponing or even avoiding further surgery. EBD may allow to diagnose disease recurrence in patients with no clinical signs/biomarkers of disease activity.

Intraductal ultrasound substantiates diagnostics of bile duct strictures of uncertain etiology

AIM:To report the largest patient cohort study investigating the diagnostic yield of intraductal ultrasound (IDUS) in indeterminate strictures of the common bile duct.METHODS:A patient cohort with bile duct strictures of unknown etiology was examined by IDUS.Sensitivity,specificity and accuracy rates of IDUS were calculated relating to the definite diagnoses proved by histopathology or long-term follow-up in those patients who did not undergo surgery.Analysis of the endosonographic report allowed drawing conclusions with respect to the T and N staging in 147 patients.IDUS staging was compared to the postoperative histopathological staging data allowing calculation of sensitivity,specificity and accuracy rates for T and N stages.The endoscopic retrograde cholangio-pancreatography and IDUS procedures were performed under fluoroscopic guidance using a side-viewing duodenoscope (Olympus TJF 160,Olympus,Ltd.,Tokyo,Japan).All procedures were performed under conscious sedation (propofol combined with pethidine) according to the German guidelines.For IDUS,a 6 F or 8 F ultrasound miniprobe was employed with a radial scanner of 15-20 MHz at the tip of the probe (Aloka Co.,Tokyo,Japan).RESULTS:A total of 397 patients (210 males,187 females,mean age 61.43 ± 13 years) with indeterminate bile duct strictures were included.Two hundred and sixty-four patients were referred to the department of surgery for operative exploration,thus surgical histopathological correlation was available for those patients.Out of 264 patients,174 had malignant disease proven by surgery,in 90 patients benign disease was found.In these patients decision for surgical exploration was made due to suspicion for malignant disease in multimodal diagnostics (computed tomography scan,endoscopic ultrasound or magnetic resonance imaging).Twenty benign bile duct strictures were misclassified by IDUS as malignant while 14 patients with malignant strictures were initially misdiagnosed by IDUS as benign resulting in sensitivity,specificity and accuracy ratesof 93.2%,89.5% and 91.4%,respectively.In the subgroup analysis of malignancy prediction,IDUS showed best performance in cholangiocellular carcinoma as underlying disease (sensitivity rate,97.6%) followed by pancreatic carcinoma (93.8%),gallbladder cancer (88.9%) and ampullary cancer (80.8%).A total of 133 patients were not surgically explored.32 patients had palliative therapy due to extended tumor disease in IDUS and other imaging modalities.Ninety-five patients had benign diagnosis by IDUS,forceps biopsy and radiographic imaging and were followed by a surveillance protocol with a follow-up of at least 12 mo;the mean follow-up was 39.7 mo.Tumor localization within the common bile duct did not have a significant influence on prediction of malignancy by IDUS.The accuracy rate for discriminating early T stage tumors (T1) was 84% while for T2 and T3 malignancies the accuracy rates were 73% and 71%,respectively.Relating to N0 and N1 staging,IDUS procedure achieved accuracy rates of 69% for N0 and N1,respectively.Limitations:Pretest likelihood of 52% may not rule out bias and overinterpretation due to the clinical scenario or other prior performed imaging tests.CONCLUSION:IDUS shows good results for accurate diagnostics of bile duct strictures of uncertain etiology thus allowing for adequate further clinical management.

Current diagnosis and treatment of benign biliary stricturesafter living donor liver transplantation

Despite advances in surgical techniques, benign biliary strictures after living donor liver transplantation(LDLT) remain a significant biliary complication and play an important role in graft and patient survival. Benign biliary strictures after transplantation are classified into anastomotic or non-anastomotic strictures. These two types differ in presentation, outcome, and response to therapy. The leading causes of biliary strictures include impaired blood supply, technical errors during surgery, and biliary anomalies. Because patients usually have non-specific symptoms, a high index of suspicion should be maintained. Magnetic resonance cholangiography has gained widespread acceptance as a reliable noninvasive tool for detecting biliary complications. Endoscopy has played an increasingly prominent role in the diagnosis and treatment of biliary strictures after LDLT. Endoscopic management in LDLT recipients may be more challenging than in deceased donor liver transplantation patients because of the complex nature of the duct-to-duct reconstruction. Repeated aggressive endoscopic treatment with dilation and the placement of multiple plastic stents is considered the first-line treatment for biliary strictures. Percutaneous and surgical treatments are now reserved for patients for whom endoscopic management fails and for those with multiple, inaccessible intrahepatic strictures or Roux-en-Y anastomoses. Recent advances in enteroscopy enable treatment, even in these latter cases. Direct cholangioscopy, another advanced form of endoscopy, allows direct visualization of the inner wall of the biliary tree and is expected to facilitate stenting or stone extraction. Rendezvous techniques can be a good option when the endoscopic approach to the biliary stricture is unfeasible. These developments have resulted in almost all patients being managed by the endoscopic approach.

Comparative analysis of ERCP,IDUS,EUS and CT in predicting malignant bile duct strictures

AIM:To compare endoscopic retrograde cholangio-pancreatography(ERCP),intraductal ultrasound(IDUS),endosonography(EUS),endoscopic transpapillary forceps biopsies(ETP)and computed tomography(CT)with respect to diagnosing malignant bile duct strictures.METHODS:A patient cohort with bile duct strictures of unknown etiology was examined by ERCP and IDUS,ETP,EUS,and CT.The sensitivity,specificity,and accuracy rates of the diagnostic procedures were calculated based on the definite diagnoses proved by histopathology or long-term follow-up in those patients who did not undergo surgery.For each of the diagnostic measures,the sensitivity,specificity,and accuracy rates were calculated.In all cases,the gold standard was the histopathologic staging of specimens or long-term follow-up of at least 12 mo.A comparison of the accuracy rates between the localization of strictures was performed by using the Mann-Whitney U-test and theχ2test as appropriate.A comparison of the accuracy rates between the diagnostic procedures was performed by using the McNemar’s test.Differences were considered statistically significant if P<0.05.RESULTS:A total of 234 patients(127 males,107 females,median age 64,range 20-90 years)with indeterminate bile duct strictures were included.A total of 161patients underwent operative exploration;thus,a surgical histopathological correlation was available for those patients.A total of 113 patients had malignant disease proven by surgery;in 48 patients,benign disease was surgically found.In these patients,the decision for surgical exploration was made due to the suspicion of malignant disease in multimodal diagnostics(ERCP,CT,or EUS).Fifty patients had a benign diagnosis and were followed by a surveillance protocol with a followup of at least 12 mo;the median follow-up was 34 mo.Twenty-three patients had extended malignant disease,and thus were considered palliative.A comparison of the different diagnostic tools for detecting bile duct malignancy resulted in accuracy rates of 91%(ERCP/IDUS),59%(ETP),92%(IDUS+ETP),74%(EUS),and 73%(CT),respectively.In the subgroup analysis,the accuracy rates(%,ERCP+IDUS/ETP/IDUS+ETP;EUS;CT)for each tumor entity were as follows:cholangiocellular carcinoma:92%/74%/92%/70%/79%;pancreatic carcinoma:90%/68%/90%/81%/76%;and ampullary carcinoma:88%/90%/90%/76%/76%.The detection rate of malignancy by ERCP/IDUS was superior to ETP(91%vs 59%,P<0.0001),EUS(91%vs74%,P<0.0001)and CT(91%vs 73%,P<0.0001);EUS was comparable to CT(74%vs 73%,P=0.649).When analyzing accuracy rates with regard to localization of the bile duct stenosis,the accuracy rate of EUS for proximal vs distal stenosis was significantly higher for distal stenosis(79%vs 57%,P<0.0001).CONCLUSION:ERCP/IDUS is superior to EUS and CT in providing accurate diagnoses of bile duct strictures of uncertain etiology.Multimodal diagnostics is recommended.

Biliary strictures complicating living donor liver transplantation:Problems,novel insights and solutions

Biliary stricture complicating living donor liver transplantation(LDLT) is a relatively common complication, occurring in most transplant centres across the world. Cases of biliary strictures are more common in LDLT than in deceased donor liver transplantation. Endoscopic management is the mainstay for biliary strictures complicating LDLT and includes endoscopic retrograde cholangiography, sphincterotomy and stent placement(with or without balloon dilatation). The efficacy and safety profiles as well as outcomes of endoscopic management of biliary strictures complicating LDLT is an area that needs to be viewed in isolation, owing to its unique set of problems and attending complications; as such, it merits a tailored approach, which is yet to be well established. The diagnostic criteria applied to these strictures are not uniform and are over-reliant on imaging studies showing an anastomotic narrowing. It has to be kept in mind that in the setting of LDLT, a subjective anastomotic narrowing is present in most cases due to a mismatch in ductal diameters. However, whether this narrowing results in a functionally significant narrowing is a question that needs further study. In addition, wide variation in the endotherapy protocols practised in most centres makes it difficult to interpret the results and hampers our understanding of this topic. The outcome definition for endotherapy is also heterogenous and needs to be standardised to allow for comparison of data in this regard and establish a clinical practice guideline. There have been multiple studies in this area in the last 2 years, with novel findings that have provided solutions to some of these issues. This review endeavours to incorporate these new findings into the wider understanding of endotherapy for biliary strictures complicating LDLT, with specific emphasis on diagnosis of strictures in the LDLT setting, endotherapy protocols and outcome definitions. An attempt is made to present the best management options currently available as well as directions for future research in the area.

Intralesional steroid injection therapy in the management of resistant gastrointestinal strictures

Esophageal strictures are a problem frequently encountered by gastroenterologists. Dilation has been the customary treatment for benign esophageal strictures, and dilation techniques have advanced over the years. Depending on their characteristics and the response to treatment, esophageal strictures can be classified into two types: 1, simple (Schatzki rings, webs, peptic injury, and following sclerotherapy) - these are easily amenable to dilation, with a low recurrence rate after initial treatment; and 2, complex (caused by caustic ingestion, radiation injury, anastomotic strictures, and photodynamic therapy) - these are difficult to dilate and are associated with higher recurrence rates. Refractory strictures are those in which it is not possible to relieve the anatomic restriction successfully up to a diameter of 14 mm over five sessions at 2-weekly in- tervals, due to cicatricial luminal compromise or fibrosis; and recurrent strictures are those in which it is not possible to maintain a satisfactory luminal diameter for 4 wk once the target diameter of 14 mm has been achieved. There are no standard recommendations for the management of refractory strictures. The various techniques used include intralesional steroid injectioncombined with dilation; endoscopic incisional therapy, with or without dilation; placement of self-expanding metal stents, Polyflex stents, or biodegradable stents; self-bougienage; and endoscopic surgery. This review discusses the indications, technique, results, and complications of the use of intralesional steroid injections combined with dilation and endoscopic incisional therapy with dilation in refractory strictures.

Interventional management of tracheobronchial strictures

Tracheobronchial balloon dilation and stent placement have been well used in the treatment of patients with benign and/or malignant diseases.Balloon dilation is the first option in the treatment of benign airway stenosis.Although balloon dilation is simple and fast,recurrence rate is high.Stent placement promptly relieves acute airway distress from malignant extraluminal and intraluminal airway obstruction.Temporary stent placement may be an alternative for benign airway strictures refractory to balloon dilation.This article reviews the indications,pre-procedure evaluation,technique,outcomes and complications of balloon dilation and stent placement with regard to benign and malignant tracheobronchial stenoses.

Role of endoscopic retrograde cholangiopancreatography inthe management of benign biliary strictures:What's new?

Benign biliary strictures comprise a heterogeneous group of diseases. The most common strictures amenable to endoscopic treatment are post-cholecystectomy, post-liver transplantation, related to primary sclerosing cholangitis and to chronic pancreatitis. Endoscopic treatment of benign biliary strictures is widely used as first line therapy, since it is effective, safe, noninvasive and repeatable. Endoscopic techniques currently used are dilation, multiple plastic stents insertion and fully covered self-expandable metal stents. The main indication for dilation alone is primary sclerosing cholangitis related strictures. In the vast majority of the remaining cases, temporary placement of multiple plastic stents with/without dilation is considered the treatment of choice. Although this approach is effective, it requires multiple endoscopic sessions due to the short duration of stent patency. Fully covered self-expandable metal stents appear as a good alternative to plastic stents, since they have an increased radial diameter, longer stent patency, easier insertion technique and similar efficacy. Recent advances in endoscopic technique and various devices have allowed successful treatment in most cases. The development of novel endoscopic techniques and devices is still ongoing.

Management issues in post living donor liver transplant biliary strictures

Biliary complications are common after living donor liver transplant(LDLT) although with advancements in surgical understanding and techniques, the incidence is decreasing. Biliary strictures are more common than leaks. Endoscopic retrograde cholangiopancreatography(ERCP) is the first line modality of treatment of post LDLT biliary strictures with a technical success rate of 75%-80%. Most of ERCP failures are successfully treated by percutaneous transhepatic biliary drainage(PTBD) and rendezvous technique. A minority of patients may require surgical correction. ERCP for these strictures is technically more challenging than routine as well post deceased donor strictures. Biliary strictures may increase the morbidity of a liver transplant recipient, but the mortality is similar to those with or without strictures. Post transplant strictures are short segment and soft, requiring only a few session of ERCP before complete dilatation. Long-term outcome of patients with biliary stricture is similar to those without stricture. With the introduction of new generation cholangioscopes, ERCP success rate may increase, obviating the need for PTBD and surgery in these patients.

Short- and long-term efficacy of endoscopic balloon dilation in Crohn's disease strictures

AIM:To evaluate short- and long-term efficacy of endoscopic balloon dilation in a cohort of consecutive patients with symptomatic Crohn's disease (CD)-related strictures. METHODS:Twenty-six CD patients (11 men; median age 36.8 year, range 11-65 years) with 27 symptomatic strictures underwent endoscopic balloon dilation (EBD).Both naive and post-operative strictures, of any length and diameter, with or without associated fistula were included. After a clinical and radiological assessment, EBD was performed with a Microvasive Rigiflex through the scope balloon system. The procedure was considered successful if no symptom reoccurred in the following 6 mo. The long-term clinical outcome was to avoid surgery. RESULTS:The mean follow-up time was 40.7 ± 5.7 mo (range 10-94 mo). In this period, forty-six EBD were performed with a technical success of 100%. No procedure-related complication was reported. Surgery was avoided in 92.6% of the patients during the entire follow-up. Two patients, both presenting ileocecal strictures associated with fistula, failed to respond to the treatment and underwent surgical strictures resection. Of the 24 patients who did not undergo surgery, 11 patients received 1 EBD, and 13 required further dilations over time for the treatment of relapsing strictures (7 patients underwent 2 dilations, 5 patients 3 dilations, and 1 patient 4 dilations). Overall, the EBD success rate after the first dilation was 81.5%. No difference was observed between the EBD success rate for naive (n = 12) and post-operative (n = 15) CD related strictures (P > 0.05). CONCLUSION:EBD appears to be a safe and effective procedure in the therapeutic management of CD-related strictures of any origin and dimension in order to prevent surgery.

Structural and molecular features of intestinal strictures in rats with Crohn's-like disease

AIM: To develop a new rat model we wanted to gain a better understanding of stricture formation in Crohn's disease(CD).METHODS: Chronic colitis was induced locally by the administration of 2,4,6-trinitrobenzenesulfonic acid(TNBS). The relapsing inflammation characteristic to CD was mimicked by repeated TNBS treatments. Animals were randomly divided into control, once, twice and three times TNBS-treated groups. Control animals received an enema of saline. Tissue samples were taken from the strictured colonic segments and also adjacent proximally and distally to its 60, 90 or 120 d after the last TNBS or saline administrations. The frequency and macroscopic extent of the strictures were measured on digital photographs. The structural features of strictured gut wall were studied by light- and electron microscopy. Inflammation related alterations in TGF-beta 2 and 3, matrix metalloproteinases 9(MMP9) and TIMP1 m RNA and protein expression were determined by quantitative real-time PCR and western blot analysis. The quantitative distribution of caspase 9 was determined by post-embedding immunohistochemistry.RESULTS: Intestinal strictures first appeared 60 d after TNBS treatments and the frequency of them increased up to day 120. From day 90 an intact lamina epithelialis, reversible thickening of lamina muscularis mucosae and irreversible thickening of the muscularis externa were demonstrated in the strictured colonic segments. Nevertheless the morphological signs of apoptosis were frequently seen and excess extracellular matrix deposition was recorded between smooth muscle cells(SMCs). Enhanced caspase 9 expression on day 90 in the SMCs and on day 120 also in myenteric neurons indicated the induction of apoptosis. The m RNA expression profile of TGF-betas after repeated TNBS doses was characteristic to CD, TGF-beta 2, but not TGF-beta 3 was up-regulated. Overexpression of MMP9 and down-regulation of TIMP1 were demonstrated. The progressive increase in the amount of MMP9 protein in the strictures was also obvious between days 90 and 120 but TIMP1 protein was practically undetectable at this time.CONCLUSION: These findings indicate that aligned structural and molecular changes in the gut wall rather than neuronal cell death play the primary role in stricture formation.