Stricture Surgery Research Articles

Safety and Efficacy of Lumen-Apposing Metal Stents for Management of Late Refractory Gastro-jejunal Structures in Patients with Roux-en-Y Gastric Bypass (with Video).

Roux-en-Y gastric bypass (RYGB) related late gastro-jejunal (GJ) strictures are often resistant to endoscopic balloon dilations. Lumen-apposing metal stents (LAMSs) have been used to treat benign strictures with favorable results. However, the data remains limited to justify LAMS use for management of post-RYGB late GJ strictures. We aim to evaluate the safety and efficacy of LAMS placement for the management of late GJ strictures that are refractory to balloon dilations in post-RYGB patients. This was a single center retrospective study that included all post-RYGB patients who underwent LAMS placement for management of late GJ strictures that had previously failed balloon dilations. Primary outcomes were technical and clinical success, and secondary outcomes were LAMS-related adverse events. A total of 28 patients underwent LAMS placement for management of GJ strictures. Median age was 60.5 (IQR 50.5, 67.0) years and majority were females (27, 96.4%). Median interval between surgery and first diagnosis of GJ stricture was 13 years (IQR 7, 17.5). 20 × 10 mm LAMS was the most used stent (n = 24, 85.7%). The median procedure time was 23.5 (IQR 14.5, 32.0) minutes. Technical and short-term clinical success of LAMS placement was 100% (95% CI 87.9-100.0). Long-term success was achieved in 19 out of 25 patients (76.0%, 95% CI 56.6-88.5) that had over 3 months follow-up after LAMS removal. Stent migration was noted in 2 (7.1%) patients, and 1 (3.6%) patient each experienced pain and minor bleeding without the need for additional interventions. No patient in our cohort required surgical revision of GJ anastomosis. Placement of LAMS is safe, technically feasible, and associated with a high clinical success rate in patients with late GJ strictures after RYGB who have failed prior balloon dilations. Placement of LAMS can be considered early in patients requiring multiple balloon dilations.

Long-term follow-up of children with Crohn's disease and small bowel mucosal lesions detected through video capsule endoscopy.

We report disease outcomes of pediatric Crohn's disease (CD) affecting the proximal small bowel (SB) and detected through video capsule endoscopy (VCE). We undertook a retrospective review of CD patients with VCE performed under age 18 between 2003 and 2017 and having received any biologics. We identified patients from our institutional registry. Eligible patients (n = 118) had their first VCE performed after a median of 0.1 years after diagnostic endoscopies at a median age of 12.2 years. The proximal SB disease group (Paris classification L4b inclusive) comprised 70 patients with extensive SB lesions in 81% and deep ulcers in 79%. Patients with Paris L1-3 disease with no findings in VCE or disease restricted to the terminal ileum comprised the control group. At first VCE, levels of albumin (34 g/L vs. 37 g/L) and hemoglobin (117 g/L vs. 127 g/L) were lower in SB patients (p < 0.02). After the first VCE, 68% were introduced to biologics, while 10% already received them. Follow-up VCE was performed after a median of 2.4 years (SB group n = 42; controls n = 21). Proximal SB findings had disappeared in 40% of SB patients, and extensive lesions and deep ulcers had decreased to 26% and 29%, respectively (p = 0.001). In the control group, one had progressed to proximal disease. During the clinical follow-up of a median of 4.7 years, one patient with SB underwent surgery for a jejunal stricture. Proximal SB disease detected through capsule endoscopy abated in most patients with biological medication.

Effective use of semi-elemental diet in managing anastomotic leakage after surgery for esophageal stricture

Anastomotic leakage occurs in ±10% of patients after surgery for esophageal stricture. Management often requires re-surgery, which increases morbidity and mortality. This case report shows successful conservative management of anastomotic leakage with semi-elemental diet.

Changes in practices concerning urethral stricture surgery: Analysis of French data for the period 2013–2022

IntroductionThe prevalence of urethral stricture is estimated at 0.9%. American, European and French recommendations have reduced the place of endoscopic treatments due to their poor outcomes, especially in the case of repeated procedures. Urethroplasty is the new reference treatment for urethral stricture. Our aim was to assess the evolution of national practices from 2013 to 2022. Material and methodsWe collected national CCAM coding data for all procedures involving urethral stricture surgery using the Scansanté internet platform produced by the Technical Agency for Information on Hospitalization, which prospectively collects all procedures coded according to CCAM coding from public, liberal and ESPIC healthcare structures. ResultsThe overall number of urethral surgical procedures has been steadily increasing over the past 10 years. Endoscopic procedures remain largely predominant in 2022, totaling 23,982, but have remained stable over the decade. Urethroplasties have been on the rise since 2019, reaching 1600 cases in 2022 compared with 1100 cases in 2020. Although urethrotomies currently outnumber urethroplasties by a factor of 10, this ratio has been consistently decreasing since 2016. The most significant contributor to the 10-year increase is urethroplasty by augmentation, particularly free flap techniques on the anterior urethra. Resection-anastomosis and urethrostomy techniques have remained stable. DiscussionIn 2022, endoscopic treatments remain by far the majority, but urethroplasties are on the increase. A significant number of patients can benefit from initial endoscopic treatment because short bulbar localization is the most common presentation, but long-term success rates are poor compared to urethroplasty, which boasts approximately 80% success rates. Urethroplasty should no longer be considered a last-resort surgery but rather a reference technique in treating urethral stricture.

The use of amniotic membrane injection as an adjunct in endoscopic urethral stricture management.

Endoscopic urethral stricture treatment has high recurrence rates. Due to research supporting amniotic membrane's (AMs) anti-inflammatory and anti-fibrotic properties reducing scar tissue formation, AM has generated interest in reconstructive urethral surgery. To the best of our knowledge, we performed the first investigation of the success rate of urethral dilation when combined with micronized AM injection for the treatment of urethral stricture. Eligible patients were adult males with anterior strictures meeting strict criteria for diameter, length, International Prostate Symptom Score (IPSS), and flow rate. Micronized AM was injected in the stricture region during urethral dilation. The primary study endpoint was an anatomical success (≥14Fr) at 6 months. Secondary endpoints were evaluated with the IPSS, urethral stricture surgery - patient-related outcome measure, International Index of Erectile Function, flow rate, and postvoid residual. Outcomes were assessed at baseline and multiple points postinjection. Injection safety was analyzed. Ten men with a mean age of 52 years were included in the study. At 6 months, 7 of 10 patients demonstrated recurrence of the urethral stricture on cystoscopy. Improvements in secondary endpoints were noted in 10 of 10 patients at 3 months and 3 of 10 patients at 6 months. No adverse events were observed. To the best of our knowledge, this is the first study evaluating micronized AM injection as an adjunct treatment at the time of urethral dilation. The urethral stricture recurrence rate did not improve with the injection of AM despite the hypothesized benefits of anti-fibrotic and anti-inflammatory properties.

History and Determinant of Adult Neourethral Stricture After Hypospadias Repair in Childhood: A Single Center Study Derived From a Single Procedure by a Single Surgeon

ObjectiveTo elucidate the incidence, presentation timing, and determinants of adulthood neourethral strictures after childhood hypospadias repair, using data from a database derived from a single procedure performed by a single surgeon. MethodsPediatric patients with hypospadias who underwent staged surgery using a foreskin-derived neourethra served as the Denominator population. Clinical data from adult neourethral stricture patients who re-visited us were analyzed. ResultsFourteen of 723 Denominator population (1.9%) revisited for adult neourethral stricture. The median age at completion of the initial hypospadias repair was 6 years (IQR 4–7). Seven patients (50.0%) underwent surgical interventions in childhood, and six (42.9%) had a history of childhood stricture surgery at the age of 4–17 years (median, 5.5). Strictures sites were meatal in 3 (21.4%), entire neourethra in 2 (14.3%), and junctional in 9 (64.3%), with a median length of 17.5 mm (IQR 15–25). Urethral self-dilation was initiated in nine patients. Eleven patients, including six initially treated with self-dilation, required open urethral repair. Time from childhood repair to stricture symptoms ranged from 18 to 34 years (median, 26.5). Median ages at urethral stricture symptoms, re-visit, and open urethral repair were 34 (IQR 25–38), 38.5 (IQR 32–45) and 45 years (IQR 37–53), respectively. Multivariate Cox hazard analysis identified childhood surgical intervention post-initial repair as the only significant risk factor for neourethral stricture (p<0.05). ConclusionsThese results highlight the importance of educating patients about the risk of late strictures following childhood hypospadias repair.

Functional outcomes after supra-pubic phalloplasty

BACKGROUNDA thorough evaluation of the functional outcomes resulting from supra-pubic phalloplasty (SPP) assessing different aspects of the phalloplasty has not been reported. PURPOSE OF THE STUDYTo report the outcomes on sexuality, urinary function, satisfaction, and regrets following an SPP performed at our centre. SUBJECTS STUDIEDAll consecutive patients who underwent the 3-steps technique of pre-expanded SPP between 2007 and 2018 and who had at least 1 year of follow-up. METHODSQuestionnaires were sent to analyse several domains of penile reconstruction: sexuality, urinary function, perceived sensitivity, and satisfaction. Sexuality was evaluated using the Self Esteem and Relationship (SEAR) questionnaire. Urinary function was analysed based on the urethral stricture surgery PROM (USS-PROM) questionnaire. MAIN FINDINGSA total of 77 patients were included, 92.2% were transmen, and 33 (42.9%) responded to the questionnaire. Urethral lengthening (UL) was performed in 28 (36.4%) procedures and erectile prosthesis was implanted in 42 patients (54.5%). The mean length of the neophallus was 15.3cm (SD 2.6) and the mean girth was 11.8cm (SD 2.1). The mean total SEAR score (/100) was 73.8 (SD 26.7). The mean six-item LUTS score (/24) was 8.4 (SD 4.6). The standing position was the usual voiding position reported by 11 patients (73.3%). CONCLUSIONPre-expanded SPP is a robust technique that can achieve substantial flap dimensions, leading to high satisfaction with neophallus appearance and the choice of the phalloplasty technique. Overall sexual outcomes are mostly favourable. UL is feasible and effective in terms of voiding in a standing position.

Artificial urinary sphincter and stricture disease: surgical principles in management.

Iatrogenic stress urinary incontinence (SUI) is the most common complication of surgical treatment of prostate cancer, regardless of operative approach, and has a major impact on patients' quality of life. Although SUI can occur after surgical treatment of benign prostatic hyperplasia, specifically transurethral prostate resection, laser enucleation of the prostate, and simple open prostatectomy, these therapeutic modalities play a much less significant role in the etiology of SUI. Artificial urethral sphincter (AUS) implantation is considered the standard treatment modality providing high success rates, including durable efficacy, and optimal patient satisfaction for moderate to severe urinary incontinence resulting mainly from radical prostatectomy. However, although complication rates are generally acceptably low, revision and/or explantation may be required due to mechanical failure and non-mechanical problems, specifically urethral atrophy/cuff deficient occlusion, infection, and cuff erosion. Several risk factors for AUS failure associated with a fragile, compromised urethra have been identified and these play a critical role in device cuff erosion and subsequent removal of the device. Among others, apparently the most impacting factors are irradiation, urethral stent placement, a previous AUS placement, and importantly presence of urethral stricture or prior urethroplasty. Generally, any clinical situation leading to a diseased urethra or lack of urethral integrity is associated with impaired local blood perfusion, and consequently lower success rates. The present review aims to evaluate the impact of the presence of prior urethral strictures and urethroplasty on the outcomes of AUS implantation on one hand, and vice-versa, the influence of AUS placement on later urethral stricture surgery, particularly following cuff erosion.

Perineal Urethrostomy for Complex Urethral Strictures: Long-Term Patient-Reported Outcomes From a Reconstructive Referral Center and a Scoping Literature Review.

There is a paucity of long-term objective and patient-reported outcomes after definitive perineal urethrostomy for complex urethral strictures. Our objective is to determine comprehensive long-term success of perineal urethrostomy with our 15-year experience at a reconstructive referral center. Patients who underwent perineal urethrostomy between 2009 and 2023 were identified. A comprehensive long-term follow-up was conducted, evaluating both objective outcomes (retreatment-free survival) and subjective outcomes through the use of validated questionnaires. Additionally, to provide further context for our findings, we conducted a scoping review of all studies reporting outcomes following perineal urethrostomy. Among 76 patients, 55% had iatrogenic strictures, with 82% previously undergoing urethral interventions. At a median follow-up of 55 months, retreatment-free survival was 84%, with 16% of patients experiencing perineal urethrostomy recurrent stenosis. Patient-reported outcomes revealed a generally satisfactory voiding function (Urethral Stricture Surgery Patient-Reported Outcome Measure Lower Urinary Tract Symptoms score) and continence (International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form), with median scores of 4 (range 0-24) and 0 (range 0-21), but with bimodal distributions of sexual function scores (median International Index of Erectile Function-Erectile Function domain: 3.5; median Male Sexual Health Questionnaire-Ejaculation Scale: 21). Treatment satisfaction was very high with a median International Consultation on Incontinence Questionnaire-Satisfaction outcome score of 21 (range 0-24). The scoping review revealed varying success rates ranging from 51% to 95%, highlighting difficulties in comparison due to variable success definitions and patient case mix. Perineal urethrostomy provides effective treatment for complex anterior urethral strictures, with high patient satisfaction, preserved continence function, and favorable voiding outcomes. It presents a viable option for older and comorbid patients, especially after thorough counseling on expected outcomes and potential risks.

Patient-Related Factors Associated With Long-Term Outcomes After Successful Endoscopic Balloon Dilation For Crohn's Disease-Associated Ileo-Colic Strictures: A Systematic Review and Meta-analysis.

Successful Crohn's disease (CD) therapy relies on timely and precise management strategies. Endoscopic balloon dilation (EBD) has been applied as a first-line treatment for symptomatic CD-associated strictures due to its minimally invasive nature and the possibility of preserving intestinal length. The aim of the present study was to determine patient-related predictive factors associated with the need for surgery for CD-associated ileocolic strictures after technically successful EBD. All original studies published before December 2023 that reported the outcomes of patients treated with EBD for ileocolic strictures secondary to CD and described follow-up for at least 1 year were included. The difference in risk of needing surgery was calculated for 8 different patient characteristics (Sex, smoking habit, previous surgery, biologic therapy, steroids, immunosuppressors, nature of the stricture, and endoscopic disease activity). There were significant differences in the risk of needing surgery after EBD among patients who underwent surgery and patients without a history of surgery (RD: -0.20 [-0.31, -0.08]), patients with endoscopic mucosal activity and patients in remission at the time of EBD (RD: 0.19 [0.04, 0.34]), patients using biologics at the time of EBD and patients not using biologics (RD: -0.09 [-0.16, -0.03]), and patients using steroids and those not using steroids at the time of EBD (RD: 0.16 [0.07, 0.26]). The use of biologics and endoscopic disease remission at the time of EBD were protective factors against the need for surgery. No previous surgery or use of steroids at the time of EBD was associated with the need for surgery during follow-up.

Urethral-sparing laparoscopic simple prostatectomy for the treatment of benign prostatic hyperplasia with asymptomatic urethral stricture after urethral stricture surgery

ObjectiveTo evaluate the efficacy of urethral-sparing laparoscopic simple prostatectomy (US-LSP) for the treatment of large-volume (>80 ml) benign prostatic hyperplasia (BPH) with asymptomatic urethral stricture (urethral lumen > 16 Fr) after urethral stricture surgery.MethodsWe retrospectively analyzed clinical data of 39 large-volume BPH patients with asymptomatic urethral stricture after urethral stricture surgery who underwent US-LSP from January 2016 to October 2021. Postoperative follow-ups were scheduled at 1, 3, and 6 months.ResultsAll patients affected by significant BPH-related lower urinary tract symptoms (LUTS) including 22 cases with asymptomatic anterior urethral stricture and 17 cases with asymptomatic posterior urethral stricture. Median operative time was 118 min (interquartile range [IQR]100–145). Median estimated blood loss was 224 ml (IQR: 190–255). 33 patients(84.6%) avoided continuous bladder irrigation. Postoperative complications occurred in 5 patients (12.8%), including 4 cases with Clavien-Dindo grade 1 and grade 2 and 1 case with grade 3a. During follow-up, US-LSP presented statistically significant improvements in LUTS compared to baseline (P < 0.05). A total of 25 patients had normal ejaculation preoperatively and 3 patients (12%) complained retrograde ejaculation postoperatively. Two patients (5.1%) reported stress urinary incontinence (SUI) and no patient reported aggravated urethral stricture during follow-up.ConclusionsUS-LSP was safe and effective in treating large-volume BPH with asymptomatic urethral stricture after urethral stricture surgery. Meanwhile, US-LSP could reduce the risk of SUI in patients with asymptomatic posterior urethral stricture and maintain ejaculatory function in a high percentage of patients.

Comparative analysis of holmium: YAG laser internal urethrotomy versus Cold-Knife optical internal urethrotomy in the management of urethral stricture - a systematic review and meta-analysis.

Urethral stricture management has posed enduring challenges in urology, demanding innovative and effective treatment modalities. This study addresses the persistent issues associated with urethral strictures, focusing on the comparative evaluation of two contemporary treatment modalities: Ho: YAG Laser Internal Urethrotomy (HIU) and Cold Knife Optical Internal Urethrotomy (CIU). A comprehensive search of PubMed, Embase, Web of Science, Cochrane Library, and ResearchGate was conducted to identify relevant studies up to November 2023. Inclusion criteria encompassed comparative studies evaluating HIU and CIU in patients with urethral stricture. Data extraction, quality assessment, and subgroup analyses were performed using standardized methods. Outcome measures included preoperative and postoperative mean the maximum urine flow rate (Qmax), mean surgical time, recurrence rates, and perioperative complications. Nine articles met the inclusion criteria, and their data were analyzed using RevMan 5.4.1. Forest plots were generated for preoperative and postoperative mean Qmax, mean surgical time, recurrence rates, and perioperative complications. While postoperative mean Qmax (MD -0.06; 95% CI: -0.28-0.16; P =0.60, I2 =75%) and mean surgical time (MD 2.16; 95% CI: -1.66-5.99; P =0.27, I2 =98%) showed no significant differences between HIU and CIU, a trend towards lower recurrence rates (RR 0.71; 95% CI: 0.48-1.06; P =0.09, I2 =46%) was observed with HIU but without statistical significance. Perioperative complications, particularly bleeding (RR 0.21; 95% CI: 0.08-0.53; P =0.001, I2 =0%), favored HIU over CIU. The subanalysis indicates that for the treatment of complex urethral strictures, the two surgical methods differ in terms of mean Qmax at 6 months postoperatively (MD -2.51; 95% CI: -4.10--0.91; P =0.002, I2 =59%) and 12 months postoperatively (MD 2.62; 95% CI: 0.93-4.30; P =0.002, I2 =0%). The HIU group shows a significant decrease in recurrence rate at 12 months postoperatively (RR 0.44; 95% CI: 0.21-0.92; P =0.03, I2 =0%). For short-segment urethral strictures with a length ≤1.5cm, CIU had a shorter operative time compared to the HIU (MD 4.49; 95% CI: 3.87-5.10; P <0.00001, I2 =44%). Overall, both interventions demonstrated similar efficacy in improving postoperative mean Qmax, mean surgical time, and recurrence rates. However, subanalysis indicates that in the short-term, CIU is more effective than HIU in improving Qmax after complex urethral stricture surgery. In long-term Qmax follow-up after surgery, HIU is significantly higher than CIU, and HIU has a low recurrence rate. In addition, for short-segment urethral stricture (≤1.5cm), CIU requires less time. In terms of complications, HIU has a lower risk of bleeding.

Surgical management of upper cervical esophagus stricture caused by ingestion of corrosive substances – a single-center experience

Introduction and aim. Corrosive strictures of the upper cervical esophagus and hypopharynx are hard to treat in the operating room because there is a high chance of aspiration during swallowing after a high-up or proximal esophageal anastomosis. In this cases, we aimed to evaluate the role of intraoperative dilatation of the proximal hypopharyngeal and cervical esophageal stumps during surgery. Material and methods. Patients who underwent surgery and had upper cervical esophageal and hypopharyngeal strictures from corrosive substance ingestion were included. Results. Out of total 27 patients, 10 had a cricopharyngeal or proximal cervical esophageal stricture with a long segment tho racic esophageal stricture that was treated with intra-operative dilatation (IOD) of the proximal hypopharyngeal stump. IOD was done in two cases with Hegar’s dilator and in three cases with wire-guided Savary Gillard dilators. In 74% (20/27) of the cases, the colon was frequently used as an esophageal substitute, while the stomach was only used in 10 cases. On follow-up, none of them developed repeated aspirations or required a tracheotomy. Conclusion. IOD of the proximal hypopharyngeal and cervical esophageal stumps during surgery for corrosive upper cervi cal esophageal or cricopharyngeal strictures helps to save the proximal stump and avoid frequent hospital stays and multiple surgeries.

Brazilian portuguese validation of the patient-reported outcome measure for urethral stricture surgery (USS-PROM) questionnaire.

Urethral stricture is a common, albeit complex, condition that predominantly affects men. The aim of this study was to translate, culturally adapt, and validate the Patient-Reported Outcome Measure questionnaire for patients undergoing urethroplasty (USS-PROM) into Brazilian Portuguese using validated psychometric criteria. The process involved translating and culturally adapting the original USS-PROM into Brazilian Portuguese (USS-PROMbr), synthesizing, back-translating, cross-culturally adapting, and analyzing the pre-final version with experts from our committee. This pre-version was administered to 10 patients who had undergone urethroplasty by the Reconstructive Urology team at the Hospital de Clínicas de Porto Alegre for face validation, linguistic, and semantic adjustments, resulting in the final USS-PROMbr version. Subsequently, well-established psychometric criteria, including content validity, internal consistency, and test-retest reproducibility, were assessed after administering the questionnaire to a total of 56 patients, with 50 of them responding to the test and retest. Evaluation of the pre-final version identified 15 questions as clear, and only one question was considered somewhat unclear necessitating modifications based on patient suggestions and subsequent reassessment by the research team. Psychometric criteria demonstrated good content validity, with a content validity index exceeding 0.80 for all questions; good internal consistency, Cronbach's alpha of 0.77, ranging from 0.70 to 0.78 with the exclusion of any item, and item-total correlations ranging from 0.33 to 0.67. The test-retest intraclass correlation coefficient was 0.74 for the lower urinary tract symptoms construct (Q1-Q6). The USS-PROMbr demonstrated acceptable cross-cultural adaptation and psychometric properties, making it a valid and useful tool for evaluating patients undergoing urethroplasty.

OP30 Endothelial cell-mediated smooth muscle hyperplasia in Crohn’s disease intestinal strictures: Caveolin 1 as a potential therapeutic target

Abstract Background Intestinal stricture is a severe and common complication of Crohn’s disease (CD). Current therapies offer limited success and surgery is often needed. Smooth muscle hyperplasia and hypertrophy play a key role in CD stricture development. This study explores the transcriptomic features of fibrostenotic CD, focusing on the endothelial contribution to smooth muscle changes within intestinal strictures. Methods 9 CD patients undergoing surgery for fibrotic strictures were prospectively enrolled. Dissected samples from the stricture and the adjacent proximal and distal non-strictured areas were obtained from fresh specimens collected directly from the operating theatre. RNA was extracted from all samples for bulk-transcriptomic analysis. Differentially expressed genes (adj. p-value &amp;lt;0.05) were identified and pathway enrichment analysis pinpointed relevant pathways. Subsequently, single-cell RNA sequencing (scRNAseq) analysis was performed using the 10x Chromium Controller® platform. A total of 31.195 cells were sequenced and bioinformatic analysis revealed 13 distinct clusters based on the expression of key lineage target genes. To better characterise the nature of clusters expressing stromal like markers and positioned closely in the UMAP plot, a further subclustering was performed. This resulted in 5 groups, including plasma cells, endothelial cells, fibroblasts, epithelial cells and dendritic like cells. Results Bulk-transcriptomic analysis identified 81 genes differentially expressed in strictures compared to both proximal and distal regions. Notably, genes associated with leukocyte and macrophage recruitment and chemotaxis, namely Platelet and Endothelial Cell Adhesion Molecule 1 (PECAM1), C-C motif Chemokine Ligand 2 (CCL2), and Endothelin Receptor Type B (EDNRB), resulted overexpressed in strictures. scRNAseq identified a distinct subset of endothelial cells (CD34+, PECAM1+). Caveolin 1 (CAV1), a gene encoding for a structural protein predominantly expressed in smooth muscle cell plasma membrane invaginations, was exclusively up-regulated in endothelial cells of ileal stricture samples. Previous research linked CAV1 to smooth muscle proliferation and fibrosis in various organs. Conclusion This study highlights the pivotal role of endothelial cells in CD strictures. The transcriptomic analysis shows the involvement of inflammatory targets featured genes involved in transendothelial immune cell migration. Furthermore, the up-regulation of CAV1 in endothelial cells within stricture segments suggests a mechanistic connection between endothelial cells and smooth muscle hyperplasia in intestinal strictures. CAV1 holds promise as a potential therapeutic target in fibrostenotic CD.

DOP61 Up-regulated Gremlin 1 in fibroblasts from Crohn’s Disease fibrotic strictures: A potential therapeutic target

Abstract Background Fibrosis is a common complication in Crohn’s disease (CD), often leading to intestinal strictures that are refractory to available biologic drugs and require surgery. Addressing this complication remains a significant unmet need. This study aims to explore the transcriptomic signature of fibrostenotic ileal CD to identify novel therapeutic targets. Methods 9 CD patients undergoing surgery for fibrotic strictures were prospectively recruited. All patients underwent magnetic resonance enterography, ileoscopy, and assessment of C-reactive protein and faecal calprotectin. A multidisciplinary team adjudicated the presence of fibrotic strictures, warranting surgical resection. Resected specimens were harvested directly from the operating theatre and delivered fresh to pathologists, who dissected samples from the strictured area, and the proximal and distal non-strictured regions. RNA was extracted from all samples for bulk-transcriptomic and single-cell RNA sequencing (scRNAseq) analysis, using the 10x Chromium Controller® platform. Differentially expressed genes (adj. p-value &amp;lt;0.05) were identified. Machine learning analyses, including PCA and PLS-DA, were employed to compare gene expression patterns among different tissue segments. Pathway enrichment analysis pinpointed relevant pathways. Further, the random forest model was constructed to evaluate the predictive significance of genes in relation to strictures, and the resulting ranked list of genes was subsequently validated through qPCR, confirming the significance of selected genes. Results Bulk-transcriptomic analysis revealed 64 significantly up-regulated genes in strictures, associated with inflammation, matrix remodeling, adipogenesis and cellular stress. Furthermore, 17 down-regulated genes were linked to epithelial barrier integrity. Normalised gene expression of GREM1, SERPINE1, FGF2, HDAC1 AND LY96 showed high predictive value for strictures compared to distal and proximal segments. Notably, qPCR confirmed the significant up-regulation of GREM1 expression exclusively in the ileal stricture samples (non-stricture vs. stricture: AUC 0.88, 95% CI 0.77-0.95). scRNAseq linked up-regulated GREM1 exclusively to the fibroblast cell population (THY1+, COL1A1+,ACTA2+). Conclusion Bulk and single-cell transcriptomics, along with qPCR validation of resected CD ileal strictures, showed the up-regulation of GREM1 in fibroblasts within stricture compared to adjacent proximal and distal intestinal samples. These findings confirmed in ileal CD previous reports from animal models, highlighting the role of GREM1 in promoting intestinal fibrosis. Therefore, GREM1 emerges an attractive target for the treatment of fibrotic strictures in CD.

A Novel Integrated Clinical-Biochemical-Radiological and Sonographic Classification of Necrotizing Enterocolitis.

To evaluate the sensitivity and specificity of clinical, laboratory, and radiological markers and the neonatologist-performed intestinal ultrasound (NP-IUS) for treatment interventions in preterm neonates who developed necrotizing enterocolitis (NEC). This was a case-control study of preterm neonates < 35 weeks with a diagnostic workup for NEC. The diagnostic workup included NP-IUS performed by trained neonatologists using a standard protocol, abdominal roentgenogram (AXR), and laboratory investigations. Intestinal ultrasound (IUS) performed by two neonatologists was standardized to detect 11 injury markers. AXRs were read independently by experienced pediatric radiologists. The investigators who retrospectively interpreted the IUS were blinded to the clinical and treatment outcomes. A total of 111 neonates were assessed. Fifty-four did not require intervention and formed the control group. Twenty cases were treated medically, 21 cases were treated with late surgery for stricture or adhesions, and 16 were treated with early surgery. The integrated model of cumulative severity of ultrasound markers, respiratory and hemodynamic instability, abdominal wall cellulitis, and C- reactive protein > 16 mg/L had an area under the curve (AUC) of 0.89 (95% confidence interval [CI]: 0.83-0.94%, p < 0.0001) for diagnosing NEC requiring surgical intervention. We also investigated the utility of Bell's classification to diagnose either the need for surgery or death, and it had an AUC of 0.74 (95% CI: 0.65-0.83%, p < 0.0001). In this cohort, a combination of specific IUS markers and clinical signs of instability, abdominal wall cellulitis, plus laboratory markers were diagnostic of NEC requiring interventions. · The diagnosis of necrotizing enterocolitis requires a combination of markers.. · The combination of specific ultrasound markers, clinical signs, and laboratory markers were diagnostic of NEC requiring intervention.. · The intestinal ultrasound performed by a trained neonatologist was the most sensitive diagnostic marker of NEC requiring surgical intervention..

Assessment of quality of life and factors affecting long-term outcomes after surgery for post-cholecystectomy benign biliary stricture

Assessment of quality of life and factors affecting long-term outcomes after surgery for post-cholecystectomy benign biliary stricture

Minimally invasive surgery for post cholecystectomy biliary stricture: current evidence and future perspectives.

Postcholecystectomy bile duct injury (BDI) remains a devastating iatrogenic complication that adversely impacts the quality of life with high healthcare costs. Despite a decrease in the incidence of laparoscopic cholecystectomy-related BDI, the absolute number remains high as cholecystectomy is a commonly performed surgical procedure. Open Roux-en-Y hepaticojejunostomy with meticulous surgical technique remains the gold standard surgical procedure with excellent long-term results in most patients. As with many hepatobiliary disorders, a minimally invasive approach has been recently explored to minimize access-related complications and improve postoperative recovery. Since patients with gallstone disease are often admitted for a minimally invasive cholecystectomy, laparoscopic and robotic approaches for repairing postcholecystectomy biliary stricture are attractive. While recent series have shown the feasibility and safety of minimally invasive post-cholecystectomy biliary stricture management, most are retrospective analyses with small sample sizes. Also, long-term follow-up is available only in a limited number of studies. The principles and technique of minimally invasive repair resemble open repair except for the extent of adhesiolysis and the suturing technique with continuous sutures commonly used in minimally invasive approaches. The robotic approach overcomes key limitations of laparoscopic surgery and has the potential to become the preferred minimally invasive approach for the repair of postcholecystectomy biliary stricture. Despite increasing use, lack of prospective studies and selection bias with available evidence precludes definitive conclusions regarding minimally invasive surgery for managing postcholecystectomy biliary stricture. High-volume prospective studies are required to confirm the initial promising outcomes with minimally invasive surgery.

Comparison of endoscopic balloon dilation and surgery for duodenal stricture in patients with Crohn’s disease

Background Few studies have compared endoscopic balloon dilation (EBD) and surgery in the treatment of duodenal stricture in patients with Crohn’s disease (CD). Methods We performed a retrospective study to compare the efficacy and safety among patients with CD-associated duodenal stricture treated with EBD or surgery from October 2013 to December 2021. Univariate and multivariate analyses were performed to evaluate factors associated with recurrence-free or surgery-free survival. Results A total of 48 eligible patients were included, including 30 patients treated with EBD only and 18 patients treated with surgery. Patients treated with surgery experienced more symptomatic improvement (100% vs. 63.33%, p = 0.003) and significantly longer recurrence-free survival (6.31 [IQR: 3.00–8.39] years vs. 2.96 [IQR: 1.06–5.42] years, p = 0.01) but suffered more postprocedural adverse events (16.67% vs. 0.74% per procedure, p = 0.001). In patients initially treated with EBD (n = 41), a total of 11 (26.83%) required subsequent surgical intervention. Younger age at CD diagnosis (HR = 0.90, 95% CI: 0.81–1.00, p = 0.04) was associated with a higher risk for subsequent surgery. Conclusions Surgery for CD-associated duodenal strictures was associated with a longer recurrence-free survival. EBD was safe and effective with minimal postprocedural adverse events but led to a high frequency of recurrence.