Long-term outcomes of an acellular dermal matrix for the treatment of complex cryptoglandular anal fistula: a pilot study

Backgound Effective, standardized treatments for complex anal fistula (CAF) still represent a clinical challenge. Emerging procedures attempted to achieve the healing rates of fistulotomy whilst preserving sphincter function. Acellular dermal matrix (ADM) used as a plug inserted through the fistulous tract is among newer treatment options. Varying success rates have been reported, most with short-term follow-up. The aim of this study was to report the long-term results of ADM-plug for CAF. Methods Retrospective analysis of a prospective database of patients treated with CAF. All consecutive patients presenting at two tertiary centers (Vall d'Hebron University Hospital and Bellvitge University Hospital, Barcelona, Spain) between November 2015 and March 2019 with a single, cryptoglandular CAF were evaluated for treatment with an ADM-plug were included. The primary endpoint was absence of discharge at clinical examination at 12 month follow-up. Results Twenty-two patients were included [7 women and 15 men, median age 56 (33-74) years]. Most patients had high transsphincteric fistulas (63.6%). The median follow-up was 42 (21-53) months. The 12 month success rate was 68.2%, with an overall healing rate of 59.1%. 77.8% of recurrences occurred within 12 months from surgery. One plug extrusion was observed. No major complications or mortality occurred during the follow-up. Patients did not report any worsening of fecal continence. Conclusions This pilot study showed that more than half of patients with CAF could benefit from ADM-plug placement, preserving continence. A minimum follow-up of 12 months is recommended, because most recurrences occur during the first year

Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat

Malaltia de Crohn; Teixit adipós; MesoteliEnfermedad de Crohn; Tejido adiposo; MesotelioCrohn’s disease; Adipose tissue; MesotheliumOur understanding of the interplay between human adipose tissue and the immune system is limited. The mesothelium, an immunologically active structure, emerged as a source of visceral adipose tissue. After investigating the mesothelial properties of human visceral and subcutaneous adipose tissue and their progenitors, we explored whether the dysfunctional obese and Crohn’s disease environments influence the mesothelial/mesenchymal properties of their adipocyte precursors, as well as their ability to mount an immune response. Using a tandem transcriptomic/proteomic approach, we evaluated the mesothelial and mesenchymal expression profiles in adipose tissue, both in subjects covering a wide range of body-mass indexes and in Crohn’s disease patients. We also isolated adipose tissue precursors (adipose-derived stem cells, ASCs) to assess their mesothelial/mesenchymal properties, as well as their antigen-presenting features. Human visceral tissue presented a mesothelial phenotype not detected in the subcutaneous fat. Only ASCs from mesenteric adipose tissue, named creeping fat, had a significantly higher expression of the hallmark mesothelial genes mesothelin (MSLN) and Wilms’ tumor suppressor gene 1 (WT1), supporting a mesothelial nature of these cells. Both lean and Crohn’s disease visceral ASCs expressed equivalent surface percentages of the antigen-presenting molecules human leucocyte antigen—DR isotype (HLA-DR) and CD86. However, lean-derived ASCs were predominantly HLA-DR dim, whereas in Crohn’s disease, the HLA-DR bright subpopulation was increased 3.2-fold. Importantly, the mesothelial-enriched Crohn’s disease precursors activated CD4+ T-lymphocytes. Our study evidences a mesothelial signature in the creeping fat of Crohn’s disease patients and its progenitor cells, the latter being able to present antigens and orchestrate an immune response.This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities (PI14/00228 and PI17/01503 to JV, SAF2015-65019-R to SF-V, BFU2015-70454-REDT and BFU2017-90578-REDT to SF-V and MMM, BFU2016-76711-R to MMM and PI15/00143 and PI18/00037 to CS) co-financed by the European Regional Development Fund (ERDF) and by Fundació La Marató de TV3 (PV170125) to SF-V and the European Crohn’s and Colitis Organization (ECCO) grant to CS. The Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM) (CB07708/0012) is an initiative of the Instituto de Salud Carlos III. AM is a recipient of a postdoctoral fellowship from FJCI-2014-23060 and IJCI-2016-30572. SF-V acknowledges support from the Miguel Servet tenure-track program (CP10/00438 and CPII16/00008) of the Fondo de Investigación Sanitaria, co-financed by the ERDF. C.S. acknowledges support from the ‘Ramón y Cajal’ program from MINECO (RYC2013-13186), co-financed by the ERDF

The role of a defunctioning stoma for colonic and perianal Crohn's disease in the biological era

OBJECTIVE: A defunctioning stoma is a therapeutic option for colonic or perianal Crohn's disease. In the pre-biologic era the response rate to defunctioning in our unit was high (86%), but intestinal continuity was only restored in 11-20%. Few data exist on the outcome of defunctioning since the widespread introduction of biologicals. MATERIAL AND METHODS: All patients undergoing a defunctioning stoma for colonic/perianal Crohn's disease since 2003-2011 were identified from a prospective database. Indications for surgery, medical therapy, response to defunctioning and long-term clinical outcome were recorded. Successful restoration of continuity was defined as no stoma at last follow up. RESULTS: Seventy-six patients were defunctioned (57 with biologicals) and at last follow up, 20 (27%) had continuity restored. Early clinical response rate (<3 months) was 15/76 (20%) and overall response 31/76 (41%). Complex anal fistulae/stenosis were associated with a very low chance of restoring continuity (10% and 0%, respectively), while colitis was associated with a higher chance of restoring continuity (48%). Endoscopic or histological improvement in colitis after defunctioning was associated with a higher rate of restoring continuity (10/16, 63%) compared to no such improvement (4/15, 27%, p = 0.05). Those failing biologics had similar chance of restoration as those not receiving biologics, 15/57 (26%) and 5/19 (26%), respectively. CONCLUSION: Overall response to colonic defunctioning was 41%. Successful restoration of continuity occurred in 27%, but 48% in the absence of perianal disease. Response is appreciably less in the pre-biologic era, so patient and physician expectations need to be managed appropriately

The role of a defunctioning stoma for colonic and perianal Crohn's disease in the biological era

OBJECTIVE: A defunctioning stoma is a therapeutic option for colonic or perianal Crohn's disease. In the pre-biologic era the response rate to defunctioning in our unit was high (86%), but intestinal continuity was only restored in 11-20%. Few data exist on the outcome of defunctioning since the widespread introduction of biologicals. MATERIAL AND METHODS: All patients undergoing a defunctioning stoma for colonic/perianal Crohn's disease since 2003-2011 were identified from a prospective database. Indications for surgery, medical therapy, response to defunctioning and long-term clinical outcome were recorded. Successful restoration of continuity was defined as no stoma at last follow up. RESULTS: Seventy-six patients were defunctioned (57 with biologicals) and at last follow up, 20 (27%) had continuity restored. Early clinical response rate (<3 months) was 15/76 (20%) and overall response 31/76 (41%). Complex anal fistulae/stenosis were associated with a very low chance of restoring continuity (10% and 0%, respectively), while colitis was associated with a higher chance of restoring continuity (48%). Endoscopic or histological improvement in colitis after defunctioning was associated with a higher rate of restoring continuity (10/16, 63%) compared to no such improvement (4/15, 27%, p = 0.05). Those failing biologics had similar chance of restoration as those not receiving biologics, 15/57 (26%) and 5/19 (26%), respectively. CONCLUSION: Overall response to colonic defunctioning was 41%. Successful restoration of continuity occurred in 27%, but 48% in the absence of perianal disease. Response is appreciably less in the pre-biologic era, so patient and physician expectations need to be managed appropriately

Segmental versus total colectomy for Crohn's disease in the biologic era. Results from The SCOTCH international, multicentric study

Background The extent of resection in colonic Crohn's disease [cCD] is still a topic of debate, depending on the number of locations, the risk of recurrence and permanent stoma, and the role of medical therapy. Methods The Segmental COlecTomy for CroHn's disease [SCOTCH] international study is a retrospective analysis on six tertiary centre prospective databases, comprising all consecutive, unselected patients operated on between 2000 and 2019 with segmental colectomy [SC] or total colectomy [TC] for cCD. The primary aim was long-term surgical recurrence. Secondary aims were perioperative complications, stoma formation and predictors of recurrence. Results Among 687 patients, SC was performed in 285 [41.5%] and TC in 402 [58.5%]. Mean age at diagnosis and surgery, disease duration, and follow-up were 30 +/- 15.8, 40.4 +/- 15.4, 10.4 +/- 8.6 and 7.1 +/- 5.2 years respectively. Isolated cCD, inflammatory pattern, perianal CD, younger age, longer disease duration and preoperative maximal therapy were more frequent in TC, while SC presented more small bowel locations and perforating disease, required fewer 90-day re-admissions, and fewer temporary and definitive stomas. Morbidity and mortality were similar. The 15-year surgical recurrence was 44% in TC and 27% in SC [p = 0.006]. In patients with one to three diseased segments, recurrence risk was related to the omission of biological therapy (hazard ratio [HR] 5.6), the number of segments [HR 2.5], perianal disease [HR 1.9] and paediatric diagnosis [HR 2.8]. Conclusion When technically feasible, SC is safe and reduces temporary and permanent stoma. Young age, number of locations and perianal disease adversely affect, but postoperative biological therapy significantly reduces, the long-term surgical recurrence