Patient-reported outcome measures and surgery for Crohn’s disease: systematic review

Outcome; Surgery; Crohn's diseaseResultado; Cirugía; Enfermedad de CrohnResultat; Cirurgia; Malaltia de CrohnBackground/Aims Crohn’s disease is an inflammatory bowel disease with up to 50 per cent of patients requiring surgery within 10 years of diagnosis. Patient-reported outcome measures (PROMs) are vital to monitor and assess patient health-related quality of life (HRQoL). This systematic review aims to evaluate PROMs within studies for perioperative Crohn's disease patients. Methods Articles from MEDLINE, Embase, Emcare and CINAHL databases were searched to find studies relating to the assessment of HRQoL in perioperative Crohn's disease patients using PROMs and patient-reported experience measures (PREMs) from 1st January 2015 to 22nd October 2023. Bias was assessed using the ROBINS-I tool was used for non-randomized interventional studies and the Cochrane RoB2 tool was used for randomized trials. Results 1714 journal articles were filtered down to eight studies. Six studies focused on ileocaecal resection, one on perianal fistulas and one on the effects of cholecystectomy on patients with Crohn's disease. Within these articles, ten different PROM tools were identified (8 measures of HRQoL and 2 measures of functional outcome). Overall improvements in patient HRQoL pre- to postoperative for ileocaecal Crohn's disease were found in both paediatric and adult patients. Outcomes were comparable in patients in remission, with or without stoma, but were worse in patients with a stoma and active disease. Conclusion There are significant variations in how PROMs are used to evaluate perioperative Crohn's disease outcomes and a need for consensus on how tools are used. Routine assessments using an internationally accepted online platform can be used to monitor patients and support areas of treatment pathways that require further support to ensure high standards of care. They also enable future statistical comparisons in quantitative reviews and meta-analyses

The Gut Microbiota Metabolite Succinate Promotes Adipose Tissue Browning in Crohn’s Disease

Succinic acid; Bacteria translocation; Beige adipose tissueÀcid succínic; Translocació de bacteris; Teixit adipós beigeÁcido succínico; Translocación de bacterias; Tejido adiposo beigeBackground and Aims Crohn’s disease [CD] is associated with complex microbe–host interactions, involving changes in microbial communities, and gut barrier defects, leading to the translocation of microorganisms to surrounding adipose tissue [AT]. We evaluated the presence of beige AT depots in CD and questioned whether succinate and/or bacterial translocation promotes white-to-beige transition in adipocytes. Methods Visceral [VAT] and subcutaneous [SAT] AT biopsies, serum and plasma were obtained from patients with active [n = 21] or inactive [n = 12] CD, and from healthy controls [n = 15]. Adipose-derived stem cells [ASCs] and AT macrophages [ATMs] were isolated from VAT biopsies. Results Plasma succinate levels were significantly higher in patients with active CD than in controls and were intermediate in those with inactive disease. Plasma succinate correlated with the inflammatory marker high-sensitivity C-reactive protein. Expression of the succinate receptor SUCNR1 was higher in VAT, ASCs and ATMs from the active CD group than from the inactive or control groups. Succinate treatment of ASCs elevated the expression of several beige AT markers from controls and from patients with inactive disease, including uncoupling protein-1 [UCP1]. Notably, beige AT markers were prominent in ASCs from patients with active CD. Secretome profiling revealed that ASCs from patients with active disease secrete beige AT-related proteins, and co-culture assays showed that bacteria also trigger the white-to-beige switch of ASCs from patients with CD. Finally, AT depots from patients with CD exhibited a conversion from white to beige AT together with high UCP1 expression, which was corroborated by in situ thermal imaging analysis. Conclusions Succinate and bacteria trigger white-to-beige AT transition in CD. Understanding the role of beige AT in CD might aid in the development of therapeutic or diagnostic interventions.This study was supported by grants from the Spanish Ministry of Science and Innovation [PI18/00037 (Instituto de Salud Carlos III, ISCIII) to C.S.; PI17/01503 and PI20/00338 (ISCIII) to J.V. and RTI2018-093919 to S.F.-V.], co-financed by the European Regional Development Fund [ERDF] and a European Crohn’s and Colitis Organization grant to C.S. The Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders [CIBERDEM] [CB07708/0012] is an initiative of the Instituto de Salud Carlos ISCIII acknowledges support from the ‘Ramón y Cajal’ programme from the Ministerio de Educación y Ciencia [RYC2013-13186], co-financed by the ERDF. S.F.-V. acknowledge support from the ‘Miguel Servet’ tenure track programme [CP10/00438, CPII16/0008] from the Fondo de Investigación Sanitaria, co-financed by the ERDF. D.M.-F. acknowledges support from PERIS-PFI-Salut SLT01720000021

Smoking Suppresses the Therapeutic Potential of Adipose Stem Cells in Crohn’s Disease Patients through Epigenetic Changes

Cell therapy; Chronic inflammatory disease; CigaretteTerapia celular; Enfermedad inflamatoria crónica; CigarrilloTeràpia cel·lular; Malaltia inflamatòria crònica; CigarretPatients with Crohn’s disease (CD) who smoke are known to have a worse prognosis than never-smokers and a higher risk for post-surgical recurrence, whereas patients who quit smoking after surgery have significantly lower post-operative recurrence. The hypothesis was that smoking induces epigenetic changes that impair the capacity of adipose stem cells (ASCs) to suppress the immune system. It was also questioned whether this impairment remains in ex-smokers with CD. ASCs were isolated from non-smokers, smokers and ex-smokers with CD and their interactions with immune cells were studied. The ASCs from both smokers and ex-smokers promoted macrophage polarization to an M1 pro-inflammatory phenotype, were not able to inhibit T- and B-cell proliferation in vitro and enhanced the gene and protein expression of inflammatory markers including interleukin-1b. Genome-wide epigenetic analysis using two different bioinformatic approaches revealed significant changes in the methylation patterns of genes that are critical for wound healing, immune and metabolic response and p53-mediated DNA damage response in ASCs from smokers and ex-smokers with CD. In conclusion, cigarette smoking induces a pro-inflammatory epigenetic signature in ASCs that likely compromises their therapeutic potential.This study was supported by a grant from the Spanish Ministry of Economy and Competitiveness (PI18/00037 to CS), co-financed by the European Regional Development Fund (ERDF). C.S. acknowledges support from “Ramón y Cajal’ program from the Ministerio de Educación y Ciencia (RYC2013-13186), co-financed by the ERDF. A.B.-T. acknowledge support from PI-AGAUR 2022-B00577. I.V. acknowledges support from INVESTIGO-AGAUR (100036TC2). D.M.-F. acknowledges support from PERIS-PFI-Salut SLT01720000021

Anti-TNF Therapies Suppress Adipose Tissue Inflammation in Crohn's Disease

Anti-TNF biologics have been shown to markedly improve the quality of life for patients with Crohn's disease (CD), yet one-third of patients fail to benefit from this treatment. Patients with CD develop a characteristic wrapping of visceral adipose tissue (VAT) in the inflamed intestinal area, termed creeping fat, and it is known that adipose tissue expansion influences the efficacy of anti-TNF drugs. We questioned whether anti-TNF therapies impact the creeping fat in CD, which might affect the outcome of the disease. Adipose tissue biopsies were obtained from a cohort of 14 patients with CD that received anti-TNF drugs and from 29 non-anti-TNF-treated patients (control group) matched by sex, age, and body mass index undergoing surgical interventions for symptomatic complications. We found that anti-TNF therapies restored adipose tissue morphology and suppressed immune cell infiltration in the creeping fat. Additionally, anti-TNF treatments appeared to markedly improve the pro-inflammatory phenotype of adipose-tissue macrophages and adipose-tissue-derived stem cells. Our study provides evidence that anti-TNF medications influence immune cells and progenitor cells in the creeping of patients with CD, suppressing inflammation. We propose that perilesional VAT should be considered when administering anti-TNF therapy in patients with C

Long-term Oncological Outcome of Segmental Versus Extended Colectomy for Colorectal Cancer in Crohn's Disease: Results from an International Multicentre Study

Background and Aims Crohn's disease increases colorectal cancer risk, with high prevalence of synchronous and metachronous cancers. Current guidelines for colorectal cancer in Crohn's disease recommend pan-proctocolectomy. The aim of this study was to evaluate oncological outcomes of a less invasive surgical approach. Methods This was a retrospective database analysis of Crohn's disease patients with colorectal cancer undergoing surgery at selected European and US tertiary centres. Outcomes of segmental colectomy were compared with those of extended colectomy, total colectomy, and pan-proctocolectomy. Primary outcome was progression-free survival. Secondary outcomes included overall survival, synchronous and metachronous colorectal cancer, and major postoperative complications. Results Ninety-nine patients were included: 66 patients underwent segmental colectomy and 33 extended colectomy. Segmental colectomy patients were older [p = 0.0429], had less extensive colitis [p = 0.0002] and no preoperatively identified synchronous lesions [p = 0.0109]. Median follow-up was 43 [31-62] months. There was no difference in unadjusted progression-free survival [p = 0.2570] or in overall survival [p = 0.4191] between segmental and extended colectomy. Multivariate analysis adjusting for age, sex, ASA score, and AJCC staging, confirmed no difference for progression-free survival (hazard ratio [HR] 1.00, p = 0.9993) or overall survival [HR 0.77, p = 0.6654]. Synchronous and metachronous cancers incidence was 9% and 1.5%, respectively. Perioperative mortality was nil and major complications were comparable [7.58% vs 6.06%, p = 0.9998]. Conclusions Segmental colectomy seems to offer similar long-term outcomes to more extensive surgery. Incidence of synchronous and metachronous cancers appears much lower than previously described. Further prospective studies are warranted to confirm these results

The colon does not reach! A technical note with tricks to avoid colorectal anastomoses under tension

Altres ajuts: acords transformatius de la UABAim: We describe two options for colorectal anastomosis suitable in cases when the colon would reach the pelvis under tension. Method: Deloyers procedure and the retro-ileal colorectal anastomosis are presented, focusing on practical tips and tricks to perform them. Insights on patients who underwent the procedures are provided to demonstrate the advantages and feasibility of the techniques. Results: Each step of both techniques is detailed. Ten patients underwent Deloyers procedure and nine underwent retro-ileal anastomosis at our unit. A minimally invasive approach was attempted in 13 patients, of whom five required conversion to open surgery due to the technical complexity of the abdominal procedure. Colorectal anastomosis was successfully performed in all patients. There were no major intra-operative complications, although five patients had postoperative complications requiring further treatment. Conclusions: Both techniques are effective in patients at risk of receiving a colorectal anastomosis under tension, and a minimally invasive approach can be used. However, owing to the complexity of surgery in this group of patients, the perioperative morbidity is not negligible. Careful postoperative management is advisable, and patients should be informed of the risks. In expert hands, the outcomes are acceptable, avoiding an ileorectal anastomosis and its constraints

Double Barreled Wet Colostomy : Initial Experience and Literature Review

Background. Pelvic exenteration and multivisceral resection in colorectal have been described as a curative and palliative intervention. Urinary tract reconstruction in a pelvic exenteration is achieved in most cases with an ileal conduit of Bricker, although different urinary reservoirs have been described. Methods. A retrospective and observational study of six patients who underwent a pelvic exenteration and urinary tract reconstruction with a double barreled wet colostomy (DBWC) was done, describing the preoperative diagnosis, the indication for the pelvic exenteration, the complications associated with the procedure, and the followup in a period of 5 years. A literature review of the case series reported of the technique was performed. Results. Six patients had a urinary tract reconstruction with the DBWC technique, 5 male patients and one female patient. Age range was from 20 to 77 years, with a medium age 53.6 years. The most frequent complication presented was a pelvic abscess in 3 patients (42.85%); all complications could be resolved with a conservative treatment. Conclusion. In the group of our patients with pelvic exenteration and urinary tract reconstruction with a DBWC, it is a safe procedure and well tolerated by the patients, and most of the complications can be resolved with conservative treatmen

Smoking Suppresses the Therapeutic Potential of Adipose Stem Cells in Crohn’s Disease Patients through Epigenetic Changes

Patients with Crohn’s disease (CD) who smoke are known to have a worse prognosis than never-smokers and a higher risk for post-surgical recurrence, whereas patients who quit smoking after surgery have significantly lower post-operative recurrence. The hypothesis was that smoking induces epigenetic changes that impair the capacity of adipose stem cells (ASCs) to suppress the immune system. It was also questioned whether this impairment remains in ex-smokers with CD. ASCs were isolated from non-smokers, smokers and ex-smokers with CD and their interactions with immune cells were studied. The ASCs from both smokers and ex-smokers promoted macrophage polarization to an M1 pro-inflammatory phenotype, were not able to inhibit T- and B-cell proliferation in vitro and enhanced the gene and protein expression of inflammatory markers including interleukin-1b. Genome-wide epigenetic analysis using two different bioinformatic approaches revealed significant changes in the methylation patterns of genes that are critical for wound healing, immune and metabolic response and p53-mediated DNA damage response in ASCs from smokers and ex-smokers with CD. In conclusion, cigarette smoking induces a pro-inflammatory epigenetic signature in ASCs that likely compromises their therapeutic potential

Colorectal cancer in inflammatory bowel disease: Results of the 3rd ECCO pathogenesis scientific workshop (I)

Epidemiological studies demonstrate an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). A detailed literature review was conducted on epidemiology, risk factors, pathophysiology, chemoprevention and outcomes of colorectal cancer (CRC) in IBD as part of the 3rd ECCO scientific pathogenesis workshop