Cohort profile: the Spanish Early-onset Colorectal Cancer (SECOC) cohort: a multicentre cohort study on the molecular basis of colorectal cancer among young individuals in Spain

Càncer colorectal; Base molecularCáncer colorrectal; Base molecularColorectal cancer; Molecular basisPurpose The Spanish Early-onset Colorectal Cancer (SECOC) study is a multicentre prospective cohort established in Spain to investigate the molecular basis of early-onset colorectal cancer (EOCRC), including metabolic alterations. Participants 220 patients with EOCRC have been enrolled since January 2019 through 18 centres across Spain. Individual-level data were collected by questionnaire, including lifestyle and other colorectal cancer-related factors. Medical record review was performed to capture clinical, histopathological and familial cancer history data. Biospecimen collection (blood, stool, tissue) at diagnosis and at various time points across treatment, as applicable, is also completed. Findings to date Participants had a median age of 44 years (range 14–49), and the majority are men (60%), with individuals age 40–49 years at EOCRC diagnosis being over-represented. Forty-three per cent of participants were diagnosed with a tumour in the rectosigmoid junction/rectum. Nearly two-thirds of EOCRC cases (64%) were diagnosed with advanced stage (III–IV) disease, and 28% of cases had no reported familial history of cancer. Future plans We are actively recruiting and observing participants; we plan to administer follow-up questionnaires and perform additional biospecimen collection. This prospective cohort offers a unique, rich resource for research on EOCRC aetiologies and will contribute to larger international efforts to disentangle the rising disease burden.This work was funded by Projects PI16/01650 and PI20/00974 to JP, from the Spanish Ministry of Health and Consumer Affairs and FEDER. ANH was supported by the National Institutes of Health (NIH) K12 HD043483 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. This work was also supported by the American Cancer Society (#IRG-19-139-59) to ANH

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

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

Adalimumab; Adipose tissue; InfliximabAdalimumab; Tejido adiposo; InfliximabAdalimumab; Teixit adipós; InfliximabAnti-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 CD.This study was supported by a grant from the Spanish Ministry of Economy and Competitiveness (PI18/00037 to C.S.), co-financed by the European Regional Development Fund (ERDF). C.S. acknowledges support from the “Ramón y Cajal” program from the Ministerio de Educación y Ciencia (RYC2013-13186), co-financed by the ERDF. A.B.-T. acknowledges support from PI-AGAUR 2022-B00577. D.M.-F. acknowledges support from PERIS-PFI-Salut SLT01720000021

Impact of the COVID-19 pandemic in the early-onset colorectal cancer

COVID-19 pandemic; Early-onset colorectal cancerPandemia de COVID-19 Cáncer colorrectal precozPandèmia de COVID-19; Càncer colorectal precoçThe COVID19 pandemic has affected the spectrum of cancer care worldwide. Early onset colorectal cancer (EOCRC) is defined as diagnosis below the age of 50. Patients with EOCRC faced multiple challenges during the COVID19 pandemic and in some institutions it jeopardized cancer diagnosis and care delivery. Our study aims to identify the clinicopathological features and outcomes of patients with EOCRC in our Centre during the first wave of the pandemic in comparison with the same period in 2019 and 2021. Patients with EOCRC visited for the first time at Vall d'Hebron University Hospital in Spain from the 1st March to 31st August of 2019, 2020 and 2021 were included in the analysis. 177 patients with EOCRC were visited for the first time between 2019 and 2021, of which 90 patients met the inclusion criteria (2019: 30 patients, 2020: 29 patients, 2021: 31 patients). Neither differences in frequency nor in stage at diagnosis or at first visit during the given periods were observed. Of note, indication of systemic therapy in the adjuvant or metastatic setting was not altered. Days to treatment initiation and enrollment in clinical trials in this subpopulation was not affected due to the COVID-19 outbreak.This work was supported by the Cancer Research UK (CRUK) grant OPTIMISTICC (C10674/A27140)

Células Madre Mesenquimales: una alternativa de tratamiento en la enfermedad de Crohn fistulizante perianal

Los pacientes con enfermedad de Crohn (EC) pueden desarrollar manifestaciones perianales solitarias o múltiples. La EC perianal fistulizante representa una de las formas más complejas de la enfermedad y, a pesar de los avances en el manejo de le EC su tratamiento es aún un verdadero desafío. La introducción de nuevas perspectivas terapéuticas como las terapias celulares obligan a buscar nuevas estrategias en el manejo de este espectro de la EC. El tratamiento de las fístulas anales en la EC empleando células madre mesenquimales (CMM) ha demostrado ser seguro y eficaz, prometiendo ser una opción terapéutica adicional a las posibilidades de tratamiento de la enfermedad. En el presente trabajo presentamos la evidencia científica existente en el manejo de la EC perianal fistulizante con CMM, así como las indicaciones, protocolo de aplicación y consideraciones especiales del uso de las CMM en la enfermedad

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