Full Thickness Resection or Endoscopic Submucosal Dissection for Difficult Colorectal Lesions.
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Neoplasms
PROVIDER: 2745298 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Among advanced resection techniques, endoscopic full thickness resection (EFTR) allows closure and full-thickness resection by the use of the non-exposed full thickness resection device (FTRD). The study is a retrospective analysis of technical failure occurring during colorectal full-thickness resection. Full thickness resection is a safe and effective procedure for "difficult" colorectal lesions. However, technical failure can occur and to date there is no evidence about type and clinical consequences in this setting.
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Project description:The concept of natural orifice transluminal endoscopic surgery (NOTES) (1) has evolved to endoscopic full thickness resection (EFTR). It represents innovation in technique that allows endoscopists to advance further into the endoscopic surgical space. EFTR has transformed the ability to tackle subepithelial tumors (SETs) and early mucosal neoplasm that are not amenable to classic ESD technique, enhance the staging accuracies for marginal lesions, and even increase the diagnostic capabilities for infiltrative disorders. Thus far, multiple methods have been described to perform EFTR, including nonexposed and exposed techniques, with the closure occuring before resection or after resection, respectively (2). Early comparative studies show no difference between the two methods (3). However, the procedures themselves are limited by the current tools available and by described techniques to achieve resection.
Investigators are described here a novel non-exposed technique, with closure before resection, using the Endomina device.
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Project description:Observational prospective multicenter study to investigate efficacy and safety of endoscopic full thickness resection in the lower GI tract using a novel over-the-scope full thickness resection device.
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Project description:Laterally spreading tumors (LSTs) are colorectal adenomas that develop into extremely large lesions but rarely become malignant. Elucidating their molecular profiles, and how these contrast with colorectal cancer (CRC), offers the opportunity to understand their biology and how they are able to grow to such large lesions without progressing to cancer. Profiling of 11 LSTs with multiple genome-wide approaches showed mutation rates comparable with microsatellite stable CRCs at 2.4 versus 2.6 mutations per megabase respectively, however copy number alterations are infrequent (averaging 1.5 per LST). Only 28.5% of genes with promoter CpG island hypermethylation showed >2-fold downregulation of expression in LST tissue relative to paired normal mucosa. Integration of genetic and epigenetic data identified driver genes not previously implicated in colorectal neoplasia (ANO5, MED12L, EPB41L4A, RGMB, SLITRK1, NRXN1, ANK2), including genes targeted by both genetic and epigenetic alterations. Alterations to pathways commonly mutated in CRCs, namely the p53, PI3K and TGFb pathways, are rare. Instead LST-altered genes converge on axonal guidance, Wnt and actin cytoskeleton signalling. Non-granular morphology, which is associated with an elevated risk of cancer, correlates with low frequencies of epigenetic inactivation and KRAS mutations and the hyperactivation of CXCR4 signalling. These data show that mutation load is a poor predictor of invasive potential and that genomic structural aberrations or alterations in key pathways is important in progression to cancer. By integrating genetic, epigenetic and transcriptional data this study identifies novel genes important in early colorectal neoplasia.
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Project description:Most of the cancers develop from the adenomatous polyps. The therapeutic methods have been established already - endoscopic polypectomy (EPE) for stalked polyps and endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for non-pedunculated polyps. EMR is preferred in European countries over ESD because of its higher feasibility. However, the local residual neoplasia (LRN) after EMR has been reported in 14 - 24 % cases. There is a higher LRN risk in sessile polyps which do not elevate sufficiently after the submucosal injection (non-lifting sign) and the piece-meal resection needs to be used. Therefore, the new method of endoscopic full-thickness resection (FTR) has been developed to resect these lesions.
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Project description:Randomized head-to-head comparison trial among patients who have undergone incomplete endoscopic resection of early colon cancer to evaluate the benefits, harms and burdens, as well as the ecological footprint and cost-effectiveness of endoscopic full thickness resection (eFTR), a minimally invasive endoscopic treatment with a colonoscope, as compared to standard-of-care surgery.
Co-primary endpoints are
* Rate of severe adverse events classified as grade III to V according to the Clavien Dindo classification within 30-days after study treatment
* CRC recurrence or sign of lymph nodes or distant metastases at 3 years after randomization comparing the two treatment groups (eFTR versus surgery).
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Project description:We use a laser-induced forward transfer (LIFT)-based method coupled with a full-length mRNA-sequencing protocol (LIFT-seq) for profiling region-specific tissues. LIFT-seq was applied to the cortex and hippocampus regions of the mouse brain for profiling gene expression.
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Project description:Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide, with 1.65 million new cases and almost 835,000 deaths in 2015. CRC is still a major cause of mortality associated with cancer, although the wide spread of the screening program has led to a reduction in the mortality rate compared to the last decades.
CRCs derive from precancerous lesions that may be polypoid or non-polypoid according to the Paris classification. Thus, resection in an early stage could led to a CRC mortality reduction.
Laterally spreading tumors (LST) are non-polypoid lesions of at least 1 cm in diameter that have lateral growth rather than upward or downward growth.
The prevalence of LSTs ranges from 1 to 6% of all colorectal lesions. LSTs can be divided into two groups: granular LSTs, which include homogeneous and granular mixed forms and non-granular (NG) LSTs, which include pseudo-depressed and flat-elevated forms.
Histologically, 90% of LSTs are adenomas and having a low incidence of invasive neoplasia, these lesions can be removed endoscopically.
However, as evidenced by a recent meta-analysis published by Bogie Roel MM et al on Endoscopy, the type of LST and the distal or proximal colonic localization could represent predictors of submucosal invasion and could simplify the therapeutic decision for the removal of these lesions. GM-LSTs and pseudo-depressed NG-LSTs predominantly localize in the distal portion of the colon and have a submucosal invasion rate of 10,5% and 31,6% respectively.
LSTs can be removed both through endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). The main limitation of EMR is that large lesions require a piecemeal approach, resulting in a non-optimal histological evaluation and a high risk of recurrence. ESD instead allows a higher rate of en bloc resections, thus resulting more curative and reducing the risk of having partial and incomplete resections, which can lead to disease recurrence/non curative resection.
LST-GM are characterized by the presence of a granular appearance with a main nodule and represent approximately 1/4 of the LSTs. There are no guidelines indicating the proper resective technique of these lesions.
The European Society of Gastrointestinal Endoscopy (ESGE) suggests to consider ESD for the removal of colorectal lesions that are > 20 mm in size, with a depressed and irregular morphology or a non-granular surface pattern, as these lesions have a high probability of having a limited submucosal invasion. Moreover ESD can be used to treat lesions that cannot be completely removed with standard polypectomy or EMR.
The investigators propose to perform a multicenter retrospective observational study to define the percentage of cancer in patients with GM-LSTs treated with endoscopic resection in order to evaluate the correlation between pre-resection and post-resection characteristics, defining the best therapeutic approach (en bloc or piecemeal) and avoiding incomplete endoscopic resections or unnecessary surgical procedures.
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Project description:Despite the recent application of single-cell RNA-sequencing to aspects of mouse skin biology, the full cellular heterogeneity of the mouse skin (including both epidermis and skin stroma) and its relationship with the hair cycle is still uncharted. In order to systematically compare the cellular composition of mouse skin during rest and hair growth, we created single-cell RNA-sequencing libraries from full thickness mouse skin cell suspensions sampled during anagen (5w) and telogen (9w).
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