Analysis of submucosal (SM) invasion site of laterally spreading tumor among subtypes
Ontology highlight
ABSTRACT:
DISEASE(S): Laterally Spreading Tumor (lst) (early Colorectal Cancer Or Adenoma)
PROVIDER: 2635539 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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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.
2016-11-12 | GSE77635 | GEO
Project description:Colorectal laterally spreading tumors (LSTs) are rare comparing to adenomas but are becoming more prevalent. Unlike many neoplasms in colons, LST grows to extremely large size, usually greater than 10mm in diameter while rarely invades deeply. Also, there is a low tendency for LSTs to become cancerous. The epigenetic landscape of LST has not been defined. In this study, we used a genome-wide methylation profiling technology, i.e. the Illumina Human Methylation 450K array, to query the main epigenetic difference between LST and para-cancerous samples. Our results suggest that LST displays significant decrease in DNA methylation, especially in some intergenic regions (IGR). By integration of public data for adenomas and colorectal cancers, we defined the commonality and specific epigenetic signatures for these three types of neoplasms in colon, in particular LST and adenomas which represent precancerous conditions. These three diseases shared little specific DNA methylation abnormalities. However, our pathway-level analysis revealed that certain pathways were common targets of epimutation. More interestingly, different diseases seem to employ distinct epigenetic insult to disturb these pathways. Between LST and adenoma, we found eight pathways were commonly targeted but the epi-mutation patterns were opposite between the two diseases. Comparison between precancerous conditions and invasive states revealed the key pathways governing the progression to malignancy, including CAMs and PI3K-Akt pathways.
2019-01-01 | GSE106556 | GEO
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.
| 2296816 | ecrin-mdr-crc
Project description:Endoscopic diagnosis of lateral spreading tumours (LST) with submucosal invasion is important in guiding the treatment strategy. The use of advanced imaging is not standard clinical practice in China. A clinical trial is now under way comparing the accuracy of narrow band imaging (NBI), endoscopic ultrasonography (EUS) and magnifying chromoendoscopy (MCE) for the diagnosis of LST with submucosal invasion.
| 2241059 | ecrin-mdr-crc
Project description:EMR and ESD are both effective and safe and are associated with a very low risk of procedure related mortality when performed for colorectal laterally spreading lesions (LSL).
Some kind of LSLs have a low risk of submucosal invasive carcinoma (SMIC) or these foci are found in well demarcated areas of the tumor. This is the case of the non-granular flat elevated (LSN-NG-FE) and the LSLs-G mixed subtypes.
The investigators aim to assess if piecemeal EMR (the older technique) for LSLs-G mixed type > 30 mm and LSLs-NG FE type > 20 mm is not inferior to ESD (the new treatment) for the need of additional surgery in the mid-term.
| 2354982 | ecrin-mdr-crc
Project description:BackgroundColorectal laterally spreading tumors (LSTs) with malignant potential require en bloc resection by endoscopic submucosal dissection (ESD), but lesions with deep submucosal invasion (SMI) are endoscopically unresectable.AimTo investigate the factors associated with high-grade dysplasia (HGD)/carcinoma and deep SMI in colorectal LSTs.MethodsThe endoscopic and histological results of consecutive patients who underwent ESD for colorectal LSTs in our hospital from June 2013 to March 2019 were retrospectively analyzed. The characteristics of LST subtypes were compared. Risk factors for HGD/carcinoma and deep SMI (invasion depth ≥ 1000 μm) were determined using multivariate logistic regression.ResultsA total of 323 patients with 341 colorectal LSTs were enrolled. Among the four subtypes, non-granular pseudodepressed (NG-PD) LSTs (85.5%) had the highest rate of HGD/carcinoma, followed by the granular nodular mixed (G-NM) (77.0%), granular homogenous (29.5%), and non-granular flat elevated (24.2%) subtypes. Deep SMI occurred commonly in NG-PD LSTs (12.9%). In the adjusted multivariate analysis, NG-PD [odds ratio (OR) = 16.8, P < 0.001) and G-NM (OR = 7.8, P < 0.001) subtypes, size ≥ 2 cm (OR = 2.2, P = 0.005), and positive non-lifting sign (OR = 3.3, P = 0.024) were independently associated with HGD/carcinoma. The NG-PD subtype (OR = 13.3, P < 0.001) and rectosigmoid location (OR = 8.7, P = 0.007) were independent risk factors for deep SMI.ConclusionBecause of their increased risk for malignancy, it is highly recommended that NG-PD and G-NM LSTs are removed en bloc through ESD. Given their substantial risk for deep SMI, surgery needs to be considered for NG-PD LSTs located in the rectosigmoid, especially those with positive non-lifting signs.
| S-EPMC9305571 | biostudies-literature
Project description:In this study, we investigated CNAs of 59 tumor samples from 27 patients with submucosal-invasive gastric cancers (SMGC) by 44k oligonucleotide-based array comparative genomic hybridization (array CGH). 23 mucosal portion of SMGC vs 23 paired submucosal (SM) portion of SMGC, 9 SM portion vs 9 paired lymph node (LN) metastasis, 12 SMGC with LN metastasis vs 15 SMGC without LN metastasis
2012-01-20 | E-GEOD-26800 | biostudies-arrayexpress
Project description:Interventions: Group A. ESD group 1. The solution of a mixture of Glyceol and 1% 1900-KDa hyaluronic acid preparation is injected into the submucosal layer. 2. Mucosal incision is started with the knife for ESD. 3. The lesion is resected with submucosal dissection.
Group B. EMR group 1. The solution of normal saline is injected into the submucosal layer. 2. The lesion is resected with an electrosurgical snare.
Primary outcome(s): the incidence of local recurrence after endoscopic resection
Study Design: Parallel Randomized
| 2616263 | ecrin-mdr-crc
Project description:Background Endoscopic ultrasonography is an effective endoscopic examination method for determining the depth of colorectal cancer invasion. Narrow-band imaging (NBI) techniques increase the contrast of vascular structures and more clearly highlight subtle structures on mucosal surfaces, thereby improving the accuracy of endoscopic assessment. This study investigated the diagnostic efficacy of NBI in colorectal laterally spreading tumor (LST) and its submucosal invasion. Methods A total of 224 patients with colorectal LST admitted to the Affiliated Hospital of Putian University from January 2015 to December 2021 were enrolled in this study. The patients were divided into NBI and endoscopic ultrasonography groups according to the different examination methods they received. Subsequently, the clinicopathological characteristics of the patients were collected, and the rates of submucosal invasion of the four subtypes (LST-G-H, LST-G-NM, LST-NG-F, LST-NG-PD) were compared between the two groups. Also, the accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of judging the depth of LST lesions of the two examination methods were compared, taking the results of pathological tissue examination as the gold standard. Results This study enrolled 224 patients with LST (mean onset age: 57.98±6.48 years), including 123 males and 101 females. In terms of tumor location, 21 cases were located in the cecum, 22 cases in the ascending colon, 38 cases in the transverse colon, 11 cases in the descending colon, 12 cases in the descending sigmoid junction, 23 cases in the sigmoid colon, and 97 cases in the rectum. The sizes of the tumors ranged from 18.81 to 52.88 mm. Moreover, there were 21 cases of lesion infiltration into the submucosa, and the infiltration rate was 9.38%. Furthermore, the accuracy of NBI in diagnosing colorectal LST was significantly higher than that of endoscopic ultrasonography (87.05% vs. 57.14%); NBI was more accurate than endoscopic ultrasonography in the preoperative diagnosis of LST lesion depth in the rectal, non-rectal, granular (LST-G), non-granular (LST-NG), <40, and ≥40 mm groups. Conclusions Gastrointestinal NBI has a superior accuracy rate and value than endoscopic ultrasonography in diagnosing colorectal LST, tumor lesion depth, and submucosal invasion. Therefore, gastrointestinal NBI deserves to be promoted in clinical work.
| S-EPMC9834577 | biostudies-literature
Project description:International guidelines recommend deciding the treatment of colorectal lesions based on the estimated histology by endoscopic optical diagnosis. However, the theoretical and practical knowledge on optical diagnosis is not widely expanded
The mail goal of this randomised controlled trial is to compare the pooled sensitivity of optical diagnosis for predicting deep submucosal invasion in large non-pedunculated polyps > 20 mm assessed in routine colonoscopies of gastroenterologists attending a e-learning module (intervention group) vs gastroenterologists who do not (control group)
The main questions the study aims to answer are:
* Is the pooled sensitivity of optical diagnosis for predicting deep submucosal invasion in large non-pedunculated polyps assessed in routine colonoscopies increased in those gastroenterologists participating in the e-learning module?
* Is the pooled diagnostic accuracy of optical diagnosis for predicting deep sm invasion in large non-pedunculated polyps ≥ 20 mm assessed in routine colonoscopies increased in those gastroenterologists participating in the e-learning module?
* In lesions with submucosal invasion, is the en bloc and complete resection rate (R0) increased in those gastroenterologists participating in the e-learning module?
* In lesions referred to surgery, is the pooled benign polyps rate decreased in those gastroenterologists participating in the e-learning module?
* In lesions treated with advanced en bloc procedures (ESD, TAMIS, fullthickness resection), is the pooled rate of histology with high-grade dysplasia, intramucosal cancer or submucosal invasion increased in those gastroenterologists participating in the e-learning module?
* In lesions treated with piecemeal endoscopic resection, is the pooled rate of histology with high-grade dysplasia, intramucosal cancer or submucosal invasion decreased in those gastroenterologists participating in the e-learning module?
* Is the diagnostic accuracy for predicting deep submucosal invasion in a test with pictures increased after participating in the e-learning module?
The participants (or subjects of study) are gastroenterologists. They will be randomised to do the e-learning course (intervention group) or not (control group).
Researchers will compare clinical outcomes of gastroenterologists participating in the e-learning module vs gastroenterologists not participating in the e-learning module to see if:
* the pooled sensitivity of optical diagnosis for predicting deep submucosal invasion in large non-pedunculated polyps > 20 mm assessed in routine colonoscopies is increased.
* the pooled diagnostic accuracy of optical diagnosis for predicting deep sm invasion in large non-pedunculated polyps > 20 mm is increased.
* the en bloc and complete resection rate (R0) is increased in lesions with submucosal invasion.
* the pooled benign polyps rate decreased in lesions referred to surgery.
* the pooled rate of histology with high-grade dysplasia, intramucosal cancer or submucosal invasion increased in lesions treated with advanced en bloc procedures (ESD, TAMIS, fullthickness resection).
* the pooled rate of histology with high-grade dysplasia, intramucosal cancer or submucosal invasion decreased in lesions treated with piecemeal endoscopic resection.
* the diagnostic accuracy for predicting deep submucosal invasion in a test with pictures after participating is increased.
| 3397 | ecrin-mdr-crc