Colorectal endoscopic mucosal resection (a procedure to remove precancerous, early-stage cancer or other abnormal tissues from the digestive tract) and reducing delayed bleeding in high risk patients
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ABSTRACT: Background and study aims
Delayed bleeding (bleeding from the bowel occurring more than 24 hours following endoscopic removal of polyps) is the most common complication following Endoscopic Mucosal Resection (EMR), occurring in up to 12% of cases depending on various risk factors. To date, there are no established guidelines to lessen this risk, with various studies of different treatment options showing some inconsistent and sometimes conflicting results. PuraStat® is a licenced product that can be applied through the endoscope directly following polyp removal to form a gel coat over the area where the polyp was removed. This product is already in use in UK hospitals in endoscopy procedures and has been proven to be completely safe.
The aim of the study is to collect data to help us understand whether applying PuraStat® after a colorectal polyp is removed can reduce the risk of delayed bleeding for a period of 30 days following EMR, compared to not using PuraStat® (standard practice).
Who can participate?
Patients undergoing EMR of colorectal polyps, and with high risk of delayed bleeding.
What does the study involve?
Patients with high delayed bleeding risk referred for EMR of colorectal polyps of 20mm or more in size will be randomised to receive either prophylactic application of PuraStat® to the EMR base (treatment group) or standard treatment (no PuraStat®, control group).
Project description:The effectiveness of colonoscopy in reducing colorectal cancer mortality relies on the detection and removal of neoplastic polyps. Because the risk of prevalent cancer and of transition to cancer increases with polyp size, effective and safe resection of large polyps is particularly important. Large polyps ≥20mm are removed by so-called endoscopic mucosal resection (EMR) using electrocautery snares. Resection of these large polyps is associated with a risk of severe complications that may require hospitalization and additional interventions. The most common risk is delayed bleeding which is observed in approximately 2-9% of patients. A recent retrospective study suggests that closure of the large mucosal defect after resection may decrease the risk of delayed bleeding. However, significant uncertainty remains about the polypectomy techniques to optimizing resection and minimizing risk. Important aspects that may affect risk include clipping of the mucosal defect and electrocautery setting.
Project description:<p>In the US, CRC incidence has declined with uptake in colonoscopy for early detection and removal of polyps, the precursor lesion, can stop a cancer from developing but in spite of this, CRC remains the second leading cause of cancer death in the United States. One third of people who undergo screening colonoscopy will have adenomatous polyps, but less than 5% of the time are these polyps presumed to go on to develop into cancer. Why does one polyp develop into cancer while another one that looks very similar does not. In this proposal we will identify what molecular genetic changes in the genome, in the mRNA expression and genetic methylation patterns will distinguish a polyp that has already transformed into cancer from one that has not.</p>
Project description:Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease. Therefore, we sought to identify gene expression changes in nasosinus inflamed mucosa and adjacent polyp tissue from subjects with aCRSwNP. Twelve asthmatic chronic rhinosinusitis (aCRS) subjects (11 with nasal polyps; aCRSwNP) provided inflamed nasosinus mucosa (11 samples) and adjacent polyp (10 samples) or a small mixed mucosa and polyp specimen (1 sample) (thus, 22 samples overall). Inflamed mucosa or polyp was from the middle meatus or anterior ethmoid cavity. As control samples, nasosinus tissue was collected from the inferior turbinate or uncinate process from normal or rhinitis subjects without nasal polyps (n=17); 4 had physician-diagnosed allergic rhinitis (AR), 2 had suspected AR, 1 had suspected vasomotor rhinitis, and 10 had no signs of nasosinus disease, allergy, or atopy. All 4 AR subjects chose to donate tissue outside of their known allergy season(s).
Project description:Colon polyps represent precursor lesions of colon cancers and their malignant potential varies according to histological subtype. A rare subtype of colon polyps is the Peutz-Jeghers (PJ) polyp. PJ polyps mostly occur in the context of Peutz-Jeghers Syndrome which is characterized by the development of multiple polyps in the intestinal tract and hyperpigmentation of oral mucosa and lips. Peutz-Jeghers Syndrome is an autosomal dominant disorder caused by germline mutations of the Serine Threonin Kinase STK11 (LKB1). PJ polyps very rarely occur outside of Peutz-Jeghers Syndrome and are then referred to as solitary PJ polyps. Contrary to Peutz-Jeghers Syndrome, the genetic basis and the malignant potential of solitary PJ polyps is currently unknown. To date, only one study described a sporadic PJ polyp finding no mutations of STK11, indicating that the molecular profile of solitary PJ polyps differs from Peutz-Jeghers syndrome. Methylome analysis revealed global hypomethylation and CpG island hypermethylation, two features that have been described as hallmarks of the colorectal cancer epigenome. These results provide a paradigm for a premalignant lesion that is defined by epigenetic changes.
Project description:Sessile serrated adenomas are now recognized as precursor lesions of a substantial subset of colorectal cancers arising via a so-called “serrated pathway”. However, their biological markers remain to be defined. The aim of our study was to identify differentially expressed genes in sessile serrated adenomas, hyperplastic polyps and tubular adenomas. Gene expression analysis demonstrated molecular differences between polyp types. Further studies using QRT-PCR on Cathepsin E demonstrated a significantly (p< 0.05) higher expression in sessile serrated adenomas as compared to both other polyp types. Trefoil Factor 1, showed the same trend of expression for sessile serrated adenomas as compared to hyperplastic polyps, and was significantly higher in both polyps compared to tubular adenomas. Immunohistochemistry for both proteins demonstrated strong cytoplasmic staining of abnormal crypts in all sessile serrated adenomas while staining in tubular adenomas and hyperplastic polyps was weak and focal. BRAF and KRAS mutation analysis were employed to further validate polyp discrimination. The findings demonstrated the positive association of the BRAF mutation, V600E, with sessile serrated adenomas and KRAS mutations with tubular adenomas (P<0.05). This study demonstrates CTSE and TFF1 over-expression in sessile serrated adenomas compared to both hyperplastic polyps and tubular adenomas. Keywords: colonic polyp tissue comparison, linear modelling, SSA
Project description:Interventions: Medical Device : After endoscopic removal of colon polyps larger than 2 cm, the mucosal defect is closured with a clips
Primary outcome(s): Complication ( delayed bleeding, delayed perforation, post electrocoagulation syndrome );Complication associated clipping ( hemorrhage, perforation)
Primary Purpose : Prevention, Intervention Model : Parallel, Blinding/Masking : Single, Blinding Target : Subject, Allocation : RCT
Project description:Adenomatous polyps adjacent to colorectal cancer (CRC) were found to exhibit two distinct microRNAs (miRs) patterns from normal mucosa to low- and separately, to high-grade dysplasia; presence in screen-detected adenoma of non-cancer patients is unknown. Global miR expression was performed on biopsies obtained from 109 healthy patients undergoing screening/surveillance colonoscopy. Included were normal mucosa (NM); hyperplastic polyp (HP); tubular adenoma (TA), tubulovillous adenoma, with or without, high-grade dysplasia (TVHG) and serrated-polyps; sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA). Logistic regression was used to model miRs predictive of histology and CRC risk. We identified 99 miRs that differed across five histologic groups (FDR=0.05) and that accurately separated on histology (Concordance Index (CI)=0.96). In HPNM, miRs-145, -143, -107a, -23b, and -24 were upregulated whereas miRs-663, -1268, -320b, -1275, and -671 where overexpressed in TVHGs (FDR P<0 .05). The expression of miR-145 and -30a showed high accuracy to separate low from high-risk polyps independent of serrated status (CI= 97.1%; AUC 93.4%). For TSAs, miR-125b and -199a were uniquely downregulated relative to HPNMs and miR-335 discriminated between non-serrated and serrated histology. Histologically advanced polyps from non-cancer patients share miR alterations with those reported for CRC and high-grade adenoma adjacent to tumor including downregulation of immune regulatory miRs-125 and -199a in TSAs; polyp that frequently present with in situ carcinoma. These data extend evidence that miR patterns of high-risk adenoma are detectable in subset of screen-detected adenoma for which measurement may be useful in in adenoma risk stratification.
Project description:scRNA-seq was applied to map the cellular landscape of colonic polyps from pediatric patients with SJP, JPS or PJS and aged-matched colonic tissues to help dissect polyp heterogeneity among different polyp subtypes and identify the underlying cellular and molecular events that may control disease outcome
Project description:FAP is an autosomal-dominant inherited disease caused by germline mutations in the APC gene 1. Two major FAP phenotypes, CFAP and AFAP, can be distinguished based on polyp numbers and age of onset. CFAP is characterized by the presence of hundreds to thousands of polyps. About half of these patients develop adenomas by age 15, and 95% develop adenomas by age 35. AFAP patients exhibit a milder phenotype than CFAP patients; AFAP is characterized by fewer polyps, later adenoma onset, and lower CRC risk. We used microarrays to analyze chromosome abberation of organids established from FAP patients.
Project description:FAP is an autosomal-dominant inherited disease caused by germline mutations in the APC gene 1. Two major FAP phenotypes, CFAP and AFAP, can be distinguished based on polyp numbers and age of onset. CFAP is characterized by the presence of hundreds to thousands of polyps. About half of these patients develop adenomas by age 15, and 95% develop adenomas by age 35. AFAP patients exhibit a milder phenotype than CFAP patients; AFAP is characterized by fewer polyps, later adenoma onset, and lower CRC risk. We used microarrays to analyze the expression profiles of organoids established from three CFAP and two AFAP patients.