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Endoscopy Mar 2024Cold snare polypectomy (CSP) is safer than and equally efficacious as hot snare polypectomy (HSP) for the removal of small (<10mm) colorectal polyps. The maximum polyp...
BACKGROUND
Cold snare polypectomy (CSP) is safer than and equally efficacious as hot snare polypectomy (HSP) for the removal of small (<10mm) colorectal polyps. The maximum polyp size that can be effectively managed by piecemeal CSP (p-CSP) without an excessive burden of recurrence is unknown.
METHODS
Resection error risks (RERs), defined as the estimated likelihood of incomplete removal of adenomatous tissue for a single snare resection pass, for CSP and HSP were calculated, based on an incomplete resection rate. Polyp area, snare size, estimated number of resections, and optimal resection defect area were modeled. Overall risk of incomplete resection (RIR) was defined as RIR=1 - (1 - p), where p is the RER and n the number of resections.
RESULTS
A 40-mm polyp has a four times greater area than a 20-mm polyp (314.16mm vs. 1256.64mm), and requires three times more resections (11 vs. 33, respectively, assuming 8-mm piecemeal resection pieces for p-CSP). RIRs for a 40-mm polyp by HSP and p-CSP were 15.1%-23% and 40.74%-60.60% respectively.
CONCLUSION
RER is more important with p-CSP than with HSP. The number of resections, n, and consequently RIR increases with increasing polyp size. Given the overwhelming safety of CSP, specific techniques to minimize the RER should be studied and developed.
Topics: Humans; Colonic Polyps; Colonoscopy; Adenoma; Electrocoagulation; Colorectal Neoplasms
PubMed: 37774737
DOI: 10.1055/a-2184-1609 -
Endocrine, Metabolic & Immune Disorders... Dec 2023Single Nucleotide Polymorphisms (SNPs) are used as drug susceptibility biomarkers in metabolic diseases. Alterations in the gene encoding triggers the enzyme flavin...
INTRODUCTION
Single Nucleotide Polymorphisms (SNPs) are used as drug susceptibility biomarkers in metabolic diseases. Alterations in the gene encoding triggers the enzyme flavin monooxygenase 3 (FMO3), involved in the Sulindac metabolization, which also is responsible for the inherited metabolic disorder. Trimethylaminuria (TMAu, OMIM: 602079). DPYD gene variants are associated with the enzyme dihydropyrimidine dehydrogenase deficiency (DPD; OMIM: 274270). This autosomal recessive metabolic disorder, ultimately leads to the inability to metabolize fluoropyrimidines, which causes severe toxicity in individuals treated with these drugs.
METHODS
Variants in genes responsible for the expression of enzymes that encode transporters or receptors involved in the metabolization pathways of certain drugs may condition the individuals response to certain drugs, compromising the therapeutic response and clinical prognosis. Thus the sequencing and identification of variants become relevant, not only gain knowledge on effects of these variants' on disease causality but also in terms of its side effects resulting from the coding enzymes responsible for drug metabolization.
RESULTS
It was found that patients with the c.472G>A (p.Glu158Lys) and c.923A>G (p.Glu308Gly) polymorphisms, in homozygosity, in FMO3 gene did not develop polyps, thus have a protective effect in the treatment of Familial Adenomatous Polyposis (PAF). However, in the case of the DPYD gene, c.1905+1G>A (IVS14+1G>A), c.1679T>G (p.Ile560Ser), c.2846A>T (p.Asp949Val) e c.1236G>A/HapB3 variants can be lethal in cancer patients indicated for fluoropyrimidine-based chemotherapy.
CONCLUSION
Knowledge on the drug mechanisms will affect the therapeutic response of patients treated with a given drug. Thus, pharmacogenetics is an essential tool in personalized medicine, since molecular studies allows the clinician to predict the probability of efficacy and toxicity of certain drugs, resulting higher efficiency in individualizing treatment and also improving the safety of the patient. From a personalized medicine perspective, the study of the characteristics of the drug and its metabolization site, the genes involved in the encoding of enzymes responsible for its metabolization will be of great interest.
PubMed: 38111112
DOI: 10.2174/0118715303271934231211085226 -
Biomedicine & Pharmacotherapy =... Aug 2023Therapeutic strategies that promote read-through of a mutant gene have proved effective for certain non-neoplastic diseases. However, the efficacy of this approach is...
Therapeutic strategies that promote read-through of a mutant gene have proved effective for certain non-neoplastic diseases. However, the efficacy of this approach is unproven regarding neoplastic diseases with germline nonsense mutations, including familial adenomatous polyposis. Here we examined the cancer-preventive efficacy of the macrolide antibiotic azithromycin, with a reported read-through effect, on intestinal tumorigenesis in C3B6F1 Apc mice harboring a nonsense Apc mutation resulting in a truncated Apc protein. Mice were given drinking water lacking azithromycin or containing 0.0125-0.2 mg/mL azithromycin from 3 weeks of age. The small intestine and cecum were analyzed for pathological changes and alterations of intestinal flora. Azithromycin suppressed the number of tumors and the proportion of adenocarcinomas, with the most effective drinking-water concentration being 0.0125 mg/mL. Furthermore, azithromycin recovered the cellular level of full-length Apc, resulting in downregulation of β-catenin and cyclin D1. Conversely, the effect of azithromycin on the diversity of the intestinal microbiota depended on the drinking-water concentration. These results suggest that the balance between azithromycin-mediate read-through of mutant Apc mRNA and antibacterial effects influences intestinal tumorigenesis. Thus, azithromycin is a potential anticancer agent for familial adenomatous polyposis patients harboring nonsense mutations.
Topics: Mice; Animals; Azithromycin; Codon, Nonsense; Alleles; Adenomatous Polyposis Coli; Cell Transformation, Neoplastic; Water; beta Catenin
PubMed: 37276642
DOI: 10.1016/j.biopha.2023.114968 -
Neuropathology and Applied Neurobiology Aug 2023The mutY DNA glycosylase encoded by the MUTYH gene prevents G:C → T:A transversions through the base excision repair DNA repair system. Germline biallelic...
AIMS
The mutY DNA glycosylase encoded by the MUTYH gene prevents G:C → T:A transversions through the base excision repair DNA repair system. Germline biallelic pathogenic variants in MUTYH cause an adenomatous polyposis called MUTYH-associated polyposis (MAP), an autosomal recessive disease (OMIM: 608456), with an increased risk of colorectal cancer. Digestive lesions in this context show an excess of G:C → T:A transversions, individualising a specific mutational signature associated with MUTYH deficiency called signature SBS36. Predisposition to other tumours in patients with germline biallelic pathogenic variants in MUTYH is suspected but remains unclear. We report the first case of medulloblastoma in a patient with MAP, carrying the homozygous pathogenic variant c.1227_1228dup, p.(Glu410Glyfs*43) in MUTYH.
METHODS
Whole exome sequencing was performed on the medulloblastoma to enlighten single nucleotide variants of interest, microsatellite status and mutational signature. The objective was to determine the involvement of MUTYH deficiency in the oncogenesis of this medulloblastoma.
RESULTS
The medulloblastoma has the mutational signature SBS36 and driver pathogenic variants in CTNNB1, PTCH1 and KDM6A corresponding to G:C → T:A transversions, suggesting a role of MUTYH deficiency in oncogenesis.
CONCLUSIONS
Therefore, medulloblastoma could be a rare manifestation associated with germline biallelic pathogenic variants in MUTYH.
Topics: Humans; Medulloblastoma; Genetic Predisposition to Disease; Adenomatous Polyposis Coli; Mutation; Cerebellar Neoplasms; Carcinogenesis; Colorectal Neoplasms
PubMed: 37524406
DOI: 10.1111/nan.12929 -
Journal of Gastroenterology and... Sep 2023Multiple duodenal polyposis associated with familial adenomatous polyposis (FAP) is a high risk of duodenal cancer development. We evaluated the feasibility of intensive... (Observational Study)
Observational Study
BACKGROUND AND AIM
Multiple duodenal polyposis associated with familial adenomatous polyposis (FAP) is a high risk of duodenal cancer development. We evaluated the feasibility of intensive endoscopic resection that is a comprehensive treatment strategy combining multiple kinds of endoscopic treatments.
METHODS
This is a retrospective observational study. From January 2012 to July 2022, a total of 28 consecutive patients in FAP who underwent endoscopic resection for multiple duodenal polyposis more than twice were included. Various endoscopic treatments, such as cold polypectomy (CP), endoscopic mucosal resection (EMR), underwater EMR (UEMR), endoscopic submucosal dissection (ESD), and endoscopic papillectomy (EP), were applied depending on lesions size and location. We evaluated individual information from patients' medical records, including patient characteristics, lesion characteristics, details of endoscopic treatment, pathologic findings, and Spigelman index (SI). We compared the differences in the number of treatments and observation periods with and without SI decrease.
RESULTS
A total of 1040 lesions were removed by 138 sessions of endoscopic resections. The median follow-up period was 3.2 years. At the beginning of the endoscopic intervention, median SI was 9 (6-11) and the proportion of Spigelman stage (SS) IV was 61%. Repeated endoscopic treatments finally reduced SI in 26 patients (93%), and the proportion of SS IV significantly decreased to 13% with every endoscopic treatment. The mean SI change was -4.2 points per year (95% confidence interval: -0.6 to -5.9). There were no patients required surgical duodenectomy during the follow-up period.
CONCLUSION
Intensive resection has a potential of downstaging duodenal lesions associated with FAP.
Topics: Humans; Adenomatous Polyposis Coli; Duodenum; Adenomatous Polyps; Endoscopy; Duodenal Neoplasms; Retrospective Studies
PubMed: 37423767
DOI: 10.1111/jgh.16281 -
Digestive and Liver Disease : Official... Sep 2023Gastric polyps represent an abnormal proliferation of the gastric mucosa. Chronic atrophic autoimmune gastritis (CAAG) targets parietal cells and results in...
BACKGROUND
Gastric polyps represent an abnormal proliferation of the gastric mucosa. Chronic atrophic autoimmune gastritis (CAAG) targets parietal cells and results in hypo-achlorhydria and hypergastrinemia, which exerts a proliferative effect on the gastric mucosa.
AIMS
We investigate the incidence of gastric polyps in CAAG patients.
METHODS
This is a single-center retrospective study examining patients with confirmed CAAG from January 1990 until June 2022. Demographic, clinical, biochemical, and serological data were collected for each included patient. The histopathological characteristics of the detected polyps were recorded.
RESULTS
A total of 176 CAAG patients were included. Eighty-nine (50.5%) had 163 incidental polyps. Seventy-six patients (85%) had 130 non-endocrine lesions, among which 118 (90.7%) were inflammatory, 6 (4.6%) adenomatous, and 4 (3%) fundic; 33 patients (37%) had gastric neuroendocrine neoplasms (gNENs), and 21 (23.6%) both; one had MALToma and one gastric adenocarcinoma. Higher circulating levels of gastrin and chromogranin A were observed among patients with polyps (median 668 vs 893 pg/ml p = 0.0237, 146 vs 207 ng/ml p = 0.0027, respectively).
CONCLUSION
CAAG implies a high incidence of gNENs and exocrine lesions. Gastrin plays a possible trophic role on the mucosa. Further evidence is needed to validate its predictive role for increased polyp risk in CAAG.
Topics: Humans; Gastrins; Retrospective Studies; Autoimmune Diseases; Gastritis; Gastritis, Atrophic; Gastric Mucosa; Stomach Neoplasms; Precancerous Conditions; Polyps
PubMed: 36858908
DOI: 10.1016/j.dld.2023.02.008 -
Arquivos de Gastroenterologia 2023Polypectomy is an important treatment option for preventing colorectal cancer. Incomplete polyp resection (IPR) is re-cognized as a risk factor for interval cancer.
BACKGROUND
Polypectomy is an important treatment option for preventing colorectal cancer. Incomplete polyp resection (IPR) is re-cognized as a risk factor for interval cancer.
OBJECTIVE
The primary objective was to evaluate the complete polyp resection (CPR) rate for cold snare polypectomy (CSP) in small non-pedunculated polyps and, secondarily, specimen retrieval and complication rates.
METHODS
We prospectively evaluated 479 polyps <10 mm removed by CSP in 276 patients by an inexperienced endoscopist.
RESULTS
A total of 476 polyps (99.4%) were resected en bloc. A negative margin (classified as CPR) was observed in 435 polyps (90.8%). An unclear or positive margin (classified as IPR) was observed in 43 cases (9.0%) and 1 case (0.2%), respectively, for an overall IPR rate of 9.2% (44/479). The IPR rate was 12.2% in the first half of cases and 5.9% in the second half (P=0.02). Dividing into tertiles, the IPR rate was 15.0% in the first tertile, 6.9% in the second tertile, and 5.7% in the third tertile (P=0.01). Dividing into quartiles, the IPR rate was 15.8% in the first quartile and 5.9% in the fourth quartile (P=0.03). The IPR rate was 6.3% for type 0-IIa lesions and 14.1% for type 0-Is lesions (P=0.01). For serrated and adenomatous lesions, the IPR rate was 9.2%. Specimen retrieval failed in 3.6% of cases. Immediate bleeding (>30 s) occurred in 1 case (0.2%), treated with argon plasma coagulation. No delayed bleeding or perforation occurred.
CONCLUSION
CSP is a safe technique that provides good results for the resection of small non-pedunculated polyps, with a short learning curve.
Topics: Humans; Colonic Polyps; Colonoscopy; Risk Factors; Adenomatous Polyps; Colorectal Neoplasms
PubMed: 38018552
DOI: 10.1590/S0004-2803.23042023-115 -
Annals of Gastroenterology 2024The incidence of colonic adenomas and colorectal cancer has been on the rise among young patients. In this study, we aimed to describe the characteristics of young...
BACKGROUND
The incidence of colonic adenomas and colorectal cancer has been on the rise among young patients. In this study, we aimed to describe the characteristics of young patients (<50 years) with adenomatous polyps and to characterize those polyps. We also aimed to determine appropriate surveillance intervals for young patients.
METHODS
We performed a retrospective chart review of patients <50 years of age who had polypectomy of 1 or more adenomatous polyps on colonoscopy between 2008 and 2021. Patient demographics, colonoscopy indication and polyp characteristics were obtained from the chart. Timing and findings on surveillance colonoscopies were recorded.
RESULTS
A total of 610 patients were included: mean age 42.9±5.9 years, 61% males, body mass index 27.5±4.7 kg/m, and over 50% smokers. The most common indications were abdominal pain (23.3%), rectal bleeding (22.3%), and change in bowel habits (17.6%). Almost half of the patients who had adenomas (299) were younger than 45 years. Tubular adenoma was the most frequently encountered type of polyp (571; 93.6%). Mean polyp size was 1.1±0.9 cm. The most common location of adenomas was the sigmoid colon (41%). Of patients with adenomas, 156 (26%) had surveillance colonoscopy within 2.9±2.3 years; 74 patients (47.4%) were found to have new adenomas.
CONCLUSIONS
Patients aged <50 years with colonic adenomas were mostly males, overweight, and smokers. Further adenomas were found in 47% of surveillance colonoscopies, and most were encountered within 5 years. High rates of recurrent adenomas in people <50 years of age may warrant frequent surveillance.
PubMed: 38779645
DOI: 10.20524/aog.2024.0872 -
The Turkish Journal of Gastroenterology... Oct 2023The aim of this study was to both classify data of familial adenomatous polyposis patients with and without duode- nal cancer and to identify important genes that may be...
BACKGROUND/AIMS
The aim of this study was to both classify data of familial adenomatous polyposis patients with and without duode- nal cancer and to identify important genes that may be related to duodenal cancer by XGboost model.
MATERIALS AND METHODS
The current study was performed using expression profile data from a series of duodenal samples from familial adenomatous polyposis patients to explore variations in the familial adenomatous polyposis duodenal adenoma-carcinoma sequence. The expression profiles obtained from cancerous, adenomatous, and normal tissues of 12 familial adenomatous polyposis patients with duodenal cancer and the tissues of 12 familial adenomatous polyposis patients without duodenal cancer were compared. The ElasticNet approach was utilized for the feature selection. Using 5-fold cross-validation, one of the machine learning approaches, XGboost, was utilized to classify duodenal cancer. Accuracy, balanced accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score performance metrics were assessed for model performance.
RESULTS
According to the variable importance obtained from the modeling, ADH1C, DEFA5, CPS1, SPP1, DMBT1, VCAN-AS1, APOB genes (cancer vs. adenoma); LOC399753, APOA4, MIR548X, and ADH1C genes (adenoma vs. adenoma); SNORD123, CEACAM6, SNORD78, ANXA10, SPINK1, and CPS1 (normal vs. adenoma) genes can be used as predictive biomarkers.
CONCLUSIONS
The proposed model used in this study shows that the aforementioned genes can forecast the risk of duodenal cancer in patients with familial adenomatous polyposis. More comprehensive analyses should be performed in the future to assess the reliability of the genes determined.
Topics: Humans; Duodenal Neoplasms; Reproducibility of Results; Adenomatous Polyposis Coli; Adenoma; Duodenum; Calcium-Binding Proteins; DNA-Binding Proteins; Tumor Suppressor Proteins; Trypsin Inhibitor, Kazal Pancreatic
PubMed: 37565794
DOI: 10.5152/tjg.2023.22346 -
Clinical and Translational... Aug 2023Patients with serrated polyposis syndrome (SPS) have an increased risk to develop colorectal cancer (CRC). Due to an abundance of serrated polyps, these CRCs are assumed...
INTRODUCTION
Patients with serrated polyposis syndrome (SPS) have an increased risk to develop colorectal cancer (CRC). Due to an abundance of serrated polyps, these CRCs are assumed to arise mainly through the serrated neoplasia pathway rather than through the classical adenoma-carcinoma pathway. We aimed to evaluate the pathogenetic routes of CRCs in patients with SPS.
METHODS
We collected endoscopy and pathology data on CRCs and polyps of patients with SPS under treatment in our center. Our primary end point was the proportion of BRAFV600E mutated CRCs, indicating serrated pathway CRCs (sCRCs). CRCs lacking BRAFV600E most likely inferred a classical adenoma-carcinoma origin (aCRCs). We assessed patient, polyp, and CRC characteristics and stratified for BRAFV600E mutation status.
RESULTS
Thirty-five patients with SPS harbored a total of 43 CRCs. Twenty-one CRCs (48.8%) carried a BRAFV600E mutation, 10 of which lacked MLH1 staining and 17 (81%) were located in the proximal colon. Twenty-two CRCs (51.1%) did not carry a BRAFV600E mutation and were MLH1 proficient. Of these 22 putatively aCRCs, 17 (77.3%) were located distally and one-third (36.4%) harbored a pathogenic KRAS or NRAS mutation. In patients with BRAFwt -CRCs, a higher ratio of the median number of conventional adenomas versus serrated polyps was found (4 vs 13) than patients with BRAFV600E -CRCs (1 vs 14).
DISCUSSION
Our study indicates that in patients with SPS, the ratio of sCRCs:aCRCs on average is 50:50. This elevated sCRC:aCRC ratio in patients with SPS, when compared with non-SPS patients, correlates well with the differences in the ratios of the numbers of sessile serrated lesions and conventional adenomas in patients with SPS and non-SPS patients, respectively.
Topics: Humans; Colonic Polyps; Colorectal Neoplasms; Adenomatous Polyposis Coli; Adenoma; Carcinoma
PubMed: 37352472
DOI: 10.14309/ctg.0000000000000611