BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to th...BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.展开更多
BACKGROUND Choosing an optimal post-polypectomy management strategy of malignant colorectal polyps is challenging,and evidence regarding a surveillance-only strategy is limited.AIM To evaluate long-term outcomes after...BACKGROUND Choosing an optimal post-polypectomy management strategy of malignant colorectal polyps is challenging,and evidence regarding a surveillance-only strategy is limited.AIM To evaluate long-term outcomes after endoscopic removal of malignant colorectal polyps.METHODS A single-center retrospective cohort study was conducted to evaluate outcomes after endoscopic removal of malignant colorectal polyps between 2010 and 2020.Residual disease rate and nodal metastases after secondary surgery and local and distant recurrence rate for those with at least 1 year of follow-up were invest-igated.Event rates for categorical variables and means for continuous variables with 95%confidence intervals were calculated,and Fisher’s exact test and Mann-Whitney test were performed.Potential risk factors of adverse outcomes were RESULTS In total,135 lesions(mean size:22.1 mm;location:42%rectal)from 129 patients(mean age:67.7 years;56%male)were enrolled.The proportion of pedunculated and non-pedunculated lesions was similar,with en bloc resection in 82%and 47%of lesions,respectively.Tumor differentiation,distance from resection margins,depth of submucosal invasion,lymphovascular invasion,and budding were reported at 89.6%,45.2%,58.5%,31.9%,and 25.2%,respectively.Residual tumor was found in 10 patients,and nodal metastasis was found in 4 of 41 patients who underwent secondary surgical resection.Univariate analysis identified piecemeal resection as a risk factor for residual malignancy(odds ratio:1.74;P=0.042).At least 1 year of follow-up was available for 117 lesions from 111 patients(mean follow-up period:5.59 years).Overall,54%,30%,30%,11%,and 16%of patients presented at the 1-year,3-year,5-year,7-year,and 9-10-year surveillance examinations.Adverse outcomes occurred in 9.0%(local recurrence and dissemination in 4 patients and 9 patients,respectively),with no difference between patients undergoing secondary surgery and surveillance only.CONCLUSION Reporting of histological features and adherence to surveillance colonoscopy needs improvement.Long-term adverse outcome rates might be higher than previously reported,irrespective of whether secondary surgery was performed.展开更多
基金Supported by the Research Grants of the National Research,Development and Innovation Office,No.K125377,No.K134863 and No.K143549New National Excellence Program of the Ministry of Human Capacities,No.UNKP-20-5-SZTE-161,No.UNKP-22-3-SZTE-233,No.UNKP-23-5-SZTE-719,No.UNKP-22-4-SZTE-296 and No.UNKP-22-3-SZTE-278+1 种基金Janos Bolyai Research Grant,No.BO/00723/22the Géza Hetényi Research Grant by Albert Szent-Györgyi Medical School,University of Szeged.
文摘BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.
基金Supported by the New National Excellence Program of the Ministry for Innovation and Technology From the Source of the National Research,Development and Innovation Fund,No.ÚNKP-22-4-SZTE-296,No.ÚNKP-23-3-SZTE-268,and No.ÚNKP-23-5-SZTE-719the EU’s Horizon 2020 Research and Innovation Program under Grant Agreement,No.739593.
文摘BACKGROUND Choosing an optimal post-polypectomy management strategy of malignant colorectal polyps is challenging,and evidence regarding a surveillance-only strategy is limited.AIM To evaluate long-term outcomes after endoscopic removal of malignant colorectal polyps.METHODS A single-center retrospective cohort study was conducted to evaluate outcomes after endoscopic removal of malignant colorectal polyps between 2010 and 2020.Residual disease rate and nodal metastases after secondary surgery and local and distant recurrence rate for those with at least 1 year of follow-up were invest-igated.Event rates for categorical variables and means for continuous variables with 95%confidence intervals were calculated,and Fisher’s exact test and Mann-Whitney test were performed.Potential risk factors of adverse outcomes were RESULTS In total,135 lesions(mean size:22.1 mm;location:42%rectal)from 129 patients(mean age:67.7 years;56%male)were enrolled.The proportion of pedunculated and non-pedunculated lesions was similar,with en bloc resection in 82%and 47%of lesions,respectively.Tumor differentiation,distance from resection margins,depth of submucosal invasion,lymphovascular invasion,and budding were reported at 89.6%,45.2%,58.5%,31.9%,and 25.2%,respectively.Residual tumor was found in 10 patients,and nodal metastasis was found in 4 of 41 patients who underwent secondary surgical resection.Univariate analysis identified piecemeal resection as a risk factor for residual malignancy(odds ratio:1.74;P=0.042).At least 1 year of follow-up was available for 117 lesions from 111 patients(mean follow-up period:5.59 years).Overall,54%,30%,30%,11%,and 16%of patients presented at the 1-year,3-year,5-year,7-year,and 9-10-year surveillance examinations.Adverse outcomes occurred in 9.0%(local recurrence and dissemination in 4 patients and 9 patients,respectively),with no difference between patients undergoing secondary surgery and surveillance only.CONCLUSION Reporting of histological features and adherence to surveillance colonoscopy needs improvement.Long-term adverse outcome rates might be higher than previously reported,irrespective of whether secondary surgery was performed.
