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
AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn&...AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease (CD) and ulcerative colitis (UC).展开更多
AIM:To assess tumor necrosis factor-a(TNF-a),infliximab(IFX)concentrations,and antibodies against IFX molecules in patients with inflammatory bowel disease(IBD)who develop loss of response,side effects,or allergic rea...AIM:To assess tumor necrosis factor-a(TNF-a),infliximab(IFX)concentrations,and antibodies against IFX molecules in patients with inflammatory bowel disease(IBD)who develop loss of response,side effects,or allergic reaction during anti TNF-a therapy.METHODS:Blood samples of 36 patients with response loss,side effects,or hypersensitivity to IFX therapy(Group?Ⅰ)and 31 patients in complete clinical remission(GroupⅡ)selected as a control group were collected to measure trough serum TNF-a level,IFX,and anti-IFX antibody(ATI)concentration.We examined the correlation between loss of response,the development of side effects or hypersensitivity,and serum TNF-a,IFX trough levels,and ATI concentrations.RESULTS:The serum TNF-a level was shown to be correlated with the presence of ATI;ATI positivity was significantly correlated with low trough levels of IFX.ATIs were detected in 25%of IBD patients with loss of response,side effects,or hypersensitivity,however no association was revealed between these patients and antibody positivity or lower serum IFX levels.Previous use of IFX correlated with the development of ATI,although concomitant immunosuppression did not have any impact on them.CONCLUSION:On the basis of the present study,we suggest that the simultaneous measurement of serum TNF-a level,serum anti TNF-a concentration,and antibodies against anti TNF-a may further help to optimize the therapy in critical situations.展开更多
AIM To evaluate the presence of submucosal and myenteric plexitis and its role in predicting postoperative recurrence.METHODS Data from all patients who underwent Crohn's disease(CD)-related resection at the Unive...AIM To evaluate the presence of submucosal and myenteric plexitis and its role in predicting postoperative recurrence.METHODS Data from all patients who underwent Crohn's disease(CD)-related resection at the University of Szeged, Hungary between 2004 and 2014 were analyzed retrospectively. Demographic data, smoking habits, previous resection, treatment before and after surgery, resection margins, neural fiber hyperplasia, submucosal and myenteric plexitis were evaluated as possible predictors of postoperative recurrence. Histological samples were analyzed blinded to the postoperative outcome and the clinical history of the patient. Plexitis was evaluated based on the appearance of the most severely inflamed ganglion or nerve bundle. Patients underwent regular follow-up with colonoscopy after surgery. Postoperativerecurrence was defined on the basis of endoscopic and clinical findings, and/or the need for additional surgical resection. RESULTS One hundred and four patients were enrolled in the study. Ileocecal, colonic, and small bowel resection were performed in 73.1%, 22.1% and 4.8% of the cases, respectively. Mean disease duration at the time of surgery was 6.25 years. Twenty-six patients underwent previous CD-related surgery. Forty-three point two percent of the patients were on 5-aminosalicylate, 20% on corticosteroid, 68.3% on immunomodulant, and 4% on anti-tumor necrosis factor-alpha postoperative treatment. Postoperative recurrence occurred in 61.5% of the patients; of them 39.1% had surgical recurrence. 92.2% of the recurrences developed within the first five years after the index surgery. Mean disease duration for endoscopic relapse was 2.19 years. The severity of submucosal plexitis was a predictor of the need for second surgery(OR = 1.267, 95%CI: 1.000-1.606, P = 0.050). Female gender(OR = 2.21, 95%CI: 0.98-5.00, P = 0.056), stricturing disease behavior(OR = 3.584, 95%CI: 1.344-9.559, P = 0.011), and isolated ileal localization(OR = 2.671, 95%CI: 1.033-6.910, P = 0.043) were also predictors of postoperative recurrence. No association was revealed between postoperative recurrence and smoking status, postoperative prophylactic treatment and the presence of myenteric plexitis and relapse.CONCLUSION The presence of severe submucosal plexitis with lymphocytes in the proximal resection margin is more likely to result in postoperative relapse in CD.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 TAMOP-4.2.2.A-11/1/KONV-2012-0035,TA-MOP-4.2.2-A-11/1/KONV-2012-0052 TAMOP-4.2.2.A-11/1/KONV-2012-0073OTKA Research Proposal PD 105948(PI:Klaudia Farkas)
文摘AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease (CD) and ulcerative colitis (UC).
基金Supported by TAMOP-4.2.2.A-11/1/KONV-2012-0035,TAMOP-4.2.2-A-11/1/KONV-2012-0052 TAMOP-4.2.2.A-11/1/KONV-2012-0073OTKA Research Proposal PD 105948(PI:Klaudia Farkas)
文摘AIM:To assess tumor necrosis factor-a(TNF-a),infliximab(IFX)concentrations,and antibodies against IFX molecules in patients with inflammatory bowel disease(IBD)who develop loss of response,side effects,or allergic reaction during anti TNF-a therapy.METHODS:Blood samples of 36 patients with response loss,side effects,or hypersensitivity to IFX therapy(Group?Ⅰ)and 31 patients in complete clinical remission(GroupⅡ)selected as a control group were collected to measure trough serum TNF-a level,IFX,and anti-IFX antibody(ATI)concentration.We examined the correlation between loss of response,the development of side effects or hypersensitivity,and serum TNF-a,IFX trough levels,and ATI concentrations.RESULTS:The serum TNF-a level was shown to be correlated with the presence of ATI;ATI positivity was significantly correlated with low trough levels of IFX.ATIs were detected in 25%of IBD patients with loss of response,side effects,or hypersensitivity,however no association was revealed between these patients and antibody positivity or lower serum IFX levels.Previous use of IFX correlated with the development of ATI,although concomitant immunosuppression did not have any impact on them.CONCLUSION:On the basis of the present study,we suggest that the simultaneous measurement of serum TNF-a level,serum anti TNF-a concentration,and antibodies against anti TNF-a may further help to optimize the therapy in critical situations.
文摘AIM To evaluate the presence of submucosal and myenteric plexitis and its role in predicting postoperative recurrence.METHODS Data from all patients who underwent Crohn's disease(CD)-related resection at the University of Szeged, Hungary between 2004 and 2014 were analyzed retrospectively. Demographic data, smoking habits, previous resection, treatment before and after surgery, resection margins, neural fiber hyperplasia, submucosal and myenteric plexitis were evaluated as possible predictors of postoperative recurrence. Histological samples were analyzed blinded to the postoperative outcome and the clinical history of the patient. Plexitis was evaluated based on the appearance of the most severely inflamed ganglion or nerve bundle. Patients underwent regular follow-up with colonoscopy after surgery. Postoperativerecurrence was defined on the basis of endoscopic and clinical findings, and/or the need for additional surgical resection. RESULTS One hundred and four patients were enrolled in the study. Ileocecal, colonic, and small bowel resection were performed in 73.1%, 22.1% and 4.8% of the cases, respectively. Mean disease duration at the time of surgery was 6.25 years. Twenty-six patients underwent previous CD-related surgery. Forty-three point two percent of the patients were on 5-aminosalicylate, 20% on corticosteroid, 68.3% on immunomodulant, and 4% on anti-tumor necrosis factor-alpha postoperative treatment. Postoperative recurrence occurred in 61.5% of the patients; of them 39.1% had surgical recurrence. 92.2% of the recurrences developed within the first five years after the index surgery. Mean disease duration for endoscopic relapse was 2.19 years. The severity of submucosal plexitis was a predictor of the need for second surgery(OR = 1.267, 95%CI: 1.000-1.606, P = 0.050). Female gender(OR = 2.21, 95%CI: 0.98-5.00, P = 0.056), stricturing disease behavior(OR = 3.584, 95%CI: 1.344-9.559, P = 0.011), and isolated ileal localization(OR = 2.671, 95%CI: 1.033-6.910, P = 0.043) were also predictors of postoperative recurrence. No association was revealed between postoperative recurrence and smoking status, postoperative prophylactic treatment and the presence of myenteric plexitis and relapse.CONCLUSION The presence of severe submucosal plexitis with lymphocytes in the proximal resection margin is more likely to result in postoperative relapse in CD.
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.
