Pub Date : 2024-08-21DOI: 10.14309/ctg.0000000000000759
Jing Wang, Zhishun Tang, Jiao Li, Anning Yin, Yaqing Xu, Liping Zou, Haixia Ren, Jian Kang, Juan Su, Qian Zhou, Yang Wang, Wei Wang, Jing Zhang, Huipeng Wan, Ping An
Introduction: Despite increasing studies confirming the efficacy of vedolizumab (VDZ) in Crohn's disease (CD), improving the responses to this biologic agent remains challenging in clinical practice. In this article, we investigated the efficacy of combined treatment of VDZ and 16-week exclusive enteral nutrition (EEN) in moderately to severely active CD.
Methods: From October 2020 to October 2023, 81 patients with moderately to severely active CD treated with VDZ from 2 inflammatory bowel disease centers were retrospectively selected. Forty-one patients received treatment of VDZ with concomitant 16-week EEN (VDZ + EEN cohort), and 40 patients received VDZ treatment alone (VDZ cohort). Clinical and biological outcomes were evaluated. Endoscopic response and mucosal healing were assessed by colonoscopy at weeks 16 and 52.
Results: There was no statistically significant difference between 2 groups at baseline for demographic and clinical characteristics. Compared with patients treated with VDZ alone, patients in the VDZ + EEN cohort achieved higher rates of clinical response (84.2% vs 40.0%), clinical remission (81.6% vs 30.0%), endoscopic response (91.4% vs 34.6%), including mucosal healing (85.7% vs 26.9%) at week 16. The superiority of VDZ + EEN treatment sustained in maintenance, with 76.7% (vs 33.3%) clinical response, 70.0% (vs 26.7%) clinical remission, 76.9% (vs 33.3%) endoscopic response, and 61.5% (vs 26.7%) mucosal healing at week 52. None of the patients experienced severe adverse events.
Discussion: VDZ with concomitant 16-week EEN might be an effective and optimized approach with solid efficacy in the induction and maintenance treatment of active CD.
背景:尽管越来越多的研究证实了维多珠单抗对克罗恩病(CD)的疗效,但在临床实践中,改善对这种生物制剂的反应仍具有挑战性。在此,我们研究了维多珠单抗和16周纯肠内营养(EEN)联合治疗中度至重度活动性克罗恩病的疗效:回顾性选取了2020年10月至2023年10月期间,来自三个IBD中心的81例接受维多珠单抗治疗的中重度活动性CD患者。41名患者接受了韦多珠单抗治疗,并同时接受了为期16周的EEN治疗(韦多珠单抗,VDZ+EEN队列),40名患者单独接受了韦多珠单抗治疗(VDZ队列)。对临床和生物学结果进行了评估。在第16周和第52周通过结肠镜检查评估内镜反应和粘膜愈合情况:结果:两组患者在人口统计学和临床特征方面的基线差异无统计学意义。与单独接受维多珠单抗治疗的患者相比,VDZ+EEN组患者在第16周时的临床应答率(84.2% vs. 40.0%)、临床缓解率(81.6% vs. 30.0%)、内镜应答率(91.4% vs. 34.6%)和粘膜愈合率(85.7% vs. 26.9%)均较高。VDZ+EEN治疗的优越性在维持治疗中得以保持,第52周时,临床应答率为76.7%(vs 33.3%),临床缓解率为70.0%(vs 26.7%),内镜应答率为76.9%(vs 33.3%),粘膜愈合率为61.5%(vs 26.7%)。没有患者出现严重不良反应:韦多珠单抗联合16周EEN可能是诱导和维持治疗活动性CD的一种有效且疗效确切的优化方法。
{"title":"Treatment of Vedolizumab With Exclusive Enteral Nutrition in Adult Patients With Moderate to Severe Crohn's Disease (Crohn Exclusive Enteral Nutrition Study).","authors":"Jing Wang, Zhishun Tang, Jiao Li, Anning Yin, Yaqing Xu, Liping Zou, Haixia Ren, Jian Kang, Juan Su, Qian Zhou, Yang Wang, Wei Wang, Jing Zhang, Huipeng Wan, Ping An","doi":"10.14309/ctg.0000000000000759","DOIUrl":"10.14309/ctg.0000000000000759","url":null,"abstract":"<p><strong>Introduction: </strong>Despite increasing studies confirming the efficacy of vedolizumab (VDZ) in Crohn's disease (CD), improving the responses to this biologic agent remains challenging in clinical practice. In this article, we investigated the efficacy of combined treatment of VDZ and 16-week exclusive enteral nutrition (EEN) in moderately to severely active CD.</p><p><strong>Methods: </strong>From October 2020 to October 2023, 81 patients with moderately to severely active CD treated with VDZ from 2 inflammatory bowel disease centers were retrospectively selected. Forty-one patients received treatment of VDZ with concomitant 16-week EEN (VDZ + EEN cohort), and 40 patients received VDZ treatment alone (VDZ cohort). Clinical and biological outcomes were evaluated. Endoscopic response and mucosal healing were assessed by colonoscopy at weeks 16 and 52.</p><p><strong>Results: </strong>There was no statistically significant difference between 2 groups at baseline for demographic and clinical characteristics. Compared with patients treated with VDZ alone, patients in the VDZ + EEN cohort achieved higher rates of clinical response (84.2% vs 40.0%), clinical remission (81.6% vs 30.0%), endoscopic response (91.4% vs 34.6%), including mucosal healing (85.7% vs 26.9%) at week 16. The superiority of VDZ + EEN treatment sustained in maintenance, with 76.7% (vs 33.3%) clinical response, 70.0% (vs 26.7%) clinical remission, 76.9% (vs 33.3%) endoscopic response, and 61.5% (vs 26.7%) mucosal healing at week 52. None of the patients experienced severe adverse events.</p><p><strong>Discussion: </strong>VDZ with concomitant 16-week EEN might be an effective and optimized approach with solid efficacy in the induction and maintenance treatment of active CD.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 10.14309/ctg.0000000000000761
Yuancheng Li, Xingchao Liu, Chengcheng Zhang, Ran Tao, Bi Pan, Wei Liu, Di Jiang, Feng Hu, Zeliang Xu, Dehong Tan, Yanjiao Ou, Xun Li, Yuemei You, Leida Zhang
Background: A precise model for predicting outcomes is needed to guide perioperative management. With the developments of liver transplantation (LT) discipline, previous models may become inappropriate or noncomprehensive. Thus, we aimed to develop a novel model integrating variables from donors and recipients for quick assessment of transplant outcomes.
Methods: The risk model was based on Cox regression in a randomly selected derivation cohort and verified in a validation cohort. Perioperative data and overall survival were compared between stratifications grouped by X-tile. Receiver operating characteristic curve and decision curve analysis were used to compare the models. Violin and raincloud plots were generated to present post-LT complications distributed in different stratifications.
Results: Overall, 528 patients receiving LT from 2 centers were included with 2/3 in the derivation cohort and 1/3 in the validation cohort. Cox regression analysis showed that cold ischemia time (CIT) (P=0.012) and the Model for End-Stage Liver Disease (MELD) (P=0.007) score were predictors of survival. After comparison with the logarithmic models, the primitive algorithms of CIT and MELD were defined as the CIT-MELD Index (CMI). CMI was stratified by X-tile (grade 1 ≤1.06, 1.06< grade 2 ≤1.87, grade 3 >1.87). In both cohorts, CMI performed better in calculating transplant outcomes than the balance of risk score, including perioperative incidents and prevalence of complications.
Conclusions: Model integrating variables from graft and recipient made the prediction more accurate and available. CMI provided new sight in outcome evaluation and risk factor management of LT.
{"title":"A brief model evaluated outcomes after liver transplantation based on the matching of donor graft and recipient.","authors":"Yuancheng Li, Xingchao Liu, Chengcheng Zhang, Ran Tao, Bi Pan, Wei Liu, Di Jiang, Feng Hu, Zeliang Xu, Dehong Tan, Yanjiao Ou, Xun Li, Yuemei You, Leida Zhang","doi":"10.14309/ctg.0000000000000761","DOIUrl":"https://doi.org/10.14309/ctg.0000000000000761","url":null,"abstract":"<p><strong>Background: </strong>A precise model for predicting outcomes is needed to guide perioperative management. With the developments of liver transplantation (LT) discipline, previous models may become inappropriate or noncomprehensive. Thus, we aimed to develop a novel model integrating variables from donors and recipients for quick assessment of transplant outcomes.</p><p><strong>Methods: </strong>The risk model was based on Cox regression in a randomly selected derivation cohort and verified in a validation cohort. Perioperative data and overall survival were compared between stratifications grouped by X-tile. Receiver operating characteristic curve and decision curve analysis were used to compare the models. Violin and raincloud plots were generated to present post-LT complications distributed in different stratifications.</p><p><strong>Results: </strong>Overall, 528 patients receiving LT from 2 centers were included with 2/3 in the derivation cohort and 1/3 in the validation cohort. Cox regression analysis showed that cold ischemia time (CIT) (P=0.012) and the Model for End-Stage Liver Disease (MELD) (P=0.007) score were predictors of survival. After comparison with the logarithmic models, the primitive algorithms of CIT and MELD were defined as the CIT-MELD Index (CMI). CMI was stratified by X-tile (grade 1 ≤1.06, 1.06< grade 2 ≤1.87, grade 3 >1.87). In both cohorts, CMI performed better in calculating transplant outcomes than the balance of risk score, including perioperative incidents and prevalence of complications.</p><p><strong>Conclusions: </strong>Model integrating variables from graft and recipient made the prediction more accurate and available. CMI provided new sight in outcome evaluation and risk factor management of LT.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 10.14309/ctg.0000000000000763
Beyza N Aydin, Emma J Stinson, Robert L Hanson, Helen C Looker, Tomás Cabeza De Baca, Jonathan Krakoff, Douglas C Chang
Introduction: Animal models indicate that hepatic insulin resistance (IR) promotes cholesterol gallstone disease (GSD). We sought to determine whether hepatic and whole-body IR is associated with incident GSD.
Methods: At baseline, 450 Southwestern Indigenous American adults without GSD were included. Participants had a 2-step hyperinsulinemic-euglycemic clamp with glucose tracer at submaximal and maximal insulin stimulation (240 and 2,400 pmol/m 2 /min) for whole-body IR (M-low and M-high) and hepatic glucose production (HGP) before and during submaximal insulin infusion (HGP-basal and HGP-insulin). Incident GSD was identified during follow-up visits conducted at ∼2-year intervals. The associations of HGP (basal, insulin, and % suppression), M-low, and M-high with risk of GSD were assessed by Cox regression models adjusted for age, sex, body fat (%), glucose, and insulin.
Results: Sixty participants (13%) developed GSD (median follow-up: 11.6 years). Participants who developed GSD were of similar age and whole-body IR as those who did not ( P 's > 0.07) but were more likely to be female; have higher body fat, higher HGP-basal, and HGP-insulin; and lower % suppression of HGP ( P 's < 0.02). In separate adjusted models, higher HGP-insulin and lower % suppression of HGP were associated with increased risk for GSD (hazard ratio [HR] per SD: HR 1.38, 95% CI 1.12-1.69, P = 0.002; HR 1.41, 95% CI 1.16-1.72, P = 0.0007). HGP-basal, M-low, and M-high were not associated with GSD in adjusted models ( P 's > 0.22).
Discussion: Resistance to insulin suppression of HGP increases risk for GSD. Hepatic IR is a link between GSD and other conditions of the metabolic syndrome.
{"title":"Hepatic Insulin Resistance Increases Risk of Gallstone Disease in Indigenous Americans in the Southwestern United States.","authors":"Beyza N Aydin, Emma J Stinson, Robert L Hanson, Helen C Looker, Tomás Cabeza De Baca, Jonathan Krakoff, Douglas C Chang","doi":"10.14309/ctg.0000000000000763","DOIUrl":"10.14309/ctg.0000000000000763","url":null,"abstract":"<p><strong>Introduction: </strong>Animal models indicate that hepatic insulin resistance (IR) promotes cholesterol gallstone disease (GSD). We sought to determine whether hepatic and whole-body IR is associated with incident GSD.</p><p><strong>Methods: </strong>At baseline, 450 Southwestern Indigenous American adults without GSD were included. Participants had a 2-step hyperinsulinemic-euglycemic clamp with glucose tracer at submaximal and maximal insulin stimulation (240 and 2,400 pmol/m 2 /min) for whole-body IR (M-low and M-high) and hepatic glucose production (HGP) before and during submaximal insulin infusion (HGP-basal and HGP-insulin). Incident GSD was identified during follow-up visits conducted at ∼2-year intervals. The associations of HGP (basal, insulin, and % suppression), M-low, and M-high with risk of GSD were assessed by Cox regression models adjusted for age, sex, body fat (%), glucose, and insulin.</p><p><strong>Results: </strong>Sixty participants (13%) developed GSD (median follow-up: 11.6 years). Participants who developed GSD were of similar age and whole-body IR as those who did not ( P 's > 0.07) but were more likely to be female; have higher body fat, higher HGP-basal, and HGP-insulin; and lower % suppression of HGP ( P 's < 0.02). In separate adjusted models, higher HGP-insulin and lower % suppression of HGP were associated with increased risk for GSD (hazard ratio [HR] per SD: HR 1.38, 95% CI 1.12-1.69, P = 0.002; HR 1.41, 95% CI 1.16-1.72, P = 0.0007). HGP-basal, M-low, and M-high were not associated with GSD in adjusted models ( P 's > 0.22).</p><p><strong>Discussion: </strong>Resistance to insulin suppression of HGP increases risk for GSD. Hepatic IR is a link between GSD and other conditions of the metabolic syndrome.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19DOI: 10.14309/ctg.0000000000000760
Simone Augustinus, Matthanja Bieze, Charlotte L Van Veldhuisen, Marja A Boermeester, Bert A Bonsing, Stefan A W Bouwense, Marco J Bruno, Olivier R Busch, Werner Ten Hoope, Jan-Willem Kallewaard, Henk J van Kranen, Marieke Niesters, Niels C J Schellekens, Monique A H Steegers, Rogier P Voermans, Judith de Vos-Geelen, Johanna W Wilmink, Jan H M Van Zundert, Casper H van Eijck, Marc G Besselink, Markus W Hollmann
Introduction: Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively.
Methods: Multicentre prospective non-randomized pilot study including patients with moderate or severe pain (NRS ≥ 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5mg/kg, was followed by continuous infusion at 1.5 mg/kg/hour. The dose was raised every 15 minutes until treatment response (up to a maximum 2mg/kg/hour) and consecutively administered for two hours. Primary outcome was the mean difference in pain severity, pre-infusion and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease ≥ 1.3 points was considered clinically relevant.
Results: Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day one was 1.1 (SD±1.3) points for patients with PDAC and 0.5 (SD±1.7) for CP patients. A clinically relevant decrease in BPI on day one was reported in 9/29 patients (31%), this response lasted up to one month. No serious complications were reported, and only three minor complications (vertigo, nausea, tingling of mouth). Treatment with lidocaine did not impact quality of life.
Conclusion: Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group, and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group.
{"title":"Intravenous lidocaine for refractory pain in patients with pancreatic ductal adenocarcinoma and chronic pancreatitis (LIDOPAN): a multicenter prospective non-randomized pilot study.","authors":"Simone Augustinus, Matthanja Bieze, Charlotte L Van Veldhuisen, Marja A Boermeester, Bert A Bonsing, Stefan A W Bouwense, Marco J Bruno, Olivier R Busch, Werner Ten Hoope, Jan-Willem Kallewaard, Henk J van Kranen, Marieke Niesters, Niels C J Schellekens, Monique A H Steegers, Rogier P Voermans, Judith de Vos-Geelen, Johanna W Wilmink, Jan H M Van Zundert, Casper H van Eijck, Marc G Besselink, Markus W Hollmann","doi":"10.14309/ctg.0000000000000760","DOIUrl":"10.14309/ctg.0000000000000760","url":null,"abstract":"<p><strong>Introduction: </strong>Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively.</p><p><strong>Methods: </strong>Multicentre prospective non-randomized pilot study including patients with moderate or severe pain (NRS ≥ 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5mg/kg, was followed by continuous infusion at 1.5 mg/kg/hour. The dose was raised every 15 minutes until treatment response (up to a maximum 2mg/kg/hour) and consecutively administered for two hours. Primary outcome was the mean difference in pain severity, pre-infusion and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease ≥ 1.3 points was considered clinically relevant.</p><p><strong>Results: </strong>Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day one was 1.1 (SD±1.3) points for patients with PDAC and 0.5 (SD±1.7) for CP patients. A clinically relevant decrease in BPI on day one was reported in 9/29 patients (31%), this response lasted up to one month. No serious complications were reported, and only three minor complications (vertigo, nausea, tingling of mouth). Treatment with lidocaine did not impact quality of life.</p><p><strong>Conclusion: </strong>Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group, and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13DOI: 10.14309/ctg.0000000000000758
Soo Kyung Park, Darwin L Conwell, Phil A Hart, Shuang Li, Kimberly Stello, Evan L Fogel, William E Fisher, Christopher E Forsmark, Stephen J Pandol, Walter G Park, Mark Topazian, Jose Serrano, Santhi Swaroop Vege, Stephen K Van Den Eeden, Liang Li, Dhiraj Yadav, Jami L Saloman
Introduction: Chronic Pancreatitis Prognosis Score (COPPS) was developed to discriminate disease severity and predict risk for future hospitalizations. In this cohort study, we evaluated if COPPS predicts the likelihood of hospitalization(s) in an American cohort.
Methods: The Chronic Pancreatitis, Diabetes, and Pancreatic Cancer consortium provided data and serum from subjects with chronic pancreatitis (N = 279). COPPS was calculated with baseline data and stratified by severity (low, moderate, and high). Primary endpoints included number and duration of hospitalizations during 12-month follow-up.
Results: The mean ± SD COPPS was 8.4 ± 1.6. COPPS correlated with all primary outcomes: hospitalizations for any reason (number: r = 0.15, P = 0.01; duration: r = 0.16, P = 0.01) and pancreas-related hospitalizations (number: r = 0.15, P = 0.02; duration: r = 0.13, P = 0.04). The severity distribution was 13.3% low, 66.0% moderate, and 20.8% high. 37.6% of subjects had ≥1 hospitalization(s) for any reason; 32.2% had ≥1 pancreas-related hospitalizations. All primary outcomes were significantly different between severity groups: hospitalizations for any reason (number, P = 0.004; duration, P = 0.007) and pancreas-related hospitalizations (number, P = 0.02; duration, P = 0.04). The prevalence of continued drinking at follow-up ( P = 0.04) was higher in the low and moderate groups. The prevalence of anxiety at enrollment ( P = 0.02) and follow-up ( P < 0.05) was higher in the moderate and high groups.
Discussion: Statistically, COPPS significantly correlated with hospitalization outcomes, but the correlations were weaker than in previous studies, which may be related to the outpatient nature of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies cohort and lower prevalence of high severity disease. Studies in other prospective cohorts are needed to understand the full utility of COPPS as a potential tool for clinical risk assessment and intervention.
{"title":"Evaluation of Chronic Pancreatitis Prognosis Score in an American Cohort.","authors":"Soo Kyung Park, Darwin L Conwell, Phil A Hart, Shuang Li, Kimberly Stello, Evan L Fogel, William E Fisher, Christopher E Forsmark, Stephen J Pandol, Walter G Park, Mark Topazian, Jose Serrano, Santhi Swaroop Vege, Stephen K Van Den Eeden, Liang Li, Dhiraj Yadav, Jami L Saloman","doi":"10.14309/ctg.0000000000000758","DOIUrl":"10.14309/ctg.0000000000000758","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic Pancreatitis Prognosis Score (COPPS) was developed to discriminate disease severity and predict risk for future hospitalizations. In this cohort study, we evaluated if COPPS predicts the likelihood of hospitalization(s) in an American cohort.</p><p><strong>Methods: </strong>The Chronic Pancreatitis, Diabetes, and Pancreatic Cancer consortium provided data and serum from subjects with chronic pancreatitis (N = 279). COPPS was calculated with baseline data and stratified by severity (low, moderate, and high). Primary endpoints included number and duration of hospitalizations during 12-month follow-up.</p><p><strong>Results: </strong>The mean ± SD COPPS was 8.4 ± 1.6. COPPS correlated with all primary outcomes: hospitalizations for any reason (number: r = 0.15, P = 0.01; duration: r = 0.16, P = 0.01) and pancreas-related hospitalizations (number: r = 0.15, P = 0.02; duration: r = 0.13, P = 0.04). The severity distribution was 13.3% low, 66.0% moderate, and 20.8% high. 37.6% of subjects had ≥1 hospitalization(s) for any reason; 32.2% had ≥1 pancreas-related hospitalizations. All primary outcomes were significantly different between severity groups: hospitalizations for any reason (number, P = 0.004; duration, P = 0.007) and pancreas-related hospitalizations (number, P = 0.02; duration, P = 0.04). The prevalence of continued drinking at follow-up ( P = 0.04) was higher in the low and moderate groups. The prevalence of anxiety at enrollment ( P = 0.02) and follow-up ( P < 0.05) was higher in the moderate and high groups.</p><p><strong>Discussion: </strong>Statistically, COPPS significantly correlated with hospitalization outcomes, but the correlations were weaker than in previous studies, which may be related to the outpatient nature of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies cohort and lower prevalence of high severity disease. Studies in other prospective cohorts are needed to understand the full utility of COPPS as a potential tool for clinical risk assessment and intervention.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.14309/ctg.0000000000000731
Sophia Rüsing, Lina Welz, Constanze Pfitzer, Danielle Monica Harris, Christoph Röcken, Philip Rosenstiel, Susanna Nikolaus, Florian Tran, Stefan Schreiber, Konrad Aden, Laura Katharina Sievers
Introduction: Patients with inflammatory bowel disease (IBD) are predisposed to the reactivation of viral infections such as cytomegalovirus (CMV). Clinical discrimination of disease flares and colonic CMV reactivation is difficult in patients with established diagnosis of IBD, and there are no reliable noninvasive diagnostic tools yet. Furthermore, the influence of novel therapeutics including biologicals and Janus kinase inhibitors on the risk of CMV colitis is unclear. The goal of this study was to identify risk factors and clinical determinants of CMV colitis that could serve as minimally invasive markers both for active CMV colitis and relapse.
Methods: To this end, a retrospective analysis of 376 patients with suspected or confirmed CMV colitis 2016-2023 was performed.
Results: Previous administration of systemic steroids increased the odds of CMV colitis to OR 4.6. Biologicals did not change the incidence of CMV colitis but decreased the OR of a relapse to 0.13. Clinical parameters such as severely bloody diarrhea, intense microscopic ulcerative damage, and decreased serum tryptophan correlated with detection of CMV. Importantly, persistent decrease of tryptophan was observed in patients with CMV relapse. Furthermore, tryptophan degradation through the kynurenine pathway was increased in CMV-positive patients.
Discussion: Taken together, we identify decreased serum tryptophan as a novel potential minimally invasive marker to aid identification of IBD patients with active CMV colitis and at high risk for relapse.
{"title":"Decreased Serum Tryptophan and Severe Ulcerative Damage of Colon Mucosa Identify Inflammatory Bowel Disease Patients With High Risk of Cytomegalovirus Colitis.","authors":"Sophia Rüsing, Lina Welz, Constanze Pfitzer, Danielle Monica Harris, Christoph Röcken, Philip Rosenstiel, Susanna Nikolaus, Florian Tran, Stefan Schreiber, Konrad Aden, Laura Katharina Sievers","doi":"10.14309/ctg.0000000000000731","DOIUrl":"10.14309/ctg.0000000000000731","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with inflammatory bowel disease (IBD) are predisposed to the reactivation of viral infections such as cytomegalovirus (CMV). Clinical discrimination of disease flares and colonic CMV reactivation is difficult in patients with established diagnosis of IBD, and there are no reliable noninvasive diagnostic tools yet. Furthermore, the influence of novel therapeutics including biologicals and Janus kinase inhibitors on the risk of CMV colitis is unclear. The goal of this study was to identify risk factors and clinical determinants of CMV colitis that could serve as minimally invasive markers both for active CMV colitis and relapse.</p><p><strong>Methods: </strong>To this end, a retrospective analysis of 376 patients with suspected or confirmed CMV colitis 2016-2023 was performed.</p><p><strong>Results: </strong>Previous administration of systemic steroids increased the odds of CMV colitis to OR 4.6. Biologicals did not change the incidence of CMV colitis but decreased the OR of a relapse to 0.13. Clinical parameters such as severely bloody diarrhea, intense microscopic ulcerative damage, and decreased serum tryptophan correlated with detection of CMV. Importantly, persistent decrease of tryptophan was observed in patients with CMV relapse. Furthermore, tryptophan degradation through the kynurenine pathway was increased in CMV-positive patients.</p><p><strong>Discussion: </strong>Taken together, we identify decreased serum tryptophan as a novel potential minimally invasive marker to aid identification of IBD patients with active CMV colitis and at high risk for relapse.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.14309/ctg.0000000000000737
Devika Dixit, Nicole C Ruiz, Steve Shen, Arvin Daneshmand, Vanessa I Rodriguez, Steve Qian, Dan Neal, S Devi Rampertab, Ellen M Zimmermann, Amir Y Kamel
Introduction: Crohn's disease and ulcerative colitis are characterized by chronic inflammation of the gastrointestinal tract. Mucosal healing (MH) is a therapeutic goal in patients with inflammatory bowel disease (IBD). Current data suggest that Black patients may experience worse clinical outcomes than White patients with IBD. This study assessed MH between Black and White patients with IBD.
Methods: Retrospective analysis was performed on Black and White adults with IBD who were hospitalized for an active flare. The presence of MH was assessed at 6-18 months after hospitalization. IBD treatments received before and during hospitalization, within 6 months, and 6-18 months after discharge were recorded. C-reactive protein (CRP) levels were collected at hospitalization and 6-18 months after discharge; the difference was reported as delta CRP.
Results: One hundred nine patients were followed up after hospitalization. Of those 88 (80.7%) were White patients, and 21 (19.3%) were Black patients. White and Black patients received similar proportions of IBD treatment before ( P = 0.2) and during ( P = 0.6) hospitalization, within 6 months ( P = 0.1), and 6-18 months ( P = 0.1) after discharge. Black patients achieved numerically higher rates of MH (15/21 = 71.4% vs 53/88 = 60.2%, P = 0.3) and delta CRP ( P = 0.2) than White patients, however, not statistically significant.
Discussion: In patients admitted to the hospital with an IBD flare with similar treatment and care, there was a trend toward higher rates of MH in Black patients compared with White patients. These data suggest that MH is likely not the only factor that is associated with Black patients experiencing worse clinical outcomes when compared with White patients.
{"title":"Mucosal Healing Among Black and White Patients With Inflammatory Bowel Disease.","authors":"Devika Dixit, Nicole C Ruiz, Steve Shen, Arvin Daneshmand, Vanessa I Rodriguez, Steve Qian, Dan Neal, S Devi Rampertab, Ellen M Zimmermann, Amir Y Kamel","doi":"10.14309/ctg.0000000000000737","DOIUrl":"10.14309/ctg.0000000000000737","url":null,"abstract":"<p><strong>Introduction: </strong>Crohn's disease and ulcerative colitis are characterized by chronic inflammation of the gastrointestinal tract. Mucosal healing (MH) is a therapeutic goal in patients with inflammatory bowel disease (IBD). Current data suggest that Black patients may experience worse clinical outcomes than White patients with IBD. This study assessed MH between Black and White patients with IBD.</p><p><strong>Methods: </strong>Retrospective analysis was performed on Black and White adults with IBD who were hospitalized for an active flare. The presence of MH was assessed at 6-18 months after hospitalization. IBD treatments received before and during hospitalization, within 6 months, and 6-18 months after discharge were recorded. C-reactive protein (CRP) levels were collected at hospitalization and 6-18 months after discharge; the difference was reported as delta CRP.</p><p><strong>Results: </strong>One hundred nine patients were followed up after hospitalization. Of those 88 (80.7%) were White patients, and 21 (19.3%) were Black patients. White and Black patients received similar proportions of IBD treatment before ( P = 0.2) and during ( P = 0.6) hospitalization, within 6 months ( P = 0.1), and 6-18 months ( P = 0.1) after discharge. Black patients achieved numerically higher rates of MH (15/21 = 71.4% vs 53/88 = 60.2%, P = 0.3) and delta CRP ( P = 0.2) than White patients, however, not statistically significant.</p><p><strong>Discussion: </strong>In patients admitted to the hospital with an IBD flare with similar treatment and care, there was a trend toward higher rates of MH in Black patients compared with White patients. These data suggest that MH is likely not the only factor that is associated with Black patients experiencing worse clinical outcomes when compared with White patients.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.14309/ctg.0000000000000744
Cynthia Levy, Stephen Caldwell, Parvez Mantry, Velimir Luketic, Charles S Landis, Jonathan Huang, Edward Mena, Rahul Maheshwari, Kevin Rank, Jun Xu, Vladislav A Malkov, Andrew N Billin, Xiangyu Liu, Xiaomin Lu, William T Barchuk, Timothy R Watkins, Chuhan Chung, Robert P Myers, Kris V Kowdley
Introduction: This proof-of-concept, open-label phase 1b study evaluated the safety and efficacy of cilofexor, a potent selective farnesoid X receptor agonist, in patients with compensated cirrhosis due to primary sclerosing cholangitis.
Methods: Escalating doses of cilofexor (30 mg [weeks 1-4], 60 mg [weeks 5-8], 100 mg [weeks 9-12]) were administered orally once daily over 12 weeks. The primary endpoint was safety. Exploratory measures included cholestasis and fibrosis markers and pharmacodynamic biomarkers of bile acid homeostasis.
Results: Eleven patients were enrolled (median age: 48 years; 55% men). The most common treatment-emergent adverse events (TEAEs) were pruritus (8/11 [72.7%]), fatigue, headache, nausea, and upper respiratory tract infection (2/11 [18.2%] each). Seven patients experienced a pruritus TEAE (one grade 3) considered drug-related. One patient temporarily discontinued cilofexor owing to peripheral edema. There were no deaths, serious TEAEs, or TEAEs leading to permanent discontinuation. Median changes (interquartile ranges) from baseline to week 12 (predose, fasting) were -24.8% (-35.7 to -7.4) for alanine transaminase, -13.0% (-21.9 to -8.6) for alkaline phosphatase, -43.5% (-52.1 to -30.8) for γ-glutamyl transferase, -12.7% (-25.0 to 0.0) for total bilirubin, and -21.2% (-40.0 to 0.0) for direct bilirubin. Least-squares mean percentage change (95% confidence interval) from baseline to week 12 at trough was -55.3% (-70.8 to -31.6) for C4 and -60.5% (-81.8 to -14.2) for cholic acid. Fasting fibroblast growth factor 19 levels transiently increased after cilofexor administration.
Discussion: Escalating doses of cilofexor over 12 weeks were well tolerated and improved cholestasis markers in patients with compensated cirrhosis due to primary sclerosing cholangitis (NCT04060147).
{"title":"Cilofexor in Patients With Compensated Cirrhosis Due to Primary Sclerosing Cholangitis: An Open-Label Phase 1B Study.","authors":"Cynthia Levy, Stephen Caldwell, Parvez Mantry, Velimir Luketic, Charles S Landis, Jonathan Huang, Edward Mena, Rahul Maheshwari, Kevin Rank, Jun Xu, Vladislav A Malkov, Andrew N Billin, Xiangyu Liu, Xiaomin Lu, William T Barchuk, Timothy R Watkins, Chuhan Chung, Robert P Myers, Kris V Kowdley","doi":"10.14309/ctg.0000000000000744","DOIUrl":"10.14309/ctg.0000000000000744","url":null,"abstract":"<p><strong>Introduction: </strong>This proof-of-concept, open-label phase 1b study evaluated the safety and efficacy of cilofexor, a potent selective farnesoid X receptor agonist, in patients with compensated cirrhosis due to primary sclerosing cholangitis.</p><p><strong>Methods: </strong>Escalating doses of cilofexor (30 mg [weeks 1-4], 60 mg [weeks 5-8], 100 mg [weeks 9-12]) were administered orally once daily over 12 weeks. The primary endpoint was safety. Exploratory measures included cholestasis and fibrosis markers and pharmacodynamic biomarkers of bile acid homeostasis.</p><p><strong>Results: </strong>Eleven patients were enrolled (median age: 48 years; 55% men). The most common treatment-emergent adverse events (TEAEs) were pruritus (8/11 [72.7%]), fatigue, headache, nausea, and upper respiratory tract infection (2/11 [18.2%] each). Seven patients experienced a pruritus TEAE (one grade 3) considered drug-related. One patient temporarily discontinued cilofexor owing to peripheral edema. There were no deaths, serious TEAEs, or TEAEs leading to permanent discontinuation. Median changes (interquartile ranges) from baseline to week 12 (predose, fasting) were -24.8% (-35.7 to -7.4) for alanine transaminase, -13.0% (-21.9 to -8.6) for alkaline phosphatase, -43.5% (-52.1 to -30.8) for γ-glutamyl transferase, -12.7% (-25.0 to 0.0) for total bilirubin, and -21.2% (-40.0 to 0.0) for direct bilirubin. Least-squares mean percentage change (95% confidence interval) from baseline to week 12 at trough was -55.3% (-70.8 to -31.6) for C4 and -60.5% (-81.8 to -14.2) for cholic acid. Fasting fibroblast growth factor 19 levels transiently increased after cilofexor administration.</p><p><strong>Discussion: </strong>Escalating doses of cilofexor over 12 weeks were well tolerated and improved cholestasis markers in patients with compensated cirrhosis due to primary sclerosing cholangitis (NCT04060147).</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.14309/ctg.0000000000000745
Alyyah Malick, Jennifer S Ferris, Chin Hur, Julian A Abrams, Ali Soroush
Introduction: Current strategies for upper gastrointestinal (UGI) cancer screening primarily target cancer-specific risk, with the strongest focus on esophageal adenocarcinoma (EAC). However, all UGI cancers are amendable to screening and early detection with an upper endoscopic examination. This study assesses and explores incidence-based mortality (IBM) for cumulative UGI cancers, aiming to identify race-based or sex-based disparities.
Methods: We used Surveillance, Epidemiology, and End Results Research data to analyze patients diagnosed with EAC, esophageal squamous cell carcinoma, cardia gastric cancer, noncardia gastric cancer, or colorectal adenocarcinoma from 2000 to 2019. Age-adjusted IBM was calculated as a rate per 100,000 population and stratified by sex and race/ethnicity. We also compared UGI cancer IBM with that of colorectal cancer, a cancer with established population-wide endoscopic screening guidelines.
Results: Cumulative IBM for UGI cancers was 8.40 (95% confidence interval [CI] 8.34-8.46). The highest cancer-specific IBM rates were for EAC (2.26, 95% CI 2.23-2.29), followed by noncardia gastric cancer (2.07, 95% CI 2.04-2.10), cardia gastric cancer (1.60, 95% CI 1.57-1.62), esophageal squamous cell carcinoma (1.21, 95% CI 1.19-1.23), and miscellaneous UGI cancer (1.27, 95% CI 1.13-1.40). UGI cancer IBM was highest among Black men (16.43, 95% CI 15.97-16.89), American Indian/Alaska Native men (15.23, 95% CI 13.75-16.82), and Hispanic men (13.76, 95% CI 13.42-14.11). These rates are significantly greater than among White men (12.81, 95% CI 12.68-12.95).
Discussion: UGI cancers impose a significantly higher mortality burden on non-White population subgroups that are not currently targeted by any systematic screening approach.
导言:目前的上消化道癌症(UGI)筛查策略主要针对癌症特异性风险,重点关注食管腺癌(EAC)。然而,所有上消化道癌症都可以通过上内窥镜检查进行筛查和早期检测。本研究评估并探讨了累积性上消化道癌症基于发病率的死亡率(IBM),旨在确定基于种族或性别的差异:我们利用监测、流行病学和最终结果研究数据分析了 2000 年至 2019 年期间确诊为 EAC、食管鳞状细胞癌 (ESCC)、贲门胃癌 (CGC)、非贲门胃癌 (NCGC) 或结直肠腺癌的患者。年龄调整后的 IBM 以每 10 万人的比率计算,并按性别和种族/人种进行分层。我们还将上消化道癌的IBM与结直肠癌的IBM进行了比较,结直肠癌已制定了全民内窥镜筛查指南:结果:上消化道癌的累积IBM为8.40(95% CI为8.34-8.46)。癌症特异性IBM率最高的是EAC(2.26,95% CI 2.23-2.29),其次是NCGC(2.07,95% CI 2.04-2.10)、CGC(1.60,95% CI 1.57-1.62)、ESCC(1.21,95% CI 1.19-1.23)和其他UGI癌症(1.27,95% CI 1.13-1.40)。UGI 癌症 IBM 在黑人男性(16.43,95% CI 15.97-16.89)、美国印第安人/阿拉斯加原住民男性(15.23,95% CI 13.75-16.82)和西班牙裔男性(13.76,95% CI 13.42-14.11)中发病率最高。这些比率明显高于白人男性(12.81,95% CI 12.68-12.95):结论:UGI 癌症给非白人人口亚群带来了更高的死亡率负担,而这些亚群目前并不是任何系统筛查方法的目标人群。
{"title":"Racial, Ethnic, and Sex Differences in Incidence-Based Mortality of Aggregate Upper Gastrointestinal Cancers.","authors":"Alyyah Malick, Jennifer S Ferris, Chin Hur, Julian A Abrams, Ali Soroush","doi":"10.14309/ctg.0000000000000745","DOIUrl":"10.14309/ctg.0000000000000745","url":null,"abstract":"<p><strong>Introduction: </strong>Current strategies for upper gastrointestinal (UGI) cancer screening primarily target cancer-specific risk, with the strongest focus on esophageal adenocarcinoma (EAC). However, all UGI cancers are amendable to screening and early detection with an upper endoscopic examination. This study assesses and explores incidence-based mortality (IBM) for cumulative UGI cancers, aiming to identify race-based or sex-based disparities.</p><p><strong>Methods: </strong>We used Surveillance, Epidemiology, and End Results Research data to analyze patients diagnosed with EAC, esophageal squamous cell carcinoma, cardia gastric cancer, noncardia gastric cancer, or colorectal adenocarcinoma from 2000 to 2019. Age-adjusted IBM was calculated as a rate per 100,000 population and stratified by sex and race/ethnicity. We also compared UGI cancer IBM with that of colorectal cancer, a cancer with established population-wide endoscopic screening guidelines.</p><p><strong>Results: </strong>Cumulative IBM for UGI cancers was 8.40 (95% confidence interval [CI] 8.34-8.46). The highest cancer-specific IBM rates were for EAC (2.26, 95% CI 2.23-2.29), followed by noncardia gastric cancer (2.07, 95% CI 2.04-2.10), cardia gastric cancer (1.60, 95% CI 1.57-1.62), esophageal squamous cell carcinoma (1.21, 95% CI 1.19-1.23), and miscellaneous UGI cancer (1.27, 95% CI 1.13-1.40). UGI cancer IBM was highest among Black men (16.43, 95% CI 15.97-16.89), American Indian/Alaska Native men (15.23, 95% CI 13.75-16.82), and Hispanic men (13.76, 95% CI 13.42-14.11). These rates are significantly greater than among White men (12.81, 95% CI 12.68-12.95).</p><p><strong>Discussion: </strong>UGI cancers impose a significantly higher mortality burden on non-White population subgroups that are not currently targeted by any systematic screening approach.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.14309/ctg.0000000000000751
Aarti Kumar, Marianne Rara, Ming Yu, Kwun Wah Wen, William M Grady, Amitabh Chak, Prasad G Iyer, Anil K Rustgi, Timothy C Wang, Joel H Rubenstein, Yue Liu, Laura Kresty, Maria Westerhoff, Richard S Kwon, Erik Wamsteker, Tom Wang, Lynne Berry, Marcia I Canto, Nicholas J Shaheen, Kenneth K Wang, Julian A Abrams, Matthew D Stachler
Introduction: Early neoplastic progression of Barrett's esophagus (BE) is often treated with endoscopic therapy. Although effective, some patients are refractory to therapy or recur after apparent eradication of the BE. The goal of this study was to determine whether genomic alterations within the treated BE may be associated with persistent or recurrent disease.
Methods: We performed DNA sequencing on pre-treatment esophageal samples from 45 patients who were successfully treated by endoscopic therapy and did not recur as well as pre-treatment and post-treatment samples from 40 patients who had persistent neoplasia and 21 patients who had recurrent neoplasia. The genomic alterations were compared between groups.
Results: The genomic landscape was similar between all groups. Patients with persistent disease were more likely to have pre-treatment alterations involving the receptor tyrosine kinase pathway ( P = 0.01), amplifications of oncogenes ( P = 0.01), and deletions of tumor suppressor genes ( P = 0.02). These associations were no longer significant after adjusting for patient age and BE length. More than half of patients with persistent (52.5%) or recurrent (57.2%) disease showed pre-treatment and post-treatment samples that shared at least 50% of their driver mutations.
Discussion: Pre-treatment samples were genomically similar between those who responded to endoscopic therapy and those who had persistent or recurrent disease, suggesting there is not a strong genomic component to treatment response. Although it was expected to find shared driver mutations in pre-treatment and post-treatment samples in patients with persistent disease, the finding that an equal number of patients with recurrent disease also showed this relation suggests that many recurrences represent undetected minimal residual disease.
导言:巴雷特食管(Barrett's esophagus,BE)的早期肿瘤性进展通常采用内窥镜治疗。虽然疗效显著,但有些患者会出现难治性或在明显根除 BE 后复发。本研究的目的是确定接受治疗的 BE 的基因组改变是否与疾病的持续或复发有关:我们对 45 名经内镜治疗成功且未复发的患者的治疗前食管样本、40 名肿瘤持续存在的患者和 21 名肿瘤复发患者的治疗前和治疗后样本进行了 DNA 测序。对各组间的基因组变化进行了比较:结果:各组间的基因组结构相似。久治不愈的患者更有可能在治疗前发生涉及受体酪氨酸激酶通路(p=0.01)、癌基因扩增(p=0.01)和抑癌基因缺失(p=0.02)的改变。在对患者年龄和BE长度进行调整后,这些关联不再显著。超过一半的顽固性疾病(52.5%)或复发性疾病(57.2%)患者在治疗前和治疗后样本中至少有50%的驱动基因突变是相同的:结论:对内镜治疗有反应的患者与疾病持续或复发的患者在治疗前样本的基因组学上相似,这表明治疗反应的基因组因素并不强。虽然预计在顽固性疾病患者的治疗前和治疗后样本中会发现共同的驱动基因突变,但发现同样数量的复发性疾病患者也显示出这种关系,这表明许多复发性疾病是未被发现的最小残留疾病。
{"title":"Molecular Analysis of Persistent and Recurrent Barrett's Esophagus in the Setting of Endoscopic Therapy.","authors":"Aarti Kumar, Marianne Rara, Ming Yu, Kwun Wah Wen, William M Grady, Amitabh Chak, Prasad G Iyer, Anil K Rustgi, Timothy C Wang, Joel H Rubenstein, Yue Liu, Laura Kresty, Maria Westerhoff, Richard S Kwon, Erik Wamsteker, Tom Wang, Lynne Berry, Marcia I Canto, Nicholas J Shaheen, Kenneth K Wang, Julian A Abrams, Matthew D Stachler","doi":"10.14309/ctg.0000000000000751","DOIUrl":"10.14309/ctg.0000000000000751","url":null,"abstract":"<p><strong>Introduction: </strong>Early neoplastic progression of Barrett's esophagus (BE) is often treated with endoscopic therapy. Although effective, some patients are refractory to therapy or recur after apparent eradication of the BE. The goal of this study was to determine whether genomic alterations within the treated BE may be associated with persistent or recurrent disease.</p><p><strong>Methods: </strong>We performed DNA sequencing on pre-treatment esophageal samples from 45 patients who were successfully treated by endoscopic therapy and did not recur as well as pre-treatment and post-treatment samples from 40 patients who had persistent neoplasia and 21 patients who had recurrent neoplasia. The genomic alterations were compared between groups.</p><p><strong>Results: </strong>The genomic landscape was similar between all groups. Patients with persistent disease were more likely to have pre-treatment alterations involving the receptor tyrosine kinase pathway ( P = 0.01), amplifications of oncogenes ( P = 0.01), and deletions of tumor suppressor genes ( P = 0.02). These associations were no longer significant after adjusting for patient age and BE length. More than half of patients with persistent (52.5%) or recurrent (57.2%) disease showed pre-treatment and post-treatment samples that shared at least 50% of their driver mutations.</p><p><strong>Discussion: </strong>Pre-treatment samples were genomically similar between those who responded to endoscopic therapy and those who had persistent or recurrent disease, suggesting there is not a strong genomic component to treatment response. Although it was expected to find shared driver mutations in pre-treatment and post-treatment samples in patients with persistent disease, the finding that an equal number of patients with recurrent disease also showed this relation suggests that many recurrences represent undetected minimal residual disease.</p>","PeriodicalId":10278,"journal":{"name":"Clinical and Translational Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}