Pub Date : 2024-02-26eCollection Date: 2024-01-01DOI: 10.2147/CEG.S439275
Zhengchun Zhu, Hong Liu, Fei Zhong
Background and objectives: Duodenal adenocarcinoma (DAC) is a rare tumor that is often accompanied by liver metastasis in advanced stages. The aim of this study was to evaluate the correlation between clinicopathological characteristics and survival in DAC patients with liver metastasis, and to explore appropriate treatment options.
Methods: 482 DAC patients with liver metastasis were retrospectively identified from the Surveillance, Epidemiology and End Results (SEER) database (2011-2020). Univariate and multivariate Cox regression analyses were performed to explore the clinicopathological factors related to survival. The Kaplan-Meier method was used to identify the independent risk factors associated with survival.
Results: The 1-year overall survival (OS) and cancer-specific survival (CSS) rates for the entire cohort were 25.4% and 28.3%, and the 5-year OS and CSS rates were 2.4% and 2.9% respectively. Univariable analysis and multivariate analysis identified chemotherapy and surgery as the independent risk factors for OS and CSS. Patients who underwent chemotherapy and surgery had better CSS and OS rates, whereas radiotherapy failed to improve outcomes.
Conclusion: We identified several prognostic factors of DAC with liver metastasis. Chemotherapy and surgery can prolong the survival of DAC patients with liver metastasis, which lays the foundation for identifying the optimal treatment strategy.
{"title":"Clinicopathological Characteristics, Treatment and Prognosis in Duodenal Adenocarcinoma with Liver Metastasis: A SEER-Based Study.","authors":"Zhengchun Zhu, Hong Liu, Fei Zhong","doi":"10.2147/CEG.S439275","DOIUrl":"10.2147/CEG.S439275","url":null,"abstract":"<p><strong>Background and objectives: </strong>Duodenal adenocarcinoma (DAC) is a rare tumor that is often accompanied by liver metastasis in advanced stages. The aim of this study was to evaluate the correlation between clinicopathological characteristics and survival in DAC patients with liver metastasis, and to explore appropriate treatment options.</p><p><strong>Methods: </strong>482 DAC patients with liver metastasis were retrospectively identified from the Surveillance, Epidemiology and End Results (SEER) database (2011-2020). Univariate and multivariate Cox regression analyses were performed to explore the clinicopathological factors related to survival. The Kaplan-Meier method was used to identify the independent risk factors associated with survival.</p><p><strong>Results: </strong>The 1-year overall survival (OS) and cancer-specific survival (CSS) rates for the entire cohort were 25.4% and 28.3%, and the 5-year OS and CSS rates were 2.4% and 2.9% respectively. Univariable analysis and multivariate analysis identified chemotherapy and surgery as the independent risk factors for OS and CSS. Patients who underwent chemotherapy and surgery had better CSS and OS rates, whereas radiotherapy failed to improve outcomes.</p><p><strong>Conclusion: </strong>We identified several prognostic factors of DAC with liver metastasis. Chemotherapy and surgery can prolong the survival of DAC patients with liver metastasis, which lays the foundation for identifying the optimal treatment strategy.</p>","PeriodicalId":10208,"journal":{"name":"Clinical and Experimental Gastroenterology","volume":"17 ","pages":"51-59"},"PeriodicalIF":2.4,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10906677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-19eCollection Date: 2024-01-01DOI: 10.2147/CEG.S435690
Yin-Gen Luo, Xiao-Wu Zhang, He Zhao, Jin-Gui Li, Jiay-Wei Tsauo, Tao Gong, Ai-Xin Ou, Tian-Hao Cong, Wen-Di Kang, Xiao Li
Objective: This study aimed to establish a rat model that simulates benign esophageal strictures induced by endoscopic submucosal dissection (ESD).
Materials and methods: Sixteen male Sprague-Dawley rats were randomly divided into mucosal resection (n = 8) and sham-operated groups (n = 8). The rats in the mucosal resection group underwent a 5-mm three-fourths mucosal resection by way of a 3-mm incision in the distal esophagus under direct visualization via laparotomy. Rats in the sham-operated group underwent a 3-mm incision of the muscularis propria layer in the distal esophagus via laparotomy without mucosal resection. Dysphagia score, weight gain, mucosal constriction rate, and histology were evaluated 2 weeks after surgery.
Results: Technical success was achieved in all the animals. One rat in the mucosal resection group died of infection, and no other complications were observed. Weight gain (P < 0.001) and luminal diameter derived from the esophagograms (P < 0.001) were significantly lower in the mucosal resection group than those in the sham-operated group. Dysphagia score (P < 0.001) and mucosal constriction rate (P < 0.001) were significantly higher in the mucosal resection group than those in the sham-operated group. The inflammation grade (P = 0.002), damage to the muscularis propria (P < 0.001), number of nascent microvessels (P = 0.006), and degree of α-SMA positive deposition (P = 0.006) were significantly higher in the mucosal resection group.
Conclusion: A rat model of benign esophageal stricture induced by ESD was successfully and safely established by mucosal resection.
{"title":"A Novel Rat Model to Simulate the Benign Esophageal Stricture Induced by Endoscopic Submucosal Dissection.","authors":"Yin-Gen Luo, Xiao-Wu Zhang, He Zhao, Jin-Gui Li, Jiay-Wei Tsauo, Tao Gong, Ai-Xin Ou, Tian-Hao Cong, Wen-Di Kang, Xiao Li","doi":"10.2147/CEG.S435690","DOIUrl":"https://doi.org/10.2147/CEG.S435690","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to establish a rat model that simulates benign esophageal strictures induced by endoscopic submucosal dissection (ESD).</p><p><strong>Materials and methods: </strong>Sixteen male Sprague-Dawley rats were randomly divided into mucosal resection (n = 8) and sham-operated groups (n = 8). The rats in the mucosal resection group underwent a 5-mm three-fourths mucosal resection by way of a 3-mm incision in the distal esophagus under direct visualization via laparotomy. Rats in the sham-operated group underwent a 3-mm incision of the muscularis propria layer in the distal esophagus via laparotomy without mucosal resection. Dysphagia score, weight gain, mucosal constriction rate, and histology were evaluated 2 weeks after surgery.</p><p><strong>Results: </strong>Technical success was achieved in all the animals. One rat in the mucosal resection group died of infection, and no other complications were observed. Weight gain (P < 0.001) and luminal diameter derived from the esophagograms (P < 0.001) were significantly lower in the mucosal resection group than those in the sham-operated group. Dysphagia score (P < 0.001) and mucosal constriction rate (P < 0.001) were significantly higher in the mucosal resection group than those in the sham-operated group. The inflammation grade (P = 0.002), damage to the muscularis propria (P < 0.001), number of nascent microvessels (P = 0.006), and degree of α-SMA positive deposition (P = 0.006) were significantly higher in the mucosal resection group.</p><p><strong>Conclusion: </strong>A rat model of benign esophageal stricture induced by ESD was successfully and safely established by mucosal resection.</p>","PeriodicalId":10208,"journal":{"name":"Clinical and Experimental Gastroenterology","volume":"17 ","pages":"41-50"},"PeriodicalIF":2.4,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10891275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-09eCollection Date: 2024-01-01DOI: 10.2147/CEG.S453345
Baldeep Kaur Mann, Janpreet Singh Bhandohal, Ishaan Kalha, Kasey Fox, Brian Jean
Introduction: Procalcitonin levels have been studied to predict the benefit of adding antibiotics in a patient with acute pancreatitis. Through this study, we are searching for any possible correlation between serum procalcitonin levels and the severity of acute pancreatitis (included acute on chronic cases) to determine whether procalcitonin levels can predict a benefit from antibiotic therapy in acute pancreatitis.
Methods: This is a retrospective cohort study involving patients with acute pancreatitis and acute on chronic pancreatitis. We included all hospitalized patients admitted to Kern Medical from January 2020 to October 2022 with a diagnosis of acute pancreatitis in a consecutive manner. The primary outcome studied was mortality related to the pancreatitis episode. Logistic regression was used to control numerous confounders.
Results: Based on univariate analysis of procalcitonin, we found starting antibiotics on the day of admission statistically significant. We also found the median differences in mortality to be mildly significant (difference = 0.79, p = 0.0640) based on procalcitonin values. In a multivariate analysis of ln(procalcitonin), we found lipase (p = 0.0249), duration of antibiotics (p = 0.0009), multi-organ failure (p = 0.0045) to be statistically significant, and lactate being mildly significant in the multivariate model (p = 0.0643).
Conclusion: The procalcitonin level can predict the initiation of antibiotics, duration of antibiotics, multi-organ failure, and mortality in patients with acute pancreatitis.
{"title":"Relevance of Procalcitonin Levels as a Marker of Severity and Predictor of Mortality, Initiation and Duration of Antibiotics in Patients Admitted with Acute Pancreatitis: A Retrospective Cohort Study.","authors":"Baldeep Kaur Mann, Janpreet Singh Bhandohal, Ishaan Kalha, Kasey Fox, Brian Jean","doi":"10.2147/CEG.S453345","DOIUrl":"10.2147/CEG.S453345","url":null,"abstract":"<p><strong>Introduction: </strong>Procalcitonin levels have been studied to predict the benefit of adding antibiotics in a patient with acute pancreatitis. Through this study, we are searching for any possible correlation between serum procalcitonin levels and the severity of acute pancreatitis (included acute on chronic cases) to determine whether procalcitonin levels can predict a benefit from antibiotic therapy in acute pancreatitis.</p><p><strong>Methods: </strong>This is a retrospective cohort study involving patients with acute pancreatitis and acute on chronic pancreatitis. We included all hospitalized patients admitted to Kern Medical from January 2020 to October 2022 with a diagnosis of acute pancreatitis in a consecutive manner. The primary outcome studied was mortality related to the pancreatitis episode. Logistic regression was used to control numerous confounders.</p><p><strong>Results: </strong>Based on univariate analysis of procalcitonin, we found starting antibiotics on the day of admission statistically significant. We also found the median differences in mortality to be mildly significant (difference = 0.79, p = 0.0640) based on procalcitonin values. In a multivariate analysis of ln(procalcitonin), we found lipase (p = 0.0249), duration of antibiotics (p = 0.0009), multi-organ failure (p = 0.0045) to be statistically significant, and lactate being mildly significant in the multivariate model (p = 0.0643).</p><p><strong>Conclusion: </strong>The procalcitonin level can predict the initiation of antibiotics, duration of antibiotics, multi-organ failure, and mortality in patients with acute pancreatitis.</p>","PeriodicalId":10208,"journal":{"name":"Clinical and Experimental Gastroenterology","volume":"17 ","pages":"31-39"},"PeriodicalIF":2.4,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-09eCollection Date: 2024-01-01DOI: 10.2147/CEG.S450262
Abdel Rahman A Al Manasra, Tarik Alhmoud, Zaid Mesmar, Ahmad Hamaydeh
Background: Sigmoid volvulus is primarily a disease of the elderly.
Case presentation: We describe a case of recurrent sigmoid volvulus in an elderly woman who refused surgery due to the high risk posed by general anesthesia and surgical intervention. She underwent endoscopic-assisted percutaneous sigmoidopexy using only three 2-shot anchor sets. No radiographic observation was necessary during the procedure. Some puncture sites were secured using endoscopic clips.
Conclusion: Endoscopic-assisted percutaneous sigmoidopexy is increasingly used as an effective alternative to surgical sigmoidopexy when surgery under general anesthesia poses a high risk. Despite clinical improvement and resolution of the recurrent volvulus, after sigmoidopexy patients may continue to experience motility dysfunction and diffuse dilation of the colon for a few weeks, which may correlate with the episodes of obstruction experienced prior to fixation.
{"title":"Endoscopic-Assisted Percutaneous Sigmoidopexy: New Highlights on Technique and Outcomes.","authors":"Abdel Rahman A Al Manasra, Tarik Alhmoud, Zaid Mesmar, Ahmad Hamaydeh","doi":"10.2147/CEG.S450262","DOIUrl":"10.2147/CEG.S450262","url":null,"abstract":"<p><strong>Background: </strong>Sigmoid volvulus is primarily a disease of the elderly.</p><p><strong>Case presentation: </strong>We describe a case of recurrent sigmoid volvulus in an elderly woman who refused surgery due to the high risk posed by general anesthesia and surgical intervention. She underwent endoscopic-assisted percutaneous sigmoidopexy using only three 2-shot anchor sets. No radiographic observation was necessary during the procedure. Some puncture sites were secured using endoscopic clips.</p><p><strong>Conclusion: </strong>Endoscopic-assisted percutaneous sigmoidopexy is increasingly used as an effective alternative to surgical sigmoidopexy when surgery under general anesthesia poses a high risk. Despite clinical improvement and resolution of the recurrent volvulus, after sigmoidopexy patients may continue to experience motility dysfunction and diffuse dilation of the colon for a few weeks, which may correlate with the episodes of obstruction experienced prior to fixation.</p>","PeriodicalId":10208,"journal":{"name":"Clinical and Experimental Gastroenterology","volume":"17 ","pages":"25-29"},"PeriodicalIF":2.4,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-27eCollection Date: 2024-01-01DOI: 10.2147/CEG.S429039
Jordi Rimola, Jean-Frédéric Colombel, Brian Bressler, Shashi Adsul, Jenifer Siegelman, Patricia E Cole, Dirk Lindner, Silvio Danese
Purpose: The VERSIFY phase 3 trial in patients with Crohn's disease (CD) treated with vedolizumab was the first to include a substudy that used a standardized magnetic resonance enterography (MRE) protocol to assess features of transmural inflammation (bowel edema and wall thickness) and extramural disease activity (enlarged lymph nodes).
Patients and methods: Patients received intravenous vedolizumab (300 mg) at weeks 0 (baseline), 2, and 6, and then every 8 weeks for 26 or 52 weeks. Post hoc analyses included a subpopulation with a Magnetic Resonance Index of Activity score of ≥7 in at least one bowel segment at baseline and at least one postbaseline MRE assessment. Changes in transmural inflammation, including intramural bowel edema and wall thickness, were evaluated. Patient-level and segment-level analyses were performed.
Results: MRE images were evaluated in 27 patients with 83 evaluable bowel segments at baseline and week 26, and 13 patients with 38 evaluable segments at baseline, week 26, and week 52. At baseline, all patients had bowel wall edema and wall thickness of >3 mm in at least one bowel segment. The proportion of patients with edema decreased at weeks 26 (17/27 [63.0%]) and 52 (4/13 [30.8%]) and the proportion with bowel wall thickness of >3 mm decreased at weeks 26 (25/27 [92.6%]) and 52 (10/13 [76.9%]).
Conclusion: In patients with CD treated with vedolizumab for 26 and 52 weeks, the number of patients, and bowel segments, with MRE-detected transmural inflammation was reduced. These results highlight the impact of vedolizumab on components of transmural inflammation in CD and demonstrate that using MRE in CD multicenter clinical trials is feasible.
Trial registration: ClinicalTrials.gov NCT02425111, April 23, 2015, http://www.clinicaltrials.gov NCT02425111; EU Clinical Trials Register EudraCT 2014-003509-13, https://www.clinicaltrialsregister.eu.
{"title":"Magnetic Resonance Enterography Assessment of Transmural Healing with Vedolizumab in Moderate to Severe Crohn's Disease: Feasibility in the VERSIFY Phase 3 Clinical Trial.","authors":"Jordi Rimola, Jean-Frédéric Colombel, Brian Bressler, Shashi Adsul, Jenifer Siegelman, Patricia E Cole, Dirk Lindner, Silvio Danese","doi":"10.2147/CEG.S429039","DOIUrl":"10.2147/CEG.S429039","url":null,"abstract":"<p><strong>Purpose: </strong>The VERSIFY phase 3 trial in patients with Crohn's disease (CD) treated with vedolizumab was the first to include a substudy that used a standardized magnetic resonance enterography (MRE) protocol to assess features of transmural inflammation (bowel edema and wall thickness) and extramural disease activity (enlarged lymph nodes).</p><p><strong>Patients and methods: </strong>Patients received intravenous vedolizumab (300 mg) at weeks 0 (baseline), 2, and 6, and then every 8 weeks for 26 or 52 weeks. Post hoc analyses included a subpopulation with a Magnetic Resonance Index of Activity score of ≥7 in at least one bowel segment at baseline and at least one postbaseline MRE assessment. Changes in transmural inflammation, including intramural bowel edema and wall thickness, were evaluated. Patient-level and segment-level analyses were performed.</p><p><strong>Results: </strong>MRE images were evaluated in 27 patients with 83 evaluable bowel segments at baseline and week 26, and 13 patients with 38 evaluable segments at baseline, week 26, and week 52. At baseline, all patients had bowel wall edema and wall thickness of >3 mm in at least one bowel segment. The proportion of patients with edema decreased at weeks 26 (17/27 [63.0%]) and 52 (4/13 [30.8%]) and the proportion with bowel wall thickness of >3 mm decreased at weeks 26 (25/27 [92.6%]) and 52 (10/13 [76.9%]).</p><p><strong>Conclusion: </strong>In patients with CD treated with vedolizumab for 26 and 52 weeks, the number of patients, and bowel segments, with MRE-detected transmural inflammation was reduced. These results highlight the impact of vedolizumab on components of transmural inflammation in CD and demonstrate that using MRE in CD multicenter clinical trials is feasible.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT02425111, April 23, 2015, http://www.clinicaltrials.gov NCT02425111; EU Clinical Trials Register EudraCT 2014-003509-13, https://www.clinicaltrialsregister.eu.</p>","PeriodicalId":10208,"journal":{"name":"Clinical and Experimental Gastroenterology","volume":"17 ","pages":"9-23"},"PeriodicalIF":2.5,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10829592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manish Thapar, Akash Singh, Kevin Robinson, Herbert Bonkovsky
{"title":"Obstacles to Early Diagnosis of Acute Hepatic Porphyria: Current Perspectives on Improving Early Diagnosis and Clinical Management","authors":"Manish Thapar, Akash Singh, Kevin Robinson, Herbert Bonkovsky","doi":"10.2147/ceg.s348507","DOIUrl":"https://doi.org/10.2147/ceg.s348507","url":null,"abstract":"","PeriodicalId":10208,"journal":{"name":"Clinical and Experimental Gastroenterology","volume":"27 17","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139394226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-14eCollection Date: 2023-01-01DOI: 10.2147/CEG.S360248
Joseph William Clinton, Raymond Keith Cross
Crohn's disease is a complex, relapsing and remitting inflammatory disorder of the gastrointestinal tract with a variable disease course. While the treatment options for Crohn's disease have dramatically increased over the past two decades, predicting individual patient response to treatment remains a challenge. As a result, patients often cycle through multiple different therapies before finding an effective treatment which can lead to disease complications, increased costs, and decreased quality of life. Recently, there has been increased emphasis on personalized medicine in Crohn's disease to identify individual patients who require early advanced therapy to prevent complications of their disease. In this review, we summarize our current approach to management of Crohn's disease by identifying risk factors for severe or disabling disease and tailoring individual treatments to patient-specific goals. Lastly, we outline our knowledge gaps in implementing personalized Crohn's disease treatment and describe the future directions in precision medicine.
{"title":"Personalized Treatment for Crohn's Disease: Current Approaches and Future Directions.","authors":"Joseph William Clinton, Raymond Keith Cross","doi":"10.2147/CEG.S360248","DOIUrl":"https://doi.org/10.2147/CEG.S360248","url":null,"abstract":"<p><p>Crohn's disease is a complex, relapsing and remitting inflammatory disorder of the gastrointestinal tract with a variable disease course. While the treatment options for Crohn's disease have dramatically increased over the past two decades, predicting individual patient response to treatment remains a challenge. As a result, patients often cycle through multiple different therapies before finding an effective treatment which can lead to disease complications, increased costs, and decreased quality of life. Recently, there has been increased emphasis on personalized medicine in Crohn's disease to identify individual patients who require early advanced therapy to prevent complications of their disease. In this review, we summarize our current approach to management of Crohn's disease by identifying risk factors for severe or disabling disease and tailoring individual treatments to patient-specific goals. Lastly, we outline our knowledge gaps in implementing personalized Crohn's disease treatment and describe the future directions in precision medicine.</p>","PeriodicalId":10208,"journal":{"name":"Clinical and Experimental Gastroenterology","volume":"16 ","pages":"249-276"},"PeriodicalIF":2.4,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10726957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138799365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of a Pharmacokinetic Model That Accounts for the Plasma Concentrations of Conjugated and Unconjugated Bilirubin Observed in a Variety of Disease States","authors":"David Levitt, Michael D Levitt","doi":"10.2147/ceg.s438140","DOIUrl":"https://doi.org/10.2147/ceg.s438140","url":null,"abstract":"","PeriodicalId":10208,"journal":{"name":"Clinical and Experimental Gastroenterology","volume":"334 ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138989707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohamed Saleh Ismail, Diane E Peters, Steven P Rowe, Ali Salavati, Sowmya Sharma, Robert Anders, M. Pomper, Barbara S Slusher, Florin M Selaru
Background Prostate-specific membrane antigen (PSMA) is highly and specifically upregulated in active-inflamed mucosa of patients with inflammatory bowel disease (IBD). We hypothesized that this upregulation would be detectable using a PSMA-targeted positron emission tomography/computed tomography (PET/CT) imaging agent, [18F]DCFPyL, enabling non-invasive visualization of inflammation. A noninvasive means of detecting active inflammation would have high clinical value in localization and management of IBD. Study We performed [18F]DCFPyL imaging in three IBD patients with active disease. Abnormally increased gastrointestinal [18F]DCFPyL uptake was observed in areas with endoscopic, histologic, and immunohistochemical inflammation, demonstrating partial overlap of segments of bowel with abnormal [18F]DCFPyL uptake and active inflammation. Conclusion This study demonstrates that PSMA-targeted [18F]DCFPyL PET can effectively detect regions of inflamed mucosa in patients with IBD, suggesting its utility as a non-invasive imaging agent to assess location, extent, and disease activity in IBD.
{"title":"PSMA-Targeted PET Radiotracer [18F]DCFPyL as an Imaging Biomarker in Inflammatory Bowel Disease","authors":"Mohamed Saleh Ismail, Diane E Peters, Steven P Rowe, Ali Salavati, Sowmya Sharma, Robert Anders, M. Pomper, Barbara S Slusher, Florin M Selaru","doi":"10.2147/CEG.S404009","DOIUrl":"https://doi.org/10.2147/CEG.S404009","url":null,"abstract":"Background Prostate-specific membrane antigen (PSMA) is highly and specifically upregulated in active-inflamed mucosa of patients with inflammatory bowel disease (IBD). We hypothesized that this upregulation would be detectable using a PSMA-targeted positron emission tomography/computed tomography (PET/CT) imaging agent, [18F]DCFPyL, enabling non-invasive visualization of inflammation. A noninvasive means of detecting active inflammation would have high clinical value in localization and management of IBD. Study We performed [18F]DCFPyL imaging in three IBD patients with active disease. Abnormally increased gastrointestinal [18F]DCFPyL uptake was observed in areas with endoscopic, histologic, and immunohistochemical inflammation, demonstrating partial overlap of segments of bowel with abnormal [18F]DCFPyL uptake and active inflammation. Conclusion This study demonstrates that PSMA-targeted [18F]DCFPyL PET can effectively detect regions of inflamed mucosa in patients with IBD, suggesting its utility as a non-invasive imaging agent to assess location, extent, and disease activity in IBD.","PeriodicalId":10208,"journal":{"name":"Clinical and Experimental Gastroenterology","volume":" 966","pages":"237 - 247"},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138610541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction Cholestasis is a common liver disorder that currently has limited treatment options. Gardenia Iridoid Glucosides (GIG) have been found to possess various physiological activities, such as cholagogic, hypoglycemic, antibacterial, and anti-inflammatory effects. The objective of this study was to investigate the effects of GIG on bile acid enterohepatic circulation and explore the underlying mechanism in cholestatic rats. Methods In order to identify key pathways associated with cholestasis, we conducted Gene Ontology (GO) Enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In vivo experiments were then performed on alpha-naphthylisothiocyanate (ANIT)-treated rats to assess the impact of GIG. We measured bile flow and various biomarkers including total bilirubin (TB), total bile acids (TBA), total cholesterol (TC), malondialdehyde (MDA), glutamic-pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and total superoxide dismutase (T-SOD) in the serum. We also examined the expression levels of bile salt export pump (BSEP), ATP-binding cassette subfamily B member 4 (ABCB4), far-nesoid X receptor (FXR), small heterodimer partner (SHP), cholesterol 7α-hydroxylase (CYP7A1), and sodium taurocholate cotransporting polypeptide (NTCP) in liver tissue. In vitro experiments were conducted on primary hepatocytes to further investigate the mechanism of action of GIG on the expression of SHP, CYP7A1, NTCP, and FXR. Results Our in vivo experiments demonstrated that GIG significantly increased bile flow and reduced the levels of TB, TBA, TC, MDA, GPT, and GOT, while increasing T-SOD levels in ANIT-treated rats. Addi-tionally, GIG ameliorated liver tissue damage induced by ANIT, upregulated the expression of BSEP and ABCB4, and modulated the protein expression of FXR, SHP, CYP7A1, and NTCP in model rats. In vitro experiments further revealed that GIG inhibited the expression of SHP, CYP7A1, and NTCP by suppressing the expression of FXR. Conclusion This study provides new insights into the therapeutic potential of GIG for the treatment of cholestasis. GIG demonstrated beneficial effects on bile acid enterohepatic circulation and liver biomarkers in cholestatic rats. The modulation of FXR and its downstream targets may contribute to the mechanism of action of GIG. These findings highlight the potential of GIG as a therapeutic intervention for cholangitis.
{"title":"Gardenia Iridoid Glucosides Protect Against α-Naphthalene Isothiocya-Nate-Induced Cholestatic Rats Through Activation of the FXR-SHP Signaling Pathway","authors":"Meng Xu, Ke Che, Cong Wang, Ya-Ru Chen, Meng-Yuan Chen, Guang-Lei Zhang, Hao Yu, Hao-Nan Xu, Ya-Bao Li, Ping Sheng, Hao Chen","doi":"10.2147/CEG.S438234","DOIUrl":"https://doi.org/10.2147/CEG.S438234","url":null,"abstract":"Introduction Cholestasis is a common liver disorder that currently has limited treatment options. Gardenia Iridoid Glucosides (GIG) have been found to possess various physiological activities, such as cholagogic, hypoglycemic, antibacterial, and anti-inflammatory effects. The objective of this study was to investigate the effects of GIG on bile acid enterohepatic circulation and explore the underlying mechanism in cholestatic rats. Methods In order to identify key pathways associated with cholestasis, we conducted Gene Ontology (GO) Enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In vivo experiments were then performed on alpha-naphthylisothiocyanate (ANIT)-treated rats to assess the impact of GIG. We measured bile flow and various biomarkers including total bilirubin (TB), total bile acids (TBA), total cholesterol (TC), malondialdehyde (MDA), glutamic-pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and total superoxide dismutase (T-SOD) in the serum. We also examined the expression levels of bile salt export pump (BSEP), ATP-binding cassette subfamily B member 4 (ABCB4), far-nesoid X receptor (FXR), small heterodimer partner (SHP), cholesterol 7α-hydroxylase (CYP7A1), and sodium taurocholate cotransporting polypeptide (NTCP) in liver tissue. In vitro experiments were conducted on primary hepatocytes to further investigate the mechanism of action of GIG on the expression of SHP, CYP7A1, NTCP, and FXR. Results Our in vivo experiments demonstrated that GIG significantly increased bile flow and reduced the levels of TB, TBA, TC, MDA, GPT, and GOT, while increasing T-SOD levels in ANIT-treated rats. Addi-tionally, GIG ameliorated liver tissue damage induced by ANIT, upregulated the expression of BSEP and ABCB4, and modulated the protein expression of FXR, SHP, CYP7A1, and NTCP in model rats. In vitro experiments further revealed that GIG inhibited the expression of SHP, CYP7A1, and NTCP by suppressing the expression of FXR. Conclusion This study provides new insights into the therapeutic potential of GIG for the treatment of cholestasis. GIG demonstrated beneficial effects on bile acid enterohepatic circulation and liver biomarkers in cholestatic rats. The modulation of FXR and its downstream targets may contribute to the mechanism of action of GIG. These findings highlight the potential of GIG as a therapeutic intervention for cholangitis.","PeriodicalId":10208,"journal":{"name":"Clinical and Experimental Gastroenterology","volume":" 47","pages":"225 - 236"},"PeriodicalIF":2.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138618489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}