Pilot Study: Personalized Medicine in Endoscopy, Can Pharmacogenomics Predict Response to Conscious Sedation?

BACKGROUND: Adequate response to moderate (conscious) sedation varies significantly between individuals. Polymorphisms in genes encoding drug metabolizing enzymes can lead to inter-individual variability in drug efficacy, potentially influencing sedation requirements during endoscopic procedures. OBJECTIVES: The aim of this study was to assess the potential role of inter-individual variation in inherited polymorphisms of drug-metabolizing enzymes, cytochrome P450 (CYP450), specifically CYP3A4 and CYP3A5, in sedation requirements for outpatient endoscopic procedures. METHODS: A retrospective analysis of sedation requirements and pharmacogenomics data in 106 unique patients who received outpatient esophagogastroduodenoscopy (EGD), colonoscopy, or both between December 2011 and February 2019 was conducted. Patients were divided into two groups based on their sedation requirements during endoscopy (high vs. normal sedation). RESULTS: Patients with reduced a CYP2C19 metabolism (poor + intermediate metabolizers) (odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.16-0.91, p = 0.03), poor CYP3A5 metabolism (OR = 0.25, 95% CI: 0.095-0.65, p = 0.0046), and poor UGT1A1 (OR = 2.76, 95% CI: 1.07-7.13, p = 0.08) had higher odds of requiring normal sedation compared to those with CYP2C19 increased metabolism, CYP3A5 intermediate metabolism, and UGT1A1 intermediate metabolism. CONCLUSION: Information about inter-individual variation in (CYP450) genes may be useful for determining the sedation requirements for outpatient endoscopic procedures. We found that patients with reduced CYP2C19 metabolism, poor CYP3A5 metabolism, and poor UGT1A1 metabolism were more likely to require normal sedation requirements during outpatient endoscopic procedures.

Incidentalomas are associated with an increase in liver transplantation in patients with cirrhosis: a single-center retrospective study.

BACKGROUND: Incidentalomas, defined as incidental findings on imaging, are a growing concern. Our aim was to determine the impact and outcomes of extrahepatic incidentalomas on liver transplantation. METHODS: Patients at a large liver transplant center, who had an initial MRI for hepatocellular carcinoma screening between January 2004 and March 2020 were identified. Clinical data were collected retrospectively. Survival analysis, utilizing Kaplan Meier estimates and Cox proportional hazards regression analysis, was utilized to determine factors associated with liver transplantation. RESULTS: 720 patients were included. NASH (24.9%), HCV (22.1%) and alcohol (20.6%) were the most common causes of cirrhosis. 79.7% of patients had an extrahepatic incidentaloma. Older age and having received a liver transplant by the end of the study were associated with an incidentaloma. MELD was not associated with the presence of an incidentaloma. On univariate Cox proportional hazards regression, male sex, history of moderate alcohol use, smoking history, MELD, and incidentalomas were predictors of liver transplantation. On multivariate analysis, only MELD and the presence of an incidentaloma were found to be significant. Discovery of an incidentaloma was associated with a 30% increase in the risk of liver transplantation. Median time to transplantation did not differ based on the presence on an incidentaloma. Patients with cirrhosis from alcohol or HCV had a significantly shorter median time to transplantation than those with NASH. Renal and pancreatic lesions comprised 91% of all incidentalomas. CONCLUSIONS: In this single-center retrospective study, extrahepatic incidentalomas were common in patients with cirrhosis. The finding of an incidentaloma was associated with a higher risk of liver transplantation despite a similar median time to transplantation if no incidentaloma was discovered.

Risk of bleeding following double balloon enteroscopy in patients on continued antiplatelet and/or anticoagulation therapy.

Background and study aims Anticoagulation (AC) and antiplatelet (AP) therapy may increase the risk of gastrointestinal bleeding after double balloon enteroscopy (DBE); however, limited data are currently available regarding the incidence. The aim of this study was to assess the incidence and clinical characteristics of post-DBE bleeding in patients on AC and AP therapy. Patients and methods The medical records of patients who underwent DBE between 2009 and 2013 at Mayo Clinic, Florida, were retrospectively reviewed. Patients were divided into three groups: 1) continued AP therapy; 2) AC therapy; and 3) neither AP nor AC at the time of DBE. Follow-up data were collected at 60 days and 1 year. Results A total of 683 patients were identified; 43 on AC, 183 on AP and 457 not on AP or AC therapy. The most common indication for DBE was obscure gastrointestinal bleeding in the groups on and not on AP (85.3 % vs 70.9 %, P  < 0.0001). There was no statistical difference in post-DBE bleeding rates in patients on AP vs not on AP at 60 days (11.5 % vs 7.5 %, P  = 0.12) or 1 year (19.9 % vs 15.7 %, P  = 0.23). Rates of bleeding in patients on AC were 11.6 % within 60 days and 22.5 % within 1 year. Multivariate analysis reflected American Society of Anesthesiologist > 3 and indication for DBE of GI bleeding were independent risk factors for post-DBE bleeding within 1 year. Conclusions Continued antiplatelet use at the time of DBE was not an independent risk factor for bleeding post-DBE at 60 days or 1 year of follow up.

Extent of eosinophilic esophagitis predicts response to treatment.

Background and study aim The clinical impact of eosinophilic esophagitis (EoE) limited to the distal esophagus (Lim-EE) vs. diffuse involvement (Dif-EE) is unknown. This study compared clinical characteristics and outcomes of Lim-EE vs. Dif-EE. Patients and methods This retrospective, single-center study of patients with EoE between December 2011 and December 2019 evaluated treatment response based on repeated pathology and/or clinical improvement using comparative statistics. Results 479 patients were identified (126 Lim-EE, 353 Dif-EE). Lim-EE patients had a higher incidence of endoscopically identified esophagitis (23.0 % vs. 14.7 %; P  = 0.04), were older (50.8 [SD 16.2] vs. 46.4 [SD 15.3] years; P  = 0.007), and were more likely to present with iron deficiency anemia (5.6 % vs. 1.7 %; P  = 0.05), dyspepsia (15.1 % vs. 8.8 %; P  = 0.06) or for Barrett's surveillance (10.3 % vs. 3.7 %; P  = 0.02). Patients with Dif-EE presented more frequently with dysphagia (57.2 % vs. 45.2 %; P  = 0.02). Both groups had similar proton pump inhibitor (87.2 % vs. 83.3 %; P  = 0.37) and steroid (12.8 % vs. 21.4 %; P  = 0.14) use. Patients with Lim-EE had a better clinicopathologic response (61.5 % vs. 44.8 %; P  = 0.009). On multivariate analysis, EoE extent predicted treatment response with an odds ratio of 1.89 (95 % confidence interval 1.13-3.20; P  = 0.02). However, treatment response based only on repeat biopsy results showed no statistical difference between Lim-EE (52.5 %) and Dif-EE (39.7 %; P  = 0.15). Conclusions Lim-EE may represent a distinct phenotype separate from Dif-EE, with more overlap with gastroesophageal reflux disease and better treatment response.

Lymphocytic Esophagitis: Assessing Risk Factors and Clinical Outcomes.

BACKGROUND: Lymphocytic esophagitis is a rare esophageal condition. Our knowledge of potential risk factors and treatment outcomes of lymphocytic esophagitis is limited. AIM: To investigate potential risk factors associated with the development of lymphocytic esophagitis and compare clinical characteristics and treatment outcomes of patients diagnosed with lymphocytic esophagitis to patients diagnosed with eosinophilic esophagitis. METHODS: This is a multicenter retrospective study. Lymphocytic esophagitis patients were identified based on pathology results between 1997 and 2019. Control groups consisted of patients with normal esophageal biopsies and patients diagnosed with eosinophilic esophagitis. Thirteen potential risk factors for lymphocytic esophagitis were analyzed using univariate and multivariate models including IBD, achalasia, hyperlipidemia, hypothyroidism, celiac sprue, CVID, H. pylori, thymoma, aspirin, opioids, ACE-I, metformin, and statin use. Comparative statistics were performed. RESULTS: Ninety-four adult patients with lymphocytic esophagitis, 344 with eosinophilic esophagitis, and 5202 control patients with normal esophageal biopsies were analyzed. Age older than 60 [adjusted odd ratio (AOR) 1.03, 95% CI 1.02-1.05, p = 0.001], aspirin use (2.7, 95% CI 1.4-4.9, p = 0.001), statin use (2.2, 95% CI 1.2-4.2, p = 0.01), or a diagnosis of achalasia (2.4, 95% 1.08-5.67, p = 0.03) were associated with lymphocytic esophagitis. Compared to eosinophilic esophagitis, lymphocytic esophagitis patients were more likely to respond to medical treatment (95% CI 2.54-12.8, p = 0.0001). CONCLUSIONS: Our data suggests that lymphocytic esophagitis is more likely to be found in older female patients and is significantly associated with achalasia, statin, and aspirin use. Compared to eosinophilic esophagitis, lymphocytic esophagitis is more likely to respond to treatment with medical therapy.