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Endoscopic remission is associated with significant reduction in risk of clinical flare, unplanned healthcare utilization and surgery, and has emerged as a preferred treatment target in patients with inflammatory bowel diseases. To achieve this target with biologic therapy, an approach that combines pharmacodynamic effect of the drug (impact of drug on biomarkers of inflammation) and pharmacokinetic optimization of therapy (achieving optimal trough concentrations) has been proposed, but there is limited data on effectiveness of such an approach. In this issue of Clinical Gastroenterology and Hepatology, Dreesen and colleagues1Dressen E. Baert F. Laharie D. et al.Monitoring a combination of calprotectin and infliximab identifies patients with mucosal healing of Crohn’s disease.Clin Gastroenterol Hepatol. 2020; 18: 637-646Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar performed a post-hoc analysis of the TAILORIX trial to examine the role of combined pharmacodynamic and pharmacokinetic monitoring during infliximab induction and maintenance therapy for targeting endocopic outcomes in patients with Crohn’s disease. They observed that during induction and maintenance therapy, progressive decline in fecal calprotectin with infliximab therapy was associated with significantly higher rates of achieving endoscopic remission at week 12 and 54, respectively. They also observed clear relationship between infliximab trough concentration during induction therapy and endoscopic remission at week 12, identifying thresholds of 23.1 mg/L at week 2 and of 10.0 mg/L at week 6. Similarly, during maintenance therapy, infliximab thresholds of 10.0 mg/L were associated with achieving endoscopic remission. In patients with subtherapeutic trough concentration, infliximab dose escalation was effective in achieving endoscopic remission only if it was associated with a decline in fCal; persistent elevation of fCal despite achieving higher infliximab concentration was associated with lack of endoscopic remission. Taken together, these results strongly support an approach that combines pharmacodynamic monitoring (for improvement in biomarkers of inflammation) with pharmacokinetic monitoring for infliximab (checking trough concentration to ensure adequate trough concentration) to ensure optimal outcome in patients with moderate to severely active Crohn’s disease. See page 637. One of the key objectives of gastroenterology fellowship programs is training in basic endoscopic procedures. Traditionally, this has been based on the apprenticeship model in which fellows learn endoscopy through hands-on experience under the supervision of multiple faculty members. However, teaching endoscopy is very challenging, and there may be significant variations in teaching style and quality. An evidence-based set of endoscopy teaching best practices can provide a framework to promote effectiveness of individual endoscopy teachers. To develop these best practices in teaching endoscopy, Kumar and colleagues2Kumar N.L. Smith B.N. Lee L.S. et al.Best practices in teaching endoscopy based on a Delphi survey of gastroenterology program directors and experts in endoscopy education.Clin Gastroenterol Hepatol. 2020; 18: 574-579Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar performed a national Delphi survey of gastroenterology fellowship program directors (n = 34) and experts in endoscopy education (n = 2), in which experts rated each of 18 endoscopy teaching competencies (identified based on literature review, personal experience, and cognitive interviews with experts) as “essential,” “important, but not essential,” or “not important.” Based on 2 rounds of Delphi consensus, experts agreed on the top 10 essential list of endoscopy teaching competencies. These include: (before each session and procedure) 1) assessing trainee’s current procedural competency, 2) discussing patient’s history and plans for procedure with trainee, 3) confirming that patient is aware of trainee’s participation and role; (during endoscopic procedure) 4) maintaining attention throughout the case, 5) providing appropriate amount of feedback during the procedure, 6) using standardized endoscopic language to guide trainee through the procedure, 7) assuming control of procedure when trainee is unable to progress or if patient safety concerns arise; and (after each procedure and session) 8) discussing next steps in the management of patient, 9) reviewing procedure note and providing feedback as needed to the trainee, and 10) providing constructive feedback to trainee at end of the session. These competencies are specific, measurable, and relevant, and provide a framework for faculty development to improve the quality of endoscopic education within fellowship programs. See page 574. Colonoscopy is considered the reference standard for diagnosing colorectal cancer (CRC) and its precursor lesions and is advocated as one of the most favored tests for screening for CRC. However, it is invasive, resource- and cost-intensive and with non-trivial risks. Alternative CRC screening strategies such as flexible sigmoidoscopy and fecal immunochemical test (FIT) are also recommended as progressively less invasive, but less sensitive options. It is essential for policy makers to know the impact of different screening programs over multiple rounds with long-term follow up. In this issue of Clinical Gastroenterology and Hepatology, Grobbee, van der Vlugt and colleagues3Grobbee E.J. van der Vlugt M. van Vuuren A.J. et al.Diagnostic yield of one-time colonoscopy vs one-time flexible sigmoidoscopy vs multiple rounds of mailed fecal immunohistochemical tests in colorectal cancer screening.Clin Gastroenterol Hepatol. 2020; 18: 667-675Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar compared the diagnostic yield of once-only colonoscopy, once-only flexible sigmoidoscopy, and 4 rounds of FIT in population-based CRC screening, including interval cancer rate. Combining data from 3 population-based trials in the Netherlands, a total of 30,052 average risk persons were invited for CRC screening. Cumulative participation rate was significantly higher for FIT screening (77%) than for flexible sigmoidoscopy (31%; P < .001) or colonoscopy (24%; P <. 001). In the primary intention-to-screen analysis, the cumulative diagnostic yield of advanced neoplasia was highest with FIT screening (4.5%; 95% CI, 4.2–4.9) than with colonoscopy (2.2%; 95% CI, 1.8–2.6) or flexible sigmoidoscopy (2.3%; 95% CI, 2.0–2.7). This higher diagnostic yield was reached with significantly fewer colonoscopies for FIT screening and flexible sigmoidoscopy screening than colonoscopy screening. No differences were found regarding the detection of CRC between all three strategies. Between participants, colonoscopy had the highest diagnostic yield for advanced neoplasia, while also detecting greater numbers of non-advanced adenomas, which are of uncertain clinical importance. Through linkage with the Netherlands Cancer Registry, proportions of patients that developed interval CRC were 0.13% for persons with a negative result from the FIT, 0.09% for persons with a negative result from flexible sigmoidoscopy, and 0.01% for persons with a negative result from colonoscopy. These findings aid in deciding on choice of screening strategies worldwide, based on expected participation rates and available colonoscopy resources. This article is highlighted by an editorial by Kevin Selby and Manuel Zorbi.4Selby K. Zorzi M. Real-world strategies for colorectal cancer screening based on studies from the Netherlands.Clin Gastroenterol Hepatol. 2020; 18: 546-547Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar See page 667. The prevalence of nonalcoholic steatohepatitis (NASH)-associated hepatocellular cancer (HCC) is increasing. Ultrasound-based HCC surveillance strategies have important limitations, particularly in patients with NASH. To address the insufficient performance of ultrasound-based surveillance in HCC detection, the GALAD score (based on age, sex, serum levels of alpha-fetoprotein [AFP], AFP isoform L3 [AFP-L3], and des-gamma-carboxy prothrombin [DCP]) was developed and has been shown to be superior to ultrasound-based HCC surveillance in early detection of HCC. In this issue of Clinical Gastroenterology and Hepatology, Best and colleagues5Best J. Bechmann L.P. Sowa J.–P. et al.GALAD score detects early hepatocellular carcinoma in an international cohort of patients with nonalcoholic steatohepatitis.Clin Gastroenterol Hepatol. 2020; 18: 728-735Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar compared the performance of serum AFP, AFP-L3, or DCP vs GALAD score to identify patients with HCC, in an international multi-center case-control study (126 cases with HCC and 231 NASH controls without HCC). They observed that the GALAD score identified patients with any stage HCC with an AUC of 0.96, significantly greater than values for serum levels of AFP (AUC, 0.88), AFP-L3 (AUC, 0.86) or DCP (AUC, 0.87). These findings were consistent in patients with vs. without cirrhosis. A cut-off of GALAD score –0.63, the GALAD score achieved an AUC of 0.91, with a sensitivity of 68% and specificity of 95% for detecting HCC within Milan criteria. In a subsequent Japanese HCC surveillance cohort of 389 patients with NASH, the investigators confirmed that the mean GALAD score was higher in patients with NASH who developed HCC than in those who did not develop HCC as early as 1.5 years before HCC diagnosis, with a cut-off of –0.63 being identified approximately 200 days before HCC diagnosis. These data support further investigation of the GALAD score as a noninvasive surveillance tool for NASH patients at risk for HCC. See page 728. /cms/asset/32314abc-4a6a-45b1-b187-16233d15e11a/mmc1.mp3Loading ... Download .mp3 (21.04 MB) Help with .mp3 files Audio Best Practices in Teaching Endoscopy Based on a Delphi Survey of Gastroenterology Program Directors and Experts in Endoscopy EducationClinical Gastroenterology and HepatologyVol. 18Issue 3PreviewTeaching endoscopy is a key objective of gastroenterology (GI) fellowship programs but the best approach is not known. We sought to characterize which teaching competencies experts considered most critical for endoscopy education. Full-Text PDF GALAD Score Detects Early Hepatocellular Carcinoma in an International Cohort of Patients With Nonalcoholic SteatohepatitisClinical Gastroenterology and HepatologyVol. 18Issue 3PreviewThe prevalence of nonalcoholic steatohepatitis (NASH) associated hepatocellular carcinoma (HCC) is increasing. However, strategies for detection of early-stage HCC in patients with NASH have limitations. We assessed the ability of the GALAD score, which determines risk of HCC based on patient sex; age; and serum levels of α-fetoprotein (AFP), AFP isoform L3 (AFP-L3), and des-gamma-carboxy prothrombin (DCP), to detect HCC in patients with NASH. Full-Text PDF Open AccessMonitoring a Combination of Calprotectin and Infliximab Identifies Patients With Mucosal Healing of Crohn’s DiseaseClinical Gastroenterology and HepatologyVol. 18Issue 3PreviewIn the TAILORIX trial, no benefit could be shown by infliximab dose escalation based on pharmacokinetic (infliximab serum concentrations) and pharmacodynamic (biomarkers and symptoms) monitoring compared with dose escalation based on symptoms alone in patients with Crohn’s disease (CD). We investigated whether integration of pharmacokinetic and pharmacodynamic monitoring can be used to evaluate responses to infliximab induction and maintenance therapy, based on findings from endoscopy. Full-Text PDF Diagnostic Yield of One-Time Colonoscopy vs One-Time Flexible Sigmoidoscopy vs Multiple Rounds of Mailed Fecal Immunohistochemical Tests in Colorectal Cancer ScreeningClinical Gastroenterology and HepatologyVol. 18Issue 3PreviewWe compared the diagnostic yields of colonoscopy, flexible sigmoidoscopy, and fecal immunochemical tests (FITs) in colorectal cancer (CRC) screening. Full-Text PDF