Ethical Implications of Artificial Intelligence in Gastroenterology: The Co-pilot or the Captain?

Though artificial intelligence (AI) is being widely implemented in gastroenterology (GI) and hepatology and has the potential to be paradigm shifting for clinical practice, its pitfalls must be considered along with its advantages. Currently, although the use of AI is limited in practice to supporting clinical judgment, medicine is rapidly heading toward a global environment where AI will be increasingly autonomous. Broader implementation of AI will require careful ethical considerations, specifically related to bias, privacy, and consent. Widespread use of AI raises concerns related to increasing rates of systematic errors, potentially due to bias introduced in training datasets. We propose that a central repository for collection and analysis for training and validation datasets is essential to overcoming potential biases. Since AI does not have built-in concepts of bias and equality, humans involved in AI development and implementation must ensure its ethical use and development. Moreover, ethical concerns regarding data ownership and health information privacy are likely to emerge, obviating traditional methods of obtaining patient consent that cover all possible uses of patient data. The question of liability in case of adverse events related to use of AI in GI must be addressed among the physician, the healthcare institution, and the AI developer. Though the future of AI in GI is very promising, herein we review the ethical considerations in need of additional guidance informed by community experience and collective expertise.

Overall Polyp Detection Rate as a Surrogate Measure for Screening Efficacy Independent of Histopathology: Evidence from National Endoscopy Database.

Adenoma detection rate (ADR) is challenging to measure, given its dependency on pathology reporting. Polyp detection rate (PDR) (percentage of screening colonoscopies detecting a polyp) is a proposed alternative to overcome this issue. Overall PDR from all colonoscopies is a relatively novel concept, with no large-scale studies comparing overall PDR with screening-only PDR. The aim of the study was to compare PDR from screening, surveillance, and diagnostic indications with overall PDR and evaluate any correlation between individual endoscopist PDR by indication to determine if overall PDR can be a valuable surrogate for screening PDR. Our study analyzed a prospectively collected national endoscopy database maintained by the National Institute of Health from 2009 to 2014. Out of 354,505 colonoscopies performed between 2009-2014, 298,920 (n = 110,794 average-risk screening, n = 83,556 average-risk surveillance, n = 104,770 diagnostic) met inclusion criteria. The median screening PDR was 25.45 (IQR 13.15-39.60), comparable with the median overall PDR of 24.01 (IQR 11.46-35.86, p = 0.21). Median surveillance PDR was higher at 33.73 (IQR 16.92-47.01), and median diagnostic PDR was lower at 19.35 (IQR 9.66-29.17), compared with median overall PDR 24.01 (IQR 11.46-35.86; p < 0.01). The overall PDR showed excellent concordance with screening, surveillance, and diagnostic PDR (r > 0.85, p < 0.01, 2-tailed). The overall PDR is a reliable and pragmatic surrogate for screening PDR and can be measured in real time, irrespective of colonoscopy indication.

The incremental yield of adenoma detection with I-Scan versus high-definition white light colonoscopy-a systematic review and meta-analysis of randomized studies.

INTRODUCTION: The incremental yield of I-Scan virtual chromoendoscopy compared to high-definition white light endoscopy (HD-WLE) in detection of colorectal adenomas has not been thoroughly elucidated. METHODS: A systematic search from inception to April 2023 was conducted to identify randomized controlled trials (RCTs) comparing I-Scan to HD-WLE for detection of adenomas. A random effects model was used to compute risk difference (RD) with corresponding 95% confidence intervals in adenoma detection rate (ADR). Influence analysis was done to assess robustness of findings. The number needed to diagnose was computed. Heterogeneity was assessed using the I2 statistic and explored further by subgroup analyses defined a priori. Certainty in effect estimates was assessed using the GRADE approach. RESULTS: We identified four studies (I-Scan n = 730, HD-WLE n = 765). I-Scan increased adenoma detection by 9% (risk difference (RD), 0.09; 0.04, 0.14; I2 02%; certainty, low). Influence analysis revealed that the gain in yield remained statistically significant with exclusion of all but one study. The number needed to capture one additional adenomatous polyp with I-Scan use was 11.2. I-Scan 1 use was associated with a statistically significant gain in ADR, whereas no significant difference in ADR was noted with I-Scan use on subgroup analysis. DISCUSSION: In conclusion, I-Scan increases the yield of adenoma detection by 9% compared to HD-WLE, with low certainty in the estimate of this effect. Data on the gain in yield of detecting large polyps, sessile serrated lesions, and on the impact of formally training endoscopists and trainees in I-Scan use and similar technology on adenoma detection rate are needed.

Is antibiotic prophylaxis necessary after endoscopic ultrasound-guided fine-needle aspiration of pancreatic cysts?

BACKGROUND/AIMS: Current society guidelines recommend antibiotic prophylaxis for 3 to 5 days after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic cystic lesions (PCLs). The overall quality of the evidence supporting this recommendation is low. In this study, we aimed to assess cyst infection and adverse event rates after EUS-FNA of PCLs among patients treated with or without postprocedural prophylactic antibiotics. METHODS: We retrospectively reviewed all patients who underwent EUS-FNA of PCLs between 2015 and 2019 at two large-volume academic medical centers with different practice patterns of postprocedural antibiotic prophylaxis. Data on patient demographics, cyst characteristics, fine-needle aspiration technique, periprocedural and postprocedural antibiotic prophylaxis, and adverse events were retrospectively extracted. RESULTS: A total of 470 EUS-FNA procedures were performed by experienced endosonographers for the evaluation of PCLs in 448 patients, 58.7% of whom were women. The mean age was 66.3±12.8 years. The mean cyst size was 25.7±16.9 mm. Postprocedural antibiotics were administered in 274 cases (POSTAB+ group, 58.3%) but not in 196 cases (POSTAB- group, 41.7%). None of the patients in either group developed systemic or localized infection within the 30-day follow-up period. Procedure-related adverse events included mild abdominal pain (8 patients), intra-abdominal hematoma (1 patient), mild pancreatitis (1 patient), and perforation (1 patient). One additional case of pancreatitis was recorded; however, the patient also underwent endoscopic retrograde cholangiopancreatography. CONCLUSION: The incidence of infection after EUS-FNA of PCLs is negligible. Routine use of postprocedural antibiotics does not add a significant benefit.

Practice patterns and adherence to society guidelines for suspected choledocholithiasis: A comparison of academic and community settings from a large US healthcare system.

Background: The American Society of Gastrointestinal Endoscopy (ASGE) has proposed practice guidelines for evaluating patients with suspected choledocholithiasis. This study aims to assess and compare practice patterns for following ASGE guidelines for choledocholithiasis in a large academic vs. community hospital setting. Methods: A total of one thousand ER indicated for choledocholithiasis were randomly selected. Patients' demographics, total bilirubin, imaging studies including magnetic resonance cholangiopancreatography (MRCP), intraoperative cholangiogram (IOC), endoscopic ultrasound (EUS), and ERCP results were retrospectively collected. Patients with prior sphincterotomy were excluded. We examined the following practice deviations from the current ASGE guidelines; (1) ERCP was potentially delayed in high probability cases while awaiting additional imaging studies, (2) ERCP was performed without additional imaging studies in cases of low/intermediate-risk, or (3) ERCP was performed in low/intermediate-risk cases when additional imaging studies were negative. Results: A total of 640 patients with native papilla who underwent ERCP were included in the final analysis. Overall, the management of 43% (275) of patients was deviated from the applicable ASGE guidelines. Academic and community provider rates of non-adherence were 32 vs. 45%, respectively (p-value: < 0.01). Of 381 high-risk cases, 54.1% had additional imaging before ERCP. (Academic vs. community; 11.7 vs. 88.3%, p-value: < 0.01). In 26.7% (69/258) of low/intermediate risk cases, ERCP was performed without additional studies; academic (14.5%) vs. community (85.5%) (p-value: < 0.01). Finally, in 11.2% (19/170) of patients, ERCP was performed despite intermediate/low probability and negative imaging; academic (26.3%) vs. community (73.7%) (p-value: 0.02). Conclusion: Our study results show that providers do not adhere to ASGE practice guidelines in 43% of suspected choledocholithiasis cases. The rate of non-adherence was significantly higher in community settings. It could be due to various reasons, including lack/delays for alternate studies (i.e., MRCP, EUS), concern regarding the length of stay, patient preference, or lack of awareness/understanding of the guidelines. Increased availability of alternate imaging and educational strategies may be needed to increase the adoption of practice guidelines across academic and community settings to improve patient outcomes and save healthcare dollars.

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) for advanced pancreatic and periampullary adenocarcinoma.

Long term prognosis and 5-year survival for pancreatic adenocarcinoma (PDAC) remains suboptimal. Endoscopic ultrasound (EUS) guided RFA (EUS-RFA) is an emerging technology and limited data exist regarding safety and long-term outcomes. The aim of this study is to report safety-profile, feasibility and outcomes of EUS-RFA for advanced PDAC. Prospective review of patients with diagnosis of locally-advanced or metastatic PDAC undergoing EUS-RFA between October 2016 to March 2018 with long-term follow up (> 30 months). Study patients underwent a total of 1-4 RFA sessions. All patients were enrolled in longitudinal cohort study and received standard of care chemotherapy. 10 patients underwent EUS-RFA. Location of the lesions was in the head(4), neck(2), body(2), and tail(2). 22 RFA sessions were performed with a range of 1-4 sessions per patient. There were no major adverse events (bleeding, perforation, infection, pancreatitis) in immediate (up to 72 h) and short-term follow up (4 weeks). Mild worsening of existing abdominal pain was noted during post-procedure observation in 12/22 (55%) of RFA treatments. Follow-up imaging demonstrated tumor progression in 2 patients, whereas tumor regression was noted in 6 patients (> 50% reduction in size in 3 patients). Median survival for the cohort was 20.5 months (95% CI, 9.93-42.2 months). Currently, 2 patients remain alive at 61 and 81 months follow-up since initial diagnosis. One patient had 3 cm PDAC with encasement of the portal confluence, abutment of the celiac axis, common hepatic and superior mesenteric artery. This patient had significant reduction in tumor size and underwent standard pancreaticoduodenectomy. In our experience, EUS-RFA was safe, well-tolerated and could be concurrently performed with standard chemotherapy. In this select cohort, median survival was improved when compared to published survival based upon SEER database and clinical trials. Future prospective trials are needed to understand the role of EUS-RFA in overall management of PDAC.

(#WomeninDDW) Persistent Speaker Gender Gap at the Premier Digestive Disease Event.

BACKGROUND: Over the last few decades, advances have been made regarding gender equality starting from medical students to trainees, to leadership in academics. The female representation in specialty academic conferences not only reflects the existing gender disparities in that specialty but also can influence young female trainees to join that field. Digestive Disease Week (DDW) is the premier digestive disease event. We aimed to calculate the proportion of female representation among speakers and moderators at the DDW meetings held from 2018 to 2020. METHODS: The data for DDW 2018-2020 were collected via the online web-based planner. The gender of speakers of presentations and moderators of sessions were identified by a google search. We further categorized the data by each participating society (AGA, ASGE, AASLD, and SSAT), by presentation track, by session track, and total overall representation in each year. RESULTS: Despite the subject of the gender gap being in focus, the proportion of female moderators and speakers was low in DDW in the last 3 years. The female speakers constituted 31.6% in 2018, 33.8% in 2019 and 34.6% in 2020. There was slightly improved female representation in sessions of Inflammatory Bowel Disease, Stomach, and Small Bowel Disorders, Microbiome in GI & Liver disease, and Basic Science over the last 3 years. CONCLUSION: Based on our study and those referenced in this article, we believe that strategies to promote the inclusivity of female moderators and speakers at DDW provide a huge opportunity to influence gender equity within GI.

Cost-effectiveness analysis of optimal diagnostic strategy for patients with symptomatic cholelithiasis with intermediate probability for choledocholithiasis.

BACKGROUND AND AIMS: EUS, MRCP, and intraoperative cholangiogram (IOC) are the recommended diagnostic modalities for patients with intermediate probability for choledocholithiasis (IPC). The relative cost-effectiveness of these modalities in patients with cholelithiasis and IPC is understudied. METHODS: We developed a decision tree for diagnosing IPC (base-case probability, 50%; range, 10%-70%); patients with a positive test were modeled to undergo therapeutic ERCP. The strategies tested were laparoscopic cholecystectomy with IOC (LC-IOC), MRCP, single-session EUS + ERCP, and separate-session EUS + ERCP. Costs and probabilities were extracted from the published literature. Effectiveness was assessed by assigning utility scores to health states, average proportion of true-positive diagnosis of IPC, and the mean length of stay (LOS) per strategy. Cost-effectiveness was assessed by extrapolating a net-monetary benefit (NMB) and average cost per true-positive diagnosis. RESULTS: LC-IOC was the most cost-effective strategy to diagnose IPC (base-case probability of 50%) among patients with cholelithiasis in health state-based effectiveness analysis (NMB of $34,612), diagnostic test accuracy-based effectiveness analysis (average cost of $13,260 per true-positive diagnosis), and LOS-based effectiveness analysis (mean LOS of 4.13) compared with strategies 2 (MRCP), 3 (single-session EUS + ERCP), and 4 (separate-session EUS + ERCP). These findings were robust on deterministic and probabilistic sensitivity analyses. CONCLUSIONS: For patients with cholelithiasis with IPC, LC-IOC is a cost-effective approach that should limit preoperative testing and may shorten hospital LOS. Our findings may be used to design institutional and organizational management protocols.

A phase II randomized double blinded trial evaluating the efficacy of curcumin with pre-operative chemoradiation for rectal cancer.

Background: In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome. Methods: From 2008-2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. Blood samples taken pre- and 1-hour post-ingestion and tissue biopsies (both collected at CRT week 2) were analyzed for pharmacokinetics. The primary outcome was surgical pCR rate. Results: Of 22 enrolled patients, 15 received curcumin. Median age was 61 years and the majority were male (n=13; 59%). The median serum curcumin concentrations before (3.04 ng/mL; range, 1.24-18.88 ng/mL) and 1 hour after (3.32 ng/mL; range, 0.84-5.36 ng/mL) curcumin intake did not differ significantly (P=0.33). Serum curcumin concentrations both increased and decreased 1-hour post-administration (range as percentage of baseline: 8.8-258.1%). Twelve curcumin patient tissue biopsies had median curcumin concentration of 33.7 ng/mg tissue (range, 0.1-4,765.7 ng/mg). Two placebo and 1 curcumin patient achieved pCRs (P=0.18). One grade 3 toxicity (infection) was experienced. Conclusions: The addition of curcumin to CRT did not increase pCR rates for LARC patients. The unpredictable bioavailability of curcumin contributes to continued uncertainties regarding curcumin efficacy. Trial Registration: ClinicalTrials.gov identifier: NCT00745134.

A potential signaling axis between RON kinase receptor and hypoxia-inducible factor-1 alpha in pancreatic cancer.

The Cancer Genome Atlas (TCGA) of a pancreatic cancer cohort identified high MST1R (RON tyrosine kinase receptor) expression correlated with poor prognosis in human pancreatic cancer. RON expression is null/minimal in normal pancreas but elevates from pan-in lesions through invasive carcinomas. We report using multiple approaches RON directly regulates HIF-1α, a critical driver of genes involved in cancer cell invasion and metastasis. RON and HIF-1α are highly co-expressed in the 101 human PDAC tumors analyzed and RON expression correlated with HIF-1α expression in a subset of PDAC cell lines. knockdown of RON expression in RON positive cells blocked HIF-1α expression, whereas ectopic RON expression in RON null cells induced HIF-1α expression suggesting the direct regulation of HIF-1α by RON kinase receptor. RON regulates HIF-1α through an unreported transcriptional mechanism involving PI3 kinase-mediated AKT phosphorylation and Sp1-dependent HIF-1α promoter activity leading to increased HIF-1α mRNA expression. RON/HIF-1α modulation altered the invasive behavior of PDAC cells. A small-molecule RON kinase inhibitor decreased RON ligand, MSP-induced HIF-1α expression, and invasion of PDAC cells. Immunohistochemical analysis on RON knockdown orthotopic PDAC tumor xenograft confirmed that RON inhibition significantly blocked HIF-1α expression. RON/HIF-1α co-expression also exists in triple-negative breast cancer cells, a tumor type that also lacks molecular therapeutic targets. This is the first report describing RON/HIF-1α axis in any tumor type and is a potential novel therapeutic target.

Bleeding Risk and Mortality Associated With Uninterrupted Antithrombotic Therapy During Percutaneous Endoscopic Gastrostomy Tube Placement.

INTRODUCTION: Antithrombotic therapy is often interrupted before the placement of a percutaneous endoscopic gastrostomy (PEG) tube because of potentially increased risk of hemorrhagic events. The aim of our study was to evaluate the risk of bleeding events and overall complication rates after PEG in patients on uninterrupted antiplatelet and anticoagulation therapy in a high-volume center. METHODS: Data regarding demographics, diagnoses, comorbidities, and clinical outcomes pertinent to PEG were collected from 2010 to 2016. Furthermore, data regarding antithrombotic therapy along with the rate of minor or major complications including bleeding associated with this procedure were analyzed. Significant bleeding was defined as postprocedure bleeding from PEG site requiring a blood transfusion and/or surgical/endoscopic intervention. RESULTS: We included 1,613 consecutive PEG procedures in this study, of which 1,540 patients (95.5%) received some form of uninterrupted antithrombotic therapy. Of those patients, 535 (34.7%) were on aspirin, 256 (16.6%) on clopidogrel, and 119 (7.7%) on both aspirin and clopidogrel. Subcutaneous heparin was uninterrupted in 980 (63.6%), intravenous heparin in 34 (2.1%), warfarin in 168 (10.9%), and direct-acting oral anticoagulation in 82 (5.3%) patients who overlapped on multiple drugs. We observed 6 significant bleeding events in the entire cohort (0.39%), and all were in subcutaneous heparin groups either alone or in combination with aspirin. No clinically significant bleeding was noted in patients on uninterrupted aspirin, warfarin, clopidogrel, or direct-acting oral anticoagulation groups. Only 5 patients (0.31%) had PEG-related mortality. DISCUSSION: The risk of significant bleeding associated with the PEG placement was minimal in patients on uninterrupted periprocedural antithrombotic therapy.

Comparing diagnostic accuracy of current practice guidelines in predicting choledocholithiasis: outcomes from a large healthcare system comprising both academic and community settings.

BACKGROUND AND AIMS: The American Society for Gastrointestinal Endoscopy (ASGE) 2010 guidelines for suspected choledocholithiasis were recently updated by proposing more specific criteria for selection of high-risk patients to undergo direct ERCP while advocating the use of additional imaging studies for intermediate- and low-risk individuals. We aim to compare the performance and diagnostic accuracy of 2019 versus 2010 ASGE criteria for suspected choledocholithiasis. METHODS: We performed a retrospective chart review of a prospectively maintained database (2013-2019) of over 10,000 ERCPs performed by 70 gastroenterologists in our 14-hospital system. We randomly selected 744 ERCPs in which the primary indication was suspected choledocholithiasis. Patients with a history of cholecystectomy or prior sphincterotomy were excluded. The same patient cohort was assigned as low, intermediate, or high risk according to the 2010 and 2019 guideline criteria. Overall accuracy of both guidelines was compared against the presence of stones and/or sludge on ERCP. RESULTS: Of 744 patients who underwent ERCP, 544 patients (73.1%) had definite stones during ERCP and 696 patients (93.5%) had stones and/or sludge during ERCP. When classified according to the 2019 guidelines, fewer patients were high risk (274/744, 36.8%) compared with 2010 guidelines (449/744, 60.4%; P < .001). Within the high-risk group per both guidelines, definitive stone was found during ERCP more frequently in the 2019 guideline cohort (226/274, 82.5%) compared with the 2010 guideline cohort (342/449, 76.2%; P < .001). In our patient cohort, overall specificity of the 2010 guideline was 46.5%, which improved to 76.0% as per 2019 guideline criteria (P < .001). However, no significant change was noted for either positive predictive value or negative predictive value between 2019 and 2010 guidelines. CONCLUSIONS: The 2019 ASGE guidelines are more specific for detection of choledocholithiasis during ERCP when compared with the 2010 guidelines. However, a large number of patients are categorized as intermediate risk per 2019 guidelines and will require an additional confirmatory imaging study.

Kras mutation rate precisely orchestrates ductal derived pancreatic intraepithelial neoplasia and pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States. Despite the high prevalence of Kras mutations in pancreatic cancer patients, murine models expressing the oncogenic mutant Kras (Krasmut) in mature pancreatic cells develop PDAC at a low frequency. Independent of cell of origin, a second genetic hit (loss of tumor suppressor TP53 or PTEN) is important for development of PDAC in mice. We hypothesized ectopic expression and elevated levels of oncogenic mutant Kras would promote PanIN arising in pancreatic ducts. To test our hypothesis, the significance of elevating levels of K-Ras and Ras activity has been explored by expression of a CAG driven LGSL-KrasG12V allele (cKras) in pancreatic ducts, which promotes ectopic Kras expression. We predicted expression of cKras in pancreatic ducts would generate neoplasia and PDAC. To test our hypothesis, we employed tamoxifen dependent CreERT2 mediated recombination. Hnf1b:CreERT2;KrasG12V (cKrasHnf1b/+) mice received 1 (Low), 5 (Mod) or 10 (High) mg per 20 g body weight to recombine cKras in low (cKrasLow), moderate (cKrasMod), and high (cKrasHigh) percentages of pancreatic ducts. Our histologic analysis revealed poorly differentiated aggressive tumors in cKrasHigh mice. cKrasMod mice had grades of Pancreatic Intraepithelial Neoplasia (PanIN), recapitulating early and advanced PanIN observed in human PDAC. Proteomics analysis revealed significant differences in PTEN/AKT and MAPK pathways between wild type, cKrasLow, cKrasMod, and cKrasHigh mice. In conclusion, in this study, we provide evidence that ectopic expression of oncogenic mutant K-Ras in pancreatic ducts generates early and late PanIN as well as PDAC. This Ras rheostat model provides evidence that AKT signaling is an important early driver of invasive ductal derived PDAC.