Tertiary Care Center Trends in Colonic Stent Placement over the Past Decade.

INTRODUCTION: Colonic endoluminal stent placement is a commonly utilized and effective endoscopic approach for the management of malignant large bowel obstruction and is an emerging approach for the management of some benign etiologies of large bowel obstruction. However, recent studies evaluating the evolution of clinical scenarios and patient populations for which stenting is performed in real-world practice are lacking. METHODS: We assessed colonic stent utilization patterns in a tertiary care academic medical center over the past 10 years. We analyzed the demographics and patient and procedure characteristics of the initial (first half of study period) and latter (second half of the study period) procedures to assess trends over time using standard descriptive statistics. RESULTS: Our analysis was notable due to its provision of some novel insights. The frequency of colonic stent placement procedures increased significantly over time by comparison of the procedure volume for the initial 5-year interval (22 colonic stent procedures) relative to the latter 5-year interval (49 colonic stent procedures) (p = 0.03). The median age of patients who underwent colonic stent placement was significantly lower in the latter 5 years, compared with the initial 5 years of the study period (mean of 81.41 vs. 58.73 years, respectively, p < 0.001). The increased diversity of indications for colonic stent placement was also noted over time. CONCLUSIONS: Our data highlight the evolution of colonic stent placement in tertiary care practice over time and are notable for some interesting trends, including the increased utilization of colonic stent placement over time, the broadening of indications for colonic stent placement to include benign indications, and lower patient age at the time of colonic stent placement over time. These findings will help inform the clinical practice of colonic stent placement and provide a foundation to guide future research on the topic.

Use Patterns, Technical Challenges and Patient Selection Associated With Single Use Duodenoscopes & Duodenoscopes With Single Use Endcaps In The United States & Canada.

BACKGROUND & AIMS: The extent of adoption, patient selection and use patterns of single use duodenoscopes and duodenoscopes with single use endcaps have not yet been characterized, nor have large scale assessments of endoscopist-reported function and challenges. METHODS: An anonymous 6-minute electronic survey assessing use and experience with single use duodensocopes and duodenoscopes with novel design features was distributed to US and Canadian endoscopy centers and responses were analyzed using descriptive statistics. RESULTS: The survey was notable for a 70.2% response rate, with representation from academic (68.9%), community (18%) and veterans affairs (8.2%) centers. Most institutions use standard reprocessable duodenoscopes and duodenoscopes with single use endcaps (34.4%), or a mix of standard reprocessable duodenoscopes, duodenoscopes with single use endcaps and single use duodenoscopes (29.5%). No center used only single use duodenoscopes (0%). 10.3% planned to transition to the duodenoscope with a single use endcap, 10.3% to a mix of single use duodenoscopes and duodenoscopes with single use endcap, and 1.7% to single use duodenoscopes alone. Challenges were reported with each type of novel duodenoscope and selection patterns for use were characterized. CONCLUSIONS: This first-of-its-kind large scale survey of use patterns and functionality of newly introduced duodenoscopes is notable for fairly widespread use of the duodenoscopes with single use endcaps and more limited use of the single use duodenoscope. Both novel duodenoscope designs are associated with mechanical limitations that respondents indicate represent challenges to successful completion of ERCPs.

Safety and efficacy of the EndoRotor device for the treatment of walled-off pancreatic necrosis after EUS-guided cystenterostomy: A systematic review and meta-analysis.

Debridement of infected walled-off pancreatic necrosis is indicated to treat and prevent sepsis-related multiorgan failure. The aim of this study was to evaluate the efficacy and safety of the EndoRotor-powered endoscopic debridement system to remove solid debris under direct endoscopic visualization. Search strategies were developed for PubMed, EMBASE, and Cochrane Library databases from inception to June 2022, in accordance with Preferred Reporting items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Outcomes of interest included technical success defined as successful use of device for debridement, clinical success defined as complete debridement and cyst resolution, and procedure-related adverse events. A random-effects model was used for analysis, and results were expressed as odds ratio along with 95% confidence interval. A total of 7 studies (n = 79 patients) were included. The mean walled-off pancreatic necrosis size was 154.6 ± 34.0 mm, whereas the mean procedure time was 71.4 minutes. The mean number of necrosectomy sessions required was 2.2 (range, 1-7). The pooled rate of clinical success was 96% (95% confidence interval, 91%-100%; I 2 = 0%) with a pooled technical success rate of 96% (91%-100%; I 2 = 0%). The pooled procedure-related adverse event rate was 8% (2%-14%; I 2 = 6%), which included procedure-associated bleeding, pneumoperitoneum, peritonitis, pleural effusion, and dislodgement of lumen-apposing metal stents. Our study shows that the novel EndoRotor device seems to be safe and effective for treating pancreatic necrosis. Patients undergoing endoscopic necrosectomy with the EndoRotor seem to require less debridement sessions when compared with studies using conventional instruments.

Pediatric advanced complex endoscopy team enhances endoscopy quality and provider satisfaction.

BACKGROUND: Therapeutic endoscopic procedures are increasingly necessary for children. Pediatric gastroenterologist training and experience with endoscopic hemostasis and other complex therapeutic endoscopy procedures are often limited. We evaluated the impact of the implementation of an advanced complex endoscopy (ACE) team, which provides 24/7 inpatient/outpatient back-up endoscopy support. METHODS: We analyzed hemostasis quality outcomes in the 2 years before implementation of ACE (2018-2020) versus the year following the implementation of ACE (2020-2021). We analyzed pediatric gastroenterology provider satisfaction and perspectives with a survey that was distributed to faculty, fellows, and advanced practice providers 1 month before implementation of ACE and again 12 months following ACE implementation. RESULTS: Endoscopy volume and outcome metrics for hemostasis procedures, including latency to endoscopy, need for reintervention, and administration/diversity of hemostatic therapy, including multimodal therapy, improved in the year following implementation of the ACE (p < 0.05 for each). Survey results demonstrated a positive impact on provider endoscopy experience and high utilization of ACE. Twenty-two percent of providers reported activating ACE in the prior month and 66% in the prior year. Most providers who activated ACE were very satisfied (85%) or satisfied (7.7%). Eighty-three percent noted ACE had a positive impact on inpatients, and 50% noted a positive impact on outpatient endoscopy. Provider anxiety with endoscopy diminished post-ACE implementation (62% vs. 28%). Respondents unanimously found ACE beneficial to patient care (100%). CONCLUSIONS: ACE implementation was associated with improved provider perspectives surrounding endoscopy and significant improvement in hemostasis quality parameters, escalation of hemostasis procedure volume, and broadening the range of hemostasis interventions.

Advanced trainee perceptions of disposable duodenoscopes and disposable endcaps: results of a nationwide survey.

INTRODUCTION: Disposable duodenoscopes and duodenoscopes with disposable endcaps are being used in clinical practice to reduce or eliminate the risk of transmitting infections. The study aim was to assess perceptions and experiences regarding the use of these duodenoscopes among advanced endoscopy fellows in a nationally representative sample. METHODS: A 17-item electronic survey was sent to 74 advanced endoscopy training programs. The survey was completed by 50 participants and their responses were included for analysis. RESULTS: Most participants were from academic training programs (82.7%) and identified as being in their 7th year of post graduate training (92%; PGY-7). Participants performed an average of 414 ERCPs. 29% reported difficulty with cannulation using disposable duodenoscopes versus 15.7% with duodenoscopes with disposable endcaps (vs. standard duodenoscope). 96% of trainees perceived disposable duodenoscopes as not cost effective and 92% stated they would not use this device during independent practice. 100% of trainees stated that they would use duodenoscopes with disposable endcaps during independent practice. For their most challenging cases, 90% of trainees preferred using standard reprocessable duodenoscopes while no trainee indicated they would prefer using a disposable duodenoscope in this scenario. 82% of participants stated that disposable duodenoscopes and disposable endcaps should be used exclusively or preferentially for high-risk patients citing cost, functionality, and concerns regarding environmental impact. DISCUSSION: Advanced endoscopy fellows perceive disposable duodenoscopes as impacting technical maneuverability. Concerns about functionality, cost effectiveness and environmental impact are barriers to adoption.

Initial experience with duodenoscopes with single-use end caps in pediatric ERCP: infection prevention comes at a cost.

BACKGROUND AND AIMS: Duodenoscopes with single-use end caps were introduced to minimize infection risk, but they are unstudied in pediatrics. METHODS: We collected clinical data and endoscopists' evaluations of duodenoscopes with single-use end caps versus reusable duodenoscopes over 18 months. RESULTS: A total of 106 ERCPs were performed for patients aged 1 to 18 (mean, 14.2) years. Forty-six involved single-use end caps, with 9 requiring crossover to reusable duodenoscopes. ERCPs involving single-use end caps resulted in more instances of mucosal trauma (10 vs 0; P < .05) and post-ERCP pancreatitis (4 vs 1; P < .05) and accounted for 8 of 9 ERCPs requiring advanced cannulation techniques. No post-ERCP infections occurred. Reported challenges included single-use end cap stiffness and difficulty with their alignment for cannulation. CONCLUSIONS: We report difficulty with advancement, greater reliance on advanced cannulation techniques, and higher rates of post-ERCP pancreatitis when using duodenoscopes with single-use end caps in pediatric ERCP. This area warrants further study.

Outcomes of ERCP in Patients With Cystic Fibrosis: A Nationwide Inpatient Assessment.

BACKGROUND: Cystic fibrosis (CF) is a multisystem disorder that leads to abnormal transport of chloride and sodium across secretory epithelia resulting in thickened, viscous secretions in the bronchi, biliary tract, pancreas, intestine, and the reproductive system. Defects in the biliary tract can predispose to stone formation requiring endoscopic retrograde cholangiopancreatography (ERCP). However, there is a paucity of data assessing ERCP outcomes in patients with CF. METHODS: We identified patients from the Healthcare Cost and Utilization Project (HCUP)-National Inpatient Sample (NIS) between the years 2016 and 2020. Our study group included patients with CF of all ages who underwent an inpatient ERCP. We used ICD10 diagnostic and procedural codes to identify patients, procedures, and complications of the procedure. RESULTS: From 2016 to 2020, a total of 860,679 inpatient ERCPs were identified. Of these procedures, 535 (0.06%) were performed in patients with CF. The mean age of patients with CF undergoing ERCP was 60.62 years, of which 48% were males and 52% were females. Patients in the CF group had a higher incidence of post-ERCP pneumothorax (0.93%) than the patients in the non-CF group (0.15%). The occurrence of other ERCP-related adverse events was similar in both groups (P>0.05). On multivariate regression analysis, patients with CF were 1.75 times more likely to develop post-ERCP infections [odds ratio (OR): 1.75; 95% CI: 1.03-2.94; P=0.035) and 7.64 times more likely to develop post-ERCP pneumothorax (OR: 7.64; 95% CI: 1.03-56.5; P=0.046) compared to patients without CF after adjusting for confounders. The groups had no significant difference in mortality, post-ERCP pancreatitis, bleeding, perforation, pneumoperitoneum, and gas embolism. There was also no significant difference in the length of stay between the study and control groups. CONCLUSIONS: ERCP is a safe procedure in patients with CF with a comparable risk of postprocedural complications and mortality to those who do not have cystic fibrosis. However, patients with CF may experience a higher risk of post-ERCP infections and post-ERCP pneumothorax. Further studies are needed to prospectively evaluate outcomes of ERCP in patients with CF and to determine methods of mitigating adverse events.

Pediatric ERCP: Evolving into an Outpatient Procedure.

BACKGROUND: While most adult ERCPs are performed on an outpatient basis, pediatric ERCPs are typically performed on an inpatient basis, or with ERCP followed by at least one night inpatient admission. We have begun performing a substantial proportion of our pediatric ERCPs on an outpatient basis, using our clinical judgment to guide the decision process. In the present study, we compare patient characteristics, indications, and adverse events associated with outpatient vs. inpatient ERCP. METHODS: Using our endoscopy database, we identified patients 18 years of age and under who underwent ERCP from 2019 to 2021. Demographics, hospitalization status, indications, findings, interventions, as well as available adverse event and clinical outcomes data were analyzed. RESULTS: 147 ERCP procedures were performed during the study period by one of two interventional endoscopists. A subset of 51 (34.7%) patients underwent outpatient ERCP. Comparison of the two groups (outpatient vs. inpatient ERCP) was notable for no statistically significant difference in patient age, range of indications, or proportion of index vs. subsequent ERCP. Overall rates of ERCP-associated adverse events were low and there was no statistically significant difference between adverse events in patients who underwent outpatient vs. inpatient ERCP. CONCLUSION: We analyzed outpatient and inpatient pediatric ERCP patient demographics and ERCP characteristics to identify factors that guide decision to determine whether pediatric ERCPs are performed on an outpatient vs. inpatient basis. There was no significant difference in adverse events associated with outpatient vs. inpatient pediatric ERCPs, attesting to the safety of outpatient ERCP for this subset of patients in the studied context. This is an area worthy of future prospective and multi-center study.

Anesthetic Considerations for Patients with Locked-In Syndrome Undergoing Endoscopic Procedures.

BACKGROUND Delivering safe anesthetic care to a patient unable to communicate easily and effectively with the anesthesia team presents many unique challenges. Communication may be limited by language, which can be resolved with translation services, or neurological conditions, such as stroke or traumatic brain injury, which are not easily remedied. In such patients, the inability to communicate effectively can lead to anxiety and negatively impact the patient-anesthesiologist relationship, especially when higher cognitive functions are preserved. CASE REPORT We present a case of a patient with locked-in syndrome (LIS), who presented to our endoscopy unit for a routine colonoscopy. The patient could only communicate with eye movements and blinking, thus limiting our ability to assess their pain or other needs in the perioperative period; however, she was otherwise cognitively intact. By utilizing the patient's home healthcare team and quickly adapting their unique communication methods during the perioperative period, we were able to provide an appropriate, safe anesthetic for this patient with LIS. CONCLUSIONS Many patients requiring an anesthetic are unable to effectively communicate due to language issues, hearing loss/mutism, neurological injury/stroke (aphasia), or developmental disabilities. The unique communication needs of this patient with LIS went beyond utilizing a translator and required the healthcare team to quickly learn a new communication method. We also discuss forms of intraoperative monitoring that can be used to differentiate consciousness from the anesthetized state in LIS patients, as well as making recommendations for future care of such patients.

Beyond duodenoscope-transmitted infections: Analysis of surface bioburden and UV-C mitigation within a tertiary care endoscopy unit.

BACKGROUND: An inpatient endoscopy unit is a care hub for patients from throughout the hospital and can be the site of health care-associated infections (HAIs). Shared surfaces and other nonmedical devices (keyboards) have been increasingly recognized as sites of pathogen transmission. Beyond standard cleaning of high-touch target areas, we queried whether the addition of automated devices delivering low-intensity doses of ultraviolet (UV)-C radiation could further reduce bioburden in an academic endoscopy unit. METHODS: Bioburden on previously identified high-touch/communal surfaces was measured before and after the installation of automated, low-intensity UV-light emitting devices (UV Angel) that passively monitor and disinfect targeted surfaces with Ultraviolet-C light (UV-C) light. RESULTS: High-touch sites (keyboards) had a baseline bacterial contamination of >80%, whereas individual procedure rooms and common areas had a >57% contamination rate. Following the implementation of automated UV-C light decontamination, bioburden was reduced on average by >91% at high-touch surfaces and within procedure rooms. DISCUSSION/CONCLUSIONS: Nonsterile hubs of patient care could serve as sites of "silent" HAI transmission. We have identified high-touch surfaces within an endoscopy unit that have a high bioburden of bacterial contamination and demonstrated that the installation of passive, automated UV-C light disinfection devices can reduce bioburden significantly, possibly mitigating HAI transmission between patients.

Adverse Events of Endoscopic Clip Placement: A MAUDE Database Analysis.

BACKGROUND: Clips are endoscopic mechanical devices with tensile and closure strength that can approximate tissue and provide hemostasis through a tamponade effect. Clips are ubiquitously used in endoscopic practice, and numerous studies have validated the clinical efficacy of clips, with recent guidelines recommending them as a first-line intervention for recurrent and persistent nonvariceal gastrointestinal bleeding. However, the safety profile for these devices has yet to be delineated, thus, we aim to investigate this feature by examining the adverse events reported to the Food and Drug Administration. METHODS: Postmarketing surveillance data from the Food and Drug Administration Manufacturer And User Facility Device Experience database were analyzed from January 2012 to January 2021. The Manufacturer And User Facility Device Experience database is a reporting software and does not independently verify the details of complications. RESULTS: Two thousand five hundred forty reports were issued, of which 287 were patient adverse events and 2766 were device problems. Activation, separation, and positioning issues were most common. No consequences or clinically significant impact on patients were seen in 1968 reports. Foreign bodies were seen in 97 cases, hemorrhage in 57 cases, tissue damage in 42 cases, embedded clips in tissues/plaques in 16 cases, perforation in 15 cases, lacerations in 6 cases, and infection in 3 cases. CONCLUSIONS: While the most commonly reported device problems involved activation, separation, and positioning, most patients were clinically unaffected. Moreover, perforation and infection were exceedingly rare, further highlighting the safety profile of endoscopic clips.

Rectal administration of tacrolimus protects against post-ERCP pancreatitis in mice.

OBJECTIVE: There is an unmet clinical need for effective, targeted interventions to prevent post-ERCP pancreatitis (PEP). We previously demonstrated that the serine-threonine phosphatase, calcineurin (Cn) is a critical mediator of PEP and that the FDA-approved calcineurin inhibitors, tacrolimus (Tac) or cyclosporine A, prevented PEP. Our recent observations in preclinical PEP models demonstrating that Cn deletion in both pancreatic and hematopoietic compartments is required for maximal pancreas protection, highlighted the need to target both systemic and pancreas-specific Cn signaling. We hypothesized that rectal administration of Tac would effectively mitigate PEP by ensuring systemic and pancreatic bioavailability of Tac. We have tested the efficacy of rectal Tac in a preclinical PEP model and in cerulein-induced experimental pancreatitis. METHODS: C57BL/6 mice underwent ductal cannulation with saline infusion to simulate pressure-induced PEP or were given seven, hourly, cerulein injections to induce pancreatitis. To test the efficacy of rectal Tac in pancreatitis prevention, a rectal Tac suppository (1 mg/kg) was administered 10 min prior to cannulation or first cerulein injection. Histological and biochemical indicators of pancreatitis were evaluated post-treatment. Pharmacokinetic parameters of Tac in the blood after rectal delivery compared to intravenous and intragastric administration was evaluated. RESULTS: Rectal Tac was effective in reducing pancreatic injury and inflammation in both PEP and cerulein models. Pharmacokinetic studies revealed that the rectal administration of Tac helped achieve optimal blood levels of Tac over an extended time compared to intravenous or intragastric delivery. CONCLUSION: Our results underscore the effectiveness and clinical utility of rectal Tac for PEP prophylaxis.

Influence of Frailty in Patients Undergoing Endoscopic Retrograde Cholangiopancreatography for Biliary Stone Disease: A Nationwide Study.

BACKGROUND AND AIMS: Pancreaticobiliary diseases are common in the elderly. To this end, frailty represents a state of vulnerability that should be considered when assessing the risks and benefits of therapeutic endoscopic procedures. We aim to determine the rate of readmissions and clinical outcomes using the validated Hospital Frailty Risk Score in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Using the National Readmissions Database, we identified patients with an admission diagnosis of cholangitis with obstructive stone from 2016 to 2019. Patients were determined to be of low frailty risk with a score of < 5, while patients of medium to high frailty risk had a score of > 5. RESULTS: During the study period, 5751 patients were identified with acute cholangitis with obstructing stone. Mean age of index admissions was 69.4 years and 51.8% were female. From the total cohort, 5119 (89.2%) patients underwent therapeutic ERCP, 38.0% (n = 1947) of whom were regarded as frail (risk score > 5). Following ERCP, frail patients had a less but statistically insignificant readmission rate compared to non-frail patients (2.76% vs 4.05%, p = 0.450). However, compared to non-frail patients, frail patients experienced higher post-ERCP complications (6.20% vs 14.63%, p < 0.001). Frail patients were more likely to have longer lengths of stay, higher hospital cost, and mortality risk. CONCLUSION: ERCP is not a risk factor for readmission among frail patients. However, frail patients are at higher risk for procedure-related complications, healthcare utilization, and mortality.

Preclinical safety evaluation of calcineurin inhibitors delivered through an intraductal route to prevent post-ERCP pancreatitis demonstrates endocrine and systemic safety.

OBJECTIVE: There is an urgent need for safe and targeted interventions to mitigate post-ERCP pancreatitis (PEP). Calcineurin inhibitors (CnIs) offer therapeutic promise as calcineurin signaling within acinar cells is a key initiating event in PEP. In previous proof-of-concept studies using experimental models, we showed that concurrent intra-pancreatic ductal administration of the CnIs, tacrolimus (Tac) or cyclosporine A (CsA) with the ERCP radiocontrast agent (RC) prevented PEP. To translate this finding clinically, we investigated potential toxic effects of intraductal delivery of a single-dose RC-CnI formulation on endocrine pancreas function and systemic toxicities in a preclinical PEP model. METHODS: C57BL/6J mice underwent ductal cannulation and received a single, intra-pancreatic ductal infusion of RC or RC with Tac or CsA (treatment groups) or underwent ductal cannulation without infusion ('sham' group). To assess endocrine function, intraperitoneal glucose tolerance test (IPGTT) was performed at two days before infusion and on day 2 and 14 post-surgery. To evaluate off-target tissue toxicities, renal and hepatic function-related parameters including blood urea nitrogen, plasma creatinine, potassium, aspartate aminotransferase, alanine aminotransferase, and total bilirubin were measured at the same time-points as IPGTT. Histological and biochemical indicators of pancreas injury and inflammation were also evaluated. RESULTS: No abnormalities in glucose metabolism, hepatic or renal function were observed on day 2 or 14 in mice administered with intraductal RC or RC with Tac or CsA. CONCLUSION: Intraductal delivery of RC-CnI formulation was safe and well-tolerated with no significant acute or subacute endocrine or systemic toxicities, underscoring its clinical utility to prevent PEP.

Prospective randomized comparison of endoscopist-facilitated endotracheal intubation and standard intubation for ERCP.

BACKGROUND AND AIMS: Complex endoscopic procedures are increasingly performed with anesthesia support, which substantially affects endoscopy unit efficiency. ERCP performed with the patient under general anesthesia presents unique challenges, as patients are typically first intubated, then transferred to the fluoroscopy table and positioned semi-prone. This requires additional time and staff while increasing the potential for patient/staff injury. We have developed the technique of endoscopist-facilitated intubation using an endotracheal tube backloaded onto an ultra-slim gastroscope as a potential solution to these issues and evaluated its utility prospectively. METHODS: Sequential patients undergoing ERCP were randomized to undergo endoscopist-facilitated intubation or to standard intubation. Demographic data, patient/procedure characteristics, endoscopy efficiency parameters, and adverse events were analyzed. RESULTS: During the study period, 45 ERCP patients were randomized to undergo either endoscopist-facilitated intubation (n = 23) or standard intubation (n = 22). Endoscopist-facilitated intubation was successful in all patients, with no hypoxic events. Median time from patient arrival in room to procedural start was shorter in patients undergoing endoscopist-facilitated intubation versus standard intubation (8.2 vs 29 minutes, P < .0001). Endoscopist-facilitated intubations were brisker than standard intubations (.63 vs 2.85 minutes, P < .0001). Patients undergoing endoscopist-facilitated intubation reported less postprocedure throat discomfort (13% vs 50%, P < .01) and fewer myalgia incidences (22% vs 73%, P < .01) than patients undergoing standard intubation. CONCLUSIONS: Endoscopist-facilitated intubation was technically successful in every patient. Median endoscopist-facilitated intubation time from patient arrival in room to procedural start was 3.5-fold lower, and median endoscopist-facilitated intubation time was >4-fold lower, than for standard intubation. Endoscopist-facilitated intubation significantly enhanced endoscopy unit efficiency and minimized staff and patient injury. General adoption of this novel approach may represent a paradigm shift in the approach to safe and efficient intubation of all patients requiring general anesthesia. Although the results of this controlled trial are promising, larger studies in a broad population are needed to validate these findings. (Clinical trial registration number: NCT03879720.).

Endoscopy and Pediatric Pancreatitis.

Children and adolescents are increasingly impacted by pancreatic disease. Interventional endoscopic procedures, including endoscopic retrograde cholangiopancreatography) and endoscopic ultrasonography, are integral to the diagnosis and management of many pancreatic diseases in the adult population. In the past decade, pediatric interventional endoscopic procedures have become more widely available, with invasive surgical procedures now being replaced by safer and less disruptive endoscopic interventions.

A systems approach points to a therapeutic role for retinoids in asparaginase-associated pancreatitis.

Among drug-induced adverse events, pancreatitis is life-threatening and results in substantial morbidity. A prototype example is the pancreatitis caused by asparaginase, a crucial drug used to treat acute lymphoblastic leukemia (ALL). Here, we used a systems approach to identify the factors affecting asparaginase-associated pancreatitis (AAP). Connectivity Map analysis of the transcriptomic data showed that asparaginase-induced gene signatures were potentially reversed by retinoids (vitamin A and its analogs). Analysis of a large electronic health record database (TriNetX) and the U.S. Federal Drug Administration Adverse Events Reporting System demonstrated a reduction in AAP risk with concomitant exposure to vitamin A. Furthermore, we performed a global metabolomic screening of plasma samples from 24 individuals with ALL who developed pancreatitis (cases) and 26 individuals with ALL who did not develop pancreatitis (controls), before and after a single exposure to asparaginase. Screening from this discovery cohort revealed that plasma carotenoids were lower in the cases than in controls. This finding was validated in a larger external cohort. A 30-day dietary recall showed that the cases received less dietary vitamin A than the controls did. In mice, asparaginase administration alone was sufficient to reduce circulating and hepatic retinol. Based on these data, we propose that circulating retinoids protect against pancreatic inflammation and that asparaginase reduces circulating retinoids. Moreover, we show that AAP is more likely to develop with reduced dietary vitamin A intake. The systems approach taken for AAP provides an impetus to examine the role of dietary vitamin A supplementation in preventing or treating AAP.

Advances in Endoscopic Ultrasound (EUS)-Guided Liver Biopsy.

Recent years have seen the emergence of endoscopic-ultrasound-guided liver biopsy (EUS-LB) as an effective alternative to traditional (percutaneous or transjugular) liver biopsy techniques. Comparative studies have demonstrated that both endoscopic and non-endoscopic approaches are similar in terms of diagnostic adequacy, accuracy, and adverse events; however, EUS-LB offers the advantage of reduced recovery time. Additionally, EUS-LB enables the sampling of both lobes of the liver as well as the advantage of portal pressure measurements. However, EUS-LB may be argued to have a high cost, although this procedure can be cost-effective if bundled with other endoscopic procedures. Approaches utilizing EUS-guided liver therapy, such as the administration of chemotherapeutic agents and EUS elastography, are in development, and their optimal integration into clinical care is likely to emerge in the coming years. In the present review, we evaluate the available literature on EUS-LB indications, contraindications, variations in needle biopsy techniques, comparative outcomes, advantages and disadvantages, and future trends and perspectives.