Daniel S. Strand

25 Years of Proton Pump Inhibitors: A Comprehensive Review

Proton pump inhibitors (PPIs) were clinically introduced more than 25 years ago and have since proven to be invaluable, safe, and effective agents for the management of a variety of acid-related disorders. Although all members in this class act in a similar fashion, inhibiting active parietal cell acid secretion, there are slight differences among PPIs relating to their pharmacokinetic properties, metabolism, and Food and Drug Administration (FDA)-approved clinical indications. Nevertheless, each is effective in managing gastroesophageal reflux disease and uncomplicated or complicated peptic ulcer disease. Despite their overall efficacy, PPIs do have some limitations related to their short plasma half-lives and requirement for meal-associated dosing, which can lead to breakthrough symptoms in some individuals, especially at night. Longer-acting PPIs and technology to prolong conventional PPI activity have been developed to specifically address these limitations and may improve clinical outcomes.

Underwater endoscopic mucosal resection is associated with fewer recurrences and earlier curative resections compared to conventional endoscopic mucosal resection for large colorectal polyps

BackgroundStudies comparing the efficacy and safety of conventional saline-assisted piecemeal endoscopic mucosal resection (EMR) to underwater EMR (UEMR) without submucosal lifting of colorectal polyps are lacking. The objective of this study was to compare the efficacy and safety of EMR to UEMR of large colorectal polyps.MethodsTwo hundred eighty-nine colorectal polyps were removed by a single endoscopist from 7/2007 to 2/2015 using EMR or UEMR. 135 polyps (EMR: 62, UEMR: 73) that measuredu2009≥15xa0mm and had not undergone prior attempted polypectomy were evaluated for rates of complete macroscopic resection and adverse events. 101 of these polyps (EMR: 46, UEMR: 55) had at least 1 follow-up colonoscopy and were studied for rates of recurrence and the number of procedures required to achieve curative resection.ResultsThe rate of complete macroscopic resection was higher following UEMR compared to EMR (98.6 vs. 87.1%, pu2009=u20090.012). UEMR had a lower recurrence rate at the first follow-up colonoscopy compared to EMR (7.3 vs. 28.3%, OR 5.0 for post-EMR recurrence, 95% CI: [1.5, 16.5], pu2009=u20090.008). UEMR required fewer procedures to reach curative resection than EMR (mean of 1.0 vs. 1.3, pu2009=u20090.002). There was no significant difference in rates of adverse events.ConclusionsUEMR appears superior to EMR for the removal of large colorectal polyps in terms of rates of complete macroscopic resection and recurrent (or residual) abnormal tissue. Compared to conventional EMR, UEMR may offer increased procedural effectiveness without compromising safety in the removal of large colorectal polyps without prior attempted resection.

The impact of bacterial colonization on graft success after total pancreatectomy with autologous islet transplantation: considerations for early definitive surgical intervention

The purpose of this study was to determine whether bacterial contamination of islets affects graft success after total pancreatectomy with islet autotransplantation (TPIAT).

Efficacy and Safety of Digital Single-Operator Cholangioscopy for Difficult Biliary Stones

BACKGROUND & AIMS: It is not clear whether digital single‐operator cholangioscopy (D‐SOC) with electrohydraulic and laser lithotripsy is effective in removal of difficult biliary stones. We investigated the safety and efficacy of D‐SOC with electrohydraulic and laser lithotripsy in an international, multicenter study of patients with difficult biliary stones. METHODS: We performed a retrospective analysis of 407 patients (60.4% female; mean age, 64.2 years) who underwent D‐SOC for difficult biliary stones at 22 tertiary centers in the United States, United Kingdom, or Korea from February 2015 through December 2016; 306 patients underwent electrohydraulic lithotripsy and 101 (24.8%) underwent laser lithotripsy. Univariate and multivariable analyses were performed to identify factors associated with technical failure and the need for more than 1 D‐SOC electrohydraulic or laser lithotripsy session to clear the bile duct. RESULTS: The mean procedure time was longer in the electrohydraulic lithotripsy group (73.9 minutes) than in the laser lithotripsy group (49.9 minutes; P < .001). Ducts were completely cleared (technical success) in 97.3% of patients (96.7% of patients with electrohydraulic lithotripsy vs 99% patients with laser lithotripsy; P = .31). Ducts were cleared in a single session in 77.4% of patients (74.5% by electrohydraulic lithotripsy and 86.1% by laser lithotripsy; P = .20). Electrohydraulic or laser lithotripsy failed in 11 patients (2.7%); 8 patients were treated by surgery. Adverse events occurred in 3.7% patients and the stone was incompletely removed from 6.6% of patients. On multivariable analysis, difficult anatomy or cannulation (duodenal diverticula or altered anatomy) correlated with technical failure (odds ratio, 5.18; 95% confidence interval, 1.26–21.2; P = .02). Procedure time increased odds of more than 1 session of D‐SOC electrohydraulic or laser lithotripsy (odds ratio, 1.02; 95% confidence interval, 1.01–1.03; P < .001). CONCLUSIONS: In a multicenter, international, retrospective analysis, we found D‐SOC with electrohydraulic or laser lithotripsy to be effective and safe in more than 95% of patients with difficult biliary stones. Fewer than 5% of patients require additional treatment with surgery and/or extracorporeal shockwave lithotripsy to clear the duct.

Safety and rate of delayed adverse events with lumen-apposing metal stents (LAMS) for pancreatic fluid collections: a multicenter study

Background and study aimsu2002 Endoscopic drainage with dedicated lumen-apposing metal stents (LAMS) is routinely performed for symptomatic pancreatic fluid collections (PFCs), walled-off necrosis (WON) and pseudocyst (PP). There has been increasing concern regarding delayed adverse events associated with the indwelling LAMS.u200a Patients and methodsu2002 Multicenter retrospective analysis of consecutive patients who underwent endoscopic ultrasound (EUS)-guided LAMS placement for PFC from January 2010 to May 2017.u200aMain outcomes included: (1) resolution of the PFC, (2) rate of delayed adverse events at follow-up, and (3) predictors of treatment failure and delayed adverse events on logistic regression. Resultsu2002 A total of 122 patients (mean age 50.9 years, 68u200a% male) underwent LAMS insertion for 64 WON (98.4u200a%) and 58 PP (98.3u200a%). PFC mean size was 10.6u200acm. PFC resolution was significantly lower for WON (62.3u200a%) vs. PP (96.5u200a%) ( P <u200a0.001) on imaging at a median of 4 weeks. Stent occlusion was identified in 18 (29.5u200a%) and 10 (17.5u200a%) patients with WON and PP, respectively ( P u200a=u200a0.13). There were no cases of delayed bleeding or buried stent on follow-up endoscopy. Use of electrocautery-enhanced LAMS was the only factor associated with treatment failure of WON (ORu200a=u200a13.2; 95u200a% ci: 3.33u200a–u200a51.82, P u200a=u200a0.02) on logistic regression. There were no patient, operator, or procedure-related factors predictive of stent occlusion. Conclusions u2002EUS-guided LAMS for PFC is associated with a low incidence of delayed adverse events. While nearly all PPs resolve at 4 weeks permitting LAMS removal shortly thereafter, many WON persist, with use of electrocautery-enhanced LAMS being the sole predictor of treatment failure.

Multicenter evaluation of the clinical utility of laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass

BACKGROUND AND AIMSnThe obesity epidemic has led to increased use of Roux-en-Y gastric bypass (RYGB). These patients have an increased incidence of pancreaticobiliary diseases, yet standard ERCP is not possible because of surgically altered gastroduodenal anatomy. Laparoscopy-assisted ERCP (LA-ERCP) has been proposed as an option, but supporting data are derived from single-center small case series. Therefore, we conducted a large multicenter study to evaluate the feasibility, safety, and outcomes of LA-ERCP.nnnMETHODSnThis is a retrospective cohort study of adult patients with RYGB who underwent LA-ERCP in 34 centers. Data on demographics, indications, procedure success, and adverse events were collected. Procedure success was defined when all the following were achieved: reaching the papilla, cannulating the desired duct, and providing endoscopic therapy as clinically indicated.nnnRESULTSnA total of 579 patients (median age, 51; 84% women) were included. Indication for LA-ERCP was biliary in 89%, pancreatic in 8%, and both in 3%. Procedure success was achieved in 98%. Median total procedure time was 152 minutes (interquartile range [IQR], 109-210), with a median ERCP time of 40 minutes (IQR, 28-56). Median hospital stay was 2 days (IQR, 1-3). Adverse events were 18% (laparoscopy related, 10%; ERCP related, 7%; both, 1%) with the clear majority (92%) classified as mild/moderate, whereas 8% were severe and 1 death occurred.nnnCONCLUSIONSnOur large multicenter study indicates that LA-ERCP in patients with RYGB is feasible with a high procedure success rate comparable with that of standard ERCP in patients with normal anatomy. The ERCP-related adverse events rate is comparable with conventional ERCP, but the overall adverse event rate was higher because of the added laparoscopy-related events.

ERCP for biliary stones in the elderly: should we stop ducking the cholecystectomy?

Since endoscopic retrograde cholangiopancreatography (ERCP) was first described in 1968, the procedure has become indispensable in management of biliary tract stones 1. Endoscopic biliary sphincterotomy, with or without papillary balloon dilation (EPBD), is considered to be highly effective for the removal of all but the most challenging stones. Even in cases where a more complex intervention is required, ERCP provides the platform for directed stone remediation via mechanical, laser, or electrohydraulic lithotripsy 2. In spite of its undeniable efficacy and central role in management of choledocholithiasis, ERCP carries a well-recognized profile of inherent risks which may occur in up to 10u200a% of patients who undergo the procedure 3. In view of that, considerable effort has been expended in identifying and stratifying patients and situations that contribute to increased risk. Particular attention is frequently given to short-term problems such as post-ERCP pancreatitis (PEP) 4. n nAs the life expectancy and proportion of elderly patients increases throughout much of the developed world 5, we can reasonably expect that the number of octogenarians and nonagenarians who undergo ERCP will increase accordingly. Indeed, an intramural survey of ERCP volume at our institution over the last 12 months demonstrated that out of well over 1000 total cases, more than 40u200a% of the procedures were performed on patients over age 65 and nearly 10u200a% were done on individuals in their 80u200as and 90u200as. Given the reasonable expectation that ERCP in the elderly will become a more common exercise among interventional gastroenterologists, a comprehensive understanding of the risks and challenges of this patient population is critical. n nIn this issue of Endoscopy International Open, Kenamori et al 6 present a large, single-center cohort study examining both the short- and long-term outcomes of patients who underwent therapeutic ERCP for choledocholithiasis between 1982 and 2011.u200aPatients included in the study were stratified by age and were classified as either young (960 patientsu200a<u200a80 years) or old (250 patientsu200a≥u200a80 years) for subsequent analysis. While it has been previously asserted that the short-term risks of ERCP in older adults are generally acceptable 7, there is a growing body of evidence regarding specific differences in this patient population. A systematic review published in the current journal by Day et al 8 suggested that patients over age 65 have a nearly 70u200a% overall reduction in post-ERCP pancreatitis when compared to younger cohorts. This is consistent with the experience reported by Kenamori et al, and when taken together with contemporary work, seems to support the notion of a “dose-dependent” protective effect of advancing age on PEP 9 10 11. Kenamori et al also suggest similar outcomes between age groups when it comes to other short-term complications such as bleeding, periprocedural infection (cholecystitis or cholangitis) and perforation. Despite the overall congruence, older patients did carry an increased risk of cardiopulmonary complications. While consistent with Day et al 8, this observation may have more to do with the medical comorbidities carried by elderly patients rather than with age alone 12 13. n nWhile most studies to date have focused on the short-term complications of ERCP in the elderly, there is relatively little published data examining long-term outcomes in these patients. What data we do have suggest that complete treatment of biliary lithiasis may affect the overall survival of the elderly who require ERCP 14. While the authors of Kenamori et al acknowledge that the broad time course of their study may have introduced unintended bias, it also permitted extended follow-up (a mean of 1278 days in the older cohort) in a fairly large number of patients. Perhaps the most interesting observation made by the authors is the increased likelihood (20.4u200a% v. 13.1u200a%) of late pancreaticobiliary complications in older patients, and the shorter mean time until their occurrence (464.3 v. 860.4 days) compared to their younger comparators. This difference was driven by both the recurrence of bile duct stones after clearance and the development of subsequent cholangitis. Both of these events occurred more commonly among older patients, long after the initial successful ERCP. The common thread in both a univariate (6-fold) and multivariate (4-fold) analysis was the presence of an in situ gallbladder with additional stones. n nThe current guidelines published by the Society of American Gastrointestinal and Endoscopic Surgeons suggest that laparoscopic cholecystectomy is indicated for any patient who has suffered a complication of cholelithiasis 15. Despite this definite recommendation, adherence to these guidelines among older patients is low 16. This occurs despite the observation that laparoscopic cholecystectomy is generally safe, even in extremely elderly patients 17 18. Surgeons often decide to pursue an intervention (or not) on the basis of a number of situational factors: patient autonomy, social support, medical comorbidities, higher American Society of Anesthesiologists (ASA) status, diminished functional capacity, and the nature of the acute illness. As with ourselves, there is likely a human tendency to make the short-term issues weightier than those of the long-term. n nIt is clear that elderly patients require special consideration when it comes to any intervention, whether it be ERCP or laparoscopic cholecystectomy. Age alone, however, does not preclude either in patients who would clearly otherwise benefit 8 16. While there is ample room to determine what pre- and post-procedure strategies might favor the proximate safety of ERCP in this setting, it is significant that the largest long-term issue uncovered by Kenamori et al may be one of “unfinished business.” Many of the patients at highest risk for subsequent biliary complications had already tolerated ERCP and its attendant tribulations successfully, but either declined or were not offered interval cholecystectomy. This pattern, congruent with other experiences 16, suggest a willingness to go “part of the way” to ERCP but not “all of the way” to cholecystectomy. While this strategy favors short-term safety, we may well be inviting a likely downstream complication in a patient who will be older (but perhaps no wiser) when it occurs. Therefore, if we are “in for a penny” when an elderly patient arrives with choledocholithiasis, should we invariably be “in for a pound”? n nERCP and laparoscopic cholecystectomy are similar, but they are clearly not the same. No blanket recommendation can be made to suggest that tolerating an ERCP for duct clearance will portend a good outcome at cholecystectomy. Despite this fact, the data provided by Kenamori et al are helpful: they solidify the short-term safety of ERCP in the elderly and serve to help us better educate our patients about downstream problems. The data also raise several questions regarding cholecystectomy, and continue to focus attention on the ongoing need for study in this vulnerable and growing group of patients.

Mo1934 MRCP is Associated With High Sensitivity and Ppv in Diagnosing Bile Duct Strictures in Patients Following Liver Transplantation as Compared to Direct Cholangiography

A S L D A b st ra ct s patients with EAS were successfully managed with endoscopic intervention, compared to 16 of 20 (80%) patients with LAS. For those successfully managed endoscopically, the time to stricture resolution was 109.91 +/-24.37 for EAS versus 293.5+/-61.13 (p=0.025) for LAS. This equated to a median of 2.5+/-3 versus 4+/-9 ERCPs respectively (p=0.0001). When baseline characteristics including known risk factors for stricturing were compared (sex, age, living versus deceased donors, need for redo operation, donor or recipient CMV status, presence of biliary sludge or stones, requirement for dilatation and ERCP complications rates), only serum bilirubin at time of stricture demonstrated a significant difference (138.17+/-46.22 versus 36.12+/-8.26, p=0.002). Conclusions: Early anastomotic biliary strictures following liver transplantation can be successfully managed endoscopically, and require a shorter treatment interval with fewer ERCPs when compared to late anastomotic strictures. Early strictures are associated with a higher serum bilirubin at diagnosis. No other patient characteristics appear to be predictive for development of either stricture type.