Endoscopic approaches to pancreatic disease.

PURPOSE OF REVIEW: Endoscopy plays a central role in the evaluation and management of patients with pancreatic disease. This review focuses on recent clinically relevant developments and timely research questions related to endoscopy in acute and chronic pancreatitis. RECENT FINDINGS: Endoscopic ultrasound (EUS) has moved to the forefront of the evaluation of unexplained pancreatitis; endoscopic retrograde cholangiopancreatography (ERCP) for recurrent acute pancreatitis remains controversial but commonly practiced; fully covered metallic stents are challenging traditional stent therapy in the treatment of benign biliary and pancreatic strictures due to chronic pancreatitis; endoscopic drainage has become central in the therapeutic algorithm for pancreatic fluid collections; EUS-guided access to the pancreatic duct in cases of unsuccessful ERCP is a promising new platform that requires additional research and development. The evidence in these areas is discussed, with an emphasis on recent high-impact publications. SUMMARY: There have been significant recent advances in our endoscopic approach to pancreatic disease; however, additional research is necessary toward providing high-quality, evidence-based care in this area. VIDEO ABSTRACT.

Prophylactic 5-Fr pancreatic duct stents are superior to 3-Fr stents: a randomized controlled trial.

BACKGROUND: Temporary prophylactic pancreatic duct stenting effectively reduces post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk patients, but the optimal stent remains unclear. We compared rate of spontaneous passage, and technical difficulty of placement for 3-Fr and 5-Fr stents. METHODS: A randomized controlled trial at a single academic medical center. Patients deemed high risk for PEP randomly received 5-Fr or 3-Fr pancreatic duct stents. Primary outcome was spontaneous stent passage by 2 weeks. Secondary outcomes were ease and time for stent placement, and number of guide wires required for the entire procedure. RESULTS: Patients (69 female [89 %]; mean age 44.9 years, standard deviation [SD] 16.8) were randomly assigned to receive 5-Fr (n = 38) and 3-Fr (n = 40) stents. Indications for stenting were similar. Seven patients in the 3-Fr group actually received a 5-Fr stent, and two in the 5-Fr group had a 3-Fr stent. Spontaneous passage or non-passage was confirmed in 64 (83 %). No statistically significant difference in spontaneous passage rates was seen (5-Fr group, 68.4 %; 3-Fr group 75.0 %; P = 0.617). Non-passage rates were 10.5 % (5-Fr group) and 10.0 % (3-Fr group) ( P = 1.00). The study was stopped after a futility analysis for the primary end point. Placement of 5-Fr stents was rated easier, at a mean score of 1.8 (5-Fr) vs. 3.4 (3-Fr), P < 0.001, with a trend towards being faster, 9.2 vs. 11.1 minutes ( P = 0.355). Fewer guide wires were required for 5-Fr stent placement, 1.5 vs. 1.9 ( P = 0.002). PEP rates did not differ ( P = 0.519). CONCLUSION: Placement of 5-Fr compared to 3-Fr pancreatic duct stents for PEP prophylaxis is easier, faster, and requires fewer wires. No statistically significant difference in spontaneous passage was found between the two sizes.

Endoscopic findings and clinical outcomes in ventricular assist device recipients with gastrointestinal bleeding.

BACKGROUND: Gastrointestinal bleeding (GIB) is an important clinical problem in recipients of ventricular assist devices (VAD), although data pertaining to the endoscopic evaluation and management of this complication are limited in the medical literature. AIMS: We sought to identify the most common endoscopic findings in VAD recipients with GIB, and to better define the diagnostic and therapeutic utility of endosopy for this patient population. METHODS: Twenty-six subjects with VAD and overt GIB were retrospectively identified. Clinical and endoscopic data were abstracted for each subject on to standardized forms in duplicate and independent fashion. Raw data and descriptive statistics were reported. RESULTS: Non-peptic vascular lesions were the most common cause of GIB. A definitive cause of bleeding was identified by endoscopy in almost 60% of subjects. Endoscopic hemostasis was achieved in 14/15 patients in whom bleeding did not stop spontaneously. Rebleeding occurred in 50% of subjects and was successfully retreated or stopped spontaneously in all cases. Colonoscopy did not establish a definitive diagnosis or deliver hemostatic therapy in any case. CONCLUSIONS: Vascular malformations account for the overwhelming majority of bleeding lesions in VAD patients with GIB. Endoscopy seems to be a safe and effective tool for diagnosing, risk stratifying, and treating this patient population, although multiple endoscopies may be necessary before therapeutic success, and the incidence of rebleeding is high. A prospective multi-center registry is necessary to establish evidence-based management algorithms for VAD recipients with GIB.

Facilitating gastrotomy closure during natural-orifice transluminal endoscopic surgery using tissue anchors.

BACKGROUND AND STUDY AIMS: Reliable and secure closure of the gastrotomy after natural-orifice transluminal endoscopic surgery (NOTES) remains a critical step for widespread acceptance and use of this mode of surgery. We describe a novel method for gastrotomy closure using endoscopic tissue anchors. METHODS: A standard upper endoscopy and wire placement as used for percutaneous endoscopic gastrostomy placement was performed in five pigs. Prior to gastrotomy, four tissue anchors were placed in four quadrants (1 cm away from the wire). A 12-mm gastrotomy was created endoscopically using a combination of needle-knife and balloon dilation. After transgastric peritoneoscopy, the sutures were approximated using a device knotting element. One additional pair of sutures was placed after evaluation of the gastric closure. The animals underwent in vivo contrast fluoroscopy, methylene blue instillation, and bursting pressure studies for assessment of the closure site. RESULTS: All animals studied showed complete sealing of the gastrotomy site without evidence of leak on fluoroscopic imaging or at final postmortem intragastric methylene blue instillation. Improved insufflation ability following gastrotomy was also noted using this technique, which enhanced overall visualization during the closure. CONCLUSION: Positioning tissue anchors prior to creating a NOTES gastrotomy was a feasible and reliable method to perform gastric closure. Follow-up survival studies will be warranted to support these preliminary findings.

A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis.

BACKGROUND: Several pharmacological agents for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) have been studied. Clinical trials evaluating the protective effect of non-steroidal anti-inflammatory drugs (NSAIDs) have yielded inconclusive results. AIM: To perform a meta-analysis of studies evaluating the effect of prophylactic rectal NSAIDs on PEP. METHODS: By searching Medline, Embase, meeting abstracts and bibliographies, two independent reviewers systematically identified prospective randomised controlled trials (RCTs) examining the effect of rectally administered prophylactic NSAIDs on the incidence of PEP pancreatitis. A meta-analysis of these clinical trials was performed. RESULTS: Four RCTs, enrolling a total of 912 patients, have been published. Meta-analysis of these studies demonstrates a pooled relative risk for PEP after prophylactic administration of NSAIDs of 0.36 (95% CI 0.22 to 0.60); patients who received NSAIDs in the periprocedural period were 64% less likely to develop pancreatitis and 90% less likely to develop moderate to severe pancreatitis. The pooled number needed to treat with NSAIDs to prevent one episode of pancreatitis is 15 patients. No adverse events attributable to the use of NSAIDs were reported in any of the clinical trials. CONCLUSION: In this meta-analysis, prophylactic NSAIDs were effective in preventing PEP. Widespread prophylactic administration of these agents may significantly reduce the incidence of PEP, resulting in major clinical and economic benefit. Given current scepticism regarding the efficacy of any prophylactic medication for ERCP, additional multicentre studies are needed for confirmation prior to widespread adoption of this strategy.

The revised Atlanta criteria more accurately reflect severity of post-ERCP pancreatitis compared to the consensus criteria.

Background and objective: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most prevalent complication after ERCP with an incidence of 3.5%. PEP severity is classified according to either the consensus criteria or the revised Atlanta criteria. In this international cohort study we investigated which classification is the strongest predictor of PEP-related mortality. Methods: We reviewed 13,384 consecutive ERCPs performed between 2012 and 2017 in eight hospitals. We gathered data on all pancreatitis-related adverse events and compared the predictive capabilities of both classifications. Furthermore, we investigated the correlation between the two classifications and identified reasons underlying length of stay. Results: The total sample consisted of 387 patients. The revised Atlanta criteria have a higher sensitivity (100 vs. 55%), specificity (98 vs. 72%) and positive predictive value (58 vs. 5%). There is a significant difference (p < 0.001) between the two classifications. In 124 patients (32%), the length of stay was influenced by concomitant diseases. Conclusion: The revised Atlanta classification is superior in predicting mortality and better reflects PEP severity. This has important implications for researchers, clinicians and patients. For the diagnosis of PEP pancreatitis, the consensus criteria remain the golden standard. However, the revised Atlanta criteria are preferable for defining PEP severity.

Endoscopic full-thickness resection of gastric tumors using a novel grasp-and-snare technique: feasibility in ex vivo and in vivo porcine models.

BACKGROUND AND STUDY AIMS: Endoscopic full-thickness resection (EFTR) is a less-invasive method of en bloc removal of gastrointestinal tract tumors. The aim of this study was to evaluate the feasibility of a grasp-and-snare EFTR technique using a novel tissue-lifting device that provides more secure tissue anchoring and manipulation. METHODS: EFTR of normal gastric tissue and model stomach tumors was performed using a double-channel therapeutic endoscope with a prototype tissue-lifting device through one channel and a prototype hexagonal snare through the other. The lifting device was advanced through the open snare and anchored to the gastric wall immediately adjacent the model tumor. The tissue-lifting device was then partially retracted into the endoscope, causing the target tissue, including tumor, to evert into the gastric lumen. The open snare was then placed distal to the tumor around uninvolved gastric tissue. Resection was performed with a blended electrosurgical current through the snare. In the live pigs, EFTR was followed by laparotomy to asses for complications. RESULTS: 24 EFTRs were performed -- 14 in explanted stomachs and 10 in live pigs. In total, 23/24 resections resulted in full-thickness gastric defects. Resection specimens measured up to 5.0 cm when stretched and pinned on a histology stage. Gross margins were negative in 17/20 model tumor resections. Two resections were complicated by gastric mural bleeding. There was no evidence of adjacent organ injury. CONCLUSIONS: EFTR of gastric tumors using the grasp-and-snare technique is feasible in pigs. This technique is advantageous in that eversion of the gastric wall avoids injury to external organs, continuous luminal insufflation is not required, and the involved techniques are familiar to endoscopists. Additional research is necessary to further evaluate safety and reliable closure.

Systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha agents for the treatment of ulcerative colitis.

BACKGROUND: Antibodies against tumour necrosis factor-alpha (anti-TNF) are effective therapies in the treatment of ulcerative colitis (UC), but their comparative efficacy is unknown. AIM: To perform a network meta-analysis comparing the efficacy of anti-TNF agents in UC. METHODS: After screening 506 studies, reviewers extracted information on seven studies. Traditional meta-analysis (TMA) was used to compare each anti-TNF agent to placebo. Bayesian network meta-analysis (NMA) was performed to compare the effects of anti-TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated. RESULTS: Compared to placebo, TMA revealed that anti-TNF agents result in a higher likelihood of induction of remission and response (RR: 2.45, 95% CI: 1.72-3.47 and RR: 1.65, 95% CI: 1.37-1.99 respectively) as well as maintenance of remission and response (RR: 2.00, 95% CI: 1.52-2.62 and RR: 1.76, 95% CI: 1.46-2.14 respectively). Individually, infliximab, adalimumab and goliumumab resulted in a higher likelihood of induction and maintenance for both remission and response. NMA found nonsignificant trends in comparisons of the individual agents. The required sample sizes for direct head-to-head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively. CONCLUSIONS: This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis. However, network meta-analysis demonstrates that no single agent is clinically superior to the others and therefore, other factors such as cost, safety, route of administration and patient preference should dictate our choice of anti-TNF agents. A randomised comparative efficacy trial between infliximab and adalimumab in UC is of practical size and should be performed.

Systematic review with network meta-analysis: the efficacy of anti-TNF agents for the treatment of Crohn's disease.

BACKGROUND: Anti-tumour necrosis factor-alpha agents (anti-TNF) are effective therapies for the treatment of Crohn's disease (CD), but their comparative efficacy is unknown. AIM: To perform a network meta-analysis comparing the efficacy of anti-TNF therapies in CD. METHODS: After screening 506 studies, reviewers extracted information on 10 studies. Traditional meta-analysis (TMA) was used to compare each anti-TNF agent to placebo. Bayesian network meta-analysis (NMA) was performed to compare the effects of anti-TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated. RESULTS: Compared to placebo, TMA revealed that anti-TNF agents result in a higher likelihood of induction of remission and response (RR: 1.66, 95% CI: 1.17-2.36 and RR: 1.43, 95% CI: 1.17-1.73, respectively) as well as maintenance of remission and response (RR: 1.78, 95% CI: 1.51-2.09 and RR: 1.68, 95% CI: 1.46-1.93, respectively). NMA found nonsignificant trends between infliximab and adalimumab or certolizumab pegol. Among subcutaneous therapies, NMA demonstrated superiority of adalimumab to certolizumab pegol for induction of remission (RR: 2.93, 95% CrI: 1.21-7.75). Sample size calculations suggest that adequately powered head-to-head comparative efficacy trials would require greater than 3000 patients. CONCLUSIONS: All anti-TNF agents are effective for induction and maintenance of response and remission in the treatment of CD. Although adalimumab is superior to certolizumab pegol for induction of remission, there is no evidence of clinical superiority among anti-TNF agents. Head-to-head trials among the anti-TNF agents are impractical in terms of size and cost.

Systematic review with network meta-analysis: pharmacological prophylaxis against post-ERCP pancreatitis.

BACKGROUND: The efficacy of many pharmacological agents for preventing post-ERCP pancreatitis (PEP) has been evaluated in randomised controlled trials (RCTs), but it is unclear which agent(s) should be used in clinical practice. Network meta-analyses of RCTs are used to simultaneously compare several agents to determine their relative efficacy and identify priority agents for comparison in future RCTs. AIM: To evaluate pharmacological agents for the prevention of PEP by conducting a network meta-analysis of RCTs. METHODS: We searched MEDLINE, EMBASE and Cochrane Library databases for RCTs that evaluated the efficacy of agents for preventing PEP. RCTs were simultaneously analysed using random-effects network meta-analysis under the Bayesian framework to identify the best agents. The efficacy of agents was ordered according to the probability of being ranked as any of the top three best performing agents. RESULTS: The network meta-analysis included 99 RCTs evaluating 16 agents in 25 313 patients. Topical epinephrine (adrenaline) was the most efficacious agent with 85.9% probability of ranking among the top three agents, followed by nafamostat (51.4%), antibiotics (44.5%) and NSAIDs (42.8%). However, in a sensitivity analysis including only rectal NSAIDs, NSAIDs moved from fourth rank to second (58.1%). Patients receiving topical epinephrine, compared with placebo, had a 75% reduced risk of PEP (OR 0.25, 95% probability interval 0.06-0.66). CONCLUSIONS: Topical epinephrine and rectal NSAIDs are the most efficacious agents for preventing post-ERCP pancreatitis, based on existing RCTs. Combinations of these agents, which act on different steps in the pathogenesis of post-ERCP pancreatitis, should be evaluated in future trials.