Biflanged metal stents versus plastic stents in the endoscopic ultrasound-guided drainage of walled-off necrosis: a randomized controlled trial.

OBJECTIVE: Endoscopic ultrasound(EUS) guided drainage of walled off necrosis(WON) with either plastic stents or metal stents is the mainstay of WON management. This is a single center randomized controlled study evaluating the efficacy of bi-flanged metal stent(BFMS) and plastic stents for WON drainage. DESIGN: Patients with symptomatic WON amenable for EUS guided drainage were randomized to either BFMS or plastic stents. Primary outcome was reintervention free clinical success at 4 weeks. Secondary outcomes were overall clinical success(complete resolution of symptoms and significant reduction in size of WON (<50% of original size and <5 cm largest diameter size at 4-week follow-up)), number of re-interventions, adverse events, hospital stay for first admission and medium term outcomes at 6 months (recurrence, disconnected pancreatic duct, chronic pancreatitis and new onset diabetes mellitus). RESULTS: 92 patients were randomized - 46 in each arm. The reintervention free clinical success was significantly higher in BFMS group(67.4% vs 43.5%; P: 0.021; ITT analysis). Overall clinical success at one month was similar in both groups. There were significantly lower number of reinterventions (median 0(IQR 0-1) vs 1(0-2) P:0.028)and hospital stay duration in BFMS group(7.04 ± 3.36 days vs 9.09 ± 5.53 days; P:0.035). There was no difference in procedure-related adverse events, mortality and medium-term outcomes. CONCLUSIONS: The BFMS provides higher reintervention free clinical success at 4 weeks with shorter hospital stay without increased risk of adverse events compared to plastic stents for EUS-guided drainage of WON. Medium term outcomes are however similar in both BFMS, and plastics stents.

Conventional versus oblique fiber-sparing endoscopic myotomy for achalasia cardia: a randomized controlled trial (with videos).

BACKGROUND AND AIMS: GERD is common after peroral endoscopic myotomy (POEM). Selective sparing of oblique fibers may reduce the incidence of reflux esophagitis after POEM. In this study, we compared the incidence of GERD between conventional myotomy (CM) versus oblique fiber-sparing (OFS) myotomy in patients with achalasia. METHODS: Eligible patients with type I and II achalasia who underwent POEM from January 2020 to October 2020 were randomized into 2 groups (CM and OFS myotomy). Exclusion criteria were type III achalasia, sigmoid esophagus, and history of Heller's myotomy. The primary study outcome was incidence of reflux esophagitis (at least grade B) in the 2 groups. Secondary outcomes were reflux symptoms, esophageal acid exposure, clinical success, and adverse events. RESULTS: One hundred fifteen patients were randomized into CM (n = 58) and OFS myotomy (n = 57) groups. POEM was technically successful in all patients. Overall, reflux esophagitis was found in 56 patients (48.7%). The incidence of at least grade B esophagitis was similar in both groups (CM vs OFS myotomy: 25.9% vs 31.6%, P = .541). The mean number of reflux episodes (48.2 ± 36.6 vs 48.9 ± 40.3, P = .933), increased esophageal acid exposure >6% (45.5% vs 31.7%, P = .266), and high DeMeester scores (38.6% vs 41.5%, P = .827) were similar in both groups. There was no difference in the rate of symptomatic reflux (GERD questionnaire score >7) or use of proton pump inhibitors at 1 year. CONCLUSIONS: Sparing of sling fibers has no significant impact on the incidence of significant reflux esophagitis after POEM. Novel strategies need to be explored to prevent reflux after POEM. (Clinical trial registration number: NCT04229342.).

Midodrine versus Albumin to Prevent Paracentesis Induced Circulatory Dysfunction in Acute on Chronic Liver Failure Patients in the Outpatient Clinic-a Randomized Controlled Trial.

Background: Paracentesis-induced circulatory disturbance (PICD) occurs in 12-20% of patients receiving human albumin for large-volume paracentesis, and can occur at lower than five liter paracentesis in acute-on-chronic liver failure (ACLF). Albumin infusions are associated with higher costs and more prolonged daycare admissions. The aim of the study was to determine if oral midodrine-hydrochloride can prevent PICD in these patients by increasing the mean arterial pressure (MAP). Methods: This open-labeled randomized controlled trial included ACLF patients undergoing paracentesis between 3 and 5 L, who were randomized to receive either 20% human albumin or midodrine hydrochloride 7.5 mg thrice daily for three days, 2 h before paracentesis. MAP was recorded daily. The primary outcome was the plasma renin activity (PRA) on day six, and a 50% increase from baseline was considered PICD. Results: 183 consecutive patients of ACLF were screened, and 50 patients were randomized to either arms. Alcohol was the most common underlying cause of cirrhosis. On day 6, PRA was non-significantly (P = 0.056) higher in the midodrine group. The absolute change of PRA between the two groups was not significant (P = 0.093). Four (16%) patients in the albumin group and five (20%) in the midodrine group developed PICD. MAP increase was not different between the albumin and midodrine arms (P = 0.851). Midodrine was found to be more cost-effective. Conclusions: Three days of oral midodrine is as effective as a human-albumin infusion in preventing PICD in ACLF patients undergoing paracentesis lesser than that done in large volume paracentesis.

Real-life benefits of intrajejunal levodopa infusion therapy in four patients with the parkinsonian variant of progressive supranuclear palsy: A 1-year follow-up data report.

BACKGROUND: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative condition presenting with different clinical endophenotypes. The parkinsonian variant of PSP (PSP-P) is characterised by early but fading responsiveness to high-dose levodopa therapy; however, high-dose oral therapy is often associated with intolerance due to dopaminergic side effects and so doses may have to be capped despite clinical benefits. Evidence from animal models and real-life registries suggest far higher doses of levodopa can be tolerated if given in a continuous drug delivery (CDD) manner. We investigated tolerance and possible clinical benefits in patients with PSP-P still responsive to levodopa after initiating CDD in the form of intrajejunal levodopa infusion (IJLI) therapy as part of a compassionate usage program (CU). METHODS: This is an observational clinical data report from the IJLI implementation program undertaken in regional tertiary referral Parkinson's centres in India and at King's College Hospital London, Dubai as part of a CU. Four patients with PSP-P receiving IJLI as a part of a CU underwent evaluations of liver and renal function, motor and nonmotor function, quality of life, sleep dysfunction, fatigue, anxiety and depression, and cognitive impairment at baseline and 6 and 12 months post-IJLI initiation. RESULTS: In total, three out of four patients successfully completed 12 months of treatment (6 months in one patient). All four patients showed good tolerability to IJLI even at higher doses (1400 and 1960 mg at 6 and 12 months, respectively) when compared to oral levodopa (812.5 ± 103 levodopa equivalent daily dose [LEDD]) and presented with overall persistent improvements in motor and nonmotor scores and quality-of-life scores at 6 and 12 months post-IJLI. All patients showed improvement in estimated glomerular filtration rate (43.50 ml/min/1.73 m2 to 67.5 ml/min/1.73 m2 and 79.5 ml/min/1.73 m2 at 6 and 12 months, respectively). CONCLUSIONS: IJLI led to persistent beneficial effects on motor and some nonmotor aspects in patients with PSP-P at up to 12 months after treatment with associated improvement in overall renal function.

Endoscopic "step-up approach" using a dedicated biflanged metal stent reduces the need for direct necrosectomy in walled-off necrosis (with videos).

BACKGROUND AND AIMS: EUS-guided drainage using plastic stents may be inadequate for treatment of walled-off necrosis (WON). Recent studies report variable outcomes even when using covered metal stents. The aim of this study was to evaluate the efficacy of a dedicated covered biflanged metal stent (BFMS) when adopting an endoscopic "step-up approach" for drainage of symptomatic WON. METHODS: We retrospectively evaluated consecutive patients with symptomatic WON who underwent EUS-guided drainage using BFMSs over a 3-year period. Reassessment was done between 48 and 72 hours for resolution. Endoscopic reinterventions were tailored in nonresponders in a stepwise manner. Step 1 encompassed declogging the blocked lumen of the BFMS. In step 2, a nasocystic tube was placed via BFMSs with intermittent irrigation. Step 3 involved direct endoscopic necrosectomy (DEN). BFMSs were removed between 4 and 8 weeks of follow-up. The main outcome measures were technical success, clinical success, adverse events, and need for DEN. RESULTS: Two hundred five WON patients underwent EUS-guided drainage using BFMSs. Technical success was achieved in 203 patients (99%). Periprocedure adverse events occurred in 8 patients (bleeding in 6, perforation in 2). Clinical success with BFMSs alone was seen in 153 patients (74.6%). Reintervention adopting the step-up approach was required in 49 patients (23.9%). Incremental success was achieved in 10 patients with step 1, 16 patients with step 2, and 19 patients with step 3. Overall clinical success was achieved in 198 patients (96.5%), with DEN required in 9.2%. Four patients failed treatment and required surgery (2) or percutaneous drainage (2). CONCLUSIONS: The endoscopic step-up approach using BFMSs was safe, effective, and yielded successful outcomes in most patients, reducing the need for DEN.

EUS-guided radiofrequency ablation for management of pancreatic insulinoma by using a novel needle electrode (with videos).

BACKGROUND AND AIMS: Insulinomas are one of the most common functional pancreatic neuroendocrine tumors. Surgical removal is the standard of care. Patients unfit for or refusing surgery need an alternative nonsurgical method to alleviate symptoms. EUS has been used to localize, aspirate, and tattoo insulinomas and to inject alcohol for local ablation. This study is aimed at assessing the feasibility of EUS-guided radiofrequency ablation (EUS-RFA) for managing patients with a symptomatic insulinoma by using a novel EUS-RFA needle electrode. METHODS: The EUS-RFA system used consists of a prototype 19-gauge needle electrode, generator, and internal cooling system. EUS-guided RFA is performed under real-time visualization at 50 W to ablate pancreatic insulinomas. RESULTS: In this observational human case series from a tertiary care center, 3 patients with a symptomatic pancreatic insulinoma, not eligible for surgery, underwent EUS-RFA by using an internally cooled prototype needle electrode. All had rapid symptom relief with biochemical improvement and remained symptom free at 11 to 12 months of follow-up. There were no procedure-related adverse events. CONCLUSIONS: EUS-RFA with the novel device can be considered in select patients with a symptomatic pancreatic insulinoma based on preliminary findings of a beneficial effect without adverse events. Assessment of the safety profile requires larger prospective trials.

Peroral endoscopic myotomy for achalasia cardia: Treatment analysis and follow up of over 200 consecutive patients at a single center.

BACKGROUND AND AIM: Peroral endoscopic myotomy (POEM) is a recently introduced technique for the treatment of achalasia cardia (AC). Data regarding safety and efficacy are still emerging. We report our experience of POEM emphasizing its safety, efficacy and follow-up data. METHODS: Patients with AC (220; mean age 39 years, range 9-74 years) underwent POEM from January 2013 to August 2014 for AC. Retrospective analysis of prospectively collected data was done. POEM was carried out by the standard technique of mucosal incision, submucosal tunneling, and myotomy of the esophageal and gastric muscle bundles followed by closure of the mucosal incision by hemoclips. Eckardt score, high-resolution manometry (HRM) and timed barium esophagogram (TBE) were used to evaluate the results. Post-procedure patients were followed up. RESULTS: Technical success rate of POEM was 96%. At 1 year, clinical success rate was 92%. Mean Eckardt score was 7.2 ± 1.55 prior to POEM and 1.18 ± 0.74 after POEM (P = 0.001). There was significant improvement of esophageal emptying on TBE (38.4 ± 14.0 % vs 71.5 ± 16.1 % (P = 0.001). Pre-procedure and post-procedure mean lower esophageal sphincter pressure was 37.5 ± 14.5 mmHg and 15.2 ± 6.3 mmHg, respectively. (P = 0.001) Erosive esophagitis was seen in 16% of patients who underwent POEM. There were no major adverse events. CONCLUSIONS: Study demonstrates excellent safety profile of POEM with significant relief of symptoms, reduced pressure at HRM and improved emptying at TBE. Further prospective studies are required to compare with other treatment modalities.

Effect of electrical stimulation of the lower esophageal sphincter using endoscopically implanted temporary stimulation leads in patients with reflux disease.

BACKGROUND: Electrical stimulation therapy (EST) has been shown to increase lower esophageal sphincter (LES) pressure in animals; however, data on the effect of EST on LES pressure in patients with gastroesophageal reflux disease (GERD) are lacking. OBJECTIVE: The aim of our study was to investigate the effect of EST on LES pressure and esophageal function in patients with GERD. METHODS: Patients with a diagnosis of GERD responsive to proton pump inhibitors (PPIs), increased esophageal acid on 24-h pH monitoring off GERD medications, basal LES pressure >5 mmHg, hernia <2 cm and esophagitis

Achalasia cardia with esophageal varix managed with endoscopic ultrasound-guided botulinum toxin injection.

Achalasia cardia is a motility disorder of the esophagus characterized by failure of relaxation of the lower esophageal sphincter. Nitrates and calcium channel blockers, pneumatic dilatation, botulinum toxin injection and surgical myotomy have been described in literature as possible management options. We present a patient who presented with achalasia and was co-incidentally diagnosed to have cryptogenic cirrhosis with portal hypertension and had esophageal varices. This clinical combination precluded the use of pneumatic dilatation and surgical myotomy. We injected botulinum toxin into the lower esophageal sphincter using a celiac plexus neurolysis needle under endoscopic ultrasound guidance; the clinical response was good.

Oral buffered esomeprazole is superior to i.v. pantoprazole for rapid rise of intragastric pH: a wireless pH metry analysis.

BACKGROUND AND AIMS: A pH of more than 6 is required for clot stability and hemostasis. Intravenous proton pump inhibitors have a rapid onset of action compared to oral and have been preferred for management of non-variceal bleeding. Intravenous pantoprazole has been used extensively. Buffered esomeprazole (BE) is an oral preparation consisting of an inner core of non-enteric-coated esomeprazole with a shell of sodium bicarbonate. The buffer protects against acid degradation of esomeprazole in addition to immediate antacid action. The aim of this study was to assess the efficacy of BE for raising and maintaining an intragastric pH of more than 6 in comparison to i.v. pantoprazole in equivalent dosing. METHODS: A randomized two-way cross-over study was conducted. Ten healthy volunteers were randomized to twice daily BE 40 mg or pantoprazole 40 mg i.v. bolus. Intragastric pH was measured with a wireless pH radiotelemetry capsule (Bravo, Medtronic). A 2-week washout period was given between doses. RESULTS: BE achieved a steady pH of more than 6 in a median time of 2 min (range 1-5 min) after the first dose. The mean % time that intragastric pH was more than 6.0 for BE was 96%, and 90% of the 24-h period compared to pantoprazole (47% and 18%), P = 0.000. A median pH (interquartile range) for the BE group was 6.2 (6.175-6.2) which was higher than i.v. pantoprazole 4.60 (4.5-5.0) (P = 0.005). CONCLUSION: BE achieves and maintains a pH of more than 6 within minutes of administration. It was significantly superior to i.v. pantoprazole in equivalent dosing. This finding could have implications in the management of non-variceal bleed where a rapid and sustained pH of more than 6 is desirable.