Safety and feasibility of same-day discharge for per-oral endoscopic myotomy.

AIMS: Per-oral endoscopic myotomy (POEM) is a recognised treatment for achalasia, with the accepted approach involving admission for imaging and dietary progression. However, recent publications suggest same-day discharge (SDD) may be possible, which could be time and cost-saving. We sought to investigate the safety of SDD following POEM. METHODS: Fifty consecutive POEMs at two referral centres in New Zealand were performed between 2020-2023. All patients were planned for early dietary introduction and were eligible for SDD if symptoms were managed. Analgesia was available in recovery and supplied at discharge. Imaging and endoscopy were performed only if there were clinical concerns. Rates of discharge clearance, discharge, complications and re-admission were analysed. RESULTS: All 50 POEMs were technically successful. A total of 41/50 (82%) received clearance for SDD. Additionally, 35/50 (70%) achieved discharge and 6/50 (12%) were observed overnight for social reasons, including lack of transport to the referring domicile. Of the patients not cleared for SDD, 7/9 (78%) were discharged within 24 hours, and the others after 48 and 72 hours. Procedural complications were recorded in three patients (6%), with one requiring endoscopic assessment and clipping. There were two re-admissions (4%), both lt;24-hour hospital stays, and managed medically. CONCLUSIONS: The majority of patients achieved same-day discharge clearance (82%) and 96% required less than 24 hours hospital stay. Complication and re-admission rates were low overall. We have demonstrated that POEM can be an SDD procedure facilitated by early dietary introduction and liberal analgesia, without the need for routine imaging or endoscopy.

Rare finding of a symptomatic epidermoid cyst of the diaphragm - a case report.

Cystic lesions of the diaphragm are rare and accordingly present a diagnostic challenge. Specific radiological features with which to clinch a diagnosis may be elusive. Herein we present the case of a patient who presented with symptoms attributable to a cyst in the left upper abdomen, irritating the diaphragm. Surgery was considered appropriate for diagnostic and symptomatic purposes. Final histology demonstrated an epidermoid cyst. Resolution of symptoms was reported after surgery. Diaphragmatic epidermoid cysts appear to be a rare entity with only three prior cases reported in the literature. Given the rarity of this lesion and the lack of unique features by which they can be characterized, accurately diagnosing epidermoid cysts of the diaphragm is likely to remain difficult without surgery, although they are presumed to have a benign behaviour.

Long-term open-label vebicorvir for chronic HBV infection: Safety and off-treatment responses.

Background & Aims: The investigational first-generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open-label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs). Methods: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171). After receiving VBR + NrtI for ≥52 weeks, stopping criteria (based on the treatment history and hepatitis B e antigen status in the parent studies) were applied, and patients either discontinued both VBR + NrtI, discontinued VBR only, or continued both VBR + NrtI. The primary efficacy endpoint was the proportion of patients with HBV DNA <20 IU/ml at 24 weeks off treatment. Results: Ninety-two patients entered the extension study and received VBR + NrtI. Long-term VBR + NrtI treatment led to continued suppression of HBV nucleic acids and, to a lesser extent, HBV antigens. Forty-three patients met criteria to discontinue VBR + NrtI, with no patients achieving the primary endpoint; the majority of virologic rebound occurred ≥4 weeks off treatment. Treatment was generally well tolerated, with few discontinuations due to adverse events (AEs). There were no deaths. Most AEs and laboratory abnormalities were related to elevations in alanine aminotransferase and occurred during the off-treatment or NrtI-restart phases. No drug-drug interactions between VBR + NrtI and no cases of treatment-emergent resistance among patients who adhered to treatment were observed. Conclusions: Long-term VBR + NrtI was safe and resulted in continued reductions in HBV nucleic acids following completion of the 24-week parent studies. Following treatment discontinuation, virologic relapse was observed in all patients. This first-generation core inhibitor administered with NrtI for at least 52 weeks was not sufficient for HBV cure. Clinical trial number: NCT03780543. Impact and implications: Approved treatments for chronic hepatitis B virus infection (cHBV) suppress viral replication, but viral rebound is almost always observed after treatment discontinuation, highlighting an unmet need for improved therapies with finite treatment duration producing greater therapeutic responses that can be sustained off treatment. First-generation core inhibitors, such as vebicorvir, have mechanisms of action orthogonal to standard-of-care therapies that deeply suppress HBV viral replication during treatment; however, to date, durable virologic responses have not been observed after treatment discontinuation. The results reported here will help researchers with the design and interpretation of future studies investigating core inhibitors as possible components of finite treatment regimens for patients with cHBV. It is possible that next-generation core inhibitors with enhanced potency may produce deeper and more durable antiviral activity than first-generation agents, including vebicorvir.

Inflammatory bowel disease in Waikato, New Zealand: incidence and prevalence.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) prevalence is rising globally; however, indigenous groups are underrepresented. Waikato, New Zealand, is a large region with a high proportion of Maori patients. In Canterbury in 2006, 1% of patients with IBD were Maori. We investigated the incidence and prevalence of IBD in Waikato over 10 years. METHODS: This was a retrospective cohort study assessing the incidence and prevalence of IBD between 2009 and 2019. The search strategy included pathology, radiology, Provation, ICD-10 coding and private clinics, using the keywords: Crohn's, Crohn, ileitis, colitis, ulcerative, inflammatory bowel disease and IBD. Collected data included current age and age at diagnosis, sex, ethnicity and IBD subtype. RESULTS: The IBD point prevalence on 31 December 2019 was 375.6/100 000 compared with 293.6/100 000 in 2010, increasing by 27.9%. The annualised incidence was static from 21.5/100 000 in 2010 to 17.5/100 000 in 2019. Female patients comprised 53.3% of the cohort. Ulcerative colitis (UC) made up 54.2% of cases, 43.8% had Crohn disease (CD) and 2.0% had indeterminate colitis. Sixty (3.7%) patients identified as Maori. In non-Maori patients, the average age at diagnosis was 36.2 years, compared with 33.0 years in Maori patients (P = 0.11). In Maori patients, 53.3% had UC and 45.0% had CD. Thirty-five percent of Maori patients lived 50 km or more from base hospital, compared with 41% of non-Maori patients (P = 0.33). CONCLUSION: IBD prevalence has increased substantially; however, the incidence has remained static. Maori IBD rates are higher than previously reported, in keeping with international indigenous trends. Maori patients were diagnosed at a similar age as non-Maori patients, with similar disease subtypes.

Conversion of locally advanced to resectable pancreatic body cancer aided by phosphorus-32 brachytherapy (OncoSil).

Nil.

Lessons learned from early experience of per oral endoscopic myotomy in children.

BACKGROUND/AIMS: Achalasia cardia (AC) is rare in children, and the standard treatment is open or Laparoscopic Heller's myotomy with or without fundoplication if pneumatic dilatation has failed. Per oral endoscopic myotomy (POEM) is a novel technique for management of achalasia with good results in adults. We report POEM in four children and the outcome with special emphasis on the technique and management of intra-operative complications. METHOD: Four children aged 7-15 years presenting with progressive dysphagia, cough, night-time aspirations, and weight loss of six months to one year were investigated with upper GI contrast study, flexible endoscopy and biopsy, oesophageal manometry, and a diagnosis of Type 1 & 2 AC was made. An experienced adult endoscopist in collaboration with the paediatric surgical team performed POEM. RESULTS: POEM was performed successfully using ERBE HYBRID knife setup and waterjet injection for the submucosal tunnelling. Operative time was 25-40 min (mean 31 min). The hospital stay was 3-8 days with last 3 patients discharged on day three. No major intraoperative or post-operative complications were seen. The Eckardt score changed from above 4 to 0 at one-month follow-up. All four are well at one year post-operatively and beyond. Two patients had subcutaneous emphysema post-operatively. One developed pneumoperitoneum intra-operatively. CONCLUSION: POEM was successfully performed with only minor adverse events in experienced hands. Anticipation and preparation for potential intraoperative complications and assigned responsibilities to each team helped the safe completion in the shortest time. Rectifying pneumoperitoneum concurrently without interruption of the operation exemplified teamwork. LEVEL OF EVIDENCE: III.

Safety and efficacy of vebicorvir administered with entecavir in treatment-naïve patients with chronic hepatitis B virus infection.

BACKGROUND & AIMS: Nucleos(t)ide reverse transcriptase inhibitors do not completely suppress HBV DNA in chronic HBV infection (cHBV). Vebicorvir (VBR) is an investigational core inhibitor that interferes with multiple aspects of HBV replication. This phase II trial evaluated the safety and efficacy of VBR in combination with entecavir (ETV) in treatment-naïve patients with cHBV. METHODS: HBeAg-positive, treatment-naïve patients without cirrhosis were randomised 1:1 in a double-blind manner to once-daily VBR 300 mg+ETV 0.5 mg or placebo (PBO)+ETV 0.5 mg for 24 weeks. The primary endpoint was change in mean log10 HBV DNA from Baseline to Week 12 and 24. RESULTS: All patients in both treatment groups (PBO+ETV: 12/12; VBR+ETV: 13/13) completed the study. At Week 12, VBR+ETV led to a greater mean (SD) reduction from Baseline in log10 IU/ml HBV DNA (-4.45 [1.03]) vs. PBO+ETV (-3.30 [1.18]; p = 0.0077). At Week 24, VBR+ETV led to a greater reduction from Baseline in log10 IU/ml HBV DNA (-5.33 [1.59]) vs. PBO+ETV (-4.20 [0.98]; p = 0.0084). Greater mean reductions in pregenomic RNA were observed at Week 12 and 24 in patients receiving VBR+ETV vs. PBO+ETV (p <0.0001 and p <0.0001). Changes in viral antigens were similar in both groups. No drug interaction between VBR and ETV was observed. Two patients experienced HBV DNA rebound during treatment, with no resistance breakthrough detected. The safety of VBR+ETV was similar to PBO+ETV. All treatment-emergent adverse events and laboratory abnormalities were Grade 1/2. There were no deaths, serious adverse events, or evidence of drug-induced liver injury. CONCLUSIONS: In this 24-week study, VBR+ETV provided additive antiviral activity over PBO+ETV in treatment-naïve patients with cHBV, with a favourable safety and tolerability profile. CLINICAL TRIAL NUMBER: NCT03577171 LAY SUMMARY: Hepatitis B is a long-lasting viral infection of the liver. Current treatments can suppress hepatitis B virus but do not offer the opportunity of cure, hence, new treatment approaches are required. Herein, we show that the combination of the novel core inhibitor vebicorvir with an existing antiviral (entecavir) in treatment-naïve patients chronically infected with hepatitis B virus demonstrated greater antiviral activity than entecavir alone. Additionally, vebicorvir was safe and well tolerated. Thus, further studies evaluating its potential role in the treatment of chronic hepatitis B are warranted.

Safety and efficacy of vebicorvir in virologically suppressed patients with chronic hepatitis B virus infection.

BACKGROUND & AIMS: HBV nucleos(t)ide reverse transcriptase inhibitors (NrtIs) do not completely suppress HBV replication. Previous reports indicate persistent viremia during NrtI treatment despite HBV DNA being undetectable. HBV core inhibitors may enhance viral suppression when combined with NrtIs. This phase II trial (NCT03576066) evaluated the efficacy and safety of the investigational core inhibitor, vebicorvir (VBR), in virologically- suppressed patients on NrtIs. METHODS: Non-cirrhotic, NrtI-suppressed patients with chronic HBV were randomised to VBR 300 mg once daily or matching placebo (PBO) for 24 weeks. Treatment was stratified by hepatitis B e antigen (HBeAg) status. The primary endpoint was change from Baseline in serum HBeAg or hepatitis B surface antigen (HBsAg) after 24 weeks. RESULTS: Of 73 patients enrolled, 47 were HBeAg positive and 26 were HBeAg negative. In HBeAg-positive and -negative patients, there were no differences in the change from Baseline at Week 24 for HBsAg or HBeAg. Using a novel, high-sensitivity assay to detect HBV DNA, a greater proportion of patients with detectable HBV DNA at Baseline achieved undetectable HBV DNA at Week 24 in the VBR+NrtI vs. PBO+NrtI group. In HBeAg-positive patients, a greater change from Baseline in HBV pregenomic (pg)RNA was observed at Week 24 with VBR+NrtI vs. PBO+NrtI. Treatment-emergent adverse events (TEAEs) in VBR+NrtI patients included upper respiratory tract infection, nausea, and pruritus. No serious adverse events, Grade 4 TEAEs, or deaths were reported. CONCLUSIONS: In this 24-week study, VBR+NrtI demonstrated a favourable safety and tolerability profile. While there were no significant changes in viral antigen levels, enhanced viral suppression was demonstrated by greater changes in DNA and pgRNA with the addition of VBR compared to NrtI alone. CLINICAL TRIALS NUMBER: NCT03576066. LAY SUMMARY: Core inhibitors represent a novel approach for the treatment of chronic hepatitis B virus (HBV) infection, with mechanisms of action distinct from existing treatments. In this study, vebicorvir added to existing therapy reduced HBV replication to a greater extent than existing treatment and was generally safe and well tolerated.

Drainage of pancreatic fluid collections using a lumen-apposing metal stent with an electrocautery-enhanced delivery system.

BACKGROUND AND AIM: Our aim was to evaluate the efficacy and safety of a lumen-apposing metal stent with an electrocautery-enhanced delivery system (EDS-LAMS) for endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) in regular clinical practice. METHODS: A retrospective and subsequent prospective analysis was undertaken of all patients who underwent EUS-guided drainage of their PFCs using the EDS-LAMS at 17 tertiary therapeutic endoscopy centers. RESULTS: Two hundred eight cases of EDS-LAMS deployment were attempted in 202 patients (mean age 52.9 years) at time of evaluation. Ninety-seven patients had pancreatic pseudocysts (PPs), 75 walled-off pancreatic necrosis (WOPN), 10 acute peripancreatic fluid collections (APFCs), 6 acute necrotic collections (ANCs), and 14 postoperative collections (POCs). Procedural technical success was achieved in 202/208 cases (97.1%). Maldeployment occurred in 7/208 cases (3.4%). Clinical success was achieved in 142/160 (88.8%) patients (PP 90%, WOPN 85.2%, APFC 100%, ANC 75%, POC 100%). Delayed adverse events included stent migration in 15/202 (7.4%), stent occlusion and infection in 16/202 (7.9%), major bleeding in 4/202 (2%), and buried EDS-LAMS in 2/202 (1%). PFC recurrence occurred in 13/142 (9.2%) patients; 9/202 (4.5%) required surgical or radiological intervention for PFC management after EDS-LAMS insertion. CONCLUSIONS: This large international multicenter study evaluating the EDS-LAMS for drainage of PFCs in routine clinical practice suggests that the EDS-LAMS are safe and effective for drainage of all types of PFCs; however, further endoscopic therapy is often required for WOPN. Major bleeding was a rare complication in our cohort.

Safety and outcomes of endoscopic ultrasound-guided drainage for malignant biliary obstruction using cautery-enabled lumen-apposing metal stent.

Background and study aims There is increasing evidence to suggest that EUS-guided biliary drainage (EUS-BD) is a safe and effective treatment alternative for patients with malignant biliary obstructions (MBOs) after failed endoscopic retrograde cholangiopancreatography. Patients and methods We performed a retrospective analysis of data prospectively collected from patients with MBO who underwent choledochoduodenostomy (CDS) or gallbladder drainage (GBD) between August 2016 and June 2020 using the electrocautery-enabled lumen-apposing metal stents (ECE-LAMS). The primary endpoint was technical and clinical success. Secondary endpoints were adverse events (AEs) and reinterventions. Results A total of 60 patients were included in the study, with 56 CDS and 4 GBD. Median age was 76 years with 57 % male (34/60). The most common indication for EUS-BD was pancreatic cancer (78 %). Technical success was achieved in 100 % of cases, with a clinical success rate of 91.7 %. Mean total bilirubin pre-procedure was 202 umol/L (normal < 20 umol/L) and 63.8 umol/L post procedure ( P  < .001). Twenty-one patients had bilirubin recorded at 2 weeks post EUS-BD with 20 of 21 patients demonstrating > 50 % reduction in bilirubin (mean bilirubin reduction 75 %). AEs occurred in 12 of 60 patients (20 %), all of which were mild. The reintervention rate was 11.7 % (7/60). Stent occlusion occurred in 10 of 60 patients (16.7 %) with a mean time to stent occlusion of 46.2 days (3-133). Stent patency of 83.3 % was observed with a mean follow up of 7.9 months. Conclusion EUS-CDS and GBD using ECE-LAMS are effective EUS-based techniques for managing patients with MBO. AEs are usually mild and resolved by reintervention.