Introduction

The appropriate whole-body management is mandatory for successful endoscopic ultrasound (EUS)-guided interventions for symptomatic pancreatic fluid collections (PFCs). However, comorbidity status has not been fully examined in relation to clinical outcomes of patients with endoscopically managed PFCs.
Methods: Using a multi-institutional cohort of 413 patients receiving EUS-guided

Aims & Methods

Using a multi-institutional cohort of 413 patients receiving EUS-guided treatment of PFCs in 2010-2019, we examined the associations of Charlson Comorbidity Index (CCI) with in-hospital mortality and other outcomes. Multivariable logistic regression analysis was conducted with adjustment for potential confounders. The findings were validated using a sample of 4,053 patients treated at 486 hospitals in 2010-2020 within a Japanese nationwide inpatient database.

Results

In the clinical cohort, CCI was positively associated with the risk of in-hospital mortality (P_trend < 0.001). Compared to patients with CCI = 0, patients with CCI of 1-2, 3-5, and ≥ 6 had adjusted odds ratios (95% confidence intervals) of 1.36 (0.41-4.47), 7.89 (2.59-24.0), and 9.68 (2.68-34.2), respectively. In the validation cohort, a similar positive association was observed; the corresponding odds ratios were 1.75 (95% confidence interval, 1.28-2.39), 1.80 (1.07-3.06), and 5.26 (2.99-9.27), respectively (P_trend < 0.001). The associations of higher CCI with higher bleeding risk and longer length of stay were observed in the nationwide cohort (P_trend < 0.001), but not in the clinical cohort (P_trend> 0.22).

Conclusion

Higher levels of CCI were associated with higher risk of in-hospital mortality among patients receiving EUS-guided treatment of PFCs, suggesting the potential of CCI in stratifying the periprocedural mortality risk in this population.

References

1) Charlson ME, Pompei P, Ales KL et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. Journal of chronic diseases 1987; 40: 373-383
2) Hamada T, Yasunaga H, Nakai Y et al. No weekend effect on outcomes of severe acute pancreatitis in Japan: data from the diagnosis procedure combination database. J Gastroenterol 2016; 51: 1063-1072
3) Banks PA, Bollen TL, Dervenis C et al. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013; 62: 102-111
4) Baron TH, DiMaio CJ, Wang AY et al. American Gastroenterological Association Clinical Practice Update: Management of Pancreatic Necrosis. Gastroenterology 2020; 158: 67-75.e61
5) Trikudanathan G, Wolbrink DRJ, van Santvoort HC et al. Current Concepts in Severe Acute and Necrotizing Pancreatitis: An Evidence-Based Approach. Gastroenterology 2019; 156: 1994-2007.e1993

Disclosure

Y.N. received research grants from Boston Scientific Japan, HOYA Corporation, and honoraria from Boston Scientific Japan, Fujifilm Corporation, Olympus Corporation. H.I. received research grants from Boston Scientific Japan, Fujifilm Corporation, Fujifilm Health Care Corporation, Gadelius Medical KK, Zeon Medical Inc., and honoraria from Boston Scientific Japan, Fujifilm Corporation, Taewoong Medical Devices, Olympus Corporation, Century Medical,Inc. and Cook Medical Japan G.K. Y.I. received honoraria from Gadelius Medical KK and Medicos Hirata.

Introduction

Pancreatic steatosis (PS) has been increasingly recognized and associated with some relevant metabolic implications. However, data on its correlation with exocrine pancreatic function remain limited. We conducted a systematic review and meta-analysis to evaluate whether PS is associated with exocrine pancreatic insufficiency (EPI).

Aims & Methods

This study aimed to investigate whether imaging-detected PS is related to exocrine pancreatic dysfunction, assessed by fecal elastase-1 (FE-1) levels. We searched PubMed, EMBASE, and Cochrane Central for studies including adults with and without PS identified on imaging, and reporting FE-1 concentrations. Data were pooled using random-effects models.

Results

Three studies evaluating a total of 1,864 patients were included. Fecal elastase levels were significantly lower in patients with PS compared to controls, indicating worse exocrine pancreatic function in this group (MD -199.78; 95% CI -303.66 to -95.91; p < 0.05; I² = 97%). Moreover, PS was associated with a significantly increased risk of exocrine pancreatic insufficiency (RR 3.13; 95% CI 1.17–8.40; p = 0.023; I² = 81%), reinforcing the link between fat accumulation in the pancreas and impaired exocrine function.

Conclusion

This meta-analysis demonstrates a significant association between PS and impaired pancreatic exocrine function, compared to individuals without known pancreas disease. These findings underscore the importance of a comprehensive metabolic assessment in patients with PS, given its potential role in pancreatic dysfunction.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, food and/or aeroallergen-mediated inflammatory disease , characterized by esophageal dysfunction and eosinophil inflammation of the esophageal mucosa. The incidence of EoE has increased in recent years, including Japan. Pathogenesis of EoE is incomplete, and the data on microbiome related with EoE are limited. The aim of this study was to identify the esophageal and salivary microbiome in patients with EoE.

Aims & Methods

Patients either with EoE or non-EOE patients with symptoms of esophageal dysfunction who underwent esophagogastroduodenoscopy(EGD) at Kawasaki Medical School hospital between April 2021 and April 2023 were enrolled. The endoscopic reference score (EREFS) is used to determine severity of endoscopic findings. EoE patients were classified as the active group, if the presence of esophageal eosinophilia greater than or equal to 15 eosinophils per high-power field were detected during the endoscopy. , Saliva and Esophageal mucous taken from esophagus using brushing samples and saliva were used to investigate microbiome in EoE patients and controls. The microbiota of samples was profiled using the Illumina MiSeq platform.

Results

Total 24 patients were enrolled including8 active EoE patients, 5 inactive EoE patients, and 11 controls.
There were no significant differences in age, PPI use, history of gastroesophageal reflux disease and H. pylori infection among the three groups.The comparative analysis of the taxonomic composition at the genus level among esophageal mucous samples indicated that Streptococcus were less abundant in the active EoE group compared to the other groups, and Stomatobaculum were more abundant in the inactive EoE group than in the controls. On salivary, The abundance of the genera Megasphaera were significantly more prevalent in the inactive EoE group than in the other groups.The abundance of the genera Streptococcus was negatively correlated with ERFFS scores.

Conclusion

Streptococcus might be involved in the pathogenesis of EOE.

Introduction

Several factors, including increasing disease prevalence, high unmet need and growing understanding of the diverse mechanisms underlying disease pathogenesis are contributing to an increased interest in clinical research in NASH and NAFLD.

Aims & Methods

We undertook an analysis of metadata from Clinicaltrials.gov (CT.gov) to characterize trends over the last 10 years and what this may tell us about the future trajectory for treatment development. CT.gov was searched for studies containing the terms "NASH" or "Nonalcoholic Steatohepatitis" or "Nonalcoholic Fatty Liver Disease" or "NAFLD" or "NASH Cirrhosis" or "Fatty Liver Disease" or "Metabolic Steatosis" posted from 01-Jan-2013 and 31-Dec-2022. Expanded access programs were excluded as these were not considered research studies. 1095 records were returned, of which 32 were excluded as their focus was on conditions other than those of interest. 1063 studies in the analysis were divided into two equal periods: P1 - 2013 to 2017, and P2 - 2018 to 2022, and analyzed by study type, study phase, intervention type and funding.

Results

Studies increased 100% in P2 vs P1, with the most marked increase in early phase studies (108%). The majority of studies were interventional (798 [75%]), which increased by 91% in P2. Observational studies also increased markedly in P2 (131%). Drugs were the most common study intervention (39%), increasing by 98% in P2. There was also a notable increase in the number of diagnostic studies in P2 (871%), the majority of which were studies of non-invasive methods for staging liver fibrosis. 64% of studies were non-industry funded, which increased by 82% in P2. Industry funded studies increased by 140%, with the largest increase in the biotech sector (174%).

Conclusion

Our data provides evidence of a marked increase in clinical research activity in NASH and NAFLD in the last 5 years, particularly in early phase drug development and non-invasive diagnostic methods as an alternative to liver biopsy for staging fibrosis. This combined with the finding that most research has been non-industry funded suggests a growth in basic science that may translate into an increase in industry research in the future. This is supported by the finding that industry funded studies have increased more sharply than non-industry in the last 5 years.

Introduction

A common finding in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) is periampullary diverticulum (PAD). It is more prevalent in females and elderly patients but is also linked to cholangitis and common bile duct stones. The anatomy may be distorted by PAD, possibly making papilla cannulation challenging. Whether PAD increases the difficulty of cannulation and whether it is linked to a higher incidence of adverse events has been debated. To provide further insights into this scenario, we conducted a nationwide registry-based study.

Aims & Methods

Our objective was to determine the impact of PAD on the cannulation rate, adverse events, and ERCP duration. We collected data on ERCP procedures performed between 2006 and 2021 from the Swedish Registry for Gallstone Surgery and ERCP (GallRiks). The 125,558 ERCPs that were registered in the registry during the study period were reduced to 73,937 after we excluded rendezvous procedures, previous sphincterotomies, previous stenting, and procedures with missing follow-up data.

Results

PAD was discovered in 12,782 (10.2%) ERCPs, with data recorded in the registry, and was present in 8,589 (11.6%) ERCPs in the study population. For 2,796 (3.8%) of the patients in the study group had the papilla inside the PAD (Boix Type 1), while 5,793 (7.8%) of the patients had a papilla on the edge of the PAD (Boix Type 2) or immediately next to it (Boix Type 3). The probability of successful cannulation was greater in non-PAD patients (89.7% vs. 88.6%; P=.002), whereas successful cannulation was reduced to only 81.1% if the papilla was located within the PAD (Type 1) (P<.001). The procedure time did not differ between the PAD (37.4 min) and non-PAD (37.5 min) groups (P=.73). There were no differences in intraprocedural complications (3.1%) or adverse events (16.4% vs. 15.5%; P=.05), whether PAD was present or not. In the PAD group, the risk of bleeding increased (1.8% vs. 1.3; P=.001). The perforation risk did not differ across the groups (PAD 0.8% vs. 0.7% non-PAD; P=.22), however PAD had a reduced incidence of cholangitis (1.8% vs. 2.3%; P=.01) and pancreatitis (4.5% vs. 5.2%; P=.008).

Conclusion

The cannulation rate is slightly reduced in the presence of PAD, and this effect is more pronounced and particularly apparent in patients with Type 1 PAD. The safety of ERCP is unaffected by the presence of PAD.

References

[1] Boix J, Lorenzo-Zúñiga V, Añaños F, et al. Impact of periampullary duodenal diverticula at endoscopic retrograde cholangiopancreatography: a proposed classification of periampullary duodenal diverticula. Surg Laparosc Endosc Percutan Tech 2006; 16: 208–211.
[2] Tham TCK, Kelly M. Association of periampullary duodenal diverticula with bile duct stones and with technical success of endoscopic retrograde cholangiopancreatography. Endoscopy 2004; 36: 1050–1053.
[3] Loffeld RJLF, Dekkers PEP. The Impact of Duodenal Diverticuli and the Execution of Endoscopic Retrograde Cholangiopancreaticography. Int Sch Res Not 2016; 2016: 5026289.
[4] Sun Z, Bo W, Jiang P, et al. Different Types of Periampullary Duodenal Diverticula Are Associated with Occurrence and Recurrence of Bile Duct Stones: A Case-Control Study from a Chinese Center. Gastroenterol Res Pract 2016; 2016: 9381759.
[5] Corral JE, Mousa OY, Kröner PT, et al. Impact of Periampullary Diverticulum on ERCP Performance: A Matched Case-Control Study. Clin Endosc 2019; 52: 65–71.
[6] Tabak F, Ji G-Z, Miao L. Impact of periampullary diverticulum on biliary cannulation and ERCP outcomes: a single-center experience. Surg Endosc 2021; 35: 5953–5961.

Introduction

We previously reported 6 months results of a prospective, randomized and sham-controlled trial comparing endoscopic pyloromyotomy (G-POEM) with a sham procedure in patients with gastroparesis (GREG, 1). G-POEM was superior to a sham procedure in terms of both symptoms improvement and gastric emptying rate. Moreover, cross-over G-POEM, which was performed after a sham procedure was effective in 75% of patients. All patients have been prospectively followed according to an original protocol. Here, we report the long-term results. Unblinding of patients occurred 6 months after the originally allocated procedure (G-POEM or sham).

Aims & Methods

In GREG trial, G-POEM has been compared to a sham procedure in patients with refractory and severe gastroparesis (gastroparesis cardinal symptom index (GCSI) > 2.3, duration of symptoms of at least 6 months, with no adequate response to conservative measures). Patients randomized to the sham group with persistent symptoms were offered cross-over G-POEM. Symptoms were assessed in all enrolled patients (including those with a sham procedure only) at 12, 24 and 36 months, gastric emptying study and upper GI endoscopy were repeated at 12 months only in patients who underwent G-POEM (either primary or cross-over). The main outcomes were proportion of patients with treatment success and recurrences. Kaplan-Meier curve has been constructed to analyze the long-term effects.

Results

From a total of 41 randomized patients with gastroparesis (17 diabetic, 13 postsurgical, 11 idiopathic; 46% male), 33 patients received G-POEM (21 primary, 12 cross-over). Among these, median follow-up was 24 months and treatments success rates evolved from 72% (95% CI: 59%-90%) at 6 months to 67% (95% CI 52%-85%) at 12 months, 64% (49%-82%) at 24 months and 36 months. The corresponding numbers for diabetic, postsurgical and idiopathic gastroparesis at 36 months were 71% (51%-100%), 36% (17%-80%) and 78% (55%-100%). Overall, 3 patients (2 diabetic, 1 postsurgical) with previous treatment success experienced a recurrence of symptoms, however none of these patients required further intervention yet. One female patient with a primary treatment failure underwent redo G-POEM with treatment success (post-surgical etiology). Median gastric retention at 4 hours did not change between 3- and 12-months follow-up (6.7% to 10.0%). Seven patients underwent a sham procedure only, 4 achieving treatment success at 6 months. There were no symptomatic recurrencies up to 36 months follow-up. Among three “only sham” patients without a treatment success, one patient died from other reason and two patients who initially refused cross-over G-POEM decided to undergo this procedure later (one with treatment success, one is scheduled).

Conclusion

Endoscopic pyloromyotomy leads to a sustained improvement in approximately two thirds of patients with refractory GP and the rate of recurrencies is low. Diabetic and idiopathic GP showed a trend towards a higher long-term effect compared to postsurgical GP. Significant improvement of symptoms after sham procedure was infrequent but long-lasting.

References

Martinek J, Hustak R, Mares J, et al. Endoscopic pyloromyotomy for the treatment of severe and refractory gastroparesis: a pilot, randomised, sham-controlled trial. Gut 2022;71:2170–8.

Introduction

Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved for the treatment of moderately to severely active ulcerative colitis (UC) and for the treatment of relapsing multiple sclerosis (RMS). Ozanimod is a first-in-class S1P receptor modulator approved for UC, and one of several S1P receptor modulators used for the treatment of RMS. Ozanimod has been extensively studied in RMS with large patient populations and long exposure times, which can provide more insight into the safety profile of ozanimod in UC.

Aims & Methods

This analysis evaluated the tolerability and safety of long-term ozanimod 0.92 mg/day treatment from clinical trial data in adults with moderately to severely active UC and from clinical trial data in adults with RMS. The UC population included patients pooled from phase 2 (NCT01647516), phase 3 (NCT02435992), and respective open-label extension (OLE; NCT02531126) trials through January 10, 2022. The RMS population included patients treated with ozanimod 0.92 mg in DAYBREAK (NCT02576717; October 16, 2015–February 1, 2022), an ongoing OLE trial of patients from phase 1‒3 ozanimod studies. Safety outcomes included treatment-emergent adverse events (TEAEs) and TEAEs of special interest based on association with S1P modulation. Exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY) were calculated to adjust for time on study.

Results

Mean (SD) ozanimod exposure in 1158 patients with UC was 28.4 (23.3) months (2714.9 total PY exposure); ozanimod exposure in 2494 patients with RMS was 56.4 (15.9) months (11,732.2 PY; UC and MS combined: 14,447.1 PY). TEAEs occurred in 74.6% of UC and 88.2% of RMS patients. Serious TEAEs were reported in 17.3% of UC and 14.1% of RMS patients, and TEAEs leading to ozanimod discontinuation in 9.3% and 3.6%, respectively. The most common TEAEs were lymphopenia (12.3%; EAIR 5.6/100 PY), anemia (8.4%; EAIR 3.7/100 PY), lymphocyte count decreased (7.9%; EAIR 3.5/100 PY), and nasopharyngitis (7.9%; EAIR 3.5/100 PY) in patients with UC, and nasopharyngitis (20.6%; EAIR 5.1/100 PY), headache (16.9%; EAIR 4.0/100 PY), and upper respiratory infection (11.9%; EAIR 2.7/100 PY) in patients with RMS. In UC and MS, respectively, EAIR/100 PY were 20.2 and 22.9 for any infection, 1.6 and 0.8 for serious infection, 1.2 and 1.4 for opportunistic infection, and 0.6 and 0.3 for malignancy. Alanine aminotransferase levels ≥5 times the upper limit of normal occurred in 2.3% and 0.8% of UC and RMS patients, respectively.

Conclusion

Long-term ozanimod 0.92 mg/day was generally well tolerated and safe for most patients with moderately to severely active UC or RMS.

Disclosure

SD: received honoraria as a speaker, consultant, and/or advisory board member from AbbVie, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, and Vifor.
BACC: received personal compensation for consulting for Alexion, Atara, Autobahn Therapeutics, Avotres, Biogen, EMD Serono, Gossamer Bio, Horizon Therapeutics, Neuron23, Novartis, Sanofi, TG Therapeutics, and Therini Bio; and received research support from Genentech.
DCW: received research honoraria as a speaker, consultant, and/or advisory board member from AbbVie, Arena, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Pfizer, and Takeda.
OA: received honoraria as a speaker from Janssen, Pfizer, and Takeda.
LC, AP, JKS, CYC, JVR, and DS: employees and/or shareholders of Bristol Myers Squibb.
FDL: participated in consulting agreements, advisory boards, and/or data and safety monitoring boards with Acorda, Actelion, Apitope, Atara, Biogen, BrainStorm Cell Therapeutics, EMD Serono, GW Pharmaceuticals, Immunic, Innate Immunotherapeutics, Jazz Pharmaceuticals, Mapi Pharma, MedDay, MedImmune/Viela Bio, Mylan, Novartis, Orion Biotechnology, Polpharma, Population Council, Receptos/Celgene, Roche/Genentech, Sanofi/Genzyme, Teva, and TG Therapeutics.
JAC: received personal compensation for consulting from Biogen, Bristol Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and Pharmaceutical Security Institute; speaking from H3 Communication; and serving as an editor of Multiple Sclerosis Journal.
DTR: received grant support from Takeda; served as a consultant for AbbVie, AltruBio, Arena Pharmaceuticals, Bristol Myers Squibb, Eli Lilly, Genentech/Roche, Gilead Sciences, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Takeda, and TechLab.

This study was sponsored and funded by Bristol Myers Squibb.