Introduction

Even though gastric varices (GV) are less frequently encountered than oesophagal varices, they are associated with severe bleeding¹. Novel endoscopic ultrasound (EUS)-guided therapeutics approaches have emerged from GV recent classification based on afferent and efferent hemodynamics^2,3.

Aims & Methods

We aim to target the feeder vessel or afferent component displaying a novel therapeutic approach comprising a combined application of cyanoacrylate (CYA) and coils. This approach is intended to address the vascular pathology of GV with enhanced precision and efficacy. A single-centre, prospective registry was conducted from Jul/2015-Oct/2023. Enrolled patients included adults ≥18 years old considered for primary or secondary prophylaxis of gastro-oesophageal varices (GOV) II and isolated GV (IGV) I. First, the location of the feeder's vessel was determined by angiography using a 10 ml water-soluble contrast. Subsequently, using a FNA needle, coils were EUS-guided deployed (10-20 mm coiled diameter, 14-20 cm straight lengths, 0.035 inches diameter), followed by CYA injection (2-Octyl-CYA). The number of deployed coils and injected CYA was documented. Outcomes were technical success, immediate disappearance, complete obliteration, recurrence rate, recurrence-free survival (RFS) and recurrence management.

Results

Over eight years, 167 patients underwent EUS-guided coils and CYA: 49.7% females, a median age of 63 years, and 19% alcohol-related cirrhosis. Child-Pugh B and C were estimated in 65.9% and 18% of patients, respectively. The most common previous therapies included B-blockers (32.3%), band ligation (26.9%), and CYA (21.0%). GV treatment was intended as secondary prophylaxis in 88.6%. More than one feeder vessel was targeted in 38.9%. In 67.7% of cases up to three coils were required, with a median injection of 3.6 ml of CYA. A 100% technical success was achieved. Among the 167 patients, 15 experienced recurrences (8.9%), with a median RFS of 4.9 months. When comparing non-recurrence vs recurrence patients, immediate disappearance was noticed in 69.7% vs 40.0% with white light endoscopy (p=0.039) and complete obliteration in 90.1% vs 73.3% during EUS (p=0.072), respectively. Immediate disappearance was a significant predictive factor for non-recurrence (OR 0.29; IC 95% 0.09 – 0.85; p=.026), with a 95% positive predictive value. All recurrences were managed with EUS-guided coils and CYA (9/15) and clips and CYA (6/15), with a 12/15 non-recurrence rate (Table 1). On multivariate analysis, a lower recurrence was associated with previous B-blockers therapy (OR 0.18; 95% CI 0.02 to 0.78; p=.045), while a previous CYA attempt represented a high-risk factor for recurrence (OR 10.2; 95% CI 1.08 to 110; p=.044).

Table 1. Management and follow-up in patients with recurrence.

Conclusion

EUS-guided coils and CYA in feeder vessels have shown high technical success and low recurrence rate in treating IGV I and GOV II. CYA attempts should be misadvised in GV. Non-immediate disappearance requires shorter follow-ups to assess for early recurrence.

References

1. Philips, C.A., Ahamed, R., Rajesh, S. et al. Beyond the scope and the glue: update on evaluation and management of gastric varices. BMC Gastroenterol 20, 361 (2020). doi: 10.1186/s12876-020-01513-7
2. Rana, S.S, Sharma, R, Dhalaria, L, Gupta R. Contrast-Enhanced Endoscopic Ultrasound-guided coil and glue injection for bleeding gastric/ectopic varices. Techniques and Innovations in Gastrointestinal Endoscopy 2021. 23 (3): 244-247. doi:10.1016/j.tige.2021.01.001
3. Romero-Castro R, Jimenez-Garcia VA, Irisawa A, Carmona-Soria I, Caunedo-Alvarez A, Teoh AYB, Giovannini M. Anatomic and hemodynamic findings during endoscopic ultrasound-guided angiography of gastric varices: a note of caution for endoscopic ultrasound-guided therapy. Endoscopy. 2022 Dec;54(S 02):E966-E967. doi: 10.1055/a-1884-9245.

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is a cornerstone in the diagnosis and treatment of pancreatobiliary diseases. However, it carries the risk of complications including potentially fatal post-ERCP pancreatitis (PEP). Despite ongoing efforts, effective strategies for managing PEP remain unestablished. Current guidelines define PEP based on symptoms and findings occurring within 24 hours after ERCP; however, early diagnosis and intervention may prevent its incidence and severity. Recently, urinary trypsinogen-2 (UT2) has emerged as a potential biomarker for early acute pancreatitis, but its role and the optimal timing for PEP remain unclear. Therefore, we aimed to evaluate the diagnostic performance of UT2 at multiple time points following ERCP.

Aims & Methods

This is a single-center prospective observational study conducted at The University of Tokyo Hospital. Patients who underwent their initial ERCP at our institution between February 2022 and June 2024 were enrolled. Patients with choledochojejunostomy, biliary pancreatitis, or those undergoing hemodialysis were excluded. UT2 levels were measured using a rapid dipstick test before ERCP, immediately after, and at 1 and 3 hours post-procedure. Serum amylase (AMY) levels were measured 3 hours after ERCP. We evaluated the diagnostic performance (sensitivity, specificity, and accuracy) of UT2 at multiple time points, for the diagnosis of PEP. PEP was defined as an elevation in pancreatic enzyme >3x upper limit of normal with abdominal pain at 24 hours post-pocedure.

Results

A total of 521 patients underwent initial ERCP during the study period, and 337 were included in the final analysis. The median age was 74 years, and 64% were male. A naïve papilla was present in 89% of patients. The indications for ERCP included bile duct stones (39%), malignant biliary obstruction due to pancreatic cancer (13%) or non-pancreatic cancer (18%), benign biliary stricture (5%), diagnostic pancreatogram (24%), and others (1.2%). EST, EPBD, and EPLBD were performed in 37%, 6.5%, and 4.5%, respectively. Prophylactic pancreatic stent placement and rectal NSAIDs administration were performed in 29% and 20%, respectively. PEP occurred in 10% (mild 8.6%, moderate 1.2%, and severe 0.3%) of patients. UT2 demonstrated a trend toward higher sensitivity compared to AMY (AMY: 52.9% vs. UT2 at 0 h: 52.9%, 1 h: 64.7%, 3 h: 64.7%), while AMY exhibited significantly higher specificity (AMY: 92.7% vs. UT2 at 0 h: 65.3%, 1 h: 64.7%, 3 h: 65.0%) and accuracy (AMY: 88.7% vs. UT2 at 0 h: 64.1%, 1 h: 64.7%, 3 h: 65.0%). Notably, 28.5% of patients were positive for UT2 prior to undergoing ERCP. These patients were significantly older (79 vs. 71 years, P < 0.01), more likely to have pancreatic cancer (19.8% vs. 9.5%, P = 0.02), and less likely to have chronic pancreatitis (3.1% vs. 12.9%, P = 0.01). After excluding 96 cases (28.5%) who were UT2-positive before ERCP, we further evaluated the diagnostic performance of UT2 and AMY. UT2 at 0 h had lower sensitivity compared to AMY (AMY: 54.2% vs. UT2 at 0 h: 37.5%, 1 h: 54.2%, 3 h: 54.2%). In contrast, specificity was similarly high across all markers (AMY: 91.7% vs. UT2 at 0 h: 88.9%, 1 h: 87.1%, 3 h: 87.1%). Diagnostic accuracy was comparable between AMY and UT2 (AMY: 88.0% vs. UT2 at 0 h: 83.8%, 1 h: 83.8%, 3 h: 83.8%).

Conclusion

UT2 showed slightly lower predictive performance for PEP compared to AMY. However, excluding UT2-positive pre-ERCP improved the diagnostic accuracy. The diagnostic performance plateaued at 1 hour after ERCP, suggesting its potential utility in predicting PEP earlier.

Disclosure

The author is affiliated with Nipro Corporation through a labor-related arrangement, but has received no financial support or remuneration related to this study.

Introduction

5-aminosalicylates (5-ASAs) are commonly used in patients with Crohn’s disease (CD), especially in mild-to-moderate disease. Over half of patients receive 5-ASA during their disease course, with up to 30% continuing long-term therapy for either active (induction of remission) or quiescent (maintenance of remission) disease. However, the evidence regarding their efficacy is mixed, with conflicting findings in systematic reviews (SRs). In preparation for the results of the STATIC trial (NCT 03261206)¹, we conducted an umbrella review to consolidate existing knowledge by identifying, evaluating, and synthesizing findings from published SRs on the use of 5-ASA in patients with active or quiescent CD.

Aims & Methods

Following Cochrane guidelines for "Overviews of Reviews" and adhering to the Preferred Reporting Items for Overviews of Reviews (PRIOR), we systematically searched major databases for relevant SRs published in English until February 28, 2024, summarizing data on 5-ASA use in induction, maintenance, or withdrawal trials of CD. We excluded SRs focusing solely on post-surgical patients or studying the chemoprevention effects of 5-ASA. Two independent reviewers screened articles, extracted data, and assessed quality using AMSTAR 2.

Results

Of 795 screened references, 8 SRs met our inclusion criteria, with the number of included RCTs ranging from 2 to 22 (Table). Most SRs included RCTs of patients with mild-to-moderate ileo-colonic CD. Three SRs focused on induction of remission, two on maintenance of medically induced remission, and three included both, while none investigated withdrawal of therapy. Two SRs were network meta-analyses (NMA) comparing 5-ASAs with other active treatments or placebo; four were Cochrane systematic reviews comparing 5-ASAs with placebo, corticosteroids, or thiopurines (AZA or 6-MP). One SR, published in 2017,used the outdated Jadad scale to assess the risk of bias of RCTs; only Cochrane reviews assessed the level of certainty of evidence. The latest NMA in 2017, including 22 RCTs for induction of remission, suggested that high-dose mesalamine was more effective than placebo, ranking higher than low-dose budesonide and sulfasalazine, though lower than systemic corticosteroid and high-dose budesonide. Conversely, the latest Cochrane review in 2016, including 12 RCTs for maintenance of remission, found no evidence of benefit for oral 5-ASAs over placebo for maintaining medically induced remission. No SRs performed subgroup analysis for duration of remission upon enrollment. Only the NMA conducted a sensitivity analysis to evaluate baseline disease activity, indicating that high-dose mesalamine was superior to placebo when restricted to RCTs with an enrollment CDAI between 150 to 450.

Conclusion

The results of this umbrella review of SRs suggest that high-dose mesalamine may be considered for inducing remission in mild-to-moderate CD. However, evidence does not support the role of 5-ASA for maintaining medically induced remission. Updating SRs with new evidence is imperative to provide guidance on patient subsets who may benefit from 5-ASA use and these results will be updated with the STATIC trial ¹.

References

1. NCT03261206. Stopping Aminosalicylate Therapy in Inactive Crohn's Disease (STATIC) https://classic.clinicaltrials.gov/ct2/show/NCT03261206

Introduction

Despite advances with chemotherapy regimens, Pancreatic adenocarcinoma (PDAC) is becoming the 2^nd cause of cancer-related death. Personalized medicine will be the game changer, but molecular characterization of pancreatic neoplasms is yet extremely cumbersome and has been performed on surgical samples or few EUS-tissue acquisition (TA) cases, mostly for DNA analysis. Our aim was to evaluate DNA and RNA extracted for research purposes from pancreatic neoplasms employing Endoscopic Ultrasound (EUS) Fine needle aspiration (FNA) and biopsy (FNB) and adequacy to molecular analyses.

Aims & Methods

From Oct 2022, patients with solid pancreatic neoplasms suggestive of either PDAC or neuroendocrine neoplasm (NEN) undergoing diagnostic EUS-TA were considered for enrollment. Employed needles were either FNA, or Franseen, Fork-tip or Three-prong, either 22G or 25G based on operator’s preference, with Rapid on Site Evaluation and, in case of adequacy within the first 2 passes, 1 additional pass with the same needle was performed for molecular analyses. DNA and RNA were then extracted with a new technique and nucleic acids were quantified and evaluated for adequacy for molecular analysis. Mann-Whitney was employed for comparison of continuous variables, and Kruskal-Wallis test for comparison between multiple groups; Logistic regression was applied to determine factors associated with adequacy to molecular tests.

Results

351 patients underwent sampling for molecular analyses, 309 with a definitive diagnosis of PDAC and 42 with NEN. 92,9% of patients were sampled with 25G FNA needles. Median quantity of DNA extracted was significantly lower in PDAC 2048 ng (95%CI: 1470 -3651) compared to NEN 6752 ng (95%CI: 3502-9655)(p<0.0144). Mean quantity of RNA extracted was similar, 312 ng for PDAC, and 444 ng for NEN (p=0.07), with a higher median RIN of 6,4 (95%CI:6,2-6,5) for PDAC versus 4,7 (95%CI:3,9-5) for NEN (p<0.0001). In terms of needle type, concerning DNA extraction, 25G FNA needles retrieved a median of 3384 ng, 25G Franseen needles (4312 ng), 22G Franseen (73864 ng), 25G Fork-tip or Three-prong (3104 ng), with no significant difference. In terms of needle type, concerning RNA extraction, 25G FNA needles retrieved a median of 310 ng (RIN 6,3), 25G Franseen needles 460 ng (RIN 5,5), 22G Franseen 884 ng (RIN 5,9), 25G Fork-tip or Three-prong 301 ng (RIN 5,15), with no significant difference. 295 (95,5%) of PDAC samples and 34 (80,9%) of NEN samples were considered adequate for sequencing. The only factor associated to adequacy for molecular analysis was tumor type, with PDAC having an OR of 5,44 (95%CI 2,06-14,37)(p=0.0006), while the type of employed needle was not

Conclusion

Molecular analysis on EUS-acquired tissue of pancreatic neoplasms will be the mainstay of personalized therapies but how to best perform tissue acquisition and sample handling for this specific purpose is yet to be defined. This is the largest study ever performed on DNA and RNA extraction from EUS-acquired samples, demonstrating superior adequacy for molecular analysis in PDAC compared to NEN. All needle types result similar in terms of performance despite the low number of needles other than 25G FNA needles.

Introduction

Nutritional deficiencies, including fat-soluble vitamins, water-soluble vitamins and minerals have been studied in the setting many autoimmune diseases, including those involving the digestive system. However, despite the well-known pancreatic involvement in IgG4-related diseases, nutritional deficiencies in autoimmune pancreatitis (AIP) have not been examined so far.

Aims & Methods

The aim of the present study was to determine the prevalence of micronutrient deficiencies in patients with AIP as well as to investigate their relationship with relapse. We retrospectively analysed medical records of patients followed up for AIP at our Pancreas Outpatient Clinic between January 2001 and March 2022. Demographic and clinical data were collected. The primary outcome was the prevalence of micronutrient deficiencies during AIP follow-up. The secondary outcome was the prevalence of AIP relapse, with exposure defined as micronutrient deficiency occurring at any time during follow-up. Micronutrient variables were solely described categorically as deficient or normal, according to the reference values at the time of each test. However, the cut-off value for vitamin D deficiency was set to below 25 nmol/L since levels between 25-50 nmol/L solely indicate an insufficiency.

Results

One hundred patients were included in the final analysis. The male-to-female ratio was 2.5:1; median age at diagnosis was 57 years (range 19-85). Median follow-up was 53 months, and during this time, 38% of patients suffered from at least one micronutrient deficiency. The most prevalent micronutrient deficiencies were vitamin D (16.1%) and zinc (25.5%). There were no statistically significant differences in prevalence of micronutrient deficiency stratified by AIP subtype. The prevalence of PEI and of at least one relapse were significantly higher in patients with micronutrient deficiencies than in those without (92.1% vs 69.4%, p = 0.01 for PEI, and 52.6% versus 27.4%, p = 0.02 for relapse). Interestingly, the prevalence of pancreatic enzyme replacement therapy (PERT) was also higher in patients with any micronutrient deficiency compared to in patients with no deficiencies 34 (89.5%) vs 40 (64.5%), p=0.01. Relapse was observed in 37% of the AIP patients. The odds for relapse were 2.9 (1.26-6.86, p=0.02), 2.71(1.36-5.41, p=0.006) and 3.38 (1.09-10.55, p=0.04) times higher in patients with any deficiency, zinc deficiency and vitamin D deficiency, respectively, compared to in non-deficient patients. However, after stratifying for AIP type 1 and adjusting for PEI and elevated IgG4 levels, this association ceased to be statistically significant.

Conclusion

Zinc and vitamin D deficiencies may be common in patients with AIP indicating that these micronutrients might play a role in the natural course of AIP probably as a result of delicate interplay between disease burden, disease severity and the consequent destruction of the gland. Importantly, any micronutrient deficiency may be prevalent even in the light of treated PEI which emphasizes the potential of micronutrients as an additional tool in the workup and follow-up of AIP patients. More studies are warranted to ascertain our findings.

References

Wessels I, Rink L. Micronutrients in autoimmune diseases: possible therapeutic benefits of zinc and vitamin D. J Nutr Biochem. 2020;77:108240.
Löhr JM, Vujasinovic M, Rosendahl J, Stone JH, Beuers U. IgG4-related diseases of the digestive tract. Nat Rev Gastroenterol Hepatol. 2022;19(3):185-97.
Sanna A, Firinu D, Zavattari P, Valera P. Zinc Status and Autoimmunity: A Systematic Review and Meta-Analysis. Nutrients. 2018;10(1)

Introduction

It is unknown how stent types relate to clinical outcomes of endoscopic ultrasound (EUS)-guided drainage of pancreatic pseudocysts. This multicenter retrospective study aimed to compare the clinical outcomes between a lumen-apposing metal stent (LAMS) and a plastic stent.

Aims & Methods

Among 357 patients with pancreatic fluid collections in a large multi-institutional WONDERFUL consortium, we included 123 patients who received EUS-guided drainage of a pancreatic pseudocyst (16 and 107 cases with LAMS and plastic stent(s), respectively). We examined clinical treatment success, procedure-related adverse events, and pseudocyst recurrence.

Results

There were no differences between the groups regarding demographics (e.g., age and sex) and disease characteristics (e.g., size, encapsulation status, and the timing of drainage in relation to the onset of acute pancreatitis). The clinical success rates were comparable between the LAMS and plastic stent groups (94% vs. 87%, respectively; P = 0.40). The stent types were not associated with the time to clinical success (median, 25 days vs. 22 days for the LAMS and plastic stent groups, respectively; P = 0.56), the overall rate of procedure-related adverse events (0% vs. 5.6%, P = 0.33), or the rate of recurrence following clinical success (6.7% vs. 17%, P = 0.19).

Conclusion

In patients receiving EUS-guided drainage of pancreatic pseudocysts, clinical outcomes appeared to be comparable between the LAMS and plastic stent groups. If validated, our findings would support the feasibility of plastic stents in this patient population, which is a more cost-effective treatment modality than LAMSs. We, the WONDERFUL study group, have launched a randomized non-inferiority trial of plastic stents compared to a LAMS in this setting (NCT#06133023).

Disclosure

H.I. declares research funding from Boston Scientific Japan, Fujifilm, and Piolax Medical Devices; and honoraria from Boston Scientific Japan, Century Medical, Create Medic, Fujifilm, Gadelius Medical, Hitachi Medical, Japan Lifeline, Kaneka, Kawasumi Laboratories, Olympus Medical, Piolax Medical Devices, Sumitomo Bakelite, UMIDAS, and Zeon Medical; and contributions from Boston Scientific Japan, Gadelius Medical, Japan Lifeline, and Zeon Medical. Y.N. is an editorial board member of Digestive Endoscopy and declares research funding from Boston Scientific Japan, Century Medical, Fujifilm, Gadelius Medical, HOYA Pentax Medical, Hitachi Medical, Kaneka, and Medico’s Hirata; and honoraria from Boston Scientific Japan, Fujifilm, Gadelius Medical, Hitachi Medical, J-MIT, Medico’s Hirata, and Olympus Medical. This work was not supported by any of those companies. The other authors declare no conflicts of interest related to this article.