Endoscopic Ultrasound(EUS) guided gastric variceal(GV) occlusion involves injecting embolization coils followed by slow-polymerizing cyanoacrylate, either n-octyl-cyanoacrylate, or lipiodol-diluted N-butyl-cyanoacrylate(NBC). Coils trap glue and prevent systemic spread. However, they also increase the cost, duration, and complexity.

Undiluted NBC solidifies rapidly in blood, and has long been used in endoscopic management of gastric varices with very rare reports of embolization. Using undiluted NBC in EUS with our modified technique can obviate the use of coils

In our retrospective case-series of EUS guided obliteration for large gastric varices(>15mm), coils were not placed if denied by patients due to financial constraints. GV embolization with coils(Group A) were compared with those who did not have coils(Group B). Primary outcome was clinically evident systemic/pulmonary embolism. Secondary outcomes were any variceal rebleed, and amount of glue required 

52 patients were included (Median age 50yrs, 32%F). Endoscopic hemostasis & cessation of doppler flow achieved in all. No patients showed evidence of systemic/pulmonary embolism. Rebleeding was seen in 13% cases (18% Group-A, 12% group-B, P=NS).  Over a median followup of 248days, only one patient had rebleeding from gastric varices(Group-A). Median size as well as amount of glue used was similar in both groups. Thus, with undiluted NBC, EUS-guided variceal occlusion without coils can have similar outcomes as with coils

Introduction: Variceal bleeding is a common and life-threatening complication of liver cirrhosis. There are several endoscopic techniques available for the management of variceal bleeding,
including band ligation, sclerotherapy, tissue adhesives, and endoscopic ultrasound-guided variceal obturation (EUS-VO) [1]. This meta-analysis aimed to compare the efficacy and safety of different endoscopic modalities for the prevention and management of variceal bleeding in patients with liver cirrhosis.

Methods: A systematic literature search was conducted in several databases, including PubMed, Embase, and Cochrane Library, from inception to September 2022. Randomized controlled trials, cohort studies, and case-control studies that compared different endoscopic modalities for the management of variceal bleeding in patients with liver cirrhosis were included. The primary outcomes of interest were initial hemostasis rates, rebleeding rates, and adverse events.

Results: A total of 15 studies (n= 1,742) met the inclusion criteria and were included in the meta-analysis. The pooled results showed that band ligation was associated with lower rebleeding rates compared to sclerotherapy (OR 0.59, 95% CI 0.44-0.79, p=0.001), while sclerotherapy was associated with a higher risk of adverse events (OR 3.21, 95% CI 1.69-6.11, p < 0.001). Tissue adhesives, such as N-butyl-2-cyanoacrylate, were associated with higher initial hemostasis rates compared to other endoscopic therapies (OR 1.82, 95% CI 1.30-2.55, p=0.001) and lower rebleeding rates (OR 0.39, 95% CI 0.20-0.77, p=0.006). EUS-VO was associated with higher initial hemostasis rates (OR 1.93, 95% CI 1.08-3.43, p=0.027) and lower rebleeding rates (OR 0.43, 95% CI0.26-0.71, p=0.001) compared to traditional endoscopic therapies.

Conclusion: Our meta-analysis suggests that band ligation and tissue adhesives may be superior to sclerotherapy for the prevention and management of variceal bleeding in patients with liver cirrhosis. EUS-VO may be a promising alternative to traditional endoscopic therapies, although further studies are needed to confirm its efficacy and safety. The choice of endoscopic technique should be individualized based on patient factors and physician expertise.

References:

1-Tang L et al., EUS-guided coil placement and cyanoacrylate glue injection for gastric variceal bleeding with obvious spontaneous portosystemic shunts. Endosc Ultrasound. 2023 Jan-Feb;12(1):84-89.doi:10.4103/EUS-D-22-00006. PMID:36510864.

Backgroud: Endoscopic ultrasound-guided gallbladder drainage (EUSGBD) is becoming an important and effective alternative to percutaneous drainage (PTD) for patients not suitable for surgery. It is also an acceptable option for biliary drainage in oncologic patient, if retrograde drainage failed. Placing of a lumen apposing metal stent (LAMS) for EUSGBD allows the removal of gallbladder stones too, so becoming a possible alternative to surgery in very selected cases.

Materials & Methods: Retrospectively analised experience with EUSGBD, from 12/2019 to 05/2023, in a single peripheral hospital, using 2 types of LAMS (10x10mm and 15x10mm), delivered with an electrocautery-enhanced catheter. 

Results: EUSGBD was at least attempted in 15 patients (9/6 male/female), median age of 83 years old (52-89), during the above mentioned period. 11 patients (73.3%) had an advanced cancer (6 pancreatic metastatic cancer, 3 cholangiocarcinoma, 1 breast metastatic cancer, 1 metastatic pulmonary NET) and the remaining were not considered suitable for surgery (whose 1 already received a PTD). EUSGBD was attempted through the duodenum in all cases but the one who previously underwent PTD (still in place), who was drained through the stomach. In one case, the stent was mis-deployed through the duodenum (without entering the gallbladder lumen), so requiring the placement of an over-the-scope-clip and a different biliary drainage for biliary obstruction in an oncological patient. A 15x10mm LAMS was used in 10 cases and a 10x10mm LAMS was used in 5 cases (including the failed one). A double pigtail 5Fr 7cm was placed through all 14 successfully placed LAMS. 3 patients underwent electrohydraulic-lithotripsy (EHL) through the LAMS after 4-8 weeks. In these 3 patients, LAMS was then removed.
Generally, except one complication, it was not described short term or long term adverse events. 7/10 (46.6%) patients died for oncological disease progression. 

Conclusion: EUSGBD represents a promising therapeutic approach in patients with high risk of mortality. Considering the high rate of clinical and technical success as well as the possibility to manage endoscopically potential complications, this approach could be also proposed in peripheral center.

Background: Several studies have demonstrated the impact of KRAS mutation testing on pancreatic ductal adenocarcinoma (PDAC) samples by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for reducing the need to repeat EUS-FNA and shorten the time to treatment initiation. Such testing however is not part of standard practice. This study aimed to analyse the proportion of non-contributive samples by endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) and to evaluate the impact of KRAS mutation testing on the diagnosis and on the theranostics.

Methods: The EUS-FNB samples, combined with KRAS testing using the Idylla® technique on liquid-based cytology from patients with PDAC obtained between February 2019 and February 2023, were retrospectively reviewed. The cytology results were classified according to the recently published guidelines of the World Health Organization (WHO) System for reporting pancreaticobiliary cytopathology.

Main findings: A total of 83 EUS-FNB specimens were reviewed. EUS-FNB sensitivity with KRAS mutation testing using the Idylla® method was 98.7% with a positive predictive value of 100%. Questionable or suspect samples (categories 5 and 6 of the guidelines from the WHO System for reporting pancreaticobiliary cytopathology) with positive KRAS mutations could have been considered as category 7 samples (positive for malignancy). Therefore, combining EUS-FNB with KRAS mutation testing would prevent having to take another sample in 42.3% of these cases. Unlike other publications, and probably due to the small number in the series, the difference in overall survival between mutation types was not statistically different (13.3 months for G12V mutation, 11.3 months for G12D mutation and 11 months for G12R mutation).

Conclusion: KRAS mutation testing on liquid-based cytology using the Idylla® or equivalent method, combined with the PDAC EUS-FNB sample, should become a standard from diagnosis to avoid delaying treatment by doing another biopsy. Furthermore, in a theranostic aim, knowledge of the KRAS status from treatment initiation can be used to isolate mutations requiring targeted treatments or inclusion in clinical research trials, especially for wild-type KRAS PDAC. In every day practice and right from diagnosis, it is a quick and easy way to get simple molecular biology in a way to offer additional therapeutic opportunities in PDAC.

Introduction: Patients with hepatobiliary tumors and hepatic metases frequently present with malignant cholestasis, which if not resolved lowers patients survival and decreases the available therapeutic options. Endoscopic retrograde cholangiopancreatography (ERCP) is the treatment of choice. In some of the patients ERCP is unsuccessful and in this situation endoscopic ultrasound-guided biliary drainage (EUS-BD) is the rescue therapy. Our study investigates the impact of EUS-BD on liver function tests (LFTs), pruritus, and quality of life (QoL) in patients with malignant biliary obstruction after unsuccessful ERCP.

Methods: This is a prospective study in which we included patients with unresectable malignant biliary obstruction and two attempts of failed ERCP. It our cohort of patients EUS-BD procedures, including hepaticogastrostomy (HGS) or choledochoduodenostomy (CDS), were successfully performed. QoL and pruritus severity were assessed using EQ-5D-5L and PSS-10 questionnaires pre- and two weeks post-EUS-BD. Serum bilirubin and LFTs were measured on the procedure day, two days, and at least 14 days after BD. Clinical data and QoL were analysed using paired tests.

Results.  We recruited a total of 37 patients (54% women, age range 34-87 years). HGS was performed in 21 of recruited patients, whereas 16 of patients underwent CDS. Pancreatic cancer was the main cause of biliary obstruction (49%) followed by cholandiocarcinoma (27%). Bilirubin and LFTs (ALT, AST, ALP, and GGT) significantly decreased two days (P<0.001) and 14 days (P<0.001) after EUS-BD. We observed a significant decrease in itch sensation, with an average reduction of 5.19 points on the PSS-10 scale (P<0.001). Also, anxiety and depression scores significantly decreased as assessed by EQ-5D-5L (P=0.013). There was no correlation between decrease in bilirubin levels and improvement of QoL or itch sensation. Overall, 11 patients were referred for palliative chemotherapy treatment after resolution of jaundice. 

Conclusions: Endoscopic ultrasound-guided biliary drainage is a valuable treatment modality in patients with malignant biliary obstruction and unsuccessful ERCP. In carefully selected patients it allows further palliative treatment.  It improves certain aspects of health-related quality of life and pruritus.   

Backround

Diagnosis and prognosis of pancreatic cystic neoplasia pose a clinical challenge. Current diagnostic methods lack sufficient sensitivity and specificity. Evaluating gene expression in pancreatic cyst fluid RNA has emerged as an additional approach for assessing the potential malignancy of these cysts. Due to methodological complexity and the limited avalailability of material, few studies have been conducted. The study aim is to evaluate the expression of specific genes involved in the pancreatic cysts oncogenesis.

Materials and methods:

The study included 15 pancreatic cyst fluid samples obtained through endoscopic ultrasound-guided fine needle aspiration (2021-2022). The collected cyst fluid was stored at −80 °C until analysis. Three groups were  identified: №1-mucinous cystic neoplasia (MCN, IPMN), №2-non-mucinous cystic neoplasia (SCN), №3-non-neoplastic cysts (pseudocysts), control group. From these samples, 9 RNA samples of satisfactory quality were obtained (group №1:n=4, №2:n=2, №3:n=3); 5 females, 4 males, the average age was 68 years. 

Target genes associated with pancreatic carcinogenesis were analyzed: FOXA1, CLDN18, GPC-1, CDK1, CCNB1, SFN. Real-time PCR using the qPCRmix-HS reaction mixture was performed on ABI 7500 amplifiers.

Results

The results revealed increased expression of all genes, except SFN, in groups №1 and №2 compared to the control group (Fig.1a). This suggests the involvement of multiple biological processes and signaling pathways in pancreatic cysts formation. There is a strong positive correlation (r > 0.9, p < 0.01) between the increased expression of each gene, indicating their synchronized activation in these patients. Mucinous cysts were found to contribute the most to the high expression of these genes (Fig.1b). Some samples exhibited outliers with elevated expression, requiring further analysis.

Figure 1. a) gene expression changes in cystic neoplasia (gr. №1 and №2) compared to the control group. b) scatterplot on the example comparing the relative expression of the GPC1 gene in all groups; blue dot-dropdown value.

Conclusion

These data suggest that analyzing the transcriptional activity of specific target genes in pancreatic cyst fluid can help identify high-risk groups for pancreatic cancer. Combined activation of these target genes in cystic neoplasia likely enhances their diagnostic value. Further studies are needed to validate this hypothesis. RT-PCR analysis of a limited gene panel is suitable for this purpose.