Introduction

Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for hepatic solid lesions has emerged as a safe technique to obtain an adequate liver tissue for diagnosis of parenchymal liver disease. However, the optimal FNB techniques have not been evaluated. Out study aimed to compare the diagnostic yield and specimen adequacy for EUS-FNB in hepatic solid lesions using different FNB techniques.

Aims & Methods

This is a single center retrospective study of EUS-FNB for hepatic solid lesions between Mar. 2015 and Jun. 2022. Each one needle pass of suction and slow-pull suction was applied for the same hepatic lesions and the sequence was randomly assigned. The primary outcomes were diagnostic yield to attain a histological diagnosis and rate of adequate specimen acquisition.

Results

A total of 119 patients (40 female, median age 70 years) underwent EUS-FNB for hepatic solid lesions. The mean size of hepatic solid lesion was 34.9+27.3 mm (range 7-150). Solid live lesions were located at S1 in 5 (4.2%), S2/3 in 97 (81.5%), S4 in 13 (10.9%), and S5/6/7/8 in 4 (3.3%). Needle puncture was approached at esophagus in 5 (4.2%), stomach in 108 (90.8%), and duodenum in 6 (5.0%). The use of needle was 20G ProCore in 44 (37.0%) and 22G in 75 (63.0%). The final diagnosis of solid liver lesions was benign in 3 (2.5%) and malignancy in 116 (97.5%) including cholangiocarcinoma (49, 41.2%), metastasis (63, 52.9%), hepatocellular carcinoma (2, 1.7%), and lymphoma (2, 1.7%). The overall diagnostic yield to obtain a tissue diagnosis was 90.8%. There was statistically no difference in diagnostic accuracy between suction and slow-pull suction (79.8% vs. 84.9%, P=0.308). Slow-pull suction obtained more adequate specimen comparing to suction (95.0% vs. 87.4%, P=0.040).

Table 1. Comparison of specimen adequacy and diagnostic performances according to EUS-FNB techniques

Conclusion

The use of slow-pull suction EUS-FNB demonstrated improved specimen adequacy compared with suction technique with no difference in diagnostic accuracy.

References

Madhok, I. K., et al. (2022). "Endoscopic Ultrasound-Guided Liver Biopsy." Clin Liver Dis 26(1): 127-138.
Gheorghiu, M., et al. (2022). "Endoscopic Ultrasound-Guided Fine-Needle Biopsy versus Fine-Needle Aspiration in the Diagnosis of Focal Liver Lesions: Prospective Head-to-Head Comparison." Diagnostics (Basel) 12(9).

Introduction

Recurrence of Crohn’s disease (CD) after ileocolic resection is common. However, reliable non-invasive monitoring methods are lacking, for instance, the use of faecal calprotectin (FC) has showed inconsistent results in this subgroup of patients.

Aims & Methods

The aim of this study was to evaluate clinical and biochemical factors associated with post-operative endoscopic recurrence in CD patients.
Retrospective single-center study including patients with CD who underwent ileocolonoscopy for CD surveillance, after ileocolic resection. The patients’ clinical status was evaluated through Harvey-Bradshaw index (HBI), with clinical remission considered as ≤ 4 points. Biochemical parameters included erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and FC. Clinical and biochemical parameters were evaluated in the 6 months prior to ileocolonoscopy. Post-operative endoscopic recurrence was defined as a Rutgeerts score ≥ i2b.

Results

A total of 81 patients and 121 ileocolonoscopies were included. Most patients were female (55.6%), with a mean age of 48±13 years. Regarding the Montreal classification, 37 patients had ileal disease (45.7%) and 44 ileocolonic disease (54.3%); 9 patients had nonstricturing, nonpenetrating disease (11.1%), 35 stricturing (43.2%) and 37 penetrating disease (45.7%). Nineteen patients had perianal disease (23.5%). The mean time between the surgery and the endoscopic evaluation was 135±79 months. Post-operative endoscopic recurrence was observed in 52 ileocolonoscopies (43.0%).
Symptomatic patients (HBI > 4 points) were 11 times more likely to have post-operative endoscopic recurrence (OR 10.686, 95%CI 2.930-38.974, p<0.001). Those with post-operative endoscopic recurrence had a significantly higher FC values (median 189 vs 69 µg/g, p<0.001) and higher ESR values (median 14 vs 9 mm, p=0.002). In fact, patients with FC values ≥ 150 µg/g and those with ESR values > 12 mm were 4 and 3 times more likely to have post-operative endoscopic recurrence (OR 3.654, 95%CI 1.605-8.316, p=0.002 and OR 3.059, 95%CI 1.397-6.696, p=0.005, respectively). The presence of post-operative endoscopic recurrence was not associated with CRP values (median 2.9 vs 2.9 mg/L, p=0.466), and neither with mean time between the surgery and the endoscopic evaluation (mean 126±83 vs 142±75 months, p=0.263).

Conclusion

The presence of symptoms (HBI > 4 points), FC values ≥ 150 µg/g and ESR values > 12 mm was associated with post-operative endoscopic recurrence in CD. Therefore, the HBI, FC and ESR values can be used to monitor CD patients after ileocolic resection, and prompt endoscopic evaluation should be performed in those with HBI > 4 points, FC values ≥ 150 µg/g and/or ESR values > 12 mm.

Introduction

​Gastric lesions associated with Helicobacter pylori, eradication issues and problems of its sometimes-insufficient effectiveness continue to remain one of the most pressing topics in modern healthcare.

Aims & Methods

The analysis aimed to assess the usage, efficacy, and safety of initial empirical treatment for H. pylori infection in Azerbaijan.
​Data were collected at e-CRF AEG-REDCap from the European Registry on Helicobacter pylori Management (Hp-EuReg) and quality reviewed from January 2020 to May 2023. All treatment-naïve cases were assessed for effectiveness by modified intention-to-treat (mITT), per-protocol (PP) analyses, and a separate multivariate analysis was performed.

Results

The study included 3,898 patients (67% reported dyspepsia). In 1.9% of patients, at least one type of allergy was reported (1.6% to penicillin). A total of 226 patients (5.8%) received concurrent medication: PPI (5.1% on demand, 0.1% daily), aceltylsalicylic acid (1.2% on demand, 0.2% daily), NSAIDs (1.3% on demand), statins (1.2% on demand, 0.1% daily). The most frequent indication for treatment was dyspepsia with normal endoscopy in 2,610 patients (67%). In total, 3,853 (99%) patients were diagnosed pre-treatment using the rapid urease test, which was the most frequently used. The following tests were likewise used in a lower number of cases: monoclonal stool antigen test (MSAT)(0.7%) and polyclonal stool antigen test (0.1%). In 2,661 (68%) cases a MSAT was used, being the most frequent post-treatment confirmation method. Additionally, in 55 (1.4%) cases an invasive method, that is endoscopy, was performed, to confirm the eradication. First-line empirical treatment prescriptions and mITT effectiveness by treatment schemes is presented in Table 1.
Triple regimens were the most frequently prescribed in over 3,000 (82%) patients, where the PPI-C+A treatment scheme represented 54% of the total of first-line prescriptions. Treatment length varied from 14 days in 56% of cases, 10 days in 27%, and 7 days in 17%. Following 14-day treatments prescriptions achieved optimal (>90%) mITT effectiveness: PPI-C+A (94%), PPI-C+M (97%), PPI-C+M+ B (96%) and PPI-C+A+B (98%). Following schemes also provided optimal results when combined with standard-dose (i.e., 40 mg omeprazole equivalent twice a day) PPIs: PPI-A+Tc (100%) and PPI-C+A+B (96%). Additionally, prescriptions concomitantly administered with high-dose (i.e., 80 mg omeprazole equivalent twice a day) PPIs provided also over 90% eradication rates: PPI-C+A (94%), PPI-C+M (97%), PPI-C+M+B(100%) and PPI-C+A+B (99%). Compliance with treatment was over 90% in the vast majority of cases. The incidence of at least one adverse event was reported in 12% of cases.
Table 1. Most frequent first-line empirical treatment prescriptions and modified intention-to-treat effectiveness in Azerbaijan.

Conclusion

The prescribed H. pylori eradication regimens during the period 2020–2023 in Azerbaijan adhered only partially to the Maastricht VI recommendations; however, most of first-line empirical therapies achieved high (≥90%) cure rates, providing a good safety profile.

Introduction

Endoscopic ultrasound (EUS) is an important tool for the evaluation of patients with common bile duct (CBD) dilation without obvious identified aetiology after ultrasonography (US), computed tomography (CT) and/or magnetic resonance cholangiopancreatography (MRCP).

Aims & Methods

The aim of this study was to evaluate the diagnostic performance of EUS for CBD dilation in patients with a negative initial study.
Retrospective, unicentric and cohort study including patients who underwent EUS for CBD dilation (diameter ≥7mm if intact anatomy or ≥10mm if prior cholecystectomy) in the absence of obvious pathology on prior imaging, including US, CT and/or MRCP, from January 2016 until June 2022. All EUS procedures were performed with a linear echoendoscope.

Results

Totally, 109 patients were included, 50 patients without symptoms or altered liver biochemistry (45.9%). Among the 41 patients with positive EUS, 33 patients had choledocholithiasis (30.3%), 6 chronic pancreatitis (5.5%) and 2 had ampullary cancer (1.8%). Older age was associated with positive EUS (median 79 vs 71 years, p=0.030). Patients with jaundice, cholelithiasis and altered liver biochemistry were 16.2 (p=0.002), 3.1 (p=0.024) and 2.9 (p=0.009) times more likely to have positive EUS, respectively.
A total of 53 patients underwent MRCP with a negative result (48.6%). In this group, 12 patients had a positive EUS, 10 had choledocholithiasis (18.9%) and 2 had chronic pancreatitis (3.8%). Of those, patients with abdominal pain and jaundice were 15.4 (p<0.001) and 20.0 (p=0.007) times more likely to have positive EUS, respectively. CBD diameter in MRCP was not associated with finding a causative lesion (p=0.473).
Considering only asymptomatic patients without altered liver biochemistry, CBD diameter ≥8.5mm, evaluated by CT, had a sensibility of 100% and specificity of 75% in predicting a positive EUS (AUC 0.734, p=0.048).

Conclusion

EUS is a useful diagnostic method for patients with unexplained CBD dilation, with a higher yield, even in patients with negative MRCP, and especially in patients with older age, symptoms such as abdominal pain and jaundice, cholelithiasis and/or altered liver biochemistry. CBD diameter evaluated by CT had a moderate discriminative ability in predicting a positive EUS in asymptomatic patients without altered liver biochemistry.

Introduction

The emergence of antimicrobial resistant Helicobacter pylori (H. pylori) has impacted treatment success rates. Local audits of prescription patterns and eradication rates are necessary to assess treatment efficacy and compliance with clinical guidelines. The first Irish consensus guidelines on the management of H. pylori were published in 2017. Clarithromycin-amoxicillin triple therapy (CTT) or bismuth quadruple therapy (BQT) were the recommended first-line options. Other key recommendations included extending treatment durations to 14 days and the use of high-dose proton pump inhibitors (PPIs).

Aims & Methods

This study aimed to (i) investigate first-line H. pylori prescription patterns and cure rates over a 10-year period in Ireland, and (ii) evaluate the impact of the first Irish consensus guidelines on these trends. Data were collected at e-CRF AEG-REDCap from the European Registry on Helicobacter pylori Management (Hp-EuReg) and quality reviewed from 2013 to 2022. All treatment-naïve cases were assessed for effectiveness by modified intention-to-treat (mITT) analysis. Multivariate analysis was performed using a logistic regression model to evaluate the relationship between mITT rates and age, sex, indication, compliance, PPI dose and treatment duration.

Results

In all, data from 1,000 patients (mean age 50±15 years; 54% (n=536) female) were included in the analysis, from those 78% (n=784) were from Tallaght University Hospital, Dublin and 22% (n=216) were from Beacon Hospital, Dublin. The most common indication was dyspepsia (92%; n=920), followed by duodenal ulcer and gastric ulcer (2%; n=20 and 1%; n=10, respectively). CTT was the most common first-line treatment (88%; n=880). BQT represented 1.7% (n=17) of prescriptions. Of the reported treatment durations (n=998), 87% (n=868) were for 14 days, 4.5% (n=45) were for 10 days and 8.5% (n=85) were for 7 days. Of the reported PPI dose prescribed (n=999), 86% (n=860) were high (i.e., 80 mg omeprazole equivalent twice daily), 0.9% (n=9) were standard (i.e., 40 mg omeprazole equivalent twice daily), and 13% (n=130) were low (i.e., 20 mg omeprazole equivalent twice daily).

The eradication rate was 80.1% (95% confidence interval (CI) 77.5-82.5%) overall and 81.4% (95% CI 78.9-83.7%) for CTT. Multivariate analysis revealed that good compliance and the use of high dose PPI were significantly associated with higher overall mITT rates (odds ratio (OR) 4.5, 95% CI 1.4-14.2, p<0.05 and OR 1.9, 95% CI 1.2-2.8, p< 0.005, respectively) and CTT mITT rates (OR 4.2, 95% CI 1.2-14.2, p<0.05 and OR 1.9, 95% CI 1.1-3.2, p<0.05, respectively).

Following publication of the Irish consensus guidelines in 2017, prescriptions for 14 days therapy increased from 39% (n=82/208) pre-2017 to 99% (n=786/790; p<0.0001) and the use of high dose PPI increased from 37% (n=77/207) pre-2017 to 99% (n=783/792; p<0.0001). In line with this, overall eradication rates significantly increased from 74.5% (95% CI 68.2-80.0%) pre-2017 to 81.6% (95% CI 78.7-84.1%; p<0.05). CTT eradication rates significantly increased from 75.7% (95% CI 68.2-81.8%) pre-2017 to 82.6% (95% CI 79.6-85.1%; p<0.05).

Conclusion

CTT was the most frequently prescribed first-line therapy between 2013-2022. BQT was rarely prescribed, reflecting difficulty accessing bismuth in Ireland. While treatment success increased following publication of the Irish consensus guidelines, cure rates remain below 90%. Alternative first-line treatment strategies are required in the Irish healthcare setting.

Introduction

The use of 3D cell culture models, including spheroids and organoids, has proven to be a valuable method to approximate in vivo conditions in basic research. Our recent work on the pathogenesis of spontaneous bacterial peritonitis (SBP) – a life-threatening complication of liver cirrhosis with a 1-year-mortality of 66% – shows that bacteria induce the degradation of important cell-cell contact proteins upon direct contact via various processes. The resulting destabilization of the epithelial barrier enables bacterial translocation and thus represents a mechanism in the development of SBP (Haderer et al., Gut 2022). To evaluate these processes under more physiological conditions, we investigate bacterial-induced effects on cell-cell contact proteins in a 3D spheroid model and subsequently in a patient-based organoid model.

Aims & Methods

To establish the method and create a reference, spheroids were generated from colon carcinoma cell line HCT116 with a concentration of 70,000 cells/ml. Spheroid development and formation of cell-cell contacts were assessed by fluorescence microscopy. Subsequently, bacterial-induced effects on the tight junction proteins Occludin, Claudin4 and Zonulin1 as well as on the adherens junction protein E-Cadherin were investigated after up to 12 hours of bacterial co-culture using qPCR, fluorescence microscopy and Western blot analysis. Bacterial co-culture was performed with the reference strain Escherichia coli (E.coli) O6:Hnt and the E. coli strain Ont:H41, which was isolated from the ascites of a patient with SBP.
In addition, organoids were generated from intestinal biopsies of patients with liver cirrhosis and co-cultured with both bacterial strains. Bacterial-induced effects on cell-cell-contact proteins were investigated using Western blot analysis.

Results

HCT116 cells formed formed spheroids composed of viable cells with well-defined cell-cell contacts. Co-culture with E. coli for up to 12 hours led to a significant degradation of Occludin (up to 60% reduction), E-Cadherin (up to 85% reduction) and Zonulin1 (up to 95% reduction), whereas Claudin4 levels remained mostly constant. Co-culture with heat-inactivated bacteria did not affect cell-cell contacts. The intensity of these effects was dependent on the respective protein, the bacterial strain used, as well as the multiplicity of infection (MOI) and the duration of the co-culture. Degradation of Occludin could also be visualized by fluorescence microscopy.
We were then able to transfer this experimental approach to an organoid setting. Bacterial-induced degradation of the epithelial barrier was confirmed in organoids, showing a clearly visible reduction of E-Cadherin, Occludin and Zonulin1 after 8 hours of bacterial co-culture. The intensity of the effects varied depending on the bacterial strain, with the patient strain showing a slightly higher level of aggressiveness.

Conclusion

Understanding the pathophysiological changes of the intestinal epithelial barrier in patients with liver cirrhosis is essential for advancing therapeutic strategies for SBP. In this context, a representative ex vivo model is crucial to draw reliable conclusions. Our work shows that relevant mechanisms of SBP, such as bacterial-induced degradation of cell-cell contacts, can be successfully modeled in spheroids and organoids. Thus, our study provides an approach for further approximation to in vivo conditions – bridging the gap between basic research and clinical utility.

References

Haderer M, Neubert P, Rinner E, Scholtis A, Broncy L, Gschwendtner H, Kandulski A, Pavel V, Mehrl A, Brochhausen C, Schlosser S, Gülow K, Kunst C, Müller M. Novel pathomechanism for spontaneous bacterial peritonitis: disruption of cell junctions by cellular and bacterial proteases. Gut. 2022 Mar;71(3):580-592. doi: 10.1136/gutjnl-2020-321663 . Epub 2021 Mar 11. PMID: 33707230 ; PMCID: PMC8862089.