Introduction

Besides increasing adequacy, Rapid-on-Site Evaluation (ROSE) during Endoscopic Ultrasound (EUS) or Endoscopic Retrograde Cholangiopancreatography (ERCP) may have an impact on choices and timing of subsequent therapeutic procedures, yet unexplored.

Aims & Methods

We conducted a retrospective evaluation of a prospectively maintained database of a tertiary, academic centre with availability of ROSE and hybrid EUS-ERCP suites.
All consecutive patients referred for pathological confirmation of suspected malignancy and Jaundice or Gastric Outlet Obstruction (GOO) between Jan-2020 and Sep-2022 were included.

Results

Of 541 patients with underlying malignancy, 323 (59.7%) required same-session pathological confirmation (male: 54.5%; age 70 [62-77]; pancreatic cancer: 76.8%, cholangiocarcinoma 16.4%). ROSE adequacy was 98.9% for EUS and 50% for ERCP-guided sampling.
Amongst 302 patients with Jaundice, ERCP cannulation was successful in 83.7%, but final drainage was completed in 97.4% thanks to 37 EUS-CholedochoDuodenostomies and 5 EUS-HepaticoGastrostomies. Amongst 21 patients requiring GOO palliation, EUS-GastroEnterostomy was performed in 15 and duodenal stenting in 6. All 53 therapeutic EUS procedures occurred after adequate ROSE.
Amongst ERCP-guided placement of stents, the use of plastic stents was significantly higher amongst patients with inadequate ROSE (10/11 [90.9%] versus 14/240 [5.8%], p<0.0001, OR=161 [19-1352]).
Median hospital stay for diagnosis and palliation was 3 [2-7] days and median time to chemotherapy was 33 [24-47] days.

Conclusion

Nearly two-thirds of oncological candidates to endoscopic symptoms palliation requires contemporary pathological diagnosis. An adequate ROSE allows same-session state-of-the-art therapeutics standardly restricted to pathologically confirmed malignancies (e.g. uncovered SEMS or therapeutic EUS), potentially leading to shorter hospital stay and time to chemotherapy.

Introduction

Experimental data have shown increased expression of angiogenic factors in portal hypertension and disruption of endothelial integrity in small intestinal mucosal vessels that is possibly correlated with antigen translocation to the portal circulation. ZO-1 is a tight junction structural protein of the intestinal epithelium. Recent data revealed that ΖΟ-1 is also expressed by endothelial and mesenchymal cells and plays a dominant role in mucosal healing. Decreased ZO-1 expression may unsettle epithelial restorative capacity following mucosal damage and contribute to the impaired endothelial integrity and bacterial translocation.

Aims & Methods

We therefore aimed to assess changes in mucosal vascular density and evaluate intestinal vessel endothelial integrity in cirrhotic patients by assessing the immunohistochemical expression of ZO-1 in small intestinal biopsy samples. Sixty-three cirrhotic patients were enrolled (M/F:35/28, mean age ±SD: 62±13) during an 18-month period. Nine non-cirrhotic patients served as controls. Patients with current or recent alcohol consumption, porto-splenic vein thrombosis, non-cirrhotic portal hypertension, hepatocellular carcinoma, transjugular intrahepatic portosystemic shunt, chronic kidney disease, celiac disease, acute infection, or any other chronic intestinal disease were excluded. Small intestine biopsy samples were taken during endoscopy and endothelial ZO-1 expression was assessed by immunohistochemistry using the indirect streptavidin biotin peroxidase method. Mucosal vascular density was evaluated by counting the number of mucosal vessels per x20 optical field. Serum lipopolysaccharide-binding protein (LBP) levels were measured by ELISA.

Results

Thirty-four patients (54%) had compensated and 29(46%) had decompensated cirrhosis. Child-Turcotte-Pugh (CTP) classification was: A 46 (73%)/B 14 (22%)/ C 3 (5%). The mean MELD score was 10.5±3.7. Mean LBP levels were 7511.97±2868.90 μg/ml. The mean number of mucosal vessels per x20 optical field did not differ between cirrhotic patients and controls (3.7±1.1 vs 3.2±0.9, p=0.238) but patients with CTP-A class had increased number of mucosal vessels compared to controls (3.8±1.1 vs 3.2±0.9, p=0.048) and CTP-B class patients (3.8±1.1 vs 3.2±0.7, p=0.045). A negative correlation was observed between the number of mucosal vessels and CTP score (r: -0.428, p=0.016). In cirrhotic patients, ZO-1 immunostaining was detected in the whole perimeter of all counted vessels per optical field in only 10/63 (16.4%) samples. Loss of endothelial ZO-1 immunostaining in more than 50% of the vessel perimeter or total loss of ZO-1 in more than 50% of counted vessels was observed more frequently in cirrhotic patient samples (42/63, 66.6%) compared to controls (1/9, 11.1%, p=0.001). Mean (±SD) LBP levels were numerically, albeit not significantly, higher in patients with than without significant loss of ZO-1 endothelial expression (7801±3698 vs 6761±1032 μg/ml, p=0.342).

Conclusion

Cirrhotic patients show increased loss of small intestinal endothelial ZO-1 expression compared to control patients. Intestinal mucosal vessel number is increased in CTP-A patients compared to control and CTP-B patients. These findings are in agreement with novel theories proposing that mechanisms leading to bacterial translocation in cirrhosis are not confined to the small intestinal lumen and merit further investigation.

Introduction

Stereotactic Body Radiation Therapy (SBRT) has proven to be a safe and effective therapy for patients with deep abdominal malignancies who are ineligible/suboptimal candidates for surgery^1,2. SBRT’s effectiveness is dependent on precise targeting, achieved through both bone imaging and implantation of small markers (fiducials) that are visible during imaging which delineate margins of the target lesion³. Fusion of computed tomography (CT) and magnetic resonance imaging (MRI) can provide enhanced soft tissue contrast and improved delineation of the tumor⁴, and is the preferred choice at our institution. Fiducials have traditionally been made of gold due to its bioinertness and visibility on CT imaging, however gold is not accurately detected on MRI⁵. Platinum fiducials have recently emerged as an attractive alternative⁵, considering their improved detectability on MRI imaging. Endoscopic ultrasound (EUS)-guided implantation techniques have largely supplanted percutaneous methods for deep abdominal targeting, due to improved access and visualization⁶.

Aims & Methods

The objective of this case series was to describe our novel platinum seed (PS) fiducials developed in house for EUS-guided fiducial SBRT application. We reviewed the adequacy of fiducial placement, quality of pre-treatment imaging, and migration rates of our fiducials.This single-center case series included patients diagnosed with cancers of the abdomen, including pancreas, adrenal, and liver, who were scheduled to undergo SBRT requiring EUS-guided fiducial implantation between January 2011-February2024. The cohort was derived from a prospectively collected EUS database at The Ottawa Hospital in Ottawa, Canada. Patient demographics (sex and age), procedure details (tumor site, number of fiducials implanted, complications), and radiologist’s interpretation of MRI/CT imaging were assessed using hospital records. Approximately 70% of patients received antibiotics ((either IV x 1 does or oral antibiotics for 5 days post-procedure (eg. Ciprofloxacin, 500mg)). Our PS fiducials are made from 0.75mm wire cut into 3mm seeds which are then autoclaved in-house. Fiducials were implanted using a 19g FNA needle and advanced using an ERCP guidewire using EUS and fluoroscopic guidance.

Results

55 patients underwent EUS implantation for a total of 176 fiducials. Preplanning CT/MRI imaging identified 166/176 (94.3%) fiducial signal voids. When evaluating fiducial placement adequacy, 52 of 55 (94.5%) patients had adequate placement for SBRT. Two patients required a repeat procedure with additional fiducial implantation. One case was due to suspected migration, and the second case was due to fiducials being placed too closely preventing adequate delineation. In a third case, no signal voids were visualized for an unknown reason, however, no repeat procedure was required as spine tracking was used. None of the patients developed post-procedure infection or other adverse events (AEs) in this case series (follow up at 1 month). Cost analysis revealed the fiducials made in-house were ~20-fold less expensive compared to commercially available solid gold, gold coil, or solid platinum fiducials.

Conclusion

Our platinum seed fiducials made in-house appear to have similar adequacy and no increased risk of AEs for EUS-implantation when compared to commercially available fiducials^7,8. For centres using fused CT-MRI imaging for SBRT planning, PS fiducials are recommended. Moreover, significant cost-saving can be achieved through in-house production.

References

1. Rwigema JM, et al. Stereotactic body radiation therapy for abdominal and pelvic oligometastases: Dosimetric targets for safe and effective local control. Pract Radiat Oncol. 2015;5(3):e183-e191.
2. Almaghrabi MY, et al. Stereotactic body radiation therapy for abdominal oligometastases: a biological and clinical review. Radiat Oncol. Aug 01 2012;7:126. doi:10.1186/1748-717X-7-126
3. Moskalenko M, et al. Fiducial Markers Allow Accurate and Reproducible Delivery of Liver Stereotactic Body Radiation Therapy. Curr Oncol. May 16 2023;30(5):5054-5061.
4. Bryant JM, et al. Stereotactic Magnetic Resonance-Guided Adaptive and Non-Adaptive Radiotherapy on Combination MR-Linear Accelerators: Current Practice and Future Directions. Cancers (Basel). Mar 30 2023;15(7).
5. Nair VJ, et al. Feasibility, detectability and clinical experience with platinum fiducial seeds for MRI/CT fusion and real-time tumor tracking during CyberKnife. J Radiosurg SBRT. 2015;3(4):315-323.
6. Pishvaian AC, et al. EUS-guided fiducial placement for CyberKnife radiotherapy of mediastinal and abdominal malignancies. Gastrointest Endosc. Sep 2006;64(3):412-7.
7. Choi JH, et al. Fiducial placement for stereotactic body radiation therapy under only endoscopic ultrasonography guidance in pancreatic and hepatic malignancy: practical feasibility and safety. Gut Liver. 2014;8(1):88-93.
8. Kataki K, et al. Prospective Evaluation Fiducial Migration after Placement for Liver SBRT and Influence on Treatment Delivery. International Journ of Rad Onc. 2019;105(1):E222.

Introduction

Inflammatory bowel disease (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation of the intestines. This is accompanied by oxidative stress, which plays an important role in the pathophysiology of IBD. Oxidative stress-related biomarkers can serve as potential biomarkers for disease activity monitoring. Systemic free thiols (FT) are found to accurately reflect oxidative stress brought on by inflammation and have shown promise as a biomarker for inflammatory disease activity in IBD. However, the clinical significance of this marker warrants validation. This prospective diagnostic study aimed to compare FT to other validated biomarkers and investigate the link between FT and endoscopic disease activity in patients with IBD.

Aims & Methods

An interim analysis was conducted in 52 patients. FT were measured using a colorimetric detection method. Clinical disease activity was quantified by the Harvey-Bradshaw Index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC. Biochemical disease activity was determined by measuring blood C-reactive protein [CRP] and fecal calprotectin [fCal] levels. Endoscopic disease activity was quantified with the Mayo endoscopic sub score for UC and the Simple Endoscopic Score (SES-CD) for CD. Serum FT levels were assessed for correlations with disease activity parameters using linear and logistic regression analyses. Discriminative capacity of FT as biomarker was assessed by calculating receiver operating characteristics (ROC) statistics.

Results

Serum FT levels demonstrated a significant inverse correlation with clinical parameters, such as the HBI (r=-0.53, p<0.05). Additionally, other inflammatory biomarkers, including CRP, exhibited a negative correlation with serum FT levels (r=-0.43, p<0.05), which were decreased in patients with active IBD . Discrimination between clinically quiescent (HBI<5) and active disease based on serum FT levels was accurate (AUC=0.80, p=0.02) with a value numerically higher than that of fCal (AUC=0.55, p=0.83). Serum FT levels did not significantly differ between biochemically quiescent and active disease based on CRP (AUC=0.69, p=0.20). Both endoscopic scores demonstrated a tendency toward negative associations with serum FT levels. Patients with moderate and severe disease activity had lower FT levels compared to those with mild disease activity (estimated marginal means [EMM] 497.2 vs 529.5 µM, p=0.43) and 447.1 vs 529.5µM , p=0.06, respectively).

Conclusion

The interim analysis of this study indicates that plasma FT levels inversely correlate with IBD activity and may surpass traditional markers like fCal in detecting disease states. Plasma FT demonstrates potential as a sensitive biomarker for both clinical and endoscopic disease activity in IBD. Further patient inclusion and longitudinal data are essential to validate FT's utility fully. Continued research could establish FT as a key tool for personalized treatment strategies, improving patient outcomes in IBD management.

Disclosure

S. Geertsema, A.R. Bourgonje., H. van Goor, G. Dijkstra, and K.N. Faber are supported by a research grant from Janssen Research & Development LLC. A.R. Bourgonje received speaker fees from AbbVie. G. Dijkstra received research grants from Royal DSM, Takeda, and Janssen Pharmaceuticals and speaker fees from AbbVie, Pfizer, Takeda, and Janssen Pharmaceuticals.

Introduction

Among patients with celiac disease (CeD), following a gluten-free diet after diagnosis is expected to reduce symptom burden. Using a large US claims database, we compared symptoms in individuals with CeD pre- and post-diagnosis with those in matched individuals without CeD to evaluate the burden of CeD.

Aims & Methods

This case-control study was conducted among individuals of all ages enrolled in MarketScan from 2002 to 2023. CeD diagnosis (index date) was defined as ≥1 inpatient or ≥2 outpatient International Classification of Diseases (ICD)-9/-10 diagnostic codes; controls were matched (1:5 ratio) for age, sex, region, and diagnosis year. All individuals had continuous medical and pharmacy enrolment for 2 years pre- and post-index. Core CeD symptoms (abdominal pain, diarrhoea, joint pain, bloating, fatigue, and nausea) were defined as ≥1 inpatient or ≥2 outpatient ICD-9/-10 codes during each 2-year period. Unadjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression comparing CeD cases versus controls.

Results

During the 21 years of data coverage, we identified 39 814 patients with CeD and 198 961 matched individuals without CeD with similar age and sex distribution (mean age 41.6 years [standard deviation 20.1]; 70.5% female). The burden of CeD symptoms pre-diagnosis was significantly higher among patients with CeD versus controls, particularly for diarrhoea, bloating, and abdominal pain. The pre-diagnosis OR (95% CI) for abdominal pain was 5.37 (5.22, 5.52), joint pain 1.87 (1.81, 1.93), diarrhoea 11.64 (11.10, 12.20), bloating 8.64 (7.86, 9.51), fatigue 3.63 (3.48, 3.79), and nausea 5.78 (5.36, 6.24). As expected, symptom burden decreased post-diagnosis, however all symptoms (except joint pain) had an approximately twofold greater burden compared with controls, 2 years post-diagnosis: OR (95% CI) abdominal pain 2.43 (2.57, 2.30), joint pain 1.61 (1.51, 1.71), diarrhoea 2.47 (2.21, 2.76), bloating 2.47 (1.86, 3.27), fatigue 2.17 (1.98, 2.38), and nausea 2.24 (1.83, 2.74). When we evaluated symptoms only among individuals with CeD, on average symptom persistence 2 years after diagnosis occurred in 29.7% of patients while an average of 6.3% had new-onset symptoms (most commonly abdominal pain; 17.0%).

Conclusion

Claims databases were able to capture CeD symptom burden and demonstrated that patients with CeD continue to experience symptoms (including new-onset) post-diagnosis. Although a gluten-free diet might control some symptoms, there is still considerable remaining burden and some unresolved symptoms (e.g. joint pain and fatigue) or new-onset symptoms.

Disclosure

MA, SM, VG, SG, RS, DAL, IP, and NC are employees and shareholders of Takeda. BL has nothing to disclose. FZ served as a speaker for Werfen and a consultant for Takeda.