Introduction

Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) has been widely used for the diagnosis of solid pancreatic lesion. Studies have shown that the wet suction technique in EUS-FNA generates better histologic diagnostic accuracy and specimen quality than the dry suction technique. However, conclusions of wet suction on the diagnostic accuracy of EUS-FNB are still controversial. Besides, the optimal number of passes for EUS-FNB has not been determined. We aimed to design a multicenter randomized trial to compare the diagnostic accuracy of dry suction versus wet suction technique in solid pancreatic lesions using 22G Franseen needles and determine the optimal number of passes required for EUS-FNB without onsite cytopathologist.

Aims & Methods

This is a multi-center, open-label, randomized controlled and non-inferiority trial with two parallel groups. The patients with solid pancreatic lesion will undergo EUS-FNB using 22G Franseen needle in 4 tertiary hospitals in China and will be randomly assigned to the dry suction group and wet suction group in a ratio of 1:1. The primary endpoint of this study is to compare the diagnostic accuracy of EUS-FNB for solid pancreatic lesions using the dry or wet suction technique. Secondary endpoints include the optimal number of needle passes, sensitivity, specificity, specimen quality, time of the procedure, and rates of complications.

Results

Of the 195 patients undergoing EUS-FNB enrolled in the final analysis, 96 were randomized to the dry suction group and 99 to the wet suction group. The diagnostic accuracy was 98.95% and 98.98% in the dry and wet groups, respectively, with a 0.05% difference in accuracy between the study groups (two-sided 90% CI, -4.88% to 4.82%, P=0.989). Diagnostic accuracy was shown to be non-inferior because the lower bound of the 90% confidence interval falls to the right of the non-inferiority margin. Compared to the wet group, no significant differences were seen in the sensitivity (98.80 % vs 98.77 %, P = 1) and specificity (100 % vs 100 %, P = 1) in the dry suction group. The overall adverse event rate was 0.52 %, with 0 and 1.02 % in the dry and wet groups, respectively (P = 1). In terms of specimen quality, no significant differences were also seen in the two groups in sample adequacy (100 % vs 98.3 %, P = 0.492) and level of blood contamination (P = 0.319). In terms of puncture time in the dry group compared to the wet group, there was no statistically significant (18.82±8.21 min vs. 18.92±8.99 min, P=0.952), but the wet suction required more time to prepare the saline and the needle. No significant improvement in diagnostic accuracy was seen with the 2nd needle compared to the 1st needle of EUS-FNB (97.41% vs 95.34%，P=0.276), and no significant improvement in diagnostic accuracy was seen with the 3rd shot compared to the 2nd shot of EUS-FNB (98.96% vs 97.41%，P=0.446).

Conclusion

The dry suction technique is non-inferior to the wet suction technique, while saving steps and time. In the absence of rapid on-site evaluation (ROSE), only 1 pass was required to reach the diagnositic accuracy≥ 95% using EUS-FNB with Franseen needle.

Disclosure

The authors disclose no conflicts.

Introduction

Uncontrolled sepsis following leak from major oesophago-gastric surgery is a devastating condition with increased morbidity and mortality and intensive care stay. We hypothesised that endoluminal vacuum therapy (EVT) could be used in the prophylactic setting to provide source-control, prevent mediastinitis and minimise sepsis related morbidity from leaks.

Aims & Methods

An ad-hoc EVT device was created using VAC granufoam (KCI) and a nasogastric-tube (16/18Fr), and placed intraluminally across the high risk anastomosis/area of repair. Continuous negative pressure (75–125mmHg) was applied. Assessment of the repair site/anastomosis was performed by radiology, endoscopy, clinical assessment or a combination following cessation of EVT and removal of the prophylactic EVT device.

Results

Twenty-seven patients had prophylactic EVT; M:F ratio was 3:1 and the median age was 68 years (range: 41-82 years). Twenty-six patients had cancer resections while 1 had benign surgery. The rationale for prophylactic EVT included preoperative factors (10), intra-operative factors (16) or both (1). The median duration of prophylactic EVT was 7 days (range: 4-14 days). The median length of stay was 19.7 days (range: 6-96 days), the two longest admissions were unrelated to the anastomosis (prolonged chyle leak, and long-term-sequelae of life-threatening bleed). One patient developed full-thickness microleak at endoscopic evaluation, remained clinically well with no systemic signs of sepsis, and was successfully managed with luminal EVT for a further 6 days in a ward-based environment. Though prophylactic EVT did not prevent the leak, it significantly minimised the systemic hit that traditionally results from leak and associated mediastinal sepsis.

Conclusion

Prophylactic EVT is a useful adjunct for management of patients with a high-risk for leak and can serve as a risk reducing strategy in select cases. There are no short-term complications, yet the additional morbidity, mortality, and length of stay associated with a fully-fledged leak is avoided. Our results lay the foundation for the use of prophylactic EVT in randomised controlled trials to further standardise selection criteria, assess longer term potential patient benefit and impact on survivorship.

References

1. Pournaras DJ, Hardwick RH, Safranek PM, Sujendran V, Bennett J, Macaulay GD, Hindmarsh A. Endoluminal vacuum therapy (E-Vac): a treatment option in oesophagogastric surgery. World journal of surgery. 2018 Aug;42:2507-11.
2. Afzal Z, Gourgiotis S, Hardwick R, Safranek P, Sujendran V, Bennett J, O'Neill R, Noorani A, Hindmarsh A. O-EGS08 Endoluminal Vacuum Therapy (EVT) for leaks in the upper gastrointestinal (UGI) tract; 10-years’ experience in a specialist Oesphagogastric centre. British Journal of Surgery. 2021 Dec 1;108(Supplement_9):znab429-022.
3. Müller PC, Morell B, Vetter D, Raptis DA, Kapp JR, Gubler C, Gutschow CA. Preemptive endoluminal vacuum therapy to reduce morbidity after minimally invasive Ivor Lewis esophagectomy: including a novel grading system for postoperative endoscopic assessment of GI-anastomoses. Annals of Surgery. 2021 Nov 1;274(5):751-7.

Introduction

The need for endoscopic necrosectomy (EN) has increased dramatically, as endoscopic EUS-guided drainage has become gold standard for treatment of pancreatic walled-off-necrosis (WON)[1,2]. Although snares and baskets are commonly used in EN procedures, they can be ineffective and dedicated instruments specifically designed for EN are scarce. Recently, an innovative powered endoscopic debridement system (EndoRotor, Interscope Inc., Northbridge, MA, USA) designed to excise and remove necrotic tissue within the WON was introduced specifically for EN with promising results[3,4]. While the first generation EndoRotor catheter was limited to 3.2 mm diameter, a larger catheter that fits into a large-channel gastroscope with a working channel of 6.0 mm has now been introduced. This study evaluates the clinical outcomes, safety, and feasibility of the novel 6.0 catheter for EN of WON.

Aims & Methods

This retrospective study was performed using prospectively collected data from all patients who underwent EN with the 6.0 catheter between December 2021 and March 2023 at Gastro Unit, Copenhagen University Hospital Hvidovre, a tertiary referral center in Denmark. All patients with symptomatic WON and need for necrosectomy were considered eligible for this study. Technical feasibility, safety, and clinical outcomes were evaluated.

Results

Sixteen patients underwent a total of 25 EN procedures with the 6.0 catheter. The mean age of the patients was 51.8 years (SD 17.7 years) and 11 (68.8%) were male. The etiology of the acute necrotizing pancreatitis was alcohol in 4 patients (25.0%), gall stones in 7 patients (43.8%), post-endoscopic retrograde cholangiopancreatography (ERCP) in 3 patients (18.8%), and idiopathic in 2 patients (12.5%). The mean size of the WON was 27.5 cm (SD 10.5 cm). The median computed tomography severity index (CTSI) was 8.5 (P25-P75: 6.0-9.0) and median modified CTSI (mCTSI) was 9.0 (P25-P75: 8.0-10). Two patients did not achieve clinical resolution (12.5%), as they died from multisystem organ failure before resolution of the WON was achieved. The median length of stay in hospital for the patients who achieved clinical resolution was 56.0 days (P25-P75: 36.5-96.0 days) and the median number of necrosectomy procedures performed to achieve clinical resolution was 5.0 (P25-P75: 2.0-8.5). All patients had EN procedures performed with snares in addition to the procedures with the powered debridement system. Five patients had necrosectomy performed with the 3.2 catheter (31.0%) as well as the 6.0 catheter. The median duration of EN with the 6.0 catheter was 60.0 minutes (P25-P75: 45.0-100 minutes) per procedure.
A device-related adverse event was noted in one instance (4.0%). The patient exhibited symptoms of peritoneal reaction in the hours following the procedure, which may have been caused by perforation of the WON into the peritoneal cavity. The patient was treated with laparoscopic peritoneal lavage and drainage and recovered without further interventions. No other procedure-related adverse events were identified. Malfunction of the catheter was observed in 7 procedures (28.0%).

Conclusion

To perform necrosectomy procedures optimally, dedicated endoscopic instruments designed for debridement of pancreatic WON are required. This study suggests that EN with the novel EndoRotor 6.0 catheter is safe and feasible with promising clinical results for EN of pancreatic WON. To assess the efficacy relative to standard techniques, comparative studies are warranted.

References

[1] Karstensen JG, Novovic S, Hansen EF, et al. EUS-guided drainage of large walled-off pancreatic necroses using plastic versus lumen-apposing metal stents: A single-centre randomised controlled trial. Gut 2022; 0: 1–7. doi:10.1136/gutjnl-2022-328225
[2] Ebrahim M, Werge MP, Hadi A, et al. Clinical outcomes following endoscopic or video-assisted retroperitoneal management of acute pancreatitis with large (>15 cm) walled-off pancreatic necrosis: Retrospective, single tertiary center cohort study. Dig Endosc 2022; 34: 1245–1252. doi:10.1111/den.14295
[3] Stassen PMC, de Jonge PJF, Bruno MJ, et al. Safety and efficacy of a novel resection system for direct endoscopic necrosectomy of walled-off pancreas necrosis: a prospective, international, multicenter trial. Gastrointest Endosc 2022; 95: 471–479. doi:10.1016/J.GIE.2021.09.025
[4] Wiel SE van der, May A, Poley JW, et al. Preliminary report on the safety and utility of a novel automated mechanical endoscopic tissue resection tool for endoscopic necrosectomy: a case series. Endosc Int Open 2020; 08: E274–E280. doi:10.1055/A-1079-5015

Introduction

There is an increasing incidence of young-onset colorectal cancer (YOCRC), which is defined as patients with colorectal cancer at age 50 years and younger. They present with a distinct clinical phenotype compared to classical-onset CRC (COCRC), with a more aggressive disease at presentation, as well as different tumour location and mutational signatures. There is an unmet clinical need to elucidate the unexplained epidemiologic rise in incidence as well as disease pathogenesis of YOCRC.

Aims & Methods

Aim: To compare the clinical presentation, tumour characteristics and survival of young-onset versus classical-onset CRC.

A retrospective evaluation of patients diagnosed with colorectal cancer from 2019 to 2022 at a district general hospital was performed. We extracted data from electronic patient records for clinical, biochemical, radiological as well as histopathological reports. Comparisons were made between patients diagnosed at </=50 years (YOCRC) and >50 years of age (COCRC) respectively, and statistical analyses were performed. A p-value of <0.05 was considered statistically significant.

Results

34 (11.1%) and 273 (88.9%) patients were diagnosed as YOCRC and COCRC respectively. There was a difference in clinical presentation between the two groups, with haematochezia (n=12, 35.3%) (p=0.03) and change in bowel habit (n=7, 20.6%) predominating in the YOCRC group, versus positive faecal immunochemical test (FIT) (n=102, 37.4%) and anaemia (n=78, 28.6%) in the COCRC group respectively. There were no differences in the tumour location between groups, with >50% of cases arising from the left colon (22 YOCRC versus 149 COCRC). Thrombocytosis (platelet count>450x10⁹/L) (24% vs 11%, p=0.038) and tumour budding (12% vs 3%, p=0.006) were significantly increased in the YOCRC group. There were no significant differences in the histological subtype, TNM staging, mutational profiling and survival between groups. 6 (17.6%) YOCRC patients had died compared to 116 (37.8%) in the COCRC cohort over a median follow-up of 16 months.

Conclusion

Young-onset colorectal cancer represents a challenging subset of CRC, which has a different clinical and tumour phenotype to classical-onset CRC. Our study reflects the reported incidence rates of YOCRC of 11%, although the true epidemiology and frequency of YOCRC remains to be clarified. Haematochezia was the commonest presentation, while thrombocytosis and tumour budding were higher in the YOCRC group, suggesting a more advanced disease at diagnosis. Although the overall survival rates were similar between groups, further research would benefit from larger prospective studies with subdivision of YOCRC cases by age as poorer survival have been suggested in patients aged <30 years. There is a need to elucidate the respective aetiologies, environmental risk factors and pathogenesis of YOCRC, to allow early targeted treatment of such cases.

Table 1: Clinical presentation of YOCRC and COCRC

References

Mauri G, Sartore-Bianchi A, Russo AG, Marsoni S, Bardelli A, Siena S. Early-onset colorectal cancer in young individuals. Mol Oncol. 2019;13(2):109-131.

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

Potential therapeutic effects of natural compounds, such as grape polyphenols, have been suggested in the prevention and treatment of mucositis induced by radiotherapy or bacterial infections. Lipopolysaccharide (LPS) significantly increases the paracellular permeability of gut epithelium downregulating the expression of tight junctions. In this study, the protective effect of proanthocyanidin-rich grape seed extract (GSE) was investigated on epithelial barrier damage and ROS production induced by LPS and ionizing radiations in an in vitro model.

Aims & Methods

GSE chemical analysis was performed by high-performance liquid chromatography (HPLC-DAD) and nuclear magnetic resonance (NMR).
Human intestinal epithelial cell line Caco-2, previously treated with LPS [10 µg/m] (pathogenic strain of Escherichia Coli 0111:B4) [1], GSE [6,25 mg/ml] and LPS + GSE, were irradiated with 10 Gy subdivided in 5 daily fractions using TrueBeam™ radiotherapy system by Varian Medical System. Epithelial barrier integrity was investigated measuring the paracellular flux of fluorescein isothiocyanate-dextran (FD-4) [1] and ROS production was assessed by adding 2′,7′-dichlorodihydrofluorescein diacetate (H2-DCF-DA) [3] using a multiplate reader (Tecan). Each experiment was performed twice in triplicates with independent controls among the three conditions.

Results

HPLC-DAD and NMR revealed a 70% content of total procyanidins in both the extract obtained from the virgin hydroalcoholic mixture and quantify 24 metabolites classified as amino acids, organic acids, classified as amino acids, organic acids, carbohydrates and miscellaneous molecules. Among them, it is interesting the presence of ascorbate, procyanidin B1 and polymeric procyanidins.
Our in vitro experiments showed a significant increased permeability was observed in LPS-treated cells over time compared to control (5.215 vs 0.3418; p<0.05), which is prevented by co-treatment with GSE (5.215 vs 0.3407; p<0.05). Irradiation significantly increased intestinal permeability over time and in a dose dependent manner compared to control both in Caco2 cells without LPS treatment (at day 5 with maximal dose of 10 Gy: 3.64 vs 0.441; p<0.05) and in LPS-treated cells (25.5 vs 2.42; p<0.05). GSE treatment significantly reduced this damage in both conditions (25.5 vs 2.04; p<0.05 and 38.87 vs 2.675; p<0.05 respectively). Moreover, LPS significantly increased ROS production in Caco2 cells (12,9 vs 104; p<0.0001) and GSE treatment significantly prevented this damage (104 vs 11.3; p<0.0001). Irradiation increased ROS production in LPS-treated cells (3056 vs 362; p<0.0001) and also in this case GSE treatment was able to reduce ROS production due to irradiation (502 vs 357; p<0.0001). this beneficial effect was observed also in LPS treated cells and then exposed to irradiation (3056 vs 681; p<0.0001).

Conclusion

In an in vitro model, GSE is able to prevent the intestinal epithelium permeability damage and ROS production induced by LPS and by ionizing radiations suggesting a potential therapeutic effect. Further studies are needed to better understand the mechanism underlying radiation-induced mucositis and the antioxidant effect of GSE in its prevention and management.

References

[1] Gori M, Altomare A, Cocca S, Solida E, Ribolsi M, Carotti S, Rainer A, Francesconi M, Morini S, Cicala M, Guarino MPL. Palmitic Acid Affects Intestinal Epithelial Barrier Integrity and Permeability In Vitro. Antioxidants (Basel). 2020 May 13;9(5):417
[2] Calabriso N, Massaro M, Scoditti E, Verri T, Barca A, Gerardi C, Giovinazzo G, Carluccio MA. Grape Pomace Extract Attenuates Inflammatory Response in Intestinal Epithelial and Endothelial Cells: Potential Health-Promoting Properties in Bowel Inflammation. Nutrients. 2022 Mar 11;14(6):1175

Introduction

Upper gastrointestinal bleeding (UGIB) is associated with an unfavorable prognosis in cancer patients. In biliary tract cancers (BTCs), little is known about the occurrence of UGIB and its prognostic relevance for the course of the disease.

Aims & Methods

The aim of this study was to analyze the prevalence of UGIB in BTC patients, compare therapeutic approaches for efficacy, and identify parameters associated with survival and recurrence rates. This retrospective observational study included all patients with BTCs and UGIB, that were treated in our tertiary care hospital between 2010 and 2023.

Results

A total of 1033 patients with BTC were analyzed. 41 (4.0%) of these patients had a total of 60 bleeding events. At the time of the bleeding event, 30.8% of patients displayed symptoms of shock, and 67.5% received red blood cell transfusions. The most common causes of bleeding were tumor infiltration (24.4%), variceal bleeding (19.5%), or ulcer bleeding (14.6%). At the time of presentation, 56.4% of patients had stage IV cancer. Most patients had perihilar (39.0%) or intrahepatic (34.1%) cholangiocarcinoma. At index bleeding, endoscopic treatment was performed in 41,5% of cases, while conservative measures (53,7%) or interventional radiological procedures (4.9%) were used in the remaining cases. In cases of bleeding caused by tumor infiltration, endoscopic hemostasis was usually performed using hemostatic powder (18.8%) or clip application (12.5%). Admission to an intermediate or intensive care unit (odds ratio 6.7; 95% CI 1.5 – 33.9) as well as symptoms of shock at the time of the bleeding event (odds ratio 2.6; 95% CI 0.5 – 15.6) were risk factors of rebleeding within 14 days. In patients with UGIB due to tumor infiltration, bleeding recurred after endoscopic therapy in 33.3% of cases. With conservative therapy, the recurrence rate was 28.6%. Survival of Patients with UGIB due to tumor infiltration was significantly shorter compared with patients having non-tumor-associated UGIB (median survival 0.93 vs. 6.5 months, log-rank test p = 0.018).

Conclusion

UGIB is a rare but serious complication in patients with BTC. Patients with major bleeding episodes should be closely monitored for short-term rebleeding. The occurrence of UGIB due to tumor infiltration is associated with adverse outcomes and significantly shortened survival time.