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

In recent years, evidence shows that long non-coding RNAs (lncRNAs) are key regulators of gene transcription and play important roles in the pathogenesis of inflammatory bowel diseases. LncRNAs are involved in the regulation of intestinal epithelial cell apoptosis, cell-cell interactions, and enhancing inflammation, among others. Biological therapies, which are considered the most potent for disease control, only benefit one-third of patients. For this reason, a deeper understanding of the mechanisms by which biological drugs elicit their effect on intestinal mucosal is needed. Hence, we aimed to unravel the ex vivo modulator effect of infliximab on the lncRNAs expression in intestinal biopsies from patients with Crohn´s Disease (CD).

Aims & Methods

We performed an unbiased transcriptomic analysis of intestinal biopsies from the ileum and colon from 30 patients [active CD = 10, quiescent CD = 10, healthy controls (HC) = 10] to identify lncRNA differentially expressed in the setting of infliximab modulation. Endoscopic biopsies were cultured with or without infliximab and the transcriptome was determined by Illumina gene expression array. We used different databases (Ensembl Biomart, RNAcentral and ToppGene) to search for non-annotated lncRNA information and data on the location (cellular component), biological process and molecular function of differentially expressed lncRNAs.

Results

Transcriptomic results revealed a widespread dysregulation of lncRNAs in ileum biopsies from patients with active CD, quiescent CD and HC compared to the colon at baseline and after infliximab culture. These differentially expressed lncRNAs were enriched in such pathways as proliferation, apoptosis, migration, inflammatory response of fibroblasts, response to wounding, posttranscriptional regulation of inflammatory genes and activation of the mitogen-activated protein kinase signaling pathways. Regarding the effect of infliximab according to intestinal location, presence of disease and activity, no significant lncRNAs were identified in the different study comparatives.

Conclusion

We have characterized the basal transcriptomic landscape of lncRNAs in patients with CD (active and quiescent) and HC both in ileum and left colon. However, we have not found differential lncRNA expression due to the effect of infliximab, suggesting that the location (ileum or colon) is more relevant when analyzing differences in lncRNA expression in the intestinal tissue.

Introduction

In Crohn’s disease (CD) a symptomatic luminal stricture occurs in up to 20% of patients at the diagnosis and in more than 50% during lifetime (1,2). Endoscopic balloon dilatation (EBD) or surgical procedures are the currently available treatments (3,4). However, a considerable percentage of patients often require further surgery for post-operative CD recurrence (5). A consequent increased burden of short bowel syndrome is warranted. The combination of biological therapy with EBD could potentially reduce this risk.

Aims & Methods

The aim of our study was to evaluate the efficacy of EBD combined with biologic therapy in symptomatic gastrointestinal strictures in CD’s patients. We conducted a retrospective study including consecutive CD patients who underwent EBD for low bowel strictures from December 2015 until November 2022 at our tertiary IBD Center. Clinical strictures recurrence, needs for steroids and for surgery due to CD stenosis relapse were the primary outcomes evaluated during a follow-up period of six and twelve months. Chi-square and univariate statistical analyses were used when appropriate.

Results

A total of 52 patients treated with EBD with an overall number of 55 strictures were included. In the study population, 14 patients (27%) were smoker, the mean age was of 46,8 (18-77) years; the median of disease duration was 9 (0-42) years. Thirty-nine patients (75%) were in active treatment with biologic therapy at the moment of EBD. Twenty-three patients (44%) underwent EBD for anastomotic stricture, 8 (15%) for ileal stricture, 11 (21%) for ileocecal valve stricture, 5 (6%) for anal stricture and 4 (8%) for colic stricture. Three patients (6%) underwent EBD for multifocal bowel stenosis. Twenty-two (42%) patients had increased CRP value, 40 patients (77%) had evidence of moderate or severe endoscopic disease activity and 42 (81%) patients showed ulcerative lesions at stricture site. EBD was performed by 8-10, 12-15 or 15-18 mm dilation balloon. Technical success was reported in 60% of procedures and no adverse events were registered.
After 6 months from EBD, at univariate analysis, active smoke resulted a risk factor for clinical stricture recurrence (OR 10,25; IC 1,350 to 135,4; p value = 0,022) and for subsequent surgery (OR 10,25; IC 1,350 to 135,4; p value = 0,022). Moreover, increased CRP at the time of dilatation resulted a risk factor for need of steroids (OR 14,63; IC 2,69 to 71,50; p value = 0,0006). Concomitant biologic therapy and presence of ulcerative lesions did not show significative correlation with considered outcomes.
After 12 months from EBD, concomitant biologic therapy resulted a protective factor for prevention of surgery (OR 0,061; IC 0,005 to 0,502; p value = 0,0047), while anastomotic strictures were associated with a lower risk of sub-occlusion events than ileal stenosis (OR 0,07; IC 0,005 to 0,651; p value = 0,015). Increased CRP at the time of EBD, ulcerative lesions at the stricture site and active smoke were not significantly correlated with the considered outcome.

Conclusion

Our results suggest that in patients with CD undergoing EBD for bowel CD stricture, concomitant biological therapy reduces the risk of surgery for CD stenosis recurrence. Further prospective and controlled studies are underway to confirm these observations.

References

1. Rieder F Managing Intestinal Fibrosis in Patients With Inflammatory Bowel Disease. Gastroenterology & hepatology. 2018. February; 14(2):120–122
2. Yoo JH, Holubar S, Rieder F. Fibrostenotic strictures in Crohn’s disease. Intest Res. 2020;0.
3. Paine E, Shen B. Endoscopic therapy in inflammatory bowel diseases (with videos). Gastrointest Endosc 2013;78:819–35.
4. Hassan C, Zullo A, De Francesco V, Ierardi E, Giustini M, Pitidis A, Taggi F, Winn S, Morini S. Systematic review:
Endoscopic dilatation in Crohn's disease. Aliment Pharmacol Ther. 2007 Dec;26(11-12):1457-64
5. Olaison G, Smedh K, Sjödahl R. Natural course of Crohn’s disease after ileocolic resection: endoscopically visualised ileal ulcers preceding symptoms. Gut 1992;33:331–5.

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.