Introduction

The biliary tree has traditionally been considered sterile under normal conditions¹. Recent evidence has revealed rich microbial communities in the biliary tract of patients affected by biliary tract disorders, supposing that biliary microbiota could play a significant role in the development of several biliary diseases, namely gallstones, autoimmune cholangiopathies, and cancer^2,3.
However, while possible connections between gut micro-organisms and biliary diseases has been studied more extensively, to date few evidences are available on how the microbiological composition may change disease’s progression⁴.
Not least it is still unclear how the modification of Oddi’s sphincter function after endoscopic sphincterotomy performed during an endoscopic retrograde cholangiopancreatography (ERCP) may represent a favorable environment for ascending bacterial colonization^5,6.

Aims & Methods

We performed a prospective observational study aimed to evaluate the prevalence of biliary pathogens of the bile in various disorders and to identify a microbial fingerprint for each disease. 162 consecutive patients with native papilla undergoing to ERCP for any indication were prospectively enrolled from July 2022 to April 2023. One bile sampling was performed after bile duct cannulation, before contrast injection and sphincterotomy, while a second one was done at the end of the procedure. Pre procedural clinical data, bile cultures and clinical follow-up were collected and analyzed.

Results

Biliary culture was obtained in 100% of patients. 52% of bile cultures were positive for at least 1 bacterium. No differences were found in microbial community before and after sphincterotomy. Out of 78 patients with positive bile cultures, 46 (59%) had cholangitis, all of them were under antibiotic therapy. Patients treated with immunomodulant agents did not have an increased risk of positive bile cultures. Multidrug-resistant bacteria were detected in pre-sphincterotomy bile cultures in 9 (5%) patients, of which 7 were extended-spectrum beta-lactamase (ESBL),1 Methicillin-resistant Staphylococcus aureus (MRSA) and 1 Vancomycin-Resistant Enterococci (VRE). No significant correlations were found between the presence of multidrug-resistant bacteria and underlying diseases, systemic cholangitis or immunomodulant exposure.

Conclusion

Our preliminary results showed how the biliary tree in patients with biliary diseases may not be sterile, even when Oddi’ s sphincter is intact. The presence of neoplastic diseases or immunosuppression therapy does not seem to correlate with an increase in positive bile cultures nor in multidrug resistant bacteria. Further analysis may be needed to assess the correlation between bile cultures and long-term outcomes.

References

1. Nicoletti, A. et al. Biliary tract microbiota: A new kid on the block of liver diseases? Eur. Rev. Med. Pharmacol. Sci. 24, 2750–2775 (2020).
2. Pereira, P., Aho, V., Arola, J., Boyd, S. & Jokelainen, K. Bile microbiota in primary sclerosing cholangitis : Impact on disease progression and development of biliary dysplasia. 1–15 (2017).
3. Chen, B., Fu, S. W., Lu, L. & Zhao, H. A preliminary study of biliary microbiota in patients with bile duct stones or distal cholangiocarcinoma. Biomed Res. Int. 2019, (2019).
4. Verdier, J., Luedde, T. & Sellge, G. Biliary Mucosal Barrier and Microbiome. Visz. Gastrointest. Med. Surg. 31, 156–161 (2015).
5. Ye, F. et al. Influence of the Biliary System on Biliary Bacteria Revealed by Bacterial Communities of the Human Biliary and Upper Digestive Tracts. 1–12 (2016). doi:10.1371/journal.pone.0150519
6. Schneider, J. et al. Risk factors for increased antimicrobial resistance : a retrospective analysis of 309 acute cholangitis episodes. 519–525 (2014). doi:10.1093/jac/dkt373

Disclosure

Cecilia Binda: Lecturer for Steris, Fujifilm, Q3 Medical, Boston Scientific
Chiara Coluccio: Lecturer for Steris
Carlo Fabbri: Lecturer for Steris, Q3 Medical, Boston Scientific

Clinical Case Summary

For decompensated advanced chronic liver disease (dACLD) individuals, the onset of refractory ascites (RA) represents a dramatic event (6-month survival rate < 50%). In this setting, a relevant proportion of RA patients develop Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI) with limited therapeutic and survival chances.
An 81-year-old female dACLD RA patient was admitted to our department to receive large-volume paracentesis (LVP). Eradicated HCV infection, type II diabetes, and chronic obstructive pulmonary disease were her comorbidities.
The AKI onset imposed the intravenous (i.v.) human albumin (HA) (1 g/kg/die) administration, followed by the proper dosage of terlipressin (for HRS-AKI) within the first 72 hours (h), subsequently discontinued due to the persistence of anuria and the worsening of respiratory failure.
To simultaneously address uremic symptoms and facilitate ascites drainage, a Tenckhoff catheter was placed, and peritoneal dialysis (PD) started with a single icodextrin dwell, resulting in the removal of 14 L of ascites and an improvement in AKI within the subsequent 72h. After one week, she was discharged, receiving a specific PD schedule. After the readmission due to the difficulties in administering i.v. HA, we proposed administering HA via the intraperitoneal route, creating an HA-enriched PD (PD+HA) home-performable schedule by adding two vials of 100 ml of HA 20% to 800 ml of icodextrin solution (40 g in 1000 ml/die; lasting: 12 hours; frequency: every other day) (Figure 1).
The patient has been performing this PD schedule for 12 months (~0.5 L of ascites is discharged every other day before performing PD+HA dwell). During the follow-up, no PD-related complications (e.g., peritonitis) and liver-related events requiring hospitalization have been observed.
We report the first successful use of PD+HA, highlighting the cruciality of a multidisciplinary (hepatologists-nephrologists) approach in the management of dACLD-RA HRS-AKI patients.

References

1. Moreau, R.; Delègue, P.; Pessione, F.; Hillaire, S.; Durand, F.; Lebrec, D.; Valla, D.-C. Clinical Characteristics and Outcome of Patients with Cirrhosis and Refractory Ascites. Liver Int 2004, 24, 457–464, doi:10.1111/j.1478-3231.2004.0991.x.
2. Moore, K.P.; Wong, F.; Gines, P.; Bernardi, M.; Ochs, A.; Salerno, F.; Angeli, P.; Porayko, M.; Moreau, R.; Garcia-Tsao, G.; et al. The Management of Ascites in Cirrhosis: Report on the Consensus Conference of the International Ascites Club. Hepatology 2003, 38, 258–266, doi:10.1053/jhep.2003.50315.
3. Nadim, M.K.; Kellum, J.A.; Forni, L.; Francoz, C.; Asrani, S.K.; Ostermann, M.; Allegretti, A.S.; Neyra, J.A.; Olson, J.C.; Piano, S.; et al. Acute Kidney Injury in Patients with Cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) Joint Multidisciplinary Consensus Meeting. J Hepatol 2024, 81, 163–183, doi:10.1016/j.jhep.2024.03.031
4. Brown, E.A.; Blake, P.G.; Boudville, N.; Davies, S.; de Arteaga, J.; Dong, J.; Finkelstein, F.; Foo, M.; Hurst, H.; Johnson, D.W.; et al. International Society for Peritoneal Dialysis Practice Recommendations: Prescribing High-Quality Goal-Directed Peritoneal Dialysis. Perit Dial Int 2020, 40, 244–253, doi:10.1177/0896860819895364.

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

Complete excision of upper gastrointestinal sub-epithelial lesions (SELs) eliminates diagnostic uncertainty, obviates the need for surveillance and may be necessary for definitive diagnosis and management. Current guidelines lack precision and cohesion, and surgery is associated with significant morbidity. Herein, we describe and report on the outcomes of our SEL algorithm for endoscopic (SAFE) resection.

Aims & Methods

SELs were enrolled prospectively over 115 months until March 2023. All underwent axial (CT) imaging and endoscopic-ultrasonography (EUS) to exclude a large exophytic component or invasion into local structures, and assess for muscularis propria involvement.

Results

106 SELs were resected (mean age 60.6±13.4, 51.9% male; 41 oesophageal, 65 gastric). Oesophageal SELs underwent ESD (n=22) or STER if MP involvement was suspected (n=19). Gastric SELs underwent STER (n=6 at cardia), ESD (n=47) or exposing-EFTR (n=12). Technical success was 97.6% and 92.3% respectively. Five (7.7%) were completed laparoscopically due to deep and broad full-thickness involvement. Five (7.7%) required laparoscopic gastrotomy and surgical retrieval after successful resection and closure due to a large lesion size (mean 47 mm). There was no delayed bleeding, perforation or recurrence at a median of 13 months.

Conclusion

Upper GI SELs are effectively and safely treated by endoscopic resection. The SAFE approach provides a framework that facilitates structured decision-making. Oesophageal SELs suspected to involve the MP should undergo STER. Gastric SELs can be best managed by ESD with a view to proceed to exposing-EFTR. A laparoscopic UGI surgeon should be available in case surgical retrieval of the specimen or laparoscopic completion is required.

Disclosure

Michael J. Bourke: Research Support: Olympus, Cook Medical, Boston Scientific.

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 &amp; 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

Although the recommended method of an initial examination of hematochezia is colonoscopy, computed-enhanced CT (CECT) is an appealing diagnostic modality for the same disorder, because it has a superior ability of detecting active bleeding and it is widely available, fast, and minimally invasive. In many centers, CECT has already become an established method for characterizing the location of hematochezia. However, its impact on clinical courses of patients with colon diverticular bleeding is fully known. We conducted this study to assess them on the basis of single-center experience in Japan.

Aims & Methods

Consecutive 370 patients with colon diverticular bleeding from April 2002 to January 2023 were enrolled. Diagnosis of colon diverticular bleeding was based on total colonoscopy. Patients were divided into two groups who underwent initial examinations via CECT and colonoscopy. 
Patient attributes, clinical data, and outcomes (length of hospital stay, re-bleeding rate, blood transfusion units and 30 days survival rate) were retrospectively analyzed. The patient characteristics and outcomes were compared between two groups using χ2 test or Fisher’s exact test.

Results

279 patients were men (75.4%). The average age was 70.0(30-94) years old.  Initial CECT was performed to 204 patients (Group A) (54.9%) and remaining 166(group B).  
Patients in group A were more likely to have cerebrovascular disorder.
Findings for other characteristics were similar between two groups. 
In Group A, CECT revealed extravasation in 110 patients (53.9%). 
Emergent colonoscopy was performed in 118 patients (extravasation positive 100: negative 18) and found bleeding point in 46 patients (extravasation positive 43: negative 3). 
In Group B, emergent colonoscopy was performed in 70 patients and found bleeding point in 19(27.1%) patients. 
Patients in group A required more blood transfusion units than group B significantly (3.36 ± 6.28 units in group A vs. 1.53 ± 2.96 units in Group B, p=0.001).
No significant difference was observed in terms of length of hospital stay (10.64 ± 7.11 days in group A vs.9.95 ± 5.37 days in Group B ,p=0.32) , recurrent bleeding rate (23.6 % in group A vs. 23.4 % in Group B, OR 1.016 ,p=1) , and 30 days survival rate (99.5% in Group A vs. 100 % in Group B, OR 1.005 ,p=1)

Conclusion

Emergent colonoscopy, subsequent to initial CECT which revealed extravasation, can detect bleeding point more efficiently in patients with colon diverticular bleeding. But, CECT did not improve clinical outcomes of these patients in this study.