Introduction

The first-line treatment for obstructed biliary or pancreatic ducts is endoscopic retrograde cholangiopancreatography (ERCP), yet access may fail (even in expert hands) in 10-15% of cases due to inability to cannulate the papilla or a challenging narrow anatomy. Endoscopic ultrasound-guided biliary drainage (EUS-BD) or EUS-guided pancreatic duct drainage (EUS-PDD) have emerged as direct duct accesses alternate to the percutaneous or surgical approach, both which carry high morbidity and mortality.

Aims & Methods

We aim to assess the anterograde’s drainage clinical and technical success in non-neoplastic obstructed biliary and pancreatic ducts. Data from patients with a history of obstructed biliary or pancreatic ducts between January 2021 and October 2022 was analyzed retrospectively. Clinical and technical success were the primary endpoints. Adverse events, re-stenosis, and re-intervention were also evaluated.

Results

A total of twenty patients were included (15/20 EUS-BD and 5/20 EUS-PDD), median age of 46 (IQR 24-77), 70% female. A) EUS-BD: inability to cannulate the papilla was due to stenosis secondary to: 6/15 laparoscopic cholecystectomy, 7/15 conventional cholecystectomy, 1/15 gallbladder neoplastic plastron, and 1/15 Y-Roux. In 4/15 a previous attempt was performed (1/4 balloon dilation, 1/4 percutaneous transhepatic biliary drainage, and 2/4 stenting). Anterograde drainage was performed in 7/15 using a single pigtail stent, 5/15 double pigtail stents and 3/15 lumen-apposing metal stent (LAMS). Stomach puncture was the preferred approach site in 13/15. A 15/15 (100%) technical success was achieved, but a 9/15 (60%) clinical success based on bilirubin decrease. During follow-up, adverse events were documented in 3/15 cases: upper bleeding, cholangitis, and subhepatic fluid collection. Stent migrated in 3/15 cases. There was no restenosis, but reintervention was necessary on 8/15. One patient died. B) EUS-PDD: anterograde drainage was decided due to acute or chronic pancreatitis and choledocholithiasis in 2/5, 1/5, and 2/5 cases, respectively; 2/5 patients were under non-opioids therapy before the procedure for pain management, and 4/5 were prescribed pancreatic enzyme supplementation. In 3/5 cautery-assisted dilation was required. In 1/5, balloon dilation was also necessary. Used stents included: single and double pigtail stents, LAMS, and self-expandable metal stents (SEMS). Technical and clinical success was achieved in 5/5 (100%), with no adverse events.

Conclusion

Anterograde EUS-BD and EUS-PDD for the management of non-neoplastic biliary and pancreatic duct drainage are valuable alternatives in patients where ERCP is not feasible. Further prospective studies are necessary to confirm the observed results.

Disclosure

Carlos Robles-Medranda is a key opinion leader and consultant for Pentax Medical, Boston Scientific, Steris, Medtronic, Motus, Micro-tech, G-Tech Medical Supply, CREO Medical, EndoSound, and mdconsgroup. The other authors declare no conflicts of interest.

Introduction

Liver fibrosis is primarily caused by the activation of hepatic stellate cells (HSCs), which results from chronic liver damage. Understanding the pathogenesis of HSC activation could identify new therapeutic targets to treat liver fibrosis.

Aims & Methods

In this study, we examined the protective role of the mammalian cleavage factor I 25 kD subunit (CFIm25, NUDT21) in inhibiting hepatic stellate cell activation. CFIm25 expression was measured in liver cirrhosis patients and a CCl4-induced mouse model. Adeno-associated viruses and adenoviruses were used to alter hepatic CFIm25 expression in vivo and in vitro to investigate how CFIm25 functions in liver fibrosis. The underlying mechanisms were explored using RNA-seq and co-IP assays.

Results

Here, we found that CFIm25 expression was drastically decreased in activated murine HSCs and fibrotic liver tissues. CFIm25 overexpression downregulated the expression of genes involved in liver fibrosis, inhibiting the progression of HSC activation, migration and proliferation. These effects resulted from direct activation of the KLF14/PPARγ signaling axis. KLF14 inhibition abrogated the CFIm25 overexpression-mediated reduction in antifibrotic effects.

Conclusion

In conclusion, we reported a protective role for CFIm25 in liver fibrosis. Our findings showed that CFIm25 reversed HSC activation and inhibited CCl4-induced liver fibrosis through the KLF14/PPARγ signaling pathway, which might provide a novel approach for liver fibrosis treatment.

References

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9. Masamha CP. The emerging roles of CFIm25 (NUDT21/CPSF5) in human biology and disease. Wiley interdisciplinary reviews RNA. 2022: e1757.

Introduction

Crohn’s Disease patients (CD) with early complicated behaviour (stenosis or fistula) are thought to have a more severe long-term disease course. To address this question, we focused on ileal CD that requires early intestinal resection after diagnosis. We aimed to assess the impact of the time to surgery from diagnosis on the risk of severe disease course in patients with ileal CD undergoing a primary ileocecal resection (ICR) or ileal resection (IR).

Aims & Methods

All CD patients who underwent ICR or IR between January 2001 and December 2015, followed in two Inflammatory Bowel Disease (IBD) tertiary centres in France were included. Data were retrieved using dedicated IBD database and patients’ medical records. Early resection was defined as a surgery performed within 6 months after diagnosis. Two control groups with patients who underwent the first surgery between 6 months and 2 years and between 2 and 5 years after diagnosis were enrolled. The primary outcome was second intestinal resection. Secondary outcomes included the need for biologic treatment after initial intestinal surgery. Patients were followed from the date of first surgery until September 2022. Kaplan Meier survival analysis and log-rank test were used to estimate the survival without second intestinal resection and biologic initiation according to the time of first intestinal resection to diagnosis.

Results

Among 396 patients who underwent ICR or IR within 5 years after diagnosis, 130 (32.2%) patients had undergone surgery within 6 months after diagnosis (Group A), 130 (32.2%) patients between 6 months and 2 years (Group B) and 136 (33.7%) patients between 2 and 5 years (Group C). Clinical data are shown in Table 1. The cumulative risk of a second ICR or IR ten years after the first surgery was 25.2% (95% CI 12.5 - 40.2) in group A, 16.2% (10.0 - 25.8) in group B and 22.8% (9.8 – 39.1) in group C, without statistically significant difference (p = 0.22). The risk of biological exposure after the first surgery was significantly different in the three groups (p = 0.006). The cumulative risk to start a biologic therapy at ten years was 47.4% (37.9 – 57.9) in group A, 56.4% (46.5 – 66.7) in group B and 63.6% (53.6 – 73.6) in group C.

Conclusion

In a bicentric cohort with long-term follow-up, intestinal resection within 6 months of CD diagnosis was not associated with an increased risk of second surgery as compared to patients with primary ICR/IR later after diagnosis. Furthermore, patients with early intestinal resection did not need more biological therapies after the first surgery. On the contrary, patients with early resection had less need for biologic after first surgery. These data suggest that early intestinal resection in CD is not a predictor of poor long-term prognosis.

Introduction

Inflammatory bowel diseases (IBD) have a peak incidence between the second and fourth decade of life, affecting women with IBD during their reproductive years, with fear, uncertainty, and poor knowledge of how the disease can impact their life. Our study aimed to assess the impact of IBD on the reproductive life of female patients with this condition.

Aims & Methods

Women aged 18-65 years with IBD followed at the IBD Unit of the Academic Hospital of Padua were enrolled. They were asked to complete a dedicated questionnaire while sitting in the waiting room for their routine follow-up visit. During the same period, healthy women of the same age were recruited among staff, familiars, and friends. Demographic and clinical data, information on fertility, hormonal therapy, endometriosis, pregnancy, and breastfeeding were collected. Logistic regression was used to analyze the risk of having specific outcomes in IBD compared to controls, expressing as odds ratio (OR) and 95% Confidential Intervals (CI). The statistical significance was set at 0.05.

Results

We enrolled 457 women, out of whom 228 had IBD, and 229 were age-matched healthy controls. The use of oral contraceptives was similar between patients and healthy controls. However, 52.5% of women with IBD took contraceptives for menstrual cycle disorders, whereas 60.5% of the healthy controls for the contraceptive purpose (p=0.003). The risk of infertility (OR 1.76, 95% CI 0.78-3.94) and endometriosis (OR 1.39, 95% CI 0.63-3.10) were similar between patients and healthy controls. The percentage of spontaneous and voluntary abortions was significantly higher in IBD patients than healthy controls (OR 2 and 3.62, respectively). The risk of pregnancy-related complications in the IBD population was more than 6 times higher in patients who experienced disease reactivation during pregnancy than in those with persistent remission (OR 6.9, 95% 1.51-31.28). Finally, we found that the chances of breastfeeding were 66% lower in patients with IBD than in controls (OR 0.44, CI 95% 0.22-0.91).

Conclusion

Our study underlines the negative impact of IBD on women's reproductive life and the importance of adequate counseling from the moment of conception choice to pregnancy and lactation. This will allow better management of the disease and reduce the impact of IBD on the daily life of IBD women.

References

Torres J., Chaparro M., Julsgaard M., et al. European Crohn's and Colitis Guidelines on Sexuality, Fertility, Pregnancy, and Lactation. J Crohns Colitis. 2023; 17:1-27