Introduction

Symptomatic luminal stricture in Crohn’s Disease (CD) occurs in up to 20% of patients at the diagnosis and in more than 50% during their lifetime. A considerable percentage of patients often require further surgery for post-operative CD recurrence, with a consequent increased burden of short bowel syndrome. In this scenario, combining biological therapy with endoscopic balloon dilation (EBD) could potentially reduce this risk.

Aims & Methods

Our study aimed to evaluate the efficacy of EBD combined with biologic therapy in symptomatic gastrointestinal strictures in CD patients. We conducted a retrospective study including consecutive CD patients who underwent EBD for low gastrointestinal strictures from December 2015 until November 2022 at our tertiary IBD Center. Subsequent subocclusive/occlusive episodes, the need for steroids, and surgery due to CD stenosis were evaluated during a follow-up period of 6, 12 months, and 24 months.

Results

A total of 52 patients treated with EBD with an overall number of 55 strictures were included. The mean age was 46,8 (18-77) years. The median of disease duration was 9 (0-42) years. Among the total of 55 studied strictures: 14 (25%) in patients with active smoking, 21 (38%) with increased CRP values at the time of dilation, 43 (78%) had evidence of moderate or severe endoscopic disease activity with ulcerative lesions at stricture site. Anastomotic strictures accounted for 26 (47%) of all 55 strictures. The remaining 29 (53%) were de novo stricture: 8 (15%) ileal, 11 (20%) at ileocecal valve, 4 (7%) colonic, and 6 (11%) anal . Forty-two patients (76%) were under biologic therapy at the time of EBD and 2 (4%) started after EBD. EBD technical success was reported in 60% of the procedures, and no adverse events were recorded. After 6 months from EBD, at univariate analysis, increased CRP at the time of dilation resulted in a risk factor for the need for steroids (OR 14,63, IC 2,690 to 71,50; p-value = 0,0006, Table 2). Concomitant biological therapy, active smoke, and the presence of ulcerative lesions did not show a significant correlation with considered outcomes. After 12 and 24 months from EBD, concomitant biological therapy resulted in being a protective factor for surgery (OR 0,06; IC 0,005 to 0,502; p-value=0,0047), while subocclusive and occlusive events were less frequent in anastomotic strictures than ileal stenosis (OR 0,07; IC 0,005 to 0,651; p-value=0,0152).

Conclusion

In patients with CD undergoing EBD for intestinal 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.

Disclosure

Antonio Gasbarrini reports personal fees for consultancy for Eisai S.r.l., 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, Sinergie S.r.l. Board MRGE, and Sanofi S.p.A, personal fees for acting as a speaker for Takeda S.p.A, AbbVie, and Sandoz S.p.A, and personal fees for acting on advisory boards
for VSL3 and Eisai. Daniela Pugliese received speaker fees from AbbVie, MSD, Takeda and Janssen, Pfizer; advisory board fees from Pfizer. Franco Scaldaferri i: advisory board for Abbvie, Janssen, MSD, Sanofi and Takeda; All the other authors have no conflict of interest to declare

Clinical Case Summary

In advanced chronic liver disease (ACLD) patients, the endoscopic evidence of esophageal and/or gastric varices denotes the presence of clinically significant portal hypertension (CPSH), representing the main clinical consequence of portal hypertension (PH).
In this setting, although infrequently, besides typical sites (i.e., esophagus and stomach), PH-related varices can manifest even in other atypical portosystemic-shunt districts, including the vagina. CSPH-related vaginal varices bleeding can occur as a rare complication documented by limited case reports.
A 62-year-old female patient with viral (eradicated Hepatitis C Virus infection)-related- decompensated (grade 2 ascites)-ACLD, complicated by CSPH (grade F2 esophageal varices), was admitted to our Department in February 2025 for microcitic anemia. Anamnesis revealed a previous gastric cancer managed with total gastrectomy resection in 2021.
On admission, abdominal imaging showed radiological signs of ACLD/PH (coarse pattern, splenomegaly, dilated splenic-portal axis). Esophagogastroduodenoscopy ruled out active sources of bleeding, whereas colonoscopy revealed anal congestive not-bleeding varices. During the hospitalization, an episode of metrorrhagia imposed gynecologic evaluation with vaginal speculum examination. This assessment documented vaginal varices with the relative rupture as the current cause of the bleeding, suggesting this site is the further district for (CS)PH manifestation consequently to potentially occurred total gastrectomy-determined changes in abdominal vascular anatomy.
In ACLD patients receiving surgery altering abdominal vascularization, variceal bleeding represents a possible CSPH-related complication occurring even in atypical sites, such as the vagina. This scenario imposes an adequate tailored management, monitoring unusual bleeding signs, and adopting appropriate preventive strategies by including gynecologic evaluation in follow-up.

References

1. McHugh PP, Jeon H, Gedaly R, Johnston TD, Depriest PD, Ranjan D. Vaginal varices with massive hemorrhage in a patient with nonalcoholic steatohepatitis and portal hypertension: Successful treatment with liver transplantation. Liver Transpl. 2008 Oct;14(10):1538-40. doi: 10.1002/lt.21506. PMID: 18825698.
2. Kreek MJ, Raziano JV, Hardy RE, Jeffries GH. Portal hypertension with bleeding vaginal varices. Ann Intern Med. 1967 Apr;66(4):756-9. doi: 10.7326/0003-4819-66-4-756. PMID: 6067181.
3. Chan G, Taqi A, Drage M, Quan D. A case report of massive vaginal variceal hemorrhage in a patient with cirrhosis secondary to nonalcoholic steatohepatitis unresolved even after successful liver transplantation. Transplant Proc. 2013 Mar;45(2):835-7. doi: 10.1016/j.transproceed.2012.04.033. Epub 2012 Sep 19. PMID: 23267803.
4. Lebrec D, Benhamou JP. Ectopic varices in portal hypertension. Clin Gastroenterol. 1985 Jan;14(1):105-21. PMID: 3872747.
5. Nagata J, et al. Vaginal bleeding in a patient with type C liver cirrhosis without a past history of laparotomy: successful treatment with partial splenic artery embolization. Clin J Gastroenterol. 2012 Aug;5(4):275-81. doi: 10.1007/s12328-012-0316-3. Epub 2012 Jun 30. PMID: 26182393.

Introduction

Primary sclerosing cholangitis (PSC) is an idiopathic cholestatic disease. Recent genome-wide studies (GWAS) have identified about 30 disease susceptible genes to PSC. We investigated the expression profiles of these genes in the liver biopsy samples of the patients with PSC, and revealed that the expression of TNFRSF14, which is a one of the risk genes for PSC, was upregulated in the biliary epithelial cell (BEC) of PSC compared to that in normal liver tissue and primary biliary cholangitis (PBC) liver tissue. TNFRSF14 is a member of the tumor necrosis factor receptor superfamily associated with inflammation and fibrosis. We also clarified that the expression of LIGHT, an active ligand for TNFRSF14, was elevated in the BEC of PSC^１). These molecules are mainly expressed on lymphocytes, and in other inflammatory diseases, many reports have mentioned to the associations between these molecules in the sera and the disease progression.

Aims & Methods

Aims: In this study, we aimed to evaluate the concentrations of these molecules in the sera and bile of PSC.
Methods: The concentrations of soluble TNFRSF14 and LIGHT in the sera and bile were measured by enzyme-linked immunosorbent assay. The samples were collected from the following cases:
• Serum: 73 patients with PSC, 35 patients with PBC and 53 healthy controls.
• Bile: 15 patients with PSC, 12 patients with malignant biliary obstruction (MBO), 19 patients with biliary lithiasis (BL).
The bile samples were obtained during endoscopic retrograde cholangiopancreatography. The median values of the serum (s) and bile (b) concentrations of each group were evaluated by Mann-Whittney U test.

Results

sTNFRSF14 in the PSC group was significantly higher than those in the healthy controls (6.301 v.s. 4,247 pg/mL, P < 0.001) and the PBC group (4,987 pg/mL, P < 0.001).
sLIGHT in the PSC group was 87 pg/mL, which was higher than those in the healthy controls (61 pg/mL, P = 0.012), and was comparable to those in the PBC group (106 pg/mL, P = 0.142).
bTNFRSF14 in the PSC group was 2,005 pg/mL, showing no significant difference compared to those in the MBO (1,794 pg/mL, P = 0.516) and the BL group (1,987 pg/mL, P = 0.504).
bLIGHT in the PSC group was 523 pg/mL, remarkably higher than those in the MBO (82 pg/mL, P < 0.001) and the BL group (268 pg/mL, P = 0.024).

Conclusion

sTNFRSF14 in the PSC group was higher than those in the healthy control and the PBC group, and this result was equivalent to the previous report about the upregulated expression in the liver biopsy samples. While soluble LIGHT was secreted non-specifically in the sera of cholestatic liver disease, the elevated bile concentration of LIGHT can be involved in in the unique biology of PSC. ​Further research is needed to elucidate the involvement of these two molecules in the pathogenesis of PSC.

References

1) Digestive Liver Disease 2024 Feb;56(2):305-311.