Introduction

Stenotic complications affect 30%-50% of patients with Crohn’s disease (CD)¹. There is currently no imaging modality to identify stricture composition, which would allow early targeted (anti-inflammatory vs surgical) treatment. Intestinal ultrasound (IUS) and its advanced modalities (contrast-enhanced and elastography) have the potential for transmural disease evaluation. The aim of the STRICTURE study was to investigate (advanced) IUS and MRI techniques to distinguish between inflammatory- (IP) and non-inflammatory predominant phenotypes (non-IP) of stricturing CD.

Aims & Methods

In this prospective, longitudinal study, consecutive patients with small bowel stricturing CD undergoing surgery were included. Patients were eligible if they had a non-passable stricture during endoscopy in the small bowel or at the valve/anastomosis and/or a stricture at cross-sectional imaging (IUS or MRE) with a bowel wall thickness (BWT) >3.0 mm in combination with narrowing of the lumen <1.0 cm or a prestenotic dilation (lumen width ≥2.5 cm)³. Clinical scores (Harvey-Bradshaw index and Crohn’s Disease Obstructive Score⁴) and biochemical parameters were collected. All patients underwent conventional IUS (B-mode/colour Doppler signal)⁵, CEUS and SWE and cine-loops were scored by one rater. After surgery, histological slides were retrieved at the same distance from the valve/anastomosis as measurements were made on IUS. Subsequently, a blinded expert pathologist scored all slides as [1] inflammatory (IP; BWT based on inflammatory infiltrates and edema according to the Nancy score), [2] fibrotic (FP; BWT based on structural changes due to fibrosis, adipose tissue and/or muscular hypertrophy⁶) or [3] mixed phenotype (MP; BWT with inflammatory and fibrotic aspects but no predominant phenotype). FP and MP were both classified as non-IP.

Results

A total of 36 patients (female: 58%, age: 42 ± 18 years) with a mean BWT of 6.7 ± 1.7 mm were included. Median time between IUS and surgery was 14 [3-50] days. A total of 7 patients had an IP, 18 a FP and 11 a MP. For the conventional IUS parameters, loss of bowel wall stratification was more frequently found in IP strictures (OR: 7.87 [1.24-50.00], p=0.029). Clinical, biochemical, other conventional IUS parameters, length of the stricture (13 [8-18] cm vs 10.5 [7.5-17.5] cm) and width of the prestenotic dilation (2.70 [1.70-2.80] cm) vs 2.30 [1.75-3.35] cm) were not significantly different between patients with IP and non-IP. However, CEUS, including wash-in and wash-out parameters, were significantly higher in IP versus non-IP strictures (Table 1). When excluding MP strictures, CEUS was the only modality that could distinguish between IP and FP. SWE inversely correlated with CEUS (Table 1) but did not differentiate between IP and non-IP (33.30 [26.00-44.80] kPa vs 43.49 [28.30-54.00] kPa, p=0.48) or IP and FP (33.30 [26.00-44.80] kPa vs 41.23 [24.36-48.60 kPa, p=0.95).

Conclusion

CEUS accurately distinguishes predominant inflammatory from not-predominant inflammatory strictures in CD and inversely correlates with SWE. CEUS, could be of additional value in this specific population to select patients most suitable for anti-inflammatory treatment. Reproducibility of advanced IUS techniques is under investigation.

References

1. Rieder F, Latella G, Magro F, et al. European Crohn’s and Colitis Organisation topical review on prediction, diagnosis and management of fibrostenosing Crohn’s disease. Journal of Crohn's and Colitis. 2016;10(8):873-885.
2. Lu C, Gui X, Chen W, Fung T, Novak K, Wilson SR. Ultrasound shear wave elastography and contrast enhancement: effective biomarkers in Crohn's disease strictures. Inflammatory Bowel Diseases. 2017;23(3):421-430.
3. Maconi G, Nylund K, Ripolles T, et al. EFSUMB recommendations and clinical guidelines for intestinal ultrasound (GIUS) in inflammatory bowel diseases. Ultraschall in der Medizin-European Journal of Ultrasound. 2018;39(03):304-317.
4. Bouhnik Y, Carbonnel F, Laharie D, et al. Efficacy of adalimumab in patients with Crohn's disease and symptomatic small bowel stricture: a multicentre, prospective, observational cohort (CREOLE) study. Gut. 2018;67(1):53-60.
5. Novak KL, Nylund K, Maaser C, et al. Expert consensus on optimal acquisition and development of the International Bowel Ultrasound Segmental Activity Score [IBUS-SAS]: a reliability and inter-rater variability study on intestinal ultrasonography in Crohn’s disease. Journal of Crohn's and Colitis. 2021;15(4):609-616.
6. Gordon IO, Bettenworth D, Bokemeyer A, et al. International consensus to standardise histopathological scoring for small bowel strictures in Crohn’s disease. Gut. 2022;71(3):479-486.

Clinical Case Summary

Introduction: Rituximab, a monoclonal anti-CD20 antibody, is widely used for treating hematologic malignancies and autoimmune disorders due to its B-cell depleting action. While gastrointestinal side effects like diarrhea are seen in up to 15% of patients, these are typically mild and self-limiting. Severe colitis is a rare but increasingly recognized complication.
Case Description: A 76-year-old diabetic male with a history of ACS (post-PTCA in 2021) presented with 2 months history of generalized abdominal pain, watery diarrhea (6–7 episodes/day), and weight loss. He had a history of follicular lymphoma diagnosed 4 years prior, treated with 6 cycles of CHOP-R followed by rituximab maintenance (375 mg/m² every 3 months). Symptoms began after the 6th maintenance dose.Physical exam revealed mild pallor;abdomen was soft, nontender. Labs showed normocytic anemia and mild neutrophilic leukocytosis. Stool tests were negative for common pathogens, including C. difficile. The patient was planned for a Colonoscopy, which revealed ulcers over the ileocecal valve and rectal erosions. Biopsies showed mixed inflammatory infiltrates, cryptitis, crypt abscesses, and crypt rupture, consistent with severe active ileocolitis. AFB culture and GeneXpert were negative for tuberculosis.The patient was started on oral mesalamine (500 mg TID) along with Rifaximin(400mg) BD for 2 weeks, showing marked clinical improvement.
Discussion: Rituximab-induced colitis is rare and poorly understood. It may result from disruption of mucosal immunoregulation due to B-cell depletion, leading to T-cell-mediated inflammation. Histology may resemble patterns seen in GVHD or autoimmune enteropathy. Most cases resolve with supportive care and discontinuation of the drug; however, some, like this case, may require treatment in the form of 5ASA, or steroids.There is no previous data on the use of rifaximin in such cases. Differentiating drug-induced IBD from primary IBD remains a diagnostic challenge.

References

There is limited evidence in the literature establishing a definitive association between rituximab therapy and the onset of colitis. However, emerging hypotheses suggest that rituximab-induced depletion of peripheral CD19+ B cells and colonic CD20+ lymphoid aggregates may disrupt mucosal immune homeostasis, thereby contributing to structural alterations in the intestinal architecture and promoting inflammation.
The role of the gut microbiota in the pathogenesis and persistence of mucosal inflammation in inflammatory bowel disease (IBD) provides a rationale for the therapeutic use of antibiotics in selected cases. While systemic antibiotics such as ciprofloxacin and metronidazole have demonstrated clinical efficacy in IBD management, their utility may be limited in drug-induced colitis due to the potential for systemic adverse effects.
In contrast, rifaximin, a non-systemic, presents a favorable safety profile and has shown promise as a therapeutic option in both idiopathic and drug-induced enterocolitis. Its targeted antimicrobial activity within the gastrointestinal tract, combined with minimal systemic exposure, renders it an attractive alternative. However, further prospective, randomized studies are warranted to substantiate its efficacy and long-term safety in this context.

Introduction

Endoscopic removal of common bile duct stones (CBDS) via endoscopic retrograde cholangiopancreatography (ERCP) is the first-line treatment. In developed countries, the number of ERCP procedures for CBDS in elderly patients is increasing with the aging population. Elderly patients often present with poor performance status (PS), are frequently on antithrombotic therapy, and have multiple comorbidities. These factors raise concerns about an increased risk of ERCP-related complications; however, the safety and efficacy of ERCP in this population have not been fully evaluated.

Aims & Methods

The aim of this study was to assess the outcomes of ERCP for CBDS in elderly patients. Among 548 patients with symptomatic CBDS treated at our institution between April 2017 and February 2024, we excluded 81 cases involving altered anatomy, use of endosonography-assisted rendezvous technique, spontaneous stone passage, and biliary pancreatitis. The remaining 467 patients undergoing ERCP at our institution were retrospectively analyzed. The patients were divided into an elderly group (E group: ≥75 years, n=241) and a younger group (Y group: <75 years, n=226), and short- and long-term outcomes were compared between the two groups.

Results

Patient Characteristics: The median age was 81 years (range: 75–99) in the E group and 68 years (range: 21–74) in the Y group. Male sex was less frequent in the E group (55% vs. 68%, p=0.006). The E group had significantly higher rates of antithrombotic use (39% vs. 24%, p=0.001), American Society of Anesthesiologists physical status ≥ III (57% vs. 35%, p=0.001), and concomitant cholangitis (52% vs. 41%, p=0.012). Median stone size was slightly larger in the E group (8 mm vs. 6 mm, p=0.14), and the median bile duct diameter was significantly wider (10 mm vs. 9 mm, p=0.001). Comorbidities were more prevalent in the E group: cardiovascular disease (34% vs. 22%, p=0.004), hypertension (52% vs. 39%, p=0.004), malignancy (33% vs. 18%, p=0.001), and dementia (11% vs. 2%, p=0.001). Although endoscopic sphincterotomy (EST) was the most common papillary intervention in both groups, endoscopic papillary large balloon dilation (EPLBD) was more frequently performed in the E group (31% vs. 10%).Lithotripsy rates were similar between groups (22% vs. 16%, p=0.2).
Outcomes: Complete stone removal was achieved in 96% of the E group and 98% of the Y group (p=0.2). The median number of treatment sessions was 1 in both groups (range: 1–3, p=0.13). Overall complication rates were comparable (8% vs. 7%, p=0.63). In the E group, complications included pancreatitis (n=15), bleeding (n=5), perforation (n=1), and aspiration pneumonia (n=1); in the Y group, pancreatitis (n=10) and bleeding (n=5) were observed. No procedure-related mortality occurred in either group. There was no significant difference in the cumulative recurrence rate of stones after complete removal (p=0.29). Multivariate analysis using variables such as age, sex, presence of cholangitis, bile duct diameter, lithotripsy, and gallbladder stones revealed no definite predictors of recurrence.

Conclusion

Although recent studies have reported the potential utility of long-term biliary stenting in elderly patients, stent occlusion leading to cholangitis remains a concern. Repeated hospitalizations in elderly patients can decrease activities of daily living. Therefore, we prioritize complete stone removal in patients with a favorable long-term prognosis. This study demonstrates that even in patients aged 75 years and older, active treatment of CBDS via ERCP might be effective and safe.

Introduction

Acute pancreatitis (AP) is one of the most common gastroenterological diseases requiring admission to the hospital. The main etiological factors of AP are gallstones and excessive alcohol consumption, but rarer causes, such as hypercalcemia, should keep on mind. Only few cases are reported in the literature, and the severity of hypercalcaemia-induced acute pancreatitis is not known.

Aims & Methods

We aim to assess the occurrence and severity of hypercalcaemia-induced AP and compare it with the clinical characteristics of AP caused by other etiological factors. We collected patients from the Hungarian Acute Pancreatitis Registry, Hungarian GOULASH study and the Europe-wide EASY study, who had AP and had a serum calcium level above 2.6 mmol/l. Patients were divided into three groups: hypercalcemia-induced AP, where no other etiology than hypercalcemia were present, mixed etiology group, where both hypercalcemia and other etiologies were revealed and the control group with normal serum calcium level. Propensity score matching adjusted by age, sex, diabetes, lipid disorder, previous pancreatic disease was made and several outcome parameters were analyzed during the statistical analysis. Hypercalcemic cases were divided into 3 subgroups based on the level of serum calcium: mild (2.6< >3.0 mmol/l), moderate (3.0 < >3.5 mmol/l) or severe hypercalcemia (>3.5 mmol/l).

Results

1.02% of our AP patients (19/1867) had clear hypercalcemic etiology and 3.75 % (70/1867) of the patients had mixed etiology, 1778 patients were in the control group. There was no difference in the mean ages of the patients in the three groups (57.3± 16.3 and 56.1 ± 20.1 vs. 55.1 ± 14.6 years). Severe AP was significantly more frequent in patients with hypercalcemia-induced AP compared to the control group [21.05% (4/19) vs 6.13% (109/1778); odds ratio: 4.08 (95% CI, 1.08-15.38)]. Renal failure was more frequent in hypercalcemic etiology compared to AP patients with normal serum calcium level [27.27% (3/11) vs 5.35% (95/1776); odds ratio: 6.63, (95% CI, 1.36-32.35)]. There was no significant difference in CRP, amylase, lipase, WBC, creatinine, length of hospital stay, mortality, intensive care admission, the presence of pancreatic necrosis, pseudocysts, and other organ failure between the hypercalcemic or mixed etiology and the control groups. There was no significant difference in the severity of AP between the mixed etiology and normal serum calcium groups. The outcome of acute pancreatitis was not influenced by the severity of hypercalcemia within the hypercalcemic group.

Conclusion

Hypercalcemia-induced AP has a higher risk for developing into severe AP and renal failure compared to other etiology.