Introduction

Usability of subcutaneous vedolizumab (SC VDZ) in inflammatory bowel diseases (IBD, ulcerative colitis [UC], Crohn’s disease [CD]) have proved via clinical trials, while real-world data collection is ongoing. Experiences of Central-European population and assessment of patient’s perspectives are lacking.

Aims & Methods

Our study aimed to evaluate the real-world efficacy, safety and patient’s preferences of SC VDZ maintenance treatment after switching from intravenous (IV) formulation in a Hungarian IBD cohort. In this prospective, multicenter cohort study, IBD patients on maintenance IV VDZ treatment were enrolled, who switched to SC administration. Baseline was the day of the switch, while 52-week follow-up was set. Clinical and demographic data were collected, while serum VDZ level and CRP was measured at baseline and at w52. A non-validated questionary was filled by patients who were on drug at w12 recording patient’ satisfaction. Primary outcome was the drug survival rate at one year, while secondary outcomes were change in corticosteroid-free clinical (CSFR, based on physicians’ global assessment score PGA<1), and biochemical remission (BR, 5 mg/l³CRP) rates to w52, safety issues and patients’ preferences and change in serum drug levels.

Results

In total, 37 IBD patients were followed (15 CD and 22 UC, male/female ratio 45.9 %, median age 42.0 [IQR 34-49] years). In CD group, 66.7% were in CSFR and 60 % in BR, while in UC group 63.6% were in CSFR and 68.2 % in BR (p=0.55 and p=0.61). Overall, 29.7 % of patients ceased SC VDZ treatment after a median of 20 (IQR 6-26) weeks. Cessation was due to secondary response losing in 3/6 and 4/5 patients in CD and UC group. In case of 2 and one patients, SC treatment was terminated due to local reactions. One patient was fear of needle. Severe adverse event did not occur. Factors associated with discontinuation did not identify. The mean serum VDZ level has higher at w52 compared to baseline in CD and UC patients (CD: 8.9 ±6.9 to 30.6 ±17.8 ug/mL, p = 0.047; UC: 13.6±13.8 to 33.6±17.6 ug/mL, p = 0.001), while disease activity was stable. 84 % of the patients who filled the questionnaire were satisfied with injection, while only one patient found it difficult to inject.

Conclusion

Transition from IV to SC maintenance VDZ treatment is effective at one year, the overall survival rate is high presumably due to the elevated serum drug levels. Severe safety issue did not raise. Satisfaction of switched patients is high, which may improve treatment adherence and save resources.

Disclosure

K.F. has received speaker’s honoraria from AbbVie, Janssen, Ferring, Takeda, and Goodwill Pharma. T.M. has received speaker’s honoraria from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer, Janssen, Sandoz, MundiPharma, Phytotec, Roche, Fresenius, and Teva. ​Remaining authors have no conflict of interest to declare.

Clinical Case Summary

Intra-ampullary papillary tubular neoplasms (IAPNs) are rare neoplastic intraepithelial lesions that occur within the ampulla. Given their well-documented malignant potential, early recognition and intervention are paramount to prevent malignant transformation. We present a case of IAPN successfully managed via endoscopic papillectomy.
A 58-year-old male was incidentally found to have a bulky-appearing ampulla of vater during esophagogastroduodenoscopy as part of routine health screening. Endoscopic ultrasonography revealed a 20-mm hyperechoic lesion at the ampulla, with histopathological evaluation demonstrating low-grade dysplasia (indeterminate for neoplasia). Laboratory investigations, including hematological parameters, biochemical profiles, and tumor markers, were within normal limits. Contrast-enhanced abdominal CT demonstrated a well-defined, homogeneously enhancing 20-mm lesion at the ampullary region without biliary/pancreatic duct dilation.
Endoscopic papillectomy was performed using a duodenoscope with snare. Prophylactic stents were placed in both the biliary and pancreatic ducts to ensure adequate drainage. Any intraprocedural bleeding was promptly controlled with hemoclip application. Histopathological analysis confirmed high-grade IAPN, characterized by a polypoid tumor with closely packed tubular glands lined by pseudostratified columnar epithelium showing loss of polarity and moderate nuclear atypia (Ki-67 index: 50%). The postoperative course was uncomplicated, with discharge achieved on the sixth postoperative day. At six-month follow-up evaluation, surveillance endoscopic ultrasonography showed no evidence of recurrence.
IAPN represents a distinct neoplastic ampullary entity within the spectrum of ampullary tumors. While endoscopic resection demonstrates therapeutic efficacy, its implementation requires advanced endoscopic expertise in specialized centers.

References

Endoscopic ultrasonography revealed a 20-mm hyperechoic lesion at the ampulla
Endoscopic papillectomy was performed using a duodenoscope with snare. Prophylactic stents were placed in both the biliary and pancreatic ducts to ensure adequate drainage. Any intraprocedural bleeding was promptly controlled with hemoclip application.
Histopathological analysis confirmed high-grade IAPN, characterized by a polypoid tumor with closely packed tubular glands lined by pseudostratified columnar epithelium showing loss of polarity and moderate nuclear atypia (Ki-67 index: 50%).

Introduction

Helicobacter pylori is a common cause of peptic ulcers and gastritis. Standard triple therapy includes a PPI with amoxicillin and either clarithromycin or levofloxacin. Rising antibiotic resistance has reduced its effectiveness. Sequential therapy offers a phased alternative with better outcomes in resistant cases.

Aims & Methods

To evaluate and compare the efficacy of clarithromycin and levofloxacin-based triple and sequential therapies for Helicobacter pylori (H. pylori) eradication in a resource-limited setting, in the context of emerging antibiotic resistance.
A prospective, randomized study was conducted at a tertiary care center from January 1, 2022, to January 1, 2025. A total of 300 treatment-naïve patients aged 18–60 years, diagnosed with H. pylori infection through stool antigen, urea breath test, or histology, were included. Patients with prior eradication therapy or recent antibiotic use were excluded. Participants were randomized into four equal groups (n=75 each):

• Clarithromycin-based triple therapy (amoxicillin, clarithromycin, PPI)
• Levofloxacin-based triple therapy (amoxicillin, levofloxacin, PPI)
• Clarithromycin-based sequential therapy (amoxicillin + PPI for 5 days, followed by clarithromycin + tinidazole + PPI for 5 days)
• Levofloxacin-based sequential therapy (amoxicillin + PPI for 5 days, followed by levofloxacin + tinidazole + PPI for 5 days) Therapeutic response was assessed post-treatment for eradication.
  

Results

Out of 300 patients (180 males, 120 females), eradication was achieved in:

• 48/75 (64%) in clarithromycin-based triple therapy
• 53/75 (70.7%) in levofloxacin-based triple therapy
• 51/75 (68%) in clarithromycin-based sequential therapy
• 61/75 (81.3%) in levofloxacin-based sequential therapy

All patients completed therapy without notable adverse events or compliance issues. Lower eradication rates in clarithromycin-based regimens suggest rising resistance.

Conclusion

Levofloxacin-based sequential therapy demonstrated the highest eradication rate, highlighting its potential as a preferred regimen in settings with rising clarithromycin resistance. Clarithromycin-based treatments showed suboptimal outcomes, emphasizing the need for region-specific antibiotic stewardship and resistance surveillance.

References

1. Kim JS, Kim BW, Hong SJ, Kim JI, Shim KN, Kim JH, Baik GH, Kim SW, Song HJ, Kim JH. Sequential Therapy versus Triple Therapy for the First Line Treatment of Helicobacter pylori in Korea: A Nationwide Randomized Trial. Gut Liver. 2016 Jul 15;10(4):556-61. doi: 10.5009/gnl15470. PMID: 27114421; PMCID: PMC4933415.
2. Chang, J.Y., Shim, KN., Tae, C.H. et al. Triple therapy versus sequential therapy for the first-line Helicobacter pylori eradication. BMC Gastroenterol 17, 16 (2017). https://doi.org/10.1186/s12876-017-0579-8

Introduction

Gut micorbiota in patients with cystic fibrosis (pwCF) is severely disrupted and a potential source of further complications. We aim to provide quantitative evidence of the differences in gut microbiota between pwCF and non-CF controls to understand CF gut flora composition and identify potential sites for microbiota modulation with special focus on time-dependent changes.

Aims & Methods

We conducted a systematic review and meta-analysis of PubMed, EMBASE, CENTRAL, Web of Science, and Scopus up to November 13, 2023 (CRD42023482792). Included were case-control studies assessing gut microbial alpha diversity or relative abundance in pwCF and controls without gut-affecting conditions or drugs. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated using a random-effects model for both outcomes. We performed subgroup analysis for alpha diversity for infants, children, and adults. We used the Joanna Briggs Institute risk of bias tool.

Results

Among 2550 studies, 11 met inclusion criteria (enrolling 1174 subjects). Alpha diversity analysis showed age-specific changes. Observed OTUs were non-significantly decreased in adult pwCF compared to controls (SMD=-1.57; 95%CI -4.21 to 1.08, across 3 studies, 80 pwCF and 100 controls). Children with CF displayed a significantly reduced Shannon index (SMD=-1.43; 95%CI -2.06 to -0.79, across 3 studies, 77 pwCF and 78 controls). However, in infants, no difference was detected in Shannon index between CF patients and controls (SMD=0.05; 95%CI -0.74 to 0.84, across 4 studies, 288 pwCF, 519 controls). Analysis of follow-up data in infants revealed a decreasing tendency of Shannon index in pwCF compared to controls during the first year of life (SMD=0.67; 95%CI -1.20 to 2.54 at 4 months vs. SMD=0.45; 95%CI -1.81 to 2.71 at 6 months vs. SMD=-0.61; 95%CI -1.98 to 0.75 at 12 months). A significant increase in the relative abundance of Veillonella and E.coli marked the CF group with a noticeable increase of Enterobacter and decrease of Bacteroides and Faecalibacterium compared to controls (see Table).

Conclusion

Gut microbial alpha diversity is reduced in adults and children with CF compared to controls, while infants with CF exhibit similar diversity, which continuously decreases during the first year of life. Perturbations in the intestinal microbial ecosystem are defined by a significant increase in E.coli and Veillonella abundances within individuals with CF compared to controls enabling specifically targeted microbiota modulation.

Introduction

Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) are frequently associated with acute (AP) or recurrent pancreatitis (RP), likely due to the mucin-induced obstruction of the main pancreatic duct (MPD). According to the 2024 Kyoto Guidelines, pancreatitis represents an indication for surgical evaluation in IPMN patients. However, pancreatic sphincterotomy (PS) may represent a less invasive alternative for patients who are unfit for surgery or as a bridge to surgery, aiming to reduce the risk of further pancreatitis episodes.

Aims & Methods

This single-center retrospective study aimed to assess the efficacy and safety of PS in patients with BD-IPMN and RP. We included 33 patients who underwent PS between 2016 and 2023, with at least 12 months of follow-up. Patients with other causes of RP or prior pancreatic surgery were excluded. The frequency of pancreatitis episodes before and after PS was compared. Clinical success was defined as complete resolution or ≥50% reduction in pancreatitis episodes. Adverse events, presence of worrisome features (WF), and progression to high-risk stigmata (HRS) were evaluated. Statistical analysis was performed using paired t-test and Fisher’s exact test, with p < 0.05 considered significant.

Results

Among the 33 patients analyzed (39.4% female, 60.6% male, mean age 59 ± 13.9 years) clinical success was achieved in 81.8% of the cases. Specifically, 72.7% of the patients experienced no further AP episodes after PS and 9.1% experienced a reduction in episode frequency, while 18.2% of patients did not respond to treatment. Adverse events occurred in 15% of patients, including: 12% with post-ERCP pancreatitis (all mild) and 3% with intra-procedural bleeding; no perforations were reported. During follow-up WF emerged in 5 patients (15%), while no cases of HRS were identified. Among the 6 non-responders, 3 underwent a second PS, with 2 achieving clinical improvement, and 3 underwent duodenocephalopancreasectomy (DCP), including 1 for a concomitant pancreatic ductal adenocarcinoma (PDAC) unrelated to IPMN progression. Notably, no cases of IPMN degeneration were observed in the series

Conclusion

Pancreatic sphincterotomy appears to be a safe and effective approach for managing recurrent pancreatitis in patients with BD-IPMN, potentially reducing the need for surgery in selected cases.

Clinical Case Summary

Introduction: Dieulafoy lesions account for less than 2% of gastrointestinal bleeds, and only 20% of these occur outside the stomach. We present a rare case of a bleeding ampullary Dieulafoy lesion with technical difficulties in management, starting with a standard forward-viewing gastroscope, subsequent use of a side-viewing duodenoscope, and eventually endoscopic retrograde cholangiopancreatography (ERCP) and stenting to allow for safe haemostasis with argon plasma coagulation (APC).
Case report: A 56-year-old male was admitted with pneumonia and fluid overload in the context of end-stage renal disease from poorly controlled diabetes mellitus and hypertensive nephrosclerosis on regular haemodialysis. He was on dual anti-platelet therapy with aspirin and ticagrelor for a recent cardiac stent.
Five days into his admission he was noted to have melena with a haemoglobin drop from 87 g/L to 56 g/L, with a urea rise of 23.9 mmol/L from a baseline of 11.0 mmol/L.
Subsequent gastroscopy revealed active bleeding from the major ampulla without any underlying ulcer or tumour, superior to the biliary orifice, consistent with an ampullary Dieulafoy lesion. The duodenoscope was then introduced for a better view and access to the major ampulla. APC was attempted at 0.8 L/min at 30 Watts due to the size and location, but haemostasis was unsuccessful.
The decision was made to proceed to ERCP and biliary stenting to prevent complications from heat injury to the bile duct and possible pancreatitis. A 7 Fr by 4 cm double pigtail biliary plastic stent was placed into the common bile duct. APC was re-applied at 0.8 L/min at 30 Watts at the bleeding spot with successful haemostasis.
Discussion: This case report aims to highlight the rare occurrence of duodenal ampullary Dieulafoy lesions and the need for prompt recognition and use of resources such as side-view duodenoscopy and ERCP for safe therapeutic management.

Disclosure

None

Introduction

Ulcerative colitis (UC) is a chronic inflammatory disease requiring sustained therapy for both induction and maintenance of remission. Biologics radically changed the natural history of UC patients and are still the cornerstone of treatment, but they have some limitations. The introduction of oral Janus kinase inhibitors (JAKi), recently approved for UC management, presents a novel treatment option. Data are needed to confirm their efficacy in a real world setting.

Aims & Methods

In this retrospective, observational study at the IBD Unit in Bologna, we enrolled consecutive UC patients treated with the JAKi tofacitinib (TOFA) and upadacitinib (UPA). We collected demographic and disease-specific data, assessing clinical activity via the partial Mayo (pMayo) score, biomarker status through C-reactive protein levels, and endoscopic activity via the Mayo endoscopic score at baseline and at 2, 6, and 12 months. Concomitant use of steroids were registered at every time point. We measured clinical response (≤3-point reduction in pMayo or discontinuation of steroids) at 2 months, clinical remission rates (pMayo < 2) and endoscopic remission (Mayo score of 0) at each time point. Need for surgery was also recorded.

Results

A total of 50 patients were treated with JAKi between December 2021 an June 2023 (39 TOFA and 11 UPA). Males were 59.57% and median age was 35.5 years. Nobody were bio-naïve and 80.86% were exposed to ≥ 2 biologics/small molecules prior to JAKi initiation. Concomitant steroids were present in 76% of cases at baseline. Clinical response at T2 was obtained in 65.30% of cases. Clinical remission rate was 40% at T2, 32.6% at T6 and 24.4% at T12. Endoscopy was performed at T2 in 24 patients, at T6 in 26 and at T12 in 10 patients; endoscopic remission was observed in 5/24, 9/26 and 4/10, respectively. Treatment optimization was adopted in 52% of cases. A total of 5 patients (10%) underwent colectomy during follow up period. No serious adverse events were observed.

Conclusion

In a cohort of multirefractory UC patients, JAKi demonstrated substantial efficacy in inducing clinical and endoscopic remission, though there was a decline in effectiveness during the maintenance phase. The rate of colectomy remained relatively low, underscoring the potential utility of JAKi in this challenging patient population.