Clinical Case Summary

Management of bleeding GIST is challenging, especially in metastatic disease. Emergent surgery for bleeding GIST lesions has a high rate of morbility and mortality in comparison to elective procedures (1). A safe and accurate method to obtain a permanent hemostasis is needed. Several endoscopic procedures are available although with limited efficacy due to the complex neoangiogenesis of these tumours that remains out of reach of contact endoscopic techniques (2). EUS-guided therapy of bleeding GIST injecting cyanoacrylate or ethanol has been published. After one adverse event of spurting bleeding after EUS-guided injection of cyanoacryalte, our group first reported the EUS-guided coil puls cyanoacrylate injection therapy for bleeding GIST in two patients (3). We report our experience in five consecutive cases of bleeding GIST successfully treated under EUS-guidance (Table 1). Given the rich network of arteries in some cases, we aim to deploy coils into de tumor .
One adverse event was observed. An intratumoral bleeding after the punction of a 22G needle, successfully managed by EUS-guided deployment of a coil plus CYA. The clinical outcome in these five patients was uneventful until scheduled surgery was performed or palliative therapy in the fifth patient with a metastatic GIST with oncologic progression disease.

CASE	AGE	LOCALZATION SIZE OF THE ARTERY	CLINICAL PRESENTATION	EUS-GUIDED PROCEDURE NEEDLE CYANOACRYLATE/COILS	ADVERSE EVENTS	CLINICAL OUTCOME SCHEDULED SURGERY
1	82	Duodenal Bulb 2 mm	Recurrent melena Two unsuccessful endoscopic injection and clipping therapy	22 gauge 1 mL CYA	None	Uneventful 4 years
2	72	Fundus 5 mm	Hematemesis and hypovolemic shock	22 gauge 1 mL CYA 19 gauge 1 coil (6 mm/20cm long) 2 mL CYA	Bleeding after injection of 1 mL CYA Hemostasis after deployment of 1 coil and 2 mL CYA	Uventful 3 years
3	79	Fundus 4 mm	Hematemesis and hypovolemic shock	19 gauge 1 coil (6mm/14 mm long)	None	Uneventful
4	43	Fundus 3 mm	Melena	19 gauge 3 coils (3 mm/14cm long) 2 mL CYA	None	Uneventful 2 years
5	63	Body Metastatic GIST with oncologic progressiion Several 4 mm arteries	Hypovolemic shock	19 gauge 1 session: 5 coils (14mm/14 cm long) plus 2 mL CYA 2 session (anemia): 6 coils (6 mm/14 cm) plus 1 mL CYA	None	Uneventful on palliative care 6 weeks

EUS-guided therapy of bleeding GIST was effective in these five cases and could be another safe and accurate endoscopic procedure in bleeding GIST aiming to obtain hemostasis until scheduled surgical therapy is carried out or as palliative therapy. In these cases there were not observed recurrent bleeding in spite of a rich network of arterial vessels.

References

(1) Liu Q, Kong F, Zhou J, et al. Management of hemorrhage in gastrointestinal stromal tumors: a review. Cancer Manag Res. 2018;10:735-43.
(2) Venezia G, Asnaghi G, Manca A, et al. Successful use of Hemospray as a bridge to surgery in life-threatening bleeding from a gastrointestinal stromal tumor of the stomach. Endoscopy 2016;48:E232-E233.
(3) Romero-Castro R, Jimenez-Garcia VA, Irisawa A, et al. Endoscopic ultrasound-guided angiotherapy in bleeding gastrointestinal stromal tumors with coil deployment and cyanoacrylate injection. Endoscopy. 2021;53(4):E124-E5.

Disclosure

Rafael Romero Castro is consultant to Cook Medical since 28th, 2023.

Introduction

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, predominantly diagnosed in patients with chronic liver diseases. The absence of specific biomarkers and the typically asymptomatic progression of the disease lead to delayed diagnosis. Patients with liver disease, including HCC, exhibit alterations in the gut microbiome and increased bacterial permeability, factors that may influence disease progression and patient outcomes. In recent years, there has been a growing interest in exploring circulating microbiome signatures as potential indicators of liver disease stutus, providing a new avenue for understanding HCC.

Aims & Methods

Aims: To identify the signatures of the circulating blood microbiome associated with hepatocellular carcinoma, response to treatment and disease prognosis.
Methods: This study conducted a post-hoc analysis of the SORAMIC clinical trial utilizing peripheral blood plasma samples. For this analysis, blood plasma samples from a cohort of 71 patients with HCC were examined (25 treated with Sorafenib and 46 with SIRT/Sorafenib). Peripheral blood samples were collected at two time points: baseline (prior to the initiation of anti-tumor therapy) with all 71 patients included, and post-therapy (7 to 9 weeks after treatment) with 39 patients included. Additionally, peripheral blood samples were obtained from 52 control subjects, who were endoscopically diagnosed with colonic diverticulosis, to compare against the patient group. The composition of the circulating blood microbiome was assessed through 16S rRNA gene sequencing, targeting the V1-V2 hypervariable regions. Subsequent analyses focused on identifying associations with potential novel biomarkers for diagnosis, prognosis, and response to treatment.

Results

Patients with HCC had significantly diminished α-diversity of the circulating blood microbiome as compared to controls. Significant differences were also observed in between microbial communities of these two cohorts based on Bray-Curtis dissimilarity index. Patients with HCC had significantly higher levels of Proteobacteria and Bacteroidetes and lower levels of Firmicutes and Campylobacterota. Differential abundance analysis revealed that families of Gordoniaceae, Cryomorphaceae, Burkholderiaceae, Comamonadaceae, Enterobacteriaceae were significantly enriched in patients with HCC. At the genus level, patients with HCC had higher levels of Gordonia, Fluviicola, Burholderia, Limnohabitans and Escherichia/Shigella and lower levels of Corynebacterium. HCC patients, who responded to treatment with SIRT/Sorafenib showed an increase in blood bacterial diversity, enrichment of families Burkholderiales incertae sedis, Arcobacteraceae, Peptostreptococcaceae, Moraxellaceae, genera Sphaerotilus, Aliacrobacter, Rhodoluna, Giesbergeria, Microbacterium, Romboutsia, Arcicella, Pseudorhodoferax and depletion in families Gordoniaceae, Cryomorphaceae and genera Cloacibacterium, Gordonia, Limnohabitans, Fluviicola after the treatment. Levels of Acinetobacter, Enhydrobacter and Micrococcus in the blood before the HCC treatment were associated with patient prognosis.

Conclusion

Patients with HCC exhibit a unique circulating blood microbiome profile characterized by reduced bacterial diversity. Response to treatment is linked to an increase in α-diversity and changes in the circulating microbiome profile. Specific members of the circulating microbiome show potential prognostic capabilities, suggesting their utility as biomarkers for predicting disease progression and treatment outcomes in HCC.

Introduction

Capsule endoscopy is the first-line examination for digestive bleeding with likely origin in the small bowel, in hemodynamically stable patients. In the 2022 update, ESGE guidelines recommend that, in the context of overt bleeding, capsule enteroscopy should be performed as soon as possible, ideally within the first 48 hours. In the previous guidelines, published in 2015, the recommended window was 14 days.

Aims & Methods

This study aimed to evaluate the improvement in yield offered by the new recommendations regarding the timing of urgent capsule enteroscopy. Patients with suspected overt middle gastrointestinal bleeding between January 2005 and November 2022 were retrospectively analyzed. Diagnostic and therapeutic yield, rebleeding rate, and mortality were compared when capsule enteroscopy was performed within the first 48 hours, within the first 14 days, or between the 3rd and 14th day after admission.

Results

A total of 138 patients were included (58.7% men, median age 66 years), 87 of whom (63.0%) underwent capsule enteroscopy within the first 48 hours after hospital admission. The median follow-up was 55 months (5-180). The diagnostic yield (presence of blood or lesions with bleeding potential) was slightly higher when capsule enteroscopy was performed within the first 48 hours (81.6% versus 76.5%, p=0.349). On the other hand, capsule enteroscopy within the first 48 hours was significantly associated with higher therapeutic yield (endoscopic, radiologic, or surgical treatment) - 54.0% versus 39.2%, p=0.02. The rebleeding rate was significantly lower in patients undergoing enteroscopy within 48 hours after admission (19.5% versus 29.4%, p=0.04). On the other hand, overall mortality at 36 months did not differ between strategies (21.8% and 25.5%, p=0.401).

Conclusion

Performing capsule endoscopy within the first 48 hours, as recommended by recently published guidelines, is associated with favourable short- and long-term clinical outcomes.

Introduction

Ustekinumab, an interleukin (IL) 12/23 inhibitor is a biologic used to treat inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Clinical and real-world evidence has demonstrated its ability to provide a clinically meaningful response and remission among patients; however, the economic impact of its use may not be favourable from the payer perspective. The objective of this targeted literature review was to understand the economic impact of ustekinumab reference product in the treatment of patients with IBD.

Aims & Methods

A literature search was conducted in MEDLINE for economic publications that evaluate the economic impact of ustekinumab or include ustekinumab within their analyses. Search terms included “budget impact model”, “budget impact analysis”, “cost-utility”, “cost-effect”, “ulcerative colitis”, “Crohn’s disease” and “ustekinumab” from database inception until Feb 8^th, 2024. Only studies published in English were eligible for inclusion.

Results

A total of 30 hits were screened for inclusion, yielding 12 relevant studies that discussed economic implications of ustekinumab. Five articles were conducted from the US payer perspective, two from the Japanese payer perspective, and one each from the Canadian, Swedish, Polish, French, and German perspectives. The economic models included budget impact models (n = 2), cost-effectiveness models (n = 8), and cost per responder/remitter analyses (n = 2). Five studies used a CD patient population, six studies focused on UC, and one study included a mixed population of CD and UC. In CD studies, two found ustekinumab was cost-effective: these studies were conducted from the perspective of Polish and Swedish payers in CD patients who failed anti-TNF therapy. Both studies used a Markov based model to assess cost-effectiveness of treatments. In the remaining CD studies, ustekinumab was associated with the highest cost per responder/remitter (Japanese payer perspective) and was dominated by other treatments in cost-effectiveness analyses (US payer perspective). The studies conducted in the UC patient population also found that, although clinically effective, ustekinumab was dominated (based on the incremental cost effectiveness ratio [ICER]) by other biologics included in the analyses (eg, vedolizumab and infliximab). Similar to the CD patient population, the cost per responder/remitter was highest for ustekinumab compared to five other therapies including tofacitinib and golimumab (US payer perspective). However, in two UC studies, ustekinumab was observed to be more effective than the most cost-effective treatment option (from the Japanese and US payer perspectives), highlighting that its price negatively affected its ICER. Moreover, cost-effectiveness analyses conducted by the German and Canadian perspectives, demonstrated that ustekinumab was not a cost-effective therapy at the current willingness to pay threshold (0% probability). Note, that no studies tested the possible cost-effectiveness of an ustekinumab biosimilar which would positively influence the cost associated with ustekinumab treatment.

Conclusion

This literature review demonstrated that, despite its high efficacy, ustekinumab is among the highest costing biologics available for the treatment of IBD with low probabilities of cost-effectiveness across several studies. As the economic burden for IBD is increasing globally, cost-saving therapeutic options such as biosimilars may help to provide savings that can be redistributed in a healthcare system or provide funds to expand patient access.

Disclosure

Kunal Shastri is an employee of Fresenius Kabi a manufacturer of biosimilars. Kerise Clarke, Margaret Ainslie-Garcia, Nicole Ferko are employees of EVERSANA a company who receives consulting fees from Fresenius Kabi.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, condition linked to a type 2 inflammatory response and frequently associated to other atopic conditions. EoE may presents either sporadically, or with aggregation of cases within a same family. Limited information has been provided on the differences in clinical characteristics and disease features between sporadic and familiar EoE, largely due to the lack of large patient cohorts.

Aims & Methods

To find differences in sporadic and familiar cases of EoE which may support distinct clinical management, a cross-sectional analysis of the multicenter EoE CONNECT registry was performed. Demographic and clinical from patients recruited at 42 hospitals in 4 European countries were extracted on March 28th, 2025. Information extracted included 1) age at diagnosis and diagnostic delay; 2) symptoms leading to diagnosis; 3) disease endoscopic and histologic features at diagnosis; and 4) atopic concomitances.

Results

	S-EoE	F-EoE
Age at diagnosis (n= 3,179) <18 years old	18.5%	30.6%
Inflammatory Score (n= 2,723)	1.62 ± 1.3	1.93 ± 1.32
Fibrosis Score (n=2,723)	1.04 ± 1.04	0.97 ± 1.08
Fibrosis (n=1,701)	58.6 %	62.8 %
EoE-Phenotype (n=3,017)
Inflammatory	75.9 %	79.6 %
Mixed	12.6 %	8.6 %
Stricturing	11.5 %	11.8 %

Overall, 4,053 patients (75.4 % males, mean age 33.3 ±15.2 years) were analyzed, including 3028 (74.7 %) sporadic (S-EoE), 714 (17.6%) without familiar data and 311 (7.7 %) familiar (F-EoE) cases including 89 families. Among the family forms, n= 76 families showed 2 affected members, n= 11 presented 3 members, and n= 2 with 4 members. In 85/89 families we identified the index case consisting in sons (13), parents (23), siblings (38), or other distant kinships.
The F-EoE forms were diagnosed at younger mean ± SD ages than S-EoE (29.8±15.6 vs. 33.7±15.1; p<0.001) and included a higher proportion of pediatric patients (considered as those below 18 at diagnosis; 30.6% vs. 18.5%; p<0.001)
Symptoms leading to EoE diagnosis were similar across study groups, with slightly higher presences of abdominal pain (as they included more pediatric cases; 7.7% vs. 4.5%; p=0.01) and chocking episodes (7.7% vs. 4.5%; p=0.01) among F-EoE.
Endoscopy presented more severe features according to EREFS among F-EoE (mean ± SD being 2.86 ± 1.66 vs. 2.64 ± 1.68; p=0.054) at the expense of both fibrotic and inflammatory features, despite only the later reach statistical significance (1.93 ± 1.32 vs. 1.62 ± 1.3; p<0.001). Esophageal biopsies exhibited higher mean ± SD peak eosinophil counts in F-EoE cases (57.11 ± 40.7 vs. 52.87 ± 37.97; p=0.04).
F-EoE were more allergic patients, as they presented a higher mean ± SD number of concomitant atopies (1.44 ± 1.25 vs. 1.25 ± 1.22; p=0.009) and all were more common among them, with conjunctivitis and hives reaching statistical significance (p=0.01 and p=0.002 respectively). Overall, a higher proportion of F-EoE had at least one atopy compared to S-EoE (69.4 % vs. 63.8%).

Conclusion

F-EoE seems to present more severely, with earlier onset, more inflammatory load in endoscopy and biopsies and higher concomitant allergic manifestations.

Introduction

Thiopurines (TP) (azathioprine AZA, and 6 mercaptopurine 6MP) are immunosuppressive drugs (IS) used in the treatment of chronic inflammatory bowel diseases (IBD), particularly Crohn's disease (CD). The aim of our work is to see if they still have an indication in monotherapy, in the era of biotherapies and small molecules.

Aims & Methods

This is a retrospective analytical study conducted at the Hepato-Gastroenterology and Proctology Department "Medicine B" from January 2012 to July 2022. 740 patients were followed for CD during this period. 407 patients were put on TP. Age, sex, different characteristics of CD, indication for and type of TP treatment, and course of treatment were collected from all patients. SPSS 20.0 software was used for statistical analysis. The khi-2 test was used to compare categorical variables. The binary logistic regression model was used for multivariate analysis.

Results

There were 375 patients followed up for CD on TP monotherapy (92.13%) and 32 on combination therapy (7.86%). The sex ratio was F/H=1.5. The average age was 39.8 years (15-72). The location was ileal in 69 patients (16.95%), colonic in 78 patients (19.16%), ileocolic in 257 patients (63.14%), 6 patients (1.47%) had upper gastrointestinal tract involvement of CD and 3 patients (0.73%) had anal CD. 99 patients (24.32%) had ano-perineal lesions (APL). The phenotype was stenosing in 47 cases (11.54%), fistulizing in 159 cases (39%), stenosing and fistulizing in 60 cases (14.74%) and inflammatory in 141 cases (34.64%). The type of TP used was AZA in 299 patients (73.46%) and 6MP in 108 patients (26.53%). TP was indicated as maintenance treatment in 270 cases (66.33%), as monotherapy in the absence of biotherapy (which was not available before 2016) in fistulizing forms in 105 cases (25.8%), and in case of cortico-dependency in 32 cases (7.86%).
Clinical remission was obtained with monotherapy in 326 cases (86.93%) and with combotherapy in 24 cases (75%), this difference is statistically non-significant p=0.08. Mucosal healing was noted with monotherapy in 124 cases (33%) in patients who performed a control endoscopy, and with combotherapy in 15 cases (46.87%), this difference is statistically not significant p=0.07.
CRP was negatived in monotherapy in 149 patients (39.73%) and in combination therapy in 27 patients (84.37%), this difference is statistically significant p<0.001. Fecal calprotectin was not always available. Among the patients who had it performed (65: 15.97%), it was negative in 18 cases (41.86%) in monotherapy and 3 cases (13.63%) in combination therapy. This difference is statistically significant p=0.015. Metabolite dosing was also rarely available. In cases where this was done (43 cases: 10.56%), 6-TGN was in the therapeutic range only in 14 cases (32.55%) and in 36 cases (83.72%) for 6-MMP, requiring therapeutic adjustment.
In multivariate analysis and adjusting for the different confounding parameters, it was found that only the combination therapy was a predictive factor for mucosal healing [OR=1.8; [0.8 - 3.9]; p=0.01].

Conclusion

The results of this study show that TPs still have a place in the therapeutic arsenal of CD, but that their combination with biotherapy allows more clinical and biological remission and especially mucosal healing.