Introduction

Cruoric thrombus in the portal vein represents the most frequent cause of infrahepatic portal hypertension. It most often complicates cirrhosis, but when it occurs in the absence of cirrhosis, it is favored by a pro-thrombotic state in 2/3 of patients. It can be total or partial, localized or extended to the spleno-mesenteric trunk. The absence of repermeabilization leads to the development of a collateral venous network known as portal cavernoma (or chronic PVT). Management is essentially based on treatment of the cause, and in the absence of contraindication, anticoagulation is recommended to prevent recurrence or extension of thrombosis. The aim of this study is to report our department's experience of the benefits of anticoagulation in cases of chronic portal thrombosis in a non-cirrhotic patient.

Aims & Methods

This is a retrospective, descriptive study over a 6-year period from 2018 to 2024, involving all patients with chronic portal thrombosis without cirrhosis on anticoagulation for more than 6 months. Curative-dose anticoagulation with vitamin K antagonsit and rivaroxaban 20mg/d was administered in patients with a major pro-thrombotic risk factor, and anticoagulation with rivaroxaban dosed at 15 mg/d in a low risk.

Results

Out of 58 patients followed for chronic portal vein thrombosis, 17 were put on anticoagulants: vitamin k antagonist (VKA) and direct oral anticoagulants (DOACs), with a prevalence of 29.31%. The mean age was 45.6 years (31-72), with a sex ratio of 0.4 M/F .Tow patient’s groups were identified: Patients with thrombosis at high risk of recurrence, requiring lifelong anticoagulantion this group included 10 patients for 58.8% : the dominant etiology is myeloprolierative syndrome in 60% of patients (n=6),followed by anti-phospholipid antibody syndrome in 40% (n=4).Treatment in these patients was based on curative anticoagulation with 3 patients on rivaroxaban 20mg/d, and 7 patients on adapted VKA with an INR target of between (2-3). In the second group at low risk of recurrence, receiving rivaroxaban 15mg/d, involving 41.1% of our patients (n=7). The etiologies were as follows: isolated protein C or S deficiency in 42.8% (n=3), celiac disease in 28.5% (n=2), hydatid cyst surgery in 14.2% (n=1), no etiology found in 14.2% of patients (n=1).The evolution was marked by the absence of thrombosis extension assessed by imaging after a minimum of 6 months' anticoagulant treatment in 58.8% of cases (n=10), a partial repermeabilization in 29.4% (n=5), And complete repermeabilization was observed in 11.7% (n=2).

Conclusion

Anticoagulant treatment proved effective in preventing recurrence and thrombotic extension in all patients in our study, as assessed by imaging, which, although not systematically recommended in the follow-up of portal cavernoma, enabled us to confirm non-extension of the thrombosis in 58.8% of cases, and partial repermeabilization in 29.4% and complete repermeabilization in 11.7% of patients , Hence the importance of early anticoagulation with etiological management.

Clinical Case Summary

Cronkhite-Canada syndrome (CCS) is a rare gastrointestinal disorder characterized by multiple polyps throughout the digestive tract, often accompanied by ectodermal changes such as onychodystrophy. Here, we present a case of CCS in a 65-year-old female with an unremarkable medical history presented with chronic abdominal pain and diarrhea containing mucus and blood, occurring 3 to 4 times per day. Clinical examination revealed signs consistent with malnutrition. Angular deformities, suggestive of onychodystrophy, were noted, while no other significant gastrointestinal abnormalities were observed.
During physical examination, the patient displayed signs of malnutrition. Abdominal palpation revealed tenderness, particularly in the lower quadrants, without palpable masses or organomegaly. Bowel sounds were present and within normal limits.
Laboratory investigations revealed elevated levels of ferritinemia. Computed tomography revealed three suspicious thickened segments within the digestive tract: one located in the antral region, the second in the cecal region, and the third in the sigmoid region. Colonoscopy demonstrated an erythematous colonic mucosa with polypoid lesions. Pathological examination revealed an illdefined colonic polyp characterized by multiple cystically dilated glands within an edematous lamina propria, accompanied by lymphocytes, plasma cells, and numerous eosinophils, favoring the diagnosis of Cronkhite-Canada syndrome.
This case highlights the importance of considering Cronkhite-Canada syndrome in the differential diagnosis of patients presenting with chronic gastrointestinal symptoms, malnutrition, and onychodystrophy. Early recognition and appropriate management, including nutritional support and surveillance for complications, are crucial in improving outcomes for patients with this rare and challenging syndrome. Further research is needed to better understand the pathogenesis and optimal treatment strategies for Cronkhite-Canada syndrome.

Introduction

Liquid biopsy in patients with pancreatic ductal adenocarcinoma (PDAC) has been challenged by the limited information obtained from systemic circulation (SC). Circulating Tumour Cells (CTCs) in portal circulation (PC) are deemed to be biologically relevant and potentially carrying prognostic significance, despite mostly been evaluated during surgery.

Aims & Methods

This prospective, single-centre, interventional study enrolled PDAC patients to assess the feasibility and safety of EUS-guided transgastric and transhepatic Portal Vein sampling (EUS-PVS) for isolating, enumerating, and characterizing CTCs. PC and paired SC samples underwent microfluidic enrichment and dielectrophoretic (DEP) single-cell sorting based on immunostaining for epithelial and mesenchymal biomarkers. Targeted next-generation KRAS sequencing was performed on CTC subpopulations in a subset of patients.

Results

Between May 2022 and October 2023, 20 PDAC patients (25% metastatic) underwent EUS-PVS with 100% feasibility and safety. CTCs were isolated in all patients from both districts, but the total CTC concentration was significantly higher in PC compared to SC (8.1 [5.8-21.3] vs. 4.1 [2.3-6] / 7.5 ml of blood, p= 0.01), particularly for mesenchymal CTCs. No associations with baseline clinical variables or disease stage were observed. A subset of CTCs exhibited KRAS codon 12 mutations, undetected in paired white blood cells.

Conclusion

EUS-PVS is a feasible, safe, and effective method for portal blood sampling, supporting subsequent molecular investigations. Despite more sensitive enrichment modalities enhance the yield of peripheral CTCs evaluation, portal circulation remains more informative, especially for detecting epithelial-to-mesenchymal transition events. DEP single-cell sorting was feasible in all patients, providing libraries of viable cells with specific 100%-pure phenotypes, potentially suitable for downstream molecular applications.

Introduction

CD is a chronic progressive disease associated with bowel damage and disability and with a globally increasing prevalence. Contemporary reports on the clinical presentation, disease outcomes, and treatment choices in newly diagnosed patients across Europe are important to inform physicians.

Aims & Methods

To describe the clinical characteristics in a contemporary European cohort of recently diagnosed CD patients. The Crohn´s Disease Cohort (CROCO) is an ongoing multicentre, European, prospective cohort study of recently diagnosed CD patients (within 12 months following diagnosis) intended to characterize bowel damage progression and disability. Herin, we report on the characteristics of CD-patients at inclusion in the study.

Results

Between Aug/21-April/24, 316 patients (58% male, 47% smoker or ex-smokers) with a median age at diagnosis of 34.4 (IQR 24.8; 49.6), were recruited from 17 centres. The median delay between symptoms onset and diagnosis was 6.5 months (IQR 2; 17.5); median disease duration at the time of inclusion was 3.9 months (IQR 1.6; 7.6); Ileal involvement (L1/L3) was reported in 86%. Overall, 15% had perianal disease and 28% had extra-intestinal manifestations, the most frequent being arthritis/arthralgia. One-third (32%) had evidence of either stricturing (B2) (17%) or penetrating (B3) (15%) phenotype; 7% had an intestinal-related surgery, and 2% perianal surgery. Fifty-nine (21%%) patients had at least one CD-related hospitalization. Median faecal calprotectin was was 236µg/g (IQR 75; 731) and median C-reactive protein was 4mg/L (IQR 1.2; 11). Regarding the therapies receiveid from diagnosis to inclusion, 54% of the patients had received systemic steroids, 18% 5ASA, 10% IM monotherapy, and 43% started biological therapy (126 anti-TNF, 6 anti-IL 12/23 and 3 anti-integrin).

Conclusion

In this prospective cohort of newly diagnosed CD-patients, more than one-third of the patients presented with a complicated phenotype despite a short delay between onset of symptoms and diagnosis. Steroids remain frequently used, however early and effective therapy was started in approximately in 40% of patients, highlighting the changing paradigm in CD treatment.

Disclosure

JB: Reports grants and personal fees from AbbVie, grants and personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillots Pharma, personal fees from Samsung Bioepis, grants and personal fees from Bristol Myers Squibb, grants from Novo Nordisk, personal fees from Pharmacosmos, personal fees from Ferring, personal fees from Galapagos, outside the submitted work. NA: received speaker fees from Ferring and Janssen. PE: educational grants Jannsen; SV: Speaker fees from Abbvie, Ferring, Janssen Takeda. IR-L: has received financial support for travelling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Celltrion, Chiesi, Danone, Dr. Falk Pharma, Ferring, Faes Farma Janssen, Galapagos, MSD, Otsuka Pharmaceutical, Pfizer, Roche, Takeda, and Tillotts Pharma. IO: has served as speaker and/or consultant and has received educational funding from MSD, Abbvie, Pfizer, Takeda, Janssen, Faes Farma and Chiesi, and has received research funding from Abbvie and Faes Farma. DD: Lecture fee/consultancy from: Takeda, Pfizer, Janssen, Ferring, AbbVie, Eli-Lilly. SS: received consulting fees and advisory board fees from Takeda, AbbVie, Merck, Ferring, Pharmacocosmos, Warner Chilcott, Janssen, Falk Pharma, Biohit, TriGenix, Celgene, and Tillots Pharma; speaker honoraria from AbbVie, Takeda, Celltrion, Pfizer, Biogen, AbbVie, Janssen, Merck, Warner Chilcott, and Falk Pharma. VH: Has served as consultant, has served as speaker, has received travel support or research funding from MSD, AbbVie, Ferring, Dr. Falk Pharma, Tillotts Pharma, Pfizer, Takeda, Janssen, KernPharma Biologics, Adacyte, Sandoz, Biogen, Fresenius-Kabi, FAES Farma and Galapagos. MN: received board membership, consultancy, or lecture fees from Abbvie, Amgen, Biogen, Celltrion, Ferring, Fresenius-Kabi, Galapagos, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Pfizer, Takeda, Viatris. MF: Lecture and consulting fees from Abbvie, Pfizer, Tillots, Takeda, Gilead, Arena, Sandoz, Celltrion, Galapagos, Celgene, Boehringer, Biogen, Viatris, Amgen, Fresenius, Celltrion, CTMA, Ferring and Janssen. MA: Speaker and consulting fees from Abbvie, Pfizer, Ferring and Janssen. BB: Speaker and consulting fees from Janssen, Takeda, Sofar, Alfasigma, Doxapharma. BB: Speaker and consulting fees from Janssen, Takeda, Sofar, Alfasigma, Doxapharma. RCU: has received consulting and/or advisory board fees from AbbVie, Bristol Myers Squibb, Celltrion, Janssen, Lilly, Pfizer, Roivant, Takeda. JC: receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda; receiving payment for lectures from AbbVie, Amgen, Anaptysbio, Allergan, Inc. Ferring Pharmaceuticals, Shire, and Takeda; receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech, Galxo Smith Kline, Japan Gastroenterological Endoscopy Society, Janssen Pharmaceuticals, Kaleido Biosciences, Imedex, Immunic, Iterative Scopes, Merck, Microba, Morgan, Lewis & Bockius LLP, Novartis, Otsuka Pharmaceutical Development PBM Capital, Pfizer, Protagonist Therapeutics Sanofi, Takeda, TiGenix, Vifor; and hold stock options in Intestinal Biotech Development. JT: Grant - AbbVie, Janssen Personal Fees - Pfizer, Janssen, Abbvie, sandoz.

Introduction

Dysbiosis of the microbiome is associated with inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), the two major forms of IBD. However, data are scarce and primarily limited to animal studies

Aims & Methods

We aimed to assess if stool microbiome characteristics are associated with disease severity, disease location, and inflammatory pathways using microbiome data obtained from the Study of a Prospective Adult Research Cohort with IBD (SPARC IBD) obtained from the IBD Plexus program of the Crohn’s & Colitis Foundation for 926 CD and 491 UC patients. Characterization of stool shotgun metagenomics was conducted with MetaPhlAn2 and HUMAnN2 to determine abundance of taxa and functional pathways, respectively. ANOVA and linear regression analyses were conducted to associate bacterial composition and functional potential with the selected clinical and exploratory measures. Mucosal inflammation was assessed with mucosal transcriptome data.

Results

Most of the samples came from Caucasians and females, and approximately 70% patients were in remission. 295 of 727 patients with CD had disease location data and 83% of these patients had ileal involvement (Table 1). We observed distinct microbial profiles between patients with active disease versus inactive disease in both CD and UC. Specifically, oral commensals belonging to Veillonella, Klebsiella, Rothia, and Megasphaera were more abundant in patients with active disease in both CD and UC, while 21 genera including butyrate producing species belonging to Anaerostipes, Ruthenibacterium, Faecalibacterium and Roseburia were more abundant in patients with inactive disease in both CD and UC. We also noted differences in relative abundances of bacterial taxa by disease activity separately within UC and CD. In UC, the fecal microbial signatures with active disease were enriched with Escherichia, Haemophilus, and Anaerococcus, while Lactococcus, Proteobacteria_unclassified, Parasutterella, and Gemella were more abundant in patients with inactive disease. In CD, 9 unique genera were more abundant in patients with active disease, and 24 unique genera were more abundant in patients with inactive disease, consistent with the fact that CD manifests in both isolated disease locations (ileum or colon) or a combination of locations (ileocolonic) and UC is limited to the colon and the rectum. Indeed, 32 out of the 33 genera specific to CD, but not UC, were found to be associated with altered enrichment in ileal or ileocolonic CD compared to colonic CD, when stratifying by disease location.

Table 1 Population characteristics including disease activity (CD and UC) and CD disease location

Conclusion

Differences in microbiota by disease location suggest separate location-specific pathologies. Location-specific interactions between host intestinal gene expressions and microbiota, suggest key immune-mediated molecular pathways and relevant bacteria in intestinal tissue, which may guide drug development and precision medicine in IBD.

Disclosure

Christopher Morehouse, Ben Sparklin, Bret Sellman, Antonio DiGiandomenico, Vancheswaran Gopalakrishnan, Bastian Angermann, Ulf Gehrmann, Jessica Neisen, Emon Khan and Junmei Cairns are all employees of AstraZeneca.