Factors Impacting Survival After Transarterial Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: A Combined Analysis of the Prospective CIRT Studies.

PURPOSE: Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with intrahepatic cholangiocarcinoma (ICC). However, optimising the timing of TARE in relation to systemic therapies and patient selection remains challenging. We report here on the effectiveness, safety, and prognostic factors associated with TARE for ICC in a combined analysis of the prospective observational CIRT studies (NCT02305459 and NCT03256994). METHODS: A combined analysis of 174 unresectable ICC patients enrolled between 2015 and 2020 was performed. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every follow-up visit. Log-rank tests and a multivariable Cox proportional hazard model were used to identify prognostic factors. RESULTS: Patients receiving a first-line strategy of TARE in addition to any systemic treatment had a median OS and PFS of 32.5 months and 11.3 months. Patients selected for first-line TARE alone showed a median OS and PFS of 16.2 months and 7.4 months, whereas TARE as 2nd or further treatment-line resulted in a median OS and PFS of 12 and 9.3 months (p = 0.0028), and 5.1 and 3.5 months (p = 0.0012), respectively. Partition model dosimetry was an independent predictor for better OS (HR 0.59 [95% CI 0.37-0.94], p = 0.0259). No extrahepatic disease, no ascites, and < 6.1 months from diagnosis to treatment were independent predictors for longer PFS. CONCLUSION: This combined analysis indicates that in unresectable ICC, TARE in combination with any systemic treatment is a promising treatment option. LEVEL OF EVIDENCE: level 3, Prospective observational.

Mimicking the Intestinal Host-Pathogen Interactions in a 3D In Vitro Model: The Role of the Mucus Layer.

The intestinal mucus lines the luminal surface of the intestinal epithelium. This mucus is a dynamic semipermeable barrier and one of the first-line defense mechanisms against the outside environment, protecting the body against chemical, mechanical, or biological external insults. At the same time, the intestinal mucus accommodates the resident microbiota, providing nutrients and attachment sites, and therefore playing an essential role in the host-pathogen interactions and gut homeostasis. Underneath this mucus layer, the intestinal epithelium is organized into finger-like protrusions called villi and invaginations called crypts. This characteristic 3D architecture is known to influence the epithelial cell differentiation and function. However, when modelling in vitro the intestinal host-pathogen interactions, these two essential features, the intestinal mucus and the 3D topography are often not represented, thus limiting the relevance of the models. Here we present an in vitro model that mimics the small intestinal mucosa and its interactions with intestinal pathogens in a relevant manner, containing the secreted mucus layer and the epithelial barrier in a 3D villus-like hydrogel scaffold. This 3D architecture significantly enhanced the secretion of mucus. In infection with the pathogenic adherent invasive E. coli strain LF82, characteristic of Crohn's disease, we observed that this secreted mucus promoted the adhesion of the pathogen and at the same time had a protective effect upon its invasion. This pathogenic strain was able to survive inside the epithelial cells and trigger an inflammatory response that was milder when a thick mucus layer was present. Thus, we demonstrated that our model faithfully mimics the key features of the intestinal mucosa necessary to study the interactions with intestinal pathogens.

Short-term Safety and Quality of Life Outcomes Following Radioembolization in Primary and Secondary Liver Tumours: a Multi-centre Analysis of 200 Patients in France.

PURPOSE: Radioembolization has emerged as a treatment modality for patients with primary and secondary liver tumours. This observational study CIRT-FR (CIRSE Registry for SIR-Spheres Therapy in France) aims to evaluate real-life clinical practice on all patients treated with transarterial radioembolization (TARE) using SIR-Spheres yttrium-90 resin microspheres in France. In this interim analysis, safety and quality of life data are presented. Final results of the study, including secondary effectiveness outcomes, will be published later. Overall, CIRT-FR is aiming to support French authorities in the decision making on reimbursement considerations for this treatment. METHODS: Data on patients enrolled in CIRT-FR from August 2017 to October 2019 were analysed. The interim analysis describes clinical practice, baseline characteristics, safety (adverse events according to CTCTAE 4.03) and quality of life (according to EORTC QLQ C30 and HCC module) aspects after TARE. RESULTS: This cohort included 200 patients with hepatocellular carcinoma (114), metastatic colorectal cancer (mCRC; 38) and intrahepatic cholangiocarcinoma (33) amongst others (15). TARE was predominantly assigned as a palliative treatment (79%). 12% of patients experienced at least one adverse event in the 30 days following treatment; 30-day mortality was 1%. Overall, global health score remained stable between baseline (66.7%), treatment (62.5%) and the first follow-up (66.7%). CONCLUSION: This interim analysis demonstrates that data regarding safety and quality of life generated by randomised-controlled trials is reflected when assessing the real-world application of TARE. TRIAL REGISTRATION: Clinical Trials.gov NCT03256994.

Non-obstructive prosthetic heart valve thrombosis (NOPVT): Really a benign entity?

AIMS: To assess the effectiveness of different treatment strategies in patients with non-obstructive prosthetic valve thrombosis (NOPVT) during hospitalization and long-term follow-up. METHODS: NOPVT was diagnosed by transesophageal echocardiography. Resolution was defined as the disappearance or reduction of the thrombus under anticoagulation. All cases were first managed with optimization of anticoagulation. At discharge, patients received oral anticoagulation (OAC) alone or OAC and antiplatelet therapy (double treatment). Adverse events were defined as cardiovascular death, recurrence, thromboembolic events or major bleeding. RESULTS: From 1997 to 2012, 47 patients (mean age: 65years; women: 60%) were diagnosed with NOPVT (mitral valve: 97%). Previous poor anticoagulation control was documented in 66% of patients. Twenty-one patients (45%) were treated with unfractionated heparin (UFH), especially those with thrombus size >10mm (19/21). Optimization of OAC was performed in the remaining patients. Treatment failed in 13 (27.6%) patients, mostly in those who received UFH (10/13), requiring surgery (53.8%) or fibrinolysis (30.7%). Forty-two patients survived and, at discharge, 44% of patients received OAC alone and 56% the double treatment. At follow-up (median 23months; range 0.03-116months), 59.5% of patients presented cardiovascular events, however no differences in outcome were observed with double treatment or OAC alone (p=0.385). CONCLUSIONS: NOPVT is a high-risk complication, not only during hospitalization but also during follow-up. Optimization of anticoagulation is efficient in most patients except in thrombi ≥10mm treated with UFH. The double treatment does not prevent adverse events or complications during follow-up.