Nonbacterial thrombotic endocarditis in a patient with gastric cancer and SARS-CoV-2 infection.

Nonbacterial thrombotic endocarditis, formerly known as marantic endocarditis, is a very rare complication of advanced malignancy and other hypercoagulable states in which sterile, fibrin vegetations develop on heart valve leaflets. The most common malignancies associated with this entity are lung, pancreatic and gastric cancer. It has also been described as a presentation of COVID-19, which is known to be frequently complicated with coagulopathy and thromboembolic events. We report the case of a 62 year-old female patient newly diagnosed with stage IV gastric cancer and acute SARS-CoV-2 infection, presenting with confusion and homonymous hemianopsia in the setting of multiple acute ischemic strokes complicating a nonbacterial thrombotic mitral endocarditis. Herein, we discuss the underlying pathophysiology and make the hypothesis that SARS-CoV-2 infection could have participated in the pathogenesis of nonbacterial thrombotic endocarditis in our patient suffering from a gastric cancer.

Prognostic value of a three-scale grading system based on combining molecular imaging with 68Ga-DOTATATE and 18F-FDG PET/CT in patients with metastatic gastroenteropancreatic neuroendocrine neoplasias.

We investigated on the added prognostic value of a three-scale combined molecular imaging with 68Ga-DOTATATE and 18F-FDG PET/CT, (compared to Ki-67 based histological grading), in gastroenteropancreatic neuroendocrine neoplasia patients. 85 patients with histologically proven metastatic gastroenteropancreatic neuroendocrine neoplasias, who underwent combined PET/CT imaging were retrospectively evaluated. Highest Ki-67 value available at time of 18F-FDG PET/CT was recorded. Patients were classified according to World Health Organization/European Neuroendocrine Tumor Society histological grades (G1, G2, G3) and into three distinct imaging categories (C1: all lesions are 18F-FDG negative/68Ga-DOTATATE positive, C2: patients with one or more 18F-FDG positive lesions, all of them 68Ga-DOTATATE positive, C3: patients with one or more 18F-FDG positive lesions, at least one of them 68Ga-DOTATATE negative). The primary endpoint of the study was Progression-Free Survival, assessed from the date of 18F-FDG PET/CT to the date of radiological progression according to Response Evaluation Criteria In Solid Tumors version 1.1. Classification according to histological grade did not show significant statistical difference in median Progression-Free Survival between G1 and G2 but was significant between G2 and G3 patients. In contrast, median Progression-Free Survival was significantly higher in C1 compared to C2 and in C2 compared to C3 patients, revealing three distinctive imaging categories, each with highly distinctive prognosis. Our three-scale combined 68Ga-DOTATATE/18F-FDG PET imaging classification holds high prognostic value in patients with metastatic gastroenteropancreatic neuroendocrine neoplasias.

Chimeric Antigen Receptor-T Cells for Targeting Solid Tumors: Current Challenges and Existing Strategies.

Chimeric antigen receptor-T cells (CAR-Ts) are an exciting new cancer treatment modality exemplified by the recent regulatory approval of two CD19-targeted CAR-T therapies for certain B cell malignancies. However, this success in the hematological setting has yet to translate to a significant level of objective clinical responses in the solid tumor setting. The reason for this lack of translation undoubtedly lies in the substantial challenges raised by solid tumors to all therapies, including CAR-T, that differ from B cell malignancies. For instance, intravenously infused CAR-Ts are likely to make rapid contact with cancerous B cells since both tend to reside in the same vascular compartments within the body. By contrast, solid cancers tend to form discrete tumor masses with an immune-suppressive tumor microenvironment composed of tumor cells and non-tumor stromal cells served by abnormal vasculature that restricts lymphocyte infiltration and suppresses immune function, expansion, and persistence. Moreover, the paucity of uniquely and homogeneously expressed tumor antigens and inherent plasticity of cancer cells provide major challenges to the specificity, potency, and overall effectiveness of CAR-T therapies. This review focuses on the major preclinical and clinical strategies currently being pursued to tackle these challenges in order to drive the success of CAR-T therapy against solid tumors.

Comparative analysis of ESD versus EMR in a large European series of non-ampullary superficial duodenal tumors.

BACKGROUND AND STUDY AIMS: The choice of endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) in non-ampullary superficial duodenal tumors (NASDTs) is challenging and the benefits of ESD remain unclear. The aim was to comparatively analyze the feasibility, outcomes and safety of these techniques in these lesions. PATIENTS AND METHODS: This is an observational and retrospective study. All consecutive patients presenting with NASDTs who underwent EMR or ESD between 2005 and 2017 were included. The following main outcomes were comparatively evaluated: en-bloc and complete (R0) resection rates, and local recurrence. Secondary outcomes were perforation and delayed bleeding. RESULTS: One hundred sixty-six tumors in 150 patients (age: 66 years, range: 31 - 83, 42.7 % males) were resected by ESD (n = 37) or EMR (n = 129) and included. The median procedure time (81 vs. 50 min, P  = 0.007) and tumor size (25 vs. 20 mm, P  = 0.01) were higher in the ESD group. The global malignancy rate was 50.3 %. There were no differences in en-bloc resection (29.7 % vs. 44.2 %, P  = 0.115), complete resection (19.4 % vs. 35.5 %, P  = 0.069), and local recurrence (14.7 % vs. 16.7 %, P  = 0.788) rates. Tumor size was associated with recurrence (28 vs. 20 mm, P  = 0.008), with a median follow-up of 6.5 months. Focal recurrence (n = 22, 13.3 %) was treated endoscopically in 86.4 %. En-bloc resection in the ESD group was comparable in large ( ≥ 20 mm) and small lesions (27.6 % vs. 37.5 %, P  = 0.587), while this outcome decreased significantly in large lesions resected by EMR (17.4 % vs. 75 %, P  < 0.001). Nine perforations were confirmed in 6 lesions (16.2 %) resected by ESD and 3 (2.3 %) by EMR ( P  = 0.001). Endoscopic therapy was successful in all but 1 patient (88.9 %) presenting with a delayed perforation. CONCLUSIONS: ESD may be an alternative to EMR and surgery in selected NASDTs, such as large duodenal tumors where EMR achieves low en-bloc resection rates and the local recurrence may be higher. However, this technique may have a higher risk of perforations.

Celyad's novel CAR T-cell therapy for solid malignancies.

Celyad recently initiated several clinical trials with the CYAD-01 product, a natural killer group 2D (NKG2D)-based chimeric antigen receptor (CAR), in both solid and hematologic tumor types. This review discusses the unique properties of CYAD-01, expecting to provide a new paradigm to fight against solid tumors.