Altering the gut microbiome and tumor microenvironment in advanced liver cancer: A phase II study of nivolumab, tadalafil and oral vancomycin in patients with refractory primary hepatocellular carcinoma or liver dominant metastatic cancer from colorectal or pancreatic cancers.

A phase II study was conducted in patients with primary hepatocellular carcinoma or liver dominant metastatic cancer from colorectal (CRC) or pancreatic (PDAC) cancers to assess the effect of nivolumab (anti-PD1), oral vancomycin and tadalafil. Patients were treated with 480 mg nivolumab intravenously every 4 weeks, oral 10 mg tadalafil daily and 125 mg vancomycin orally every 6 h days 1-21 of a 28-day cycle. The primary endpoint was best overall response.

An Open-Source Normothermic Perfusion System Designed for Research Scientists.

The integration of ex vivo perfusion machines for human organs prior to transplantation has improved outcomes for recipients and increased organ availability while revealing novel avenues of investigation for translational medicine. However, these machines have limited availability for experimental modifications while presenting a significant upfront cost investment and prohibitive per-use cost to the research scientist. Furthermore, there is a significant need for improved pre-clinical models in biomedical research that allow for authentic interrogation of cellular processes in the multi-cellular organ setting.

Anti-vascular endothelial growth factor treatment potentiates immune checkpoint blockade through a BAFF- and IL-12-dependent reprogramming of the TME.

Anti-vascular endothelial growth factor (VEGF) treatment has shown clinical activity together with immune checkpoint blockade (ICB), but the exact mechanism is not known. We show that VEGF blockade in combination with anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) + anti-programmed death-ligand 1 (PD-L1) in cholangiocarcinoma (CCA) potentiated a multimodal mechanism dependent on B cell activating factor (BAFF), leading to a proinflammatory B cell response. It led to a BAFF- and interleukin (IL)-12-dependent expansion and rewiring of T regulatory cells (Tregs) toward an anti-tumor T helper-1 (Th-1)-like fragile state.

Quantifying morphologic variations as an alternate to standard response criteria for unresectable primary liver tumors after checkpoint inhibition therapy.

Purpose: The aim of this study was to assess the feasibility of quantifying morphologic changes in tumors during immunotherapy, as a reflection of response or survival.

Methods And Materials: A retrospective single-center analysis was performed in patients with unresectable liver cancer previously enrolled in clinical trials combining immunotherapy (tremelimumab ± durvalumab) and locoregional treatment (either ablation or transarterial chemoembolization). Conventional response (RECIST 1.

Taurine-conjugated bile acids and their link to hepatic S1PR2 play a significant role in hepatitis C-related liver disease.

Background: Bile acids mediate gut-liver cross-talk through bile acid receptors. Serum, hepatic, and microbial bile acid metabolism was evaluated in HCV-compensated chronic liver disease.

Methods: Patients underwent liver biopsy; portal and peripheral blood were obtained before (HCVi), and 6 months after sustained virologic response (SVR), splenic blood was obtained only after SVR.

Timing, incidence and management of delayed bleeding after partial nephrectomy in patients at risk for recurrent, bilateral, multifocal renal tumors.

Introduction: Delayed bleeding is a potentially serious complication after partial nephrectomy (PN), with reported rates of 1%-2%. Patients with multiple renal tumors, including those with hereditary forms of kidney cancer, are often managed with resection of multiple tumors in a single kidney which may increase the risk of delayed bleeding, though outcomes have not previously been reported specifically in this population. The objective of this study was to evaluate the incidence and timing of delayed bleeding as well as the impact of intervention on renal functional outcomes in a cohort primarily made up of patients at risk for bilateral, multifocal renal tumors.

The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial.

The multi-cohort phase 2 trial NCT02203513 was designed to evaluate the clinical activity of the CHK1 inhibitor (CHK1i) prexasertib in patients with breast or ovarian cancer. Here we report the activity of CHK1i in platinum-resistant high-grade serous ovarian carcinoma (HGSOC) with measurable and biopsiable disease (cohort 5), or without biopsiable disease (cohort 6). The primary endpoint was objective response rate (ORR).

Combined immune checkpoint inhibition with durvalumab and tremelimumab with and without radiofrequency ablation in patients with advanced biliary tract carcinoma.

Background: Current standard of care for advanced biliary tract cancer (BTC) is gemcitabine, cisplatin plus anti-PD1/PD-L1, but response rates are modest. The purpose of this study was to explore the efficacy and safety of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4), with and without an interventional radiology (IR) procedure in advanced BTC.

Methods: Eligible patients with advanced BTC who had received or refused at least one prior line of systemic therapy were treated with tremelimumab and durvalumab for four combined doses followed by monthly durvalumab alone with and without an IR procedure until the progression of disease or unacceptable toxicity.

VB-111 (ofranergene obadenovec) in combination with nivolumab in patients with microsatellite stable colorectal liver metastases: a single center, single arm, phase II trial.

Background: Microsatellite stable colorectal liver metastases (MSS CLM) maintain an immunosuppressive tumor microenvironment (TME). Historically, immune-based approaches have been ineffective. VB-111 (ofranergene obadenovec) is a genetically-modified adenoviral vector targeting the TME; its unique dual mechanism induces an immune response and disrupts neovascularization.

Dynamic Elevation of Aromatic Amino Acids in Hepatitis C Virus-Induced Cirrhosis After a Standard Meal.

Introduction: Perturbations in aromatic (AAAs) and branched-chain amino acids (BCAAs) are seen in decompensated liver disease. The aim of this study was to evaluate the dynamic, postprandial relationship between hepatitis C virus-induced liver disease and amino acid concentrations in patients with compensated liver disease.

Methods: Patients infected with hepatitis C virus underwent a baseline liver biopsy to determine Ishak Fibrosis Score and evaluate the liver transcriptome.

A Simple, Rapid, and Effective Heparinase Protocol to Enable Nucleic Acid Study from Frozen Heparinized Plasma.

Cell-free RNAs (cfRNAs) are promising analytes as non-invasive biomarkers and have even greater potential if tied in with metabolomics. Plasma is an optimal source for cfRNAs but is often derived from a variety of anticoagulants. Plasma obtained in heparin is suitable for metabolomics but is difficult to utilize for qPCR-based downstream analysis.

Non-selective dampening of the host immune response after hepatitis C clearance and its association with circulating chemokine and endotoxin levels.

Background & Aims: Direct-acting antiviral (DAA) therapy has revolutionized treatment for the hepatitis C virus (HCV). While DAA therapy is common, little is known about the intrahepatic immunological changes after sustained virologic response (SVR). We aim to describe transcriptional alterations of the gut microbiome and the liver after SVR.

Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine.

Background: The four co-circulating and immunologically interactive dengue virus serotypes (DENV1-4) pose a unique challenge to vaccine design because sub-protective immunity can increase the risk of severe dengue disease. Existing dengue vaccines have lower efficacy in DENV seronegative individuals but higher efficacy in DENV exposed individuals. There is an urgent need to identify immunological measures that are strongly associated with protection against viral replication and disease following sequential exposure to distinct serotypes.

Longitudinal multi-omics analyses of the gut-liver axis reveals metabolic dysregulation in hepatitis C infection and cirrhosis.

The gut and liver are connected via the portal vein, and this relationship, which includes the gut microbiome, is described as the gut-liver axis. Hepatitis C virus (HCV) can infect the liver and cause fibrosis with chronic infection. HCV has been associated with an altered gut microbiome; however, how these changes impact metabolism across the gut-liver axis and how this varies with disease severity and time is unclear.

Metastatic Grade 3 Neuroendocrine Tumor in Multiple Endocrine Neoplasia Type 1 Expressing Somatostatin Receptors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) may occur in 30% to 90% of patients with multiple endocrine neoplasia type 1 (MEN1). However, only 1% of GEP-NETs are grade 3 (G3). Given the rarity of these aggressive tumors, treatment of advanced G3 GEP-NETs in MEN1 is based on the treatment guidelines for sporadic GEP-NETs.

Cone-Beam Computed Tomography-Based Spatial Prediction of Drug Dose After Transarterial Chemoembolization Using Radiopaque Drug-Eluting Beads in Woodchuck Hepatocellular Carcinoma.

Objectives: The aims of this study were to develop a model to estimate drug dose delivered to tumors after transarterial chemoembolization (TACE) with radiopaque drug-eluting beads (DEBs) based on DEB density on cone-beam computed tomography (CT) and to evaluate drug penetration into tissue in a woodchuck hepatoma model.

Materials And Methods: Transarterial chemoembolization was performed in woodchucks with hepatocellular carcinoma (N = 5) using DEBs (70-150 μm, LC Bead LUMI) loaded with doxorubicin. Livers were resected 45 minutes after embolization, immediately frozen, and cut using liver-specific, 3D-printed sectioning molds.

Case Report: Fatal Complications of BK Virus-Hemorrhagic Cystitis and Severe Cytokine Release Syndrome Following BK Virus-Specific T-Cells.

BK virus (BKV)-hemorrhagic cystitis (HC) is a well-known and rarely fatal complication of hematopoietic stem cell transplantation (HSCT). Treatment for BKV-HC is limited, but virus-specific T-cells (VST) represent a promising therapeutic option feasible for use posttransplant. We report on the case of a 16-year-old male with dedicator of cytokinesis 8 (DOCK8) deficiency who underwent haploidentical HSCT complicated by severe BKV-HC, catastrophic renal hemorrhage, and VST-associated cytokine release syndrome (CRS).

Predictors of F-DCFPyL PET/CT Positivity in Patients with Biochemical Recurrence of Prostate Cancer After Local Therapy.

Our objective was to investigate the factors predicting scan positivity and disease location in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after primary local therapy using prostate-specific membrane antigen-targeted F-DCFPyL PET/CT. This was a 2-institution study including 245 BCR PCa patients after primary local therapy and negative results on conventional imaging. The patients underwent F-DCFPyL PET/CT.

Tumor Doubling Time Using CT Volumetric Segmentation in Metastatic Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy with an overall unfavorable prognosis. Clinicians treating patients with ACC have noted accelerated growth in metastatic liver lesions that requires rapid intervention compared to other metastatic locations. This study measured and compared the growth rates of metastatic ACC lesions in the lungs, liver, and lymph nodes using volumetric segmentation.

A Comparison of F-DCFPyL, F-NaF, and F-FDG PET/CT in a Prospective Cohort of Men with Metastatic Prostate Cancer.

F-DCFPyL, F-sodium fluoride (F-NaF), and F-FDG PET/CT were compared in a prospective cohort of men with metastatic prostate cancer (PCa). Sixty-seven men (group 1) with documented metastatic PCa underwent F-DCFPyL and F-NaF PET/CT and a subgroup of 30 men (group 2) underwent additional imaging with F-FDG PET/CT. The tracers were compared for their detection rates, imaging concordance, associations with prostate-specific antigen (PSA), treatment at the time of imaging, and castration status.

HepQuant SHUNT Detects Portal Hypertension in Early Stages of Clinically Compensated Chronic Liver Disease.

Physicians use portal pressure measurements in clinical practice and research but the methods are invasive, can cause complications, and are resource intensive. Herein we describe preliminary findings of the minimally invasive HepQuant-SHUNT test in the diagnosis of portal hypertension in precirrhotic and compensated cirrhotic patients.

Pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers.

OATP1B3 is expressed de novo in primary prostate cancer tissue and to a greater degree in prostate cancer metastases. Gadoxetate disodium is a substrate of OATP1B3, and its uptake has been shown to correlate with OATP1B3 expression in other cancers. We aimed to evaluate use of gadoxetate disodium to image prostate cancer and to track its utility as a biomarker.

Long-term outcomes in patients with advanced adrenocortical carcinoma after image-guided locoregional ablation or embolization.

Background: To evaluate outcomes and survival rates in patients with metastatic adrenocortical carcinoma (ACC) who were treated with image-guided locoregional treatments (IGLTs).

Purpose: To evaluate the overall survival (OS) and clinical impact of IGLT in the management of patients with advanced metastatic ACC.

Methods: Retrospective review of 39 patients treated with IGLT between 1999 and 2018 was performed.