Clinical trial protocol for PanDox: a phase I study of targeted chemotherapy delivery to non-resectable primary pancreatic tumours using thermosensitive liposomal doxorubicin (ThermoDox®) and focused ultrasound.

Background: The dense stroma of pancreatic ductal adenocarcinomas is a major barrier to drug delivery. To increase the local drug diffusion gradient, high doses of chemotherapeutic agent doxorubicin can be released from thermally-sensitive liposomes (ThermoDox®) using ultrasound-mediated hyperthermia at the tumour target. PanDox is designed as a Phase 1 single centre study to investigate enhancing drug delivery to adult patients with non-operable pancreatic ductal adenocarcinomas.

Immune checkpoint inhibition: a future guided by radiology.

The limitation of the function of antitumour immune cells is a common hallmark of cancers that enables their survival. As such, the potential of immune checkpoint inhibition (ICI) acts as a paradigm shift in the treatment of a range of cancers but has not yet been fully capitalised. Combining minimally and non-invasive locoregional therapies offered by radiologists with ICI is now an active field of research with the aim of furthering therapeutic capabilities in medical oncology.

Thermosensitive liposomes: a promising step toward localised chemotherapy.

Introduction: Many small molecules and biologic therapeutics have been developed for solid tumor therapy. However, the unique physiology of tumors makes the actual delivery of these drugs into the tumor mass inefficient. Such delivery requires transport from blood vessels, across the vasculature and into and through interstitial space within a tumor.

Increased monocyte level is a risk factor for radiological progression in patients with early fibrotic interstitial lung abnormality.

Background: Interstitial lung abnormalities (ILA) are specific spatial patterns on computed tomography (CT) scan potentially compatible with early interstitial lung disease. A proportion will progress; management involves risk stratification and surveillance. Elevated blood monocyte levels have been shown to associate with progression of idiopathic pulmonary fibrosis.

Quantifying cell death induced by doxorubicin, hyperthermia or HIFU ablation with flow cytometry.

Triggered release and targeted drug delivery of potent anti-cancer agents using hyperthermia-mediated focused-ultrasound (FUS) is gaining momentum in the clinical setting. In early phase studies, tissue biopsy samples may be harvested to assess drug delivery efficacy and demonstrate lack of instantaneous cell death due to FUS exposure. We present an optimised tissue cell recovery method and a cell viability assay, compatible with intra-cellular doxorubicin.

Large-Volume Hyperthermia for Safe and Cost-Effective Targeted Drug Delivery Using a Clinical Ultrasound-Guided Focused Ultrasound Device.

Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically.

Role of diffusion-weighted imaging in monitoring treatment response following high-intensity focused ultrasound ablation of recurrent sacral chordoma.

Chordoma is the most common malignant tumor of the sacrum and is associated with significant neurologic morbidity. Local recurrence is very common, and the long-term prognosis is poor. High-intensity focused ultrasound (HIFU) is a noninvasive and nonionising ablative therapy that has been successful in treating other tumor types and is being evaluated as a new therapy for sacral chordoma.

Ultrasound-Guided High Intensity Focused Ultrasound Ablation for Symptomatic Uterine Fibroids: Preliminary Clinical Experience.

Objective:  To evaluate the middle-term efficacy and complications of ultrasound-guided high intensity focused ultrasound (USgHIFU) for the treatment of symptomatic uterine fibroids in an NHS population.

Methods:  A prospective observational single-center study at a single university hospital in Oxford, UK. Patients with symptomatic uterine fibroids who declined standard surgical/radiological intervention and were referred to the HIFU unit were considered for USgHIFU treatment.

Focused Ultrasound Hyperthermia for Targeted Drug Release from Thermosensitive Liposomes: Results from a Phase I Trial.

Purpose To demonstrate the feasibility and safety of using focused ultrasound planning models to determine the treatment parameters needed to deliver volumetric mild hyperthermia for targeted drug delivery without real-time thermometry. Materials and Methods This study was part of the Targeted Doxorubicin, or TARDOX, phase I prospective trial of focused ultrasound-mediated, hyperthermia-triggered drug delivery to solid liver tumors ( ClinicalTrials.gov identifier NCT02181075).

Long-term radiological and histological outcomes following selective internal radiation therapy to liver metastases from breast cancer.

Liver metastasis from breast cancer is associated with poor prognosis and is a major cause of early morbidity and mortality. When liver resection is not feasible, minimally invasive directed therapies are considered to attempt to prolong survival. Selective internal radiation therapy (SIRT) with yttrium-90 microspheres is a liver-directed therapy that can improve local control of liver metastases from colorectal cancer.

Safety and feasibility of ultrasound-triggered targeted drug delivery of doxorubicin from thermosensitive liposomes in liver tumours (TARDOX): a single-centre, open-label, phase 1 trial.

Background: Previous preclinical research has shown that extracorporeal devices can be used to enhance the delivery and distribution of systemically administered anticancer drugs, resulting in increased intratumoural concentrations. We aimed to assess the safety and feasibility of targeted release and enhanced delivery of doxorubicin to solid tumours from thermosensitive liposomes triggered by mild hyperthermia, induced non-invasively by focused ultrasound.

Methods: We did an open-label, single-centre, phase 1 trial in a single UK hospital.

Clinical trial protocol for TARDOX: a phase I study to investigate the feasibility of targeted release of lyso-thermosensitive liposomal doxorubicin (ThermoDox®) using focused ultrasound in patients with liver tumours.

Background: TARDOX is a Phase I single center study of ultrasound triggered targeted drug delivery in adult oncology patients with incurable liver tumours. This proof of concept study is designed to demonstrate the safety and feasibility of targeted drug release and enhanced delivery of doxorubicin from thermally sensitive liposomes (ThermoDox®) triggered by mild hyperthermia induced by focused ultrasound in liver tumours. A key feature of the study is the direct quantification of the doxorubicin concentration before and after ultrasound exposure from tumour biopsies, using high performance liquid chromatography (HPLC).

High-intensity focused ultrasonic ablation of sacral chordoma is feasible: a series of four cases and details of a national clinical trial.

High-intensity focused ultrasound describes the use of high-intensity focused ultrasound (HIFU) to ablate tumours without requiring an incision or other invasive procedure. This technique has been trialled on a range of tumours including uterine fibroids, prostate, liver and renal cancer. We describe our experience of using HIFU to ablate sacral chordoma in four patients with advanced tumours.

Esophageal Atresia: Improved Outcome in High-Risk Groups Revisited.

Objectives Improved survival in infants with esophageal atresia (EA) with a birth weight < 1,500 g or a major cardiac anomaly has been reported when compared with the original Spitz classification proposed in 1994. Aim We reviewed outcome data for infants born over the last decade in our institution to update previously reported survival statistics. Materials and Methods The records of all neonates (n = 200) with a diagnosis of EA managed in a single institution between 2001 and 2011 were reviewed and compared with data from the original Spitz study and the subsequent reported cohort from the same institution.

Genome-wide molecular characterization of central nervous system primitive neuroectodermal tumor and pineoblastoma.

Central nervous system primitive neuroectodermal tumor (CNS PNET) and pineoblastoma are highly malignant embryonal brain tumors with poor prognoses. Current therapies are based on the treatment of pediatric medulloblastoma, even though these tumors are distinct at both the anatomical and molecular level. CNS PNET and pineoblastoma have a worse clinical outcome than medulloblastoma; thus, improved therapies based on an understanding of the underlying biology of CNS PNET and pineoblastoma are needed.

Atypical presentation of purpura fulminans following sepsis in an adult.

A 67-year-old morbidly obese female with a background of stage 4 chronic renal failure, ischaemic heart disease, congestive cardiac failure, atrial fibrillation and type 2 diabetes mellitus presented with sepsis and necrotic lesions of the proximal lower limbs. Initial histological findings were consistent with the clinical diagnosis of calciphylaxis and supportive treatment was commenced with addition of a phosphate binder and dietary restriction. Due to high anaesthetic risk, her wounds were managed with larva therapy in the first instance, however, ultimately surgical debridement was the required.

Multimodal microglia imaging of fiber tracts in acute subcortical stroke.

Objective: Case series with (11)C-PK11195 and positron emission tomography (PET) in stroke patients suggest that activated microglia may be detected in remote brain regions with fiber tract connections to the lesion site as an indicator of poststroke neuroinflammation. However, the specificity of these imaging findings remains to be demonstrated.

Methods: In a prospective controlled study, we measured microglia activity using (11)C-PK11195-PET along the pyramidal tract, as defined by diffusion tensor imaging, in 21 patients with first-time acute subcortical ischemia within 2 weeks of stroke.

Chlorophyll biomass in the global oceans: airborne lidar retrieval using fluorescence of both chlorophyll and chromophoric dissolved organic matter.

For three decades airborne laser-induced fluorescence has demonstrated value for chlorophyll biomass retrieval in wide-area oceanic field experiments, satellite validation, and algorithm development. A new chlorophyll biomass retrieval theory is developed using laser-induced and water Raman normalized fluorescence of both (a) chlorophyll and (b) chromophoric dissolved organic matter (CDOM). This airborne lidar retrieval theory is then independently confirmed by chlorophyll biomass obtained from concurrent (1) ship-cruise retrievals, (2) satellite inherent optical property (IOP) biomass retrievals, and (3) satellite standard band-ratio chlorophyll biomass retrievals.

Chlorophyll biomass in the global oceans: satellite retrieval using inherent optical properties.

In the upper layer of the global ocean, 2082 in situ chlorophyll biomass values (Chl) are retrieved by concurrent satellite-derived inherent optical properties (IOP). It is found that (1) the phytoplankton absorption coefficient IOP alone does not provide satisfactory (Chl) retrieval; (2) the chromophoric dissolved organic matter (CDOM) absorption coefficient IOP must also be used to obtain satisfactory retrieval through (Chl) alpha a ph + pa CDOM where p is a constant and a ph and aCDOM are, respectively, the phytoplankton and CDOM absorption coefficients; (3) the IOP-based (Chl) retrieval performance is comparable to standard satellite reflectance ratio retrievals (that have CDOM absorption intrinsically embedded within them); (4) inclusion of the total backscattering coefficient IOP does not contribute significantly to (Chl) retrieval; and (5) the new IOP-based algorithm may provide the possibility for future research to establish the actual role of extracellular CDOM from all sources in the intracellular production of chlorophyll biomass.

Validation of Terra-MODIS phytoplankton chlorophyll fluorescence line height. I. Initial airborne lidar results.

The Moderate Resolution Imaging Spectroradiometer (MODIS) aboard the Terra spacecraft contains spectral bands that allow retrieval of solar-induced phytoplankton chlorophyll fluorescence emission radiance. Concurrent airborne laser-induced (and water-Raman normalized) phytoplankton chlorophyll fluorescence data is used to successfully validate the MODIS chlorophyll fluorescence line height (FLH) retrievals within Gulf Stream, continental slope, shelf, and coastal waters of the Middle Atlantic Bight portion of the western North Atlantic Ocean for 11 March 2002. Over the entire approximately 480-km flight line a correlation coefficient of r2 = 0.