Microbubbles bound to drug-eluting beads enable ultrasound imaging and enhanced delivery of therapeutics

Transarterial chemoembolization (TACE) is an image-guided minimally invasive treatment for liver cancer which involves delivery of chemotherapy and embolic material into tumor-supplying arteries to block blood flow to a liver tumor and to deliver chemotherapy directly to the tumor. However, the released drug diffuses only less than a millimeter away from the beads. To enhance the efficacy of TACE, the development of microbubbles electrostatically bound to the surface of drug-eluting beads loaded with different amounts of doxorubicin (0–37.5 mg of Dox/mL of beads) is reported. Up to 400 microbubbles were bound to Dox-loaded beads (70–150 microns). This facilitated ultrasound imaging of the beads and increased the release rate of Dox upon exposure to high intensity focused ultrasound (HIFU). Furthermore, ultrasound exposure (1 MPa peak negative pressure) increased the distance at which Dox could be detected from beads embedded in a tissue-mimicking phantom, compared with a no ultrasound control

Ultrasound and x-ray imageable poloxamer-based hydrogel for loco-regional therapy delivery in the liver

Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery

SELNET clinical practice guidelines for bone sarcoma

Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context

Diurnal patterns of salivary cytokines differentially correlate with greater fluctuations in cortisol and diet composition: A pilot study

Chronic stress and elevated cortisol are associated with adverse metabolic profiles and lifestyle patterns, systemic low-grade inflammation, and increased chronic disease risk; however, it is less clear how the degree of cortisol fluctuations impacts these parameters. Adult men and women (18-70y) were recruited to participate in a 5-day observational study, in which they underwent a baseline health and body composition assessment, completed 5-day diet, exercise, and stress records, and provided saliva samples in the morning, afternoon, and evening to measure fluctuations in cortisol, interleukin-1β (IL-1β), and IL-6. Degree of cortisol variability over the 5-day period (highest cortisol measure - lowest cortisol measure) was used to classify subjects into high (n = 9) and low (n = 9) cortisol fluctuation groups. Participants with greater fluctuations in salivary cortisol had higher salivary cortisol concentrations on average, which was attributed to higher maximal and morning cortisol. A greater proportion of individuals with higher cortisol flux worked in first responder/emergency professions, and exhibited minimal dietary pattern differences compared to those with low cortisol flux. While body fat percentage and mass positively correlated with minimum salivary cortisol measures, body composition and blood pressure did not differ between low vs. high salivary cortisol flux groups. Interestingly, we observed diurnal patterns of salivary IL-1β concentrations, with higher IL-1β in the morning, and greater afternoon IL-1β in the high cortisol flux group compared to the low cortisol flux group. Independent of cortisol flux, waking satiety and intake patterns of dietary nutrients and food groups/type differentially correlated with salivary cytokine concentrations in a time of day-dependent manner. Our findings suggest that greater fluctuations in cortisol are associated with distinct diurnal salivary cortisol and IL-1β concentrations but minimal lifestyle and dietary factors, whereas dietary patterns are strongly and differentially associated with salivary cytokine profiles

Liver-specific 3D sectioning molds for correlating in vivo CT and MRI with tumor histopathology in woodchucks (Marmota monax).

PurposeTo evaluate the spatial registration and correlation of liver and tumor histopathology sections with corresponding in vivo CT and MRI using 3D, liver-specific cutting molds in a woodchuck (Marmota monax) hepatic tumor model.MethodsFive woodchucks chronically infected with woodchuck hepatitis virus following inoculation at birth and with confirmed hepatic tumors were imaged by contrast enhanced CT or MRI. Virtual 3D liver or tumor models were generated by segmentation of in vivo CT or MR imaging. A specimen-specific cavity was created inside a block containing cutting slots aligned with an imaging plane using computer-aided design software, and the final cutting molds were fabricated using a 3D printer. Livers were resected two days after initial imaging, fixed with formalin or left unfixed, inserted into the 3D molds, and cut into parallel pieces by passing a sharp blade through the parallel slots in the mold. Histopathology sections were acquired and their spatial overlap with in vivo image slices was quantified using the Dice similarity coefficient (DSC).ResultsImaging of the woodchucks revealed heterogeneous hepatic tumors of varying size, number, and location. Specimen-specific 3D molds provided accurate co-localization of histopathology of whole livers, liver lobes, and pedunculated tumors with in vivo CT and MR imaging, with or without tissue fixation. Visual inspection of histopathology sections and corresponding in vivo image slices revealed spatial registration of analogous pathologic features. The mean DSC for all specimens was 0.83+/-0.05.ConclusionUse of specimen-specific 3D molds for en bloc liver dissection provided strong spatial overlap and feature correspondence between in vivo image slices and histopathology sections