Monte Carlo based dosimetry of extraoral photobiomodulation for prevention of oral mucositis.

Photobiomodulation therapy (PBMT) is recommended for prevention and treatment of oral mucositis, a painful condition that occurs in cancer patients. Intraoral PBMT is limited to treating distal oral mucosa and oropharynx. Extraoral PBMT may provide a more efficient intervention. The goal of this study was to develop a clinically viable protocol for extraoral PBMT. Monte Carlo modeling was used to predict the distribution of 850 nm light for four treatment sites, using anatomical data obtained from MRI and optical properties from the literature. Simulated incident light power density was limited to 399 mW/cm2 to ensure treatment safety and to prevent tissue temperature increase. The results reveal that total tissue thickness determines fluence rate at the oral mucosa, whereas the thickness of individual tissue layers and melanin content are of minor importance. Due to anatomical differences, the fluence rate varied greatly among patients. Despite these variations, a universal protocol was established using a median treatment time methodology. The determined median treatment times required to deliver efficacious dose between 1 and 6 J/cm2 were within 15 min. The developed PBMT protocol can be further refined using the combination of pretreatment imaging and the Monte Carlo simulation approach implemented in this study.

Multistep IgE Mast Cell Desensitization Is a Dose- and Time-Dependent Process Partially Regulated by SHIP-1.

Multistep mast cell desensitization blocks the release of mediators following IgE crosslinking with increasing doses of Ag. Although its in vivo application has led to the safe reintroduction of drugs and foods in IgE-sensitized patients at risk for anaphylaxis, the mechanisms of the inhibitory process have remained elusive. We sought to investigate the kinetics, membrane, and cytoskeletal changes and to identify molecular targets. IgE-sensitized wild-type murine (WT) and FcεRIα humanized (h) bone marrow mast cells were activated and desensitized with DNP, nitrophenyl, dust mites, and peanut Ags. The movements of membrane receptors, FcεRI/IgE/Ag, actin, and tubulin and the phosphorylation of Syk, Lyn, P38-MAPK, and SHIP-1 were assessed. Silencing SHIP-1 protein was used to dissect the SHIP-1 role. Multistep IgE desensitization of WT and transgenic human bone marrow mast cells blocked the release of ß-hexosaminidase in an Ag-specific fashion and prevented actin and tubulin movements. Desensitization was regulated by the initial Ag dose, number of doses, and time between doses. FcεRI, IgE, Ags, and surface receptors were not internalized during desensitization. Phosphorylation of Syk, Lyn, p38 MAPK, and SHIP-1 increased in a dose-response manner during activation; in contrast, only SHIP-1 phosphorylation increased in early desensitization. SHIP-1 phosphatase function had no impact on desensitization, but silencing SHIP-1 increased ß-hexoxaminidase release, preventing desensitization. Multistep IgE mast cell desensitization is a dose- and time-regulated process that blocks ß-hexosaminidase, impacting membrane and cytoskeletal movements. Signal transduction is uncoupled, favoring early phosphorylation of SHIP-1. Silencing SHIP-1 impairs desensitization without implicating its phosphatase function.

A man with panda eyes after a fall.

Most commonly caused by trauma, basal skull fractures present with a range of clinical signs. These include periorbital ecchymosis, as seen in this case, as well as rhinorrhea, otorrhoea and post-mastoid ecchymosis. Suspected cases must be managed with appropriate imaging and medical or surgical treatment as indicated.

Oligometastatic Disease in the Liver: The Role of Interventional Oncology.

Oligometastatic disease represents a clinically discrete intermediate stage of cancer progression and is an expanding area of research. While surgical metastatectomy has been recognized for decades as an effective treatment option in select patients, options for metastasis-directed therapy have broadened in scope with advancements in the armamentarium of non- and minimally invasive modalities. Recent preclinical studies investigating the immunology surrounding liver metastases demonstrate treatment resistance to immunotherapy in affected patients and show how locoregional therapy has the ability to overcome this resistance. In this paper, we review advancements in our understanding of oligometastatic disease, metastasis-directed therapy, effect of liver metastasis on response to immunotherapy, and the burgeoning role of image-guided interventions in complementing cancer immunotherapy at the exciting crossroads of interventional oncology and immuno-oncology.

Image-guided Percutaneous Biopsy of the Liver.

Percutaneous Biopsy of the Liver (PBL) is a cornerstone in the diagnosis of parenchymal liver disease and focal hepatic lesions. The indications for PBL can broadly be divided into those used to garner information regarding diagnosis, prognosis, or treatment. While the diagnosis of many common liver diseases can usually be made with imaging and serologic testing alone, PBL may be indicated in situations where the diagnosis is in question. Furthermore, liver biopsies are a foundational element for personalized treatment approaches for cancer patients; increasing emphasis is being placed on acquiring sufficient tissue for molecular profiling. While a variety of image guidance and procedural techniques have been applied to PBL, following conventional principles can ensure technical success and minimize complication risks. In this technique article, we review the practical periprocedural considerations of PBL with emphasis on recent advancements and societal recommendations.

Validation of a Monte Carlo Modelling Based Dosimetry of Extraoral Photobiomodulation.

An in vivo validation study was performed to confirm the accuracy of extraoral photobiomodulation therapy (PBMT) dosimetry determined by modelling. The Monte Carlo technique was utilized to calculate the fluence rate and absorbed power of light delivered through multi-layered tissue. Optical properties used during Monte Carlo simulations were taken from the literature. Morphological data of four study volunteers were acquired using magnetic resonance imaging (MRI) scans. Light emitting diode (LED) coupled to a power meter were utilized to measure transmitted power through each volunteer's cheek, in vivo. The transmitted power determined by Monte Carlo modelling was compared to the in vivo measurements to determine the accuracy of the simulations. Experimental and simulation results were in good agreement for all four subjects. The difference between the mean values of the measured transmission was within 12% from the respective transmission obtained using Monte Carlo simulations. The results of the study indicate that Monte Carlo modelling is a robust and reliable method for light dosimetry.

Hyperthermia and Tumor Immunity.

Thermal ablation is a cornerstone in the management of cancer patients. Typically, ablation procedures are performed for patients with a solitary or oligometastatic disease with the intention of eradicating all sites of the disease. Ablation has traditionally played a less prominent role for patients with a widely metastatic disease. For such patients, attempting to treat numerous sites of disease compounds potential risks without a clear clinical benefit and, as such, a compelling justification for performing an intervention that is unlikely to alter a patient's clinical trajectory is uncommon. However, the discovery of immune checkpoints and the development of immune checkpoint inhibitors have brought a new perspective to the relevance of local cancer therapies such as ablation for patients with a metastatic disease. It is becoming increasingly apparent that local cancer therapies can have systemic immune effects. Thus, in the new perspective of cancer care centered upon immunologic principles, there is a strong interest in exploring the utility of ablation for patients with a metastatic disease for its immunologic implications. In this review, we summarize the unmet clinical need for adjuvant interventions such as ablation to broaden the impact of systemic immunotherapies. We additionally highlight the extant preclinical and clinical data for the immunogenicity of common thermal ablation modalities.

Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Series and Review.

ABSTRACT: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy that frequently has cutaneous manifestations. The diagnosis can be a challenge because of its heterogenous clinical presentation, ranging from a brown or violaceous solitary nodule or patch to mixed, disseminated lesions. Furthermore, BPDCN tumor cells express immunohistochemical markers in common with acute myeloid leukemia, which can lead to misdiagnosis. Timely diagnosis requires awareness of its cutaneous manifestations and unique histopathology and immunophenotype. We present a case series of patients diagnosed with BPDCN and review the cutaneous and histopathologic characteristics of this uncommon entity.

The Path to an Evidence-Based Treatment Protocol for Extraoral Photobiomodulation Therapy for the Prevention of Oral Mucositis.

Oral mucositis is a painful complication of hematopoietic stem cell transplantation for which photobiomodulation therapy (PBMT) is a safe and effective intervention. Extraoral delivery of PBMT has clinical advantages over intraoral delivery but requires additional dosimetric considerations due to the external tissue layers through which the light must propagate before reaching the oral mucosa. Additionally, to date there has been no dose modeling study, a task essential to developing a justified treatment protocol. We review here some of the complexities surrounding extraoral photobiomodulation therapy and offer that may help guide researchers toward an evidence-based treatment protocol for the prevention of oral mucositis.