Successful MRI-Guided Focused Ultrasound Uterine Fibroid Treatment Despite an Ostomy and Significant Abdominal Wall Scarring

We present a case of successful magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) of a uterine fibroid in a patient with extensive anterior abdominal wall surgical scars from two longitudinal laparotomies, a total colectomy and ileostomy. This case demonstrates that MRgFUS can be safely used in patients with an ostomy and significant abdominal wall scarring, but careful pretreatment planning and positioning during treatment is needed

Epistatic interactions between mutations of TACI (TNFRSF13B) and TCF3 result in a severe primary immunodeficiency disorder and systemic lupus erythematosus

Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies where monogenetic causes account for only a fraction of cases. On this evidence, CVID is potentially polygenic and epistatic although there are, as yet, no examples to support this hypothesis. We have identified a non-consanguineous family, who carry the C104R (c.310T>C) mutation of the Transmembrane Activator Calcium-modulator and cyclophilin ligand Interactor (TACI, TNFRSF13B) gene. Variants in TNFRSF13B/TACI are identified in up to 10% of CVID patients, and are associated with, but not solely causative of CVID. The proband is heterozygous for the TNFRSF13B/TACI C104R mutation and meets the Ameratunga et al. diagnostic criteria for CVID and the American College of Rheumatology criteria for systemic lupus erythematosus (SLE). Her son has type 1 diabetes, arthritis, reduced IgG levels and IgA deficiency, but has not inherited the TNFRSF13B/TACI mutation. Her brother, homozygous for the TNFRSF13B/TACI mutation, is in good health despite profound hypogammaglobulinemia and mild cytopenias. We hypothesised that a second unidentified mutation contributed to the symptomatic phenotype of the proband and her son. Whole-exome sequencing of the family revealed a de novo nonsense mutation (T168fsX191) in the Transcription Factor 3 (TCF3) gene encoding the E2A transcription factors, present only in the proband and her son. We demonstrate mutations of TNFRSF13B/TACI impair immunoglobulin isotype switching and antibody production predominantly via T-cell-independent signalling, while mutations of TCF3 impair both T-cell-dependent and -independent pathways of B-cell activation and differentiation. We conclude that epistatic interactions between mutations of the TNFRSF13B/TACI and TCF3 signalling networks lead to the severe CVID-like disorder and SLE in the proband.We thank AMRF, A+ Trust, IDFNZ, ASCIA and the Australian National Health and Medical Research Council (NHMRC, Program Grant 1054925, Project Grant 1127198 and Independent Research Institutes Infrastructure Support Scheme Grant 361646) for grant support. We also received support from Bloody Long Way (BLW) the Victorian State Government Operational Infrastructure scheme and Walter and Eliza Hall Institute (WEHI) Innovation Grant. CAS is supported by NHMRC postgraduate scholarship 1075666

Artificial intelligence in cancer imaging: Clinical challenges and applications

Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care

Impact of an Information Technology–Enabled Initiative on the Quality of Prostate Multiparametric MRI Reports

Rationale and Objectives: Assess the impact of implementing a structured report template and a computer-aided diagnosis (CAD) tool on the quality of prostate multiparametric MRI (mp-MRI) reports. Materials and Methods: Institutional Review Board approval was obtained for this HIPAA-compliant study performed at an academic medical center. The study cohort included all prostate mp-MRI reports (n=385) finalized 6 months before and after implementation of a structured report template and a CAD tool (collectively the IT tools) integrated into the PACS workstation. Primary outcome measure was quality of prostate mp-MRI reports. An expert panel of our institution’s subspecialty trained abdominal radiologists defined prostate mp-MRI report quality as optimal, satisfactory or unsatisfactory based on documentation of 9 variables. Reports were reviewed to extract the predefined quality variables and determine whether the IT tools were used to create each report. Chi-square and Student’s t-tests were used to compare report quality before and after implementation of IT tools. Results: The overall proportion of optimal or satisfactory reports increased from 29.8% (47/158) to 53.3% (121/227) (p<0.001) after implementing the IT tools. While the proportion of optimal or satisfactory reports increased among reports generated using at least one of the IT tools (47/158=[29.8%] vs. 105/161=[65.2%]; p<0.001), there was no change in quality among reports generated without use of the IT tools (47/158=[29.8%] vs. 16/66=[24.2%]; p=0.404). Conclusion: The use of a structured template and CAD tool improved the quality of prostate mp-MRI reports compared to free-text report format and subjective measurement of contrast enhancement kinetic curve

A Perfect Script? Manchester United's Class of ‘92

The Class of ’92 is a documentary film featuring six Manchester United F.C. players who recount their time during a pivotal period for the club, English football and English society. The documentary claims to offer a commentary on Britain in the 1990s, but appears, without acknowledging the fact, to be a promotional vehicle to establish the six men as a brand labeled the Class of ’92 (CO92). Creating this brand necessarily involved presenting a selective account of their time and places with the film being little more than an advertisement, masquerading as an observational documentary. The film draws freely upon the symbolic capital held by the club and the city of Manchester and uses the Busby Babes/Munich chapter and the more recent “Madchester scene” to forge the Class of ’92 brand by editing out those elements that did not accord with this project. The article argues that a more complete representation of ’90s Britain, while disrupting the intended narrative, would acknowledge the significant structural and commercial changes experienced by the club, the sport, and the city in the last decade of the 20th century. We suggest that the Class of ’92 invites the viewer to consider how the documentary film genre can contribute to brand development and promotion

Variability in MRI vs. ultrasound measures of prostate volume and its impact on treatment recommendations for favorable-risk prostate cancer patients: a case series

Background: Prostate volume can affect whether patients qualify for brachytherapy (desired size ≥20 mL and ≤60 mL) and/or active surveillance (desired PSA density ≤0.15 for very low risk disease). This study examines variability in prostate volume measurements depending on imaging modality used (ultrasound versus MRI) and volume calculation technique (contouring versus ellipsoid) and quantifies the impact of this variability on treatment recommendations for men with favorable-risk prostate cancer. Methods: We examined 70 patients who presented consecutively for consideration of brachytherapy for favorable-risk prostate cancer who had volume estimates by three methods: contoured axial ultrasound slices, ultrasound ellipsoid (height × width × length × 0.523) calculation, and endorectal coil MRI (erMRI) ellipsoid calculation. Results: Average gland size by the contoured ultrasound, ellipsoid ultrasound, and erMRI methods were 33.99, 37.16, and 39.62 mLs, respectively. All pairwise comparisons between methods were statistically significant (all p < 0.015). Of the 66 patients who volumetrically qualified for brachytherapy on ellipsoid ultrasound measures, 22 (33.33%) did not qualify on ellipsoid erMRI or contoured ultrasound measures. 38 patients (54.28%) had PSA density ≤0.15 ng/dl as calculated using ellipsoid ultrasound volumes, compared to 34 (48.57%) and 38 patients (54.28%) using contoured ultrasound and ellipsoid erMRI volumes, respectively. Conclusions: The ultrasound ellipsoid and erMRI ellipsoid methods appeared to overestimate ultrasound contoured volume by an average of 9.34% and 16.57% respectively. 33.33% of those who qualified for brachytherapy based on ellipsoid ultrasound volume would be disqualified based on ultrasound contoured and/or erMRI ellipsoid volume. As treatment recommendations increasingly rely on estimates of prostate size, clinicians must consider method of volume estimation

Ultrasound-Guided Radiofrequency Thermal Ablation of Uterine Fibroids: Medium-Term Follow-Up

Previous studies have shown that radiofrequency thermal ablation (RFA) of uterine fibroids through a percutaneous ultrasound (US)-guided procedure is an effective and safe minimally invasive treatment, with encouraging short-term results. The aim of this study was to assess the results in terms of volume reduction and clinical symptoms improvement in the midterm follow-up of fibroids with a diameter of up to 8 cm. Eleven premenopausal females affected by symptomatic fibroids underwent percutaneous US-guided RFA. Symptom severity and reduction in volume were evaluated at 1, 3, 6, 9, and 12 months. The mean symptom score (SSS) before the procedure was 50.30 (range 31.8–67.30), and the average quality of life (QOL) score value was 62 (range 37.20–86.00). The mean basal diameter was 5.5 cm (range 4.4–8) and the mean volume was 101.5 cm3 (range 44.58–278 cm3). The mean follow-up was 9 months (range 3–12 months). The mean SSS value at the end of the follow-up was 13.38 (range 0–67.1) and the QOL 90.4 (range 43.8–100). At follow-up the mean diameter was 3.0 cm (range 1.20–4.5 cm), and the mean volume was 18 cm3 (range 0.90–47.6 cm3). In 10 of 11 patients we obtained total or partial regression of symptoms. In one case the clinical manifestations persisted and it was thus considered unsuccessful. In conclusion, US-guided percutaneous RFA is a safe and effective treatment even for fibroids up to 8 cm

Investigation of Cellular and Molecular Responses to Pulsed Focused Ultrasound in a Mouse Model

Continuous focused ultrasound (cFUS) has been widely used for thermal ablation of tissues, relying on continuous exposures to generate temperatures necessary to induce coagulative necrosis. Pulsed FUS (pFUS) employs non-continuous exposures that lower the rate of energy deposition and allow cooling to occur between pulses, thereby minimizing thermal effects and emphasizing effects created by non-thermal mechanisms of FUS (i.e., acoustic radiation forces and acoustic cavitation). pFUS has shown promise for a variety of applications including drug and nanoparticle delivery; however, little is understood about the effects these exposures have on tissue, especially with regard to cellular pro-homing factors (growth factors, cytokines, and cell adhesion molecules). We examined changes in murine hamstring muscle following pFUS or cFUS and demonstrate that pFUS, unlike cFUS, has little effect on the histological integrity of muscle and does not induce cell death. Infiltration of macrophages was observed 3 and 8 days following pFUS or cFUS exposures. pFUS increased expression of several cytokines (e.g., IL-1α, IL-1β, TNFα, INFγ, MIP-1α, MCP-1, and GMCSF) creating a local cytokine gradient on days 0 and 1 post-pFUS that returns to baseline levels by day 3 post-pFUS. pFUS exposures induced upregulation of other signaling molecules (e.g., VEGF, FGF, PlGF, HGF, and SDF-1α) and cell adhesion molecules (e.g., ICAM-1 and VCAM-1) on muscle vasculature. The observed molecular changes in muscle following pFUS may be utilized to target cellular therapies by increasing homing to areas of pathology