ABSTRACT
Urogenital tuberculosis (UGTB) can affect the entire urinary tract including the kidneys, ureters (strictures), urinary bladder, prostate in addition to involving reproductive tracts. In modern day practice, both ultrasound and cross-sectional imaging play an important role in the radiological diagnosis of UGTB. The sequalae of untreated UGTB is morbid and can lead to end-stage renal failure, infertility, and life-threatening systemic infection. UGTB is less commonly observed in developed countries and may mimic other pathologies including malignancy. Thus, it is important that radiologists consider the differential diagnosis early, particularly individuals with risk factors such as travel to endemic regions, to allow optimal treatment and ensure best prognostic outcomes. UGTB can typically be managed by Infectious Disease clinicians with multidrug chemotherapy. We have presented a case of microbiologically proven extrapulmonary tuberculosis (TB) predominantly involving the genitourinary tract. The response to TB agents and lack of evidence of co-infection with another organism, might suggest this as the first published case of emphysematous tuberculous prostatitis. Emphysematous prostatitis is indicative of a gas-forming infection of the prostate, and is associated with abscess formation in the vast majority of case and is an easily identified radiological feature on CT. It is not a well-recognised feature of Mycobacterium tuberculosis infection and thus microbiological diagnosis should be sought to confirm the diagnosis.
ABSTRACT
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. Contrast-enhanced magnetic resonance imaging is typically used to evaluate tumor perfusion following HIFU; however, its utility is limited in poorly perfused tumors. Diffusion-weighted imaging (DWI) provides tissue contrast based on differences in the diffusion of extracellular water without using gadolinium-based contrast agents. We present novel DWI findings following a planned partial HIFU ablation of a large sacral chordoma which had recurred after radiotherapy. Following HIFU, the treated tumor volume demonstrated loss of restriction on DWI correlating with photopenia on positron emission tomography. This suggests successful ablation and tumor necrosis. This novel finding may provide guidance for sequence selection when evaluating HIFU therapy for sacral chordoma and other tumor types for which contrast-enhanced magnetic resonance imaging may have limited utility.
ABSTRACT
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). Ten participants (age range, 49-68 years; average age, 60 years; four women) were treated from March 2015 to March 2017 by using a clinically approved focused ultrasound system to release doxorubicin from lyso-thermosensitive liposomes. Ultrasonic heating of target tumors (treated volume: 11-73 cm3 [mean ± standard deviation, 50 cm3 ± 26]) was monitored in six participants by using a minimally invasive temperature sensor; four participants were treated without real-time thermometry. For all participants, CT images were used with a patient-specific hyperthermia model to define focused ultrasound treatment plans. Feasibility was assessed by comparing model-prescribed focused ultrasound powers to those implemented for treatment. Safety was assessed by evaluating MR images and biopsy specimens for evidence of thermal ablation and monitoring adverse events. Results The mean difference between predicted and implemented treatment powers was -0.1 W ± 17.7 (n = 10). No evidence of focused ultrasound-related adverse effects, including thermal ablation, was found. Conclusion In this 10-participant study, the authors confirmed the feasibility of using focused ultrasound-mediated hyperthermia planning models to define treatment parameters that safely enabled targeted, noninvasive drug delivery to liver tumors while monitored with B-mode guidance and without real-time thermometry. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Dickey and Levi-Polyachenko in this issue.
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Doxorubicin/administration & dosage , Hyperthermia, Induced/methods , Liver Neoplasms/therapy , Ultrasonic Therapy/methods , Aged , Drug Delivery Systems , Drug Liberation , Feasibility Studies , Female , Humans , Liposomes , Male , Middle Aged , Pharmaceutical Vehicles , Prospective StudiesABSTRACT
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. We present a case of a patient with a ductal breast adenocarcinoma, who developed liver and bone metastasis despite extensive treatment with systemic chemotherapies. Following SIRT to the liver, after an initial response, the patient ultimately progressed in the liver after 7 months. Liver tumor histology obtained 20 months after the SIRT intervention demonstrated the presence of the resin microspheres in situ. This case report demonstrates the long-term control that may be achieved with SIRT to treat liver metastases from breast cancer that is refractory to previous chemotherapies, and the presence of microspheres in situ long-term.
ABSTRACT
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. Adult patients (aged ≥18 years) with unresectable and non-ablatable primary or secondary liver tumours of any histological subtype were considered for the study. Patients received a single intravenous infusion (50 mg/m2) of lyso-thermosensitive liposomal doxorubicin (LTLD), followed by extracorporeal focused ultrasound exposure of a single target liver tumour. The trial had two parts: in part I, patients had a real-time thermometry device implanted intratumourally, whereas patients in part II proceeded without thermometry and we used a patient-specific model to predict optimal exposure parameters. We assessed tumour biopsies obtained before and after focused ultrasound exposure for doxorubicin concentration and distribution. The primary endpoint was at least a doubling of total intratumoural doxorubicin concentration in at least half of the patients treated, on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02181075, and is now closed to recruitment. FINDINGS: Between March 13, 2015, and March 27, 2017, ten patients were enrolled in the study (six patients in part I and four in part II), and received a dose of LTLD followed by focused ultrasound exposure. The treatment resulted in an average increase of 3·7 times in intratumoural biopsy doxorubicin concentrations, from an estimate of 2·34 µg/g (SD 0·93) immediately after drug infusion to 8·56 µg/g (5·69) after focused ultrasound. Increases of two to ten times were observed in seven (70%) of ten patients, satisfying the primary endpoint. Serious adverse events registered were expected grade 4 transient neutropenia in five patients and prolonged hospital stay due to unexpected grade 1 confusion in one patient. Grade 3-4 adverse events recorded were neutropenia (grade 3 in one patient and grade 4 in five patients), and grade 3 anaemia in one patient. No treatment-related deaths occurred. INTERPRETATION: The combined treatment of LTLD and non-invasive focused ultrasound hyperthermia in this study seemed to be clinically feasible, safe, and able to enhance intratumoural drug delivery, providing targeted chemo-ablative response in human liver tumours that were refractory to standard chemotherapy. FUNDING: Oxford Biomedical Research Centre, National Institute for Health Research.
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Doxorubicin/analogs & derivatives , Hyperthermia, Induced , Liver Neoplasms/drug therapy , Ultrasonography , Aged , Doxorubicin/administration & dosage , Drug Delivery Systems , Female , Humans , Male , Middle Aged , Polyethylene Glycols/administration & dosageABSTRACT
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). METHODS/DESIGN: The study is conducted in two parts: Part 1 includes minimally-invasive thermometry via a thermistor or thermocouple implanted through the biopsy co-axial needle core, to confirm ultrasound-mediated hyperthermia, whilst Part 2 is carried out without invasive thermometry, to more closely mimic the ultimately intended clinical implementation of the technique. Whilst under a general anaesthetic, adult patients with incurable confirmed hepatic primary or secondary (metastatic) tumours receive a single cycle of ThermoDox®, immediately followed by ultrasound-mediated hyperthermia in a single target liver tumour. For each patient in Part 1, the HPLC-derived total doxorubicin concentration in the ultrasound-treated tumour is directly compared to the concentration before ultrasound exposure in that same tumour. For each patient in Part 2, as the tumour biopsy taken before ultrasound exposure is not available, the mean of those Part 1 tumour concentrations is used as the comparator. Success of the study requires at least a two-fold increase in the total intratumoural doxorubicin concentration, or final concentrations over 10 µg/g, in at least 50% of all patients receiving the drug, where tissue samples are evaluable by HPLC. Secondary outcome measures evaluate safety and feasibility of the intervention. Radiological response in the target tumour and control liver tumours are analysed as a tertiary outcome measure, in addition to plasma pharmacokinetics, fluorescence microscopy and immunohistochemistry of the biopsy samples. DISCUSSION: If this early phase study can demonstrate that ultrasound-mediated hyperthermia can effectively enhance the delivery and penetration of chemotherapy agents intratumorally, it could enable application of the technique to enhance therapeutic outcomes across a broad range of drug classes to treat solid tumours. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02181075, Edura-CT Identifier: 2014-000514-61.Ethics Number: 14/NE/0124.
ABSTRACT
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. Patients were treated under general anaesthetic or sedation using an ultrasound-guided HIFU device. HIFU therapy was associated with a reduction in tumour volume over time in three patients for whom follow up scans were available. Tumour necrosis was reliably demonstrated in two of the three patients. We have established a national trial to assess if HIFU may improve long-term outcome from sacral chordoma, details are given.