Toxicity and clinical outcomes of single-fraction high-dose-rate brachytherapy combined with external beam radiotherapy for high-/very high-risk prostate cancer: A dosimetric analysis of toxicity.

PURPOSE: The purpose of this study was to investigate the clinical outcomes, urinary function, quality of life (QOL), and toxicities in high- or very high-risk prostate cancer patients undergoing single-fraction high-dose-rate brachytherapy (HDR-BT) with external beam radiotherapy (EBRT) and analyze the relationship between dosimetric parameters and toxicities. MATERIALS AND METHODS: Between April 2014 and April 2019, 124 patients underwent 13-Gy HDR-BT followed by EBRT (46 Gy/23 fractions). Urinary function and QOL were evaluated using IPSS and 7-grade QOL Scale, respectively. Biochemical progression-free survival (bPFS) was calculated. RESULTS: Median follow-up period was 35.8 months; all patients received neoadjuvant hormonal therapy and very high-risk patients received adjuvant hormonal therapy. Only one patient developed a grade 3 toxicity (hematuria). Multivariate analysis showed the dose covering 30% of the urethral volume, bladder volume receiving 75% of the dose, and dose covering 2 cc of rectum were independent predictors of acute G2 urinary frequency, acute G2 urinary retention, and late G2 rectal hemorrhage. IPSS and QOL scores significantly increased following HDR-BT and returned to baseline within 6 months. The 2-year bPFS was 99.2%. CONCLUSION: The single-fraction HDR-BT with EBRT is a safe treatment for quicker recovery of urinary symptoms and QOL. The dose of at-risk organs correlated with toxicities. Single-fraction high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) for prostate cancer is a safe treatment allowing for quicker recovery of urinary symptoms and QOL. The dose of at-risk organs correlated with toxicities.

Sagittal plane deformity after temporary epiphysiodesis of the distal femur for correcting limb length discrepancy.

BACKGROUND: Outcome of the temporary epiphysiodesis procedure for limb length discrepancy (LLD) is commonly evaluated in the coronal plane. The purpose of this study was to investigate implant position and complications of the distal femur and patella in the sagittal plane after the temporary epiphysiodesis. METHODS: We retrospectively reviewed 27 patients with LLD who underwent temporary epiphysiodesis of the distal femur using staples (11 patients) or eight-plates (16 patients) between 2007 and 2015. The mean age was 9.7 years (range, 6.3-13.8) at the time of epiphysiodesis. The implants were removed after a mean period of 2.6 years (range, 0.8-4.8) from the epiphysiodesis. Correction amount of LLD was measured on anteroposterior long leg standing radiographs. Implant position, extension deformity of the distal femur (>5° from epiphysiodesis to removal of implant) and patella baja (the epiphyseal line midpoint method < 1.0) were evaluated using lateral knee radiographs. RESULTS: The average correction amount of LLD was 17.4 mm (range, 2-34). The average implant position was 43.1% (range, 35-55) from the anterior edge of the distal femoral epiphysis. At removal surgery, 16 patients (59%) had extension deformity of the distal femur and 14 patients (52%) showed patella baja. There were significant correlations between implant position and extension deformity (r = -0.51, p < 0.01) and as well as between correction amount of LLD and patella baja (r = -0.64, p < 0.01). CONCLUSION: After temporary epiphysiodesis for the treatment of LLD, extension deformity of the distal femur and patella baja occurred frequently. Anterior placement of the implants is associated with extension deformity of the distal femur. The implant should be placed in the center of distal femoral physis, not the center of femoral shaft. Excessive correction of LLD should be avoided due to a risk of patella baja.

Usefulness of dual-phase cone-beam computed tomography during arteriography and automated tumour-feeder detection software in transarterial embolization for obscure arterial bleeding in the abdomen.

We report the usefulness of dual-phase cone-beam computed tomography during angiography (CBCTA) and automated tumour-feeder detection software (AFD) in transarterial embolization (TAE) for three consecutive cases of obscure arterial bleeding in the abdomen. Two patients presented with lower gastrointestinal bleeding and one showed bleeding into the pancreatic pseudocyst. Superior mesenteric or common hepatic angiography did not demonstrate extravasation, but dual-phase CBCTA and AFD could identify extravasation and an access route to the bleeding point. TAE with gelatin sponge particles and a microcoil was successfully performed under AFD guidance in all patients without any complication, and haemostasis could be achieved.

Is the timing of surgery associated with avascular necrosis after unstable slipped capital femoral epiphysis? A multicenter study.

BACKGROUND: An unstable slipped capital femoral epiphysis (SCFE) is associated with a high rate of avascular necrosis (AVN). The etiology of AVN seems to be multifactorial, although it is not thoroughly known. The aims of our study were to determine the rate of AVN after an unstable SCFE and to investigate the risk factors for AVN, specifically evaluating the notion of an "unsafe window", during which medical interventions would increase the risk for AVN. METHODS: This retrospective multicenter study included 60 patients with an unstable SCFE diagnosed between 1985 and 2014. Timing of surgery was evaluated for three time periods, from acute onset of symptoms to surgery: period I, <24 h; period II, between 24 h and 7 days; and period III, >7 days. Multivariate logistic regression analysis was used to identify risk factors for AVN. RESULTS: Closed reduction and pinning was performed in 43 patients and in situ pinning in 17. Among these cases, 16 patients (27%) developed AVN. The rate of AVN was significantly higher in patients treated by closed reduction and pinning (15/43, 35%) than in those treated by in situ pinning (1/17, 5.9%) (p = 0.022). In patients treated by closed reduction and pinning, the incidence of AVN was 2/11 (18%) in period I, 10/13 (77%) in period II and 3/15 (20%) in period III, showing the significantly higher rate in period II (p = 0.002). The surgery provided in period II was identified as an independent risk factor for the development of AVN. CONCLUSIONS: Our rate of AVN was 27% using two classical treatment methods. Time-to-surgery, between 24 h and 7 days, was independently associated with AVN, supporting the possible existence of an "unsafe window" in patients with unstable SCFE treated by closed reduction and pinning.

Clinical Results and Complications of Lower Limb Lengthening for Fibular Hemimelia: A Report of Eight Cases.

Fibular hemimelia is a rare but the most common congenital long bone deficiency, encompassing a broad range of anomalies from isolated fibular hypoplasia up to substantial femoral and tibial shortening with ankle deformity and foot deficiency. Most cases of fibular hemimelia manifest clinically significant leg length discrepancy (LLD) with time that requires adequate correction by bone lengthening for stable walking. Bone lengthening procedures, especially those for pathological bones, are sometimes associated with severe complications, such as delayed consolidation, fractures, and deformities of the lengthened bones, leading to prolonged healing time and residual LLD at skeletal maturity. The purpose of this study was to review our clinical results of lower limb lengthening for fibular hemimelia.This study included 8 Japanese patients who diagnosed with fibular hemimelia from physical and radiological findings characteristic of fibular hemimelia and underwent single or staged femoral and/or tibial lengthening during growth or after skeletal maturity. LLD, state of the lengthened callus, and bone alignment were evaluated with full-length radiographs of the lower limb. Previous interventions, associated congenital anomalies, regenerate fractures were recorded with reference to medical charts and confirmed on appropriate radiographs. Successful lengthening was defined as the healing index <50 days/cm without regenerate fractures.A significant difference was observed in age at surgery between successful and unsuccessful lengthening. The incidence of regenerate fractures was significantly correlated with callus maturity before frame removal. LLD was corrected within 11 mm, whereas mechanical axis deviated laterally.Particular attention should be paid to the status of callus maturation and the mechanical axis deviation during the treatment period in fibular hemimelia.

Atypical extraventricular neurocytoma in a 3-year-old girl: case report with radiological-pathological correlation.

BACKGROUND: Extraventricular neurocytoma (EVN) is a rare neuronal tumor histologically similar to central neurocytoma but arising in the brain parenchyma outside the ventricles. The minority of EVNs show atypical features including increased proliferative index, microvascular proliferation, or necrosis, and are called atypical EVN. Most of atypical EVNs occur in adults, and the tumors in children are extremely rare. A radiological-pathological correlation and radiological clue to atypical EVNs have not been clarified. CASE REPORT: We report a case of atypical EVN in a 3-year-old girl. Magnetic resonance imaging (MRI) revealed an extraventricular intraparenchymal tumor in the left frontal lobe, which was composed of homogeneous well-demarcated cystic component and peripheral ill-delineated solid component with enhancement. Angiography demonstrated vascular proliferation and arteriovenous shunting in the tumor. Histologically, the resected tumor was diagnosed as atypical EVN. Types of the tumor borders (well-circumscribed or infiltrative) and MRI findings correlated closely. Morphology of the tumor vasculature was remarkable for microvascular proliferation and dilated, thickened veins, which corresponded to the angiographic features. CONCLUSION: Although rare, atypical EVN should be included in the differential diagnosis of a cystic mass in the cerebral hemispheres in children. Radiological evaluation of tumor borders and angiographic characteristics might be useful for predicting atypicality of the tumor.

Orthopaedic manifestations and diagnostic clues in children with Guillain-Barré syndrome.

INTRODUCTION: Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyneuropathy characterized by symmetric limb weakness. Children with GBS sometimes consult the orthopaedists because of limb pain and gait disturbance. The orthopaedists, however, are unfamiliar with GBS, since it has rarely been delineated in detail in the orthopaedic literature. In the present study, we specifically describe orthopaedic manifestations and diagnostic clues in pediatric GBS. METHODS: We reviewed seven patients with pediatric GBS in regard to age, gender, clinical symptoms, department at the first medical consultation, initial diagnosis, physical and laboratory findings, medical interventions, and the latest clinical outcome. RESULTS: There were five boys and two girls, with a mean age at presentation of 7.2 years. Gait disturbance associated with lower limb pain and weakness was the most frequent early clinical symptom. Among the five patients who presented initially at the orthopaedic department, three were misdiagnosed. Loss of deep tendon reflexes was seen in all patients. Anti-ganglioside antibodies were positive in three and protein levels of cerebrospinal fluid were elevated in five patients. Six patients recovered completely after intravenous immunoglobulin (IVIG) treatment, while one patient who had not undergone IVIG treatment showed minor residual disability. CONCLUSIONS: Acute symmetrical limb pain and gait disturbance associated with loss of tendon reflexes were important clinical manifestations of pediatric GBS. Early diagnosis is essential to prevent delayed recovery, long-term weakness, and permanent functional disabilities.

Crystal and electronic structure and magnetic properties of divalent europium perovskite oxides EuMO3 (M = Ti, Zr, and Hf): experimental and first-principles approaches.

A comparative study of the crystal and electronic structure and magnetism of divalent europium perovskite oxides EuMO(3) (M = Ti, Zr, and Hf) has been performed on the basis of both experimental and theoretical approaches playing complementary roles. The compounds were synthesized via solid-state reactions. EuZrO(3) and EuHfO(3) have an orthorhombic structure with a space group Pbnm at room temperature contrary to EuTiO(3), which is cubic at room temperature. The optical band gaps of EuZrO(3) and EuHfO(3) are found to be about 2.4 and 2.7 eV, respectively, much larger than that of EuTiO(3) (0.8 eV). On the other hand, the present compounds exhibit similar magnetic properties characterized by paramagnetic-antiferromagnetic transitions at around 5 K, spin flop at moderate magnetic fields lower than 1 T, and the antiferromagnetic nearest-neighbor and ferromagnetic next-nearest-neighbor exchange interactions. First-principles calculations based on a hybrid Hartree-Fock density functional approach yield lattice constants, band gaps, and magnetic interactions in good agreement with those obtained experimentally. The band gap excitations are assigned to electronic transitions from the Eu 4f to Mnd states for EuMO(3) (M = Ti, Zr, and Hf and n = 3, 4, and 5, respectively).

Effects of alteplase, a thrombolytic agent, in a rat photothrombotic middle cerebral artery occlusion model.

In this study, we examined the effects of alteplase, a recombinant tissue-type plasminogen activator (t-PA), in a simple and reproducible rat middle cerebral artery (MCA) occlusion model induced by photoillumination with 12 mg/kg of rose bengal. A clinically equivalent dose of alteplase (3 mg/kg), which was administered just after thrombotic occlusion of the MCA, significantly reopened the thrombotic MCA occlusion in 16 of 23 animals (69.6%) when compared with vehicle-treated animals (8 of 22 animals, 36.4%). In addition, alteplase significantly reduced cerebral damage and improved neurological deficits. Although it has been reported that t-PA possesses neurotoxicity, the present findings suggest that alteplase was effective in a rat acute stroke model due to reopening of thrombotic MCA occlusion. This new model is very useful for investigating the efficacy of thrombolytic agents in stroke research, providing a condition similar to the clinical setting.

Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung.

How effectively and quickly endothelial caveolae can transcytose in vivo is unknown, yet critical for understanding their function and potential clinical utility. Here we use quantitative proteomics to identify aminopeptidase P (APP) concentrated in caveolae of lung endothelium. Electron microscopy confirms this and shows that APP antibody targets nanoparticles to caveolae. Dynamic intravital fluorescence microscopy reveals that targeted caveolae operate effectively as pumps, moving antibody within seconds from blood across endothelium into lung tissue, even against a concentration gradient. This active transcytosis requires normal caveolin-1 expression. Whole body gamma-scintigraphic imaging shows rapid, specific delivery into lung well beyond that achieved by standard vascular targeting. This caveolar trafficking in vivo may underscore a key physiological mechanism for selective transvascular exchange and may provide an enhanced delivery system for imaging agents, drugs, gene-therapy vectors and nanomedicines. 'In vivo proteomic imaging' as described here integrates organellar proteomics with multiple imaging techniques to identify an accessible target space that includes the transvascular pumping space of the caveola.

Dual-modality imaging of function and physiology.

Dual-modality imaging is a technique in which computed tomography (CT) or magnetic resonance imaging is combined with positron emission tomography or single-photon emission CT to acquire structural and functional images with an integated system. The data are acquired in a single procedure; the patient remains on the scanner table while undergoing both x-ray and radionuclide studies to facilitate correlation between the structural and functional images. The resulting data can aid in localization, enabling more specific diagnosis than can be obtained with a conventional imaging study. In addition, the anatomic information can be used to compensate the correlated radionuclide data for physical perturbations such as photon attenuation, scatter radiation, and partial volume errors. Thus, dual-modality imaging provides a priori information that can improve both the visual quality and the quantitative accuracy of the radionuclide images. Dual-modality imaging systems are also being developed for biologic research involving small animals. Small-animal dual-modality systems offer advantages for measurements that currently are performed invasively with autoradiography and tissue sampling. By acquiring data noninvasively, dual-modality imaging permits serial studies in a single animal, enables measurements to be performed with fewer animals, and improves the statistical quality of the data.

Dual-modality imaging of cancer with SPECT/CT.

Dual-modality imaging is an in vivo diagnostic technique that obtains structural and functional information directly from patient studies in a way that cannot be achieved with separate imaging systems alone. Dual-modality imaging systems are configured by combining computed tomography (CT) with radionuclide imaging (using positron emission tomography (PET) or single-photon emission computed tomography (SPECT)) on a single gantry which allows both functional and structural imaging to be performed during a single imaging session without having the patient leave the imaging system. A SPECT/CT system developed at UCSF is being used in a study to determine if dual-modality imaging offers advantages for assessment of patients with prostate cancer using (111)In-ProstaScint, a radiolabeled antibody for the prostate-specific membrane antigen. (111)In-ProstaScint images are reconstructed using an iterative maximum-likelihood expectation-maximization (ML-EM) algorithm with correction for photon attenuation using a patient-specific map of attenuation coefficients derived from CT. The ML-EM algorithm accounts for the dual-photon nature of the 111In-labeled radionuclide, and incorporates correction for the geometric response of the radionuclide collimator. The radionuclide image then can be coregistered and overlaid in color on a grayscale CT image for improved localization of the functional information from SPECT. Radionuclide images obtained with SPECT/CT and reconstructed using ML-EM with correction for photon attenuation and collimator response improve image quality in comparison to conventional radionuclide images obtained with filtered backprojection reconstruction. These results illustrate the potential advantages of dual-modality imaging for improving the quality and the localization of radionuclide uptake for staging disease, planning treatment, and monitoring therapeutic response in patients with cancer.