Uncovering the armpit of SBRT: An institutional experience with stereotactic radiation of axillary metastases.

Purpose/objectives: The growing use of stereotactic body radiotherapy (SBRT) in metastatic cancer has led to its use in varying anatomic locations. The objective of this study was to review our institutional SBRT experience for axillary metastases (AM), focusing on outcomes and process. Materials/methods: Patients treated with SBRT to AM from 2014 to 2022 were reviewed. Cumulative incidence functions were used to estimate the incidence of local failure (LF), with death as competing risk. Kaplan-Meier method was used to estimate progression-free (PFS) and overall survival (OS). Univariate regression analysis examined predictors of LF. Results: We analyzed 37 patients with 39 AM who received SBRT. Patients were predominantly female (60 %) and elderly (median age: 72). Median follow-up was 14.6 months. Common primary cancers included breast (43 %), skin (19 %), and lung (14 %). Treatment indication included oligoprogression (46 %), oligometastases (35 %) and symptomatic progression (19 %). A minority had prior overlapping radiation (18 %) or surgery (11 %). Most had prior systemic therapy (70 %).Significant heterogeneity in planning technique was identified; a minority of patient received 4-D CT scans (46 %), MR-simulation (21 %), or contrast (10 %). Median dose was 40 Gy (interquartile range (IQR): 35-40) in 5 fractions, (BED10 = 72 Gy). Seventeen cases (44 %) utilized a low-dose elective volume to cover remaining axilla.At first assessment, 87 % had partial or complete response, with a single progression. Of symptomatic patients (n = 14), 57 % had complete resolution and 21 % had improvement. One and 2-year LF rate were 16 % and 20 %, respectively. Univariable analysis showed increasing BED reduced risk of LF. Median OS was 21.0 months (95 % [Confidence Interval (CI)] 17.3-not reached) and median PFS was 7.0 months (95 % [CI] 4.3-11.3). Two grade 3 events were identified, and no grade 4/5. Conclusion: Using SBRT for AM demonstrated low rates of toxicity and LF, and respectable symptom improvement. Variation in treatment delivery has prompted development of an institutional protocol to standardize technique and increase efficiency. Limited followup may limit detection of local failure and late toxicity.

Multidisciplinary Management of Phyllodes Tumours and Breast Sarcoma: A Cross-sectional Survey of Clinical Practice across the UK and Ireland.

AIMS: Phyllodes tumours and breast sarcomas are uncommon tumours and their rarity poses significant challenges in diagnosis and management. This cross-sectional study was conducted to evaluate the multidisciplinary clinical practice for these tumours across the UK and Ireland, with the aim of identifying gaps in knowledge and providing direction for establishing national guidelines. MATERIALS AND METHODS: An international survey was adapted and circulated to breast and/or sarcoma surgeons and oncologists in the UK and Ireland through national organisations. Multidisciplinary team (MDT) responses were analysed anonymously. RESULTS: Twenty-eight MDTs participated in this study, predominately from high-volume units (85.5%). Although only 43% of the surveyed units were part of a trust that holds a sarcoma MDT, 68% of units managed malignant phyllodes and angiosarcoma, whereas 64.5% managed soft-tissue sarcoma of the breast. Across all subtypes, axillary surgery was recommended by 14-21% of the MDTs and the most recommended resection margins for breast surgery were 'no tumour on ink' in benign phyllodes (39%) and 10 mm in the remaining subtypes (25-29%). Immediate breast reconstruction was supported by 11-18% of MDTs for breast sarcoma subtypes, whereas 36% and 32% advocated this approach in benign and borderline phyllodes tumours, respectively. Adjuvant radiotherapy and chemotherapy were recommended by up to 29% and 11% of the MDTs, respectively. CONCLUSION: The results of this study demonstrate a wide variation in clinical practice across the surveyed MDTs. As only 28 MDTs participated in our study, with under-representation from low-volume units, our results might be an underestimation of the variability in practice across the UK and Ireland. This multi-institutional study sheds light on controversial aspects in the management of phyllodes tumours and breast sarcoma, identifies the need for national guidelines to inform best practice, and calls for the centralisation of the management of breast sarcoma within specialist centres.

Whole-body three-dimensional short tau inversion recovery and T1-weighted in/opposed phase MRI in the detection of neuroblastoma bone marrow metastasis: comparative study with PET/CT utilising bone marrow biopsy as the reference standard.

AIM: To evaluate the diagnostic accuracy of whole-body (WB) magnetic resonance imaging (MRI) utilising three-dimensional (3D) short tau inversion recovery (STIR) and T1-weighted in/opposed-phase MRI in the detection of neuroblastoma bone marrow metastasis compared to 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT). MATERIALS AND METHODS: A prospective study of 20 consecutive histopathologically proven neuroblastoma patients enrolled in this study from January 2021 to August 2022. WB MRI and FDG-PET/CT were performed for all cases. Bone marrow biopsy served as the standard of reference. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were calculated. In addition, lesion-by-lesion analysis was performed and the number of bone marrow metastatic lesions in different body segments using both imaging methods was recorded and compared. RESULTS: WB MRI correctly identified true positives and true negatives in all cases with a sensitivity and specificity of 100%. In contrast, FDG-PET/CT showed two false-negative cases that resulted in a sensitivity, specificity, PPV, NPV, and accuracy of 86.7%, 100%, 100%, 71.4%, and 92%, respectively. In the lesion-by-lesion analysis, WB MRI detected more (24.3%) bone marrow metastatic lesions than FDG-PET/CT. CONCLUSION: Whole-body MRI can reliably identify neuroblastoma bone marrow infiltration, and could be an alternative to PET/CT in that regard.

Natural history and management of posterior cerebral artery aneurysms: a systematic review and meta-analysis of individual patient data.

We conducted a comprehensive review and meta-analysis to investigate clinical, radiographic characteristics, and treatment outcomes of posterior cerebral artery aneurysms (PCAA). We systematically reviewed English-language articles investigating available treatments (parent artery occlusion (PAO), microsurgery, reconstructive endovascular (rEVT), and conservative treatments) for PCAA and analyzed the based on aneurysm morphology and rupture status. Six-hundred-eighty-five patients with 698 PCAA were identified from 59 studies. Overall, 371 (54.2%) aneurysms were ruptured, 325 (49%) were saccular, and 342 (51%) were non-saccular aneurysms. The mean age of the saccular was lower (40 years) than non-saccular aneurysm group (50 years) (P < .05). In ruptured PCAA, favorable clinical outcomes were comparable between the treatment groups except for patients treated conservatively, which had lower rates of favorable clinical outcomes (35.6%) and higher mortality (55.7%) (P < .0001). Ruptured aneurysms treated with rEVT (22.6%) had the highest recanalization rates compared to PAO (9.2%, P = 0.0001) and microsurgery (3.8%, P = 0.005). In unruptured PCAA, clinical outcomes were similar; higher complication rates were noted in microsurgery (40.4%, P = 0.026) and PAO (21.5%, P = 0.015) compared to rEVT (13.2%), which had higher recanalization rates (15.6%, P < .0001). The rates of subsequent stroke following PAO were 21.8% for unruptured and 32.3% for ruptured PCAA (P = 0.078). Ruptured PCAA portend worse prognosis and typically require an intervention to achieve better outcome whereas the benefit of an intervention in unruptured PCAA is much less clear. rEVT is promising for PCAA management with a good clinical and safety profile but more recurrence compared to PAO and microsurgery.

Combined CSF-venous Fistula and middle meningeal artery embolization for treatment of spontaneous intracranial hypotension.

Transvenous Onyx embolization was recently described as an effective treatment of spontaneous intracranial hypotension caused by CSF-venous fistulas. Patients with CSF-venous fistulas can present with a wide spectrum of clinical and imaging findings, sometimes including spontaneous subdural hematomas, subdural hygromas, or a combination of both. Here, we describe four patients with spontaneous intracranial hypotension complicated by subdural fluid collections caused by CSF-venous fistulas. The patients were treated with transvenous Onyx embolization of their CSF-venous fistulas and transarterial particle embolization of the bilateral middle meningeal arteries, with both procedures performed in a single treatment session. All four patients had clinical improvement and decreased size or resolution of their subdural fluid collections. Based on our findings, we believe that middle meningeal embolization could be a useful adjunct to CSF-venous fistula embolization. A case-control study comparing patients who did or did not undergo middle meningeal embolization will be necessary to validate this supposition.

Patient engagement in the Continuing Professional Development programs within the department of radiation oncology at the University of Toronto (UTDRO): A qualitative study.

INTRODUCTION: There is little research regarding patient engagement (PE) in Continuing Professional Development (CPD) programs in radiation oncology. This study aims to understand the barriers and enablers to PE in the design and implementation process of CPD programs, and advance PE in these programs moving forward. METHODS: This qualitative study involved 17 semi-structured interviews, with 5 cancer patients and 12 educators, conducted from June 2019 to April 2020. Interview data identified common themes, such as: the current state of PE in CPD programming, and key barriers and recommendations on how to engage patients in meaningful and practical ways. RESULTS: Six themes were identified related to PE: the concept of PE, ethical considerations, barriers, key considerations in planning resources, and the anticipated impact of PE on curriculum planning. CONCLUSION: Both patients and educators emphasized that creating and sustaining meaningful educator-patient relationships and giving patients an active and effective role in CPD planning would improve curriculum content. The University of Toronto Department of Radiation Oncology (UTDRO) should consider building this initiative into its strategic CPD priorities and ensure the appropriate infrastructure is in place.

Gastric motility disorders and their endoscopic and surgical treatments other than bariatric surgery.

Gastroparesis is the most common gastric motility disorder. The cardinal symptoms are nausea, vomiting, gastric fullness, early satiety, or bloating, associated with slow gastric emptying in the absence of mechanical obstruction. Delayed gastric emptying is demonstrated by a gastric emptying scintigraphy or by a breath test. Gastroparesis can be idiopathic, post-operative, secondary to diabetes, iatrogenic, or post-infectious. Therapeutic care must be multidisciplinary including nutritional, medical, endoscopic and surgical modes. The complications of delayed gastric emptying must be sought and addressed, particularly malnutrition, in order to identify and correct vitamin deficiencies and fluid and electrolyte disturbances. An etiology should be identified and treated whenever possible. Improvement in symptoms can be treated by dietary regimes and pharmaceutical treatments, including prokinetics. If these are not effective, specialized endoscopic approaches such as endoscopic or surgical pyloromyotomy aim at relaxing the pyloric sphincter, while the implantation of an electrical stimulator of gastric muscle should be discussed in specialized centers.

Venous Causes of Pulsatile Tinnitus: Clinical Presentation, Clinical and Radiographic Evaluation, Pathogenesis, and Endovascular Treatments: A Literature Review.

Tinnitus is an abnormal perception of a sound without external stimulation. Venous pulsatile tinnitus (VPT) is a specific form of tinnitus characterized by an objective and often subjective bruit that occurs as a result of localized venous abnormalities. Clinical evaluation relies on sound quality, duration, and precipitating factors. Idiopathic intracranial hypertension (IIH) and transverse sinus stenosis (TSS) are among the most common causes of VPT. Other causes include sigmoid sinus wall abnormalities (SSWAs), jugular vein anomalies (JVAs), and emissary veins anomalies. These anomalies can be detected on magnetic resonance imaging, magnetic resonance angiography/magnetic resonance venography, and high-resolution temporal bone computed tomography. The pathogenesis behind the VPT includes turbulent blood flow as a result of luminal stenosis or abnormal dilation, amplification of internal sound due to temporal bone defects, and abnormal position of the venous sinus system structures adjacent to the bony structures of the auditive apparatus. Based on these theories, different interventional treatment modalities can be applied to treat the underlying causes. Endovascular treatments have shown high efficacy and safety among those treatments which include stenting of the lateral sinus stenosis in IIH and TSS, coiling of the SSWA and JVA, and embolization of emissary veins anomalies. Further studies are needed to understand the natural history of these anomalies and the efficacy of treatments of VPT, which-unlike other types of tinnitus-can be cured with proper treatment.

A Comprehensive Study of Spindle Cell Oncocytoma of the Pituitary Gland: Series of 6 Cases and Meta-Analysis of 85 Cases.

OBJECTIVE: To discuss optimal treatment strategy for spindle cell oncocytoma (SCO) of the pituitary gland. METHODS: Institutional cases were retrospectively reviewed. A systematic literature search and subsequent quantitative synthesis were performed for further analysis. The detailed features were summarized and the tumor control rate (TCR) was calculated. RESULTS: Eighty-five patients (6 institutional and 79 literature) were included. The annual incidence was approximately 0.01-0.03/100,000. The mean age was 56 years. Vision loss was present in 60%. Seventy-three percent showed hormonal abnormalities. On magnetic resonance imaging, tumor was avidly enhancing, and the normal gland was commonly displaced anterosuperiorly. Evidence of hypervascularity was seen in 77%. Gross total resection (GTR) was achieved in only 24% because of its hypervascular, fibrous, and adhesive nature. The mean postoperative follow-up was 3.3 years for institutional cases and 2.3 years for the integrated cohort. The TCR was significantly better after GTR (5-year TCR, 75%; P = 0.012) and marginally better after non-GTR + upfront radiotherapy (5-year TCR, 76%; P = 0.103) than after non-GTR alone (5-year TCR, 24%). The TCRs for those with low Ki-67 index (≤5%) were marginally better than those with higher Ki-67 index (5-year rate, 57% vs. 23%; P = 0.110). CONCLUSIONS: Frequent endocrine-related symptoms, hypervascular signs, and anterosuperior displacement of the gland support preoperative diagnosis of SCO. GTR seems to have better long-term tumor control, whereas the fibrous, hypervascular, and adhesive nature of SCO makes it difficult to achieve GTR. In patients with non-GTR, radiotherapy may help decrease tumor progression.

Genetic profiling of CAH Egyptian children: rapid guide to clinical interpretation of common mutations.

OBJECTIVES: The prevalence of CAH in Egypt is reported to be ten times more than that of the worldwide prevalence. The study aimed at genetic screening of children diagnosed with 21-alpha hydroxylase deficiency congenital adrenal hyperplasia (21OHD-CAH). In addition, the study offers a rapid and easy guide for clinical reporting of common mutations for endocrinologists. METHODS: A cohort of 174 unrelated Egyptian children with 21OHD-CAH were screened for 11 common CYP21A2 gene mutations using a strip hybridization assay, and then, bioinformatics analysis was done to report the pathogenicity of the common mutations for clinical classification. RESULTS: The most common mutations were I2 splice and p.Q318X. Deletions/conversions comprised 45.9% of the cohort, whereas 7.4% of the cases were negative for all mutations. The least positively detected point mutations were p.P453S, cluster E6, p.R483P, and p.L307FS, which were detected in fewer than 5% of cases. CONCLUSION: Strip hybridization assay is a rapid screening tool for the diagnosis of CAH. The authors hypothesized an easy and rapid scheme for clinical interpretation of the strip results to gain the highest value of the strip in diagnosis.

Carotid artery revascularization: endarterectomy versus endovascular therapy.

Carotid endarterectomy is considered the gold standard for primary and secondary stroke prevention in patients with asymptomatic and symptomatic carotid artery stenosis. The role of CEA has been defined by multiple randomized multicenter trials and CEA is the most studied surgical procedure. In recent years, with advances in endovascular techniques, carotid angioplasty, and stenting (CAS) has been proposed as an alternative to CEA especially in high-risk patients. In this article, we review some of the most important trials on the invasive treatment of carotid artery stenosis and summarized the most recent treatment recommendations based on current evidence. The data overwhelmingly supports revascularization of patients with symptomatic stenosis between 70-90%, with a clear preference for CEA over CAS to be done within 14 days of symptom onset is possible. However, CAS is an acceptable alternative to CEA in certain symptomatic patients such as those with severe medical comorbidities, high riding plaques, contralateral occlusion, restenosis after prior CEA, and radiation-induced stenosis. Treatment of asymptomatic patients remains controversial because of advanced of modern medical therapy and large trials are underway to define the role of invasive revascularization in these patients.

Investigation of process parameters in orthogonal cutting using finite element approaches.

The cutting force in orthogonal cutting of steel AISI 1045 was predicted by applying 2D finite element analysis (FEA) using two methods; (i) Lagrangian (LAG) and (ii) Arbitrary Lagrangian Eulerian (ALE). Johnson-Cook (J-C) models were used for defining plastic and failure properties of simulated materials. The predicted force was validated experimentally by using dynamometer. Comparison held between the simulation methods and experimental work in terms of results accuracy, reading stability, and chip morphology. Furthermore, this study adopted new modeling idea to control the excessive distortion of mesh elements along chip separation line by defining nearly zero damage criterion for these elements. The results demonstrated that LAG and ALE methods could predict the cutting force but with different accuracy, as LAG and ALE results deviated from experimental results with minimum error percentage 3.6% and 0.14% respectively. As well, ALE method showed stable force readings and continues smooth chip during simulation, while LAG method showed unstable force readings and discontinuous realistic chip.

Advanced vacuolation indicates propagation of various salmonid alphavirus type 2 isolates in Acholeplasma-infected BF-2 cells.

During previous routine inspections of bluegill fry (BF-2) and rainbow trout gonad (RTG-2) cells incubated with organ samples from asymptomatic Arctic char Salvelinus alpinus, brook trout Salvelinus fontinalis, and rainbow trout Oncorhynchus mykiss, a distinctive, reproducible cytopathic effect (CPE) appeared. The striking CPE, involving progressive vacuolation turning into slowly proceeding pyknotic degeneration, was originally attributed exclusively to enhanced growth of Acholeplasma sp. However, at a recent re-examination of re-infected BF-2 cells using electron microscopy (EM), conventional PCR, and quantitative PCR (qPCR), a virus was also detected. Two days post inoculation (dpi), EM revealed characteristic virions inside cytoplasmic vacuoles and next to bacteria outside the cells. The nucleotide sequences of the viral nsP3 gene fragment obtained from supernatants of infected cells were 100% identical and representative for salmonid alphavirus type 2 (SAV 2). The 16S RNA gene (16S rDNA) fragment sequences of the Mollicutes-specific PCR product obtained from SAV-infected as well as virus-free BF-2 control cells were identical with Acholeplasma laidlawii. In addition, qPCR results indicated enhanced propagation of virus and bacteria increasing with vacuolation between 5 and 8 dpi. Advanced vacuolation can be regarded as a CPE of both SAV and A. laidlawii, suggesting a viral impact on the bacterial infection that turns a latent intracellular stage into an apparent degenerative condition.

First confirmation of salmonid alphavirus infection in Arctic char Salvelinus alpinus and in Austria.

To date, sleeping disease (SD) caused by salmonid alphavirus 2 (SAV 2) has been reported in freshwater rainbow trout Oncorhynchus mykiss and Atlantic salmon Salmo salar. This study describes for the first time the occurrence of SD in farm-reared Arctic char Salvelinus alpinus and the occurrence of SAV in Austria. Clinical symptoms were indicative of the disease, and the diagnosis was confirmed by histopathology, infectivity in first passages of CHSE-214 cells and PCR. The phylogenetic analysis of the amplified SAV-nonstructural protein-3 (nsP3) fragment revealed the affiliation to the SAV 2 genotype.

Rapid detection and differentiation of carp oedema virus and cyprinid herpes virus-3 in koi and common carp.

Carp oedema virus (CEV) and koi herpes virus (KHV) are of major concern to common carp breeders and koi enthusiasts worldwide. The viruses cause diseases that exhibit similar external signs; thus, it is difficult to distinguish between them clinically. In this study, we developed and optimized rapid and accurate single- and multiplex isothermal diagnostic tools, based on recombinase polymerase amplification (RPA), for detection and differentiation of CEV and KHV. The assays were combined with a lateral flow dipstick to enable visual detection of amplification products and simplify post-amplification analysis. Both CEV- and KHV-RPA assays were specific for their target virus. The lower detection limits of the assays were similar to those of established diagnostic PCR tests for the viruses. A sample preparation method was optimized to eliminate the need for total DNA extraction from fish tissues. The estimated time to perform these RPA assays, from receiving the sample to having a result, is 50 min, compared to 10 and 7 hr for CEV- and KHV-PCR tests, respectively. The assays can be performed in field situations to improve screening of fish and reduce spread of these viruses and thereby enhance the common carp and koi industries.

Re-irradiation of Vertebral Body Metastases: Treatment in the Radiosurgery Era.

Vertebral bodies remain one of the most common sites of metastases. In cases where surgical intervention is not indicated or appropriate, conventional external radiation therapy (cEBRT) has been the standard treatment modality. Unfortunately, cEBRT is typically limited, with low complete response and poor local control rates. Disappointing results with re-irradiation using cEBRT highlight the need for innovative salvage therapeutic strategies, such as stereotactic body radiotherapy. A detailed description of this complex treatment strategy is outlined, as is a systematic review of current literature. Although data are limited to single institution series, re-irradiation has consistently been found to be effective with respect to local control (1 year rates range from 66 to 90%) and pain response. Importantly, the treatment is shown to be safe, with the crude rate of radiation myelopathy <1% and a rate of vertebral compression fracture of 12%. As further research and technologic advances continue to refine therapy, stereotactic body radiotherapy is now a recommended option for the treatment of previously irradiated vertebral body metastases.

The clinical development of vaccines for HER2+ breast cancer: Current landscape and future perspectives.

Human epidermal growth factor receptor 2 (HER2) is a tumor associated antigen over-expressed in 20-30% of cases of breast cancer. Passive immune therapy with HER2-directed monoclonal antibodies (mabs) has changed the natural history of this subset of breast tumors both in the localized and metastatic settings. The safety and efficacy of HER2 vaccines have been assessed in early phase clinical trials but to date clinically relevant results in late phase trials remain an elusive target. Here, we review the recent translational discoveries related to the interactions between the adaptive immune system and the HER2 antigen in breast cancer, results of published clinical trials, and future directions in the field of HER2 vaccine treatment development.

Thermally enhanced TLD output: Impacts on the response curve.

Pre-irradiation background reading of thermoluminescent LiF dosimeters results in severe changes in the glow curve qualitatively and quantitatively. Current work focuses on the possible changes in the response of TLD-700 dosimeters after this effect. This work examines changes in the level of the glow curve as a whole and on the level of individual peaks as well. It was found that the response of TLD-700 dosimeters has increased by factors ranging from 20% to 44% in terms of area under the glow curve. Changes in individual peaks were examined by performing deconvolution for the glow curves. Results confirmed that the response due to such effect is not uniform over the studied temperature range and each individual peak has its own behavior either in terms of peak area or peak intensity. It was observed that the third peak (P3) leads these changes as the change in its area after being exposed to this thermally enhanced thermoluminescence output (TETO) effect was in the range from 4.1 to 3.0 folds compared to the corresponding values obtained without reading the background prior to irradiation. Peak intensity possesses similar behavior where peaks P2 and P4 are following to P3 in their response, the rest of peaks are either neutral or have negative response to TETO. Response curves of each deconvoluted peak in terms of peak area and maximum intensity are analyzed over the range (0.05-30) Gy and discussed in details.

Gold Nanoparticles as a Direct and Rapid Sensor for Sensitive Analytical Detection of Biogenic Amines.

A new optical sensor was developed for rapid screening with high sensitivity for the existence of biogenic amines (BAs) in poultry meat samples. Gold nanoparticles (GNPs) with particle size 11-19 nm function as a fast and sensitive biosensor for detection of histamine resulting from bacterial decarboxylation of histidine as a spoilage marker for stored poultry meat. Upon reaction with histamine, the red color of the GNPs converted into deep blue. The appearance of blue color favorably coincides with the concentration of BAs that can induce symptoms of poisoning. This biosensor enables a semi-quantitative detection of analyte in real samples by eye-vision. Quality evaluation is carried out by measuring histamine and histidine using different analytical techniques such as UV-vis, FTIR, and fluorescence spectroscopy as well as TEM. A rapid quantitative readout of samples by UV-vis and fluorescence methods with standard instrumentation were proposed in a short time unlike chromatographic and electrophoretic methods. Sensitivity and limit of detection (LOD) of 6.59 × 10-4 and 0.6 µM, respectively, are determined for histamine as a spoilage marker with a correlation coefficient (R 2) of 0.993.