Diagnostic utility of 11 C-methionine PET/CT in primary hyperparathyroidism in a UK cohort: A single-centre experience and literature review.

OBJECTIVE: Primary hyperparathyroidism is a common endocrine disorder, with 80% of all cases usually caused by one single hyperfunctioning parathyroid adenoma. Conventional imaging modalities for the diagnostic work-up of primary hyperparathyroidism (PHPT) include ultrasound of the neck, 99mTc-sestamibi scintigraphy, and four-dimensional computed tomography (4D-CT). However, the role of other imaging modalities, such as 11C-methionine PET/CT, in the care pathway for PHPT is currently unclear. Here, we report our experience of the diagnostic utility of 11C-methionine PET/CT in a single-center patient cohort (n = 45). DESIGN: Retrospective single-center cohort study. PATIENTS AND MEASUREMENTS: The data of eligible patients that underwent 11C-methionine PET/CT between 2014 and 2022 at Addenbrooke's Hospital (Cambridge, UK) were collected and analyzed. The clinical utility of imaging modalities was determined by comparing the imaging result with histopathological and biochemical outcomes following surgery. RESULTS: In patients with persistent primary hyperparathyroidism following previous surgery, 11C-methionine PET/CT identified a candidate lesion in 6 of 10 patients (60.0%), and histologically confirmed in 5 (50.0%). 11C-methionine PET/CT also correctly identified a parathyroid adenoma in 9 out of 12 patients (75.0%) that failed to be localized on other imaging modalities. 11C-methionine PET/CT had a sensitivity of 70.0% (95% CI 55.8 - 84.2%) for the detection of parathyroid adenomas. CONCLUSIONS: This study highlights a diagnostic role for 11C-methionine PET/CT in patients that have undergone unsuccessful prior surgery or have equivocal or negative prior imaging results, aiding localization and a targeted surgical approach.

Giant aneurysm arising from a cortical middle cerebral artery branch presenting as an extra-axial tumour: a case report.

The size and anatomical complexity make giant intracranial aneurysms challenging surgical lesions. There is limited literature available for those arising from distal branches. The cases that have been reported in the literature have all presented with symptoms from a rupture leading to an intracranial haemorrhage. In this case report, the authors present a case of a giant aneurysm arising from a cortical branch of the middle cerebral artery presenting as an extra-axial tumour. A 76-year-old gentleman presented with a 2-day history of subjective left arm numbness. Imaging revealed a large conical right-sided parietal lesion. Intraoperatively, it was found that the lesion was being supplied by a single vascular pedicle. Histology was consistent with an aneurysm. In this case, that patient did not have any evidence of a rupture unlike all reported cases of cortical giant aneurysms. This case highlights the myriad location and presentation of giant intracranial aneurysms.

Intrathyroidal parathyroid adenomas: Scoping review on clinical presentation, preoperative localization, and surgical treatment.

Intrathyroidal parathyroid adenomas (IPAs) are a rare cause of primary hyperparathyroidism. They are often difficult to localize preoperatively and intraoperatively, making diagnosis and treatment challenging. Current data on IPAs are sparse and fragmented in the literature. This makes it difficult to compare the effectiveness of different imaging and surgical techniques. To address this issue, this scoping review maps the literature on IPAs, focusing on four domains: clinical presentation, current localization methods, different surgical techniques, and histopathological features. A search of MEDLINE, Embase, and the Cochrane Library was conducted, with 19 studies meeting the inclusion criteria. The characteristics of IPAs on ultrasound, fine-needle aspiration, CT, MRI, sestamibi-based techniques, and selective venous sampling are summarized. Emerging imaging modalities, including autofluorescence, are introduced. Surgical methods and intraoperative factors that correlate with high success rates for removal are highlighted. This review also identifies gaps in knowledge to guide further research into this area.

The impact of neuroradiology collaboration in head and neck cancer radiotherapy peer review.

OBJECTIVE: To quantify the impact of neuroradiologist presence on head and neck cancer (HNC) radiotherapy peer review (PR) changes. METHODS: Prospective data were collected from HNC radiotherapy PR meetings; major, minor, and organ at risk (OAR) changes recorded. Differences in changes made with a neuroradiologist present were determined. χ2 tests of statistical significance were performed. Multivariate logistic regression identified potential predictors of changes. RESULTS: Prospective PR was performed in 125/160 (78%) patients undergoing radical (chemo)radiotherapy for HNC between October 2018 and September 2019. Full PR documentation was available for 120/160 meetings (75%), with a neuroradiologist present in 53/120 (44%). Overall, 51/120 (42.5%) had changes made to target volumes or OARs. When a neuroradiologist was present, 29/53 (55%) of plans had changes made, compared to 22/67 (33%) in their absence. On multivariate analysis, neuroradiologist presence significantly influenced any changes made during the PR meetings (OR 2.59; 95% CI 1.05-6.43; p = 0.039). CONCLUSION: Neuroradiologist presence at PR meetings significantly influences changes made to HNC contouring, likely improving consistency and enhancing quality assurance. ADVANCES IN KNOWLEDGE: This is the first published UK series demonstrating that a collaborative approach between radiology and oncology in PR meetings is significant in leading to contour changes for HNC.

An Approach to a Patient With Primary Hyperparathyroidism and a Suspected Ectopic Parathyroid Adenoma.

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia driven by excess parathyroid hormone (PTH) secretion. PHPT is a common endocrine condition with a prevalence of 1 to 7 cases per 1000 adults. PHPT typically presents in the fifth or sixth decade and shows significant female preponderance. Solitary hyperfunctioning parathyroid adenomas account for 85% to 90% of PHPT cases. The remaining 10% to 15% include cases of multiglandular disease (multiple adenomas or hyperplasia) and, rarely, parathyroid carcinoma (1%). Ectopic parathyroid adenomas may arise due to abnormal embryological migration of the parathyroid glands and can be difficult to localize preoperatively, making surgical cure challenging on the first attempt. The potential existence of multiglandular disease should be considered in all patients in whom preoperative localization fails to identify a target adenoma or following unsuccessful parathyroidectomy. Risk factors for multiglandular disease include underlying genetic syndromes (eg, MEN1/2A), lithium therapy, or previous radiotherapy. In addition to multifocal disease, the possibility of an ectopic parathyroid gland should also be considered in patients requiring repeat parathyroid surgery. In this article, we use illustrative clinical vignettes to discuss the approach to a patient with primary hyperparathyroidism (PHPT) and a suspected ectopic parathyroid adenoma.

BRAF V600E Mutant Lung Adenocarcinoma Presenting With a Skull Base Metastasis and Pituitary Adenoma Collision Tumour.

We report an unusual initial presentation for metastatic lung adenocarcinoma (LAC) with progressive loss of vision, a rare molecular phenotype and rapid visual response to surgical resection. A 60-year-old female presented with rapid and progressive visual loss over four weeks. Contrast-enhanced CT and MRI scans showed an enhancing lobulated mass in the base of skull infiltrating into the sella turcica. The patient underwent transnasal endoscopic debulking of the mass with rapid improvement in her vision. Histology showed a collision tumour with a pituitary adenoma and a microacinar metastatic adenocarcinoma. Staging CT of the chest, abdomen and pelvis showed a T4 N2 M1 right LAC. Molecular profiling of the metastasis confirmed an activating mutation involving codon 600 of BRAF gene (BRAF V600E). The patient was treated with combination chemotherapy but rapidly deteriorated and unfortunately died due to progressive disease. Efforts to access BRAF/MEK inhibitors for off-label use were unsuccessful. We believe our patient would have benefited from a BRAF/MEK inhibitor. This case illustrates the very unusual presentation of metastatic LAC with visual loss secondary to a collision tumour containing a pituitary adenoma and metastatic adenocarcinoma.

A single-centre retrospective analysis of cinacalcet therapy in primary hyperparathyroidism.

Primary hyperparathyroidism (pHPT) is a common endocrine disorder that can be cured by parathyroidectomy; patients unsuitable for surgery can be treated with cinacalcet. Availability of surgery may be reduced during COVID-19, and cinacalcet can be used as bridging therapy. In this single-centre retrospective analysis, we investigated the utility and safety of cinacalcet in patients with pHPT receiving cinacalcet between March 2019 and July 2020, including pre-parathyroidectomy bridging. We reviewed and summarised the published literature. Cinacalcet dosages were adjusted by endocrinologists to achieve target calcium < 2.70 mmol/L. Eighty-six patients were identified, with the most achieving target calcium (79.1%) with a mean dose of 39.4 mg/day (±17.1 mg/day) for a median duration of 35 weeks (1-178 weeks). Calcium was normalised in a median time of 5 weeks. The majority of patients commenced cinacalcet of 30 mg/day (78 patients) with the remainder at 60 mg/day (8 patients). Forty-seven patients commencing lower dose cinacalcet (30 mg/day) achieved target calcium without requiring 60 mg/day. Baseline PTH was significantly higher in patients requiring higher doses of cinacalcet. 18.6% of patients reported adverse reactions and 4.7% discontinued cinacalcet. Patients treated with cinacalcet pre-parathyroidectomy required a higher dose and fewer achieved target calcium compared to medical treatment with cinacalcet alone. Post-operative calcium was similar to patients who were not given pre-parathyroidectomy cinacalcet. In summary, cinacalcet at an initial dose of 30 mg/day is safe and useful for achieving target calcium in patients with symptomatic or severe hypercalcaemia in pHPT, including those treated for pre-parathyroidectomy. We propose a PTH threshold of >30 pmol/L to initiate at a higher dose of 60 mg/day.

Response to BRAF and MEK1/2 inhibition in a young adult with BRAF V600E mutant epithelioid glioblastoma multiforme: A Case Report and Literature Review.

Epithelioid glioblastoma multiforme (eGBM) is a rare and aggressive variant of glioblastoma multiforme (GBM) that predominantly affects younger patients and can be difficult to distinguish from other gliomas. Data on how patients with eGBM might be best treated are limited, although genomic analyses have shown that almost half of tumours harbour activating BRAF gene mutations. Here we present the case of a young female with BRAF V600E-mutant eGBM who had a prolonged response to targeted therapy with the BRAF and MEK1/2 inhibitors dabrafenib and trametinib. We review current knowledge about eGBM, including the emerging role for BRAF- ± MEK1/2- targeted therapy.

When Should We Stop Scanning Older Patients with Vestibular Schwannomas?

Objective Observation is a well-accepted management for small- to medium-sized vestibular schwannomas (VSs). Although there are good data on the natural history of this disease within adults, no studies have looked specifically at those aged over 70 years. Thus, there is a need for a surveillance protocol to determine if and when we can stop imaging safely patients aged 70 years and over with a new diagnosis of VSs when managed with observation. Design Over a 13-year period, we retrospectively analyzed all skull base unit patients with a sporadic unilateral VSs managed with an imaging surveillance protocol. All data were collected prospectively with a minimum follow-up of 5 years. Setting Tertiary referral skull base unit Participants Patients aged 70 years and over with sporadic VSs at diagnosis Main Outcome Measures Main outcome measures Results A total of 112 patients met inclusion criteria. The median age at diagnosis was 74 years (range: 70-87 years). The mean follow-up was 82 months (range: 60-144). The size of the VSs at diagnosis was intracanalicular (IC) in 46%, small in 41%, medium in 12%, and large in 2%. Growth was more likely where tumors were extracanalicular (EC) rather than IC at presentation ( p = 0.036) and within the first 18 months after diagnosis ( p < 0.001). Twenty-nine percent of VSs displayed growth (6% continued surveillance, 23% received active treatment). Good hearing at diagnosis did not predict tumor stability for IC or EC tumors ( p = 0.162 and p = 0.536). Conclusions Since no VSs grew after 42 months from diagnosis, our data support an initial magnetic resonance imaging (MRI) at 6 months after diagnosis followed by an annual MRI for 3 years. At this point, consideration could be given to discussing discontinuation or further imaging with patients.

Clinical pathophysiology of thyroid eye disease: The Cone Model.

The clinical features of thyroid eye disease are dictated by the orbit's compartmentalisation; particularly, the muscle cone, which is delimited by the rectus muscles, their inter-muscular septa and the posterior sclera. The cone is anchored to the orbit apex and contains the posterior globe, the muscle bellies, a fat pad, and the blood circulation, optic nerve, and CSF sheath. It is surrounded by mobile extraconal fat, retained by the orbital septum.Thyroid eye disease is caused by expansion of muscle bellies and fat within the cone. Mechanical properties of the cone determine that the disease partitions into three phases: circumferential expansion, with forward displacement of extraconal fat; axial elongation, with increasing cone pressure; impedance of posterior venous outflow, with cone oedema and venous flow reversal.Venous flow reversal can be observed in the conjunctival circulation. It is initially transient, accompanying rises in cone pressure caused by eye movements, but later becomes permanent. It is a useful clinical sign that locates diseased muscles and anticipates venous compressive crises.Strabismus arises when inflamed rectus muscles, swollen by hydrated glycosaminoglycans, lose contractility and compliance. The incomitance is moderated by increasing stiffness affecting all the rectus muscles, as they are stretched during cone expansion.Immunomodulation, which rapidly reduces cone volume, relieving muscle elongation and stiffness, may paradoxically unmask strabismus. However, ciclosporin A suppresses late post-inflammatory fibrosis and only 4 of 71 patients so-treated required strabismus surgery.The cone model also accounts for the variety of clinical presentations of thyroid eye disease.

T2-relaxation mapping and fat fraction assessment to objectively quantify clinical activity in thyroid eye disease: an initial feasibility study.

Imaging in thyroid eye disease (TED) is used to exclude other diagnoses, assess for apical crowding and plan surgery. But to quantify TED activity objectively, subjective clinical scoring assessments remain the norm. Magnetic resonance imaging (MRI) T2-relaxation times correlate with extra-ocular muscle (EOM) inflammation, but are confounded by signal from fat. We investigated whether T2-relaxation mapping in combination with fat fraction (FF) measurements could quantify disease activity in EOMs objectively. Sixty-two TED patients and six controls were enroled for coronal short tau inversion recovery (STIR), T2 multi-echo fast-spin echo and multi-echo fast-gradient echo MRI of the orbits. STIR signal intensity ratios (SIRs), T2-relaxation times and percentage FF were derived for inferior, lateral, superior and medial recti bilaterally. Twelve patients were re-scanned following immunosuppressive treatment. The results found a positive correlation for all subjects between T2 and SIR (p < 0.001), but only mean T2 differed significantly between patients and controls (p < 0.001). We measured FF in EOMs for the first time and found it greater in TED (p < 0.001). There was also a significant reduction in mean T2 after treatment, with a corresponding reduction in the clinical activity score (CAS) in almost all patients. We show that T2-relaxation times differentiate between normal and inflamed EOMs and are responsive to treatment. Combined, uniquely, with FF measurement in EOMs, an objective, quantitative marker of inflammation in TED-affected muscles could be derived. T2-relaxation times mirrored improvements in CAS after treatment, occasionally preceding them. Rarely, they diverged, suggesting limitations in the CAS as a disease burden marker.

A Comparison of Repeatability and Usability of Semi-Automated Volume Segmentation Tools for Measurement of Vestibular Schwannomas.

OBJECTIVE: Semi-automated volume segmentation tools (SAVST) offer a less time consuming technique compared with manual volume segmentation method. No data exists to suggest which of the available applications are optimal for use with vestibular schwannomas (VS). This study aims to compare repeatability and usability of three different SAVST for measurement of VS. STUDY DESIGN: Experimental comparison of three SAVST. SETTING: Tertiary skull base unit. PATIENTS: Twenty-four patients with a unilateral VS imaged with T1-weighted Gadolinium enhanced MRI. INTERVENTION: Repeated measurements made to determine intra and inter-observer agreement. This was repeated using three different SAVST. MAIN OUTCOME MEASURES: 1) Intra- and inter-observer intraclass correlation coefficients (ICC), repeatability coefficients (RC), and relative smallest detectable differences (%SDD).2) Usability as determined by the mean number of steps and time required per tumor measurement and the proportion of cases where manual editing was required. RESULTS: Intra-observer ICCs were significantly better for SliceOmatic and OleaSphere than AW VolumeShare (0.998 versus 0.994, p < 0.05). Inter-observer ICCs were also better for SliceOmatic (0.994) and OleaSphere (0.989) compared with AW VolumeShare (0.976), however, this was only significant for SliceOmatic (p = 0.012). SliceOmatic had a poorer usability profile requiring more manual editing, time, and individual steps per measurement but its "watershed segmentation" algorithm was better at measuring cystic or heterogenous tumors. CONCLUSIONS: This is the first study to compare three SAVST for measurement of VS. While SliceOmatic had the highest repeatability, Olea Sphere combined comparable repeatability with improved usability and a greater degree of automation and was, therefore, deemed optimal for use in routine clinical practice.

A comparison of semi-automated volumetric vs linear measurement of small vestibular schwannomas.

OBJECTIVE: Accurate and precise measurement of vestibular schwannoma (VS) size is key to clinical management decisions. Linear measurements are used in routine clinical practice but are prone to measurement error. This study aims to compare a semi-automated volume segmentation tool against standard linear method for measuring small VS. This study also examines whether oblique tumour orientation can contribute to linear measurement error. STUDY DESIGN: Experimental comparison of observer agreement using two measurement techniques. SETTING: Tertiary skull base unit. PARTICIPANTS: Twenty-four patients with unilateral sporadic small (< 15 mm maximum intracranial dimension) VS imaged with 1 mm-thickness T1-weighted Gadolinium enhanced MRI. MAIN OUTCOME MEASURES: (1) Intra and inter-observer intraclass correlation coefficients (ICC), repeatability coefficients (RC), and relative smallest detectable difference (%SDD). (2) Mean change in maximum linear dimension following reformatting to correct for oblique orientation of VS. RESULTS: Intra-observer ICC was higher for semi-automated volumetric when compared with linear measurements, 0.998 (95% CI 0.994-0.999) vs 0.936 (95% CI 0.856-0.972), p < 0.0001. Inter-observer ICC was also higher for volumetric vs linear measurements, 0.989 (95% CI 0.975-0.995) vs 0.946 (95% CI 0.880-0.976), p = 0.0045. The intra-observer %SDD was similar for volumetric and linear measurements, 9.9% vs 11.8%. However, the inter-observer %SDD was greater for volumetric than linear measurements, 20.1% vs 10.6%. Following oblique reformatting to correct tumour angulation, the mean increase in size was 1.14 mm (p = 0.04). CONCLUSION: Semi-automated volumetric measurements are more repeatable than linear measurements when measuring small VS and should be considered for use in clinical practice. Oblique orientation of VS may contribute to linear measurement error.

The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS).

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.