Ultrasonography led multimodal diagnostic pathway for giant cell arteritis.

OBJECTIVES: To establish the sensitivity and negative predictive value of a multimodal pathway incorporating ultrasonography, 18-fluorodeoxyglucose labelled positron emission tomography computed tomography and temporal artery biopsy for the diagnosis of giant cell arteritis. METHODS: 1000 consecutive referrals for a new diagnosis of giant cell arteritis were analysed. All patients had a protocolized examination. Patients with a negative ultrasonography and a C-reactive protein of ≥ 20 mg/l received an extended ultrasound examination. If that was negative, and there was no other explanation for their presentation, a second test in the form of either a temporal artery biopsy or an 18-fluorodeoxyglucose labelled positron emission tomography computed tomography was offered. We calculated the sensitivity and negative predictive value of the interventions for diagnosing giant cell arteritis. RESULTS: 279/1000 patients had positive ultrasonography for giant cell arteritis. 202 had bilateral superficial temporal arterial involvement. Ultrasonography of the axillary artery and other head/neck arteries increased the yield by 53 and 24 patients respectively. 181 patients were referred for a second test. 24/139 temporal artery biopsies and 7/42 18-fluorodeoxyglucose labelled positron emission tomography computed tomography scans were positive. The sensitivity and negative predictive value rise from 62.3% and 84.7% respectively for imaging superficial temporal arteries alone, to 95.7% and 98.0% respectively for extended ultrasonography plus a second test. CONCLUSIONS: This is the first real world evidence of the utility of ultrasonography for the diagnosis of giant cell arteritis as part of a multimodal diagnostic pathway.

Incidence of primary large vessel vasculitis in Norfolk, UK from 2011 to 2020.

OBJECTIVES: To report the annual incidence of primary large vessel vasculitis (LVV) in the adult population of Norfolk County, UK, including giant cell arteritis (GCA) (in those ≥50 years) and Takayasu arteritis (TAK). METHODS: Individuals diagnosed by histology or imaging who lived in NR1-NR30 postcode districts were included. Validated criteria from 1990 and 2022 were applied for final classification. Population data were available from the Office of National Statistics, UK. RESULTS: 270 individuals were diagnosed with primary LVV over 4.7 million person-years. The annual incidence (95% CI) of primary LVV was 57.5 (50.8, 64.7)/million person-years in the adult population. 227 and 244 individuals were diagnosed with GCA over ~2.5 million person-years using 1990 and 2022 criteria, respectively. The annual incidence (95% CI) of GCA was 91.6 (80.0, 104.3)/million person-years aged ≥50 years using 1990 criteria and 98.4 (86.4, 111.6)/million person-years aged ≥50 years using 2022 criteria. 13 and 2 individuals were diagnosed with TAK over 4.7 million person-years. The annual incidence (95% CI) of TAK was 2.8 (1.5, 4.7)/million person-years using 1990 criteria and 0.4 (0.0, 1.4)/million person-years using 2022 criteria, in the adult population. The incidence of GCA rose sharply in 2017 coincident with the introduction of a fast-track pathway and fell during the pandemic when the pathway was disrupted. CONCLUSIONS: This is the first study that reports the incidence of objectively verified primary LVV in the adult population. The incidence of GCA may be affected by the availability of diagnostic pathways. The use of the 2022 classification criteria results in a rise in the classification of GCA and fall in that of TAK.

Effectiveness of SPECT/CT Imaging for Sentinel Node Biopsy Staging of Primary Cutaneous Melanoma and Patient Outcomes.

PURPOSE: Coregistered SPECT/CT can improve accuracy of sentinel node biopsy (SNB) for staging melanoma. This benefit has implications for pathology services and surgical practice with increased diagnostic and surgical workload. The purpose of this study was to investigate the effectiveness of SPECT/CT imaging. METHODS: SNB data were collected over a 10-year period. Preoperative SLN mapping was performed by using planar lymphoscintigraphy (LSG) for all patients (n = 1522) and after October 2015, patients underwent a second co-registered SPECT/CT scan (n = 559). The patients were stratified according to the imaging protocol. The number of nodes and nodal basins were assessed. The reasons for cancellation also were assessed. RESULTS: A total of 95% (1446/1522) of patients underwent a successful SNB procedure. Significantly more sentinel nodes were identified by the SPECT/CT protocol (3 vs. 2; p < 0.0001). More patients were cancelled in the SPECT/CT cohort (9.3% vs. 2.5%; p < 0.0001). Head & neck, lower limb, and AJCC IB primaries were significantly less likely to proceed to SNB. SPECT/CT identified significantly more positive SNBs (20.9% vs. 16.5%; p = 0.038). SPECT/CT imaging was associated with improved disease-free (hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54-1.0); p = 0.048) and disease-specific survival (HR = 0.48; 95% CI: 0.3-0.78; p = 0.003). Patients who did not proceed to SNB had a significantly increased nodal relapse rate (23.5% vs. 6.8%; HR = 3.4; 95% CI: 1.9-6.2; p < 0.0001) compared with those who underwent SNB. CONCLUSIONS: This large cohort study confirms the increased accuracy of SPECT/CT for identifying SLN metastases, which would appear to have a significant therapeutic benefit, although an increased risk of cancellation of the SNB procedure on the day of surgery.

Positron Emission Tomography Computed Tomography: A Guide for the General Radiologist.

Cancer remains a leading cause of death in Canada and worldwide. Whilst advances in anatomical imaging to detect and monitor malignant disease have continued over the last few decades, limitations remain. Functional imaging, such as positron emission tomography (PET), has improved the sensitivity and specificity in detecting malignant disease. In combination with computed tomography (CT), PET is now commonly used in the oncology setting and is an integral part of many cancer patients' pathways. Although initially the CT component of the study was purely for attenuation of the PET imaging and to provide anatomical coregistration, many centers now combine the PET study with a diagnostic quality contrast enhanced CT to provide one stop staging, thus refining the patient's pathway. The commonest tracer used in everyday practice is FDG (F18-fluorodeoxyglucose). There are many more tracers in routine clinical practice and those with emerging roles, such as 11C-choline, useful in the imaging of prostate cancer; 11C-methionine, useful in imaging brain tumours; C11-acetate, used in imaging hepatocellular carcinomas; 18F-FLT, which can be used as a marker of cellular proliferation in various malignancies; and F18-DOPA and various 68Ga-somatostatin analogues, used in patients with neuroendocrine tumours. In this article we concentrate on FDG PETCT as this is the most commonly available and widely utilised tracer now used to routinely stage a number of cancers. PETCT alters the stage in approximately one-third of patients compared to anatomical imaging alone. Increasingly, PETCT is being used to assess early metabolic response to treatment. Metabolic response can be seen much earlier than a change in the size/volume of the disease which is measured by standard CT imaging. This can aid treatment decisions in both in terms of modifying therapy and in addition to providing important prognostic information. Furthermore, it is helpful in patients with distorted anatomy from surgery or radiotherapy when there is suspicion of recurrent or residual disease. FDG PETCT is not specific for malignancy and can also be used for diagnosing and monitoring a number of inflammatory and infectious conditions that can be difficult to diagnose on anatomical imaging, some of which carry significant morbidity. FDG PETCT is increasingly used in patients with pyrexia of unknown origin and in patients with metastatic malignancies of unidentified primary on conventional imaging. This article reviews the uses of PETCT including an overview of the more common incidental lesions and conditions. It also provides guidance of how to approach a PETCT as a nonradionuclide radiologist and how to interpret a study in the multidisciplinary team setting.

Non-small cell lung carcinoma: accuracy of PET/CT in determining the size of T1 and T2 primary tumors.

OBJECTIVE: The purpose of this study was to compare the measurements of primary T1 and T2 non-small cell lung carcinomas (NSCLCs) at PET/CT to determine which modality has the more accurate correlation with the histologic findings. MATERIALS AND METHODS: A retrospective study was performed with the images of 59 patients who underwent surgical resection of T1 and T2 NSCLC and preoperative PET/CT. The maximum measurement of the primary lung tumor was recorded on the PET and unenhanced CT (soft-tissue and lung windows) scans in the largest plane and compared with the maximum dimensions of the histologic specimen. RESULTS: PET and CT measurements both had high concordance with the histologic measurements. CT soft-tissue window measurements had the highest concordance with histologic measurements, but PET had a smaller SD. The greatest linear correlation was between CT soft-tissue and CT lung window measurements, indicating they can be used interchangeably. Outliers were found in both the PET (four tumors) and the two CT (five tumors) groups owing to low (18)F-FDG uptake due to tumor type and surrounding consolidation, respectively. CONCLUSION: PET is better for delineating primary NSCLC if surrounding collapse or consolidation is present. Otherwise, CT with either soft-tissue or lung windows is accurate. Owing to low FDG accumulation, CT is more accurate for assessment of alveolar cell carcinoma.

Erdheim-Chester Disease: Two cases from an ophthalmic perspective.

PURPOSE: We report two patients who presented initially to ophthalmology clinics with symptoms and signs of orbital inflammation that led to a diagnosis of Erdheim-Chester Disease (ECD). OBSERVATIONS: ECD is a rare form of non-Langerhans cell histiocytosis (LCH) which is characterised by multi-system organ involvement and poor prognosis with standard therapies. Both patients were positive for the BRAF V600E mutation on genetic testing and were treated with the BRAF inhibitors Vemurafenib and Dabrafenib respectively. These cases highlight the variable clinical presentation and course of ECD, the classical radiological and histopathological findings, and the high degree of clinical suspicion necessary to reach this diagnosis. CONCLUSIONS AND IMPORTANCE: The combination of xanthelasma and bilateral, diffuse intraconal orbital masses must suggest to the clinician the possibility of ECD; and consideration to arrange further investigation with a full body CT or FDG PET/CT scan should be given, even in the absence of wider systemic symptoms or signs. With the advent of targeted therapies such as BRAF inhibitors, it is of even more importance that a diagnosis of ECD is established in a timely manner in order to give these patients the best chance of reduced morbidity and increased survival.

Unexpected changes in clinical diagnosis: early abdomino-pelvic computed tomography compared with clinical evaluation.

BACKGROUND: To evaluate the value of early computed tomography (CT) on identifying clinically "unexpected" diagnosis in patients presenting with "non specific" acute abdominal pain. MATERIALS AND METHODS: All patients presenting to on-call surgeons with acute abdominal pain were eligible study participants. Patients were randomised to CT within one hour of admission or supine abdominal and erect chest radiography. Ninety-nine patients randomized to CT arm were reviewed for the purpose of this study. The number and severity of unexpected and/or incidental diagnoses detected on the CT were assessed. RESULTS: In 20 of the 99 patients CT revealed primary or secondary diagnoses, which were unexpected following the initial clinical examination and led to completely different therapeutic options. In 15 of those 20 patients CT revealed clinically unexpected conditions, whereas in two patients severe complications of the clinically suspected diagnosis were detected on CT. Five patients had significant incidental findings in addition to their primary diagnosis on CT. In two of these patient CT also revealed clinically unexpected diagnoses. CONCLUSION: Early CT has the advantage of detecting unexpected clinically significant primary and secondary diagnoses in patients presenting with acute abdominal pain and best guides the surgeon to the appropriate patient management.

Parotid incidentalomas on positron emission tomography: what is their clinical significance?

OBJECTIVE AND AIM: The increased use of PET/CT in cancer staging has resulted in more incidental findings in unexpected locations, making this a challenge for the radiologist interpreting the study. Our aim was to determine the frequency of parotid incidentalomas and to assess the ability of PET/CT to characterize them. PATIENTS AND METHODS: At the Norfolk and Norwich University Trust, in between October 2010 to October 2015, 4044 patients had a PET/CT examination. The issued clinical reports that contained the word 'parotid' were traced and all patients selected for this study had no known or suspected parotid disease before the PET/CT scan. RESULTS: The prevalence of parotid incidentalomas was 1.73%; higher than expected as was the mean age of our study group. Ten per cent of patients had no focal lesion identified on subsequent ultrasound. Thirty-two per cent of patients had a biopsy which showed that the majority of these findings were benign and 13% had metastatic deposits, with the primary carcinoma in these cases being neuroendocrine colon carcinoma, non-Hodgkin's lymphoma and melanoma. CONCLUSION: The most common benign salivary tumour in our study was Warthin's tumour and the majority of these patients had a primary lung carcinoma. Given that the main predisposing factor for both pathologies is smoking, potentially this suggests an association between the incidence of primary lung carcinoma and Warthin's tumour. Ten (14%) patients in our study had a standardized uptake value of below 3.2 (using the VUE Point HD algorithm). These patients had either no identifiable lesion on ultrasound or no malignant features on histology; therefore, we propose that a cut-off of 3.2 on PET/CT could be used to differentiate between physiological or benign uptake from malignant fluorine-18-fluorodeoxyglucose uptake in the parotid gland.

Survival outcomes and interval between lymphoscintigraphy and SLNB in cutaneous melanoma- findings of a large prospective cohort study.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) in cutaneous melanoma (CM) is performed to identify patient at risk of regional and distant relapse. We hypothesized that timing of lymphoscintigraphy may influence the accuracy of SLNB and patient outcomes. METHODS: We reviewed prospective data on patients undergoing SLNB for CM at a large university cancer-center between 2008 and 2015, examining patient and tumor demographics and time between lymphoscintigraphy (LS) and SLNB. Kaplan-Meier survival analysis assessed disease-specific (DSS) and overall-survival (OS), stratified by timing of LS. Cox multivariate regression analysis assessed independent risk factors for survival. RESULTS: We identified 1015 patients. Median follow-up was 45 months (IQR 26-68 months). Univariate analysis showed a 6.8% absolute DSS (HR 1.6 [1.03-2.48], p = 0.04) benefit and a 10.7% absolute OS (HR 1.64 [1.13-2.38], p = 0.01) benefit for patients whose SLNB was performed < 12 h of LS (n = 363) compared to those performed >12 h (n = 652). Multivariate analysis identified timing of LS as an independent predictor of OS (p = 0.007) and DSS (p = 0.016) when competing with age, sex, Breslow thickness (BT) and SLN status. No difference in nodal relapse rates (5.2% v 4.6%; p = 0.67) was seen. Both groups were matched for age, sex, BT and SLN status. CONCLUSION: These data have significant implications for SLNB services, suggesting delaying SLNB >12 h after LS using a Tc99-labelled nanocolloid has a significant negative survival impact for patients and should be avoided. We hypothesise that temporal tracer migration is the underlying cause and advocate further trials investigating alternative, 'stable' tracer-agents.

Healthy passive cigarette smokers have increased pulmonary alveolar permeability.

QUESTION: Does passive smoking have a measurable effect on lung function in otherwise healthy subjects? There is current interest concerning passive smoking but no objective evidence showing that it has any impact on lung function. METHODS: The pulmonary clearance rate of (99m)Tc-DTPA was measured in 21 healthy volunteers after inhalation as a radio-aerosol and compared between healthy cigarette smokers, passive smokers and non-smokers. All volunteers had normal lung function. RESULTS: Clearance half-times in healthy passive smokers (n=5) were longer than in healthy smokers (n=6) but clearly shorter compared with healthy non-smokers (n=10) with respective mean values of 45.2 (SD 8.3), 24.3 (8.6) and 80.3 (20) min. CONCLUSION: Passive smoking has a functional impact on the lung blood/gas barrier.

Technetium-99m Methylene Diphosphonate Single-photon Emission Computed Tomography/Computed Tomography of the Foot and Ankle.

The complex anatomy and function of the foot and ankle can make it difficult to determine the cause of symptoms in patients with foot and ankle pathology. Following initial clinical and radiographic assessment, additional imaging with magnetic resonance imaging may be required, which is often seen as the modality of choice. Although sensitive to pathological changes in bone metabolism and vascularity, technetium-99m (Tc-99m) bone scintigraphy often lacks the specificity and resolution required to evaluate the structures of the foot and ankle. Tc-99m methylene diphosphonate single-photon emission computed tomography/computed tomography (SPECT/CT) combines this sensitivity with the superior anatomical detail of CT, enabling better localization of pathological uptake and evaluation of associated structural changes. As a result, SPECT/CT has been growing in popularity for the assessment of patients with foot and ankle pathology where it can provide additional information that may change the initial diagnosis and subsequent management plan. Studies have reported modification of the surgical approach and site of intra-articular local anesthetic injections following SPECT/CT with good results. Interpretation of SPECT/CT studies requires an understanding of the pathological changes that result in increased tracer accumulation in addition to the CT changes that may be seen. This review aims to highlight the advantages of SPECT/CT, potential applications and explain the imaging appearances of common pathologies that may be observed.

MicroRNA expression in a phosphaturic mesenchymal tumour.

Phosphaturic mesenchymal tumours are a heterogeneous set of bone and soft tissue neoplasms that can cause a number of paraneoplastic syndromes such as tumour induced osteomalacia. The term phosphaturic comes from the common finding that these tumours secrete high levels of fibroblast growth factor 23 which causes renal phosphate wasting leading to hypophosphatemia. Phosphaturic mesenchymal tumours are rare and diagnosis is difficult. A very active 68 year old male presented with bone pain and muscle weakness. He was hypophosphataemic and total alkaline phosphatase was markedly elevated. The patient was placed on vitamin D supplementation but his condition progressed. In the fifth year of presentation the patient required the use of a wheelchair and described "explosive" bone pain on physical contact. Serum 1,25 dihydroxyvitamin D was low and serum fibroblast growth factor 23 was significantly elevated, raising suspicion of a phosphaturic mesenchymal tumour. A lesion was detected in his left femoral head and the patient underwent a total hip replacement. The patient displayed a rapid improvement to his condition and during a three year follow up period he returned to an active lifestyle. As molecular testing may help provide a robust diagnosis and is particularly useful in rare diseases we took a next generation sequencing approach to identify a differential expression of small RNAs in the resected tumour. Small RNAs are non-coding RNA molecules that play a key role in regulation of gene expression and can be used as specific biomarkers. We found an upregulation of miR-197. We also found a downregulation of miR-20b, miR-144 and miR-335 which is a small RNA profile typical of osteosarcoma. MiR-21, the most frequently upregulated microRNA in cancer, was downregulated. We conclude that the specific small RNA profile is typical of osteosarcoma except for the downregulation of oncogenic miR-21. Transcriptional plasticity of miR-197, which is computationally predicted to target fibroblast growth factor 23 messenger RNA, may be upregulated in a cellular effort to correct the ectopic expression of the protein.

Does 99mTc-MDP bone scintigraphy add to the investigation of patients with symptomatic unicompartmental knee replacement?

AIM: The purpose of this study was to determine whether nuclear medicine (99m)Tc-Methyl diphosphonate bone scintigraphy ((99m)Tc-MDP bone scintigraphy) added information over plain radiographs loosening infection in symptomatic unicompartmental knee replacements (UKRs). METHODS AND MATERIALS: A cohort of 39 patients who presented with knee pain following UKR was retrospectively reviewed. All had undergone nuclear medicine bone scans for possible loosening or infection of the prosthesis. The findings of the bone scintigraphy were compared to subsequent operative findings during diagnostic arthroscopic investigation or revision surgery for those patients who had undergone these procedures. RESULTS: Of the 39 patients with painful knees following UKR, surgical findings confirmed that 11 had either loose (n=9) or infected (n=2) implants. Logistic regression analysis demonstrated no statistically significant combination of features on nuclear medicine or radiographs associated with failure of the prosthesis due to infection or loosening (p>0.05). Classification of a satisfactory position of the UKR on plain radiography exhibited a high negative predictive value (96% for infections, and 80% for loosening). However, plain radiograph was not sensitive for loosening (50%) or infection (37%) of the UKR with very low positive predictive values (9.1% for infection and 27.3% for loosening). CONCLUSION: This study provides no evidence to support the routine use of (99m)Tc-MDP bone scintigraphy in the clinical decision-making for patients with a painful UKR. LEVEL OF EVIDENCE: level 4.

Can 16-detector multislice CT exclude skeletal lesions during tumour staging? Implications for the cancer patient.

Current imaging guidelines recommend that many cancer patients undergo soft-tissue staging by computed tomography (CT) whilst the bones are imaged by skeletal scintigraphy (bone scan). New CT technology has now made it feasible, for the first time, to perform a detailed whole-body skeletal CT. This advancement could save patients from having to undergo duplicate investigations. Forty-three patients with known malignancy were investigated for bone metastasis using skeletal scintigraphy and 16-detector multislice CT. Both studies were performed within six weeks of each other. Whole-body images were taken 4 h after injection of 500 Mbq (99m)Tc-MDP using a gamma camera. CT was performed on a 16-detector multislice CT machine from the vertex to the knee. The examinations were reported independently and discordant results were compared at follow-up. Statistical equivalence between the two techniques was tested using the Newcombe-Wilson method within the pre-specified equivalence limits of +/-20%. Scintigraphy detected bone metastases in 14/43 and CT in 13/43 patients. There were seven discordances; four cases were positive on scintigraphy, but negative on CT; three cases were positive on CT and negative on scintigraphy. There was equivalence between scintigraphy and CT in detecting bone metastases within +/-19% equivalence limits. Patients who have undergone full whole-body staging on 16-detector CT may not need additional skeletal scintigraphy. This should shorten the cancer patient's diagnostic pathway.