Development of a simple standardized scoring system for assessing large vessel vasculitis by 18F-FDG PET-CT and differentiation from atherosclerosis.

PURPOSE: This study is to develop a structured approach to distinguishing large-artery vasculitis from atherosclerosis using 18-fluorodeoxyglucose positron emission tomography combined with low-dose computed tomography (FDG PET/CT). METHODS: FDG PET/CT images of 60 patients were evaluated, 30 having biopsy-proven giant cell arteritis (GCA; the most common form of large-artery vasculitis), and 30 with severe atherosclerosis. Images were evaluated by 12 nuclear medicine physicians using 5 criteria: FDG uptake pattern (intensity, distribution, circularity), the degree of calcification, and co-localization of calcifications with FDG-uptake. Criteria that passed agreement, and reliability tests were subsequently analysed for accuracy using receiver operator curve (ROC) analyses. Criteria that showed discriminative ability were then combined in a multi-component scoring system. Both initial and final 'gestalt' conclusion were also reported by observers before and after detailed examination of the images. RESULTS: Agreement and reliability analyses disqualified 3 of the 5 criteria, leaving only FDG uptake intensity compared to liver uptake and arterial wall calcification for potential use in a scoring system. ROC analysis showed an area under the curve (AUC) of 0.90 (95%CI 0.87-0.92) for FDG uptake intensity. Degree of calcification showed poor discriminative ability on its own (AUC of 0.62; 95%CI 0.58-0.66). When combining presence of calcification with FDG uptake intensity into a 6-tiered scoring system, the AUC remained similar at 0.91 (95%CI 0.88-0.93). After exclusion of cases with arterial prostheses, the AUC increased to 0.93 (95%CI 0.91-0.95). The accuracy of the 'gestalt' conclusion was initially 89% (95%CI 86-91%) and increased to 93% (95%CI 91-95%) after detailed image examination. CONCLUSION: Standardised assessment of arterial wall FDG uptake intensity, preferably combined with assessment of arterial calcifications into a scoring method, enables accurate, but not perfect, distinction between large artery vasculitis and atherosclerosis.

Use of Diffusion-Weighted Imaging and 18F-Fluorodeoxyglucose Positron Emission Tomography Combined With Computed Tomography in the Response Assessment for (Chemo)radiotherapy in Head and Neck Squamous Cell Carcinoma.

AIMS: Our purpose was to assess the diagnostic accuracy and prognostic value of diffusion-weighted imaging (DWI) and 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) carried out 3-6 months after (chemo)radiotherapy in head and neck squamous cell carcinoma. MATERIALS AND METHODS: For this retrospective cohort study we included 82 patients with advanced-stage head and neck squamous cell carcinoma treated between 2012 and 2015. Primary tumours and lymph nodes were assessed separately. DWI was analysed qualitatively and quantitatively. 18F-FDG-PET/CT was evaluated using the Hopkins criteria. Dichotomous qualitative analysis was carried out for both modalities. Cox regression analysis was used for univariate analysis of recurrence-free survival (RFS). Significant univariate parameters were included in multivariate analysis. RESULTS: In 12 patients, locoregional recurrence occurred. With all imaging strategies, either single-modality or multi-modality, a high negative predictive value (NPV) was achieved (94.3-100%). In response evaluation of the primary site, the preferred strategy is 18F-FDG-PET/CT only, which resulted in a sensitivity of 85.7%, specificity of 86.5%, positive predictive value (PPV) of 37.5% and NPV of 98.5%. For response evaluation of the neck, the best results were obtained with a sequential approach only including the second modality in positive reads of the first modality. It did not matter which modality was assessed first. This strategy for lymph node assessment resulted in a sensitivity, specificity, PPV and NPV of 83.3%, 95.6%, 62.5%, and 98.5%, respectively. After correction for received treatment and human papillomavirus status, primary tumour (P = 0.009) or lymph node (P < 0.001) Hopkins score ≥4 on 18F-FDG-PET/CT remained significant predictors of RFS. CONCLUSION: For response evaluation of the primary tumour 18F-FDG-PET/CT only is the preferred strategy, whereas for the neck a sequential approach including both DWI and 18F-FDG-PET/CT resulted in the best diagnostic accuracy for follow-up after (chemo)radiotherapy. Qualitative analysis of 18F-FDG-PET/CT is a stronger predictor of RFS than DWI analysis.

Extracranial giant cell arteritis: A narrative review.

A systematic literature search was performed to summarise current knowledge on extracranial giant cell arteritis (GCA), i.e. large-artery involvement in patients with or without clinically apparent temporal arteritis (cranial GCA). Extracranial GCA is increasingly recognised, both in patients with cranial GCA and with solitary extracranial GCA, due to increased awareness among physicians and development of modern imaging modalities. The literature on the pathogenesis and histopathology of extracranial GCA is scarce. It is considered to be similar to cranial GCA. Patients with solitary extracranial GCA often present with non-specific signs and symptoms, although vascular manifestations, mostly secondary to stenosis, may occur. Due to the non-specific clinical presentation and low sensitivity of temporal artery biopsies, extracranial GCA is usually diagnosed by imaging. 18F-FDG-PET, MRI, CT angiography and ultrasound are used for this purpose. At present, the optimal diagnostic strategy is undetermined. The choice for a particular modality can be guided by the clinical scenario that raises suspicion of extracranial GCA, in addition to local availability and expertise. Extracranial complications in GCA consist of aortic aneurysm or dissection (mainly the ascending aorta), aortic arch syndrome, arm claudication and posterior stroke (although this is technically a cranial complication, it often results from stenosis of the vertebrobasilar arteries). Mortality is generally not increased in patients with GCA. Treatment of patients with solitary extracranial and those with extracranial and cranial GCA has been debated in the recent literature. In general, the same strategy is applied as in patients with temporal arteritis, although criteria regarding who to treat are unclear. Surgical procedures may be indicated, in which case optimal medical treatment prior to surgery is important.

Large-vessel vasculitis: interobserver agreement and diagnostic accuracy of 18F-FDG-PET/CT.

INTRODUCTION: (18)F-FDG-PET visualises inflammation. Both atherosclerosis and giant cell arteritis cause vascular inflammation, but distinguishing the two may be difficult. The goal of this study was to assess interobserver agreement and diagnostic accuracy of (18)F-FDG-PET for the detection of large artery involvement in giant cell arteritis (GCA). METHODS: 31 (18)F-FDG-PET/CT scans were selected from 2 databases. Four observers assessed vascular wall (18)F-FDG uptake, initially without and subsequently with predefined observer criteria (i.e., vascular wall (18)F-FDG uptake compared to liver or femoral artery (18)F-FDG uptake). External validation was performed by two additional observers. Sensitivity and specificity of (18)F-FDG-PET were determined by comparing scan results to a consensus diagnosis. RESULTS: The highest interobserver agreement (kappa: 0.96 in initial study and 0.79 in external validation) was observed when vascular wall (18)F-FDG uptake higher than liver uptake was used as a diagnostic criterion, although agreement was also good without predefined criteria (kappa: 0.68 and 0.85). Sensitivity and specificity were comparable for these methods. The criterion of vascular wall (18)F-FDG uptake equal to liver (18)F-FDG uptake had low specificity. CONCLUSION: Standardization of image assessment for vascular wall (18)F-FDG uptake promotes observer agreement, enables comparative studies, and does not appear to result in loss of diagnostic accuracy compared to nonstandardized assessment.

DNA hypermethylation analysis in sputum for the diagnosis of lung cancer: training validation set approach.

BACKGROUND: Lung cancer has the highest mortality of all cancers. The aim of this study was to examine DNA hypermethylation in sputum and validate its diagnostic accuracy for lung cancer. METHODS: DNA hypermethylation of RASSF1A, APC, cytoglobin, 3OST2, PRDM14, FAM19A4 and PHACTR3 was analysed in sputum samples from symptomatic lung cancer patients and controls (learning set: 73 cases, 86 controls; validation set: 159 cases, 154 controls) by quantitative methylation-specific PCR. Three statistical models were used: (i) cutoff based on Youden's J index, (ii) cutoff based on fixed specificity per marker of 96% and (iii) risk classification of post-test probabilities. RESULTS: In the learning set, approach (i) showed that RASSF1A was best able to distinguish cases from controls (sensitivity 42.5%, specificity 96.5%). RASSF1A, 3OST2 and PRDM14 combined demonstrated a sensitivity of 82.2% with a specificity of 66.3%. Approach (ii) yielded a combination rule of RASSF1A, 3OST2 and PHACTR3 (sensitivity 67.1%, specificity 89.5%). The risk model (approach iii) distributed the cases over all risk categories. All methods displayed similar and consistent results in the validation set. CONCLUSIONS: Our findings underscore the impact of DNA methylation markers in symptomatic lung cancer diagnosis. RASSF1A is validated as diagnostic marker in lung cancer.

Vasculitis revealed by posterior stroke.

Posterior ischaemic stroke is relatively uncommon, and its occurrence should alert clinicians to possible uncommon underlying disease. We report a patient with occipital brain infarction. The combination of age, gender, general malaise and elevated erythrocyte sedimentation rate led to the clinical suspicion of giant cell arteritis. Vertebral artery vasculitis was confirmed by 18-FD G positron emission tomography, combined with CT angiography, and immediate immunosuppressive therapy was started. Symptoms of stroke should, in a particular clinical context, raise suspicion of giant cell arteritis.

Imaging modalities for the staging of patients with colorectal cancer.

Dutch guidelines made the following recommendations for staging colorectal cancer (CRC). For liver metastases, computed tomography (CT) or magnetic resonance imaging (MRI) could be used. For lung metastases, imaging could be limited to chest X-ray. The primary aim of this survey was to summarise the use of imaging modalities and the variation in techniques. Three surveys were created and sent to three groups of medical specialists, namely surgeons, radiologists and nuclear medicine physicians. The management survey included questions on the role of different modalities for evaluation of synchronous liver, lung and extrahepatic metastases. The radiological survey included questions concerning the technical aspects of ultrasound (US), CT and MRI. The nuclear medicine survey included questions concerning the technical aspects of FDG-PET and FDG-PET/CT. The management and radiological surveys were sent to abdominal surgeons and abdominal radiologists within 88 hospitals and the nuclear medicine survey to specialists within 34 hospitals. Response rates were 75.0% (n=66/88), 77.3% (n=68/88) and 64.7% (n=22/34) for the management, radiological and nuclear medicine surveys, respectively. For liver metastases, the first modality of choice was CT in 52 (78.8%) and US in 12 hospitals (18.2%). Lung metastases were evaluated by either chest X-ray or chest CT and extrahepatic metastases mainly by CT (n=55). In the radiological and nuclear medicine surveys, some variations in techniques of US, CT, MRI , FDG-PET and FDG-PET/CT were seen. CT is primarily used for liver and extrahepatic metastases and both chest CT and chest X-ray for lung metastases. There are discrepancies between the survey of daily practice and the present guidelines. Comparative studies on different staging strategies for colon and rectal cancer, including comparing a strategy of CT liver/abdomen versus MRI liver/abdomen for the evaluation of liver and extrahepatic disease and chest X-ray or chest CT for lung metastases would be important for well-founded adjustments of the present guidelines.

Clinical applications of FDG-probe guided surgery.

BACKGROUND: For a definitive diagnosis in many oncological, inflammatory and infectious diseases histological examination is required. Non-palpable lesions detected with PET/CT scanning that cannot be localized with conventional imaging methods can be localized and excised using FDG-probe guided surgery. We describe the application of FDG-probe guided surgery in 9 patients. METHODS: The application of FDG-probe guided surgery used in 9 consecutive patients with oncological and infectious diseases is described. Four hours before surgery, 3.5 MBq/Kg body weight FDG was intravenously administered after which a FDG-PET-scan was performed to confirm the FDG-avid lesion(s). The lesions with highest activity were detected with the FDG-probe and the lesions were subsequently excised and sent for histopathological examination. RESULTS: In all of the 9 cases the target lesion was successfully identified and subsequently removed. When multiple and/or macroscopically normal lymph nodes were found, the use of the FDG-probe allowed selection of the PET-avid lymph nodes for resection. CONCLUSION: FDG-probe guided surgery is a relatively simple surgical technique to identify and excise FDG-accumulating suspicious lesions in oncological, inflammatory and infectious diseases.

Cardiac PET-CT: advanced hybrid imaging for the detection of coronary artery disease.

Hybrid imaging of positron emission tomography (PET) together with computed tomography (CT) is rapidly emerging. In cardiology, this new advanced hybrid imaging modality allows quantification of cardiac perfusion in combination with assessment of coronary anatomy within a single scanning session of less than 45 minutes. The near-simultaneous anatomical evaluation of coronary arteries using CT and corresponding functional status using PET provides a wealth of complementary information in patients who are being evaluated for (suspected) coronary artery disease, and could help guide clinical patient management in a novel manner. Clinical experience gained with this recently introduced advanced hybrid imaging tool, however, is still limited and its implementation into daily clinical practice remains largely unchartered territory. This review discusses principles of perfusion PET, its diagnostic accuracy, and potential clinical applications of cardiac PET-CT in patients with ischaemic heart disease. (Neth Heart J 2010;18:90-8.).

2-Deoxy-2[F-18]FDG-PET for detection of recurrent laryngeal carcinoma after radiotherapy: interobserver variability in reporting.

PURPOSE: To evaluate accuracy and interobserver variability in the assessment of 2-deoxy-2[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) for detection of recurrent laryngeal carcinoma after radiotherapy. PROCEDURES: Eleven experienced nuclear physicians from eight centres assessed 30 FDG-PET scans on the appearance of local recurrence (negative/equivocal/positive). Conservative (equivocal analysed as negative) and sensitive (equivocal analysed as positive) assessment strategies were compared to the reference standard (recurrence within 6months after PET). RESULTS: Seven patients had proven recurrences. For the conservative and sensitive strategy, the mean sensitivity was 87% and 97%, specificity 81% and 63%, positive predictive values 61% and 46% and negative predictive values 96% and 99%, respectively. Interobserver variability showed a reasonable relation in comparison to the reference standard (kappa = 0.55). CONCLUSIONS: FDG-PET has acceptable interobserver agreement and yields good negative predictive value for detection of recurrent laryngeal carcinoma. It could therefore be used as first diagnostic step and may reduce futile invasive diagnostics.

An unusual hotspot in a young woman with Hodgkin's lymphoma.

A young woman has started cancer treatment because of a Hodgkin's lymphoma. After four months of chemotherapy, a PET scan showed an unexplained hotspot in the right lower abdomen. This was later explained by an unsuspected pregnancy. Our case emphasizes the importance of a pregnancy test in all women in the reproductive age before starting cancer treatment.

2-Deoxy-2-[F-18]fluoro-D-glucose joint uptake on positron emission tomography images: rheumatoid arthritis versus osteoarthritis.

PURPOSE: Previous positron emission tomography (PET) studies have shown increased 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake in joints of patients with osteoarthritis (OA) and inflamed joints of patients with rheumatoid arthritis (RA). This study compares FDG uptake in joints of RA and OA patients and FDG-uptake with clinical signs of inflammation. PROCEDURES: FDG-PET scans of hands and wrists were performed in patients with RA and primary OA. PET data were compared with clinical data. RESULTS: 29% of RA joints and 6% of OA joints showed elevated FDG-uptake. The level of uptake in PET-positive OA joints was not significantly different from that in RA joints. The majority of PET results of RA joints corresponded with clinical findings. Clinical synovitis was found some OA joints with FDG-uptake. CONCLUSIONS: FDG-uptake was observed in the majority of clinically inflamed RA joints and in a few OA joints with no significant difference in uptake level. The latter may be due to secondary synovitis.

Limited additional value of positron emission tomography in staging oesophageal cancer.

BACKGROUND: The detection of distant metastases in patients with oesophageal cancer may be improved with [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), preventing unnecessary surgical explorations. The aim of this study was to assess the additional value of FDG-PET after a state-of-the-art preoperative staging protocol. METHODS: All patients in this prospective cohort study were staged with multidetector computed tomography, endoscopic ultrasonography and external ultrasonography of the neck, both combined with selective fine-needle aspiration cytology. Patients considered eligible for curative surgery after these investigations underwent FDG-PET. RESULTS: FDG-PET revealed suspicious hot spots in 30 (15.1 per cent) of 199 patients. Metastases were confirmed in eight (4.0 per cent). In six of these, distant metastases were confirmed before surgery, but exploratory surgery was necessary for histological confirmation in the other two. All eight upstaged patients had clinical stage III-IV disease before FDG-PET (6.6 per cent of 122 with stage III-IV disease). In seven patients (3.5 per cent) hot spots appeared to be synchronous neoplasms, mainly colonic polyps. However, those in the remaining 15 (7.5 per cent) were false positive, leading to unnecessary additional investigations. CONCLUSION: FDG-PET improves the selection of patients with oesophageal cancer for potentially curative surgery, especially in stages III-IV. However, the diagnostic benefit is limited after state-of-the-art staging, and so broad implementation in daily clinical practice is questionable.

Evidence-base guideline on management of colorectal liver metastases in the Netherlands.

A dutch national evidence-based guideline on the diagnosis and treatment of patients with colorectal liver metastases has been developed. The most important recommendations are as follows. For synchronous liver metastases, spiral computed tomography (CT) or magnetic resonance imaging (MRI) should be used as imaging. For evaluation of lung metastases, imaging can be limited to chest radiography. For detection of metachronous liver metastases, ultrasonography could be performed as initial modality if the entire liver is adequately visualised. In doubtful cases or potential candidates for surgery, CT or MRI should be performed as additional imaging. For evaluation of extrahepatic disease, abdominal and chest CT could be performed. Fluorodeoxyglucose positron emission tomography could be valuable in patients selected for surgery based on CT (liver/abdomen/chest), for identifying additional extrahepatic disease. Surgical resection is the treatment of choice with a five-year survival of 30 to 40%. Variation in selection criteria for surgery is caused by inconclusive data in the literature concerning surgical margins.

Evaluation of pulmonary nodules: comparison of a prototype dual crystal (LSO/NAI) dual head coincidence camera and full ring positron emission tomography (PET).

PURPOSE: To determine the concordance of a prototype dual head coincidence camera (LSO-PS) and full ring PET (BGO-PET) using (18)F-fluorodeoxyglucose (FDG) in the evaluation of pulmonary nodules (PNs). MATERIALS AND METHODS: Patients referred for evaluation of < or =3 PNs (< or =3 cm diameter) were prospectively studied on the same day with both BGO-PET and LSO-PS. Imaging was performed at 60 and 120 min after injection of 370MBq FDG, respectively. Images were independently interpreted by four observers with each observer blinded to the other modality for the same patient. Lesions were scored in terms of relative intensity versus background. Non-attenuation corrected (nonAC) BGO-PET was used as the reference test. RESULTS: Forty-seven patients with 54 PNs (mean diameter 1.7 cm, S.D. 0.7) were included. Twelve nodules were in the < or =1.0 cm - 27 in the 1.1-2.0 cm - and 15 in the 2.1-3.0 cm range. Interobserver agreement was similar for both FDG imaging modalities. Using a sensitive assessment strategy with LSO-PS (> or = faint intensity deemed positive), there was a 97% (38/39, 95%CI 87-100%) concordance with BGO-PET and one false positive case with LSO-PS. Conservative reading (moderate or intense intensity deemed positive) resulted in a 92% (36/39, 95%CI 80-97%) concordance with BGO-PET, without false positives. The only lesion missed by LSO-PS using both assessment strategies involved a nodule 1.5 cm diameter that demonstrated moderate increased FDG uptake on BGO-PET. CONCLUSION: Depending on the test positivity criteria, LSO-PS demonstrates a high concordance (92-97%) with nonAC BGO-PET for the characterization of pulmonary nodules.

Cerebral microdialysis and positron emission tomography after surgery for aneurysmal subarachnoid hemorrhage in grade I patients.

BACKGROUND: Using cerebral microdialysis, baseline values for energy-related chemical markers have been reported in awake patients. Radionuclide studies have demonstrated a locally decreased metabolism, thought to be the result of brain retraction. These baseline values, however, may not be applicable to patients after surgical aneurysm repair following a subarachnoid hemorrhage (SAH). We assessed metabolic chemical marker levels in World Federation of Neurological Surgeons Committee (WFNS) grade I SAH patients after aneurysm surgery and compared them with previously reported baseline values. METHODS: In 5 WFNS grade I SAH patients, energy-related chemical marker levels were obtained using microdialysis in the area of brain retraction after aneurysm surgery. In addition, an [(18)F]2-deoxy-d-glucose positron emission tomography (FDG-PET) was performed. RESULTS: The FDG-PET showed a decrease of glucose metabolism in the frontotemporal area. Comparing the mean values for chemical markers of this study with reported baseline values, the most striking difference was a mild decrease of pyruvate and an increase of the lactate/pyruvate ratio. In individual patients, some markers indicated possible ischemia. A consistent pattern or ischemic profile for all markers, however, was not found. CONCLUSION: FDG-PET scanning confirmed postoperative metabolic changes found in previous studies. Mean interstitial chemical marker levels ranged from normal to mildly deviant compared with reference chemical marker levels for awake patients and are likely to be applicable in SAH patients after aneurysm repair.

[Persistent fever in a patient with Salmonella typhimurium gonarthritis]. / Persisterende koorts bij Salmonella typhimurium-artritis.

A 65-year-old patient with systemic lupus erythematodes (SLE) developed fever and gonarthritis whilst taking prednisone and hydrochloroquine. Salmonella typhimurium, sensitive to amoxicillin, was grown in cultures of synovial fluid, blood and urine. After high dosages of intravenous amoxicillin, blood cultures and knee punctate became negative, but fever seemingly without a clinical focus persisted. By means of a fluoro-18-deoxyglucose positron emission tomography (FDG-PET) scan, an abscess was located in the left upper leg and successfully treated. In patients with impaired cell-mediated immunity, an extra-intestinal manifestation of Salmonella should be taken into consideration particularly if there appears to be no clinical focus. This may be detected by FDG-PET.