Improved stratification of stage-specific survival for cervical uterine cancer by integrating FDG-PET/CT and MRI for lymph node staging in 2018 FIGO classification.

OBJECTIVE: Staging carcinoma of the uterine cervix (CCU) by FIGO-2018 suggests stage migration of FIGO-2009 stage I-III patients with lymph node metastasis into FIGO-2018 stage IIIC. We aimed to investigate the prognostic value of lymph node metastases identified by imaging. METHODS: We enrolled all patients with biopsy-verified CCU from 2007 to 2016 at Odense University Hospital, Denmark. FDG-PET/CT and MRI were performed before clinical examination in general anesthesia. Disease-specific mortality was compared between women with lymph node-positive and lymph node-negative imaging. RESULTS: In total, 488 patients underwent clinical staging according to FIGO-2009. Lymph node-positive imaging was identified in 146 (30%) patients: 0/36 (0%) in stage IA, 22/195 (11%) in IBI, 14/30 (47%) in IB2, 70/164 (43%) in II and 40/63 (63%) in III. The 5-year cumulative incidence of death due to CCU lymph node-negative vs. lymph node-positive patients was 0.8% vs. 7.1% (p = 0.034) in stage IBI, 0% vs. 34.5% (p = 0.003) in stage IB2, 15.1% vs. 41.4% (p < 0.0001) in stage II, and 33.3% vs. 46.6% (p = 0.28) in stage III by FIGO-2009. CONCLUSIONS: One of three women with FIGO-2009 stage I-III CCU had suspected lymph node metastasis on imaging and is upstaged to stage IIIC according to FIGO-2018. The cancer-specific mortality by CCU was significantly lower in the lymph node-negative women stages IBI-II, thus supporting stage migration due to suspected lymph node metastasis. However, the exact prognostic value within stage IIIC is challenged, and future revision of FIGO stages may include new sub-stages.

Carotid artery molecular calcification assessed by [18F]fluoride PET/CT: correlation with cardiovascular and thromboembolic risk factors.

OBJECTIVES: There is growing evidence that sodium fluoride ([18F]fluoride) PET/CT can detect active arterial calcifications at the molecular stage. We investigated the relationship between arterial mineralization in the left common carotid artery (LCC) assessed by [18F]fluoride PET/CT and cardiovascular/thromboembolic risk. METHODS: In total, 128 subjects (mean age 48 ± 14 years, 51% males) were included. [18F]fluoride uptake in the LCC was quantitatively assessed by measuring the blood-pool-corrected maximum standardized uptake value (SUVmax) on each axial slice. Average SUVmax (aSUVmax) was calculated over all slices and correlated with 10-year risk of cardiovascular events estimated by the Framingham model, CHA2DS2-VASc score, and level of physical activity (LPA). RESULTS: The aSUVmax was significantly higher in patients with increased risk of cardiovascular (one-way ANOVA, p < 0.01) and thromboembolic (one-way ANOVA, p < 0.01) events, and it was significantly lower in patients with greater LPA (one-way ANOVA, p = 0.02). On multivariable linear regression analysis, age ( = 0.07, 95% CI 0.05 - 0.10, p < 0.01), body mass index ( = 0.02, 95% CI 0.01 - 0.03, p < 0.01), arterial hypertension ( = 0.15, 95% CI 0.08 - 0.23, p < 0.01), and LPA ( = -0.10, 95% CI -0.19 to -0.02, p=0.02) were independent associations of aSUVmax. CONCLUSIONS: Carotid [18F]fluoride uptake is significantly increased in patients with unfavorable cardiovascular and thromboembolic risk profiles. [18F]fluoride PET/CT could become a valuable tool to estimate subjects' risk of future cardiovascular events although still major trials are needed to further evaluate the associations found in this study and their potential clinical usefulness. KEY POINTS: • Sodium fluoride ([18F]fluoride) PET/CT imaging identifies patients with early-stage atherosclerosis. • Carotid [18F]fluoride uptake is significantly higher in patients with increased risk of cardiovascular and thromboembolic events and inversely correlated with the level of physical activity. • Early detection of arterial mineralization at a molecular level could help guide clinical decisions in the context of cardiovascular risk assessment.

Risk of Malignancy in FDG-Avid Thyroid Incidentalomas on PET/CT: A Prospective Study.

BACKGROUND: Due to a substantial risk of malignancy, patients with focal FDG-avid thyroid incidentalomas (FFTIs) on PET/CT are in most of Denmark referred to Head and Neck Cancer (HNC) fast track programs. The aim of this study was to determine the risk of malignancy in FFTI managed in a HNC fast track program. METHODS: A prospective cohort study including all patients with FFTI referred to the HNC fast track program, Odense University Hospital between September 1, 2016 and August 31, 2017. Ultrasonography (US) and fine-needle aspiration biopsy (FNAB) were intended to be done in all patients. Nodules with cytology of Bethesda 1, 3, 4, 5, or 6 were planned for surgical removal. RESULTS: A total of 104 patients were included. All patients had US and 101 patients (97%) had FNAB. Forty-two patients had benign cytology classified as Bethesda 2. The remaining 62 patients underwent surgery except from 11 patients, mainly due to comorbidity. The overall risk of malignancy for patients with FFTI referred to our HNC fast track program was calculated to be 24% (23/95) based on patients with unequivocal cytology and/or histology. The only statistically significant US characteristic to predict malignancy was the appearance of irregular margins with a sensitivity of 47% and specificity of 96%. CONCLUSION: The risk of malignancy of FFTIs handled in our HNC fast track program is 24%.

Up-front PET/CT changes treatment intent in patients with head and neck squamous cell carcinoma.

PURPOSE: In patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), we wanted to examine the differences in overall treatment decisions, i.e. curative versus palliative treatment intent, reached by a multidisciplinary team conference (MDTC) based on 18F-fluoro-deoxy-glucose-positron emission tomography/computed tomography (PET/CT) or chest X-ray + MRI of the head and neck (CXR/MRI). PATIENTS AND METHODS: This was a prospective blinded cohort study based on paired data. Consecutive patients with histologically verified primary HNSCC were invited to participate. All included patients underwent CXR/MRI and PET/CT before diagnostic biopsy. An ordinary MDTC using all available imaging was conducted as per standard practice. After at least 3 months (to eliminate recall bias in the team), the first project MDTC was conducted, based on either CXR/MRI or PET/CT, and the tumor board drew conclusions regarding treatment. After an additional 3 months, a second project MDTC was conducted using the complementary imaging modality. RESULTS: A total of 307 patients were included. Based on CXR/MRI, 303 patients (99%) were recommended for curative treatment and only four patients (1%) for palliative treatment. Based on PET/CT, the MDTC concluded that 278 (91%) patients were suitable for curative treatment and 29 (9%) patients for palliative treatment. The absolute difference of 8% was statistically significant (95% CI: 4.8%-11.5%, p < 0.001). CONCLUSIONS: A PET/CT-based imaging strategy significantly changed the decisions regarding treatment intent made by a MDTC for patients diagnosed with HNSCC, when compared with the standard imaging strategy of CXR/MRI.

PET/CT and prediction of thyroid cancer in patients with follicular neoplasm or atypia.

PURPOSE: To examine whether addition of 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT) to fine needle aspiration biopsy (FNAB) would improve prediction of thyroid cancer in patients with FNAB-derived follicular neoplasm or atypia, classified according to focal, multifocal, diffuse, or no FDG uptake. MATERIALS AND METHODS: Consecutive patients with FNAB-derived follicular neoplasm or atypia planned for surgery from September 2013 to March 2016 were prospectively included and considered for analysis. All patients underwent preoperative PET/CT and a clinical head and neck examination, including ultrasound of the neck and the thyroid gland. Patients with obvious signs of thyroid malignancy were excluded from the study. Histology of the surgical specimen was used as reference standard for statistical analysis. RESULTS: Of the 108 patients included (85 women, median age 53.4 years), 31 (29%) had a thyroid nodule that was histologically verified as malignant. Sensitivity and specificity for PET/CT in detection of thyroid cancer was 79 and 32%, respectively, including a derived positive predictive value (PPV) of 31%, and a negative predictive value (NPV) of 79%. Univariate and multivariate analyses showed no significant increase in the risk of thyroid cancer among patients with focal or multifocal FDG uptake compared to patients with no FDG uptake. CONCLUSION: Addition of PET/CT to FNAB did not improve prediction of thyroid cancer in patients with FNAB-derived follicular neoplasm or atypia.

Thoracic aorta calcification but not inflammation is associated with increased cardiovascular disease risk: results of the CAMONA study.

PURPOSE: Arterial inflammation and vascular calcification are regarded as early prognostic markers of cardiovascular disease (CVD). In this study we investigated the relationship between CVD risk and arterial inflammation (18F-FDG PET/CT imaging), vascular calcification metabolism (Na18F PET/CT imaging), and vascular calcium burden (CT imaging) of the thoracic aorta in a population at low CVD risk. METHODS: Study participants underwent blood pressure measurements, blood analyses, and 18F-FDG and Na18F PET/CT imaging. In addition, the 10-year risk for development of CVD, based on the Framingham risk score (FRS), was estimated. CVD risk was compared across quartiles of thoracic aorta 18F-FDG uptake, Na18F uptake, and calcium burden on CT. RESULTS: A total of 139 subjects (52 % men, mean age 49 years, age range 21 - 75 years, median FRS 6 %) were evaluated. CVD risk was, on average, 3.7 times higher among subjects with thoracic aorta Na18F uptake in the highest quartile compared with those in the lowest quartile of the distribution (15.5 % vs. 4.2 %; P < 0.001). CVD risk was on average, 3.7 times higher among subjects with a thoracic aorta calcium burden on CT in the highest quartile compared with those in the lowest two quartiles of the distribution (18.0 % vs. 4.9 %; P < 0.001). CVD risk was similar in subjects in all quartiles of thoracic aorta 18F-FDG uptake. CONCLUSION: Our findings indicate that an unfavourable CVD risk profile is associated with marked increases in vascular calcification metabolism and vascular calcium burden of the thoracic aorta, but not with arterial inflammation.

Delayed ¹8F-fluorodeoxyglucose PET/CT imaging improves quantitation of atherosclerotic plaque inflammation: results from the CAMONA study.

BACKGROUND: This study aimed to determine if delayed (18)F-fluorodeoxyglucose ((18)FDG) PET/CT imaging improves quantitation of atherosclerotic plaque inflammation. Blood-pool activity can disturb the arterial (18)FDG signal. With time, blood-pool activity declines. Therefore, delayed imaging can potentially improve quantitation of vascular inflammation. METHODS AND RESULTS: 40 subjects were prospectively assessed by dual-time-point PET/CT imaging at approximately 90 and 180 minutes after (18)FDG administration. For both time-points, global uptake of (18)FDG was determined in the carotid arteries and thoracic aorta by calculating the blood-pool corrected maximum standardized uptake value (cSUVMAX). A target-to-background ratio (TBR) was calculated to determine the contrast resolution at 90 and 180 minutes. Furthermore, we assessed whether the acquisition time-point affected the relation between cSUVMAX and the estimated 10-year risk for fatal cardiovascular disease (SCORE %). A significant increase in carotid cSUVMAX (23%, P < .0001), carotid TBR (20%, P < .0001), aortic cSUVMAX (14%, P < .0001), and aortic TBR (20%, P < .0001) was observed with time. At 90 minutes, cSUVMAX did not relate to SCORE %, whereas at 180 minutes significant positive relations were observed between SCORE % and carotid (τ = 0.25, P = .045) and aortic (τ = 0.33, P = .008) cSUVMAX. CONCLUSIONS: Delayed (18)FDG PET/CT imaging at 180 minutes improves quantitation of atherosclerotic plaque inflammation over imaging at 90 minutes. Therefore, the optimal acquisition time-point to assess atherosclerotic plaque inflammation lies beyond the advocated time-point of 90 minutes after (18)FDG administration.

Delayed sodium 18F-fluoride PET/CT imaging does not improve quantification of vascular calcification metabolism: results from the CAMONA study.

BACKGROUND: This study aimed to determine if delayed sodium (18)F-fluoride (Na(18)F) PET/CT imaging improves quantification of vascular calcification metabolism. Blood-pool activity can disturb the arterial Na(18)F signal. With time, blood-pool activity declines. Therefore, delayed imaging can potentially improve quantification of vascular calcification metabolism. METHODS AND RESULTS: Twenty healthy volunteers and 18 patients with chest pain were prospectively assessed by triple time-point PET/CT imaging at approximately 45, 90, and 180 minutes after Na(18)F administration. For each time point, global uptake of Na(18)F was determined in the coronary arteries and thoracic aorta by calculating the blood-pool-corrected maximum standardized uptake value (cSUV(MAX)). A target-to-background ratio (TBR) was calculated to determine the contrast resolution at 45, 90, and 180 minutes. Furthermore, we assessed whether the acquisition time-point affected the relation between cSUV(MAX) and the estimated 10-year risk for fatal cardiovascular disease (SCORE %). Coronary cSUV(MAX) (P = .533) and aortic cSUV(MAX) (P = .654) remained similar with time, whereas the coronary TBR (P < .0001) and aortic TBR (P < .0001) significantly increased with time. Even though the contrast resolution improved with time, positive correlations between SCORE % and coronary cSUV(MAX) (P < .020) and aortic cSUV(MAX) (P < .005) were observed at all investigated time points. CONCLUSIONS: Delayed Na(18)F PET/CT imaging does not improve quantification of vascular calcification metabolism. Although contrast resolution improves with time, arterial Na(18)F avidity is invariant to the time between Na(18)F administration and PET/CT acquisition. Therefore, the optimal PET/CT acquisition time-point to quantify vascular calcification metabolism is achieved as early as 45 minutes after Na(18)F administration.

Coronary computed tomography angiography - tolerability of ß-blockers and contrast media, and temporal changes in radiation dose.

OBJECTIVE: To determine the risk in administering ß-blockers, contrast-induced nephropathy (CIN) and the trend in X-ray use, during coronary computed tomography angiography (CCTA). METHODS: A total of 416 patients were referred for elective CCTA. To achieve a resting heart rate below 60 beats per minute, oral and/or intravenous ß-blockers were administered. Using questionnaires, information on the adverse effects of ß-blockers was collected from the patients. The levels of s-creatinine and estimated GFR (eGFR) were measured before and after contrast enhanced CCTA. Radiation exposure was compared with the exposure 3 years earlier. RESULTS: There was no significant difference in the symptoms (dizziness, lipothymia and palpitations) between patients with and patients without ß-blocker pretreatment. Compared to baseline values, the decrease in s-creatinine was not significant (75.2 vs. 74.6 µmol/L, p = 0.09), while the increase in eGFR was not significant (78 vs. 79 mL/min, p = 0.17). Also, subgroups of patients with hypertension, hypercholesterolemia, diabetes or pre-existing slight impairment in renal function did not develop CIN. The mean radiation exposure decreased from 17.5 to 6.7 mSv, p < 0.0001. CONCLUSIONS: In terms of the side effects of ß-blockers and contrast media, there were no short term complications to CCTA. Furthermore, the radiation dose has been dramatically diminished over the last three years.

A "package solution" fast track program can reduce the diagnostic waiting time in head and neck cancer.

In 2007, a fast track program for patients with suspicion of head and neck cancer (HNC) was introduced in Denmark to reduce unnecessary waiting time. The program was based on so called "package solutions" including pre-booked slots for outpatient evaluation, imaging, and diagnostic surgical procedures. The purpose of this study is to present a model for fast track handling of patients suspicious of cancer in the head and neck region and to evaluate the effect of implementation on the diagnostic work up time. Patients with suspicion of HNC referred to the same university department of ENT Head and Neck Surgery during three comparable time intervals 2006-2007, 2007-2008, and 2011-2012 (groups 1-3) were investigated. We recorded the time from patient referral, to first consultation and final diagnosis. The first interval was before initiation of the "package solution", the second just after the introduction, and the third interval represents the current situation. The median time from referral to first consultation was reduced from eight calendar days in group 1 to only one day in groups 2 and 3 (p < 0.001). The combined median time from referral to the final cancer diagnosis decreased from 24 calendar days in group 1 to 7 and 10 days in groups 2 and 3, respectively (p < 0.005). The hit rate of finding malignancy was 41% in group 1, 49% in group 2, and 43% in group 3 with no difference among the groups (p = 0.13). The frequency of newly diagnosed HNC was 19% in group 1, 21% in group 2, and 17% in group 3 (p = 0.52). A "package solution" including pre-booked slots for diagnostic procedures is feasible and can significantly reduce the waiting time for patients with suspicion of HNC.

Serial fractional flow reserve, coronary flow reserve and index of microcirculatory resistance after percutaneous coronary intervention in patients treated for stable angina pectoris assessed with PET.

BACKGROUND: Cardiac 15 O-water PET is a noninvasive method to evaluate epicardial and microvascular dysfunction and further quantitate absolute myocardial blood flow (MBF). AIM: The aim of this study was to assess the impact of revascularization on MBF and myocardial flow reserve (MFR) assessed with 15 O-water PET and invasive flow and pressure measurements. METHODS: In 21 patients with single-vessel disease referred for percutaneous coronary intervention (PCI), serial PET perfusion imaging and fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were performed during PCI and after 3 months. RESULTS: In the affected myocardium, stress MBF and MFR increased significantly from before revascularization to 3 months after revascularization: stress MBF 2.4 ±â€…0.8 vs. 3.2 ±â€…0.8; P  < 0.001 and MFR 2.5 ±â€…0.8 vs. 3.4 ±â€…1.1; P  = 0.004. FFR and CFR increased significantly from baseline to after revascularization and remained stable from after revascularization to 3-month follow-up: FFR 0.64 ±â€…0.20 vs. 0.91 ±â€…0.06 vs. 0.91 ±â€…0.07; P  < 0.001; CFR 2.4 ±â€…1.2 vs. 3.6 ±â€…1.9 vs. 3.6 ±â€…1.9; P  < 0.001, whereas IMR did not change significantly: 30.3 ±â€…22.9 vs. 30.1 ±â€…25.3 vs. 31.9 ±â€…25.2; P  = ns. After revascularization, an increase in stress MBF was associated with an increase in FFR ( r  = 0.732; P  < 0.001) and an increase in MFR ( r  = 0.499; P  = 0.021). IMR measured before PCI was inversely associated with improvement in stress MBF, ( r  = -0.616; P  = 0.004). CONCLUSION: Recovery of myocardial perfusion after PCI was associated with an increase in FFR 3 months after revascularization. Microcirculatory dysfunction was associated with less improvement in myocardial perfusion.

Hybrid CT angiography and quantitative 15O-water PET for assessment of coronary artery disease: comparison with quantitative coronary angiography.

PURPOSE: CT angiography (CTA) can rule out significant stenoses with a very high reliability, whereas its ability to confirm significant stenoses is suboptimal. In contrast, measurements of myocardial blood flow (MBF) provide information on the haemodynamic consequences of stenoses. Therefore, a combination of the two might improve diagnostic accuracy. We conducted a head-to-head comparison of CTA, measurement of MBF by (15)O-water PET, and hybrid PET/CTA for the detection of significant coronary artery stenoses. METHODS: The study group comprised 44 outpatients scheduled for invasive coronary angiography (ICA) with an intermediate pretest likelihood of coronary artery disease. The patients underwent 64-slice CTA and baseline and hyperaemic PET before ICA with quantitative coronary angiography analysis. RESULTS: On a per-patient basis, the negative predictive values (NPV; 95% confidence intervals in parentheses) were 88 % (64 - 97%) for CTA, 90% (71 - 97%) for PET and 92% (74 - 98%) for PET/CTA, and the positive predictive values (PPV) were 71% (53 - 85%) for CTA, 87% (68 - 95%) for PET and 100% (84 - 100%) for PET/CTA. Similarly, on a per-vessel basis the NPVs (which were generally high) were 97% (94 - 100%) for CTA, 95 % (90 - 99%) for PET and 97% (95 - 100%) for PET/CTA, and the PPVs (which were lower, but higher with PET/CTA) were 53% (39 - 66%) for CTA, 53 % (40 - 66%) for PET and 85 % (73 - 97%) for PET/CTA. In six patients, CTA analysis was hampered by the presence of severe calcifications. However, with the addition of the PET data, all six patients were correctly categorized. CONCLUSION: Cardiac quantitative hybrid PET/CTA imaging has better diagnostic accuracy than CTA alone and PET alone. CTA has a suboptimal PPV, suggesting that hybrid PET/CTA imaging should be used to assess the significance of coronary stenoses diagnosed by CTA.

Prognosis in patients with suspected or known ischemic heart disease and normal myocardial perfusion: long-term outcome and temporal risk variations.

BACKGROUND: The prognostic value of a normal myocardial perfusion scintigraphy (MPS) may be well described, but long-term follow-up data are sparse, and temporal variations in risk are insufficiently elucidated. METHODS AND RESULTS: During long-term follow-up (mean 6.2 years) of 1,327 consecutive Danish patients with normal MPS, the rate of all-cause death (ACD) was 1.9%/year (differing by gender) and of cardiac death (CD)/myocardial infarction (MI) 0.8%/year (differing by coronary artery disease, CAD). Female gender (HR: 0.60), age (HR: 1.07 per-year increment), and known CAD without prior revascularization (HR: 2.17) were statistically significant factors for ACD, whereas diabetes and previous MI per se were not. Known CAD with previous revascularization carried a low risk of ACD when adjusted for gender and age (HR: 0.56). For CD/MI, risk increased with age and threefold with known CAD, previous MI, and previous percutaneous coronary intervention. Judged from smoothed hazard functions, mortality risk increased further with time for men, elderly, and diabetics and markedly further with known CAD without prior revascularization. CONCLUSIONS: Following a normal MPS, rates of death and hard cardiac events were low. Risk varied with age, gender, and disease history. Novel aspects of temporal risk variation suggested a general warranty period of 5 years, but less in risk groups.

Head-to-Head Comparison of Tc-99m-sestamibi SPECT/CT and C-11-L-Methionin PET/CT in Parathyroid Scanning Before Operation for Primary Hyperparathyroidism.

PURPOSE: The preferred nuclear medicine method for identification of hyperfunctioning parathyroid glands in hyperparathyroidism (HPT) develops continuously in relation to the technological progress. Diagnostic methods based on PET/CT have during recent years evolved with new tracer possibilities competing with traditional scintigraphic methods. This investigation is a head-to-head comparison of Tc-99m-sestamibi SPECT/CT gamma camera scintigraphy (sestamibi SPECT/CT) and C-11-L-methionin PET/CT imaging (methionine PET/CT) for preoperative identification of hyperfunctioning parathyroid glands. PROCEDURES: The study is a prospective cohort study including 27 patients diagnosed with primary hyperparathyroidism (PHPT). Two nuclear medicine physicians assessed all examinations independently and blinded. All scanning assessments were matched to the final surgical diagnosis as confirmed by histopathology. Biochemical monitoring of the therapeutical effects was performed preoperatively by PTH-measurements and followed postoperatively for up to 12 months. Comparisons were made for differences in sensitivity and positive predictive value (PPV). RESULTS: Twenty-seven patients (18 females, 9 males; mean age (range): 58.9 years (34.1-79)) were enrolled into the study. The 27 patients had a total of 33 identified sites of lesions of which 28 (85%) turned out to be histopathological verified hyperfunctioning parathyroid glands. The sensitivity and PPV for sestamibi SPECT/CT were 0.71 and 0.95; that of methionine PET/CT was 0.82 and 1, respectively. Both sensitivity and PPV were slightly lower for sestamibi SPECT/CT than for methionine PET PET/CT (-0.11, 95% confidence interval (95% CI): -0.29 to 0.08; -0.05, 95% CI: -0.14 to 0.04, respectively), but not to a statistically significant extent (p=0.38 and p=0.31). The sensitivity and PPV for diagnostic CT were 0.64 (95% CI: 0.44 to 0.81) and 1 (95% CI: 0.81 to 1). CONCLUSIONS: Methionine PET/CT performed comparable to sestamibi SPECT/CT with respect to identification and localization of hyperfunctioning parathyroid glands prior to surgery.

Duration of 18F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination.

PURPOSE: The aim of our study was to investigate the occurrence of fluorodeoxyglucose (FDG) avidity in draining axillary lymph nodes after vaccination against influenza (H1N1v pandemic and seasonal) and to determine the period of increased FDG uptake. METHODS: During December 2009, patients referred for (18)F-FDG positron emission tomography (PET)/CT scans (n = 293) filled in a questionnaire concerning vaccination type (seasonal and/or H1N1v), time and anatomical localization of vaccination. Only injections in deltoid regions were evaluated, thus ensuring that draining lymph nodes were axillary. If more vaccinations had been given, only the latest vaccination was evaluated in each deltoid region. RESULTS: Of all patients who underwent PET/CT scans during December 2009, 26% had been vaccinated with at least one influenza vaccination in the deltoid region. A total of 92 'draining' and 60 'reference' (i.e. contralateral, non-vaccinated) axillary lymph nodes were evaluated in 61 patients (19 of 61 patients were scanned twice). The maximal intensity in FDG uptake (SUV(max)) in draining lymph nodes was 5 g/ml body weight (BW), whereas the maximal intensity in reference lymph nodes was 1.9 g/ml BW. The SUV(max) was normalized approximately 40 days after vaccination. No significant enlargement of metabolically active draining lymph nodes could be demonstrated on CT scan. Chemotherapy or immunosuppressive drugs given within 2 weeks from vaccination did not affect SUV(max) in the axillary lymph nodes. CONCLUSION: Influenza vaccination may lead to FDG-avid draining lymph nodes beyond 1 month.

PET/CT without capacity limitations: a Danish experience from a European perspective.

OBJECTIVES: We report the 3-year clinical experience of a large new Danish PET/CT centre without capacity limitations in relation to national and European developments. METHODS: The use of PET/CT in cancer was registered from early 2006 to early 2009 to judge the impact on patient management and to compare it with national and European trends. RESULTS: 6056 PET/CT examinations were performed in 4327 patients. Activity increased by 86 examinations per month compared with the same month the year before. Referrals came primarily from oncology (23.0%), haematology (21.6%), surgery (12.6%), internal medicine (12.7%) and gynaecology (5.5%). Referral indications were diagnosis (31.3%), staging (22.3%), recurrence detection (21.2%), response evaluation (17.0%) and other (8.2%). Response from nearly 60% of users showed that PET/CT caused a change in diagnosis and/or staging and/or treatment plan in 36.0% of cases. During the study period, there was a steep increase in the national use of FDG and in the European use of PET/CT. CONCLUSIONS: We recorded a constantly increasing use of PET/CT that caused a change in diagnosis and/or staging and/or treatment plan in 36.0% of cases. In line with national and European trends this may suggest a shift in favour of functional rather than anatomical imaging.

Synchronous detection of SDHA-related gallbladder paraganglioma and pancreatic neuroendocrine tumor.

Primary gallbladder paragangliomas (PGLs) are exceedingly rare. PGLs are extraadrenal neuroendocrine tumors that are morphologically inseparable from intraadrenal pheochromocytomas. PGLs and pheochromocytomas are some of the most heritable tumor types in the body and are often associated with other tumors or part of a genetic syndrome. We report a case of gallbladder PGL presenting synchronously with pancreatic neuroendocrine tumor (NET) and pulmonary IgG4-related disease in a 74-year old male patient with disseminated prostate adenocarcinoma. Due to the high rate of germline mutations and the possible syndromal manifestation of PGLs as well as pancreatic NETs, this patient was offered genetic testing, and a pathogenic SDHA germline mutation was found. Immunohistochemically, there was loss of SDHA and SDHB in the PGL but neither in the NET nor in the prostate adenocarcinoma. To our knowledge, this case is the first report of gallbladder PGL associated with pancreatic NET. It is likely that the identified SDHA germline mutation played a role in the development of gallbladder PGL in this patient.

15O-Water Positron Emission Tomography of Myocardial Ischemia in Patients Referred for Percutaneous Coronary Intervention.

The diagnostic accuracy of non-invasive diagnostic methods for detecting coronary artery disease has increased in recent years. This study aimed to assess the diagnostic performance of 15O-water positron emission tomography (PET) in terms of stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with single-vessel disease referred for percutaneous coronary intervention (PCI), using fractional flow reserve (FFR) value of ≤0.80 as the reference for a significant stenosis. We also assessed the influence of the index of microcirculatory resistance (IMR) on the diagnostic performance of PET. 15O-water PET FFR and IMR were measured before PCI in 26 patients with single-vessel disease. Stress MBF < 2.5 ml/min/g (95% confidence interval [CI]) had sensitivity 78% (95% CI: 52%-94%), specificity 50% (95% CI: 16%-84%), positive predictive value (PPV) 78% (95% CI: 63%-88%), negative predictive value (NPV) 50% (95% CI: 25%-75%), and accuracy 69% (95% CI: 48%-86%). MFR < 2.5 had sensitivity 72% (95% CI: 47%-90%), specificity 75% (95% CI: 35%-97%), PPV 87% (95% CI: 65%-96%), NPV 55% (95% CI: 34%-74%), and accuracy 73% (95% CI: 52%-88%). In patients with IMR > 24, stress MBF correlated with FFR (r = 0.651; p = 0.016) whereas stress MBF did not correlate with FFR in patients with IMR < 24. In conclusion, stress MBF and MFR had modest diagnostic performance compared to invasive FFR measurements in patients with single-vessel disease.

Up-front F18-FDG PET/CT in suspected salivary gland carcinoma.

OBJECTIVE: To investigate whether a 18F-FDG PET/CT (PET/CT)-based diagnostic strategy adds decisive new information compared to conventional imaging in the evaluation of salivary gland tumours and the detection of cervical lymph node metastases, distant metastases, and synchronous cancer in patients with salivary gland carcinoma. METHODS: The study was a blinded prospective cohort study. Data were collected consecutively through almost 3 years. All patients underwent conventional imaging-magnetic resonance imaging (MRI) and chest X-ray (CXR)-in addition to PET/CT prior to surgery. Final diagnosis was obtained by histopathology. MRI/CXR and PET/CT were interpreted separately by experienced radiologists and nuclear medicine physicians. Interpretation included evaluation of tumour site, cervical lymph node metastases, distant metastases, and synchronous cancer. RESULTS: Ninety-one patients were included in the study. Thirty-three patients had primary salivary gland carcinoma and eight had cervical lymph node metastases. With PET/CT, the sensitivity was 92% and specificity 29% regarding tumour site. With MRI/CXR, the sensitivity and specificity were 90% and 26%, respectively. Regarding cervical lymph node metastases in patients with salivary gland carcinoma, the sensitivity with PET/CT was 100% and with MRI/CXR 50%. PET/CT diagnosed distant metastases in five patients, while MRI/CXR detected these in two patients. Finally, PET/CT diagnosed two synchronous cancers, whereas MRI/CXR did not detect any synchronous cancers. CONCLUSIONS: Compared with MRI/CXR PET/CT did not improve discrimination of benign from malignant salivary gland lesions. However, PET/CT may be advantageous in primary staging and in the detection of distant metastases and synchronous cancers.

PET/CT Versus Standard Imaging for Prediction of Survival in Patients with Recurrent Head and Neck Squamous Cell Carcinoma.

The purpose of this study was to examine whether staging with 18F-FDG PET/CT better predicts survival in patients with recurrent head and neck squamous cell carcinoma (HNSCC) than chest x-ray (CXR) plus head and neck MRI or chest CT (CCT) plus head and neck MRI. Methods: This was a prospective cohort study based on paired data. Consecutive patients with histologically verified HNSCC recurrence were enrolled from September 2013 to March 2016. All patients underwent CXR/MRI, CCT/MRI, and PET/CT on the same day and before biopsy. All imaging studies underwent masked interpretation by separate teams of experienced nuclear physicians or radiologists. Recurrent carcinomas were categorized as localized (equivalent to primary stages I-II), locally advanced (equivalent to primary stages III-IVB), or metastatic (equivalent to primary stage IVC). Discriminative abilities for each imaging strategy with respect to cancer-specific and stage-based survival were compared using Kaplan-Meier analysis, Cox proportional-hazards regression with the Harrell concordance index (C-index), and net reclassification improvement. Results: In total, 110 patients (90 men and 20 women; median age, 66 y; range, 40-87 y) were included. PET/CT significantly changed the assigned tumor stage when compared with imaging strategies based on CXR/MRI or CCT/MRI (P < 0.001 for both). Kaplan-Meier analysis of PET/CT-based staging showed progressively worsened prognosis with localized, locally advanced, or metastatic disease (log-rank test, P < 0.001), whereas CXR/MRI and CCT/MRI were unable to distinguish between these groups in terms of survival (log-rank test, P = 0.18 and P = 0.58, respectively). Overall discriminative ability in predicting cancer-specific mortality was significantly greater for PET/CT (C-index, 0.72) than for CXR/MRI (C-index, 0.55) (P = 0.001) and CCT/MRI (C-index, 0.55)(P < 0.001). The addition of PET/CT to either CXR/MRI or CCT/MRI was associated with a significantly positive net reclassification improvement (P < 0.001 for both). Conclusion: Contrary to standard imaging strategies, PET/CT-based staging in recurrent HNSCC was able to significantly discriminate among the survival courses of patients with local, locally advanced, or metastatic disease and predict their respective survival probability.