Peripheral artery disease in patients with schizophrenia as compared to controls.

BACKGROUND: Patients with schizophrenia have an increased prevalence of risk factors for peripheral artery disease (PAD) and is expected to have an increased prevalence of PAD. PAD can be detected utilizing toe-brachial index (TBI) which screens for vascular pathology proximal to the toes. METHODS: Using a cross-sectional design, we defined the subpopulations: (1) Patients diagnosed with schizophrenia less than 2 years before inclusion (SCZ < 2), (2) Psychiatric healthy controls matched to subpopulation 1 on sex, age, and smoking status, and (3) Patients diagnosed with schizophrenia 10 or more years before inclusion (SCZ ≥ 10). TBI was calculated by dividing toe pressures by systolic brachial blood pressure, and PAD was defined by TBI < 0.70. Logistic regression analysis with PAD as outcome and sex, age, smoking status, BMI, skin temperature, diagnosis of schizophrenia, and comorbidities as explanatory variables was conducted. RESULTS: PAD was present in 26.2% of patients diagnosed with SCZ < 2 (17 of 65) and in 18.5% of psychiatric healthy controls (12 of 65) with no statistically significant difference in prevalence rates (p = 0.29). PAD was present in 22.0% of patients diagnosed with SCZ ≥ 10 (31 of 141). In logistic regression, patients diagnosed with SCZ < 2 had an increased odds of PAD with psychiatric healthy controls as reference (Odds ratio = 2.80, 95% confidence interval 1.09-7.23, p = 0.03). The analysis was adjusted for age, sex, smoking status, BMI and comorbidities such as hypertension, diabetes and heart disease. CONCLUSIONS: This study did not find statistically significant increased prevalence rates of PAD in patients with schizophrenia even though patients with SCZ were compared to psychiatric healthy controls using TBI. Utilizing logistic regression PAD was associated with schizophrenia diagnosis within the last 2 years, age and skin temperature. As PAD is initially asymptomatic, screening could be relevant in patients with schizophrenia if other risk factors are prevalent. Further large-scale multicenter studies are warranted to investigate schizophrenia as a potential risk factor for PAD. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02885792.

The clinical consequences of routine 68Ga-PSMA-11 PET/CT in patients with newly diagnosed prostate cancer, ISUP grade 5 and no metastases based on standard imaging - preliminary results.

AIM: To evaluate the clinical consequences of prostate specific membrane antigen (PSMA) PET/CT for primary staging in patients with ISUP grade 5 (Gleason score ≥9) prostate cancer (PCa), and no definitive distant metastases based on standard imaging. METHODS: At our tertial referral center, PSMA PET/CT became standard of care from August 2018 for primary staging of prostate cancer given the following criteria: (1) no prior treatment for prostate cancer, (2) ISUP grade 5, (3) no definitive metastases on standard imaging (contrast enhanced CT and bone scintigraphy), and (4) deemed suitable for treatment with curative intent based on comorbidity and life expectancy. We present the preliminary results of first six months recruitment with 12 months of follow-up. RESULTS: Forty-eight patients (mean age 69 years, median PSA 13.0 ng/mL, 20 patients with locally advanced PCa) were included. CT was positive in pelvic lymph nodes in two patients, bone scintigraphy was equivocal in three patients. PSMA PET/CT showed pathological uptake outside the prostatic bed in 22 patients (46%) of which 13 patients (27%) showed lesions confined to regional lymph nodes, and nine patients (19%) showed nonregional lymph node metastases and/or bone metastases. PSMA PET/CT changed the treatment strategy from curatively intended treatment to palliative treatment in 18 patients (38%). CONCLUSION: PMSA PET/CT revealed pathological uptake in a large proportion of high-risk patients at primary staging among patients with no definite metastases on standard imaging leading to change of patient management in 38% of the patients.

Influence of Prior Imaging Information on Diagnostic Accuracy for Focal Skeletal Processes-A Retrospective Analysis of the Consistency between Biopsy-Verified Imaging Diagnoses.

INTRODUCTION: Comparing imaging examinations with those previously obtained is considered mandatory in imaging guidelines. To our knowledge, no studies are available on neither the influence, nor the sequence, of prior imaging and reports on diagnostic accuracy using biopsy as the reference standard. Such data are important to minimize diagnostic errors and to improve the preparation of diagnostic imaging guidelines. The aim of our study was to provide such data. MATERIALS AND METHODS: A retrospective cohort of 216 consecutive skeletal biopsies from patients with at least 2 different imaging modalities (X-ray, CT and MRI) performed within 6 months of biopsy was identified. The diagnostic accuracy of the individual imaging modality was assessed. Finally, the possible influence of the sequence of imaging modalities was investigated. RESULTS: No significant difference in the accuracy of the imaging modalities was shown, being preceded by another imaging modality or not. However, the sequence analyses indicate sequential biases, particularly if MRI was the first imaging modality. CONCLUSION: The sequence of the imaging modalities seems to influence the diagnostic accuracy against a pathology reference standard. Further studies are needed to establish evidence-based guidelines for the strategy of using previous imaging and reports to improve diagnostic accuracy.

Use of 18F-NaF PET in the staging of skeletal metastases of newly diagnosed, high-risk prostate cancer patients: a nationwide cohort study.

OBJECTIVE: To determine whether preoperative staging of high-risk prostate cancer with 18F-sodium-fluoride (18F-NaF) positron emission tomography (PET) reduces the risk of skeletal metastases. DESIGN: Nationwide, population-based cohort study using real-world data. SETTING: The study used national health registries, including all sites in Denmark from 2011 to 2018. PARTICIPANTS: Newly diagnosed high-risk prostate cancer patients who underwent radical prostatectomy from 2011 to 2018. Patients were stratified into two groups according to the preoperative imaging modality of either 18F-NaF PET or bone scintigraphy. MAIN OUTCOME MEASURES: The risk of skeletal-related events (SREs) as a proxy for skeletal metastases following radical prostatectomy. The secondary endpoint was overall survival. RESULTS: Between 1 January 2011 and 31 December 2018, 4183 high-risk patients underwent radical prostatectomy. Of these patients, 807 (19.3%) underwent 18F-NaF PET and 2161 (51.7%) underwent bone scintigraphy. The remaining 30% were examined by a different imaging method or did not undergo imaging. Using the inverse probability of treatment weighting to control potential confounding, the HR of experiencing an SRE for patients in the 18F-NaF PET group versus the bone scintigraphy group was 1.15 (95% CI 0.86 to 1.54). The 3-year survival rates were 97.4% (95% CI 96.1 to 98.7) and 97.1% (95% CI 96.4 to 97.9) for patients receiving 18F-NaF PET and bone scintigraphy, respectively. CONCLUSION: Patients with high-risk prostate cancer undergoing preoperative staging with 18F-NaF PET did not display a lower risk of developing SREs after prostatectomy compared with patients undergoing bone scintigraphy. The survival rates were similar between the two groups.

Observer experience and accuracy of 18F-sodium-fluoride PET/CT for the diagnosis of bone metastases in prostate cancer.

OBJECTIVE: To evaluate the diagnostic accuracy of observers with different levels of experience in reading 18F-sodium fluoride (NaF) PET/CT images for the diagnosis of bone metastases in prostate cancer (PCa) patients. METHODS: Nine observers with varying NaF PET/CT experience, ranging from no experience to 2000+ examinations, evaluated 211 NaF PET/CT scans from PCa patients participating in one of four prospective trials. Each observer evaluated each NaF PET/CT on a patient level using a trichotomous scale: M0 (no bone metastases), Me (equivocal for bone metastases) and M1 (bone metastases). Subsequently, a dichotomous evaluation was conducted (M0/M1). The final diagnosis was retrieved from the original study. For each observer, ROC curves and the diagnostic accuracy were calculated based on dichotomous and trichotomous scales; in the latter case, Me was first regarded as M1 and then M0. RESULTS: Across all experience levels, the sensitivity, specificity and accuracy using the dichotomous scale ranged from 0.81 to 0.89, 0.93 to 1.00 and 0.91 to 0.94, respectively. Employing the trichotomous scale, novice and experienced observers chose Me in up to 20 vs. 10% of cases, respectively. Considering Me as M0, the sensitivity, specificity and accuracy ranged from 0.78 to 0.89, 0.95 to 1.00 and 0.91 to 0.95, respectively. Considering Me as M1, the sensitivity, specificity and accuracy ranged from 0.86 to 0.92, 0.71 to 0.96 and 0.77 to 0.94, respectively. CONCLUSION: Novice observers used the equivocal option more frequently than observers with NaF PET/CT experience. However, on the dichotomous scale, all observers exhibited high and satisfactory accuracy for the detection of bone metastases, making NaF PET/CT an effective imaging modality even in unexperienced hands.

Comparison of nuclear imaging techniques and volumetric imaging for the prediction of postoperative mortality and liver failure in patients undergoing localized liver-directed treatments: a systematic review.

BACKGROUND/AIMS: Although volumetric imaging by computed tomography (CT) is the gold standard for preoperative assessment of the future liver remnant, nuclear imaging studies have shown promising data. This systematic review summarized the results from trials investigating volumetric and nuclear medicine imaging for the prediction of postoperative mortality and liver failure (LF). METHODS: MEDLINE and Web of Science were searched for papers investigating nuclear imaging methods for the prediction of postoperative clinical outcomes in patients undergoing local, liver-directed treatments. Only papers investigating both preoperative nuclear imaging and CT or magnetic resonance imaging (MR) for the prediction of postoperative mortality and/or LF were included. RESULTS: Twenty-five trials were qualified for this review. All trials but two used technetium-based tracers for the nuclear imaging examination. Four papers used MR imaging and the remaining used CT for the volumetric evaluation. Overall, the studies were heterogeneous both in terms of methodology and imaging technique. Of the thirteen studies reporting on postoperative mortality, most were descriptive without detailed diagnostic data. A few with detailed data found that nuclear imaging had better predictive value than volumetric imaging. Nineteen studies investigated the prediction of postoperative LF of which seven papers investigated the predictive value of both modalities in multivariable regression analysis. Two papers found that only nuclear imaging parameters were predictive of LF, one paper found that the CT parameter was predictive, and four papers found that combined nuclear and CT/MR imaging parameters were predictive of LF. CONCLUSION: Both methodologies were useful in the preoperative assessment of patients scheduled for liver interventions, especially in combination, but nuclear imaging demonstrated better predictive value for postoperative mortality and LF in a few trials. The overall technical and methodological heterogeneity of the included studies complicates the ability to directly compare the clinical utility of the two imaging techniques.

Validity of negative bone biopsy in suspicious bone lesions.

BACKGROUND: The presence of malignant cells in bone biopsies is considered gold standard to verify occurrence of cancer, whereas a negative bone biopsy can represent a false negative, with a risk of increasing patient morbidity and mortality and creating misleading conclusions in cancer research. However, a paucity of literature documents the validity of negative bone biopsy as an exclusion criterion for the presence of skeletal malignancies. PURPOSE: To investigate the validity of a negative bone biopsy in bone lesions suspicious of malignancy. MATERIAL AND METHOD: A retrospective cohort of 215 consecutive targeted non-malignant skeletal biopsies from 207 patients (43% women, 57% men, median age 64, and range 94) representing suspicious focal bone lesions, collected from January 1, 2011, to July 31, 2013, was followed over a 2-year period to examine any additional biopsy, imaging, and clinical follow-up information to categorize the original biopsy as truly benign, malignant, or equivocal. Standard deviations and 95% confidence intervals were calculated. RESULTS: 210 of 215 biopsies (98%; 95% CI 0.94-0.99) showed to be truly benign 2 years after initial biopsy. Two biopsies were false negatives (1%; 95% CI 0.001-0.03), and three were equivocal (lack of imaging description). CONCLUSION: Our study documents negative bone biopsy as a valid criterion for the absence of bone metastasis. Since only 28% had a confirmed diagnosis of prior cancer and not all patients received adequately sensitive imaging, our results might not be applicable to all cancer patients with suspicious bone lesions.

Usefulness of Imaging Response Assessment after Irreversible Electroporation of Localized Pancreatic Cancer-Results from a Prospective Cohort.

(1) Background: Irreversible electroporation (IRE) is a nonthermal ablation technique that is being studied in nonmetastatic pancreatic cancer (PC). Most published studies use imaging outcomes as an efficacy endpoint, but imaging interpretation can be difficult and has yet to be correlated with survival. The aim of this study was to examine the correlation of imaging endpoints with survival in a cohort of IRE-treated PC patients. (2) Methods: Several imaging endpoints were examined before and after IRE on 18F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography. Separate analyses were performed at the patient and lesion levels. Mortality rate (MR) ratios for imaging endpoints after IRE were estimated. (3) Results: Forty-one patients were included. Patient-level analysis revealed that progressive disease (PD), as defined by RECIST 1.1, is correlated with a higher MR at all time intervals, but PD, as defined by EORTC PET response criteria, is only correlated with the MR in the longest interval. No correlation was found between PD, as defined by RECIST, and the MR in the lesion-level analysis. (4) Conclusions: Patient-level PD, as defined by RECIST, was correlated with poorer survival after IRE ablation, whereas no correlations were observed in the lesion-level analyses. Several promising lesion-level outcomes were identified.

Response evaluation of bone metastasis in prostate cancer: Preliminary comparison of computerized bone scan index versus standardized clinical criteria.

OBJECTIVE: The correlation between the computer-assisted bone scan index (BSI) responses versus clinical response classification if bone metastases in prostate cancer patients are not clear. We compared changes in BSI with Prostate Cancer Working Group-3 (PCWG3) and MD Anderson (MDA) criteria. MATERIALS AND METHODS: Fifty-six consecutive patients with at least two bone scans (BS) within 12 months were included, who had BS before and after treatment with the same anticancer agent. RESULTS: Progressive disease (PD) by PCWG3 criteria was seen in 28% of the cases (median BSI increased by 1.69 units) versus non-PD in 72% (BSI change -0.13). MDAnderson showed PD in 34% (BSI increase 0.49), 45% stable disease (BSI change 0.00), and 20% partial responses (BSI decrease 1.44). Absolute BSI changes differed significantly among response categories by PCWG3 and MDA criteria (both P<0.0001). Response classification using dichotomized BSI data (>0/≤0 and >0.3/≤0.3 BSI units) showed a significant correlation with PCWG3 and MDA criteria (all P<0.001). Absolute BSI changes and dichotomized BSI correlated to prostate-specific antigen responses (both P<0.001) but not to clinical responses. CONCLUSION: Absolute changes in BSI and BSI response classification correlated significantly with standardized clinical response criteria for the assessment of treatment responses of skeletal metastases in prostate cancer.

The frequency and malignancy rate of incidental focal breast lesions identified by 18F-fluorodeoxyglucose positron emission tomography.

OBJECTIVE: To evaluate the frequency and malignancy rate of incidental focal uptake of 18F-fluorodeoxyglucose (FDG) in the breast on PET/computed tomography (CT). MATERIAL AND METHODS: All PET/CT scan reports from a single institution from 2010 to 2017 were electronically searched for words or phrases related to FDG uptake in the breast. Potentially eligible PET/CT scans were manually reviewed for the presence of focal incidental findings in the breast, and a final diagnosis was established based on pathology, clinical examinations, and clinical follow-up. RESULTS: A total of 19 551 PET/CT scans were reviewed, from which 66 patients (0.3%) presented with unexpected focal FDG-avid lesions of the breast. Fifty-three patients (80.3%) had follow-up evaluations. The final diagnosis showed malignancies in 38 patients. Thirty-four patients had biopsy-verified cancer (primary breast cancers, n = 30; metastasis, n = 4), and four patients with known lymphoma showed a tumour response in the breast after chemotherapy. The malignancy rate was 85.0% among patients who underwent biopsy (34 of 40 patients). The SUVmax was significantly higher in patients with a final malignant diagnosis (n = 38) than in those with a benign diagnosis (n = 15) (4.5 ± 2.9 vs. 2.7 ± 1.3, P = 0.03). CONCLUSION: Incidental uptake of FDG in the breast was rare. However, the malignancy rate was high among these patients, particularly among patients who had a follow-up biopsy. We recommend biopsy or thorough follow-up in patients with incidental focal uptake of FDG in the breast.

The frequency of thyroid incidental findings and risk of malignancy detected by 68Ga-labeled prostate-specific membrane antigen PET/CT in prostate cancer.

OBJECTIVE: Gallium-68-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) has become a well-established imaging method for the evaluation of patients with prostate cancer. However, several cases have revealed PSMA uptake in a large variety of conditions other than prostate cancer. Prostate-specific membrane antigen uptake in thyroid cancer has also been reported. The aim of the present study was to systematically investigate the prevalence and clinical significance of thyroid incidental findings in patients undergoing 68Ga-PSMA PET/CT. MATERIALS AND METHODS: We retrospectively identified all patients referred for 68Ga-PSMA PET/CT at the Department of Nuclear Medicine, Aalborg University Hospital, Denmark between May 2015 and May 2019. Patients with increased PSMA uptake in the thyroid gland were included in the analysis. Follow-up included imaging, biochemical, and/or histopathological collected over six months. RESULTS: A total of 341 patients were included. Increased 68Ga-PSMA uptake in the thyroid gland was observed in 13 patients (4%). Focal uptake was observed in seven patients, diffuse uptake in five patients and mixed focal and diffuse uptake in one patient. Malignancy was verified in two patients (2/13 patients, 15%), both patients with focal PSMA uptake. CONCLUSION: Gallium-68-PSMA thyroid incidental findings are rare in prostate cancer patients. However, cases of focal PSMA uptake in the thyroid gland should be further investigated, as these findings may represent metastatic or primary malignancy of the thyroid gland.

Inter- and intraobserver agreement in standard and ultra-fast single-photon emission computed tomography/computed tomography for the assessment of bone metastases.

OBJECTIVE: To investigate inter- and intraobserver agreement using standard (std)-single-photon emission computed tomography/computed tomography (SPECT/CT) or ultra-fast acquisition (UF)-SPECT/CT as an add-on to planar whole-body bone scintigraphy (WB-BS) for the detection of bone metastases in patients with known cancer. METHODS: Images from patients (n = 104) participating in a prospective trial comparing SPECT/CT as an add-on to WB-BS with two different acquisition methods (std-SPECT/CT; 20 s per view, 32 views and UF-SPECT/CT; 16 views of 10 s per view) were included. The combinations of WB-BS with the two different SPECT/CT acquisition methods were independently evaluated by two experienced observers using a three-point scale (M0: no metastases, Me: equivocal for bone metastases and M1: bone metastases). The observers re-evaluated the scans 6 months later. Inter- and intraobserver agreement was calculated using linear weighted kappa. RESULTS: The linear weighted kappa for the interobserver agreement was 0.78 [95% confidence interval (CI) 0.61-0.94] for WB-BS with std-SPECT/CT and 0.84 (95% CI 0.67-1.00) for WB-BS with UF-SPECT/CT. Similar values were observed for the intraobserver agreement, in which the linear weighted kappa was 0.76 (95% CI 0.60-0.92) and 0.73 (95% CI 0.57-0.90) for std-SPECT/CT and UF-SPECT/CT, respectively. CONCLUSION: Satisfactory inter- and intraobserver agreement was seen for both acquisition methods, emphasizing that the use of SPECT/CT as an add-on to WB-BS is a robust method for the detection of bone metastases even when conducted with a very short acquisition time.

Imaging response evaluation after local ablative treatments in locally advanced pancreatic cancer: an expedited systematic review.

BACKGROUND: Several local ablative modalities have been introduced for the treatment of locally advanced pancreatic cancer (LAPC). However, there is no consensus on how to evaluate the imaging response after treatment. A systematic review was performed regarding the use of imaging for response assessment in LAPC. METHODS: A systematic literature search was conducted in PubMed. Studies reporting imaging outcomes were included in the review. Studies were excluded if the imaging outcomes could not be differentiated between different disease stages, tumor histology or surgical approaches. RESULTS: Thirty-four studies were included in the analysis. Fourteen studies used standardized response criteria, while six studies did not report the response evaluation method. The rest used self-determined criteria, absolute size comparisons or similar methods. One study found a correlation between early systemic progression (<6 months) and overall survival. CONCLUSION: There was notable variation in the use of imaging for response assessment in LAPC. This significantly hinders cross-comparison of results among studies. There is currently only sparse evidence of an association between imaging responses and overall survival. The field calls for standardized recommendations regarding the choice of response assessment method, timing of scans, target definition and reporting of outcomes.

Added value of 68Ga-PSMA PET/CT for the detection of bone metastases in patients with newly diagnosed prostate cancer and a previous 99mTc bone scintigraphy.

PURPOSE: To investigate the added value and diagnostic accuracy of 68Ga-PSMA PET/CT versus bone scintigraphy (BS) for bone metastasis detection at the primary staging of prostate cancer (PCa). METHODS: Inclusion criteria involved consecutive patients with newly diagnosed intermediate- to high-risk PCa, who had undergone BS, mostly with supplementary SPECT/low-dose CT, and 68Ga-PSMA-11 PET/CT within less than 3 months without therapy initiation between the two investigations. BS was evaluated according to clinical routine and reported as no bone metastases (M0), bone metastases (M1), or equivocal (Me). The 68Ga-PSMA-11 PET/CT was blindly evaluated by three specialists as M0, M1, or Me at the patient level. Sensitivity analyses were conducted using a "best valuable comparator" using all available imaging and clinical follow-up as a reference. RESULTS: In total, 112 patients were included; 68Ga-PSMA-11 PET/CT showed a sensitivity of 1.00, specificity of 0.93-0.96, positive predictive value of 0.74-0.81, and negative predictive value of 1.00. 68Ga-PSMA-11 PET/CT revealed bone metastases in 8 of 81 patients with M0 disease according to BS. 68Ga-PSMA-11 PET/CT confirmed the presence of bone metastases in all patients (n = 9) with M1 disease according to BS. In patients with Me by BS, 68Ga-PSMA PET/CT provided a definite result in 20 of 22 patients. 68Ga-PSMA-11 PET/CT resulted in a false-positive answer in four patients with solitary rib lesions. CONCLUSION: 68Ga-PSMA-11 PET/CT revealed bone metastases in 10% of patients without bone metastases on BS and in 36% patients with indeterminate BS. However, solitary PSMA-avid lesions in the ribs should be interpreted cautiously as they may represent false-positive findings.

PSMA PET for primary lymph node staging of intermediate and high-risk prostate cancer: an expedited systematic review.

BACKGROUND: PSMA PET is a promising method for primary lymph node staging in prostate cancer. However, recent systematic reviews have identified only a limited number of studies with histopathology as a reference test. METHODS: A systematic search was performed in PubMed and the Cochrane Library. An expedited systematic review was performed where we identified diagnostic studies in prostate cancer where a preoperative PSMA PET for primary lymph node staging was compared to histopathology. The trials must have diagnostic data on a patient level. RESULTS: Eighteen eligible clinical trials included 969 patients. The median patient number per study was 32 (range 10 to 208). Five trials were prospective, and nine trials had a consecutive enrolment of patients. Sixteen studies used Ga-68-PSMA-11; there was one study with Cu-64-PSMA and one study with F-18-DCDFPyL. Twelve studies used PET/CT, four trials used PET/MR. Most trials included patients with intermediate and high-risk. Diagnostic accuracy varied notably among the studies; sensitivity ranged from 23 to 100%, specificity 67-100%, positive predictive value 20-100%, and negative predictive value 41-100%. Weighted sensitivity was 59%, weighted specificity was 93%. Four studies compared PSMA PET with anatomical imaging (CT or MRI); in all cases, sensitivity and specificity were superior with PSMA PET. Three studies compared PSMA PET with multi-parametric or diffusion-weighted MRI with mixed results. CONCLUSIONS: PSMA PET showed promising diagnostic accuracy for primary lymph node staging with pathology as reference. Recommendation for PSMA PET for high-risk patients in clinical guidelines should be supported by confirmatory, prospective trials with patient-relevant outcomes.

68Ga-PSMA PET/CT Uptake in the Ureter Caused by Ligand Expression in Urothelial Cancer.

Ga-PSMA PET/CT has become a well-established imaging modality to detect prostate cancer (PCa) metastases in biochemical recurrence. Despite its claimed specificity for PCa, Ga-PSMA uptake in tissues unrelated to PCa, particularly in the neovascular tissue of other cancers, has been reported in numerous studies. A 73-year-old man underwent Ga-PSMA PET/CT for biochemical recurrence of PCa 7 years after radical prostatectomy. The Ga-PSMA PET/CT showed 1 lesion with PSMA uptake in the distal left ureter. Histology revealed a low-grade noninvasive papillary urothelial carcinoma. By immunohistochemistry, PSMA expression was observed in the neoplastic urothelial cells and in the vessels of the papillary structures.

68Ga-PSMA PET/CT compared with MRI/CT and diffusion-weighted MRI for primary lymph node staging prior to definitive radiotherapy in prostate cancer: a prospective diagnostic test accuracy study.

BACKGROUND: The aim was to compare the diagnostic accuracy of 68Ga-PSMA PET/CT with conventional cross-sectional imaging and diffusion-weighted MRI (DW-MRI) for detecting lymph node metastasis (LNM) to stage prostate cancer patients. Twenty consecutive, newly- diagnosed prostate cancer patients were prospectively enrolled and underwent 68Ga-PSMA-11 PET/CT, anatomical MRI or contrast-enhanced CT, and DW-MRI prior to laparoscopic, template-based, extended lymph node dissection. Histopathological findings served as the reference test. RESULTS: Histopathology showed LNM in 13 of 20 patients (19 high-risk, 1 intermediate risk). Five patients had metastasis-suspected lymph nodes on 68Ga-PSMA PET/CT. Patient-based analysis showed that the sensitivity and specificity for detecting LNM were 39% and 100% with 68Ga-PSMA PET/CT, 8% and 100% with MRI/CT, and 36% and 83% with DW-MRI, respectively. The positive and negative predictive values were 100% and 49% with 68Ga-PSMA PET/C, 100% and 37% with MRI/CT, and 80% and 42% with DW-MRI. Of 573 dissected lymph nodes, 33 were LNM from 26 regions. True-positive LNM on 68Ga-PSMA PET/CT was 9-11 mm in diameter, whereas false-negative LNM had a median diameter of 4 mm, with only 3 of 30 lymph nodes being larger than 10 mm. LNM were positive for PSMA by immunostaining. CONCLUSIONS: The sensitivity of 68Ga-PSMA PET/CT was notably better than that of MRI/CT and comparable to that of DW-MRI. Some false positive findings with DW-MRI reduced its specificity and positive predictive value compared with those of 68Ga-PSMA PET/CT and MRI/CT.

Reporting and handling of equivocal imaging findings in diagnostic studies of bone metastasis in prostate cancer.

BACKGROUND: Equivocal scanning results occur. It remains unclear how these results are presented and their management influence diagnostic characteristics. PURPOSE: To investigate the reporting and handling of equivocal imaging findings in diagnostic studies of bone metastases, and to assess the impact on diagnostic performance of the methods used to analyze equivocal findings. The conceptual issue was reified based on two actual observations. MATERIAL AND METHODS: A recent meta-analysis of bone metastases in prostate cancer was conducted and data were obtained from a large clinical trial with a true reference of bone metastasis, where diagnostic characteristics were calculated with equivocal scans handled by: removal; considered malignant; considered benign; and intention-to-diagnose. RESULTS: The meta-analysis included 18 trials where the median proportion of reported equivocal results was 27%. Eleven (61%) studies reported an equivocal option for the index test, 42% reported equivocal results and described how these were analyzed. The clinical trial included 583 prostate cancer patients with 20% equivocal results. The different methods of managing equivocal findings resulted in highly variable outcomes: sensitivity = 85%-100%; specificity = 78%-99%; and positive and negative predictive values = 44%-94% and 97%-100%, respectively. The diagnostic performances obtained using the four methods were differentially susceptible to the proportion of equivocal imaging findings and the prevalence of bone metastases. CONCLUSION: Reporting of equivocal results was inadequate in bone imaging trials. The handling of equivocal findings strongly influenced diagnostic accuracy.

Observer Agreement and Accuracy of 18F-Sodium Fluoride PET/CT in the Diagnosis of Bone Metastases in Prostate Cancer.

Our aim was to evaluate the interobserver agreement in 18F-sodium fluoride (NaF) PET/CT for the detection of bone metastases in patients with prostate cancer (PCa). Methods:18F-NaF PET/CT scans were retrieved from all patients who participated in 4 recent prospective trials. Two experienced observers independently evaluated the 18F-NaF PET/CT scans on a patient level using a 3-category scale (no bone metastases [M0], equivocal for bone metastases, and bone metastases present [M1]) and on a dichotomous scale (M0/M1). In patients with no more than 10 lesions, the location and number of lesions were recorded. On a patient level, the diagnostic performance was calculated using a sensitivity analysis, in which equivocal lesions were handled as M0 as well as M1. Results:18F-NaF PET/CT scans from 219 patients with PCa were included, of whom 129 patients were scanned for primary staging, 67 for biochemical recurrence, and 23 for metastatic castration-resistant PCa. Agreement between the observers was almost perfect on a patient level (3-category unweighted κ = 0.83 ± 0.05, linear weighted κ = 0.90 ± 0.06, and dichotomous κ = 0.91 ± 0.07). On a lesion level (dichotomous scale), the observers agreed on the number and location of bone metastases in 205 (93.6%) patients. In the remaining 14 patients, the readers disagreed on the number of lesions in 13 patients and the location of bone metastases in 1 patient. A final diagnosis of bone metastases was made for 211 of 219 patients. The sensitivity ranged from 0.86 to 0.92, specificity from 0.83 to 0.97, positive predictive value from 0.70 to 0.93, and negative predictive value from 0.94 to 0.96. Conclusion: The interobserver agreement on 18F-NaF PET/CT for the detection of bone metastases in patients with PCa was very high among trained observers, both on a patient level and on a lesion level. Moreover, the diagnostic performance of 18F-NaF PET/CT was satisfactory, rendering 18F-NaF PET/CT a robust tool in the diagnostic armamentarium.

Comparison of simultaneous plasma clearance of 99mTc-DTPA and 51Cr-EDTA: can one tracer replace the other?

Both 99mTc-DTPA and 51Cr-EDTA are widely used to determine glomerular filtration rate (GFR), but few direct comparative studies exist. The shortage of 51Cr-EDTA makes a direct comparison highly relevant. The aim of the study was to investigate if there is any clinically relevant difference between plasma clearance of 99mTc-DTPA and 51Cr-EDTA. Patients ≥18 years of age referred for routine GFR measurement by 51Cr-EDTA were prospectively enrolled. The two tracers (10 MBq 99mTc-DTPA (CaNa3-DTPA) and 2.5 MBq 51Cr-EDTA) were intravenously injected at time zero. A standard 4-sample technique was applied with samples collected at 180, 200, 220 and 240 min, if the estimated GFR (eGFR) was ≥30 mL/min. A comparison of single-sample GFR based on the 200 min sample was also conducted. Fifty-six patients were enrolled in the study. All patients had an estimated GFR >30 mL/min/1.73 m2. No patients suffered from ascites or significant oedema. The mean 51Cr-EDTA plasma clearance was 82 mL/min (range 16-226). The plasma clearances determined by the two methods were highly correlated (r = 0.993). The plasma clearance was significantly higher when measured by 99mTc-DTPA than by 51Cr-EDTA (p = 0.01), but the numerical difference was minimal (mean difference 1.4 mL/min; 95% limits of agreement (LOA) -6.6 to 9.4). The difference between the two methods was independent of the level of renal function. Similar results were found for one-sample GFR. No clinically relevant differences were found between the plasma clearance of 99mTc-DTPA and that of 51Cr-EDTA. Therefore, 99mTc-DTPA can replace 51Cr-EDTA when needed.