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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 (

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.

Aim: To determine if additional 18F-sodium fluoride PET/CT (NaF-PET/CT) improves the prognostic accuracy in the initial staging of prostate cancer patients with normal bone scintigraphy undergoing prostatectomy. Methods: A prospective cohort study examined NaF-PET/CT in intermediate- or high-risk prostate cancer with negative bone scintigraphy who were scheduled for prostatectomy. Biochemical response: PSA levels

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.

Simple Summary Irreversible electroporation (IRE) is a novel therapy that is being studied for the treatment of nonmetastatic pancreatic cancer. The current methods for evaluating the treatment response after IRE have been adapted from the Response Evaluation Criteria in Solid Tumors (RECIST). However, it is uncertain whether these methods are appropriate, because the methods have not been validated. The aim of the current study was to evaluate the correlation between survival time and the most commonly used imaging assessment methods on FDG-PET/CT scans. We confirmed that the Response Evaluation Criteria in Solid Tumors (RECIST) are correlated with survival, when applied as intended. However, no correlation was found when the often-used lesion-level method was used. FDG-PET-derived data did not provide any benefit over conventional CT data. Several novel methods for lesion-level analysis were explored. Abstract (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.

Hepatobiliary scintigraphy (HBS) is an important tool in diagnosing biliary atresia in infants. There is limited evidence on the use of single photon emission computed tomography/computed tomography (SPECT/CT) as an additional imaging method to planar imaging. We evaluated the value of SPECT/CT in unclear cases of planar HBS.Consecutive patients with suspected biliary atresia who underwent guideline-compliant HBS from January 2010 until March 2020 were reviewed, and cases with SPECT/CT were identified. Each step within the imaging procedure (dynamic, static [early and late], and SPECT/CT) was blindly reread in consensus by two observers and categorized based on a 5-point scale: 0, definitely no bowel excretion (i.e., atresia confirmed); 1, probably positive; 2,equivocal; 3, probably negative; and 4, definite negative (i.e., atresia not confirmed). In this analysis, categories were dichotomized as negative for biliary atresia (scores 3-4) or positive (scores 0-2, including equivocal scans). Available follow-up information constituted the standard of truth (SoT).Twenty-three infants had HBS, among which ten (4 boys and 6 girls; mean age 36 days; range 8-108) underwent SPECT/CT. Single photon emission computed tomography SPECT/CT was performed as early examination (8h) in 3 subjects and late (8 to 24 h) in 7 infants. Reread SPECT/CT was categorized as positive for atresia in three infants and negative in seven infants. The SoT showed biliary atresia in one of ten patients. Single photon emission computed tomography/CT was true positive in one case, false positive in two, and true negative in seven. No false negative cases were noted. The diagnostic performance of SPECT/CT showed a sensitivity of 100%, specificity of 78%, positive predictive value (PPV) of 33%, negative predictive value (NPV) of 100%, and accuracy of 90%. For comparison, the diagnostic performance of planar HBS showed a sensitivity of 100%, specificity of 67%, PPV of 25%, NPV of 100%, and accuracy of 70%. In summary, the addition of SPECT/CT to planar HBS improved specificity andaccuracyand marginally improved PPV. Single photon emission computed tomography/CT provided more confidence in the final conclusion in 8/10 patients. In the remaining two cases, SPECT/CT did not improve the level of confidence (one remained equivocal, and one changed from probably no excretion to equivocal).These preliminary data demonstrated increased accuracy of add-on SPECT to planar HBS predominantly due to improved specificity. This finding is consistent with the existing but limited literature and supports the recommendation of routine use of SPECT/CT or SPECT.

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.

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.

Purpose of the Report The aim of this study was to prospectively investigate the detection rate of 68Ga-PSMA PET/CT in biochemical recurrence (BCR) of prostate cancer and its impact on patient management. Materials and Methods Patients with BCR after curatively intended treatment of prostate cancer were included. Each patient underwent a 68Ga-PSMA PET/CT. Changes in patient management based on the results of 68Ga-PSMA PET/CT were assessed. Results Seventy patients were included. Sixty-four patients (91%) had radical prostatectomy, of whom 17 patients (24%) received salvage radiation therapy due to first biochemical relapse. Six patients (9%) underwent radiation therapy as the primary treatment. 68Ga-PSMA PET/CT detected recurrent disease in 37 patients (53%). The detection rate was 22% for prostate-specific antigen (PSA) levels up to 0.5 ng/mL compared with 83% for PSA levels greater than 0.5 ng/mL. Pathological uptake of 68Ga-PSMA was observed in 4 (16%) of 21, 4 (44%) of 9, 0 of 1, 7 (70%) of 10, and 22 (88%) of 25 patients with PSA levels from 0.2 to 0.3 ng/mL, 0.31 to 0.4 ng/mL, 0.41 to 0.5 ng/mL, 0.51 to 1 ng/mL, and greater than 1 ng/mL, respectively. Prostate-specific antigen was significantly higher in PSMA-positive patients than in PSMA-negative patients. In 15 (22%) of 69 patients, the results caused a definite change in patient management, and in another 15 (22%) of 69 patients, 68Ga-PSMA PET/CT guided the choice of treatment. Conclusions 68Ga-PSMA PET/CT detects lesions in a large proportion of patients with BCR. Detection rates at low PSA levels (

OBJECTIVE: The aim of this study was to investigate the contribution of contrast-enhanced computed tomography (CE-CT) to the localization of parathyroid adenomas compared with the dual-phase Tc-99m MIBI SPECT with low-dose CT (LD-CT).PATIENTS AND METHODS: This retrospective study included consecutive patients with primary hyperparathyroidism who underwent a preoperative dual-phase MIBI SPECT/CT followed by surgical resection. The standard of care was dual-phase MIBI SPECT/CT, acquired with LD-CT in the early phase and CE-CT in the late phase (SPECT/CE-CT). The presence and localization of positive sites were extracted from study reports. To examine the role of CE-CT, patient cases were independently re-reviewed, with the early LD-CT fused with early and late SPECT (SPECT/LD-CT). The two SPECT/CT methods were compared for sensitivity, and the positive predictive value and histopathology were used as a reference.RESULTS: In total, 138 patients were included. The investigation was positive for suspected adenomas in 124 patients using SPECT/CE-CT and in 122 patients using SPECT/LD-CT. The per-patient sensitivity was 87.5% [95% confidence interval (CI): 80.7-92.6%] for SPECT/CE-CT and was not statistically significantly different from SPECT/LD-CT (85.3%; 95% CI: 78.2-90.8%) (P=0.39). The positive predictive value was 95.2% (95% CI: 95.4-99.9%) with SPECT/CE-CT versus 100% (95% CI: 96.8-100%) with SPECT/LD-CT. For small adenomas (≤500 mg), the sensitivity was low with SPECT/CE-CT (67%) as well as with SPECT/LD-CT (64%).CONCLUSION: Late CE-CT, compared with late LD-CT, did not significantly improve the sensitivity of dual-phase Tc-99m MIBI parathyroid SPECT/CT in a population of patients with primary hyperparathyroidism. These findings were consistent regardless of the size, location, or histology of the adenomas.

OBJECTIVE: To prospectively determine the prognostic value of the bone scan index (BSI) for time to development of castration-resistant prostate cancer (CRPC) in consecutive, hormone-naïve patients with newly diagnosed prostate cancer.PATIENTS AND METHODS: Eligible patients participated in a prospective, observational, multi-center study of the value of bone scintigraphy (BS) at staging. BSI was determined using the EXINIBone(BSI)-software in 208 consecutive patients undergoing androgen deprivation therapy. The presence or absence of bone metastases at staging was classified by BS with or without supplementary imaging. Follow-up was performed >5 years after including the last patient.RESULTS: During follow-up, 149 of the 208 patients (72%) were diagnosed with CRPC. Median time to CRPC was 20 months. Median follow-up time was 4.4 years in patients without CRPC. In univariate analyses, M1 (hazard ratio [HR] 3.00, 95% confidence interval [95%CI] 2.10 - 4.30), Gleason grade (HR 1.53, 95%CI 1.31 - 1.79), and BSI (HR 1.17, 95%CI 1.12 - 1.23) but not PSA significantly predicted time to CRPC (all, p1, pCONCLUSIONS: BSI is an independent risk factor for the time from ADT initiation to CRPC in hormone-naïve patients. The significant prognostic factors, in rank order, were M1-status, Gleason grade, and BSI.

Our aim was to evaluate the interobserver agreement in (18)F-sodium fluoride (NaF) PET/CT for the detection of bone metastases in patients with prostate cancer (PCa). Methods: (18)F-NaF PET/CT scans were retrieved from all patients who participated in 4 recent prospective trials. Two experienced observers independently evaluated the (18)F-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: (18)F-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 (18)F-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 (18)F-NaF PET/CT was satisfactory, rendering (18)F-NaF PET/CT a robust tool in the diagnostic armamentarium.

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 has become a well-established imaging modality to detect prostate cancer (PCa) metastases in biochemical recurrence. Despite its claimed specificity for PCa, 68Ga-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 68Ga-PSMA PET/CT for biochemical recurrence of PCa 7 years after radical prostatectomy. The 68Ga-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.

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.

BackgroundEquivocal scanning results occur. It remains unclear how these results are presented and their management influence diagnostic characteristics.PurposeTo 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 MethodsA 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.ResultsThe 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.ConclusionReporting of equivocal results was inadequate in bone imaging trials. The handling of equivocal findings strongly influenced diagnostic accuracy.

REPLY: We thank the authors for the insightful comments on our study ([1][1]). We very much agree with the authors that bone metastases are preceded by bone marrow metastases and that both bone scintigraphy and 18F-NaF PET/CT indirectly visualize skeletal metastases via the osteoblastic reaction to

BACKGROUND AND AIMS: Classically, peripheral arterial disease (PAD) is diagnosed by a low ankle-brachial index (ABI), but the diagnosis can also be made based on toe-brachial index (TBI) measurements. The objective of this study was to characterize patients with low TBI but normal ABI, and chart potential underestimation of PAD prevalence by solitary use of ABI.METHODS: A total of 3739 consecutive patients with known or suspected PAD referred for ABI and TBI measurements in a four-year period were compared to an age- and gender matched control group (n = 17,340).RESULTS: In the patient cohort, 65.0% had low ABI, 20.5% had low TBI but normal ABI, and 14.5% had normal indices. When comparing the frequencies of comorbidities related to atherosclerotic disease (myocardial infarction, congestive heart failure, cerebrovascular disease, diabetes mellitus, chronic kidney failure), there were no significant differences among patients with low ABI or low TBI with normal ABI in any of the variables (all p > 0.06). Of the patients with low TBI and normal ABI, 18.7% were diagnosed with diabetes mellitus type I or II, and 8.2% with chronic kidney disease.CONCLUSIONS: Patients with low TBI but normal ABI represented 20.5% of patients referred with the suspicion of PAD. Furthermore, patients with low TBI but normal ABI presented similar comorbid characteristics to patients with low ABI, who have a well-described increased risk of cardiovascular morbidity and mortality. The solitary use of ABI underestimated the prevalence of PAD in the population, and PAD screening could potentially be improved by routine application of TBI.

Ventilation/perfusion single-photon emission computed tomography performed using an aerosol of carbon-coated technetium is frequently used for diagnosing pulmonary embolism. Certain patients may suffer from chronic obstructive pulmonary disease (COPD); for such patients, the formation of mucus clots in airways can cause accumulation of the aerosol in the larger airways. This centralized deposition of the aerosol leads to insufficient activity in peripheral lung segments and subsequently results in ventilation images of substandard or even nondiagnostic quality. Continuous positive airway pressure (CPAP) therapy improves airway dynamics and quality of life for COPD patients. We report for the first time the results for two patients for whom initial ventilation scans were of insufficient quality, but diagnostic-quality images were obtained after CPAP therapy.

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 (CaNa 3-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 m 2. 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.

Background: Semi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. However, simple tumor volume measures may be inadequate for assessment of prognosis in DLBCL as other characteristics such as growth pattern and metabolic heterogeneity may be just as important. In addition, MTV measurements require delineation of tumor lesions by semi-automated software, which can be time-consuming. We hypothesized that a simple visual assessment of tumor volume performs as well as standardized MTV measurements in DLBCL prognostication. Materials and methods: Quantitative and visual analyses of pre-therapy 18F-FDG PET/CT scans in 118 patients with newly diagnosed DLBCL were conducted. Quantitative analyses were performed using Hermes TumourFinder® to obtain MTV 2.5 (SUV 2.5 cut-off) and MTV 41 (41% SUVmax isocontour cut-off). Visual assessments included a binary prediction (good/poor prognosis) as well as tumor burden based on a visual analog scale (MTV VAS ) and an estimated volume (eMTV). Three experienced nuclear medicine physicians who were blinded to clinical outcome performed visual evaluations. Progression-free survival was evaluated by Kaplan-Meier curves and log-rank test. Inter-observer variability was evaluated by Fleiss’ kappa for multiple observers. Results: In the quantitative analysis, a ROC-determined MTV 2.5 cut-off (log-rank p = 0.11) seemed to outperform MTV 41 (log-rank p = 0.76) for PFS prediction. TLG2.5 (log-rank p = 0.14) and TLG41 (log-rank p = 0.34) were not associated with outcomes. By visual analysis, all three reviewers were able to stratify patients into good/poor prognosis (reviewer A log-rank p = 0.002, reviewer B log-rank p = 0.016, and reviewer C log-rank p = 0.012) with fair inter-observer agreement (Fleiss’ kappa 0.47). MTV VAS and eMTV were not consistently correlated with the outcome. Conclusion: Predictions of outcome after first-line treatment for DLBCL were surprisingly good when left to the unsupervised, subjective judgment of experienced readers of lymphoma 18F-FDG-PET/CT. The study highlights the importance of non-standardized clinical judgments and shows potential loss of valuable prognostic information when relying solely on semi-automated MTV measurements.

Oligometastatic disease represents a clinical and anatomical manifestation between localised and polymetastatic disease. In prostate cancer, as with other cancers, recognition of oligometastatic disease enables focal, metastasis-directed therapies. These therapies potentially shorten or postpone the use of systemic treatment and can delay further metastatic progression, thus increasing overall survival. Metastasis-directed therapies require imaging methods that definitively recognise oligometastatic disease to validate their efficacy and reliably monitor response, particularly so that morbidity associated with inappropriately treating disease subsequently recognised as polymetastatic can be avoided. In this Review, we assess imaging methods used to identify metastatic prostate cancer at first diagnosis, at biochemical recurrence, or at the castration-resistant stage. Standard imaging methods recommended by guidelines have insufficient diagnostic accuracy for reliably diagnosing oligometastatic disease. Modern imaging methods that use PET-CT with tumour-specific radiotracers (choline or prostate-specific membrane antigen ligand), and increasingly whole-body MRI with diffusion-weighted imaging, allow earlier and more precise identification of metastases. The European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group suggests clinical algorithms to integrate modern imaging methods into the care pathway at the various stages of prostate cancer to identify oligometastatic disease. The EORTC proposes clinical trials that use modern imaging methods to evaluate the benefits of metastasis-directed therapies. ispartof: LANCET ONCOLOGY vol:19 issue:10 pages:E534-E545 ispartof: location:England status: published

AIM: To compare18F-sodium fluoride positron emission tomography/computed tomography (NaF PET/CT) and99mTc-labelled diphosphonate bone scan (BS) for the monitoring of bone metastases in patients with prostate cancer undergoing anti-cancer treatment.MATERIAL AND METHODS: Data from 64 patients with prostate cancer were included. The patients received androgen-deprivation therapy (ADT), next-generation hormonal therapy (NGH) or chemotherapy. The patients had a baseline scan and 1-3 subsequent scans during six months of treatment. Images were evaluated by experienced nuclear medicine physicians and classified for progressive disease (PD) or non-PD according to the Prostate Cancer Working Group 2 (PCWG-2) criteria. The patients were also classified as having PD/non-PD according to the clinical and prostate-specific antigen (PSA) responses.RESULTS: There was no difference between NaF PET/CT and BS in the detection of PD and non-PD during treatment (McNemar's test, p = .18). The agreement between BS and NaF PET/CT for PD/non-PD was moderate (Cohen's kappa 0.53, 95% confidence interval 0.26-0.79). Crude agreement between BS and NaF PET/CT for the assessment of PD/non-PD was 86% (89% for ADT, n = 28; 88% for NGH, n = 16, and 80% for chemotherapy, n = 20). In most discordant cases, BS found PD when NaF PET/CT did not, or BS detected PD on an earlier scan than NaF PET/CT. Biochemical progression (27%) occurred more frequently than progression on functional imaging (BS, 22% and NaF PET/CT, 14%). Clinical progression was rare (11%), and almost exclusively seen in patients receiving chemotherapy.CONCLUSION: There was no difference between NaF PET/CT and BS in the detection of PD and non-PD; however, BS seemingly detects PD by the PCWG-2 criteria earlier than NaF-PET, which might be explained by the fact that NaF-PET is more sensitive at the baseline scan.

Incidental focal uptake of 18F-fluorodeoxyglucose (FDG) in the thyroid on positron emission tomography (PET/CT) is rare but often associated with malignancy. The epidemiology of thyroid incidentalomas has only to some extent been described in countries with iodine deficiency. Here we report data from Denmark, a country with known iodine deficiency and wide access to PET/CT. All FDG PET/CT comprising the head and neck region, during 2014, were retrospectively reviewed, and patients with focal FDG uptake in the thyroid gland were identified. A total of 2451 patients had an FDG PET/CT of which 59 (2.4%) patients presented with FDG-avid focal lesions in the thyroid gland. Among the 59 patients with FDG-avid lesions, 33 patients (56%) received work up with ultrasound, thyroid technetium scintigraphy, fine needle aspiration, and/or histology of which 20 patients had a conclusive pathology report. Ten patients with FDG-avid lesions were identified with thyroid malignancy. The risk of thyroid malignancy was 16.9% among patient with incidental FDG-avid thyroid lesions. Our findings indicated a similar frequency of FDG thyroid incidentalomas and malignancy rates in an iodine deficient population compared to summary data from prior studies, studies mostly performed in geographical areas of normal or excess iodine supplementation.

In horses, pathological healing with formation of exuberant granulation tissue (EGT) is a particular problem in limb wounds, whereas body wounds tend to heal without complications. Chronic inflammation has been proposed to be central to the pathogenesis of EGT. This study aimed to investigate levels of inflammatory acute phase proteins (APPs) in interstitial fluid from wounds in horses. A novel approach for absolute quantification of proteins, selected reaction monitoring (SRM)-based mass spectrometry in combination with a quantification concatamer (QconCAT), was used for the quantification of five established equine APPs (fibrinogen, serum amyloid A, ceruloplasmin, haptoglobin, and plasminogen) and three proposed equine APPs (prothrombin, α-2-macroglobulin, and α-1-antitrypsin). Wound interstitial fluid was recovered by large pore microdialysis from experimental body and limb wounds from five horses at days 1, 2, 7, and 14 after wounding and healing without (body) and with (limb) the formation of EGT. The QconCAT included proteotypic peptides representing each of the protein targets and was used to direct the design of a gene, which was expressed in Escherichia coli in a media supplemented with stable isotopes for metabolically labeling of standard peptides. Co-analysis of wound interstitial fluid samples with the stable isotope-labeled QconCAT tryptic peptides in known amounts enabled quantification of the APPs in absolute terms. The concentrations of fibrinogen, haptoglobin, ceruloplasmin, prothrombin, and α-1-antitrypsin in dialysate from limb wounds were significantly higher than in dialysate from body wounds. This is the first report of simultaneous analysis of a panel of APPs using the QconCAT-SRM technology. The microdialysis technique in combination with the QconCAT-SRM-based approach proved useful for quantification of the investigated proteins in the wound interstitial fluid, and the results indicated that there is a state of sustained inflammation in equine wounds healing with formation of EGT.

Objective Cutaneous hyperalgesia is prominent in the ultraviolet-B (UVB) model of inflammatory pain. This study investigated possible interactions between cutaneous and deep tissues hyperalgesia. Methods A total of 16 healthy volunteers participated in the study. Skin inflammation was induced unilaterally by UVB irradiation (three times of the individual minimal erythema dose) in square-shaped areas on the upper-trapezius and lower-back. Moderate delayed onset muscle soreness (DOMS) was induced bilaterally in the low-back by eccentric exercise. Cutaneous blood flow, mechanical thresholds, pressure pain thresholds (PPTs), temporal summation to repetitive pressure stimulation, and stimulus-response functions (SR curve) relating graded pressure stimulations and pain intensity were measured within and outside the irradiated areas, before and 24 hours after irradiation and eccentric muscle exercise. Results Compared with baseline (P < 0.05): the assessments 24 hours after irradiation demonstrated: 1) increased superficial blood flow inside and outside the irradiated areas and in the DOMS site; 2) reduced mechanical thresholds within the irradiated areas; 3) left-shifted SR curve function within and outside the irradiated areas; and 4) facilitated temporal summation of pain inside the irradiated areas and in the DOMS site. There was no significant influence of muscle hyperalgesia on skin measures in normal or UVB-inflamed skin. Conclusions Moderate degrees of muscle sensitization could not facilitate UVB-induced cutaneous mechanical sensitivity, whereas UVB-induced neurogenic inflammation is enhanced when the DOMS is present.

OBJECTIVE: The aim of the study was to assess the agreement in the interpretation of bone scintigraphy (BS) in a newly diagnosed prostate cancer.MATERIALS AND METHODS: A total of 635 consecutive patients had their planar whole-body BS independently reviewed by three nuclear medicine physicians and classified by two grading systems: (a) a four-category scale (1: benign; 2: equivocal; 3: most likely malignant; and 4: multiple metastases) and (b) a dichotomous scale (bone metastasis present or absent).RESULTS: Agreement in the same category, or with one or two categories of differences, was found in 66, 34, and 1.3% of the readings, respectively. Average κ-values were 0.59, 0.72, and 0.83 for unweighted, linear, and quadratic weighted variants, respectively. Very high agreement was observed (96% of the readings) with the dichotomous scale (average κ=0.87); a comparison with a final imaging diagnosis with additional CT or MRI showed a sensitivity of 83% and a specificity of 98%. BS categories 1, 3, and 4 were consistent with the final imaging diagnosis in 96-99% of cases. The prevalence of metastasis was 10% in category 2. To optimize the diagnostic characteristics, category 2 should be regarded as a separate option.CONCLUSION: Close agreement was found among trained observers for the evaluation of BS in prostate cancer. The high level of agreement with a dichotomous scale was hampered by diagnostic misclassification. A scale with equivocal findings on planar BS is considered important to allow for additional imaging and correct staging at the bone level of BS in a population with newly diagnosed prostate cancer.

BACKGROUND: Filaggrin is key for the integrity of the stratum corneum. Mutations in the filaggrin gene (FLGnull) play a prominent role in the atopic dermatitis (AD) pathogenesis. Persons with AD have an increased susceptibility to irritants. However, little is known about the effect of filaggrin genotype and AD phenotype concerning irritant response and skin regeneration.OBJECTIVES: To investigate the role of FLGnull and AD concerning skin reaction and recovery after Sodium Lauryl Sulfate (SLS) irritation.METHODS: Case-control study comprising 67 subjects, including healthy controls and patients with and without FLGnull and AD. Reactivity to different doses of SLS at 24, 48, 72 and 145 hours after SLS application was measured by transepidermal water loss (TEWL) and laser Doppler flowmetry (LDF). Reactivity was assessed univariately and by pattern analysis technique.RESULTS: All patient groups showed a higher degree of skin barrier disruption and inflammation than did controls in response to SLS. Assessing reactivity by ∆AUC both TEWL and LDF showed significant difference between healthy controls and those with the AD phenotype irrespective of filaggrin mutation. The poorest regeneration was among those with the AD phenotype. The two AD phenotype groups were separated by multivariate technique, due to earlier inflammatory reactivity among subjects with FLGnullplusAD compared to the AD phenotype alone.CONCLUSIONS: Both skin reaction and regeneration was significantly different between the patient population and the healthy controls. Additionally, response severity and regeneration depended more on phenotype (atopic dermatitis) than on filaggrin genotype, whereas the response was more rapid among FLGnullplusAD individuals. This article is protected by copyright. All rights reserved.

Purpose: To prospectively compare diagnostic accuracies for detection of bone metastases by 68Ga-PSMA PET/CT, 18F-NaF PET/CT and diffusion-weighted MRI (DW 600-MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR). Methods: Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent 68Ga-PSMA PET/CT, a 18F-NaF PET/CT and a DW 600-MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm 2). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic. Results: Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98–1.00 and 0.89–0.90 for 68Ga-PSMA PET/CT (n = 68 patients); 0.90, 0.90–0.98 and 0.90–0.94 for 18NaF PET/CT (n = 67 patients); and 0.25–0.38, 0.87–0.92 and 0.59–0.62 for DW 600-MRI (n = 60 patients). The diagnostic performance of DW 600-MRI was significantly lower than that of 68Ga-PSMA PET/CT and 18NaF PET/CT for diagnosing bone metastases (p < 0.01), and no significant difference in the AUC was seen between 68Ga-PSMA PET/CT and 18NaF PET/CT (p = 0.65). Conclusion: 68Ga-PSMA PET/CT and 18F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW 600-MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

Bone scintigraphy is key in imaging skeletal metastases in newly diagnosed prostate cancer. Unfortunately, a notable proportion of scans are not readily classified as positive or negative but deemed indeterminate. The extent of reporting of indeterminate bone scans and how such scans are handled in clinical trials are not known. A systematic review was conducted using electronic databases up to October 2016. The main outcome of interest was the reporting of indeterminate bone scans, analyses of how such scans were managed, and exploratory analyses of the association of study characteristics and the reporting of indeterminate bone scan results. Seventy-four eligible clinical trials were identified. The trials were mostly retrospective (85%), observational (95%), large trials (median 195 patients) from five continents published over four decades. The majority of studies had university affiliation (72%), and an author with imaging background (685). Forty-five studies (61%) reported an indeterminate option for the bone scan and 23 studies reported the proportion of indeterminate scans (median 11.4%). Most trials (44/45, 98%) reported how to handle indeterminate scans. Most trials (n = 39) used add-on supplementary imaging, follow-up bone scans, or both. Exploratory analyses showed a significant association of reporting of indeterminate results and number of patients in the study (p = 0.024) but failed to reach statistical significance with other variables tested. Indeterminate bone scan for staging of prostate cancer was insufficiently reported in clinical trials. In the case of indeterminate scans, most studies provided adequate measures to obtain the final status of the patients.

BACKGROUND: (68) Ga-labelled prostate-specific membrane antigen (PSMA) is a promising PET ligand for the detection of prostate cancer. Little attention has been given to the ability of (68) Ga-PSMA PET/CT to detect malignant bone lesions and whether this approach is superior to existing bone imaging modalities.AIM: To review the existing data of (68) Ga-PSMA PET/CT for the diagnosis of bone metastases in prostate cancer.METHODS: Systematic review of the peer-reviewed literature.RESULTS: Among 1858 papers in the original search, 37 papers were included in the analysis (six case reports and 31 case series). The vast majority of the studies were low-level evidence studies. Most studies presented data on detection rates without a reference standard. All but two studies were of a retrospective nature. Several cohort studies showed bone metastasis in 5-60% of patients with prostate cancer, including in patients with very low-PSA values. For primary staging, (68) Ga-PSMA PET/CT outperformed bone scans, while the superiority of (68) Ga-PSMA PET/CT compared with bone scans with respect to biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC) remains to be demonstrated.CONCLUSION: (68) Ga-PSMA PET/CT has shown to be a promising technique for use in prostate cancer. (68) Ga-PSMA PET/CT shows more lesions than bone scans, but data on diagnostic performance are very limited and indicate improved diagnostic performance in primary staging but not in mCRPC. Properly designed studies are needed to clarify the diagnostic performance of (68) Ga-PSMA PET/CT as well as its superiority over existing methods before (68) Ga-PSMA PET/CT can be routinely used for bone imaging.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.urology.2017.05.060. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Localization of prostate cancer recurrence, particularly in the bones, is a major challenge with standard of care imaging in patients with biochemical recurrence following curatively intended treatment. Gallium-68-labeled prostate specific membrane antigen positron emission tomography/computed tomography ((68)Ga-PSMA PET/CT) is a novel and promising method for imaging in prostate cancer. The present study reports two cases of patients with prostate cancer with biochemical recurrence, with evidence of bone metastases on (68)Ga-PSMA PET/CT images and low prostate specific antigen PSA levels (6 months. The bone metastases were verified by supplementary imaging with (18)F-sodium fluoride PET/CT and magnetic resonance imaging as well as biochemical responses to androgen deprivation therapy. Therefore, (68)Ga-PSMA PET/CT is promising for the restaging of patients with prostate cancer with biochemical recurrence, including patients with low PSA levels and low PSA kinetics.

PURPOSE The aim of this study was to evaluate the clinical safety profile of the Ga-PSMA-11 ligand for PET/CT imaging in prospective clinical trials. METHODS Eighty-eight patients with newly diagnosed or recurrent prostate cancer participated in 2 prospective trials. Safety reporting was identical in the 2 trials. The Ga-PSMA-11 ligand was administered as 2 MBq/kg body weight (mean, 9.2 μg, 9.7 nmol). The reporting of clinical adverse events (AEs) and the measurement of blood pressure (BP) and heart rate (HR) were performed prior to injection (baseline); immediately after injection of Ga-PSMA-11 (postinjection); at 1, 10, and 60 minutes after injection; and after acquisition of the PET/CT scan (postscan). All hemodynamic assessments were performed in the supine position, except for the postscan measurement (sitting). The patients were interviewed regarding any AEs at baseline, postinjection, or postscan. In addition, the patients were instructed to report any AEs during the investigation and to contact the investigator if AEs occurred during the rest of the day. Adverse events were classified as mild, moderate, or severe by the patients and categorized by the investigator using the CTCAE (Common Terminology Criteria for Adverse Events) version 4.0. RESULTS There were no reported clinical AEs. There were significant decreases in systolic BP (P < 0.001) and HR (P < 0.001) over time. In comparison, the diastolic BP increased significantly (P < 0.001). After removal of the last observation (supine position), there was no time-dependent change in systolic or diastolic BP, but the significant change in HR remained. The mean changes over the entire observation period were minimal (systolic BP, -6 to 5 mm Hg; diastolic BP, -2 to 3 mm Hg; HR, decrease of 5 beats/min). No patients developed hypotension. Fifty-five patients presented with hypertension at baseline, which increased by 1 CTCAE grade in 15 patients and by 2 grades in 2 patients. A large number of cases of asymptomatic (grade 1) bradycardia were observed, primarily in patients with preexisting bradycardia. One patient developed transient grade 1 tachycardia. No patients required medical intervention for cardiovascular perturbations. CONCLUSIONS Ga-PSMA-11 PET/CT was very well tolerated. We consider Ga-PSMA-11 to be safe for human application.

As in other fibroproliferative disorders, hypoxia has been suggested to play a key role in the pathogenesis of exuberant granulation tissue (EGT). The purpose of this study was to investigate metabolism and blood flow locally in full-thickness wounds healing with (limb wounds) and without (body wounds) formation of EGT. Microdialysis was used to recover endogenous metabolites from the wounds, and laser Doppler flowmetry was used to measure blood flow. Measurements were performed before wounding and 1-28 days after wounding. Blood flow was consistently lower in limb wounds than in body wounds throughout the study period with no change over time. After wounding and throughout the study period, the glucose concentration was significantly lower in limb wounds than in body wounds, whereas the lactate level showed a significantly higher concentration in limb wounds. The lactate/glucose ratio displayed a significant difference between body and limb wounds. In conclusion, the metabolic disturbances may suggest an inadequate oxygen supply during the wound healing process in equine limb wounds healing with EGT. This may be related to the inherently decreased perfusion in the wound bed of limb wounds.

Topical capsaicin is a well-established model of experimental hyperalgesia. Its application to the study of animals has been limited to few species. The effect of topical capsaicin on hyperalgesia in porcine skin was evaluated as part of a study of inflammatory pain in the pig. Two experiments were carried out on pigs of 27 ± 5 kg (n = 8) and 57 ± 3 kg (n = 16). Thermal and mechanical noxious stimuli were provided (CO2 laser and Pressure Application Measurement device) to assess avoidance behaviours. Capsaicin induced significant thermal hyperalgesia in the smaller pigs (P

Laser Doppler imaging (LDI) and laser Doppler flowmetry (LDF) can measure localized skin perfusion. The purpose of the study was to directly compare LDF with LDI as a tool for measuring skin blood changes in an experimental model of chemically-induced skin inflammation. Regions of interest 1.8 cm2 in area on the forearm skin of eight healthy volunteers were randomized and exposed to 0.25, 0.5, 1, or 2 % topical sodium lauryl sulfate (SLS) or vehicle for 24 h. Mean blood flow was measured by LDI and LDF at 24, 48, and 72 h. Inflammation was clinically graded using a standardized, clinical score. Sodium lauryl sulfate induced significant, dose-dependent local inflammation. Both Doppler methods were significantly correlated with the clinical grading (LDF, r = 0.755; LDI, r = 0.836). LDF and LDI showed similar significance differences with regard to dose- and time-response patterns compared to the vehicle. The absolute and relative LDF and LDI values were significantly correlated. Laser Doppler flowmetry and LDI showed similar dose- and time-response relations in irritant-induced inflammatory skin reactions. For the assessment of localized skin reactions, LDI possesses no apparent advantages over the less expensive LDF method for grading dermal inflammatory reactions.

Microdialysis is a method for sampling compounds from extracellular fluid with minimal tissue trauma. Small hollow probes that are 0.2-0.5mm in diameter are inserted into the tissue and slowly perfused. The probe membrane is semi-permeable and a flux of the solutes occurs exclusively according to the concentration gradients. The recovered dialysate reflects changes in the composition of the extracellular water phase with a minor time delay. Because microdialysis is a continuous sampling method, it differs from point sample methods, such as blood sampling. The ability to obtain local measurements in the tissues has led to important discoveries in the detection of tissue changes within the areas of pharmacokinetics, pharmacodynamics, pathology and pathophysiology. New technological solutions, such as transportable pumps, fluid collectors and bedside analysers, have made microdialysis an indispensable tool for the surveillance of critically ill human patients, such as after brain injuries and reconstructive surgeries. The use of microdialysis in equine medicine has been sparingly described with only 14 published studies within muscle, pulmonary and hoof lamellar tissue, nasal mucosa, intestinal wall, uterine, allantoic and cerebrospinal fluid and blood. Only a few papers have been published within each area, indicating that few equine researchers are aware of the unique opportunities provided by the technique. This review discusses the theory and applications of microdialysis with a special emphasis on clinical and experimental equine studies, which may be useful to veterinary experimental and clinical researchers.

Background Among the current translational inflammatory pain models, the ultraviolet (UV) irradiation is of rapidly growing interest. The development of primary thermal and mechanical hyperalgesia has been observed in humans and rodents. The pig as a translational animal model might be advantageous due to its great homology with humans. Methods The skin in the flank of awake pigs was irradiated by a UV-B light source (1 J/cm2) and changes in thermal and mechanical sensitivity 24 and 48 h following irradiation were measured via assessment of nociceptive behaviours. Results Thermal sensitivity increased significantly within the inflamed site 24 h after irradiation as indicated by the reduction of latency to respond to thermal stimulation from baseline to 24 h (P

Mercury-in-silastic strain gauge pletysmography (SGP) is a well-established technique for blood flow and blood pressure measurements. The aim of this study was to examine (i) the possible influence of clinical clues, e.g. the presence of wounds and color changes during blood pressure measurements, and (ii) intra- and inter-observer variation of curve interpretation for segmental blood pressure measurements.A total of 204 patients with known or suspected peripheral arterial disease (PAD) were included in a diagnostic accuracy trial. Toe and ankle pressures were measured in both limbs, and primary observers analyzed a total of 804 pressure curve sets. The SGP curves were later reanalyzed separately by two observers blinded to clinical clues. Intra- and inter-observer agreement was quantified using Cohen's kappa and reliability was quantified using intra-class correlation coefficients, coefficients of variance, and Bland-Altman analysis.There was an overall agreement regarding patient diagnostic classification (PAD/not PAD) in 202/204 (99.0%) for intra-observer (κ = 0.969, p0.001), and 201/204 (98.5%) for inter-observer readings (κ = 0.953, p0.001). Reliability analysis showed excellent correlation between blinded versus non-blinded and inter-observer readings for determination of absolute segmental pressures (all intraclass correlation coefficients ≥ 0.984). The coefficient of variance for determination of absolute segmental blood pressure ranged from 2.9-3.4% for blinded/non-blinded data and from 3.8-5.0% for inter-observer data.This study shows a low inter-observer variation among experienced laboratory technicians for reading strain gauge curves. The low variation between blinded/non-blinded readings indicates that SGP measurements are minimally biased by clinical clues.

Purpose The aim of this study was to assess observer agreement on the evaluation of treatment responses of bone metastases by bone scintigraphy (BS) using different scoring methods in prostate cancer patients. Patients and methods Sixty-three paired BS from 55 patients were included. BS was performed before and after more than 12 weeks of anticancer treatment. A panel of experienced nuclear medicine physicians from several institutions evaluated treatment response using three different methods: (a) standard clinical assessment, (b) MD Anderson criteria, and (c) Prostate Cancer Working Group 2 (PCWG-2) criteria. All methods were based on the evaluation of paired before-after bone scans. Results Readers were able to classify the presence of bone metastases at baseline with a high level of agreement [Cohen's κ=0.94, 95% confidence interval (CI) 0.82-1.00]. Observer agreement on bone response by PCWG-2 criteria showed considerable agreement (Cohen's κ=0.84, 95% CI: 0.69-0.99). Evaluation using standard clinical assessment and MD Anderson criteria showed moderate agreement (0.52, 95% CI: 0.36-0.69 and 0.64, 95% CI: 0.48-0.79, respectively). There was considerable variation among readers for regional lesion count on individual scans, with limits of agreement of -10 to 10 lesions or more for the majority of anatomical regions, including the thorax, spine, and pelvis. Conclusion Observer agreement on treatment response by BS varied notably across methods. Optimal agreement was achieved by the PCWG-2 criteria. Variation in the classification of treatment response of bone metastases may have a significant impact on clinical decision-making, emphasizing the need for a uniform approach, including during clinical practice. Response assessment by lesion counting on repeated BS without access to previous scans cannot be recommended. Fil: Fonager, Randi F.. Aalborg University; Dinamarca Fil: Zacho, Helle D.. Aalborg University; Dinamarca Fil: Albertsen, Signe. Aalborg University; Dinamarca Fil: Fledelius, Joan. Herning Hospital; Dinamarca Fil: Ejlersen, June A.. Herning Hospital; Dinamarca Fil: Christensen, Mette H.. Viborg Regional Hospital; Dinamarca Fil: Aleksyniene, Ramune. Aalborg University; Dinamarca Fil: Biurrun Manresa, José Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Aalborg University; Dinamarca Fil: Petersen, Lars J.. Viborg Regional Hospital; Dinamarca

The European Association of Urology (EAU), along with most other urological guidelines, recommends bone scintigraphy and aortoabdominal computed tomography (CT) or magnetic resonance imaging for st...

Treatment with bone-seeking radionuclides may provide palliation from pain originating from bone metastases. However, most studies have been conducted in patients with prostate cancer and patients with breast cancer. We aimed to perform a systematic review of the use of radionuclide treatment in lung cancer in accordance with the PRISMA guidelines. In the eligible trials, pain relief was reported in 75% of the patients included in the studies. The onset of pain relief was seen within 1-5 weeks after treatment, lasting up to 6 months. However, the methodology in the included trials was poor-only two randomised trials were eligible, and none of them compared radionuclide treatments with placebo or best standard of care. The remaining trials were case series with inherent problems of methodology reporting. Particularly challenging was the lack of reporting of baseline disease status and use of prior/concomitant analgaesics. Large randomised controlled trials are needed to clarify the efficacy of radionuclide treatment in lung cancer.

Ga-PSMA PET/CT is becoming the most promising imaging modality for detecting recurrent prostate cancer. The modality has the advantage of being able to detect recurrent disease, even at very low prostate-specific antigen levels. However, several studies report Ga-PSMA uptake in tissue unrelated to prostate cancer. We present a 74-year-old man who underwent Ga-PSMA PET/CT for recurrent prostate cancer 5 years after radical prostatectomy. The Ga-PSMA PET/CT showed an intramuscular lesion with increased PSMA uptake in the left vastus medialis muscle. The lesion was surgically removed, and histopathology found it to be an intramuscular myxoma that showed immunohistochemical PSMA expression.

ObjectiveTo assess the accuracy of a fully automated portable device (APD) for diagnosing peripheral arterial disease (PAD) by measuring the toe–brachial index (TBI) and using mercury-in-silastic, strain-gauge plethysmography (SGP) as reference.DesignProspective, randomised, double-blinded diagnostic accuracy study.Materials and methodsA total of 204 consecutive patients with known or suspected PAD were randomly assigned to measurement of TBI by the portable device followed by the SGP technique or the opposite sequence. Finally, ankle–brachial index (ABI) was assessed by SGP.ResultsThe APD showed a sensitivity of 98.8%, a specificity of 61.0%, a positive predictive value of 91.0% and a negative predictive value of 92.6% for detecting PAD compared to a full SGP test comprised of ABI and TBI. According to the SGP test, 35 patients (17.2%) had an ABI > 0.90 but a TBI

BACKGROUND: Dynamic mechanical allodynia is traditionally induced by manual brushing of the skin. Brushing force and speed have been shown to influence the intensity of brush-evoked pain. There are still limited data available with respect to the optimal stroke number, length, force, angle and speed. Therefore, an automated brushing device (ABD) was developed, for which brushing angle and speed could be controlled to enable quantitative assessment of dynamic mechanical allodynia.OBJECTIVES: To compare the ABD with manual brushing using capsaicin-induced allodynia, and to investigate the role of stroke angle and speed on pain intensity.METHODS: Experimental dynamic mechanical allodynia was induced by an intradermal injection of capsaicin (100 μg) into the volar forearm of 12 healthy, male volunteers. Dynamic mechanical allodynia was rated on a 10 cm visual analogue scale (VAS) after each set of strokes at angles of 30°, 60° and 90° with speeds of 17 mm/s, 21 mm/s and 25 mm/s for each angle. A two-way ANOVA with repeated measures was performed to assess the influence of brushing parameters. To evaluate test-retest reliability, Bland-Altman 95% limits of agreement, including a coefficient of repeatability and an intraclass correlation coefficient (ICC), were determined.RESULTS: The angle and speed exhibited a significant impact on pain intensity (PCONCLUSIONS: A controlled, automatic brushing method can be used for quantitative investigations of allodynic reactions, and is more reliable for quantitative assessment of dynamic mechanical allodynia compared with traditional manual brushing.

Ga-PSMA PET/CT is increasingly used to assess prostate cancer. Avid Ga-PSMA uptake by thyroid cancer and renal cell carcinoma (RCC) has been reported in few cases. A 75-year-old man who received a diagnosis of RCC in 2006 and prostate cancer in 2009 presented with elevated prostate-specific antigen levels (0.7 ng/mL) following prostatectomy. Ga-PSMA PET/CT showed avid Ga-PSMA uptake in 1 pelvic and 1 retroperitoneal lymph node and focal Ga-PSMA accumulation in the thyroid. Excised retroperitoneal lymph node and thyroid tissues showed metastases from RCC, whereas the pelvic lymph node exhibited metastasis from prostate cancer.