Coronary Physiological Indices to Evaluate Myocardial Ischemia in Patients with Aortic Stenosis Undergoing Valve Replacement.

BACKGROUND: Evaluation of myocardial ischemia in patients with aortic valve stenosis (AS) with concomitant coronary artery disease (CAD) and possible microvascular dysfunction (MVD) is challenging because fractional flow reserve (FFR) and resting full-cycle ratio (RFR) have not been validated in this clinical setting. OBJECTIVES: The objectives of this study in patients with AS and CAD are: 1. to describe the relationship between hyperemic and resting indices. 2. to investigate the acute and long-term effects of aortic valve replacement (AVR) on epicardial indices and microvascular function. 3. To assess the impact of these changes on clinical decision making. 4. To determine FFR/RFR ischemia cut-off points in AS. METHODS: In this prospective multicentric study, we performed serial measurements of FFR, RFR, and evaluated MVD by means of coronary flow reserve (CFR), the index of microvascular resistance (IMR) and microvascular resistance reserve (MRR) in patients with severe AS and intermediate-to-severe CAD, before and six months after AVR. Patients underwent myocardial perfusion single-photon emission computed tomography (SPECT) before AVR. RESULTS: In total, 146 coronary lesions in 116 patients were included. Before AVR, we observed high FFR/RFR discordance according to standard cut-off values: FFR-negative (>0.80)/RFR-positive (≤0.89) in 42.3% (68/137) of these lesions. Acutely after AVR, FFR decreased significantly (-0.0120 ± 0.0192, p=0.0045) while RFR remained stable (0.0140 ± 0.0673, p=0.3089). Six months after AVR, FFR decreased (-0.0279±0.0368) while RFR increased significantly (+0.0410±0.0487) (p<0.0001 for both), resulting in 21.5% (21/98) and 39.8% (39/98) of lesions crossing traditional FFR and RFR cut-off lines, respectively. LV-mass decreased significantly (153.68g ± 44.22 before vs 134.66g ± 37.26 after, p<0.0001). MVD was frequently observed at baseline (32.1% abnormal IMR; 68.6% abnormal MRR) with all microvascular parameters improving after AVR. Most accurate cut-offs to predict ischemia were FFR ≤0.83 and RFR ≤0.85 with comparable accuracy (75-80%). CONCLUSIONS: In patients with severe AS and CAD, FFR ≤0.83 and RFR ≤0.85 appear to predict myocardial ischemia more accurately. Six months after AVR, FFR decreases while RFR increases significantly, with simultaneous decrease of LV mass and improvement of microvascular function.

Advanced imaging shows extra-articular abscesses in two out of three adult patients with septic arthritis of the native hip joint.

Background: Septic arthritis (SA) of the native adult hip is a rare orthopaedic emergency requiring prompt diagnosis and treatment. As clinical presentation and laboratory findings are frequently atypical, advanced imaging is often requested. This retrospective study aimed to investigate the prevalence and pattern of extra-articular infectious manifestations and their implications for pre-operative advanced imaging in patients with proven SA of the native hip joint. Methods: Out of 41 patients treated surgically for SA of the native hip during a 16-year period at our tertiary referral hospital, 25 received advanced imaging (computed tomography (CT), magnetic resonance imaging (MRI), or fluorodeoxyglucose positron emission tomography (FDG PET-CT)) prior to initial intervention. For each investigation, a specific set of variables was systematically interpreted, and the most suitable surgical approach was determined. The prognostic value was evaluated by comparing specific outcome measures and the extent of extra-articular involvement. Results: It was found that 32 % of patients had an abscess in one anatomical region, 32 % of patients had abscesses in multiple anatomical regions, and only 36 % of patients had no substantial abscess. Gluteal abscesses were especially common in patients with SA due to contiguous spread. Abscesses in the iliopsoas region were more common in patients with SA due to hematogenous seeding. A combination of several different surgical approaches was deemed necessary to adequately deal with the various presentations. No significant prognostic factors could be identified. Conclusion: We recommend performing advanced imaging in patients with suspected or proven septic arthritis of the native hip joint, as extra-articular abscesses are present in 64 % and might require varying anatomical approaches.

Standardized 4-point scoring scale of [18F]-FDG PET/CT imaging helps in the diagnosis of renal and hepatic cyst infections in patients with autosomal dominant polycystic kidney disease: a validation cohort.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is prone to multiple complications, including cyst infection (CyI). 2-Deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) imaging has proved useful in the diagnosis of renal and hepatic CyI. A 4-point scale comparing the uptake of [18F]-FDG in the suspected infected cyst versus the hepatic physiological background has been recently proposed. We performed an independent validation of this semi-quantitative scoring system. Methods: All ADPKD patients hospitalized between January 2009 and November 2019 who underwent an [18F]-FDG PET/CT for suspected CyI were retrospectively identified using computer-based databases. Medical files were reviewed. CyI was conventionally defined by the combination of fever (≥38°C), abdominal pain, increased plasma C-reactive protein levels (≥70 mg/L), absence of any other cause of inflammation and favourable outcome after ≥21 days of antibiotics. [18F]-FDG uptake of the suspected CyI was evaluated using a 4-point scale comparing the uptake of [18F]-FDG around the infected cysts with the uptake in the hepatic parenchyma. Statistics were performed using SAS version 9.4. Results: Fifty-one [18F]-FDG PET/CT scans in 51 patients were included, of which 11 were cases of CyI. The agreement between the 4-point scale and the gold-standard criteria of CyI was significant [odds ratio of 6.03 for CyI in case of a score ≥3 (P = .014)]. The corresponding sensitivity, specificity, and positive and negative predictive values of [18F]-FDG PET/CT using the 4-point scale were 64% [Clopper-Pearson 95% confidence interval (CI) 30%-89%], 78% (95% CI 62%-89%), 44% (95% CI 20%-70%) and 89% (95% CI 73%-97%), respectively. Conclusions: Our independent validation cohort confirms the use of a semi-quantitative 4-point scoring system of [18F]-FDG PET/CT imaging in the diagnosis of CyI in patients with ADPKD. Considering its performance metrics with high specificity and negative predictive value, the scoring system is particularly useful to distinguish other causes of clinical inflammation than CyI and as such avoid unnecessarily long antibiotic treatment.

A multi-label CNN model for the automatic detection and segmentation of gliomas using [18F]FET PET imaging.

PURPOSE: The aim of this study was to develop a convolutional neural network (CNN) for the automatic detection and segmentation of gliomas using [18F]fluoroethyl-L-tyrosine ([18F]FET) PET. METHODS: Ninety-three patients (84 in-house/7 external) who underwent a 20-40-min static [18F]FET PET scan were retrospectively included. Lesions and background regions were defined by two nuclear medicine physicians using the MIM software, such that delineations by one expert reader served as ground truth for training and testing the CNN model, while delineations by the second expert reader were used to evaluate inter-reader agreement. A multi-label CNN was developed to segment the lesion and background region while a single-label CNN was implemented for a lesion-only segmentation. Lesion detectability was evaluated by classifying [18F]FET PET scans as negative when no tumor was segmented and vice versa, while segmentation performance was assessed using the dice similarity coefficient (DSC) and segmented tumor volume. The quantitative accuracy was evaluated using the maximal and mean tumor to mean background uptake ratio (TBRmax/TBRmean). CNN models were trained and tested by a threefold cross-validation (CV) using the in-house data, while the external data was used for an independent evaluation to assess the generalizability of the two CNN models. RESULTS: Based on the threefold CV, the multi-label CNN model achieved 88.9% sensitivity and 96.5% precision for discriminating between positive and negative [18F]FET PET scans compared to a 35.3% sensitivity and 83.1% precision obtained with the single-label CNN model. In addition, the multi-label CNN allowed an accurate estimation of the maximal/mean lesion and mean background uptake, resulting in an accurate TBRmax/TBRmean estimation compared to a semi-automatic approach. In terms of lesion segmentation, the multi-label CNN model (DSC = 74.6 ± 23.1%) demonstrated equal performance as the single-label CNN model (DSC = 73.7 ± 23.2%) with tumor volumes estimated by the single-label and multi-label model (22.9 ± 23.6 ml and 23.1 ± 24.3 ml, respectively) closely approximating the tumor volumes estimated by the expert reader (24.1 ± 24.4 ml). DSCs of both CNN models were in line with the DSCs by the second expert reader compared with the lesion segmentations by the first expert reader, while detection and segmentation performance of both CNN models as determined with the in-house data were confirmed by the independent evaluation using external data. CONCLUSION: The proposed multi-label CNN model detected positive [18F]FET PET scans with high sensitivity and precision. Once detected, an accurate tumor segmentation and estimation of background activity was achieved resulting in an automatic and accurate TBRmax/TBRmean estimation, such that user interaction and potential inter-reader variability can be minimized.

[18F] MFBG PET imaging: biodistribution, pharmacokinetics, and comparison with [123I] MIBG in neural crest tumour patients.

PURPOSE: Despite its limitations, [123I]MIBG scintigraphy has been the standard for human norepinephrine transporter (hNET) imaging for several decades. Recently, [18F]MFBG has emerged as a promising PET alternative. This prospective trial aimed to evaluate safety, biodistribution, tumour lesion pharmacokinetics, and lesion targeting of [18F]MFBG and perform a head-to-head comparison with [123I]MIBG in neural crest tumour patients. METHODS: Six neural crest tumour patients (4 phaeochromocytoma, 1 paraganglioma, 1 neuroblastoma) with a recent routine clinical [123I]MIBG scintigraphy (interval: - 37-75 days) were included. Adult patients (n = 5) underwent a 30-min dynamic PET, followed by 3 whole-body PET/CT scans at 60, 120, and 180 min after injection of 4 MBq/kg [18F]MFBG. One minor participant underwent a single whole-body PET/CT at 60 min after administration of 2 MBq/kg [18F]MFBG. Normal organ uptake (SUVmean) and lesion uptake (SUVmax; tumour-to-background ratio (TBR)) were measured. Regional distribution volumes (VT) were estimated using a Logan graphical analysis in up to 6 lesions per patient. A lesion-by-lesion analysis was performed to compare detection ratios (DR), i.e. fraction of detected lesions, between [18F]MFBG and [123I]MIBG. RESULTS: [18F]MFBG was safe and well tolerated. Its biodistribution was overall similar to that of [123I]MIBG, with prominent uptake in the salivary glands, liver, left ventricle wall and adrenals, and mainly urinary excretion. In the phaeochromocytoma subgroup, the median VT was 37.4 mL/cm3 (range: 18.0-144.8) with an excellent correlation between VT and SUVmean at all 3 time points (R2: 0.92-0.94). Mean lesion SUVmax and TBR at 1 h after injection were 19.3 ± 10.7 and 23.6 ± 8.4, respectively. All lesions detected with [123I]MIBG were also observed with [18F]MFBG. The mean DR with [123I]MIBG was significantly lower than with [18F]MFBG (61.0% ± 26.7% vs. 99.8% ± 0.5% at 1 h; p = 0.043). CONCLUSION: [18F]MFBG is a promising hNET imaging agent with favourable imaging characteristics and improved lesion targeting compared with [123I]MIBG scintigraphy. TRIAL REGISTRATION: Clinicaltrials.gov : NCT04258592 (Registered: 06 February 2020), EudraCT: 2019-003872-37A.

[68Ga]Ga-DOTATATE-avid tumor volume, uptake and inflammation-based index correlate with survival in neuroendocrine tumor patients treated with [177Lu]Lu-DOTATATE PRRT.

To meet the increasing demand for PRRT in the treatment of patients with inoperable/disseminated well-differentiated neuroendocrine tumors (NETs) and to guide optimization strategies, adequate and accessible predictive tools that allow to stratify patients who will benefit from treatment from those who will not are becoming indispensable. Previously, we have investigated the role of baseline [68Ga]Ga-DOTATOC PET tumor uptake and volumetric parameters and a blood-derived inflammatory biomarker, the inflammation-based index (IBI), for outcome prediction in NET patients treated with [90Y]Y-DOTATOC. In this retrospective study in 83 NET patients treated with [177Lu]Lu-DOTATATE in a routine clinical setting, we aimed to evaluate the generalizability of our previous findings to [177Lu]Lu-DOTATATE treatment combined with a pre-therapeutic [68Ga]Ga-DOTATATE PET. A semi-automatic customized SUV threshold-based approach was used for tumor delineation. The previously identified SUVmean cut-off of 13.7 for better survival could not be applied to this patient cohort. Instead, a more optimal cut-off could be identified: an SUVmean lower or equal than 11.2 was associated with worse overall survival (OS) (hazard ratio (HR) 2.28; P = 0.008). Also in line with our previous study, a [68Ga]Ga-DOTATATE-avid tumor volume (TV) higher than 672 mL and an elevated baseline IBI were correlated with worse OS (HR 3.13 (P = 0.0001) and HR 2.00 (P = 0.034), respectively). Multivariate analysis confirmed independent associations between OS and baseline IBI (P = 0.032), SUVmean (P = 0.027) and [68Ga]Ga-DOTATATE-avid TV (P = 0.001). Taking baseline IBI, [68Ga]Ga-DOTATATE-avid TV and [68Ga]Ga-DOTATATE uptake into account may help guide PRRT treatment decisions.

Antiviral treatment with fluoxetine for rituximab-associated chronic echovirus 13 meningoencephalitis and myofasciitis.

BACKGROUND AND PURPOSE: Enterovirus infections pose a serious threat for patients with humoral deficiencies and may be lethal, whilst the efficacy of proposed treatment options such as corticosteroids, intravenous immunoglobulins and fluoxetine remains debated. METHODS: Viral clearance was investigated in a patient with rituximab-induced B-cell depletion and chronic echovirus 13 (E13) meningoencephalitis/myofasciitis in response to intravenous immunoglobulins and fluoxetine using sequential semi-quantitative E13 viral load measurements by real-time reverse transcription polymerase chain reaction. Fluoxetine concentrations in plasma and cerebrospinal fluid were determined by liquid chromatography mass spectrometry. RESULTS: Intravenous immunoglobulins appeared ineffective in this case of E13 infection, whereas virus clearance in cerebrospinal fluid was obtained after 167 days of oral fluoxetine. Since treatment with corticosteroids resulted in a flare of symptoms, rechallenge with viral load measurements was not attempted. CONCLUSION: In this report of a patient with rituximab-associated chronic echovirus 13 meningoencephalitis, viral clearance in response to single treatment options is assessed for the first time. Our observations further support the in vivo efficacy of fluoxetine against enteroviral infections. More research is needed to establish its efficacy in different enterovirus strains.

Value of [68Ga]Ga-somatostatin receptor PET/CT in the grading of pulmonary neuroendocrine (carcinoid) tumours and the detection of disseminated disease: single-centre pathology-based analysis and review of the literature.

BACKGROUND: Although most guidelines suggest performing a positron emission tomography/computed tomography (PET/CT) with somatostatin receptor (SSTR) ligands for staging of pulmonary carcinoid tumours (PC), only a limited number of studies have evaluated the role of this imaging tool in this specific patient population. The preoperative differentiation between typical carcinoid (TC) and atypical carcinoid (AC) and the extent of dissemination (N/M status) are crucial factors for treatment allocation and prognosis of these patients. Therefore, we performed a pathology-based retrospective analysis of the value of SSTR PET/CT in tumour grading and detection of nodal and metastatic involvement of PC and compared this with the previous literature and with [18F]FDG PET/CT in a subgroup of patients. METHODS: SSTR PET/CT scans performed between January 2007 and May 2020 in the context of PC were included. If available, [18F]FDG PET/CT images were also evaluated. The maximum standardized uptake (SUVmax) values of the primary tumour, of the pathologically examined hilar and mediastinal lymph node stations, as well as of the distant metastases, were recorded. Tumoural SUVmax values were related to the tumour type (TC versus AC) for both SSTR and [18F]FDG PET/CT in diagnosing and differentiating both tumour types. Nodal SUVmax values were compared to the pathological status (N+ versus N-) to evaluate the diagnostic accuracy of SSTR PET/CT in detecting lymph node involvement. Finally, a mixed model analysis of all pathologically proven distant metastatic lesions was performed. RESULTS: A total of 86 SSTR PET/CT scans performed in 86 patients with PC were retrospectively analysed. [18F]FDG PET/CT was available in 46 patients. Analysis of the SUVmax values in the primary tumour showed significantly higher SSTR uptake in TC compared with AC (median SUVmax 18.4 vs 3.8; p = 0.003) and significantly higher [18F]FDG uptake in AC compared to TC (median SUVmax 5.4 vs 3.5; p = 0.038). Receiver operating characteristic (ROC) curve analysis resulted in an area under the curve (AUC) of 0.78 for the detection of TC on SSTR PET/CT and of 0.73 for the detection of AC on [18F]FDG PET/CT. A total of 267 pathologically evaluated hilar and mediastinal lymph node stations were analysed. ROC analysis of paired SSTR/[18F]FDG SUVmax values for the detection of metastasis of TC in 83 lymph node stations revealed an AUC of 0.91 for SSTR PET/CT and of 0.74 for [18F]FDG PET/CT (difference 0.17; 95% confidence interval - 0.03 to 0.38; p = 0.10). In a sub-cohort of 10 patients with 12 distant lesions that were pathologically examined due to a suspicious aspect on SSTR PET/CT, a positive predictive value (PPV) of 100% was observed. CONCLUSION: Our findings confirm the higher SSTR ligand uptake in TC compared to AC and vice versa for [18F]FDG uptake. More importantly, we found a good diagnostic performance of SSTR PET/CT for the detection of hilar and mediastinal lymph node metastases of TC. Finally, a PPV of 100% for SSTR PET/CT was found in a small sub-cohort of patients with pathologically investigated distant metastatic lesions. Taken together, SSTR PET/CT has a very high diagnostic value in the TNM assessment of pulmonary carcinoids, particularly in TC, which underscores its position in European guidelines.

Value of 18F-FDG pet/CT for prognostic assessment in patients with infective endocarditis.

BACKGROUND: 18F-FDG PET/CT is a valuable diagnostic tool in infective endocarditis (IE). However, the prognostic value is unclear. This study aims to evaluate the prognostic performance of 18F-FDG PET/CT in native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE). METHODS: We retrospectively included 76 patients treated for definite IE (NVE and PVE) that underwent 18F-FDG PET/CT between January 2016 and December 2018. Clinical, echocardiographic and 18F-FDG PET/CT (pathologic valvular 18F-FDG uptake, extracardiac complications (ECC)) data were collected. The primary endpoint was defined as mortality or recurrence of IE at a one-year follow-up. RESULTS: Pathologic valvular 18F-FDG uptake was detected in 32 of 57 (56.1%) patients, 30% (9/30) in NVE and 85.2% (23/27) in PVE group. Atrial fibrillation (OR 3.90, 95% CI = 1.14-16.3), prior anticoagulation treatment (OR 6.37, 95% CI = 1.89-26.7), large vegetation (≥ 10 mm) (OR 4.05, 95% CI = 1.14-16.1), perivalvular complications (OR 7.22, 95% CI = 1.68-55.1) and abscess (OR 10.9, 95% CI = 1.84-283) were associated with positive PET/CT. Extracardiac complications were found in 27 of 76 (35.5%) patients, 42.9% (18/42) in the NVE and 26.5% (9/34) in the PVE group. Pathological valvular tracer uptake (HR 1.20, 95% CI = 0.43-3.37) or extracardiac complications (HR 0.58, 95% CI = 0.21-1.62) were not associated with the occurrence of the primary endpoint. CONCLUSION: Our study could not demonstrate a prognostic value of 18F-FDG PET/CT in IE, but confirms high diagnostic performance, which may compromise prognostic significance by accelerated optimal treatment because of earlier diagnostic certainty.

Prospective comparison of simultaneous [68Ga]Ga-PSMA-11 PET/MR versus PET/CT in patients with biochemically recurrent prostate cancer.

OBJECTIVES: PSMA-PET has become the PET technique of choice to localise the site of biochemically recurrent prostate cancer (PCa). With hybrid PET/MRI, the advantages of MRI are added to molecular characteristic of PET. The aim of this study was to investigate the incremental value of PET/MR versus PET/CT in patients with biochemically recurrent PCa by head-to-head comparison. METHODS: Thirty-four patients with biochemically recurrent PCa were prospectively included. They underwent [68Ga]Ga-PSMA-11 PET/CT, followed by simultaneous PET/MR. All PET (PETCT, PETMR), CT and MR images were evaluated for number of lesions and location. The number of lesions at specific sites was compared using Wilcoxon-sign-rank test. For PET, the maximum and mean standardised uptake values (SUVs) were calculated for each lesion compared using a two-sided paired t test. RESULTS: PETCT and PETMR scans were positive in 19 and 20 patients, detecting 73 and 79 lesions respectively. All lesions detected on PETCT were also detected on PETMR. CT and MRI only were positive in 14 and 17 patients, detecting 38 and 50 lesions, respectively, which was significantly lower than PETCT and PETMR respectively. Combined interpretation showed more lesions on PET/MR than on PET/CT (88 vs 81). No significant difference in detection of presence of local recurrence nor distant metastases was found. SUVmean and SUVmax values were significantly higher on PETMR than on PETCT in local recurrence and lymph node metastases. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/MR was able to detect biochemically recurrent PCa at least as accurately as PET/CT for local recurrence, lymph node metastasis and distant metastasis. KEY POINTS: • PSMA PET/MRI detects the location of biochemical recurrence at least as accurately as PET/CT. • Substitution of PET/CT by PET/MRI adds sensitivity in PSMA lesion detection also in the setting of distant recurrence due to both the MR and TOF PET components.

The coronary and microcirculatory measurements in patients with aortic valve stenosis study: rationale and design.

Although concomitant coronary artery disease (CAD) is frequent in patients with severe aortic stenosis (AS), hemodynamic assessment of CAD severity in patients undergoing valve replacement for severe AS is challenging. Myocardial hypertrophic remodeling interferes with coronary blood flow and may influence the values of fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). The aim of the current study is to investigate the effect of the AS and its treatment on current indices used for evaluation of CAD. We will compare intracoronary hemodynamics before, immediately after, and 6 mo after aortic valve replacement (AVR) when it is expected that microvascular function has improved. Furthermore, we will compare FFR and resting full-cycle ratio (RFR) with myocardial perfusion single-photon emission-computed tomography (SPECT) as indicators of myocardial ischemia in patients with AS and CAD. One-hundred consecutive patients with AS and intermediate CAD will be prospectively included. Patients will undergo pre-AVR SPECT and intracoronary hemodynamic assessment at baseline, immediately after valve replacement [if transcatheter AVR (TAVR) is chosen], and 6 mo after AVR. The primary end point is the change in FFR 6 mo after AVR. Secondary end points include the acute change of FFR after TAVR, the diagnostic accuracy of FFR versus RFR compared with SPECT for the assessment of ischemia, changes in microvascular function as assessed by the index of microcirculatory resistance (IMR), and the effect of these changes on FFR. The present study will evaluate intracoronary hemodynamic parameters before, immediately after, and 6 mo after AVR in patients with AS and intermediate coronary stenosis. The understanding of the impact of AVR on the assessment of FFR, NHPR, and microvascular function may help guide the need for revascularization in patients with AS and CAD planned for AVR.

18F-FDG PET/CT Sheds Light on a Case of Hyponatremia.

A 76-y-old man with hypoosmolar hyponatremia of unknown origin was referred to the nuclear medicine department for 18F-FDG PET/CT to exclude a malignant cause. Increased 18F-FDG uptake in both adrenal glands was observed and investigated.

Influence of medication and PTH levels on detection of parathyroid adenomas with dual isotope parathyroid scintigraphy.

Localization of parathyroid adenomas is a crucial step to facilitate minimally invasive parathyroidectomy. In this study, we investigated sensitivity and positivity rate of SPECT-based dual isotope parathyroid scintigraphy in detecting parathyroid adenomas, and the effect of medication and parathyroid hormone (PTH)-level on detection of adenomas. Two hundred and thirty-seven patients with primary hyperparathyroidism undergoing dual isotope parathyroid scintigraphy with SPECT-CT in our centre between January 1st 2013 and December 31st 2017 were included in this retrospective study. Sensitivity and positivity rate for accurate location of parathyroid adenomas, based on histopathological findings after surgery and follow-up PTH and calcium, were calculated. The impact of pre-operative medication (thyroxin, calcium-antagonists, antacids, vitamin D, bisphosphonates and calcium) and PTH-levels between positive and negative scans was evaluated by using univariate and multivariate analysis, and a ROC analysis respectively. Overall patient-based sensitivity of scintigraphy for finding parathyroid adenomas was 72% for scintigraphy, with a positivity rate of 60%. No significant effect of investigated medication on positivity rate was found. PTH-level was significantly higher in patients with positive scintigraphy (median 96.3 ng/L vs 75.2 ng/L, P < 0.01). Optimum cut-off for detection of adenomas for PTH was 79.4 ng/L with a sensitivity of 67% and a specificity of 63%. In this retrospective cohort, sensitivity and positivity rate of dual-isotope SPECT-CT for parathyroid adenomas were in line with previous studies. No statistically significant influence of medication on positivity of scintigraphy was found, suggesting these medication types should not be stopped prior to scintigraphy. PTH level was no useful parameter to predict positivity of scintigraphic imaging.

Parameters predicting [18F]PSMA-1007 scan positivity and type and number of detected lesions in patients with biochemical recurrence of prostate cancer.

BACKGROUND: Detection of the site of recurrence using PSMA-PET/CT is important to guide treatment in patients with biochemical recurrence of prostate cancer (PCa). The aim of this study was to evaluate the positivity rate of [18F]PSMA-1007-PET/CT in patients with biochemically recurrent PCa and identify parameters that predict scan positivity as well as the type and number of detected lesions. This monocentric retrospective study included 137 PCa patients with biochemical recurrence who underwent one or more [18F]PSMA-1007-PET/CT scans between August 2018 and June 2019. PET-positive malignant lesions were classified as local recurrence, lymph node (LN), bone or soft tissue lesions. The association between biochemical/paraclinical parameters, as PSA value, PSA doubling time, PSA velocity, Gleason score (GS) and androgen deprivation therapy (ADT), and scan positivity as well as type and number of detected lesions was evaluated using logistic regression analysis (binary outcomes) and Poisson models (count-type outcomes). RESULTS: We included 175 [18F]PSMA-1007-PET/CT scans after radical prostatectomy (78%), external beam radiation therapy (8.8%), ADT (7.3%), brachytherapy (5.1%) and high intensity focused ultrasound (0.7%) as primary treatment (median PSA value 1.6 ng/ml). Positivity rate was 80%. PSA value and PSA velocity were significant predictors of scan positivity as well as of the presence of bone and soft tissue lesions and number of bone, LN and soft tissue lesions, both in uni- and/or multivariable analysis. Multivariable analysis also showed prior ADT as predictor of bone and soft tissue lesions, GS as predictor of the number of bone lesions and ongoing ADT as predictor of the number of LN lesions. CONCLUSION: [18F]PSMA-1007-PET/CT showed a high positivity rate in patients with biochemically recurrent PCa. PSA value and PSA velocity were significant predictors of scan positivity as well as of the presence and number of bone and soft tissue lesions and the number of LN lesions. Our findings can guide clinicians in optimal patient selection for [18F]PSMA-1007-PET/CT and support further research leading to the development of a prediction nomogram.

Curative, Organ-Sparing, Multimodal, Perioperative Treatment of a Young Patient with a Rectoanal Inflammatory Myofibroblastic Tumor.

INTRODUCTION: We report the case of a young female patient with a technically resectable, nonmetastatic, rectoanal, anaplastic lymphoma kinase gene (ALK)-translocated inflammatory myofibroblastic tumor (IMFT). CASE PRESENTATION: The patient was successfully treated preoperatively with the tyrosine kinase inhibitor (TKI) crizotinib, to downsize the primary tumor, followed by sphincter-sparing surgery, and adjuvant radiotherapy and crizotinib. She is now in follow-up with good sphincter function and with no evidence of active disease. CONCLUSION: Pre- and postoperative treatment administration of crizotinib can be given with curative intent to patients with locally advanced, nonmetastatic IMFTs to avoid mutilating surgery.

Site-specific relapse patterns of patients with biochemical recurrence following radical prostatectomy assessed by 68Ga-PSMA-11 PET/CT or 11C-Choline PET/CT: impact of postoperative treatments.

BACKGROUND: Salvage radiotherapy (RT) (± androgen deprivation therapy (ADT)) is often used as a treatment in patients with biochemical recurrence (BCR) following radical prostatectomy (RP). Unfortunately, even after RT ± ADT, a significant number of patients will develop 'second' BCR. The aim of this study was to investigate the impact of postoperative treatments (adjuvant/salvage radiotherapy (RT) ± androgen deprivation therapy) on the recurrence pattern in patients with BCR following RP assessed by 11C-Choline PET/CT or 68 Ga-PSMA PET/CT. METHODS: Patients who developed BCR following RP and who had at least one positive lesion on PET/CT were retrospectively assessed. Positive spots were mapped as local, lymph node (LN), skeletal or visceral recurrence. A distinction was made between locoregional (prostate bed and pelvic LN) and extrapelvic recurrence (skeletal, visceral and/or extrapelvic LN). Patients were categorized according to postoperative treatment received in three subgroups (RT, ADT and RT + ADT) and compared with the reference group (RP only). The impact of the radiation field was also investigated. RESULTS: We identified 200 patients assessed by 68Ga-PSMA-11 (80%) or 11C-Choline PET/CT (20%). Patients who received postoperative RT + ADT had less LN recurrence distal to the common iliac bifurcation (26.7% vs 66.6%; p = 0.0004), but more recurrence to retroperitoneal LN than the reference group (38% vs. 14.4%, p = 0.02). Moreover, the RT + ADT subgroup had more extrapelvic recurrence compared to the reference group (66.2% vs 40.8%, p = 0.02). Patients who received RT to the prostate bed had more recurrence distal to the common iliac bifurcation compared to those who received RT to the prostate bed + pelvic LN (51.6% vs 26.1%, p = 0.0069). CONCLUSION: Post-prostatectomy treatments (ADT and/or RT) and the postoperative radiation field (prostate bed vs. prostate bed + pelvis) have a significant impact on the recurrence pattern. This knowledge can help clinicians to counsel their patients on their chances of being eligible for (locoregional) metastasis-directed therapies.

Bacteraemia after leadless pacemaker implantation.

BACKGROUND: Transvenous 3 permanent pacemaker-related infection is a severe condition associated with significant morbidity and mortality. Leadless pacemakers may be more resistant to bacterial seeding during bloodstream infection because of its small surface area and encapsulation in the right ventricle. This study reports the incidence and outcomes of bacteraemia in patients implanted with a Micra leadless pacemaker. We present 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) findings obtained in a subgroup of patients. METHODS: We report a retrospective cohort study of 155 patients who underwent a Micra TPS implant procedure at the University Hospitals of Leuven between July 2015 and July 2019. We identified the patients who developed an episode of bacteraemia, proved by ≥2 positive blood cultures. RESULTS: Of the 155 patients, 15 patients presented an episode of bacteraemia at a median of 226 days (range: 3-1129) days after the implant procedure. Gram-positive species accounted for 73.3% (n = 11) of the bacteraemia including Staphylococcus (n = 5), Enterococcus (n = 3), and Streptococcus (n = 3). The source of infection was identified in nine patients (60%) including endocarditis in four patients, urinary tract in three patients, and skin in two patients. 18 F-FDG PET/CT imaging performed in six patients did not show sign of infection around the leadless pacemaker. Bacteraemia was resolved in all patients after adequate antibiotherapy. Four patients died early during follow up. For all other patients, there were no recurrence of systemic infection during a median follow up of 263 days (range: 15-1134). CONCLUSION: In our small cohort, no leadless pacemaker endocarditis was observed among patients with bacteraemia.

All that glitters is not prostate cancer: incidental finding of PSMA-avid meningioma.

We present a case of a 79 year old patient with a medical history of unilateral nerve-sparing radical prostatectomy due to a pT3aN0 (Gleason score 7) prostate carcinoma. Because of slightly elevated prostate specific antigen (PSA) level (0.35ng/dL), a fluorine-18-prostate specific membrane antigen (18F-PSMA)-1007 positron emission tomography/computed tomography (PET/CT) scan was performed, showing no signs of malignant recurrence. However, a moderately PSMA-avid nodular lesion was observed in the left occipital region with homogeneous contrast enhancement, suggestive for a meningioma, which was confirmed on magnetic resonance imaging (MRI). One year later, the lesion was resected due to a small but significant growth. Histology confirmed the diagnosis of a transitional type meningioma (WHO grade 1).

Influence of pretreatment with everolimus or sunitinib on the subacute hematotoxicity of 177Lu-DOTATATE PRRT.

Background: Peptide receptor radionuclide therapy (PRRT) is a validated treatment for somatostatin receptor overexpressing neuroendocrine tumors (NETs). The NETTER-1 trial demonstrated a pronounced positive effect on progression-free-survival compared to high dose somatostatin analogs (SSAs), with a strong tendency toward overall survival benefit. Our aim was to investigate the influence of pretreatment with everolimus and/or sunitinib on subacute hematotoxicity of PRRT. To assess the influence of prior treatment with everolimus/sunitinib might be of clinical relevance due to the link between short-term hematotoxicity and increased incidence of late hematotoxicity.Material and methods: Our single-center retrospective study enrolled all patients treated with 177Lu-DOTATATE PRRT (1-4 cycles of 7.4 GBq), between November 2013 and July 2018. Patients were assigned to two groups according to their pretreatment: no targeted agents (N = 41), or targeted agents (everolimus, sunitinib or both; N = 41). The end point was subacute hematotoxicity, defined as the nadir value between the first administration until 3 months after the last administration, using the CTCAE 4.03 classification. The impact of splenectomy was also explored.Results: Eighty percent of patients had a primary gastroenteropancreatic NET. No statistically significant differences in severe subacute hematotoxicity were seen in the pretreated group vs. the naive group for hemoglobin (grade 3/4: 12% vs. 22%), neither for leucocytes (grade 3/4: 10% vs. 7%), neutrophils (grade 3/4: 5% vs. 7%), lymphocytes (grade 3/4: 49% vs. 37%) and platelets (grade 3/4: 15% vs. 15%). Furthermore, we observed significantly lower toxicity for total white blood cells, lymphocytes and platelets in the subgroup that had splenectomy (N = 12). Limitations of this study include the potential bias in lack of use of targeted agents in patients more susceptible to toxicity, and the limited number of patients and events.Conclusions: In a patient cohort with NET pretreated with everolimus and/or sunitinib, we could not demonstrate a significant effect of prior/pretreatment with everolimus and/or sunitinib on the subacute hematotoxicity of 177Lu-DOTATATE PRRT.