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Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the ten known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers and to offer gene-informed medical management including enhanced surveillance and prevention. Clinically, we now treat an entire family of tumors of the paraganglia, with the exact phenotype varying by specific gene. In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. Treatment options have also been substantially enriched by the application of minimally invasive and adrenal-sparing surgery. Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment and surveillance of this rare neoplasm. [ABSTRACT FROM AUTHOR]

Background: Focal radiation therapy has gained of interest in treatment of patients with primary prostate cancer (PCa). The question of how to define the intraprostatic boost volume is still open. Previous studies showed that multiparametric MRI (mpMRI) or PSMA PET alone could be used for boost volume definition. However, other studies proposed that the combined usage of both has the highest sensitivity in detection of intraprostatic lesions. The aim of this study was to demonstrate the feasibility and to evaluate the tumour control probability (TCP) and normal tissue complication probability (NTCP) of radiation therapy dose painting using 68Ga-HBED-CC PSMA PET/CT, mpMRI or the combination of both in primary PCa.Methods: Ten patients underwent PSMA PET/CT and mpMRI followed by prostatectomy. Three gross tumour volumes (GTVs) were created based on PET (GTV-PET), mpMRI (GTV-MRI) and the union of both (GTV-union). Two plans were generated for each GTV. Plan95 consisted of whole-prostate IMRT to 77 Gy in 35 fractions and a simultaneous boost to 95 Gy (Plan95PET/Plan95MRI/Plan95union). Plan80 consisted of whole-prostate IMRT to 76 Gy in 38 fractions and a simultaneous boost to 80 Gy (Plan80PET/Plan80MRI/Plan80union). TCPs were calculated for GTV-histo (TCP-histo), which was delineated based on PCa distribution in co-registered histology slices. NTCPs were assessed for bladder and rectum.Results: Dose constraints of published protocols were reached in every treatment plan. Mean TCP-histo were 99.7% (range: 97%-100%) and 75.5% (range: 33%-95%) for Plan95union and Plan80union, respectively. Plan95union had significantly higher TCP-histo values than Plan95MRI (p = 0.008) and Plan95PET (p = 0.008). Plan80union had significantly higher TCP-histo values than Plan80MRI (p = 0.012), but not than Plan80PET (p = 0.472). Plan95MRI had significantly lower NTCP-rectum than Plan95union (p = 0.012). No significant differences in NTCP-rectum and NTCP-bladder were observed for all other plans (p > 0.05).Conclusions: IMRT dose escalation on GTVs based on mpMRI, PSMA PET/CT and the combination of both was feasible. Boosting GTV-union resulted in significantly higher TCP-histo with no or minimal increase of NTCPs compared to the other plans. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to assess the feasibility and image quality of dual-source photon-counting detector computed tomography (PCD-CT) in evaluating small-sized coronary artery stents with respect to different acquisition modes in a phantom model., Methods: Utilizing a phantom setup mimicking the average patient's water-equivalent diameter, we examined six distinct coronary stents inflated in a silicon tube, with stent sizes ranging from 2.0 to 3.5 mm, applying four different CT acquisition modes of a dual-source PCD-CT scanner: "high-pitch," "sequential," "spiral" (each with collimation of 144 × 0.4 mm and full spectral information), and "ultra-high-resolution (UHR)" (collimation of 120 × 0.2 mm and no spectral information). Image quality and diagnostic confidence were assessed using subjective measures, including a 4-point visual grading scale (4 = excellent; 1 = non-diagnostic) utilized by two independent radiologists, and objective measures, including the full width at half maximum (FWHM)., Results: A total of 24 scans were acquired, and all were included in the analysis. Among all CT acquisition modes, the highest image quality was obtained for the UHR mode [median score: 4 (interquartile range (IQR): 3.67-4.00)] ( P = 0.0015, with 37.5% rated as "excellent"), followed by the sequential mode [median score: 3.5 (IQR: 2.84-4.00)], P = 0.0326 and the spiral mode [median score: 3.0 (IQR: 2.53-3.47), P > 0.05]. The lowest image quality was observed for the high-pitch mode [median score: 2 (IQR: 1- 3), P = 0.028]. Similarly, diagnostic confidence for evaluating stent patency was highest for UHR and lowest for high-pitch ( P < 0.001, respectively). Measurement of stent dimensions was accurate for all acquisition modes, with the UHR mode showing highest robustness (FWHM for sequential: 0.926 ± 0.061 vs. high-pitch: 0.990 ± 0.083 vs. spiral: 0.962 ± 0.085 vs. UHR: 0.941 ± 0.036, P = non-significant, respectively)., Conclusion: Assessing small-sized coronary stents using PCD-CT technology is feasible. The UHR mode offers superior image quality and diagnostic confidence, while all modes show consistent and accurate measurements., Clinical Significance: These findings highlight the potential of PCD-CT technology, particularly the UHR mode, to enhance non-invasive coronary stent evaluation. Confirmatory research is necessary to influence the guidelines, which recommend cardiac CT only for stents of 3 mm or larger.

Aims: To determine the conditions under which early hypoattenuated leaflet thickening (HALT) after transcatheter aortic valve implantation (TAVI) becomes haemodynamically relevant., Methods and Results: The study included 100 patients (age: 81.5 ± 5.5 years; female 63%), thereof 50 patients with HALT. After anonymization and randomization, blinded readers measured maximum thrombus thickness per prosthesis (MT&#95;pr) and movement restriction (MR&#95;pr) on electrocardiogram (ECG)-gated whole heart cycle computed tomography angiography. These measurements were compared with echocardiographic mean pressure gradient (mPG), its increase from baseline (ΔmPG), and Doppler velocity index (DVI). Haemodynamic valve deterioration (HVD) was defined as mPG > 20 mmHg. Age, body mass index, valve type, valve size, left ventricular ejection fraction, and atrial fibrillation were considered as influencing factors. Multiple regression analysis revealed that only valve size (P = 0.001) and MT&#95;pr (P = 0.02) had a significant influence on mPG. In an interaction model, valve size moderated the effect of MT&#95;pr on mPG significantly (P = 0.004). Sub-group analysis stratified by valve sizes showed a strong correlation between MT&#95;pr and echocardiographic parameters for 23 mm valves (mPG: r = 0.57, ΔmPG: r = 0.68, DVI: r = 0.55, each with P < 0.001), but neither for 26 nor 29 mm valves (r < 0.2, P > 0.2 for all correlations). Six of seven prostheses with HVD had a 23 mm valve diameter, while one had 29 mm (P = 0.02)., Conclusion: Early HALT rarely causes significant mPG increase. Our study shows that valve size is a key factor influencing the haemodynamic impact of HALT. In small valve sizes, mPG is more likely to increase. Our study is the first to offer in vivo evidence supporting previous in vitro findings on this topic., Competing Interests: Conflict of interest: F.B.: Bayer Healthcare, speakers bureau and unrestricted research grant Siemens Healthineers, speakers bureau and unrestricted research grant, unrelated to this work. C.L.S.: Siemens Healthineers, unrestricted research grant, unrelated to this work. J.T.: funding by Deutsche Forschungsgesellschaft (DFG, German Research Foundation)—TA 1438/1–2. T; speakers bureau Siemens Healthcare GmbH and speakers bureau Bayer AG, reviewer Universimed Cross Media Content GmbH and consultant Core Lab Black Forrest GmbH, all unrelated to this work. M.S.: electronic presentation sponsored by Bayer AG, unrelated to this work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Recently introduced photon-counting CT may improve noninvasive assessment of patients with high risk for coronary artery disease (CAD). Purpose To determine the diagnostic accuracy of ultrahigh-resolution (UHR) coronary CT angiography (CCTA) in the detection of CAD compared with the reference standard of invasive coronary angiography (ICA). Materials and Methods In this prospective study, participants with severe aortic valve stenosis and clinically indicated CT for transcatheter aortic valve replacement planning were consecutively enrolled from August 2022 to February 2023. All participants were examined with a dual-source photon-counting CT scanner using a retrospective electrocardiography-gated contrast-enhanced UHR scanning protocol (tube voltage, 120 or 140 kV; collimation, 120 × 0.2 mm; 100 mL of iopromid; no spectral information). Subjects underwent ICA as part of their clinical routine. A consensus assessment of image quality (five-point Likert scale: 1 = excellent [absence of artifacts], 5 = nondiagnostic [severe artifacts]) and a blinded independent reading for the presence of CAD (stenosis ≥50%) were performed. UHR CCTA was compared with ICA using area under the receiver operating characteristic curve (AUC). Results Among 68 participants (mean age, 81 years ± 7 [SD]; 32 male, 36 female), the prevalence of CAD and prior stent placement was 35% and 22%, respectively. The overall image quality was excellent (median score, 1.5 [IQR, 1.3-2.0]). The AUC of UHR CCTA in the detection of CAD was 0.93 per participant (95% CI: 0.86, 0.99), 0.94 per vessel (95% CI: 0.91, 0.98), and 0.92 per segment (95% CI: 0.87, 0.97). Sensitivity, specificity, and accuracy, respectively, were 96%, 84%, and 88% per participant ( n = 68); 89%, 91%, and 91% per vessel ( n = 204); and 77%, 95%, and 95% per segment ( n = 965). Conclusion UHR photon-counting CCTA provided high diagnostic accuracy in the detection of CAD in a high-risk population, including subjects with severe coronary calcification or prior stent placement. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Williams and Newby in this issue.

Importance: Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management., Objective: To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence., Design, Setting, and Participants: This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019., Exposures: Total or cortical-sparing adrenalectomy., Main Outcomes and Measures: Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality., Results: Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutations were detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survival was associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma., Conclusions and Relevance: Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma.

Purpose: The exact detection and delineation of the intraprostatic tumour burden is crucial for treatment planning in primary prostate cancer (PCa). We compared 68 Ga-HBED-CC-PSMA PET/CT with multiparametric MRI (mpMRI) for diagnosis and tumour delineation in patients with primary PCa based on slice by slice correlation with histopathological reference material., Methodology: Seven patients with histopathologically proven primary PCa underwent 68 Ga-HBED-CC-PSMA PET/CT and MRI followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and prepared for histopathology. Invasive PCa was delineated on a HE stained histologic tissue slide and matched to ex-vivo CT to obtain gross tumor volume (GTV-)histo. Ex-vivo CT including GTV-histo and MRI data were matched to in-vivo CT(PET). Consensus contours based on MRI (GTV-MRI), PSMA PET (GTV-PET) or the combination of both (GTV-union/-intersection) were created. In each in-vivo CT slice the prostate was separated into 4 equal segments and sensitivity and specificity for PSMA PET and mpMRI were assessed by comparison with histological reference material. Furthermore, the spatial overlap between GTV-histo and GTV-PET/-MRI and the Sørensen-Dice coefficient (DSC) were calculated. In the case of multifocal PCa (4/7 patients), SUV values (PSMA PET) and ADC-values (diffusion weighted MRI) were obtained for each lesion., Results: PSMA PET and mpMRI detected PCa in all patients. GTV-histo was detected in 225 of 340 segments (66.2%). Sensitivity and specificity for GTV-PET, GTV-MRI, GTV-union and GTV-intersection were 75% and 87%, 70% and 82%, 82% and 67%, 55% and 99%, respectively. GTV-histo had on average the highest overlap with GTV-union (57±22%), which was significantly higher than overlap with GTV-MRI (p=0.016) and GTV-PET (p=0.016), respectively. The mean DSC for GTV-union, GTV-PET and GTV-MRI was 0.51 (±0.18), 0.45 (±0.17) and 0.48 (±0.19), respectively. In every patient with multifocal PCa there was one lesion which had both the highest SUV and the lowest ADC-value (mean and max)., Conclusion: In a slice by slice analysis with histopathology, 68 Ga-HBED-CC-PSMA PET/CT and mpMRI showed high sensitivity and specificity in detection of primary PCa. A combination of both methods performed even better in terms of sensitivity (GTV-union) and specificity (GTV-intersection). A moderate to good spatial overlap with GTV-histo was observed for PSMA PET/CT and mpMRI alone which was significantly improved by GTV-union. Further studies are warranted to analyse the impact of these preliminary findings for diagnostic (multimodal guided TRUS biopsy) and therapeutic (focal therapy) strategies in primary PCa., Competing Interests: Author PTM received research grants from Piramal and GE. Author MM received research grants from Philips Medical Systems. Author CZ declares that he has no conflict of interest. Author ALG declares that she has no conflict of interest. Author UW declares that he has no conflict of interest. Author TIB declares that she has no conflict of interest. Author HCR declares that he has no conflict of interest. Author VD declares that she has no conflict of interest. Author MW declares that he has no conflict of interest. Author CAJ declares that she has no conflict of interest. Author WSS declares that he has no conflict of interest. Author MW declares that he has no conflict of interest. Author FS declares that he has no conflict of interest. Author ML declares that he has no conflict of interest. Author MB declares that he has no conflict of interest. Author TK declares that he has no conflict of interest.

Aims: To evaluate the feasibility of a non-contrast three-dimensional (3D)-FLASH magnetic resonance angiography (MRA) protocol for pre-procedural aortic annulus assessment for transcatheter aortic valve replacement (TAVR) in comparison with cardiac dual-source computed tomography angiography (CTA)., Methods and Results: In this prospective study, 69 of 104 consecutive patients (mean age 81.8 ± 5.4 years, 37.7% arrhythmic) with severe aortic stenosis who had undergone pre-TAVR cardiac CTA received a respiratory and ECG-triggered, non-contrast 3D-FLASH MRA at 3 T. Annular area measurements were obtained at mid-diastole for both modalities whereas maximum systolic area was assessed by CTA only. Systolic MRA dimensions were modelled, by adding the relative difference of systolic and diastolic CTA area dimensions as a corrective factor. Hypothetical prosthesis sizing was performed based on systolic CTA, diastolic, and modelled systolic MRA area measurements. MR image quality and degree of annular calcifications were evaluated using 4-point-grading scales. The mean acquisition time was 14 ± 4.2 min. The mean image quality was 3.1 ± 0.9 with only two examinations rated non-diagnostic. The mean degree of calcifications was equal. As assessed by Bland-Altman analysis, there was no relevant systematic difference between area measurements for modelled systolic MRA and systolic CTA [the mean difference -3.1 mm(2) (limits of agreement -44.4 mm(2); 38.2 mm(2))]. Agreement for hypothetical prosthesis sizing was found in 63 of 67 (94%) patients for systolic CTA and modelled systolic MRA., Conclusion: The employed non-contrast 3D-FLASH MRA protocol allows for reliable assessment of aortic annulus dimensions and calcifications even in the presence of arrhythmias in an all-comers pre-TAVR population. Implementation of this technique appears legitimate in patients at an increased risk for contrast-induced nephropathy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: Lesion formation during catheter ablation crucially depends on catheter-tissue contact. We sought to evaluate the impact of anatomical characteristics of the left atrium (LA) and the pulmonary veins (PVs) on contact force (CF) measurements., Methods and Results: An anatomical map of the LA was obtained in 25 patients prior to catheter ablation of atrial fibrillation. Contact force (operator blinded) and local bipolar electrogram amplitudes (EGM) were measured in eight pre-defined segments around the PVs. After unblinding, points with low CF (≤5 g) were corrected to CF >5 g, and the distance between points was measured. In a pre-procedural computed tomography of the heart, LA volume as well as sizes and circumferences of the PV ostia were measured and correlated to CF measurements. Four hundred and twenty-six points in eight pre-defined LA locations were assessed. Low CF (<5 g) was found in 25.0% (43.5%) of points superior, 33.3% (66.7%) anterior, 32.1% (44.4%) inferior, and 15.5% (15.9%) posterior to the right (left) PVs. The mean distance after correction was 5.8 ± 3.4 mm. Local bipolar electrogram amplitudes between low- and high-CF points did not differ (1.21 ± 1.54 vs. 1.13 ± 1.3 mV, P = ns). The mean CF at the left PVs was significantly lower than at the right PVs (7.91 ± 3.74 vs. 13.95 ± 6.34 g, P < 0.001), with the lowest CF anterior to the left PVs (5.2 ± 3.6 g). Contact force measurements did not correlate to LA volume, size, and circumference of the PVs., Conclusion: Contact force during LA mapping significantly differs according to the location within the LA. These differences are independent of LA volume and anatomy of the PV ostia., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)