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The optimal treatment strategy for patients with small non-functioning VHL-related incidentalomas is unclear. We searched the Freiburg VHL registry for patients with radiologic evidence of pheochromocytoma/paraganglioma (PHEO/PGL). In total, 176 patients with single, multiple, and recurrent tumours were identified (1.84 tumours/patient, range 1–8). Mean age at diagnosis was 32 ± 16 years. Seventy-four percent of tumours were localised to the adrenals. Mean tumour diameter was 2.42 ± 2.27 cm, 46% were P < 0.025) and before surgery (4.89 ± 3.47 cm vs 1.36 ± 0.43 cm; P < 0.02). Disease was stable in 67% of 21 patients with evaluable tumours ≤1.5 cm according to RECIST and progressed in 7. Time till surgery in these patients was 29.5 ± 20.0 months. A total of 155 patients underwent surgery. PHEO/PGL was histologically excluded in 4 and proven in 151. Of these, one had additional metastatic disease, one harboured another tumour of a different type, and in 2 a second surgery for suspected disease recurrence did not confirm PHEO/PGL. Logistic regression analysis revealed 50% probability for a positive/negative biochemical test result at 1.8 cm tumour diameter. Values of a novel symptom score were positively correlated with tumour size (Rs = 0.46, P < 0.0001) and together with a positive biochemistry a linear size predictor (P < 0.01). Results support standardised clinical assessment and measurement of tumour size and metanephrines in VHL patients with non-functioning incidentalomas

Introduction Hemangioblastomas are rare, histologically benign, highly vascularized tumors of the brain, the spinal cord, and the retina, occurring sporadically or associated with the autosomal dominant inherited von Hippel-Lindau (VHL) disease. Children or adults with VHL disease have one of > 300 known germline mutations of the VHL gene located on chromosome 3. They are prone to develop hemangioblastomas, extremely rarely starting at age 6, rarely at age 12–18, and, typically and almost all, as adults. There is a plethora of VHL-associated tumors and cysts, mainly in the kidney, pancreas, adrenals, reproductive organs, and central nervous system. Due to a lack of causal treatment, alleviation of symptoms and prevention of permanent neurological deficits as well as malignant transformation are the main task. Paucity of data and the nonlinear course of tumor progression make management of pediatric VHL patients with hemangioblastomas challenging. Methods The Freiburg surveillance protocol was developed by combining data from the literature and our experience of examinations of > 300 VHL patients per year at our university VHL center. Results Key recommendations are to start screening of patients at risk by funduscopy with dilated pupils for retinal tumors with admission to school and with MRI of the brain and spinal cord at age 14, then continue biannually until age 18, with emergency MRI in case of neurological symptoms. Indication for surgery remains personalized and should be approved by an experienced VHL board, but we regard neurological symptoms, rapid tumor growth, or critically large tumor/cyst sizes as the key indications to remove hemangioblastomas. Since repeated surgery on hemangioblastomas in VHL patients is not rare, modern neurosurgical techniques should encompass microsurgery, neuronavigation, intraoperative neuromonitoring, fluorescein dye-based intraoperative angiography, intraoperative ultrasound, and minimally invasive approaches, preceded in selected cases by endovascular embolization. Highly specialized neurosurgeons are able to achieve a very low risk of permanent morbidity for the removal of hemangioblastomas from the cerebellum and spinal cord. Small retinal tumors of the peripheral retina can be treated by laser coagulation, larger tumors by cryocoagulation or brachytherapy. Conclusion We consider management at experienced VHL centers mandatory and careful surveillance and monitoring of asymptomatic lesions are required to prevent unnecessary operations and minimize morbidity.

Aim: The present study analyzes in depth the impact of different calcification patterns on disturbances of the conduction system in transcatheter aortic valve replacement (TAVR) patients. Methods and Results: A total of 169 preprocedural TAVR multislice computed tomography scans from consecutive transfemoral (TF) TAVRs performed between 2014 and 2017 using either Edwards SAPIEN or Medtronic Evolut R valves were retrospectively evaluated. The volume, distribution, and orientation of annular and valvular aortic valve calcification were measured and their impact on postoperative conduction disturbances was determined using linear and logistic regression analyses. The total volume of calcification and distribution at the aortic annulus or valve did not influence the conduction system. Oval calcification of the left aortic cusp was independently associated with an elevated risk for an increase in atrioventricular block degree (+0.6, p = 0.03). Moreover, orthogonal calcifications at the level of the aortic annulus were associated with an increased risk for QRS prolongation (+26 ms, p = 0.004) and an increased risk for permanent pacemaker implantation (OR 4.3, p = 0.03) after TF TAVR. This was more pronounced in patients undergoing TF TAVR using a balloon-expandable Edwards SAPIEN 3 valve (QRS +38.195 ms, p < 0.001; OR permanent pacemaker 15.48, p = 0.013). Conclusion: Orthogonal annular calcification confers an increased risk for conduction disturbances after TAVR. This is even more pronounced after implantation of balloon-expandable valves.

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel–Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10–75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P P = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

To validate the risk stratification algorithm of the Prostate Imaging Reporting and Data System (PI-RADSv2) for intermediary risk lesions (PI-RADSv2 category 3) in the peripheral zone based on focal contrast enhancement and to compare cancer rates in category 3, upgraded category 4 and category 4 based on markedly low ADC value.We retrospectively analyze 172 consecutive patients undergoing prostate MRI with 315 histopathologically verified lesions. We select all lesions either assigned category 3 or category 4 in the peripheral zone for further analysis. We compare cancer rates with the two-sided chi-squared test. To determine inter-observer agreement about contrast enhancement two blinded radiologists evaluate the subset of category 3 lesions based on the diffusion weighted sequence.The frequency of peripheral PI-RADS 3, upgraded PI-RADS 4 and PI-RADS 4 lesions based on markedly low ADC value is 10.8%, 10.8% and 20.3%, respectively. Cancer rates (significant cancer only) in these subgroups are 8.8% (3/34), 23.5% (8/34) and 40.6% (26/64), P 0.01. Inter-observer agreement is moderate for evaluation of contrast enhancement with kappa values between 0.46 and 0.5.We demonstrate a trend of increasing cancer rate from PI-RADSv2 category 3 to upgraded category 4 to category 4 based on markedly low ADC value. Peripheral lesions of intermediary risk in the diffusion weighted sequence account for 21.6% of all prostate lesions encountered. Since it is likely that patient management recommendations will be linked to assessment categories in future versions of PI-RADS, cancer rates in upgraded category 4 and category 4 based on markedly low ADC values should be in a similar range. We conclude that in future studies of PI-RADSv2 upgraded category 4 and category 4 based on markedly low ADC value should be reported separately to generate a database for meta-analysis of cancer rates.

Transcatheter aortic valve implantation (TAVI) has evolved into an alternative procedure to surgical valve replacement for high-risk patients with aortic valve stenosis. Despite technical innovations, there is still a risk of complications during and after the intervention. After a TAVI procedure, ECG-gated multidetector computed tomography (MDCT) plays an important role in the early diagnosis of local complications. In this article, we explain for the first time how the technical acquisition of MDCT in the region of the aortic root is performed as post-interventional control of the TAVI prosthesis. In the second part normal post-interventional findings of different prosthetic valves as well as classic and uncommon complications in the implant area will be illustrated in several case studies. In this review the current literature from PubMed about ECG-gated MDCT after TAVI is summarized and structured. It is supplemented by several case studies from our institution. Using retrospectively ECG-gated MDCT, an aortic valve prosthesis after TAVI can be visualized with high spatial resolution in several phases of the cardiac cycle. Images of the implanted aortic valve at all time points of the cardiac cycle enable a functional analysis of prosthetic leaflets similar to echocardiography. MDCT is superior to transthoracic echocardiography with respect to the direct detection of prosthetic leaflet thrombosis. The position of the device in relation to the coronary ostia and correct unfolding of the stent frame need to be evaluated. There are different types of stents carrying the valve leaflets with distinct ideal positions. Any stent should cover the left ventricular outflow tract (LVOT) along its whole circumference. Life-threatening complications in the implant area, such as annulus rupture, can be diagnosed reliably with CT. · ECG-gated multidetector CT (MDCT) after transcatheter aortic valve implantation (TAVI) can provide early detection of postinterventional complications of the prosthetic valve and the aortic root.. · MDCT is superior to echocardiography with respect to the direct detection of prosthetic leaflet thrombosis.. · MDCT can also reveal hypokinesia of the thrombotic valve leaflets.. · Correct position of the device und unfolding of the stent frame differ according to the type of prosthesis.. · The integrity of the native aortic root should be carefully assessed..· Soschynski M, Capilli F, Ruile P et al. Post-TAVI Follow-Up with MDCT of the Valve Prosthesis: Technical Application, Regular Findings and Typical Local Post-Interventional Complications. Fortschr Röntgenstr 2018; 190: 521 - 530. Die Transkatheter-Aortenklappen-Implantation (TAVI) hat sich als Alternative zum chirurgischen Klappenersatz für Patienten mit hohem Operationsrisiko etabliert. Trotz technischer Optimierungen besteht immer noch ein Risiko für Komplikationen während und nach dem Eingriff. Für die postinterventionelle Kontrolle der stentgetragenen Klappenprothese spielt die EKG-getriggerte Multidetektor-Computertomografie (MDCT) eine wichtige Rolle in der frühzeitigen Diagnostik von lokalen Komplikationen. In diesem Artikel gehen wir zunächst auf die technische Durchführung der MDCT im Bereich der Aortenwurzel zur Kontrolle der TAVI-Klappenprothese ein. Im zweiten Schritt werden anhand mehrerer Fallbeispiele postinterventionelle Normalbefunde verschiedener Klappentypen sowie klassische und seltene Komplikationen im Implantationsgebiet illustriert. Die Übersichtsarbeit fasst die Literatur in PubMed zum Thema EKG-getriggerte MDCT nach TAVI strukturiert zusammen und wird um eine Fallsammlung aus unserem Institut ergänzt. Mittels retrospektiv EKG-getriggerter MDCT kann die Aortenklappenprothese nach TAVI räumlich hochaufgelöst in mehreren Phasen des Herzzyklus darstellt werden. Die Darstellung der Klappenprothese über den gesamten Herzzyklus erlaubt eine Funktionsanalyse der bewegten Klappe ähnlich der Echokardiografie. Die MDCT ist der transthorakalen Echokardiografie im direkten Nachweis einer Klappenthrombose überlegen. Bei der Befundung muss die Lage der stentgetragenen Klappe in Bezug zu den Koronargefäßen und die Stententfaltung evaluiert werden. Je nach Klappentyp bestehen unterschiedliche Stentformen und ideale Positionen. Jeder Stent sollte mit der gesamten Zirkumferenz dem linksventrikulären Ausflusstrakt anliegen. Lebensbedrohliche Komplikationen im Implantationsgebiet wie eine Annulusruptur können im CT sicher diagnostiziert werden. · Mit der EKG-getriggerten Multidetektor-CT (MDCT) nach Transkatheter-Aortenklappen-Implantation (TAVI) können postinterventionelle Komplikationen an der Klappenprothese und der Aortenwurzel frühzeitig erkannt werden.. · Die MDCT ist der Echokardiografie im direkten Nachweis einer Klappenthrombose überlegen.. · Das Erkennen einer Hypokinesie bei Klappenthrombose ist ebenfalls mittels MDCT möglich.. · Die korrekte Stentlage und die Stententfaltung unterscheiden sich je nach Klappentyp.. · Auf die Integrität der Aortenwurzel ist gesondert zu achten..· Soschynski M, Capilli F, Ruile P et al. Post-TAVI Follow-Up with MDCT of the Valve Prosthesis: Technical Application, Regular Findings and Typical Local Post-Interventional Complications. Fortschr Röntgenstr 2018; 190: 521 – 530.

Purpose The exact detection and delineation of the intraprostatic tumour burden is crucial for treatment planning in primary prostate cancer (PCa). We compared 68Ga-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 68Ga-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 Sorensen-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, 68Ga-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.

Purpose PET/CT directed extended salvage radiotherapy (esRT) of involved lymph-node (LN) regions may be a salvage strategy for patients with nodal recurrent prostate cancer (PCa) after primary therapy or after previous prostate fossa salvage RT. The aim of the study was to determine the time until prostate-specific antigen (PSA) progression, pattern of failure and toxicity after esRT. Material and methods 25 patients with nodal or nodal + local recurrent PCa confirmed by Choline-PET/CT and Magnetic Resonance Imaging (MRI) were treated with esRT at the sites of recurrence. Acute and late toxicity was recorded. In case of subsequent PSA progression, imaging was performed to confirm next relapse. Mean follow-up was 2.9 years. Results According to Choline-PET/CT and MRI findings, 84% (21/25) of esRT were treatment of pelvic only, 12% (3/25) of retroperitoneal only and 4% (1/25) of both pelvic and retroperitoneal regions. 40% (10/25) received concomitant irradiation of the prostatic fossa (after primary radical prostatectomy). Median time to PSA progression of the whole cohort was 19.6 months. Median time to PSA progression for patients with 1–2 PET-positive LN ( n = 15) was 34.9 months versus median 12.7 months for patients with PET-positive LN ≥ 3 ( n = 10), p -value: 0.0476. Acute and late toxicity was mild to moderate, no grade-3 adverse events were observed. Conclusion PET/CT and MRI directed esRT of nodal recurrent PCa with or without local recurrence is feasible with low acute and late toxicity. Patients with only one or two PET-positive LN treated by esRT achieved prolonged complete biochemical remission.

Objective. In this study, we compared prostate cancer detection rates between MRI-TRUS fusion targeted and systematic biopsies using a robot-guided, software based transperineal approach. Methods and Patients. 52 patients received a MRIT/TRUS fusion followed by a systematic volume adapted biopsy using the same robot-guided transperineal approach. The primary outcome was the detection rate of clinically significant disease (Gleason grade ≥ 4). Secondary outcomes were detection rate of all cancers, sampling efficiency and utility, and serious adverse event rate. Patients received no antibiotic prophylaxis. Results. From 52 patients, 519 targeted biopsies from 135 lesions and 1561 random biopsies were generated (total n=2080). Overall detection rate of clinically significant PCa was 44.2% (23/52) and 50.0% (26/52) for target and random biopsy, respectively. Sampling efficiency as the median number of cores needed to detect clinically significant prostate cancer was 9 for target (IQR: 6–14.0) and 32 (IQR: 24–32) for random biopsy. The utility as the number of additionally detected clinically significant PCa cases by either strategy was 0% (0/52) for target and 3.9% (2/52) for random biopsy. Conclusions. MRI/TRUS fusion based target biopsy did not show an advantage in the overall detection rate of clinically significant prostate cancer.

Objectives To evaluate a systolic ECG-gated high-pitch aortoiliac computed tomography (CT) angiography for planning transcatheter aortic valve implantation (TAVI). Methods Patients referred for TAVI underwent a combined CT imaging with retrospective, multiphasic ECG-gating of the heart and systolic ECG-gated high-pitch aortoiliac CT angiography. Consecutive patients were retrospectively included in this study group. Heart rate (HR) and heart rate variability (HRV) were assessed during the high-pitch ECG prediction phase. Aortic annulus area (AAA) was planimetrically quantified on both datasets. While only one moment of cardiac cycle was available for measurements in the high-pitch CT, the point of time in the multiphasic CT was chosen, where AAA yielded maximum size. Hypothetical prosthesis sizing was compared between multiphasic vs. high-pitch CT. Results Among 61 patients (44.2 % men, mean age: 83.3 ± 5.5 years) average heart rate and HRV were 71.0 ± 13.4 bpm and 7.3 ± 8.5 bpm. 20 patients (32.7 %) had atrial fibrillation at the time of image acquisition. There was a strong correlation of AAA as derived from multiphasic vs. the high-pitch CT (r = 0.98). The difference in AAA was 10.5 ± 17.1mm2 (455.1 ± 83.0 mm2 for multiphasic vs. 444.5 ± 87.2 mm2 for high-pitch CT) and did not reach statistical significance (p = 0.08). Hypothetical prosthesis sizing showed an agreement in 55 of 61 patients (90.2 %). A sizing based on the high-pitch CT resulted in smaller prosthesis choice in 6 patients, all of them suffering from atrial fibrillation. Mean effective radiation dose was 10.9 ± 6.1 mSv for cardiac CTA and 4.1 ± 1.0 mSv for high-pitch CTA. Conclusion For patients with sinus rhythm, systolic high-pitch aortoiliac CTA provides adequate prosthesis size selection as compared with multiphasic ECG-gated cardiac CTA and may result in significantly reduced radiation exposition.

Purpose Patients hospitalized for infection with SARS-CoV-2 typically present with pneumonia. The respiratory failure is frequently complicated by pulmonary embolism in segmental pulmonary arteries. The distribution of pulmonary embolism in regard to lung parenchymal opacifications has not been investigated yet. Methods All patients with COVID-19 treated at a medical intensive care unit between March 8th and April 15th, 2020 undergoing computed tomography pulmonary angiography (CTPA) were included. All CTPA were assessed by two radiologists independently in respect to parenchymal changes and pulmonary embolism on a lung segment basis. Results Out of 22 patients with severe COVID-19 treated within the observed time period, 16 (age 60.4 ± 10.2 years, 6 female SAPS2 score 49.2 ± 13.9) underwent CT. A total of 288 lung segment were analyzed. Thrombi were detectable in 9/16 (56.3%) patients, with 4.4 ± 2.9 segments occluded per patient and 40/288 (13.9%) segments affected in the whole cohort. Patients with thrombi had significantly worse segmental opacifications in CT (p, Highlights (mandatory) • In COVID-19 respiratory failure, thrombi in segmental pulmonary arteries are common. • All Thrombi detected were localized in opacitated (presumably COVID-19 affected) lung segments. • This might suggest local clot formation.

To determine the value of a radiomics MRI phenotype of the transition zone to explain PSA level in patients with low suspicion for clinically significant cancer to confirm hyperplastic changes.T2 weighted images from 36 consecutive PI-RADS 2 and 3 cases with volume adapted systematic transperineal biopsy as reference standard (all biopsies negative, 34.8 biopsy cores per patient in average, mean PSA level 10.77 ng/mL) are manually segmented to define transition zone (TZ) volume. 54 radiomic features (RF) are derived for each TZ. RF are tested for significant correlation with PSA level, Bonferroni correction is applied. We build regression models to explain PSA level with a) TZ volume b) RF c) TZ volume+RF. We apply all models to a control group with clinically significant transition zone cancer.TZ volume is moderately correlated with PSA level (r = 0.44). 5/54 RF are significantly correlated with PSA level (r: 0.53-0.69, p 0.05). Inclusion of each of these five features into the regression model significantly improves the explanatory value for PSA level (p 0.05). Furthermore, RF alone better explain PSA level compared to TZ volume alone (p 0.01). A systematic and significant trend for positive residuals is observed when regression models are applied to the malignant control group.A radiomics analysis of the transition zone has the potential to improve explanation of corresponding PSA level in patients with low suspicion. This knowledge may reassure radiologists to read prostate MRI cases as unremarkable, despite present hyperplastic changes.

WOS: 000439200100008, PubMed ID: 29794110, 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.

Background: Adrenalectomy is standard of care for phaeochromocytomas, but for bilateral phaeochromocytoma, the recommendations are inconsistent. However, large studies systematically investigating long-term outcomes for total adrenalectomies compared to those for patients with adrenal-sparing operations are lacking. Methods: A multi-center consortium-based registry was established to study clinical, genetic and surgical data in 623 patients with bilateral phaeochromocytomas. Findings: Of 623 patients, median age at diagnosis was 30 (range 3-79) years and 48% were female. Synchronous bilateral phaeochromocytomas were diagnosed in 396 patients and metachronousphaeochromocytomas in 227 (36%); interval to second operations were up to 40 (median 6) years. In 96% of tested patients germline mutations were detected in the genes RET (56%), VHL (34%), and others (10%). Of 849 operations, 385 (45%) surgeries in 326 patients were planned as adrenal-sparing which was successful in 251. 372 patients became steroid-dependent. Follow-up was up to 53 (median 11) years. Adrenal crises developed in 67 patients (18%) during follow-up, and 49 (13%) had manifestations of iatrogenic Cushing syndrome. Of the steroid-independent patients, 34 (14%) had developed another phaeochromocytoma within the remnant adrenal after up to 27, median 8 years, all treated with removal of the new phaeochromocytoma. Overall survival was mainly influenced by non-phaeochromocytoma comorbidities, whereas only 1% died of metastatic phaeochromocytoma. Cortical-sparing operations did not affect survival. Interpretation: Cortical-sparing operations avert lifelong steroid-dependency without affecting survival. Preoperative genetic testing is recommended even in unilateral phaeochromocytoma presentations to identify patients at heritable risk, to guide surgical approach, and inform for gene-specific extra-adrenal morbidities. Funding Statement: Supported in part by the grant AZV 16-32665A to Sarka Dvorakova and Petr Vlcek, and the Blank Foundation to Charis Eng. Declaration of Interests: None of the authors have relevant conflicts of interest. Ethics Approval Statement: The institutional review boards for human subjects’ protection or ethical committees of all participating centers approved this study. Patients provided written informed consent according to the protocols of respective institutional review boards. In The Netherlands data were collected anonymously, and no further Institutional Review Board approval is required.

Hartmut P.H. Neumann is supported by grants from the Deutsche Krebshilfe (Grant 107995 to H.P.H.N.). Stephane Richard is supported by grants from the Direction Generale de l’Organisation des Soins (French Department of Health), the Institut National du Cancer (INCa; French NCI), and the Ligue Nationale contre le Cancer (Comites du Cher et de l’Indre; French League against Cancer).

Concerning rates of pulmonary vein (PV) stenosis were reported following PV isolation (PVI) with a circular pulmonary vein ablation catheter (PVAC). As this may depend on intraprocedural imaging, we evaluated the incidence of PV stenosis in patients undergoing PVAC-PVI with continuous surveillance by intracardiac echocardiography (ICE). Multi-slice computed tomography was performed before and 3 months after PVAC-PVI with continuous ICE surveillance in 30 patients (37 % male, 65 ± 9 years). PV areas at two levels (ostial and 1 cm distally) and left atrial (LA) volumes were measured. PV area/LA volume ratio was calculated to correct for reverse LA remodelling. PV stenosis was classified as mild (25–50 %), moderate (50–75 %) and severe (>75 %). One hundred sixteen veins were isolated with PVAC with additional touch-up ablation in one patient. One patient was excluded from analysis for untriggered CT acquisition. Left atrial volume decreased from 109.1 ± 30.9 cm3 before to 98.4 ± 34.4 cm3 after ablation (p

To examine the diagnostic performance of PI-RADSv2 T2w and diffusion weighted imaging (DWI) based lexicon descriptors, inter-observer agreement for descriptor assignment and diagnostic accuracy of the PI-RADSv2 assessment categories for multiparametric prostate MRI.176 lesions in 79 consecutive patients are analyzed, lesions are histopathologically verified by MRI-ultrasound fusion biopsy. All lesions are rated according to the PI-RADSv2 lexicon, descriptors for T2w and DWI sequences and resulting assessment categories are assigned by two independent blinded radiologists. We perform receiver-operating-characteristic analysis using the assessment categories. To analyze inter-observer agreement, we calculate weighted kappa values for assessment category assignment and unweighted kappa values for descriptor assignment.PI-RADSv2 assessment categories yield an area under the curve of 0.76/0.74 (radiologist 1/radiologist 2), P0.05. Weighted kappa for agreement is 0.601 in the peripheral zone and 0.580 in the transition zone. We detect a difference in the cancer rate for PI-RADSv2 category 3 between peripheral zone (32%) and transition zone (12%), P0.05. We obtain moderate agreement at most for descriptor assignment with kappa values ranging from 0.082 (T2w shape in the transition zone) to 0.407 (T2w signal intensity in the peripheral zone) and 0.493 (ADC pattern in the peripheral zone). Our analysis corroborates typical descriptors for benign/malignant lesions, but also reveals insights into potential pitfalls - T2w wedge shaped lesions in the peripheral zone have a considerable cancer rate, despite being labelled category 2 in the lexicon.Agreement for descriptor assignment in the PI-RADSv2 lexicon is at most moderate in our study. Typical descriptors for benign and malignant lesions are validated, whereas the discriminatory power of some descriptors is challenged. The difference in the cancer rate for PI-RADSv2 category 3 between peripheral zone and transition zone should be considered when management recommendations are linked to assessment categories in the future.

Acute transmural myocardial infarction by coronary embolism in a patient with JAK2 V617F-positive essential thrombocythemia

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.

Purpose: To prospectively investigate computed tomographic (CT) image quality parameters by using different protocols and to calculate radiation dose estimates for noninvasive coronary angiography performed with dual-source CT in the step-and-shoot (SAS) mode. Materials and Methods: This study was local ethics board approved; written informed consent was obtained from all patients. In the preliminary portion of the study, 40 patients underwent CT coronary angiography in the SAS mode: at 100 kV (protocol A) in 22 patients with a body mass index (BMI) of less than 25 kg/m2 and at 120 kV (protocol B) in 18 patients with a BMI of 25–30 kg/m2. Both protocols involved use of an attenuation-based tube current and 1 mL of contrast material per kilogram of body weight. The final portion of the study involved 50 additional patients: 21 patients with a BMI of 25–30 kg/cm2 assigned to protocol B and 29 patients with a BMI of less than 25 kg/cm2 assigned to protocol C, which was performed with 100 kV, an attenuation-b...

Nodal pelvic/retroperitoneal recurrent prostate cancer (PCa) after primary therapy can be treated with salvage lymph node dissection (salvage-LND) in order to delay disease progression and offer cure for a subset of patients. Whether adjuvant radiotherapy (ART) in affected regions improves the outcome by elimination of residual tumour burden remains unclear. A total of 93 patients with exclusively nodal PCa relapse underwent choline-positron-emission tomography-computed-tomography-directed pelvic/retroperitoneal salvage-LND; 46 patients had surgery only and 47 patients received ART in regions with proven lymph node metastases. In case of subsequent prostate specific antigen (PSA) progression, different imaging modalities were performed to confirm next relapse within or outside the treated region (TR). Mean follow-up was 3.2 years. Lymphatic tumour burden was balanced between the two groups. Additional ART resulted in delayed relapse within TR (5-year relapse-free rate 70.7 %) versus surgery only (5-year relapse-free rate 26.3 %, p

We evaluated the diagnostic accuracy of choline positron emission tomography/computerized tomography for nodal relapse of prostate cancer according to topographical site and tumor infiltration size in lymph nodes.A total of 72 patients with nodal prostate cancer relapse after primary therapy underwent pelvic and/or retroperitoneal salvage lymph node dissection. Salvage was done after whole body positron emission tomography/computerized tomography with (11)C-choline or (18)F-fluoroethylcholine showed positron emission tomography positive lymph nodes but no other detectable metastasis. Diagnostic accuracy was evaluated in 160 dissected lymph node regions (pelvic left/right and retroperitoneal), 498 subregions (common, external and internal iliac, obturator, presacral, aortic bifurcation, aortal, vena caval and interaortocaval) and 2,122 lymph nodes.Lymph node metastasis was present in 32% of resected lymph nodes (681 of 2,122), resulting in 238 positive subregions and 111 positive regions. Positron emission tomography/computerized tomography was positive for 110 regions and 209 subregions. Sensitivity, specificity, positive and negative predictive values, and accuracy were 91.9%, 83.7%, 92.7%, 82.0% and 89.4% (region based), 80.7%, 93.5%, 91.9%, 84.1% and 87.3% (subregion based), and 57.0%, 98.4%, 94.5%, 82.6% and 84.9% (lesion based), respectively. Of 393 positive lymph node metastases detected by this method 278 (70.7%) were in lymph nodes with a less than 10 mm short axis diameter. Imaging sensitivity was 13.3%, 57.4% and 82.8% for a tumor infiltration depth of 2 or greater to less than 3 mm, 5 or greater to less than 6 mm and 10 or greater to less than 11 mm, respectively. Lymph node metastasis site and the radiotracer ((11)C-choline/(18)F-fluoroethylcholine) had no substantial impact on diagnostic accuracy.Choline positron emission tomography/computerized tomography detects affected lymph node regions (pelvic left/right and retroperitoneal) in patients with prostate cancer relapse with high accuracy and it seems helpful for guiding salvage lymph node dissection. Sensitivity decreases with the size of metastatic infiltration in lymph nodes. This technique detects metastasis in a significant fraction of lymph nodes that are not pathologically enlarged on computerized tomography.

Supplemental Digital Content is available in the text, Pancreatic ductal adenocarcinoma (PDAC) is characterized by a strong fibrotic stromal reaction and diffuse growth pattern. Peritumoral fibrosis is often evident during surgery but only distinguishable from tumor by microscopic examination. The aim of this study was to investigate the role of clearance of fibrotic stromal reaction at the mesopancreatic resection margin as a criterion for radical resection and preoperative assessment of resectability. Mesopancreatic stromal clearance status (S-status) was defined as the presence or absence (S+/S0) of fibrotic stromal reaction at the mesopancreatic resection margin. Detailed retrospective clinicopathologic re-evaluation of margin status and preoperative cross-sectional imaging was performed in a cohort of 91 patients operated for pancreatic head PDAC from 2001 to 2011. Conventional margin positive resection (R+, tumor cells directly at the margin) was found in 36%. However, S-status further divided the margin negative (R0) group into patients with median survival of 14 months versus 31 months (S+ versus S0, P = 0.005). Overall rate of S+ was 53%. S-status and lymph node ratio constituted the only independent predictors of survival. Stranding of the superior mesenteric artery fat sheath was the only independent radiologic predictor of S+ resection, and achieved a 71% correct prediction of S-status. Mesopancreatic stromal clearance is a major determinant of curative resection in PDAC, and preoperative prediction by cross-sectional imaging is possible, setting the basis for a new definition of borderline resectability.

Objectives To compare the impact of unenhanced and contrast-enhanced multi-detector computed tomography (MDCT) for the detection of urinary stones and urinary obstruction in patients with suspected renal colic. Methods 95 patients with suspected renal colic underwent a three-phase MDCT for evaluation of the urinary tract. The unenhanced scan and the multiphase examination were reviewed retrospectively by two radiologists for the characterization of urinary stones and signs of obstruction. Results of unenhanced MDCT were compared with those obtained during the second review of the entire multiphase examination. Results Overall diagnosis of urinary stones revealed an accuracy of 97.0% for unenhanced, and 98.9% for multiphase MDCT with a significant difference between both protocols (mixed-effects logistic regression: odds ratio 3.3; p = 0.019). With 3 versus 15 false positive ratings, multiphase MDCT was superior to unenhanced MDCT for the diagnosis of urinary stones. There was no significant difference in detecting signs of obstruction. Inter-reader agreement for overall stone detection was excellent on both unenhanced (kappa 0.84) and multiphase (kappa 0.88) MDCT. Conclusion Contrast-enhanced multiphase MDCT offers distinct advantages compared to an unenhanced approach for the assessment of urinary stone disease, and therefore should be considered as a complementary examination for patients with inconclusive findings.

Vascular endothelial growth factor (VEGF) that is secreted by tumor cells plays a key role in angiogenesis. Matrix metalloproteinase 9 (MMP-9) is produced by inflammatory cells, such as stromal granulocytes (PMN), remodels the extracellular matrix and is known to promote angiogenesis indirectly by interacting with VEGF. The aim of this study was to determine the role of PMN-derived MMP-9, its interaction with VEGF, and the efficacy of anti-angiogenic therapy targeting MMP-9 with oral Doxycycline and VEGF with Bevacizumab in pancreatic cancer (PDAC).Inhibitors to MMP-9 (Doxycycline) and VEGF (Bevacizumab) were used alone or in combination in an in vitro angiogenesis assay to test their effect on angiogenesis caused by MMP-9, VEGF, PMN and PDAC cells. In an in vivo model of xenografted PDAC, treatment effects after 14 days under monotherapy with oral Doxycycline or Bevacizumab and a combination of both were evaluated. In vitro, PMN-derived MMP-9 had a direct and strong proangiogenic effect that was independent and additive to PDAC-derived VEGF. Complete inhibition of angiogenesis required the inhibition of VEGF and MMP-9. In vivo, co-localization of MMP-9, PMN and vasculature was observed. MMP inhibition with oral Doxycycline alone resulted in a significant decrease in PDAC growth and mean vascular density comparable to VEGF inhibition alone.PMN derived MMP-9 acts as a potent, direct and VEGF independent angiogenic factor in the context of PDAC. MMP-9 inhibition is as effective as VEGF inhibition. Targeting MMP-9 in addition to VEGF is therefore likely to be important for successful anti-angiogenic treatment in pancreatic cancer.

A 71-year-old woman underwent diagnostic workup for progressive shortness of breath. Transthoracic echocardiography showed a dilated main pulmonary artery (MPA) and an anomalous configuration of the pulmonary valve. CT revealed a bicuspid pulmonary valve (BPV) and confirmed MPA dilation. Further congenital abnormalities were excluded. An isolated finding of BPV is rather rare. To our knowledge we present the first 4-dimensional CT images of a BPV. As in this case, 4-dimensional cine cardiac CT may be helpful to reveal the underlying cause of MPA dilation.

Purpose: Endovascular aneurysm repair of the infrarenal or thoracic aorta has been shown to be a less invasive alternative to open surgery. A combined aneurysm of the thoracic and abdominal aorta is complex and challenging; the involvement of renal and/or visceral branches requires new treatment methods. Methods: A hybrid approach is currently an accepted alternative to conventional surgery. Renal and/or visceral revascularisation enables subsequent stent-graft placement into the visceral portion of the aorta. Results: Knowledge of the surgical procedure and a precise assessment of the vascular morphology are crucial for pre-procedural planning and for detection of post-procedural complications. Multi-detector computed tomography angiography (MDCTA) combined with two- and three-dimensional (2D and 3D) rendering is useful for pre-interventional planning and for the detection of post-procedural complications. Three-dimensional rendering allows proper anatomical analyses, influencing interventional strategies and resulting in a better outcome. Conclusions: With the knowledge of procedure-specific MDCTA findings in various vascular conditions, the radiologist and surgeon are able to perform an efficient pre-interventional planning and follow-up examination. Based on our experience with this novel technique of combined open and endovascular aortic aneurysm treatment, this pictorial review illustrates procedure-specific imaging findings, including common and rare complications, with respect to 2D and 3D post-processing techniques

Objective We investigated the performance of low-dose dual-source computed tomography (DSCT) coronary angiography in the step-and-shoot (SAS) mode for the diagnosis of significant coronary artery stenoses in comparison with conventional coronary angiography (CCA). Design, Setting and Patients Prospective, single-center study conducted in a referral center enrolling 120 patients (71 males, age 68±9 years, BMI 26.2±3.2 kg/m2). All study participants underwent DSCT in the SAS mode and CCA within 14 days. Twenty-seven patients were given IV beta-blockers for heart rate reduction prior to CT. Patients were excluded if a target heart rate >70 bpm could not be achieved by beta-blockers or when the patients were in non-sinus rhythm. Two blinded readers independently evaluated coronary artery segments for assessability and for the presence of significant (>50%) stenoses. Sensitivity, specificity, negative (NPV) and positive predictive value (PPV) were determined with CCA being the standard of reference. Radiation dose values were calculated. Results DSCT coronary angiography in the SAS mode was successfully performed in all 120 patients. Mean heart rate during scanning was 59±6bpm (range 44-69bpm). 1773/1803 coronary segments (98%) were depicted with a diagnostic image quality in 109/120 patients (91%). The overall patient-based sensitivity, specificity, PPV, and NPV for the diagnosis of significant stenoses were 100%, 93%, 94%, and 100%. The mean effective dose of the CT protocol was 2.5±0.8mSv (range 1.2-4.4mSv). Conclusions DSCT coronary angiography in the SAS mode allows in selected patients with a regular heart rate for the accurate diagnosis of significant coronary stenoses at a low radiation dose.

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 (