Finn Edler von Eyben

68Ga-Labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography for Prostate Cancer: A Systematic Review and Meta-analysis

CONTEXT 68Gallium prostate-specific membrane antigen (PSMA) ligand 68Ga-HBED-CC-PSMA (68Ga-PSMA) is a promising radiotracer for positron emission tomography (PET)/computed tomography (CT) of prostate cancer. OBJECTIVE To conduct a meta-analysis to evaluate detection rate, diagnostic test accuracy, and adverse effects of 68Ga-PSMA PET/CT or PET/magnetic resonance imaging (MRI) for staging of prostate cancer and for restaging of rising prostate-specific antigen (PSA) after initial treatment. EVIDENCE ACQUISITION Following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, our systematic review searched for articles in PubMed and EMBASE databases from 2012 to July 2016. The reference standard was pathology after biopsy or surgery. The analyses used a random effect model and a hierarchical summary receiver operating characteristic model. EVIDENCE SYNTHESIS Fifteen 68Ga-PSMA PET/CT studies with 1256 patients met the inclusion criteria. Seven studies of staging PET/CT or PET/MRI detected a regional site of cancer for 203 of 273 patients (74%). Nine studies of restaging PET/CT detected sites of recurrence in 799 of 983 patients (81%) with a 50% detection rate (74 of 147 patients) for restaging PSA of 0.2-0.49 ng/ml and a 53% detection rate (56 of 195 patients) for restaging PSA of 0.50-0.99 ng/ml. Staging 68Ga-PSMA PET/CT in the studies had higher detection rates of sites in the prostate bed than restaging 68Ga-PSMA PET/CT (mean 57% vs 14%, p=0.031, t test). Both staging and restaging 68Ga-PSMA PET/CT found that a subgroup of the patients had metastatic sites in pelvic lymph nodes or distant organs. Eight studies of staging PET/CT undertook histologic correlations. We performed prostate-segment-based analysis specifically regarding the primary cancer lesion for four of these studies, and patient-based analysis specifically regarding pelvic lymph node metastases for four other studies. The pooled sensitivities for staging in the two groups of studies were 70% and 61%, and the pooled specificities were 84% and 97%. None of the studies reported complications from the PET/CT imaging. CONCLUSIONS 68Ga-PSMA PET/CT has clinical relevance to detect sites of recurrence for patients with PSA recurrence after radical prostatectomy (RP) with PSA levels less than 1.0 ng/ml. PATIENT SUMMARY Choline positron emission tomography (PET)/computed tomography (CT) can detect sites of recurrent prostate cancer in an earlier phase of prostate-specific antigen (PSA) recurrence than bone scans and CT scans, but choline PET/CT is rarely positive for patients with restaging PSA levels under 1 ng/ml. A new radiotracer called 68Ga-PSMA for PET/CT was able to detect sites of recurring cancer in up to 50% of patients who had an early rise in PSA exceeding 0.5 ng/ml after initial radical prostatectomy. The published studies did not report adverse effects of 68Ga-PSMA PET/CT imaging.

Smoking, low density lipoprotein cholesterol, fibrinogen and myocardial infarction before 41 years of age: A Danish case–control study

Background Of major coronary risk factors, smoking and total cholesterol were significant in a previous Danish case-control study of myocardial infarction at a young age. Objective To determine whether smoking was an important coronary risk factor in the context of new and major anthropometric and biochemical risk factors for myocardial infarction in individuals less than 41 years of age. Methods A prevalence hospital-based matched case-control study of young individuals. We selected 22 Caucasian cases and 24 Caucasian controls without coronary heart disease matching for age and gender and studied a series of major coronary risk factors and newer anthropometric and biochemical variables. Results In conditional univariate logistic regression analyses, the following factors were significantly associated with the coronary risk: Family history, social class, smoking, intraabdominal adipose tissue area as percentage of total abdominal adipose tissue area on a CT scan, glycosylated haemoglobin level, systolic blood pressure, total cholesterol, low density lipoprotein (LDL) cholesterol, homocysteine, and fibrinogen levels (P< 0.05). However, in multiple conditional logistic regression analyses, only smoking, LDL cholesterol, and fibrinogen levels remained significant. Ten cases (46%) and none of the 24 controls were smokers with a LDL cholesterol level 4.5mmol/l and a fibrinogen level 3.7 g/l (P=0.0003, Fishers exact test). Conclusion Out of a series of major and newer coronary risk factors in young Western Caucasians, smoking, and levels of LDL cholesterol, and fibrinogen were independent significant coronary risk factors. The findings need to be validated in prospective studies.

Smoking and other major coronary risk factors and acute myocardial infarction before 41 years of age: two Danish case-control studies.

Objective - The aim of two case-control studies of adults younger than 41 years of age was to assess how the major coronary risk factors, family history of acute myocardial infarction (AMI), obesity, hypertension and hypercholesterolemia add to the risk of AMI from self-reported current smoking (smoking). Design - An evaluation study included 35 patients and 70 individually matched controls. Results - The risk from smoking increased less than linearly and the risk from serum cholesterol concentration (cholesterol) increased linearly. In multiple conditional logistic regression analyses, smoking as a discrete variable and cholesterol as a continuous variable were significant coronary risk factors. In a final logistic regression model, the odds ratio was 6.4 (95% confidence interval (CI) 1.7-24.1) for smoking and 1.6 (CI 1.1-2.3) for each mmol/L cholesterol. A risk score summarizing the combined risk of the major coronary risk factors did not add to the final logistic regression model (p = 0.56). A validation study included 79 patients and 64 matching control patients. Conclusion - The major coronary risk factors were similar for the cases/patients and the two control groups in the two studies. Therefore, the final logistic regression model may reflect a general pattern in Denmark. Primary prevention in individuals less than 41 years of age should focus on smoking and cholesterol instead of the summarizing risk score.Objective - The aim of two case-control studies of adults younger than 41 years of age was to assess how the major coronary risk factors, family history of acute myocardial infarction (AMI), obesity, hypertension and hypercholesterolemia add to the risk of AMI from self-reported current smoking (smoking). Design - An evaluation study included 35 patients and 70 individually matched controls. Results - The risk from smoking increased less than linearly and the risk from serum cholesterol concentration (cholesterol) increased linearly. In multiple conditional logistic regression analyses, smoking as a discrete variable and cholesterol as a continuous variable were significant coronary risk factors. In a final logistic regression model, the odds ratio was 6.4 (95% confidence interval (CI) 1.7-24.1) for smoking and 1.6 (CI 1.1-2.3) for each mmol/L cholesterol. A risk score summarizing the combined risk of the major coronary risk factors did not add to the final logistic regression model (p = 0.56). A validati...

Plasminogen Activator Inhibitor 1 Activity and Other Coronary Risk Factors

Because only some coronary risk factors have been evaluated for an association with plasma plasminogen activator inhibitor 1 (PAI-1) activity, this cross-sectional study examined the association between 27 coronary risk factors and PAI-1 in 24 healthy persons without coronary heart disease (control persons) and 22 patients who had survived myocardial infarction (cases). The coronary risk factors included major coronary risk factors such as age, anthropometric measures such as intraabdominal fat, and biochemical analytes such as serum concentration of triglyceride and plasma von Willebrand factor activity. The associations were analyzed in univariate and multiple linear regression analyses. For the control persons, triglyceride and von Willebrand factor were significantly associated with PAI-1 activity (p=0.0002, R2=0.55). In contrast for the 24 cases, age and intraabdominal adipose tissue were significantly associated with PAI-1 (p=0.0011, R2=0.51). Coronary risk factors explained more than half the variation of PAI-1 activity for both study groups. However, healthy persons and patients with previous myocardial infarction differed regarding coronary risk factors associated with PAI-1.

177 Lu-PSMA-617 radioligand therapy for a patient with lymph node metastatic prostate cancer

Prostate specific membrane antigen (PSMA) is expressed in unfavorable prostate cancer. PSMA is basis for new diagnostics and theranostics. PET/CT using PSMA is more sensitive than choline PET/CT. 177Lu-PSMA radioligand therapy is mainly used for patients with end-stage prostate cancer. This report describes a patient with a third recurrence in lymph nodes. The recurrence was treated with 177Lu-PSMA radioligand therapy instead of chemotherapy with docetaxel. The effect was in part evaluated relative to that of two established salvage treatments. Prior salvage radiotherapy and abiraterone of the first and second recurrence in lymph nodes had given only a partial reduction of PSA. Nevertheless within five months of follow-up, 177Lu-PSMA radioligand therapy of the third recurrence in lymph nodes reduced PSA for a period to unmeasurable levels. 177Lu-PSMA radioligand therapy gave only mild adverse effects. In conclusion, for a patient with lymph node metastatic prostate cancer, 177Lu-PSMA-617 radioligand therapy had an attractive therapeutic profile. A follow-up study of similar patients is being planned.

Adjuvant Radiotherapy for Lymph‐node Positive Prostate Cancer

The best treatment for lymph-node positive prostate cancer remains a matter for debate. Previously, urologists gave life-long androgen-deprivation therapy (ADT) and did not use loco-regional treatment, as they thought that widespread micrometastatic disease had the highest impact on survival. Recent years have seen an increased interest in loco-regional control. In a recent series of patients with prostate cancer treated with only radical prostatectomy (RP) and pelvic lymph node dissection, 65% had biochemical recurrence after 5 years, 35% developed distant metastases, and 28% died within 10 years [1]. A controlled study showed a synergism between radiotherapy (RT) and ADT [2]. Now urologists offer selected patients RP and pelvic lymph node dissection, followed by ADT. New cohort studies reported patients treated with RP and ADT with or without adjuvant external beam RT (EBRT).

Frequency and Markers of Precursor Lesions and Implications for the Pathogenesis of Testicular Germ Cell Tumors

Background The World Health Organization classification of urologic cancer 2016 describes 3 noninvasive precursor lesions for testicular germ cell tumor type II (TGCT) of young adults. Germ cell neoplasia in situ is the initial precursor lesion. Intratubular seminoma (ITSE), and intratubular embryonal carcinoma (ITEC) are 2 intermediate precursor lesions. Microinvasive testicular germ cell tumor (MGCT) is an invasive precursor lesion. Materials and Methods We undertook a retrospective study of testes obtained using orchiectomy for TGCT and examined precursor lesions. The examinations included immunohistochemical staining of the precursor lesions for octamer‐binding transcription factor 4 (OCT4), CD117, and CD30. We examined 63 consecutive and evaluable patients. Results Of the patients, 44 had seminoma and 19 had a nonseminomatous TGCT. MGCT was more frequent than ITSE (P = .002; χ2 test). None of the testes had ITEC. Immunohistochemistry showed that 72 of 77 precursor lesions (93%) stained positive for OCT4 and CD117 and negative for CD30. The pattern represents a seminomatous immunophenotype. A meta‐analysis of the published studies regarding precursor lesions included 1007 patients. Overall, the pooled rate of ITSE was 29% (95% confidence interval [CI], 18%‐40%) and the pooled rate of MGCT was 21% (95% CI, 15%‐27%). Conclusion MGCT is a frequent intermediate precursor lesion. Micro‐Abstract The recent World Health Organization classification of urologic cancer 2016 describes 3 precursor lesions for testicular germ cell tumor type II (TGCT); germ cell neoplasia in situ is the initial precursor lesion. Intratubular seminoma (ITSE) and intratubular embryonal carcinoma (ITEC) are 2 other noninvasive intermediate precursor lesions. Microinvasive germ cell tumor (MGCT) is an invasive precursor lesion. We undertook a retrospective cohort study in Denmark to evaluate the frequency of the precursor lesions concomitant with a macroscopically overt TGCT. We examined 63 testes with TGCT. ITSE as well as MGCT were relatively frequent but we did not find ITEC. Most precursor lesions had a seminomatous immunophenotype, positive for octamer‐binding transcription factor 4 and CD117 and negative for CD30. We conclude that MGCT is a frequent intermediate precursor lesion.