[Radium-223 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) : The androgen receptor-independent active agent in the therapeutic sequence]. / Radium-223 zur Therapie des metastasierten kastrationsresistenten Prostatakarzinoms (mCRPC) : Der androgenrezeptorunabhängige Wirkstoff in der therapeutischen Sequenz.

BACKGROUND: Radium-223 improves overall survival and preserves quality of life in patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases and no known visceral metastases. Radium-223 can be used in combination with a luteinizing hormone releasing hormone (LHRH) analogue and as part of a sequential treatment scheme if disease progresses after at least two prior lines of systemic mCRPC therapies or if no other available systemic treatment is eligible. OBJECTIVES: Today physicians are faced with a previously unknown multitude and complexity of options for the treatment of mCRPC. An increasing number of clinical trials contribute to the dynamics of the therapeutic landscape. Radium-223 was approved for mCRPC treatment in 2013. Up to now the recommendations of use have been adjusted several times. Highlighting recent clinical trials and practice, this paper explores the position of radium-223 within the therapeutic sequence and outlines key elements for the interdisciplinary cooperation between uro-oncologists and nuclear medicine specialists. RESULTS: The mode of action of radium-223 does not depend on the androgen receptor (AR) pathway. Thus, it is an option in the therapeutic sequence when the efficacy of other agents is reduced by resistance. Furthermore, the efficacy of prior or subsequent medications are neither reduced nor enhanced by radium-223. The opportunity of an AR-independent and survival-prolonging medication should be taken as soon as the indication criteria are met because the incidence of visceral metastases increases during disease progression. According to current mCRPC guidelines, the osteoprotective use of bisphosphonates or denosumab is recommended, before treatment with radium-223 is started or resumed.

Sentinel Lymph Node Biopsy in Patients with Breast Cancer: Comparison of Peritumoral and Periareolar Injection.

Introduction: Intradermal periareolar injection technique for sentinel lymph node biopsy (SLNB) may offer an advantage by including multifocal breast cancer as an additional indication. In May 2008 we changed our standard procedure from peritumoral (PT) to periareolar (PA) injection. We compared the results for corresponding periods before and after the change in procedure. Material and Method: A total of 117 patients (pts.) were investigated the year after we changed our technique; a total of 152 pts were investigated in the reference period 2007. We investigated the identification rates for sentinel lymph nodes (SLN) identified scintigraphically and surgically as well as the rates of metastatic involvement (LN). Results: After PT injection, scintigraphic detection of SLN failed in 5/152 pts., and in a further 10 pts. SLN was not found at surgery. In 7 of 15 pts. in whom SLN was not detected, histology demonstrated nodal involvement. Metastases were found in the SLN of 28 of 137 pts. with successful detection of SLN; no other lymph nodes were affected in 21 of these pts. (75.0 % of pts. with positive SLN detection). With PA injection at least one SLN could always be detected using scintigraphy; only 2/117 SLN could not be found intraoperatively. Metastasis was found in SLN in 34/115 pts.; in 19/34 pts., metastatic involvement was limited to the SLN with no other lymph nodes involved (55.9 % of pts. with positive detection of SLN). Discussion: The detection rate for SLN was significantly higher using PA injection (98.3 % vs. 90.1 %). As axillary dissection was not done in SLN-negative patients, rates of false-negative detection cannot be determined. PA injection not only results in better detection rates, it also offers the advantage that the technique can be performed correctly regardless of tumour localisation.

Myocardial sympathetic innervation in diabetic patients with symptomatic coronary artery disease.

AIM: In non-diabetic patients, sympathetic innervation can be preserved even if there is major impairment of myocardial blood supply. Matters may be more complex in diabetic patients because denervation can be caused by cardiac autonomic neuropathy (CAN) or by ischemic injury. Our aim was to determine whether restrictions in myocardial blood supply have a pronounced influence on sympathetic innervation in diabetics and if this effect can be differentiated from CAN. PATIENTS, METHODS: We analyzed 20 diabetics with advanced coronary artery disease (CAD) and without known CAN. We determined quantitative myocardial blood flow using (13)N-ammonia-PET, myocardial viability with (18)F-FDG, and cardiac innervation with (11)C-HED. We investigated the relationship between regional HED retention, blood flow, and coronary flow reserve (CFR). Attenuated heart rate response to adenosine was taken as indicator for CAN (HR ratio). RESULTS: There was minor correlation of segmental stress flow and HED retention (r(2)=0.063, p<0.0001). Correlation improved when stress flow as well as HED retention were normalized to the individual maximum (r(2)=0.162, p<0.0001). In nine patients, a HR ratio <1.2 implicated subclinical CAN. Duration of diabetic disease or glycaemic control (HbA1c) did not correlate with mean HED retention in the viable segments, but with its variation coefficient. CONCLUSIONS: As in non-diabetic patients, a slight correlation exists between CFR and sympathetic innervation. The sensitivity of sympathetic nerves to reductions in CFR does not seem to be increased as compared to the results reported for non-diabetics. Besides impaired blood supply, long duration of diabetic disease and bad glycaemic control also seem to impair sympathetic innervation provoking higher heterogeneity.

[Effect of caffeine on myocardial blood flow during pharmacological vasodilation]. / Effekt von Koffein auf den myokardialen Blutfluss unter pharmakologischer Vasodilatation.

Pharmacologic stress with adenosine is frequently used for noninvasive detection of coronary artery disease. Dietary intake of caffeinated food, beverages or medications might alter adenosine-induced hyperemic blood flow, thereby compromising the diagnostic sensitivity of adenosine stress testing. In this case we report on a male patient with CAD. Myocardial blood flow at rest and during adenosine-induced hyperemia 2 hours after consumption of decaffeinated coffee and again without caffeine intake were quantified by ammonia PET. After caffeine intake there was a clearly diminished increase of myocardial blood flow during adenosine. The average coronary flow reserve in the myocardium was 1.3 after caffeine. In the baseline study without caffeine the coronary flow reserve has been improved to 2.3. Caffeine intake alters the coronary vasodilatory capacity. These findings emphasize the importance of carefully screening patients for intake of caffeinated food prior to adenosine stress testing.

Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients.

Visualisation of primary prostate cancer, its relapse and its metastases is a clinically relevant problem despite the availability of state-of-the-art methods such as CT, MRI, transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). The aim of this study was to evaluate the efficacy of carbon-11 acetate and (18)F-FDG PET in the detection of prostate cancer and its metastases. Twenty-five patients were investigated during the follow-up of primary prostate cancer, suspected relapse or metastatic disease using (11)C-acetate PET; 15 of these patients were additionally investigated using (18)F-FDG PET. Fourteen patients were receiving anti-androgen treatment at the time of the investigation. Lesions were detected in 20/24 (83%) patients using (11)C-acetate PET and in 10/15 (75%) patients using (18)F-FDG PET. Based on the results of both PET scans, one patient was diagnosed with recurrent lung cancer. Median (18)F-FDG uptake exceeded that of (11)C-acetate in distant metastases (SUV =3.2 vs 2.3). However, in local recurrence and in regional lymph node metastases, (11)C-acetate uptake (median SUVs =2.9 and 3.8, respectively) was higher than that of (18)F-FDG (median SUVs =1.0 and 1.1, respectively). A positive correlation was observed between serum PSA level and both (11)C-acetate uptake and (18)F-FDG uptake. (11)C-acetate seems more useful than (18)F-FDG in the detection of local recurrences and regional lymph node metastases. (18)F-FDG, however, appears to be more accurate in visualising distant metastases. There may be a role for combined (11)C-acetate/(18)F-FDG PET in the follow-up of patients with prostate cancer and persisting or increasing PSA.