[Metachronous oligometastatic prostate cancer-the more the better or only local treatment?] / Metachron oligometastasiertes Prostatakarzinom ­ viel hilft viel oder alleinige lokale Therapie?

BACKGROUND: Prostate cancer metastases may occur at diagnosis (de novo) or metachronous after treatment for localized disease. OBJECTIVE: To describe location, prognosis, and individual treatment concepts for metachronous oligometastatic prostate cancer. MATERIALS AND METHODS: Analysis of current treatment guidelines and literature for hormone sensitive, metachronous metastatic prostate cancer. RESULTS: Modern imaging modalities lead to earlier diagnosis of metachronous oligometastatic prostate cancer, which offers the opportunity to develop metastasis-directed treatment concepts. Oligometastatic recurrence may occur in locoregional lymph nodes (N1) or as distant disease (M1). N1 disease is predominantly treated by salvage lymph node dissection or radiation. Distant metastasis may be radiated in order to delay systemic treatment. The combination of androgen deprivation and novel androgen receptor-targeted drugs such as apalutamide or enzalutamide are associated with a significant survival benefit compared to castration alone in bone or visceral oligometastatic metachronous disease. CONCLUSION: Metachronous oligometastatic prostate cancer is heterogeneous with slow progression compared to men with high volume metastasis. Individual treatment concepts may decrease risk of progression and, thus, delay time to medical treatment. Multimodal approaches are currently being evaluated in clinical trials.

Tired of feeling tired - The role of circulating inflammatory biomarkers and long-term cancer related fatigue in breast cancer survivors.

BACKGROUND: Low-grade inflammation has been associated with cancer related fatigue (CRF). However, most studies focused on CRF during or shortly after treatment. Longitudinal studies are rare with inconsistent results. We assessed the association of inflammatory biomarkers with total CRF and all subdomains (physical, cognitive, affective) in long-term breast cancer survivors. METHOD: Patients recruited between 2002 and 2005 provided information on CRF at first follow-up (FU1) (N = 1292) and second follow-up (FU2) (N = 1205), after a median of 6.2 years and 11.7 years, respectively. Associations of 11 inflammatory biomarkers with CRF at FU1 and at FU2 were assessed using linear regression models. Logistic regression models were used to compare patients fatigued at both time-points and those never fatigued (N = 932). RESULTS: C-reactive protein (CRP) was significantly associated with total CRF at FU1 (ß = 1.47, 95%CI = 0.62-2.31, p = 0.0007), at FU2 (ß = 1.98, 95 %CI = 0.96-2.99, p = 0.0001) and with persistent CRF (OR = 1.29, 95%CI = 1.13-1.47, p < 0.0001). IL-6 levels were associated with total CRF at FU1 (ß = 1.01, 95%CI = 0.43-1.59, p = 0.0006), but not with CRF at FU2 or persistent CRF. No association remained significant after adjustment for relevant covariates. DISCUSSION: CRP and Il-6 were associated with risk of CRF in long-term breast cancer survivors, but were not independent of other known risk factors, suggesting that currently studied inflammatory markers are not suitable to identify patients at risk of long-term CRF.

A skin disease and needs assessment analysis of the displaced Rohingya population in the Kutupalong refugee camp, Bangladesh.

The physical, psychological and financial burden of skin disease in low- to middle-income countries, where access to skincare is limited, is poorly understood. A group that we know very little about in this regard are refugees. There are limited data on the range of skin diseases and skincare needs of this group. To better understand the skincare needs of the displaced Rohingya population residing in the Kutupalong refugee camp, Bangladesh, we collected data on demographics, living conditions and range of dermatoses. In the 380 patients assessed, fungal skin infections, predominantly dermatophytes, were by far the most common skin disease seen (n = 215), followed by dermatitis (n = 81). Skin disease can be the presenting feature in many systemic conditions and may cause significant secondary complications itself. Developing a better understanding of the skincare needs of the refugee population is essential for future healthcare planning for this vulnerable group.

The 2020 International Alliance for the Control of Scabies Consensus Criteria for the Diagnosis of Scabies.

BACKGROUND: Scabies is a common parasitic skin condition that causes considerable morbidity globally. Clinical and epidemiological research for scabies has been limited by a lack of standardization of diagnostic methods. OBJECTIVES: To develop consensus criteria for the diagnosis of common scabies that could be implemented in a variety of settings. METHODS: Consensus diagnostic criteria were developed through a Delphi study with international experts. Detailed recommendations were collected from the expert panel to define the criteria features and guide their implementation. These comments were then combined with a comprehensive review of the available literature and the opinion of an expanded group of international experts to develop detailed, evidence-based definitions and diagnostic methods. RESULTS: The 2020 International Alliance for the Control of Scabies (IACS) Consensus Criteria for the Diagnosis of Scabies include three levels of diagnostic certainty and eight subcategories. Confirmed scabies (level A) requires direct visualization of the mite or its products. Clinical scabies (level B) and suspected scabies (level C) rely on clinical assessment of signs and symptoms. Evidence-based, consensus methods for microscopy, visualization and clinical symptoms and signs were developed, along with a media library. CONCLUSIONS: The 2020 IACS Criteria represent a pragmatic yet robust set of diagnostic features and methods. The criteria may be implemented in a range of research, public health and clinical settings by selecting the appropriate diagnostic levels and subcategories. These criteria may provide greater consistency and standardization for scabies diagnosis. Validation studies, development of training materials and development of survey methods are now required. What is already known about this topic? The diagnosis of scabies is limited by the lack of accurate, objective tests. Microscopy of skin scrapings can confirm the diagnosis, but it is insensitive, invasive and often impractical. Diagnosis usually relies on clinical assessment, although visualization using dermoscopy is becoming increasingly common. These diagnostic methods have not been standardized, hampering the interpretation of findings from clinical research and epidemiological surveys, and the development of scabies control strategies. What does this study add? International consensus diagnostic criteria for common scabies were developed through a Delphi study with global experts. The 2020 International Alliance for the Control of Scabies (IACS) Criteria categorize diagnosis at three levels of diagnostic certainty (confirmed, clinical and suspected scabies) and eight subcategories, and can be adapted to a range of research and public health settings. Detailed definitions and figures are included to aid training and implementation. The 2020 IACS Criteria may facilitate the standardization of scabies diagnosis.

[PSA increase after definitive treatment]. / PSA-Anstieg nach definitiver Therapie.

Following definitive treatment with curative intent a subset of patients with prostate cancer experience biochemical recurrence. In these patients clinical parameters are mostly used to decide if a local or systemic disease recurrence is present. While salvage radiation treatment is advocated for local recurrence after radical prostatectomy, no standard recommendations exist in cases of local recurrence after primary radiation therapy although salvage prostatectomy may be considered. Imaging procedures have traditionally not routinely been recommended for the onset of prostate-specific antigen (PSA) relapse; however, prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) exhibits high detection rates even at low PSA values. Thus, the current German guidelines state that PSMA PET/CT can be considered if this could result in a decisive change in further treatment management. Currently, a positive influence on oncological long-term outcome, however, has not yet been proven.

[CEUS-diagnosis of solid renal tumors]. / CEUS ­ Diagnostik solider Nierentumoren.

CLINICAL ISSUE: Renal lesions are detected earlier, often as a result of ultrasound examinations. However, the imaging-based differential diagnosis of different tumour entities remains challenging STANDARD RADIOLOGICAL METHODS: All renal tumours >1 cm should be evaluated for malignancy by computed tomography (CT) or magnetic resonance imaging (MRI). If an angiomyolipoma diagnosis cannot be established with imaging, further diagnostics are appropriate or if malignant progression is suspected, then multidisciplinary discussion for TNM-staging based uro-oncologic therapy is usual. METHODICAL INNOVATIONS: Contrast-enhanced ultrasound (CEUS) gives clear information about the microperfusion of renal tumours. PERFORMANCE: CEUS is helpful for the differentiation of renal cysts and especially papillary renal cell carcinomas. Moreover, CEUS advances renal tumour detection compared to B­mode and Doppler ultrasound per se. Cortical pseudolesions may be confidently ruled out using CEUS. ACHIEVEMENTS: Clear differentiation of benign and malignant renal lesions >1 cm remains challenging, and only in rare cases is it possible with CEUS alone. Nevertheless CEUS is, in combination with other ultrasound techniques, eminently suitable for diagnosing focal pyelonephritis, renal abscesses and suspected renal lymphoma and supports the planning of ultrasound-assisted tumour biopsies. PRACTICAL RECOMMENDATIONS: Combining different imaging techniques is essential to accurately diagnose renal tumors. These imaging results (including the ultrasound/CEUS clips) should be viewed by the multidisciplinary cancer tumour board to facilitate individual treatment concepts for each patient.

Impact of 68Ga-PSMA-PET imaging on target volume definition and guidelines in radiation oncology - a patterns of failure analysis in patients with primary diagnosis of prostate cancer.

BACKGROUND: 68Ga-PSMA-PET-imaging has proven to be a highly sensitive and specific diagnostic element for patients with prostate cancer (PC). Does the standard clinical target volume (CTV) cover the majority of 68Ga-PSMA-PET detected lymph nodes (LNs) in a primary setting? METHODS: 25 out of 159 patients with primary PC who underwent 68Ga-PSMA-PET-imaging were analyzed in the process of this study. These 25 high-risk patients had a total of 126 LNs with positive 68Ga-PSMA-ligand uptake. A standard CTV according to the 'Radiation Therapy Oncology Group' consensus was delineated and LNs were judged whether they were in- or outside of this target volume. With a Pearson correlation we additionally evaluated whether the Gleason score, the prostate-specific antigen (PSA) value or the risk according to the Roach formula correlate with a higher chance of LNs being outside of the CTV in uncommon LN locations. RESULTS: 81 (64.3%) of 126 LNs were covered by the CTV with a complete coverage of all positive LNs inside the respective radiation volume in 11 of 25 patients (44%). LNs that were not covered by the CTV included (para-aortic,) common-iliac, pre-sacral, obturatoric, para-rectal, para-vesical and pre-acetabular locations. In a statistical analysis neither the Gleason score, nor the PSA value, nor the calculated risk with the Roach formula correlated with LNs being inside or outside of the CTV in this patient group. CONCLUSION: 68Ga-PSMA-PET-imaging proves to be a valuable asset for patients and physicians for primary diagnosis and treatment planning. In our study, trusting the RTOG consensus for CTV delineation would have led to up to 35.7% of all LNs not to be included in the clinical radiation volume, which might have resulted in insufficient radiation dose coverage.

[PSMA-radioguided surgery in localised recurrent prostate cancer]. / "PSMA-radioguided surgery" beim lokalisierten Prostatakarzinomrezidiv.

Recently, prostate-specific membrane antigen radioguided surgery (PSMA-RGS) was introduced for targeted resection of localised prostate cancer recurrence. Preliminary results show that PSMA-RGS is very sensitive and specific in tracking suspicious lesions intraoperatively. Prerequisite for PSMA-RGS is a positive 68Ga-PSMA positron emission tomography (PET) scan with a preferably singular soft tissue or lymph node recurrence. The first 63 patients treated with PSMA-RGS were analyzed. The extracorporal analysis of a total of 277 tissue specimens yielded the following test quality criteria regarding the presence of malignant tissue: sensitivity 86.2%, specificity 96.4%, positive predictive value 94%, negative predictive value 91.5%. Oncological follow-up data was available from 59 patients. There was a drop in PSA (prostate specific antigen) below 0.2 ng/ml in 38 patients (67%). Of these 38 patients, 17 (45%) are free of biochemical recurrence after a median follow-up of 12.3 months (6.7-31.9 months). Clavien-Dindo grade III complications occurred in 6 of 63 patients (9.5%). In summary, PSMA-RGS proved to be of high value in patients with localised prostate cancer recurrence for exact localisation and resection of oftentimes small metastatic tissue using intraoperative and ex vivo gamma-probe measurements. Furthermore, PSMA-RGS has the potential to positively influence oncological outcomes. However, patient identification on the basis of 68Ga-PSMA PET imaging and clinical parameters is crucial to obtain satisfactory results.

Surface plasmons in suspended graphene: launching with in-plane gold nanoantenna and propagation properties.

Graphene physics and plasmonics are two fields which, once combined, promise a variety of exciting applications. One of those applications is the integration of active nano-optoelectronic devices in electronic systems, using the fact that plasmons in graphene are tunable, highly confined and weakly damped. A crucial challenge remains before achieving these active devices: finding a platform enabling a high propagation of Graphene Plasmons Polaritons (GPPs). Suspended graphene presenting ultrahigh electron mobility has given rise to increasing interest. We numerically studied the plasmonic properties of suspended graphene. We propose a hybrid configuration and a set of conditions to launch graphene plasmons via an in-plane gold nanoantenna, for micrometric propagation of surface plasmons in suspended graphene. Finally, we propose a realistic optoelectronic device based on the use of suspended graphene.

[PET-CT and PET-MRI of the prostate : From 18F-FDG to 68Ga-PSMA]. / PET-CT/-MRT der Prostata : Von 18F-FDG zu 68Ga-PSMA.

CLINICAL/METHODICAL ISSUE: In the last few years nuclear medical diagnostics have experienced a unprecedented renaissance in the diagnostics of prostate cancer, due to the availability of hybrid imaging with positron emission tomography computed tomography (PET/CT), PET magnetic resonance imaging (PET/MRI) and single photon emission computed tomography (SPECT) CT as well as the development of prostate-specific radiopharmaceuticals. METHODICAL INNOVATIONS: The use of fluorodeoxyglucose (FDG), which has been successfully implemented for many years in PET diagnostics, is only helpful in dedifferentiated tumors due to the biological characteristics of prostate cancer. New specific radiopharmaceuticals, such as choline-derivatives, which are incorporated into the prostate cancer cell and built into the cell membrane as well as the recently developed highly specific ligands for prostate-specific membrane antigen (PSMA) are revolutionizing prostate cancer imaging and (re-) staging. PRACTICAL RECOMMENDATIONS: The 68 Ga-labeled PSMA ligands for PET-CT and PET-MRI are highly specific tracers for primary diagnostics and detection of metastases of prostate carcinoma. In risk patients, which includes patients with intermediate and high-risk tumors, they have largely replaced choline-based PET-CT, especially in the case of very low PSA values <0.5 ng/ml in the diagnostics of recurrence. The use in the primary diagnostics as PET-MRI, also in combination with multiparametric MRI (mpMRI), is promising with respect to early diagnostics and image fusion-assisted biopsy as well as surgery and irradiation planning.

Patterns of failure after radical prostatectomy in prostate cancer - implications for radiation therapy planning after 68Ga-PSMA-PET imaging.

BACKGROUND: Salvage radiotherapy (SRT) after radical prostatectomy (RPE) and lymphadenectomy (LAE) is the appropriate radiotherapy option for patients with persistent/ recurrent prostate cancer (PC). 68Ga-PSMA-PET imaging has been shown to accurately detect PC lesions in a primary setting as well as for local recurrence or for lymph node (LN) metastases. OBJECTIVE: In this study we evaluated the patterns of recurrence after RPE in patients with PC, putting a highlight on the differentiation between sites that would have been covered by a standard radiation therapy (RT) field in consensus after the RTOG consensus and others that would have not. METHODS AND MATERIALS: Thirty-one out of 83 patients (37%) with high-risk PC were the subject of our study. Information from 68Ga-PSMA-PET imaging was used to individualize treatment plans to include suspicious lesions as well as possibly boost sites with tracer uptake in LN or the prostate bed. For evaluation, 68Ga-PSMA-PET-positive LN were contoured in a patient dataset with a standard lymph drainage (RTOG consensus on CTV definition of pelvic lymph nodes) radiation field depicting color-coded nodes that would have been infield or outfield of that standard lymph drainage field and thereby visualizing typical patterns of failure of a "blind" radiation therapy after RPE and LAE. RESULTS: Compared to negative conventional imaging (CT/MRI), lesions suspicious for PC were detected in 27/31 cases (87.1%) by 68Ga-PSMA-PET imaging, which resulted in changes to the radiation concept. There were 16/31 patients (51.6%) that received a simultaneous integrated boost (SIB) to a subarea of the prostate bed (in only three cases this dose escalation would have been planned without the additional knowledge of 68Ga-PSMA-PET imaging) and 18/31 (58.1%) to uncommon (namely presacral, paravesical, pararectal, preacetabular and obturatoric) LN sites. Furthermore, 14 patients (45.2%) had a changed TNM staging result by means of 68Ga-PSMA-PET imaging. CONCLUSION: Compared to conventional CT or MRI staging, 68Ga-PSMA-PET imaging detects more PC lesions and, thus, significantly influences radiation planning in recurrent prostate cancer patients enabling individually tailored treatment.

[Stroke prophylaxis in atrial fibrillation : When, how and for whom?] / Schlaganfallprophylaxe bei Vorhofflimmern : Wann, wie und bei wem?

In patients suffering from atrial fibrillation (AF), modern antithrombotic therapy and anticoagulation strategies should be individualized based on shared decision making including patient preferences and the absolute and relative risks of stroke and bleeding. Estimation of the individual risk for stroke is still based on the CHA2DS2-VASc score. Based on the most recent guidelines for the management of AF, oral anticoagulation therapy should be considered for men with a CHA2DS2-VASc score ≥1 and women with a score ≥2, balancing the expected stroke reduction, risk of bleeding and patient preference. Both vitamin K antagonists and novel oral anticoagulants (NOAC) are effective for the prevention of stroke in AF. In AF patients treated with NOAC, kidney function should be regularly monitored to refine risk estimation and to enable dose adaptation. As an alternative to oral anticoagulation therapy, left atrial appendage occlusion may be considered for stroke prevention in patients with AF and contraindications for long-term anticoagulant treatment. This article provides a review of the indications and contraindications of modern stroke prophylaxis and discusses the approach to frequent clinical scenarios, such as treatment of patients with an acute coronary syndrome, coronary stent intervention or catheter ablation of AF.

[Significance of PSMA imaging in prostate cancer]. / Stellenwert der PSMA-Liganden-Bildgebung beim Prostatakarzinom.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignancies of men in developed countries. To improve clinical diagnostics of PCa, 68Ga-PSMA-11 was recently introduced as a new PET tracer. 68Ga-PSMA-11 is able to specifically bind to the prostate-specific membrane antigen (PSMA), which is upregulated on the surface of prostate cancer cells in most patients. OBJECTIVES: To analyse the current significance of 68Ga-PSMA-11 PET imaging in prostate cancer in relation to staging of men with initial diagnosis, biochemical recurrence and metastatic disease. MATERIALS AND METHODS: Retrospective analysis of current literature (PubMed search) regarding 68Ga-PSMA-11 PET diagnostics in primary staging, in biochemical recurrence and in metastasized disease. RESULTS: Compared to conventional imaging, 68Ga-PSMA-11 PET/CT reaches a higher sensitivity with an excellent specificity in the clinical diagnosis of primary staging as well as staging for recurrence and advanced, metastasized disease. In biochemical recurrence, 68Ga-PSMA-11 PET/CT shows significantly higher detection rates in comparison to choline PET/CT, especially in patients with low PSA values. In the clinical diagnosis of recurrent disease, therapy concepts were changed in more than a quarter of the patients due to the use of 68Ga-PSMA-11 PET/CT. The significance of staging with 68Ga-PSMA-11 PET/CT in advanced metastasized patients remains uncertain. CONCLUSIONS: Due to the excellent results of 68Ga-PSMA-11 PET imaging, even in patients with slightly elevated PSA levels, it will continue to play an important role in clinical diagnostics of prostate cancer and, thus, its clinical utilization will become more widely spread.