Staging for distant metastases in operable breast cancer: a suggested expansion of the ESMO guideline recommendation for staging imaging of node-negative, hormonal receptor-negative disease

We evaluated the impact of staging procedures to detect asymptomatic distant metastases (DM) in the management of women with operable invasive breast cancer (BC, entire cohort: n = 866). Out of 472 patients with lymph node (LN)-negative disease (pN0), DM were found in four cases (detection rate: 0.8%). All four patients presented with established risk factors: hormone receptor (HR)-negative status, HER2-positive status, n = 3; ‘triple-negative' disease, n = 1. Considering the subgroup of LN-negative patients whose tumors showed the risk factor ‘negative HR status' (n = 66), the detection rate of DM was 6%. The detection rates of DM in higher pN categories were as follows: pN1:1.7%; pN2:9.5%; pN3:13.5%. We generally support the international guidelines, including those published by the European Society for Medical Oncology (ESMO) which emphasize that patients with early-stage BC do not profit from radiological staging for the detection of DM and recommend refraining from this. However, we would expand these guidelines and propose that screening should be carried out in node-negative patients whose tumors show established tumor-related risk factors (e.g. HR-negative and HER2-positive status), since in this particular subcohort, the detection rate of DM is with 6% similarly high as that of patients with four to nine positive LN

Geoarchaeological evidence of Ostia’s river harbour operating until the fourth century AD

Ancient Ostia at the mouth of the River Tiber into the Tyrrhenian Sea was largely significant for the economic supply of Rome. Ostia itself experienced an extraordinary period of prosperity in the second century AD. Starting in AD 42, a first new harbour at Portus was built by Emperor Claudius close to Ostia. It reached its full functionality under Emperor Trajan in the early second century AD, only. At Ostia itself, previous archaeological and geoarchaeological studies have brought to light a lagoon-type harbour at the western fringe of the city operating between the fourth and the second century BC in an artificially excavated harbour basin. From the second century BC onwards, a considerably smaller and shallower part of this western harbour basin was still in function as a fluvial harbour. So far, it was unclear whether Ostia’s western harbour was still in use when the harbour at Portus was set into function in the first to second century AD, or if the latter partially replaced Ostia’s harbour infrastructure. According to archaeological evidence, Ostia’s navalia-temple-complex, the main building at the eastern fringe of the western river harbour basin, was built in the second quarter of the first century AD. Was this prestigious harbour building erected although the associated harbour seemed to have been already given up before? We conducted detailed geoarchaeological investigations at the immediate western front of the navalia-temple complex. Results were compared with archaeological data obtained from excavations carried out in 2000/2001. A multi-proxy approach was used to reconstruct the history and evolution of the harbour. It was possible to identify subsurface structures and evaluate the local stratigraphy. Vibracoring brought to light a more than 1 m thick section of an opus reticulatum wall with parts of the original opus latericium on top. Such walls originally separated vaulted shipshed chambers of the navalia-temple complex at Ostia, which in turn formed the substructure of a temple complex located above it. Another core revealed the sedimentary infill of a former chamber of the building. Based on radiocarbon dating, the navalia was in use between the first and the fourth centuries AD with a water depth of maximum ca. 1.2 m at the immediate western front. This is in agreement with the date of construction of the navalia-temple complex in the second quarter of the first century AD. The relative sea level at that time was around 0.64 m below the present sea level. The harbour and the navalia were obviously accessible only for flat-keeled lighters and cargo boats. Larger cargo ships were either unloaded along the riverbank to the north of ancient Ostia (Hadler et al. 2019) or moored offshore, their freight being reloaded to smaller lighters. Chronostratigraphic data further show that the navalia-temple complex was in use until the second half of the fourth century AD. It was not before AD 355–363 or shortly afterwards, that the harbour site was abandoned. Ostia’s western river harbour was neither abandoned nor completely silted up before the harbour at Portus was established as previously assumed by other authors. Actually, the western front of the navalia-temple complex was hit by an extreme wave event, leaving a sand layer approx. 0.5 m thick, at or shortly after AD 355–363 which led to the final abandonment of Ostia’s western river harbour. This event is interpreted as a tsunami that may have hit the wider coastal region

The optical system of the H.E.S.S. imaging atmospheric Cherenkov telescopes, Part II: mirror alignment and point spread function

Mirror facets of the H.E.S.S. imaging atmospheric Cherenkov telescopes are aligned using stars imaged onto the closed lid of the PMT camera, viewed by a CCD camera. The alignment procedure works reliably and includes the automatic analysis of CCD images and control of the facet alignment actuators. On-axis, 80% of the reflected light is contained in a circle of less than 1 mrad diameter. The spot widens with increasing angle to the telescope axis. In accordance with simulations, the spot size has roughly doubled at an angle of 1.4 degr. from the axis. The expected variation of spot size with elevation due to deformations of the support structure is visible, but is completely non-critical over the usual working range. Overall, the optical quality of the telescope exceeds the specifications.Comment: 23 pages, 13 figure

The metastatic potential of seminomatous germ cell tumours is associated with a specific microRNA pattern

Background Seminomatous germ cell tumours (SGCT) are the most frequent malignancy in young men. Reliable prognostic biomarkers for the prediction of metastasis at diagnosis and the risk of relapse in clinical stage I (CSI) are lacking. Adjuvant therapies carry a risk of overtreatment, whereas salvage therapies have a risk of high toxicities. Thus, the identification of reliable prognostic biomarkers is highly desirable to identify patients who will benefit from early adjuvant treatment. MicroRNAs (miRNAs) regulate tumour development and progression, and their potential as biomarkers has already been proven in a variety of malignancies. Objectives The aim of our study was to define a specific miRNA expression pattern that discriminates metastatic from non‐metastatic primary SGCT. Materials and methods Total RNA was isolated from 24 formalin‐fixed paraffin‐embedded (FFPE) primary SGCT tumours (10 non‐metastatic, five metachronously and nine synchronously metastatic) and from 10 normal testicular tissue samples. Microarray analysis was performed for global miRNA expression profiling. The results were validated by quantitative real‐time polymerase chain reaction (qRT‐PCR). Statistical analysis was performed using SPSS. Results Microarray analyses revealed a specific miRNA pattern that distinguishes metastatic from non‐metastatic SGCT. Sixty‐three miRNAs were differentially expressed in metastatic compared to non‐metastatic tumours (P < .01). Microarray results were confirmed by qRT‐PCR for three out of five selected miRNAs (miR‐29c‐5p, miR‐506‐3p and miR‐371a‐5p; P < .05). All five miRNAs (miR‐29c‐5p, miR‐506‐3p, miR‐1307‐5p, miR‐371a‐5p and miR‐371a‐3p) showed differential expression between tumour and normal tissues (P < .05). Conclusion Metastatic primary SGCTs are characterized by a specific miRNA expression pattern. Therefore, specific miRNAs could represent a new tool to predict the metastatic potential in SGCT patients

Antibody-based immunotherapy for ovarian cancer: where are we at?

Cytoreductive surgery and chemotherapy continue to be the mainstay of ovarian cancer treatment. However, as mortality from advanced ovarian cancer remains very high, novel therapies are required to be integrated into existing treatment regimens. Immunotherapy represents an alternative and rational therapeutic approach for ovarian cancer based on a body of evidence supporting a protective role of the immune system against these cancers, and on the clinical success of immunotherapy in other malignancies. Whether or not immunotherapy will have a role in the future management of ovarian cancer is too early to tell, but research in this field is active. This review will discuss recent clinical developments of selected immunotherapies for ovarian cancer which fulfil the following criteria: (i) they are antibody-based, (ii) target a distinct immunological pathway, and (iii) have reached the clinical trial stage. Specifically, the focus is on Catumaxomab (anti-EpCAM × anti-CD3), Abagovomab, Oregovomab (anti-CA125), Daclizumab (anti-CD25), Ipilimumab (anti-CTLA-4), and MXD-1105 (anti-PD-L1). Catumaxomab has reached phase III clinical trials and exhibits promise with reports, showing that it can cause a significant and sustained reduction in ascites. Phase I-III clinical trials continue to be conducted on the other antibodies, some of which have had encouraging reports. We will also provide our perspective on the future of immunotherapy for ovarian cancer, and how it may be best employed in treatment regimen

An unidentified TeV source in the vicinity of Cygnus OB2

Deep observation (∼113 hrs) of the Cygnus region at TeV energies using the HEGRA stereoscopic system of air Čerenkov telescopes has serendipitously revealed a signal positionally inside the core of the OB association Cygnus OB2, at the edge of the 95% error circle of the EGRET source 3EG J2033+4118, and ∼0.5° north of Cyg X-3. The source centre of gravity is RA αJ2000: 20hr32m07s± 9.2stats±2.2syss, Dec δJ2000: +41°30′30″2.0stat±0.4′sys. The source is steady, has a post-trial significance of +4.6σ, indication for extension with radius 5.6′ at the ∼3σ level, and has a differential power-law flux with hard photon index of - 1.9 ± 0.3stat ± 0.3sys. The integral flux above 1 TeV amounts ∼3% that of the Crab. No counterpart for the TeV source at other wavelengths is presently identified, and its extension would disfavour an exclusive pulsar or AGN origin. If associated with Cygnus OB2, this dense concentration of young, massive stars provides an environment conducive to multi-TeV particle acceleration and likely subsequent interaction with a nearby gas cloud. Alternatively, one could envisage γ-ray production via a jet-driven termination shock.F. A. Aharonian, ... G. P. Rowell, ... [et al

Single-boson exchange functional renormalization group application to the two-dimensional Hubbard model at weak coupling

We illustrate the algorithmic advantages of the recently introduced single-boson exchange (SBE) formulation for the one-loop functional renormalization group (fRG), by applying it to the two-dimensional Hubbard model on a square lattice. We present a detailed analysis of the fermion-boson Yukawa couplings and of the corresponding physical susceptibilities by studying their evolution with temperature and interaction strength, both at half filling and finite doping. The comparison with the conventional fermionic fRG decomposition shows that the rest functions of the SBE algorithm, which describe correlation effects beyond the SBE processes, play a negligible role in the weak-coupling regime above the pseudo-critical temperature, in contrast to the rest functions of the conventional fRG. Remarkably, they remain finite also at the pseudo-critical transition, whereas the corresponding rest functions of the conventional fRG implementation diverge. As a result, the SBE formulation of the fRG flow allows for a substantial reduction of the numerical effort in the treatment of the two-particle vertex function, paving a promising route for future multiboson and multiloop extensions