Prognostic Value of Disseminated Tumor Cells in the Bone Marrow of Patients with Operable Primary Breast Cancer: A Long-term Follow-up Study

Background

Detection of disseminated tumor cells (DTC) in primary breast cancer (BC) patients’ bone marrow (BM) seems to be a surrogate marker of tumor spread and an independent prognostic factor for disease-free and overall survival.

Methods

Here we present the largest single-center cohort of patients (n = 1378) with the longest observation time (median 82.0 months). Immunocytochemical staining was performed using murine monoclonal antibody 2E11 with the avidin–biotin complex technique.

Results

At primary surgery, 49 % of patients showed MUC-1 positive cells inside their BM. Patients without BM DTC had significantly more often T1-tumors (P = 0.007) with less often affected axillary lymph nodes (P < 0.001). We observed a significantly higher incidence of distant metastases in DTC positive patients (P < 0.001). This leads to a reduced disease-free survival (P < 0.0001). Furthermore, in DTC positive patients there was a higher mortality rate and, accordingly, a reduced overall survival (P < 0.0001).

Conclusions

Due to the presence of BM DTC, patients with a clinically poorer outcome can be identified at primary surgery. We therefore suggest that DTC analysis can be used as a prognostic factor and monitoring tool in clinical trials. Future study concepts relating to DTC should aim at identification of BC patients who may profit from adjuvant systemic therapy.     

Functional evaluation of central cholinergic circuits in patients with Parkinson’s disease and REM sleep behavior disorder: a TMS study

Central cholinergic dysfunction has been reported in patients with Parkinson?s disease (PD) and hallucinations by evaluating short latency afferent inhibition (SAI), a transcranial magnetic stimulation protocol which gives the possibility to test an inhibitory cholinergic circuit in the human brain. REM sleep behavior disorder (RBD) was also found to be associated with cognitive impairment in PD patients. The objective of the study was to assess the cholinergic function, as measured by SAI, in PD patients with RBD (PD-RBD) and PD patients without RBD (PD-nRBD). We applied the SAI technique in 10 PD-RBD patients, in 13 PD-nRBD patients and in 15 age-matched normal controls. All PD patients and control subjects also underwent a comprehensive battery of neuropsychological tests. Mean SAI was significantly reduced in PD-RBD patients when compared with PD-nRBD patients and controls. Neuropsychological examination showed mild cognitive impairment in 9 out of the 10 PD-RBD patients, and in 5 out of the 13 PD-nRBD. SAI values correlated positively with neuropsychological tests measuring episodic verbal memory, executive functions, visuoconstructional and visuoperceptual abilities. Similar to that previously reported in the idiopathic form of RBD, SAI abnormalities suggest a cholinergic dysfunction in PD patients who develop cognitive impairment, and present findings indicate that RBD is an important determinant of MCI in PD.     

Cortical morphology and illness insight in patients with schizophrenia

European Archives of Psychiatry and Clinical Neuroscience - Insight into illness in schizophrenia (SZ) patients has a major impact on treatment adherence and outcome. Previous studies have linked...     

Use of single‐representative reverse‐engineered surface‐models for RSA does not affect measurement accuracy and precision

Implant migration can be accurately quantified by model‐based Roentgen stereophotogrammetric analysis (RSA), using an implant surface model to locate the implant relative to the bone. In a clinical situation, a single reverse engineering (RE) model for each implant type and size is used. It is unclear to what extent the accuracy and precision of migration measurement is affected by implant manufacturing variability unaccounted for by a single representative model. Individual RE models were generated for five short‐stem hip implants of the same type and size. Two phantom analyses and one clinical analysis were performed: “Accuracy‐matched models”: one stem was assessed, and the results from the original RE model were compared with randomly selected models. “Accuracy‐random model”: each of the five stems was assessed and analyzed using one randomly selected RE model. “Precision‐clinical setting”: implant migration was calculated for eight patients, and all five available RE models were applied to each case. For the two phantom experiments, the 95%CI of the bias ranged from ?0.28 mm to 0.30 mm for translation and ?2.3° to 2.5° for rotation. In the clinical setting, precision is less than 0.5 mm and 1.2° for translation and rotation, respectively, except for rotations about the proximodistal axis (<4.1°). High accuracy and precision of model‐based RSA can be achieved and are not biased by using a single representative RE model. At least for implants similar in shape to the investigated short‐stem, individual models are not necessary. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:903–910, 2016.

     

The hippocampus and exercise: histological correlates of MR-detected volume changes

Growing evidence indicates that physical exercise increases hippocampal volume. This has consistently been shown in mice and men using magnetic resonance imaging. On the other hand, histological studies have reported profound alterations on a cellular level including increased adult hippocampal neurogenesis after exercise. A combined investigation of both phenomena has not been documented so far although a causal role of adult neurogenesis for increased hippocampal volume has been suggested before. We investigated 20 voluntary wheel running and 20 sedentary mice after a period of 2 month voluntary wheel running. Half of each group received focalized hippocampal irradiation to inhibit neurogenesis prior to wheel running. Structural MRI and histological investigations concerning newborn neurons (DCX), glial cells (GFAP), microglia, proliferating and pyknotic cells, neuronal activation, as well as blood vessel density and arborisation were performed. In a regression model, neurogenesis was the marker best explaining hippocampal gray matter volume. Individual analyses showed a positive correlation of gray matter volume with DCX-positive newborn neurons in the subgroups, too. GFAP-positive cells significantly interacted with gray matter volume with a positive correlation in sham-irradiated mice and no correlation in irradiated mice. Although neurogenesis appears to be an important marker of higher hippocampal gray matter volume, a monocausal relationship was not indicated, requesting further investigations.