Supersensitive PSA-Monitored neoadjuvant hormone treatment of clinically localized prostate cancer: Effects on positive margins, tumor detection and epithelial cells in bone marrow

Objective: The present study was done to investigate the effects of supersensitive PSA-controlled inductive treatment on positive margins, detection of tumor and epithelial cells in bone marrow of 101 patients with untreated and clinically localized prostatic carcinoma (cT1-3N0M0). Methods: Hormonal treatment was given until PSA (DPD Immulite(R) third-generation assay) reached 0.3 ng/ml in only 1 case. Of the 101 patients, 82 had a measurable hypoic lesion on initial transrectal ultrasound. 84% of these became smaller, 7.5% remained unchanged and 8.5% increased. Of the 101 prostatectomy specimens, 20 (20%) were margin-positive. The incidence of affected margins was relatively high (35% from 55 patients) with cT3 tumors, but almost negligible (2% from 46 patients) in cT1-2 tumor. Our pathologists, despite their great experience in evaluating hormonally treated prostates (>500 cases) and using immunohistochemical staining, were unable to detect carcinoma in 15 (15%) specimens. Whereas only 2 (4%) of the 55 cT3 specimens were without detectable tumor, this incidence rised to 28% (13 of 46 prostates) in patients with cT1-2 tumors. Of the initial 29 patients with epithelial cells in bone marrow, only 4 (14%) remained positive after controlled induction and all of them had fewer cells than before. Conclusion: Endocrine induction controlled by a supersensitive PSA assay and continued until reaching PSA nadir is highly effective in clearing surgical margins and eliminating tumor cells from bone marrow. It seems to be clearly superior to the conventional 3 months of pretreatment at least in cT1-2 tumors in respect to surgical margins and detectability of tumor in the resected prostate. A definitive statement about the value of endocrine induction can only be given by prospective randomized studies, with optimal drugs, doses and treatment time. But the conventional 3 months of pretreatment are far from exploiting the possibilities of this therapeutic option

Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases

The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (A?). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer’s disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that A? is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of A? in the glia limitans in Alzheimer’s disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of A?. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance