Multiparametric MRI characteristics of prostatitis and atrophy in the peripheral zone in men without prostate cancer.

PURPOSE: To analyse multiparametric magnetic resonance imaging (mpMRI) characteristics and appearance of histopathologically proven non-cancerous intraprostatic findings focussing on quantity of prostatitis and atrophy in the peripheral zone. METHOD: In this retrospective analysis consecutive patients with mpMRI followed by MRI/TRUS-fusion biopsy comprising targeted (TB) and systematic biopsy (SB) cores without prostate cancer (PC) at histopathology were included. Subgroup analysis was performed in younger men (≤50 years). The proportions of prostatitis and atrophy were quantified for each biopsy core based on histopathology. MRI findings in the peripheral zone (PZ) and index lesions (IL, most suspicious/representative lesion) were characterized regarding changes in T2w, ADC value, and enhancement of dynamic contrast enhancement (DCE) and correlated with quantity of prostatitis and atrophy. RESULTS: Seventy-two patients were analysed. The median baseline characteristics were PSA 5.4 ng/ml (4.0-7.9), PI-RADS classification 3 (2-4), prostate volume 43 ml (33-57), and PSA density 0.13 ng/ml2 (0.10-0.19). Prostatitis was found in 44 % (n = 32) and atrophy in 65 % (n = 47) of cases. The quantity of atrophy demonstrated a significant correlation to T2w changes, ADC increase and DCE enhancement (p = 0.05, p = 0.05, p = 0.01), whereas quantity of prostatitis did not show any significant correlation to the MRI changes (p = 0.68, p = 0.58, p = 0.95). Quantity of prostatitis and atrophy increased with PI-RADS classification. Younger men had lower PSA (4.4 vs. 7.8 ml/ng; p < 0.001), smaller prostate volume (40 vs. 59 ml; p = 0.001), and lower PI-RADS classification (2-3 vs. 3-4; p = 0.005) and prostatitis and atrophy were less frequently observed (p ≤ 0.01, p = 0.03). CONCLUSIONS: Quantity of atrophy and prostatitis had different influence on MRI characteristics and increased within higher PI-RADS classification. Younger men had diffuse hypointense changes at T2w images, but less quantity of prostatitis and atrophy.

Long-term outcome prediction by clinicopathological risk classification algorithms in node-negative breast cancer--comparison between Adjuvant!, St Gallen, and a novel risk algorithm used in the prospective randomized Node-Negative-Breast Cancer-3 (NNBC-3) trial.

BACKGROUND: Defining risk categories in breast cancer is of considerable clinical significance. We have developed a novel risk classification algorithm and compared its prognostic utility to the Web-based tool Adjuvant! and to the St Gallen risk classification. PATIENTS AND METHODS: After a median follow-up of 10 years, we retrospectively analyzed 410 consecutive node-negative breast cancer patients who had not received adjuvant systemic therapy. High risk was defined by any of the following criteria: (i) age <35 years, (ii) grade 3, (iii) human epithelial growth factor receptor-2 positivity, (iv) vascular invasion, (v) progesterone receptor negativity, (vi) grade 2 tumors >2 cm. All patients were also characterized using Adjuvant! and the St Gallen 2007 risk categories. We analyzed disease-free survival (DFS) and overall survival (OS). RESULTS: The Node-Negative-Breast Cancer-3 (NNBC-3) algorithm enlarged the low-risk group to 37% as compared with Adjuvant! (17%) and St Gallen (18%), respectively. In multivariate analysis, both Adjuvant! [P = 0.027, hazard ratio (HR) 3.81, 96% confidence interval (CI) 1.16-12.47] and the NNBC-3 risk classification (P = 0.049, HR 1.95, 95% CI 1.00-3.81) significantly predicted OS, but only the NNBC-3 algorithm retained its prognostic significance in multivariate analysis for DFS (P < 0.0005). CONCLUSION: The novel NNBC-3 risk algorithm is the only clinicopathological risk classification algorithm significantly predicting DFS as well as OS.

[Radioprotection of human endothelial cells by sodium selenite]. / Radioprotektion humaner Endothelzellen durch Natriumselenit.

BACKGROUND: Sodium selenite is applied in tumor patients during chemo- or radiotherapy due to its cytoprotective effects. Aim of our study was to evaluate the effect of exposure with sodium selenite on proliferation of human endothelial and tumor cells after irradiation. MATERIALS AND METHODS: We studied the proliferative activity of human umbilical vein endothelial cells in comparison to tumor cells of the HeLa, MIA Paca-2 and SiHa cell line after single-dose irradiation with 2 or 10 Gy and controls without irradiation. All cells had been exposed to different concentrations of sodium selenite prior to irradiation. Evaluation was done by BrdU-ELISA. RESULTS: Exposure of human endothelial cells with sodium selenite concentrations > or = 100 micrograms/l led to an increase of BrdU proliferation index. This effect was markedly weaker in HeLa cells and not found in SiHa and MIA Paca-2. CONCLUSIONS: High concentrations of sodium selenite can counteract the decrease of proliferative activity caused by irradiation in human endothelial cells and thus exert a radioprotective effect on these cells. This effect was observed by far stronger in endothelial cells than in tumor cells, implying the possible clinical use of sodium selenite as a protective agent for normal tissue in radiotherapy.

Radioprotection of human endothelial cells with amifostine.

MATERIALS AND METHODS: We studied the effect of amifostine on radiation sensitivity of human endothelial cells and several tumor cell lines (HeLa, MIA PaCa-2 and BxPC-3). The cells were incubated in medium with a concentration of 1 microgram/microliter amifostine and after 1 hour irradiated with 10 or 20 Gy single dose. Proliferation index was measured by BrdU assay after another 8 and 24 hours. RESULTS: The results show a higher proliferation rate of endothelial cells following radiation plus amifostine, compared with radiation alone. Amifostine induced an increase of proliferation in the control/non-irradiated human endothelial cells. After irradiation with 10 Gy single dose the proliferation of amifostine treated human endothelial cells was still higher. Amifostine exerts no apparent proliferative effect on the tumor cells. CONCLUSIONS: The results presented indicate that amifostine acts as an activation of proliferation of the human endothelial cells in a simple in-vitro system and indicate that amifostine supplementation prior to radiation therapy might exert a radioprotective effect to healthy tissue without spurring tumor growth.

[Lethal osteochondrodysplasias: prenatal and postnatal differential diagnosis]. / Letale Osteochondrodysplasien: pränatale und postnatale Differentialdiagnostik.

PURPOSE: Lethal osteochondrodysplasias show an abnormal maturation and a disturbed growth of cartilage and bones. They represent a heterogeneous group of rare genetic diseases. Their incidence is 1 to 3 in 10,000 births. MATERIAL AND METHODS: We report altogether 5 cases: two of thanatophoric dysplasia, one of achondrogenesis type II and two cases of the rare fibrochondrogenesis. The differential diagnosis in respect to ultrasonographic, morphologic, radiographic and histopathologic criteria of the most common of these diseases are discussed together with a review of the literature. RESULTS: On the basis of the ultrasound finding of the short-rib-syndrome, it is possible to differentiate between viable and lethal osteochondrodysplasias at 19 to 22 weeks of gestation. The short-rin-syndrome leads to pulmonary hypoplasia. CONCLUSIONS: It is essential to obtain an exact diagnosis postnatally by radiographic and histopathological examinations to counsel the parents concerning the risk of recurrency. The risk in this heterogeneous group of genetic diseases ranges between less than 1% up to 50% depending on the final diagnosis. Our two cases of fibrochondrogenesis in a consanguineous couple strongly suggest an autosomal recessive inheritance in this disease.

Prune-belly syndrome: therapeutic options including in utero placement of a vesicoamniotic shunt.

The prune-belly syndrome (PBS) consists of abdominal wall distention with deficiency of the abdominal wall musculature, urinary tract abnormalities, and cryptorchidism. The impaired drainage of the bladder leads to oligohydramnios and pulmonary hypoplasia. We present 4 cases of PBS diagnosed by prenatal sonography. In 2 cases, vesicoamniotic shunt therapy was not indicated because of a poor prognosis based on sonographic and laboratory findings; the pregnancies were terminated. In another case, treatment was not performed because of a twin pregnancy, and the neonate with PBS died the day of delivery by cesarean section at 31 weeks' menstrual age. In the other case, vesicoamniotic shunt therapy was successfully performed, and a healthy child was delivered. Several conditions must be met for vesicoamniotic shunt therapy to have a good chance of success: the karyotype must be normal, other malformations must be excluded by careful sonographic examination, and renal function must be normal, as determined by serial analyses of fetal urine. Generally, the shunt should be inserted as early as possible.

Expression of heat shock proteins 72/73 in human peritoneal mesothelial cells in vivo and in vitro.

Leukocyte accumulation during peritonitis leads to an injurious microenvironment which is involved in the host defense reaction but is also thought to cause peritoneal damage. We tested the hypothesis that mesothelial cells (MC) respond to the injurious microenvironment during peritonitis by an increased expression of heat shock proteins (HSP 72/73), a basic way by which cells are protected against injury. Comparison of resting MC and activated MC during peritonitis in vivo by means of immunohistochemistry revealed an increased expression of HSP 72/73. As assessed by Western immunoblotting, incubation of MC in vitro with tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) caused a time-dependent induction of HSP 72/73 expression, which was maximal 6 h after stimulation. We suggest that the increased HSP 72/73 expression of MC during peritonitis is in part induced by TNF-alpha and IL-1beta and may exert a cell-protective function, lessening MC damage during peritonitis.