Capsular penetration in prostate cancer. Significance for natural history and treatment

We established the location and extent of complete capsule penetration by prostate cancer in 176 radical prostatectomy specimens and related these findings to cancer volume, location of positive surgical margins, and presence of nodal metastases or seminal vesicle (SV) invasion. Extent of capsule penetration, cancer volume, and positive nodes/SV were strongly intercorrelated. It could not be shown that capsule penetration was related to prognosis independently of its correlation with cancer volume. Twelve cubic centimeters was a critical cancer volume; above that, combinations of extensive capsule penetration, positive surgical margins, and positive nodes/SV were almost universal. In cancers under 12 cc, positive surgical margins were only moderately correlated with cancer volume; they often represented surgical resection into the capsule rather than a complication of capsule penetration by tumor and were most common at the apex, where dissection is most difficult. In non-transition zone cancers (148 cases), capsule penetration was most common posterolaterally, where nerves penetrate the capsule. In transition zone cancers (28 cases), capsule penetration was much less common and was located more anteriorly. Apical positive margins were also relatively common in transition zone cancers, but seminal vesicle invasion was never seen.     

The predictive value of cranial ultrasound and of somatosensory evoked potentials after nerve stimulation for adverse neurological outcome in preterm infants

Thirty-nine preterm infants were studied to compare the predictive value of somatosensory evoked responses (SEPs) following median-nerve and posterior tibial-nerve stimulation with the predictive value of cranial ultrasound. With regard to the SEP, a normal median-nerve response was by no means a guarantee of a normal outcome. A normal posterior tibial-nerve response, however, almost guaranteed a normal outcome, but the test was very time consuming and the number of false positive responses was high (sensitivity. 95.6%, specificity 50%). The presence of parenchymal involvement, either due to a haemorrhage or cystic leukomalacia predicted cerebral palsy with a sensitivity of 95.6% and a specificity of 68.5%. The combination of an abnormal posterior tibial response and the presence of parenchymal brain lesions had the best predictive value with a sensitivity of 91.3% and a specificity of 81.2%. These results show that, although posterior tibial-rferve responses have a better predictive value than median-nerve responses, these values were lower than that of cranial ultrasound. The best prediction was obtained when a combination of posterior-tibial responses and cranial ultrasound was used.     

Stage A versus stage B adenocarcinoma of the prostate: morphological comparison and biological significance

Morphological features in radical prostatectomy specimens from 11 stage A and 73 stage B prostatic carcinomas were compared by mapping of tumor locations, and determinations of cancer volumes and histological patterns. Small stage A cancers were located anteromedially, while small stage B carcinomas were concentrated against the posterior capsule at the rectal surface. Small stage A carcinomas commonly invaded the anterior fibromuscular stroma and benign prostatic hyperplasia nodules, features that were uncommon even in large stage B tumors. Stage A cancers often appeared to arise within benign prostatic hyperplasia nodules and had a distinctive histological appearance. Even when large, stage A carcinomas tended not to spread close to the rectal surface of the gland. Stages A and B cancers spanned a roughly comparable volume range, and both showed progressive dedifferentiation with increasing volume. It is proposed that stages A and B cancers are biologically similar malignancies, distinguished only by their site of origin. Prognosis for patients with stage A carcinoma probably is closely related to tumor volume and dedifferentiation, features that are not reliably estimated in tissue samples removed at operation for benign prostatic hyperplasia.     

Peritoneal pockets and endometriosis. Confirmation of an important relationship, with further observations

Of 132 women with endometriosis, almost one-fifth had peritoneal pockets. Two-thirds of the structures had endometriosis either around the rim or inside. Since one-third of the pockets lacked endometriosis and fibrosis was not present as a possible cause, endometriosis does not seem to have been the likely primary cause. Rather, such peritoneal invaginations and endometriosis may be ontologically related to a separate codevelopmental factor.     

A Potential Shift From Adaptive Immune Activity to Nonspecific Inflammatory Activation Associated With Higher Depression Symptoms in Chronic Heart Failure Patients

BackgroundChronic heart failure (CHF) patients with elevated depression symptoms are at greater risk of morbidity and mortality. The mechanisms linking symptoms of depression with disease progression in CHF are unclear. However, research studies have found evidence of alterations in immune activity associated with depression symptoms that may influence heart function. The present study sought to determine the relationship between depression symptoms and chemotaxis of peripheral blood mononuclear cells (PBMCs) in CHF patients, both at rest and in response to moderate exercise.Methods and ResultsSixty-five patients diagnosed with CHF (mean age, 59.8 ± 14.5 years) and 45 non-CHF control subjects (mean age, 52.1 ± 11.6) completed the Beck Depression Inventory (BDI) before undergoing a moderate 20-minute bicycle exercise task. Chemotaxis of PBMCs was examined in vitro to a bacterial peptide f-met leu phe (fMLP) and a physiologic chemokine, stromal cell derived factor-1 (SDF-1) immediately before and after exercise. CHF patients had reduced chemotaxis to SDF-1 (P = .025) compared with non-CHF subjects. Higher BDI scores were associated with reduced baseline chemotaxis to SDF-1 in both CHF and non-CHF subjects (P = .027). In contrast, higher BDI scores were associated with increased chemotaxis to fMLP (P = .049) and SDF-1 (P = .018) in response to exercise in the CHF patients.ConclusionThe present study suggests a shift in immune cell mobility in CHF patients with greater depression symptom severity, with reduced chemotaxis to a physiologically specific chemokine at rest but increased chemotaxis to both nonspecific and specific chemical attractants in response to physical activity. This could have implications for cardiac repair and remodeling in CHF patients and therefore may affect disease progression.     

Nucleotide oligomerization domain 1 is a dominant pathway for NOS2 induction in vascular smooth muscle cells: comparison with Toll-like receptor 4 responses in macrophages

Background and purpose:

Gram-negative bacteria contain ligands for Toll-like receptor (TLR) 4 and nucleotide oligomerization domain (NOD) 1 receptors. Lipopolysaccharide (LPS) activates TLR4, while peptidoglycan products activate NOD1. Activation of NOD1 by the specific agonist FK565 results in a profound vascular dysfunction and experimental shock in vivo.

Experimental approach:

Here, we have analysed a number of pharmacological inhibitors to characterize the role of key signalling pathways in the induction of NOS2 following TLR4 or NOD1 activation.

Key results:

Vascular smooth muscle (VSM) cells expressed NOD1 mRNA and protein, and, after challenge with Escherichia coli or FK565, NOS2 protein and activity were induced. Macrophages had negligible levels of NOD1 and were unaffected by FK565, but responded to E. coli and LPS by releasing increased NO and expression of NOS2 protein. Classic pharmacological inhibitors for NF-κB (SC-514) and mitogen-activated protein kinase (SB203580, PD98059) signalling pathways inhibited responses in both cell types regardless of agonist. While TLR4-mediated responses in macrophages were specifically inhibited by the pan-caspase inhibitor z-VAD-fmk and the PKC inhibitor Gö6976, NOD1-mediated responses in VSM cells were inhibited by the Rip2 inhibitor PP2.

Conclusions and implications:

Our findings suggest a selective role for NOD1 in VSM cells, and highlight NOD1 as a potential novel therapeutic target for the treatment of vascular inflammation.