After radical retropubic prostatectomy 'insignificant' prostate cancer has a risk of progression similar to low-risk 'significant' cancer

OBJECTIVE

To assess progression and survival among patients with small‐volume, well‐differentiated, organ‐confined prostate cancer found at radical retropubic prostatectomy (RRP), often defined as being ‘insignificant’, thus testing whether they are indeed ‘insignificant’.

PATIENTS AND METHODS

We identified 6496 men treated for prostate cancer by RRP between 1990 and 1999, and defined ‘insignificant’ tumours as those in men having a prostate‐specific antigen (PSA) level of <10 ng/mL before RRP, a cancer volume of ≤0.5 mL, a specimen Gleason of score ≤6 and stage ≤pT2. Survival was assessed using the Kaplan‐Meier method and compared using the two‐sided log‐rank test.

RESULTS

‘Insignificant’ tumours were found in 354 (5.5%) men, of whom only one had metastatic progression and none died from prostate cancer, with a median (range) follow‐up of 9.2 (0.8–15.6) years. Biochemical progression‐free survival (87% vs 85%, respectively, at 10 years, P = 0.5), systemic progression‐free survival (100% vs 99%, P = 0.3), overall survival (91% vs 88%, P = 0.16) and cancer‐specific survival (100% in each group, P = 0.32) were each similar among men with ‘insignificant’ prostate cancer and men with low‐risk (defined by Gleason score, preoperative PSA level, seminal vesicle and surgical margin status) ‘significant’ cancer. Clinical stage, biopsy Gleason score and preoperative PSA doubling time were multivariably predictive of ‘insignificant’ tumours at RRP.

CONCLUSIONS

‘Insignificant’ prostate cancer at RRP is associated with a comparable risk of biochemical progression as low‐risk ‘significant’ cancer. Although clinical predictors for ‘insignificant’ pathology can be identified, it remains to be established whether such patients can be safely managed conservatively.     

Infiltration of sarcomas into the hip joint: comparison of CT,MRI and histologic findings in 67 cases

We analyzed the incidence, route, and characteristics of hip joint infiltration in pelvic or proximal femoral sarcomas. 67 patients with a sarcoma that originated around the hip joint (50 pelvic and 17 femoral) were included in this study. Preoperative CT and MRI were matched with the histological findings in tumor specimens. Tumor infiltration into the hip joint was suspected on the basis of preoperative imaging in 29 patients due to articular cartilage disruption, diffuse signal changes in the acetabulum or femoral neck, signs of a tumor in the joint, or markedjoint effusion. Of these 29 patients, 15 showed tumor invasion on histological examination. 12 of 31 chondrosarcomas, none of 12 Ewing's sarcomas, and 3 of 24 osteosarcomas infiltrated into the hip joint (p = 0.008). 10 of 26 low-grade sarcomas and 5 of 41 high-grade sarcomas infiltrated into the hip joint (p = 0.02). The joint infiltration rate of the chondrosarcomas was related to their size. Of 10 tumors originating in the acetabulum, 9 penetrated through or around the osseous-ligamentous junction and one through the acetabular cartilage. In 5 proximal femur lesions, all infiltrated the joint through the femoral neck, 3 of them also through the ligamentum teres.     

Molecular determinants of milk lipid secretion

Mammary epithelial cells secrete lipids by an envelopment process that produces lipid droplets coated by membranes derived from the plasma membrane and possibly secretory vesicles. This secretion process, which resembles viral budding, is hypothesized to be mediated by specific interactions between molecules on the surface of intracellular lipids and membrane elements of the cell. Multiple lines of evidence indicate that milk lipid secretion occurs through a tripartite complex between the integral transmembrane protein, butyrophilin (BTN); the soluble metabolic enzyme, xanthine oxidoreductase (XOR); and the lipid droplet surface protein, adipophilin (ADPH). However, topological evidence from freeze-fracture replica immunolabelling (FRIL) challenge this model and suggests that milk lipid secretion is mediated by butyrophilin alone. Advances in our understanding of the molecular, structural, and functional properties of these proteins now make it possible to understand the physiological functions of each of these molecules in detail and to identify the specific molecular determinants that mediate milk lipid secretion.     

Neuroendocrine expression in node positive prostate cancer: correlation with systemic progression and patient survival

PURPOSE: Neuroendocrine cells are ubiquitous but uncommon in benign and neoplastic prostate epithelium, and they are considered important for regulating cell growth and differentiation. The predictive value of neuroendocrine immunoreactivity for patient outcome after radical prostatectomy is uncertain. In this study we determined the expression of 2 important neuroendocrine markers, chromogranin and serotonin, in benign epithelium, primary prostate cancer and lymph node metastases, and correlated cellular expression with patient outcome. MATERIALS AND METHODS: We studied 196 patients with node positive prostate adenocarcinoma who underwent bilateral pelvic lymphadenectomy and radical prostatectomy at Mayo Clinic between 1987 and 1992. Mean followup was 6.8 years (range 0.3 to 11). The cellular expression of chromogranin and serotonin in matched samples of benign tissue, primary prostate cancer and lymph node metastases from the same patients was evaluated by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, pathological findings (Gleason score, DNA ploidy and cancer volume) and patient outcome, including clinical progression, cancer specific and all cause survival. RESULTS: Chromogranin immunoreactivity was greater in benign prostatic epithelium and primary cancer cases (99% each) than in those of lymph node metastases (37.5%) (pairwise comparisons with metastases p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 6% (median 5%), 6% (median 3%) and 2.2% (median 0%), respectively. Serotonin immunoreactivity was greatest in benign prostate epithelium cases (98.5%) with less in primary cancer (95%) and lymph node metastases (21.5%) (pairwise comparisons p <0.001). The mean incidence of immunoreactive cells in benign epithelium, primary cancer and metastases was 2.2% (median 3%), 2.4% (median 2%) and 0.4% (median 0%), respectively. Chromogranin expression was invariably greater than that of serotonin for all 3 diagnostic categories (p <0.0001). There was a marginally significant positive trend in the level of chromogranin expression in benign prostatic epithelium and systemic progression (p = 0.05) but no significant association with cancer specific or all cause survival (p >0.1). No significant association was observed of chromogranin expression in primary cancer or lymph node metastases with any patient outcomes (p >0.1). There was a significant association of the level of serotonin expression in benign prostatic epithelium with cancer specific survival (p = 0.03) but no significant association with systemic progression or all cause survival (p > 0.1). There were positive trends in the association of serotonin immunoreactivity in primary cancer with systemic progression (p = 0.09) and cancer specific survival (p = 0.05) but not with all cause survival (p >0.1). No significant association was observed of serotonin expression in lymph node metastases with any patient outcomes (p >0.1). CONCLUSIONS: Benign prostatic epithelium and primary prostate cancer express a significantly greater number of chromogranin and serotonin immunoreactive cells than lymph node metastases, suggesting that decreased expression of neuroendocrine markers is involved in cancer progression. However, neuroendocrine expression was marginally useful for predicting the outcome in patients with node positive prostate cancer treated with radical prostatectomy.     

Angiotensin-converting enzyme activity and the ACE Alu polymorphism in autosomal dominant polycystic kidney disease.

BACKGROUND: Previous studies concerning Alu I/D polymorphism in the ACE gene and ADPKD severity have used the Alu genotypes as a representative of the true biological variable, namely ACE activity. However, wide individual and ethnic differences in the proportion of variance in ACE activity explained by the I/D genotype may have confounded these studies. This investigation examines the association between ADPKD severity and ACE in terms of plasma enzyme activity and I/D genotypes in individuals from three different countries. METHODS: Blood samples were collected from 307 ADPKD patients (116 Australian, 124 Bulgarian and 67 Polish) for determination of ACE activity levels and I/D genotypes. Chronic renal failure (CRF) was present in 117 patients and end-stage renal failure (ESRF) in 68 patients. RESULTS: ACE activity was related to the I/D genotype, showing a dosage effect of the D allele (P=0.006). The proportion of variance due to the Alu polymorphism was 14%. No difference in ACE activity and I/D genotype distribution was found between patients with CRF versus normal renal function (P=0.494; P=0.576) or between those with ESRF versus those without ESRF (P=0.872; P=0.825). No effect of the I/D genotype on age at development and progression to renal failure (CRF; ESRF) was detected in the overall group, and in subgroups based on ethnic origin, linkage status and sex. CONCLUSION: ACE is not likely to play a role as a determinant of ADPKD phenotype severity.     

Diode laser thermokeratoplasty – first clinical experience

Purpose: Pulsed holmium lasers are currently used to correct hyperopia by means of laser thermokeratoplasty (LTK). Series of μs laser pulses are applied with a high repetition rate to induce shrinkage of corneal collagen fibers. The pulsed energy application results in intrastromal temperature peaks of up to 200 °C. A continuously emitting laser diode can – as we demonstrated recently in an invivo study on minipigs – be used for LTK and may be of advantage because the temperature rise is more steady. The aim of this study was to examine the safety, amount, and stability of hyperopic correction of diode LTK on blind human eyes. Methods: We used a laserdiode that was set to continuously emit light at λ = 1.854 μm/μ_a = 1.04 mm^–1(group I, n = 4) or 1.87 μm/μ_a = 1.92 mm^–1 (group II, n = 4). Radiation energy was 100 to 150 mW for 10 s per coagulation. Eight coagulations on a single ring (group I) and 16 coagulations on a double ring (group II) diameter were applied in the cornea concentric to the entrance pupil by means of a vacuum-fixed application mask (group I = conjunctival fixation; group II = corneal fixation) and a handpiece with a focusing optic. Preoperatively as well as 1 week, 1, 2, 3, 6 12 and 18 months postoperative ophthalmologic controls were performed and the corneal refractive power was measured. Results: In group I initial refractive changes of up to + 4.9 D were achieved (1 week postoperative). However, due to the great penetration depth of the laser irradiation, large endothelial defects resulted beneath the stromal coagulations. In group II an initial refractive change of up to + 6.8 D was achieved and as a result of the reduced penetration depth, the endothelial cell damage was much reduced. Partial regression of the refractive effect occured in all subjects, which continued in higher refractive changes during the 2^nd postoperative year. The refractive effect at 12 months was + 0.6 to + 1.5 D in group I and + 0.9 to + 5.7 D in group II. At 12 months the induced astigmatism was 0.5 to 2.2 D in group I and 0.3 to 1.6 D in group II. No serious adverse effects were noticed. Conclusion: A continously emitting laser diode working at a wavelength of 1.87 μm can be used to correct hyperopia by means of LTK safely and effectively. Regression occurs predominantly in the first 6 postoperative months. Further studies must be conducted to determine the importance of patient inherent parameters such as age in establishing a nomogram.      

Mucosal Integrity Testing Can Detect Differences in the Rectums of Patients with Inflammatory Bowel Disease Compared to Controls: A Pilot Study

Digestive Diseases and Sciences - While the pathogenesis of inflammatory bowel disease (IBD) is incompletely understood, disruption of epithelial integrity is suspected to play a prominent role in...     

The Effect of Pain on Major Cognitive Impairment in Older Adults

Older adults frequently report pain; cross-sectional studies have shown that pain is associated with worse cognitive function. However, longitudinal studies are lacking. We prospectively studied 441 participants without dementia, including 285 with pain, aged 65 years and older, enrolled in the Central Control of Mobility in Aging study, a prospective cohort study. We analyzed the longitudinal association between pain (measured with the Medical Outcomes Study pain severity scale) and major cognitive impairment (measured with the Repeatable Battery for the Assessment of Neuropsychological Status and the Trail Making Test Delta) using Cox regression analysis adjusted for age, gender, ethnicity, and education. Over a mean follow-up of 2.75 years (standard deviation?=?1.94), there was no difference in the risk of developing cognitive impairment between participants with pain and participants without pain. However, among those with pain, risk for developing major memory impairment was higher among those with high levels of pain than those with low levels of pain (adjusted hazard ratio?=?3.47, 95% confidence interval?=?1.42–8.46). The association with pain and incident impairments in attention or executive function was not significant. We did not find that pain is associated with incident cognitive impairment in general, but among older adults with pain, a high level of pain is associated with increased risk of developing incident memory impairment.