Prostate Risk Index (PRIX) as a New Method of Risk Classification for Clinically Localized Prostate Cancer

PURPOSE: The aim of this study is (1) to develop a new method of risk classification for clinically localized prostate cancer; (2) to examine it in terms of compatibility with existing data such as nomograms; and (3) to compare it with existing risk-grouping methods. MATERIAL AND METHODS: The new grading system introduced here consists of three factors. The first is a prostate-specific antigen (PSA) of 4.1-10.0 ng/ml (score 0), 10.1-20.0 ng/ml (score 1), and >20.0 ng/ml (score 2). The second is a Gleason score (GS) of 6 (score 0), 7 (score 1), and 8-10 (score 2). The third is T classifications (UICC 2002) of T1c-T2a (score 0), T2b-T2c (score 1), and T3a (score 2). The sum of the three scores was named Prostate Risk Index (PRIX). Then, the compatibility of PRIX with the Partin Table, Kattan Nomogram, and Roach's formula was examined. At the same time, PRIX was compared with D'Amico, the National Comprehensive Cancer Network (NCCN), and Seattle classifications. RESULTS: PRIX 0 corresponded to 1-2% of pathologic lymph node involvement (pLN+) according to the Partin Table; PRIX 1 to 3-4%; PRIX 2 to 7-10%; PRIX 3 to 14-18%; PRIX 4 to 24-29%; PRIX 5 to 32-37%; and PRIX 6 to 42%. PRIX well separated the risks with relatively narrow ranges of probability, while D'Amico, NCCN, and Seattle classifications generally gave wide ranges especially for high-risk groups, both in the Partin Table and Kattan Nomogram. Roach's formula sometimes overestimated the risk compared to the Partin Table. CONCLUSION: PRIX fully corresponded to the Partin Table in terms of pLN+, and corresponded to the other nomograms better than any existing risk-grouping method. PRIX may thus function as a prognostic factor or contribute to patient selection in clinically localized prostate cancer.     

Successful catheter ablation for incessant ventricular tachycardia in a patient with hypertrophic cardiomyopathy.

A 35-year-old man was referred to Nihon University Hospital because of repetitive ventricular tachycardia (VT) at 180-200 beats/min. QRS morphology of the VT was right bundle branch block with a northwest axis. Transthoracic echocardiography showed hypertrophic cardiomyopathy. Coronary angiography was normal and left ventriculography showed neither obstruction in the left ventricle (LV) nor any pressure gradients within the LV or between the LV and aorta. Hemodynamic deterioration occurred during VT. Intracardiac mapping showed that the VT originated from the posteroseptal portion of the LV near the apex and Purkinje potentials that preceded the onset of the QRS complex by 58-70 ms were documented. Radiofrequency ablation at these sites terminated the VT, which has not recurred for 25 months.     

Co-operative mineralization and protein self-assembly in amelogenesis: silica mineralization and assembly of recombinant amelogenins in vitro

An amorphous silica mineralization technique was used to produce inorganic/protein composites to elucidate the structure and mechanism of formation of amelogenin assemblies, which may play an important role in regulating enamel structure during the initial stages of amelogenesis. Full-length recombinant amelogenins from mouse (rM179) and pig (rP172) were investigated along with key degradation products (rM166 and native P148) lacking the hydrophilic C terminus found in parent molecules. The resulting products were examined using transmission electron microscopy and/or small-angle X-ray scattering. Using protein concentrations of 0.1–3 mg ml⁻¹, large monodisperse spheres of remarkably similar mean diameters were observed using rM179 (124 ± 4 nm) and rP172 (126 ± 7 nm). These spheres also exhibited 'internal structure', comprising nearly spherical monodisperse particles of ≈ 20 nm in diameter. In the presence of rM166, P148, and bovine serum albumin (control), large unstructured and randomly shaped particles (250–1000 nm) were observed. Without added protein, large dense spherical particles of silica (mean ≈ 500 nm) lacking internal structure were produced. These findings demonstrate that full-length amelogenins have the ability to form higher-order structures, whereas amelogenins that lack the hydrophilic C terminus do not. The results also suggest that full-length amelogenin can guide the formation of organized mineralized structures through co-operative interactions between assembling protein and forming mineral.     

Properties of membranes from polyelectrolyte complexes consisting of methyl glycol chitosan, [2-(diethylamino)ethyl]dextran,and poly(potassium vinyl sulfate)

Water-insoluble polyelectrolyte complexes (PEC) were prepared by mixing methyl glycol chitosan (MGC, 1 ) and [2-(diethylamino)ethyl]dextran (EA, 2 ) with poly(potassium vinyl sulfate) (PVSK, 3 ) in aqueous solution at various hydrogen ion concentrations. Elemental analyses, IR spectroscopy, and solubilities of PEC reveal that PEC differ in molecular structure and properties according to pH. It seems that the degree of dissociation and the conformation of MGC, EA, and PVSK change with pH. PEC membranes were made by casting from solutions of all kinds of PEC, and transport phenomena through the membrane of PEC prepared in 4 wt.-% HCl solution were investigated under various conditions. The driving force of the transport depends on the membrance potential, Donnan potential, and diffusion potential, according to measurements of the transport ratio of Na⁺ and the electric potential difference between the left- and right-hand side of the membrane. Moreover, the permeability of K⁺ is higher than that of Na⁺.     

Intravesical instillation therapy with bacillus Calmette-Guérin for superficial bladder cancer: Study of the mechanism of bacillus Calmette-Guérin immunotherapy

AIM: In order to clarify the initial step of the mechanism by which bacillus Calmette-Guérin (BCG) exhibits antitumor activity via the immune response induced in the bladder submucosa after intravesical BCG therapy for human bladder cancer, various cytokines secreted in the urine after BCG instillation were measured. METHODS: After transurethral resection of bladder cancer, a 6-week course of BCG instillation was performed. At the first and sixth weeks' dosings, spontaneously excreted urine was collected before and 4, 8, and 24 h after BCG instillation. The urinary cytokines were determined by Sandwich enzyme-linked immunosorbent assay using monoclonal antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1beta, IL-8, interferon (IFN)-gamma, and IL-12. RESULTS: After the BCG therapy, various cytokines, such as GM-CSF, TNF-alpha, G-CSF, IL-1beta, IL-8, IFN-gamma, and IL-12 were secreted, comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-alpha 4 h after the sixth week's instillation were significantly higher than the pre-instillation levels. There were no significant increases in the urinary IFN-gamma or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-alpha level 4 h after the sixth week's instillation had a strong tendency towards the absence of recurrence, with a mean follow-up of 54.1 months. The Kaplan-Meier curve showed the 2, 5, and 10-year recurrence-free survival rates were 72.4%, 65.8%, and 56.4%, respectively. CONCLUSIONS: We suggested that the urinary levels of TNF-alpha might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence.     

The prognostic value of E-cadherin, α-, β- and γ-catenin in bladder cancer patients who underwent radical cystectomy

OBJECTIVES: To determine the value of the loss of expression of E-cadherin and cadherin associated molecules as useful markers for both prognosis and chemosensitivity in bladder cancer patients who have undergone radical cystectomy. PATIENTS AND METHODS: In 55 paraffin embedded specimens of radical cystectomy at our hospital from 1982 to 2000, the expression of E-cadherin, alpha-, beta- and gamma-catenin was examined by immunohistochemical staining. To evaluate the prognostic significance of these molecules, Kaplan-Meier survival curves were constructed and a statistical analysis was calculated by a log-rank test. A multivariate test (tumor stage, tumor grade, lymph node metastasis, configuration, the expression of E-cadherin, alpha-, beta- and gamma-catenin) was performed to detect prognostic markers. RESULTS: Normal expression was found in 33 cases (60.0%) for E-cadherin, 29 (52.7%) for alpha-catenin, 31 cases (56.4%) for beta-catenin, and 31 cases (56.4%) for gamma-catenin. The expression patterns for E-cadherin, alpha-, beta- and gamma-catenin were significantly correlated with each other (P < 0.01). Survival analysis showed a significant difference between normal and aberrant expression in each staining. A multivariate analysis revealed that the expression of alpha- catenin was an independent prognostic factor (P = 0.0191). In 23 patients that received adjuvant chemotherapy, there was a significant difference in survival between the normal and aberrant expression of alpha-catenin, but not other molecules. CONCLUSION: Alpha-catenin may not only be a good prognostic marker, but also one of key molecules that determine the chemosensitivities in patients with invasive bladder cancer.     

Chronic acid ingestion promotes renal stone formation in rats treated with vitamin D3

OBJECTIVE: Although hypercalciuria, a well-established adverse effect of vitamin D3, can be a risk factor of renal stone formation, the risk of nephrolithiasis has not been well defined. The consumption of a diet high in acid precursors is often cited as a risk factor for the development of calcium-based kidney stones. In the present study, we investigated the effect of chronic acid ingestion on kidney stone formation in rats treated with calcitriol (1-25[OH]2 D3). METHODS: Control rats (C-C), calcitriol-treated rats (C-V; three treatments of 0.5 microg of calcitriol per week) and acid-ingested (water containing 0.21 mol/L NH4Cl), calcitriol-treated (three treatments of 0.5 microg of calcitriol per week) rats (A-V) were fed in metabolic cages. After 1 month, urine, blood, kidney and bone samples were analyzed. RESULTS: The A-V rats exhibited elevated serum calcium concentrations, urinary calcium and phosphate excretion, urinary type I collagen cross-linked N-peptide (NTx)/creatinine values, mRNA expression of osteopontin in the kidney, and renal calcium contents as well as decreased bone mineral densities, compared with the C-C and C-V rats. Urinary citrate excretion was lower and NaDC-1 mRNA expression in the kidney was higher in the A-V rats than in the C-C and C-V rats. Calcium phosphate kidney stones were found in the A-V rats. CONCLUSIONS: The ingestion of NH4Cl, an acid precursor, promotes calcium phosphate kidney stone formation in calcitriol-treated rats. The chronic intake of a diet rich in acid precursors may be a risk factor for the development of kidney stones in subjects who are being treated with calcitriol.     

Effect of Inflammation on Costimulation Blockade-Resistant Allograft Rejection

Previously, we reported that allogeneic skin grafts were rapidly rejected by CD28 and CD40 ligand double deficient mice mediated by CD8⁺ T cells. These results indicated that some elements in addition to CD28- and CD40-mediated costimulation provide stimulatory signals for the activation of donor-specific CD8⁺ T cells. In this report, we investigated the role of inflammation associated with transplantation on costimulation-independent priming of CD8⁺ T cell during graft rejection. B6 RAG1 KO mice were transplanted with BALB/c-skin and adoptively transferred with syngeneic CD8⁺ T cells the same day or 50 days after transplantation. When blockade of CD28- and CD40-mediated costimulation failed to prevent acute rejection of freshly transplanted skin grafts, it efficiently delayed rejection of well-healed skin grafts. These results showed that factors associated with transplantation have essential roles in inducing costimulation blockade-resistant allograft rejection. Costimulation blockade failed to prevent acute graft-infiltration of NK cells and increasing expression of intragraft IL-12 and IL-15. These factors may trigger the graft-infiltration and priming of CD8⁺ T cells to induce costimulation blockade-resistant allograft rejection.     

Late-onset chylothorax after pulmonary resection and systematic mediastinal lymph node dissection for lung cancer

Late-onset chylothorax occurred 49 days after right lower lobectomy for lung cancer in a 76-year-old man. Chylothorax was successfully managed by conservative treatment with chest tube drainage and an enteral low-fat diet. Chylothorax may occur in the late period after pulmonary resection and systematic mediastinal lymph node dissection for lung cancer, for which conservative management is the treatment of choice.