Prognostic and predictive factors in prostate cancer: historical perspectives and recent international consensus initiatives.

An understanding of prognosis in cancer medicine is important for patient care, research and cancer control programs. In prostate cancer, prognostic (predictive) factors are particularly important given the marked heterogeneity of this disease at clinical, morphologic and biomolecular levels. Clinical stage and histologic grade have historically played major roles in defining heterogeneity in prostate cancer.

Immunohistochemical stains for p63 and alpha-methylacyl-CoA racemase, versus a cocktail comprising both, in the diagnosis of prostatic carcinoma: a comparison of the immunohistochemical staining of 430 foci in radical prostatectomy and needle biopsy tissues.

The diagnosis of prostatic carcinoma and especially minimal prostatic carcinoma can sometimes be challenging on needle core biopsy and occasionally immunohistochemistry is an aid in the diagnosis. Immunostains, such as those directed against the basal cell marker p63 and, more recently, employing antibodies reactive with alpha-methylacyl-CoA racemase (AMACR), can be useful in this situation. The aim of this investigation was to assess the diagnostic utility of a p63/AMACR antibody cocktail and compare the staining pattern it produces with that using the individual antibodies alone.

Value of CDX2, villin, and alpha-methylacyl coenzyme A racemase immunostains in the distinction between primary adenocarcinoma of the bladder and secondary colorectal adenocarcinoma.

Primary adenocarcinoma of the urinary bladder is an uncommon neoplasm that can be indistinguishable morphologically from colorectal adenocarcinoma secondarily involving the bladder by direct extension or metastasis. In the current study, 17 enteric-type primary adenocarcinomas of the bladder were immunohistochemically examined for the expression of CDX2, villin and alpha-methylacyl coenzyme A racemase (AMACR), immunomarkers preferentially expressed in colorectal adenocarcinoma. For comparison, 17 secondary colorectal adenocarcinomas involving the bladder, 23 primary colorectal adenocarcinomas and 14 conventional urothelial carcinomas were similarly studied.

Neoplasms of the renal medulla: radiologic-pathologic correlation.

Tumors of the renal medulla cover a wide spectrum, with characteristic histomorphology and variable biologic profiles. Renal medullary tumors can be categorized into benign and malignant neoplasms based on histologic features and clinico-biologic behavior. They can be further classified into pediatric and adult tumors based on the patient age group.

High-grade prostatic intraepithelial neoplasia in needle biopsy as risk factor for detection of adenocarcinoma: current level of risk in screening population.

Objectives: To assess the current incidence of prostate carcinoma detection in serial biopsies in a prostate-specific antigen-based screening population after a diagnosis of isolated high-grade prostatic intraepithelial neoplasia (HG-PIN) in needle biopsy tissue.

Methods: We retrospectively identified 190 men with a diagnosis of isolated HG-PIN in needle biopsy tissue. Most men (86%) were diagnosed from 1996 to 2000.

Telavancin, a multifunctional lipoglycopeptide, disrupts both cell wall synthesis and cell membrane integrity in methicillin-resistant Staphylococcus aureus.

The emergence and spread of multidrug-resistant gram-positive bacteria represent a serious clinical problem. Telavancin is a novel lipoglycopeptide antibiotic that possesses rapid in vitro bactericidal activity against a broad spectrum of clinically relevant gram-positive pathogens. Here we demonstrate that telavancin's antibacterial activity derives from at least two mechanisms.

Urinary bladder pathology 2004: an update.

The field of urinary bladder pathology is advancing at a rapid rate, with generation of significant new knowledge on molecular pathogenesis and cell and tissue-based diagnosis. The aim of this presentation is to survey selected, recent advances in this broad field, with specific focus on histologic typing, grading, staging, molecular classification, and reporting on neoplasia of the urinary bladder.

The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo.

1 Tegaserod (Zelnorm) is a potent 5-hydroxytryptamine4 (5-HT4) receptor agonist with clinical efficacy in disorders associated with reduced gastrointestinal motility and transit. The present study investigated the interaction of tegaserod with 5-HT2 receptors, and compared its potency in this respect to its 5-HT4 receptor agonist activity. 2 Tegaserod had significant binding affinity for human recombinant 5-HT2A, 5-HT2B and 5-HT2C receptors (pKi=7.

Relating biopsy and clinical variables to radical prostatectomy findings: can insignificant and advanced prostate cancer be predicted in a screening population?

Objectives: To assess the capacity of several clinical and needle biopsy pathologic parameters to predict insignificant and advanced prostate carcinoma (CaP) in radical prostatectomy tissue from men enrolled in a prostate-specific antigen screening program.

Methods: We captured multiple clinical variables and measures of needle biopsy tumor extent from 152 men with Stage T1c CaP with a mean of six biopsy cores who were treated with radical prostatectomy. Insignificant CaP was defined as a tumor volume of less than 0.

Expression of alpha-methylacyl-coenzyme A racemase in nephrogenic adenoma.

Nephrogenic adenoma is a benign lesion composed of small glandular structures that develops along the urothelium with uncertain pathogenesis. Some investigators believe that nephrogenic adenoma develops by a metaplastic process in response to injury to the urothelium, while others believe that it arises from detached renal tubules. Nephrogenic adenoma may be present in the prostatic urethra and morphologically mimic prostatic adenocarcinoma.

Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer.

Purpose: In the prostate testosterone is converted to dihydrotestosterone (DHT) by the enzymes 5alpha-reductase (5alphaR) types 1 and 2 (5alphaR1 and 5alphaR2). Suppression of DHT formation by 5alphaR inhibition may be beneficial in early treatment or prevention of prostate cancer. Although 5alphaR2 is the dominant enzyme in the prostate, evidence indicates that 5alphaR1 may be up-regulated in some prostate cancers.

Cellular actions of somatostatin on rat periaqueductal grey neurons in vitro.

Functional studies indicate that the midbrain periaqueductal grey (PAG) is involved in the analgesic actions of somatostatin; however, the cellular actions of somatostatin in this brain region are unknown. In the present study, whole-cell patch clamp recordings were made from rat PAG neurons in vitro. In 93% of acutely isolated neurons, somatostatin inhibited Ca(2+)-channel currents.

Enhanced renal parenchymal cryoablation with novel 17-gauge cryoprobes.

Objectives: To evaluate novel, 17-gauge cryoprobes with a modified heat exchange mechanism to evaluate the area of ablation that could be achieved with 17-gauge (1.47-mm) cryoprobes.

Methods: Eleven pigs were divided into four groups.

Percent carcinoma in prostatectomy specimen is associated with risk of recurrence after radical prostatectomy in patients with pathologically organ confined prostate cancer.

Purpose: We evaluated tumor size, measured as the percent of the prostate involved by cancer, as a predictor of tumor recurrence after radical prostatectomy in patients with pathologically organ confined prostate cancer.

Materials And Methods: One of us (WJC) performed radical retropubic prostatectomy in 1,850 men who had pathologically organ confined prostate cancer with tumor size recorded between January 1988 and February 2003. The percent of prostate tissue involved by carcinoma in the radical prostatectomy specimen was estimated by visual inspection.

Enhanced renal cryoablation with hilar clamping and intrarenal cooling in a porcine model.

Objectives: To evaluate the effects of renal vascular control and intrarenal cooling on the size of renal lesions attainable with a 3.4-mm cryoprobe.

Methods: Three groups of pigs underwent unilateral laparoscopic renal cryoablation with a 3.

Laparoscopic mid sagittal hemicystectomy and bladder reconstruction with small intestinal submucosa and reimplantation of ureter into small intestinal submucosa: 1-year followup.

Purpose: We evaluated the long-term results of laparoscopic hemicystectomy and bladder replacement with small intestinal submucosa (SIS) with ureteral reimplantation into the SIS material.

Materials And Methods: A total of 12 minipigs underwent laparoscopic hemicystectomy. Six pigs underwent bladder reconstruction with SIS and ipsilateral ureteral reimplantation.

Expression of beta-catenin in prostatic adenocarcinomas: a comparison with colorectal adenocarcinomas.

We studied 101 prostatic adenocarcinomas (72 acinar 29 ductal) and 16 cases with high-grade prostatic intraepithelial neoplasia (HPIN) immunohistochemically for the expression of beta-catenin and compared the staining patterns with those of nonneoplastic prostatic epithelium and 24 colorectal adenocarcinomas. While nuclear staining for beta-catenin was evident in 20 (83%) colorectal adenocarcinomas, predominantly, membranous staining was observed in 89 prostatic adenocarcinomas (88%); the remaining 12 cases showed no immunoreactivity. In prostatic tumors expressing beta-catenin, staining intensity was comparable, increased, and decreased in 81, 4, and 4 cases, respectively compared with adjacent nonneoplastic prostatic epithelium.

A novel methodology for the synthesis of complexes containing long carbon chains linking metal centres: molecular structures of [Ru(dppe)Cp*]2(mu-C14) and [Co3(mu-dppm)(CO)7]2(mu3:mu3-C16).

Elimination of AuX(PR3)(X = halogen, R = Ph, tol) occurs readily in reactions between compounds containing C(sp)- or C(sp2)-X bonds and alkynyl or polyynyl gold(I) complexes; this reaction has been applied to the syntheses of complexes containing a variety of metal centres linked by C(n) chains (n up to 16).

Functional regulation of P2X6 receptors by N-linked glycosylation: identification of a novel alpha beta-methylene ATP-sensitive phenotype.

Investigation of rat recombinant P2X(6) receptors has been limited because of the difficulty in obtaining functional expression in heterologous systems. In this study, we demonstrate glycosylation-dependent regulation of recombinant P2X(6) receptor function and associated conferral of a novel phenotype that is sensitive to the P2X(1) and P2X(3) receptor agonist, alphabeta-methylene ATP. In cells functionally expressing P2X(6) receptors, ATP and alphabeta-methylene ATP evoked slowly desensitizing inward currents (EC(50) values, 0.

Prostate pathology of genetically engineered mice: definitions and classification. The consensus report from the Bar Harbor meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee.

The Pathological Classification of Prostate Lesions in Genetically Engineered Mice (GEM) is the result of a directive from the National Cancer Institute Mouse Models of Human Cancer Consortium Prostate Steering Committee to provide a hierarchical taxonomy of disorders of the mouse prostate to facilitate classification of existing and newly created mouse models and the translation to human prostate pathology. The proposed Bar Harbor Classification system is the culmination of three meetings and workshops attended by various members of the Prostate Pathology Committee of the Mouse Models of Human Cancer Consortium. A 2-day Pathology Workshop was held at The Jackson Laboratory in Bar Harbor, Maine, in October 2001, in which study sets of 93 slides from 22 GEM models were provided to individual panel members.

Somatostatin induces striatal dopamine release and contralateral turning behaviour in the mouse.

Application of somatostatin to the striatum of the anaesthetized rat has previously been shown to elicit large increases in extracellular levels of dopamine and GABA via a glutamate-dependent mechanism. These actions have been ascribed to the SSTR2 receptor. Here we describe experiments designed to investigate whether these effects occur in C57Bl6 mice and if they elicit rotational behaviours associated with increased dopamine in the striatum.

Gleason grading and prognostic factors in carcinoma of the prostate.

Gleason grade of adenocarcinoma of the prostate is an established prognostic indicator that has stood the test of time. The Gleason grading method was devised in the 1960s and 1970s by Dr Donald F Gleason and members of the Veterans Administration Cooperative Urological Research Group. This grading system is based entirely on the histologic pattern of arrangement of carcinoma cells in H&E-stained sections.