Gleason Score Evolution and the Effect on Prostate Cancer Outcomes.

Objectives: We evaluated how the changes in Gleason grading affected the long-term outcomes of a large prostatectomy cohort.

Methods: We obtained long-term follow-up (16.7 years) in 581 patients having undergone radical retropubic prostatectomy between 1985 and 1995.

Diagnosing Osteomyelitis: A Histology Guide for Pathologists.

Histopathologic examination of bone specimens coupled with bone culture is considered the gold standard for the diagnosis of osteomyelitis (OM). Despite this, studies have demonstrated interpathologist agreement in the diagnosis of OM as low as 30%, largely stemming from a lack of specific definitions and diagnostic criteria. Review of the literature has provided insight into the lifecycle of OM, illustrating the histologic progression of OM phases from acute to chronic, and provides support for defining subcategories of OM.

A pilot study in intraparenchymal therapy delivery in the prostate: a comparison of delivery with a porous needle vs standard needle.

Background: New biologic therapies directly injected into the prostate are in clinical trials for prostatic diseases. There is a need to understand distribution of injected therapies as a function of prostatic anatomy, physiology, and device design.

Methods: A needle with a porous length of customizable-length was tested and its performance compared with a standard needle.

Failure of Ploidy and Proliferative Fraction to Predict Long-Term Outcome After Prostatectomy.

Background: Historically, ploidy and S phase percentage appeared to be promising predictors for prostate cancer recurrence. Lack of uniformity and consistency hampered their development. We evaluated ploidy and S phase for prostate cancer death in a cohort of patients with long-term follow-up.

TRIG on TRACK: educating pathology residents in genomic medicine.

Genomic technologies are dramatically changing the practice of medicine. Next-generation sequencing has allowed prognostic stratification of cancer patients, personalized drug therapy and the identification of genetic risk factors for a multitude of diseases. As the physicians who oversee tissue- and laboratory-based diagnostic testing, pathologists must understand and utilize this new technology for the benefit of patients; however, only a minority of pathology residency programs currently provide training in genomics.

Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study.

Background: Optimum management of clinically localised prostate cancer presents unique challenges because of the highly variable and often indolent natural history of the disease. To predict disease aggressiveness, clinicians combine clinical variables to create prognostic models, but the models have limited accuracy. We assessed the prognostic value of a predefined cell cycle progression (CCP) score in two cohorts of patients with prostate cancer.

Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710).

Objective: • To determine whether the effect of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) on the survival of patients with locally advanced urothelial carcinoma (UC) of the bladder treated with radical cystectomy varies with the presence of non-urothelial components in the tumour.

Patients And Methods: • This is a secondary analysis of the Southwest Oncology Group-directed intergroup randomized trial S8710 of neoadjuvant MVAC followed by cystectomy versus cystectomy alone for treatment of locally advanced UC of the bladder. • For the purpose of these analyses, tumours were classified based on the presence of non-urothelial components as either pure UC (n= 236) or mixed tumours (n= 59).

Quality of pathologic response and surgery correlate with survival for patients with completely resected bladder cancer after neoadjuvant chemotherapy.

Background: In a retrospective study of Southwestern Oncology Group (SWOG)-S8710/INT-0080 (radical cystectomy [RC] alone vs 3 cycles of neoadjuvant chemotherapy [NC] with methotrexate, vinblastine, doxorubicin, and cisplatin before RC for bladder cancer), factors found to be associated with improved overall survival (OS) included pathologic complete response, defined as P0; treatment with NC; completion of RC with negative surgical margins; and >or=10 pelvic lymph nodes (LNs) removed.

Methods: The authors used stratified Cox regression to retrospectively study the association of quality of pathologic response after RC with OS in the subset of S8710 patients who received NC and RC with negative surgical margins.

Results: Of 154 patients who received NC, 68 (44.

Selective inhibition of prostaglandin E2 receptors EP2 and EP4 induces apoptosis of human endometriotic cells through suppression of ERK1/2, AKT, NFkappaB, and beta-catenin pathways and activation of intrinsic apoptotic mechanisms.

Endometriosis is a benign chronic gynecological disease of reproductive-age women characterized by the presence of functional endometrial tissues outside the uterine cavity. It is an estrogen-dependent disease. Current treatment modalities to inhibit biosynthesis and actions of estrogen compromise menstruation, pregnancy, and the reproductive health of women and fail to prevent reoccurrence of disease.

Induction of peritoneal endometriosis in nude mice with use of human immortalized endometriosis epithelial and stromal cells: a potential experimental tool to study molecular pathogenesis of endometriosis in humans.

Objective: To determine whether a mixed population of immortalized human endometriosis epithelial and stromal cells is able to induce peritoneal endometriosis in nude mice.

Design: Prospective experimental study. Human immortalized endometriosis epithelial and stromal cells were xenografted into ovariectomized nude mice.

Benign breast disease.

Benign breast disease includes all nonmalignant conditions of the breast, including benign tumors, trauma, mastalgia, mastitis, and nipple discharge. Benign tumors include pathologic changes that do not increase a patient's risk for developing cancer, lesions that confer a slightly increase risk, and lesions that are associated with an up to 50% risk of developing breast cancer. Both benign and malignant breast disorders can present with a palpable mass; skin dimpling, thickening, or erythema; pain; nipple discharge and inversion or distortion; or an abnormal screening mammogram with no clinical findings.

Cyclooxygenase-2 regulates survival, migration, and invasion of human endometriotic cells through multiple mechanisms.

Endometriosis is a debilitating disease characterized by the presence of functional endometrial glandular epithelium and stroma outside the uterine cavity that affects up to 20% of women of child-bearing age. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme in the biosynthesis of prostaglandin E(2) (PGE(2)), is highly expressed in endometriotic tissues and results in increased concentrations of peritoneal PGE(2) in women. In this study, we determined the expression of COX-2 protein in ectopic and eutopic endometria in humans and the role of COX-2 in endometriotic cell survival, migration, and invasion in humans.

Global hypomethylation is common in prostate cancer cells: a quantitative predictor for clinical outcome?

This study was designed to determine if cytological detection of 5-methylcytosine (5MC) was feasible on prostate tumor sections and to determine if levels of 5MC differed in malignant compared to normal prostate tissue. We further sought to see if 5MC levels correlated with any clinical outcome data. Thirty prostate tumor sections were obtained from patients who underwent radical prostatectomies from 1988 to 1995; these represented a mix of low to high grade tumors.

Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer.

Background: Despite aggressive local therapy, patients with locally advanced bladder cancer are at significant risk for metastases. We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy.

Methods: Patients were enrolled if they had muscle-invasive bladder cancer (stage T2 to T4a) and were to be treated with radical cystectomy.

Evaluation of immunohistochemistry and multiple-level sectioning in sentinel lymph nodes from patients with breast cancer.

Context: Previous investigations on sentinel lymph node biopsies have demonstrated their importance in nodal staging of patients with breast cancer. However, sentinel node biopsy in breast cancer is currently a controversial procedure and continues to provoke debate.

Objectives: We designed our study to determine the usefulness of a standard protocol for evaluating sentinel lymph node metastases and to assess the value of sentinel node biopsy as the only procedure in nodal staging in breast cancer patients.

Unusual case of stridor and wheeze in an infant: tracheal bronchogenic cyst.

Bronchogenic cysts are congenital anomalies that represent aberrant development of the foregut. Bronchogenic cysts in the mediastinum have been documented in both children and adults, but only one case of tracheal bronchogenic cyst in an infant was found in the literature. We report on a case of an infant with wheeze, stridor, and retractions, caused by a midtracheal bronchogenic cyst.

Frozen section diagnosis of metastatic prostate adenocarcinoma in pelvic lymphadenectomy compared with nomogram prediction of metastasis.

Objectives: To compare the sensitivity and negative predictive values of frozen section analysis of pelvic lymphadenectomy in patients undergoing radical retropubic prostatectomy for prostate adenocarcinoma with the predictive power of published nomograms for metastasis to lymph nodes.

Methods: A retrospective review was performed on all patients who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for prostate adenocarcinoma between 1991 and early 1997. The sensitivity and negative predictive values were computed comparing frozen section analysis, and patients were grouped by risk stratification.

Gene expression of insulin-like growth factors and receptors in neoplastic prostate tissues: correlation with clinico-pathological parameters.

The insulin-like growth factor (IGF) system has been shown to regulate prostate cancer cell growth in vitro and, possibly, in vivo. In this study we examined RNA expression of IGF ligands and their receptors in 23 paired benign and neoplastic prostate tissues. In addition to comparing gene expression of IGF ligands and receptors between benign and neoplastic tissue samples, we correlated IGF-I, IGF-II, IGFR-1, and IGFR-2 RNA levels in tumor samples with prognostic clinico-pathological parameters such as stage, grade, Gleason score, perineural or extraprostatic invasion.

Hypermethylation of the caveolin-1 gene promoter in prostate cancer.

Background: Hypermethylation of CpG islands in the promoter regions of tumor suppressor genes is one mechanism of tumorigenesis. Caveolin-1 (Cav-1), a gene coding for the structural component of cellular caveolae, is involved in cell signaling and has been proposed to be a tumor suppressor gene in several malignancies. This gene maps to 7q31.

Use of age-specific normal ranges for serum prostate-specific antigen.

Background: The traditional normal range for prostate-specific antigen has been 0.0 to 4.0 ng/mL.

Differential expression of insulin-like growth factor binding proteins in high versus low Gleason score prostate cancer.

Purpose: The insulin-like growth factor (IGF) system appears to be important in human prostate cancer biology. Expression of specific IGF binding proteins (IGFBPs) by prostate cancer tissues may modulate IGF cellular actions, and possibly determine both IGF-dependent tumor growth and biological aggressiveness in vivo. The purpose of this study was to examine the differential expression of all six IGFBP genes in benign and malignant prostate tissue samples.