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Biomedical subjects

Ronald J Cohen

Publications and source records attributed to Ronald J Cohen.

13 recordsLinked to original sources

Incidental renal tumours: the frequency of benign lesions and the role of preoperative core biopsy.

OBJECTIVE: To determine the incidence of benign renal lesions in incidentally discovered small renal tumours, increasingly detected by the widespread use of abdominal imaging, and to evaluate whether preoperative renal core biopsy is effective in identifying benign lesions. MATERIALS AND METHODS: In a retrospective study, renal core biopsies for incidental tumours over a 5-year period were analysed. The biopsies were correlated with the final pathology of the nephrectomy specimens, or with patient follow-up if nephrectomy was avoided. RESULTS: Of 70 diagnostic core biopsies, a third of cases were considered benign. The sensitivity and specificity for both benign and malignant lesions when compared to definitive pathology was 100% in all cases subjected to nephrectomy. Of the 30 non-diagnostic biopsies, three were proved to be benign, and 18 likely to be benign. The only complication of renal biopsy was one case of bleeding after biopsy. CONCLUSION: A higher than previously anticipated proportion of incidentally detected small renal masses are benign. Given the high sensitivity and specificity, there is value in taking a core biopsy of small incidental renal lesions, a procedure with a low complication rate (1%). When analysed by a pathologist familiar with renal biopsy, this might avoid radical nephrectomy in many patients.

Adult↗

Polymerase chain reaction-based identification of Propionibacterium acnes types isolated from the male urinary tract: evaluation of adolescents, normal adults and men with prostatic pathology.

OBJECTIVE: To assess whether colonization of the male urinary tract with Propionibacterium acnes, in particular types IB and II (which are associated with inflammation in radical prostatectomy specimens and might be involved in the development of prostate cancer), is associated with prostate disease, and thus to develop a urine test to detect men at risk of prostate disease. PATIENTS, SUBJECTS AND METHODS: We developed the first polymerase chain reaction (PCR)-based technique for identifying P. acnes types IA, IB and II, and used this in combination with selective culture medium to compare the prevalence of these subtypes in the urinary tract of adolescent males, healthy adult men and patients with confirmed prostate pathology. RESULTS: P. acnes types IB and II were no more prevalent in the urinary tract of patients with prostate pathology than in normal control men. However, the prevalence of types IB and II appeared to be higher in adult men (at 11 of 15 and six of 15, respectively) than in adolescents (two of six and one of six), suggesting an age-related increase. Comparison of urinary tract and facial skin P. acnes from three subjects showed that type IA was more often predominant on facial skin, whereas types IB or II were more often predominant in the urinary tract. CONCLUSIONS: A urine test might not be useful for detecting men with prostatic P. acnes infection and thus at greater risk of associated prostate disease. However, this work validated our technique for detecting and identifying the three P. acnes subtypes, and identified some interesting trends worth further investigation.

Adolescent↗

Links between Propionibacterium acnes and prostate cancer.

Incidental foci of prostate cancer are found at autopsy in 30% of men in their third decade, and by their eighth decade more than 75% have histological evidence of cancer. This unprecedented cancer prevalence points to a ubiquitous causative agent or perhaps an interaction between multiple common carcinogenic cofactors. We propose that one of these carcinogens is Propionibacterium acnes. Several characteristics of prostate cancer suggest the involvement of an infectious agent and we provide evidence that P. acnes is an excellent candidate. We have cultured P. acnes from a substantial proportion of prostate glands containing cancer and shown a significant positive association with prostatic inflammation. P. acnes is well suited to cause persistent, low-grade infection involving a marked inflammatory response and the P. acnes subtypes most frequently associated with prostate cancer become highly prevalent in the urinary tract of males following puberty.

Gram-Positive Bacterial Infections↗

Propionibacterium acnes associated with inflammation in radical prostatectomy specimens: a possible link to cancer evolution?

PURPOSE: Inflammation is commonly observed in the prostate gland and has been implicated in the development of prostate cancer. The etiology of prostatic inflammation is unknown. However, the involvement of a carcinogenic infectious agent has been suggested. MATERIALS AND METHODS: Prostatic tissue from 34 consecutive patients with prostate cancer was cultured to detect the presence of bacterial agents. Prostatic inflammation was assessed by histological examination of wholemount tissue sections. RESULTS: The predominant microorganism detected was Propionibacterium acnes, found in 35% of prostate samples. A significantly higher degree of prostatic inflammation was observed in cases culture positive for P. acnes (p =0.007). P. acnes was separated into 3 groups based on cell surface properties, phenotype and genetic grouping. All skin control isolates were classified as group 1 whereas most prostatic isolates were classified as groups 2 and 3. CONCLUSIONS: P. acnes has been isolated from prostatic tissues in men who underwent radical prostatectomy for localized cancer and has been shown to be positively associated with prostatic inflammation. This inflammation may then be linked to the evolution of carcinoma. Furthermore, organisms infecting these patients with prostate cancer differ genetically and phenotypically from the commonly identified cutaneous P. acnes isolates, suggesting that specific subtypes may be involved in development of prostatic inflammation.

Bacteriological Techniques↗

Primary renal synovial sarcoma confirmed by cytogenetic analysis: a lesion distinct from sarcomatoid renal cell carcinoma.

Primary synovial sarcoma rarely originates in the renal parenchyma. When this occurs, origin of this unusual tumor type has been the subject of debate in the literature, with a suggestion that previously reported cases may be more correctly described as renal cell carcinoma with sarcomatoid dedifferentiation. Synovial sarcoma and sarcomatoid renal cell carcinoma may be indistinguishable on pure histologic and immunohistochemical grounds, but these tumors contain distinctly different sets of chromosomal abnormalities. Most previous cases of primary renal synovial sarcoma were confirmed by molecular biology techniques, which detected the SYT-SSX gene fusion transcript typical of this tumor, but no details of the other chromosomal anomalies have been published. We report a case of primary renal synovial sarcoma confirmed by standard cytogenetic analysis, showing the characteristic t(X; 18)(p11.2:q11.2) translocation and other chromosomal aberrations that are typical of synovial sarcoma as opposed to sarcomatoid renal cell carcinoma.

Carcinoma, Renal Cell↗

Gene expression patterns in renal cell carcinoma assessed by complementary DNA microarray.

Renal cell carcinoma comprises several histological types with different clinical behavior. Accurate pathological characterization is important in the clinical management of these tumors. We describe gene expression profiles in 41 renal tumors determined by using DNA microarrays containing 22,648 unique cDNAs representing 17,083 different UniGene Clusters, including 7230 characterized human genes. Differences in the patterns of gene expression among the different tumor types were readily apparent; hierarchical cluster analysis of the tumor samples segregated histologically distinct tumor types solely based on their gene expression patterns. Conventional renal cell carcinomas with clear cells showed a highly distinctive pattern of gene expression. Papillary carcinomas formed a tightly clustered group, as did tumors arising from the distal nephron and the normal kidney samples. Surprisingly, conventional renal cell carcinomas with granular cytoplasm were heterogeneous, and did not resemble any of the conventional carcinomas with clear cytoplasm in their pattern of gene expression. Characterization of renal cell carcinomas based on gene expression patterns provides a revised classification of these tumors and has the potential to supply significant biological and clinical insights.

Adenocarcinoma, Clear Cell↗

Intraoperative lymph node staging of prostate cancer: the case against.

BACKGROUND: Intraoperative frozen section analysis of obturator nodes is an accepted screening procedure, excluding from prostatectomy that group of node-positive patients who are presumed to almost always have disseminated cancer. The overall efficacy of this procedure depends not only on the near inevitability of cancer progression in these patients, but also the procedure morbidity (previously estimated at 8.4%), the additional costs (currently estimated at A$1200) and the infrequency of positive nodes. We evaluate the efficacy of lymph node staging for prostate cancer. METHODS: We have evaluated the efficacy of intraoperative screening by node dissection in 123 prostatectomy cases. These cases were prescreened from a series of 261 radical prostatectomies by evaluating preoperative serum PSA and Gleason grade. RESULTS: Three patients were identified with nodal disease, representing a detection rate of 2.4%. The present study confirms that current trends in prostate cancer identification and selection of individuals for radical surgery very rarely identify node-positive disease even after preselection with accepted 'high-risk' markers. CONCLUSION: Considering the attendant cost and morbidity, there appears to be no justification for lymph node dissection as a routine preliminary to prostatectomy.

Adult↗

Rhabdoid differentiation of chromophobe renal cell carcinoma.

AIMS: Rhabdoid change represents an aggressive form of divergent differentiation previously reported in conventional (clear-cell) and papillary renal cell carcinoma. This study aims to characterise rhabdoid differentiation in a case of chromophobe renal cell carcinoma (ChRCC) and to investigate its origin by genetic analysis. METHODS: A large tumour mass arising in the right kidney of a 76-year-old male was investigated using routine stains (H&E, Hale's colloidal iron), immunostains (vimentin, cytokeratin) and genetic analysis for loss of heterozygosity (LOH) on chromosomes 1, 2, 3p, 6q, 10q, 13q, 17q, 17p and 21q. RESULTS: The tumour mass was comprised of the following histological subtypes: (i) typical ChRCC, (ii) eosinophilic variant ChRCC and (iii) rhabdoid variant RCC. Tumour cells of all three different histological subtypes had a positive reaction to Hale's colloidal iron stain, negative immunostaining for vimentin and LOH on chromosomes 2, 10q, 13q and 17p. These results are consistent with a diagnosis of ChRCC and indicate a common genetic origin for all three histological cell types. CONCLUSIONS: This study confirms that the aggressive rhabdoid variant can arise from ChRCC, as has been previously demonstrated for conventional (clear-cell) and papillary RCC.

Adenoma, Oxyphilic↗

Transition zone carcinoma of the prostate gland: a common indolent tumour type that occasionally manifests aggressive behaviour.

AIMS: Tumours arising in the transition zone (TZ) of the prostate gland are often well differentiated and considered clinically unimportant. We have observed examples of high-grade TZ cancers that prompted this study. METHODS: Review of 654 radical prostatectomy specimens previously assessed by systematic whole organ histology identified 187 (29%) TZ cancers of which 76 (11.6%) represented the index (main) tumour. These were compared with a volume-matched group of 76 peripheral zone (PZ) carcinomas. RESULTS: Fifty-nine of 76 TZ index carcinomas had additional minor tumours mainly located in the PZ. Compared to PZ tumours of similar size, TZ tumours had significantly lower Gleason scores, less Gleason grade 4/5 and lower rates of capsular penetration and positive surgical margins. However, within this TZ tumour group, seven carcinomas had a major Gleason grade 4 or 5 component with high rates of capsular penetration (57%) and positive surgical margins (43%). Positive anterior and bladder neck margins were more common in TZ carcinoma than peripheral tumours and transperineal biopsy was the method of choice for TZ cancer diagnosis. CONCLUSIONS: A subset of TZ carcinoma characterised by high tumour grade has a significant risk of extraprostatic spread, margin positivity and possible biochemical failure. We recommend transperineal prostate biopsy for TZ tumour diagnosis and histological sampling of the anterior TZ at radical prostatectomy, even if macroscopically normal, to detect patients at risk from aggressive TZ carcinoma.

Adult↗

Epithelial differentiation of the lower urinary tract with recognition of the minor prostatic glands.

Preservation of tissues in glutaraldehyde-based fixatives allows identification of prostatic glandular secretions without resorting to immunostaining. This has enabled detailed histological assessment of the entire male urethra and bladder and has confirmed prostatic epithelial cells outside the confines of the prostate gland. Male and female lower urinary tracts are also compared. Three intact bladders and penile urethras from radical surgical specimens, tissue from 10 radical prostatectomies, 12 penile urethral biopsy specimens, and 40 samples of of metaplastic bladder mucosa were evaluated after undergoing glutaraldehyde-based fixation (Solufix, Tissugen, Western Australia). All sections were immunostained for prostate-specific antigen (PSA) and high molecular-weight cytokeratin. Selected formalin-fixed samples also were assessed and stained for androgen receptor status, and 10 female control subjects also were evaluated. Prostatic epithelial cells, as recognized by their content of prostate secretory granules (PSG), were identified in almost all periurethral glands seen along the length of the penile urethra. These "minor prostatic glands" were composed entirely of prostatic cells or, more commonly, mixed prostatic and mucinous epithelium. The penile urethra was lined by transitional epithelium, whereas the prostatic urethra was lined by glandular cells with superficial androgen receptor-positive cells that had lost much of their secretory function. Foci of cystitis cystica/glandularis contained prostatic cells in more than half of the cases evaluated, and in all cases PSG secretion in extraprostatic sites was commensurate with PSA secretion. No prostatic secretion was seen in the female control cases, and the female urethra, in contrast to the male urethra, was lined entirely by glycogenated stratified squamous epithelium similar to the epithelium lining the vagina and vulva. This study defines the entity of minor prostatic glands and confirms their extensive normal distribution in the adult male subject. Minimal but persistently elevated levels of serum PSA occuring after successful radical prostatectomy may be related in part to this phenomenon. The female lower urinary tract differs considerably from the male but has similar features related to the lower genital tract.

Biomarkers↗

Adult rhabdoid renal cell carcinoma.

BACKGROUND: Pediatric rhabdoid tumor of the kidney is regarded as a distinct neoplasm, whereas rhabdoid differentiation in adult renal cell carcinoma is usually found in association with conventional (clear cell) tumor, from which it is thought to evolve. OBJECTIVE: To further characterize the rhabdoid phenotype in adult renal cell carcinoma and to determine its origin by genetic analysis. DESIGN: We performed histologic, immunophenotypic, and genetic analyses on 5 cases of adult renal cell carcinoma with rhabdoid differentiation, 3 samples of adjacent conventional (clear cell) tumor, and 6 conventional (clear cell) control tumors. RESULTS: Rhabdoid tumors differed from conventional (clear cell) carcinoma as follows: (1) macroscopically, rhabdoid tumors were solid white uniform masses; (2) microscopically, they had large rhabdoid cells with abundant eosinophilic cytoplasm, reduced lipid content, and the absence of a branching vascular pattern; and (3) biologically, they had a high metastatic potential. Despite these differences, loss of chromosome 3p in both the rhabdoid and clear cell carcinoma samples from 1 patient suggested a clonal origin. An identical mutation of the VHL gene in both rhabdoid and clear cell tumor samples from 2 patients confirmed a clonal origin for the histologically distinct tumor types in those cases. CONCLUSION: Adult rhabdoid renal cell carcinoma can in some cases arise from conventional (clear cell) renal carcinoma and should be considered a clinically important form of renal cell carcinoma separate from, but analogous to, sarcomatoid change.

Adenocarcinoma, Clear Cell↗