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Jonathan I Epstein

Publications and source records attributed to Jonathan I Epstein.

At least 73 records · Page 4Linked to original sources

Urothelial neoplasms in patients 20 years or younger: a clinicopathological analysis using the world health organization 2004 bladder consensus classification.

PURPOSE: Urothelial neoplasms in patients younger than 20 years are rare, with conflicting data regarding clinical outcomes. MATERIALS AND METHODS: We identified 23 patients 4 to 20 years old with urothelial neoplasms, reclassified the microscopic diagnoses using the 2004 WHO/International Society of Urologic Pathology grading classification and collected data on presentation, risk factors and outcomes. RESULTS: Pathological grading revealed 2 urothelial papillomas, 10 papillary urothelial neoplasms of low malignant potential (PUNLMPs), and 8 low grade and 3 high grade papillary urothelial cancers, all without invasion. Mean patient age was 13.2 years (range 4 to 20), 19 patients were male and 19 presented with gross hematuria. All lesions were solitary and measured 0.1 to 6 cm. One patient had a history of smoking and 1 had parents who smoked. Three patients (13%) had recurrences classified as either urothelial papilloma (1) or PUNLMP (2). All patients were alive with no evidence of disease after a mean followup of 4.5 years (range 6 months to 13 years). CONCLUSIONS: Urothelial neoplasms in individuals younger than 20 years more commonly occur in males and are predominantly low grade with a favorable clinical outcome. Before the current classification system the 10 patients with a diagnosis of PUNLMP would have been classified as having papillary carcinoma. Thus, the diagnostic category of PUNLMP allowed 43.5% of patients in this series to avoid being labeled with "cancer" at a young age.

Adolescent↗

Obesity and capsular incision at the time of open retropubic radical prostatectomy.

PURPOSE: The goal of radical prostatectomy (RP) is complete removal of the intact prostate. Obese men can represent a technical challenge. However, to our knowledge objective data linking obesity with technically inferior surgery are lacking. Therefore, we examined the association between body mass index (BMI) and capsular incision at RP as a surrogate of a poor technical operation in men treated for prostate cancer by several high volume surgeons at a center of excellence. MATERIALS AND METHODS: The study population consisted of 7,027 men treated with anatomical retropubic RP between 1996 and 2004 by 7 high volume surgeons. We evaluated the association between BMI and capsular incision using logistic regression, adjusting for clinical and pathological variables, and for the surgeon. RESULTS: Overall capsular incision was noted in 4.6% of all RP specimens. After adjustment for preoperative prostate specific antigen, patient race, height, year of surgery, clinical stage, pathological Gleason sum, prostate weight, extraprostatic extension and seminal vesicle invasion increased BMI was associated with increased odds of capsular incision (p trend = 0.005). After further adjustment for surgeon mild obesity was associated with 30% increased odds of capsular incision (OR 1.30, 95% CI 0.92 to 1.83), while moderate and severe obesity was associated with 57% increased odds of capsular incision (OR 1.57, 95% CI 0.82 to 3.00) relative to normal weight men (p trend = 0.06). CONCLUSIONS: In a study of more than 7,000 men treated by 7 experienced surgeons BMI was positively related to capsular incision. This suggests that open retropubic RP is technically more difficult in obese men, which results in a greater likelihood of a less than technically ideal operation. Although this may be predicted to have a negative impact on disease-free survival outcomes in obese men, it is unlikely to alone explain the worse outcomes in obese men noted in previous RP series.

Aged↗

Little or no residual prostate cancer at radical prostatectomy: vanishing cancer or switched specimen?: a microsatellite analysis of specimen identity.

With more vigilant screening for prostate cancer, there has been an associated increase in patients with little or no residual cancer at radical prostatectomy after an initial diagnosis of minute cancer on needle biopsy. This raises a critical question as to whether the biopsy and subsequent radical prostatectomy in these patients are from the same patient. We used PCR-based microsatellite marker analysis to perform identity test in 46 men (35 with minute cancer and 11 with no residual cancer). Of them, 41 were interpretable, including 31 with minute cancer and 10 with no residual cancer. All 31 interpretable cases with minute cancer showed match between the initial biopsy and radical prostatectomy specimens. Nine of the 10 interpretable cases with no residual cancer showed match and 1 showed mismatch. The remaining 5 cases (4 with minute cancer and 1 with no residual cancer) were considered uninterpretable due to technical problems. The initial biopsy of the mismatched case had high-grade cancer (Gleason score 4 + 4 = 8) measuring 9.6 mm in length with perineural invasion. Our results confirm that, in most cases of "vanishing cancer" in radical prostatectomy specimens, it reflects a chance sampling of a minute cancer and not a switch in specimens. However, specimen switch can rarely occur, and if there is high grade or a lot of cancer on the biopsy with no or very minimal cancer in the radical prostatectomy specimen, one should evaluate for patient identity.

Adenocarcinoma↗

Fibroepithelial polyp of the lower urinary tract in adults.

OBJECTIVE: Fibroepithelial polyps of the urinary tract are rare with most cases reported in children. DESIGN: We report the clinicopathologic features of 12 fibroepithelial polyps of the lower urinary tract in adults. PATIENTS: There were 9 males, 2 females, and 1 patient where the gender was unknown (median age, 44 years; range, 17-70 years). RESULTS: Chief clinical symptoms were hematuria, urinary urgency, and hesitancy. Five patients were asymptomatic, where the lesions were discovered incidentally. Most lesions were located near the verumontanum or the bladder neck. Ten patients were treated by transurethral resection. Of the 10 patients with follow-up information, none showed recurrence (mean, 20 months; median, 17 months). Histologically, all of the fibroepithelial polyps were lined by normal-appearing urothelium, with in one lesion the additional finding of a columnar epithelial lining. There were three overall architectural patterns seen within fibroepithelial polyps. The most common pattern (Pattern 1) seen in 5 cases consisted of a polypoid mass with club-like projections resembling a cloverleaf with florid cystitis cystica et glandularis of the nonintestinal type in the stalk. The second pattern (Pattern 2) seen in 4 cases consisted of a papillary tumor composed of numerous small, rounded fibrovascular cores containing dense fibrous tissue. The last morphologic pattern (Pattern 3) consisted of a polypoid lesion with secondary tall finger-like projections, which was seen in 3 cases. All lesions lacked prominent edema and inflammation seen in polypoid cystitis. Fibroepithelial polyps contained broader stalks with dense fibrous tissue, in contrast to the thin delicate loose fibroconnective tissue seen in the stalk of papillomas. One lesion contained atypical degenerative-appearing stromal cells. CONCLUSIONS: Although fibroepithelial polyps have been considered to be congenital, we think that some of these polyps could develop after birth because all of our patients first showed clinical symptoms in adulthood. Because fibroepithelial polyps in adults are rare, some of these cases can be misdiagnosed as urothelial neoplasms or reactive conditions. Recognition of the precise histologic features of fibroepithelial polyp can facilitate its correct diagnosis.

Adolescent↗

Clear cell papillary cystadenoma of the epididymis and mesosalpinx: immunohistochemical differentiation from metastatic clear cell renal cell carcinoma.

Clear cell papillary cystadenoma is a rare epithelial tumor of the epididymis, which may present as an isolated lesion or as a component of von Hippel-Lindau disease (VHLD). Recently, tumors have also been described in the female genital tract with similar histology. Recognition of clear cell papillary cystadenoma is critical because of its association with VHLD and its potential diagnostic confusion with metastatic renal cell carcinoma because of a shared architecture and clear cells. In this study, we report on the immunohistochemical differentiation of 5 clear cell papillary cystadenomas, 3 of the epididymis and 2 of the mesosalpinx, from metastatic renal cell carcinoma. In 2 cases, there was a history of renal cell carcinoma in the setting of VHLD; and in 1 of these cases, an epididymal papillary cystadenoma was initially considered to be metastatic renal cell carcinoma. Immunohistochemically, tumor cells were moderately intensely positive for cytokeratin AE1/AE3 and epithelial membrane antigen, strongly positive for CK7 and negative for CK20 and RCC. Four of 5 cases were negative for CD10. This staining profile contrasts with that reported for clear cell renal cell carcinomas, which are typically negative for CK7 and immunoreactive for renal cell carcinoma (RCC) and CD10. Our findings indicate that, in cases where there is uncertainty about the histologic diagnosis of clear cell papillary cystadenoma, the above immunohistochemical panel helps to rule out metastatic renal cell carcinoma.

Adenocarcinoma, Clear Cell↗

Small glandular proliferations on needle biopsies: most common benign mimickers of prostatic adenocarcinoma sent in for expert second opinion.

The current study aimed to determine the incidence of various benign mimickers of prostatic adenocarcinoma most commonly encountered in a busy consultation practice. All prostate needle biopsies from the consult service of one of the authors were prospectively evaluated over a 7-month period. Only cases with foci where the contributor questioned malignancy and which upon expert review the entire case was determined to be benign were included in this study. A total of 567 separate suspected atypical foci from 345 patients of a total of 4,046 patients (8.5%) received in consultation were identified. Of these, 281 foci (49.5%) had immunohistochemical (IHC) studies performed by the outside institution, which included high molecular weight cytokeratin (HMWCK) (n = 280), alpha-methylacyl-CoA racemase (AMACR) (P504s) (n = 45), and p63 (n = 34). The most common mimicker was partial atrophy (203 of 567; 35.8%). Technically adequate IHC for basal cells was performed in 117 cases of partial atrophy with patchy or patchy/negative staining seen in 102 of 117 (87%), with the remaining 13% of cases completely negative. A total of 15 of 19 (79%) cases of partial atrophy were positive with AMACR. Crowded benign glands, insufficiently crowded or numerous to warrant a diagnosis of adenosis, was the second most common mimicker (146 of 567; 25.7%). Crowded benign glands had patchy or patchy/negative IHC for basal cells in 66 of 81 (81%) cases with the remaining 19% of cases completely negative. A total of 7 of 11 (64%) cases of crowded glands were positive for AMACR. In the past, complete atrophy, adenosis, seminal vesicle, and granulomatous prostatitis were considered common mimickers of prostate cancer on prostatic needle biopsies. Our study shows that currently partial atrophy and crowded benign glands are the most common benign changes causing diagnostic difficulty and prompting consultation. Negative or patchy staining for basal cells and positive staining for AMACR may contribute to diagnostic difficulty in these entities.

Adenocarcinoma↗

Perineural involvement by benign prostatic glands on needle biopsy.

Uncommonly, benign prostatic glands can be seen in the perineural space, known as "benign perineural involvement." This phenomenon has not been specifically studied on needle biopsies; 27 needle biopsy cases with perineural involvement were evaluated; 22 (81.4%) were received in consultation, while 5 (18.5%) were in-house cases. In 15 of 22 (68.2%) consult cases, a question was raised by the submitting pathologist regarding the focus. The following patterns of perineural involvement were observed: indentation 14 (51.8%) cases, by up to 3 glands; tracking 8 (29.6%) cases, by up to 6 glands; wrapping 7 (25.9%) from one half to three fourths around the nerve, by up to 3 glands, 1 case showed 95% wrapping; intraneural 4 (14.8%) cases by up to 3 glands; adjacent 2 (7.4%) cases by up to 2 glands. Partial atrophy in the involved glands was seen in 10 (38.4%) cases and complete atrophy in 6 (23%). Of 8 cases with the lesion still present on slides for immunohistochemistry, high molecular weight cytokeratin (HMWCK) and p63 were positive in 6 (75%) and negative in the 2 (25%) cases with partial atrophy. A total of 6 (27%) cases had more than one pattern of perineural involvement. On hematoxylin and eosin sections, basal cells were not identified in 12 (46%) cases, including 2 negative and 1 positive cases stained for HMWCK. Patterns most closely mimicking cancer included intraneural and incomplete perineural encirclement. Perineural invasion by benign atrophic glands cause diagnostic difficulty, especially with negative HMWCK. Careful attention to hematoxylin and eosin morphology and comparison of perineural involvement to adjacent and distant benign glands are necessary.

Biopsy, Needle↗

Minute foci of Gleason score 8-10 on prostatic needle biopsy: a morphologic analysis.

Prostatic needle biopsies showing high-grade cancer typically contain abundant tumor. However, the histologic features of a minute focus of high-grade cancer on biopsy have not been well studied. A total of 100 cases with a single minute focus (< or = 1 mm) of Gleason score (GS) 8-10 adenocarcinoma were identified from a large consultative service, systematically studied, and compared with the submitting institutions' provisional diagnoses. The mean size of the minute foci was 0.52 mm. A total of 29 cases were GS 8 with cribriform glands (n = 15), poorly formed glands (n = 6), fused glands (n = 3), or combinations of the three (n = 5). A total of 38 cases were GS 9, with: single cells and poorly formed glands (n = 20); extremely poorly formed glands/borderline pattern 4/5 (n = 4); combinations of single cells, sheets, or nests of cells mixed with glands that were either poorly formed, cribriform, or fused (n = 14). A total of 33 cases were GS 10, with single cells (n = 23), single cells with nests (n = 9), or single cells with sheets of cells (n = 1). A total of 69 foci were located adjacent to benign glands, while 31 were on the edge or at the end of the core. Perineural invasion was observed in only 1 case. A total of 72 cases showed moderate to abundant amphophilic cytoplasm. Frequent prominent nucleoli (n = 11), mitoses (n = 8), and apoptotic bodies (n = 11) were infrequently observed. Of 59 cases with known provisional diagnoses, 46 were diagnosed as atypical (n = 37) or as cancer with GS < 8 (n = 9). Pathologists must be attuned to the complex and varied architectural patterns seen in low-volume, high-grade prostate cancer as its diagnosis has both important prognostic and therapeutic implications.

Adenocarcinoma↗

Mucosal benign epithelioid nerve sheath tumors.

Mucosal nerve sheath tumors have been well described in the gastrointestinal tract and other mucosal sites. In a series of mucosal biopsies, we have encountered a distinct subset of mucosal peripheral nerve sheath tumors characterized by small epithelioid cells and a benign clinical course. Such epithelioid nerve sheath tumors have been observed as a component of a larger study of colorectal "schwannomas," but herein we describe them in detail. A series of 7 of these lesions detected on mucosal biopsies (6 colonic, 1 bladder) was received by a single large institution in consultation material. The histologic and clinicopathologic features of the cases were reviewed. The mean age at presentation was 58.6 years with a slight female predominance (4 females, 3 males). Five of the colonic lesions were from the left colon and one from the right colon. The bladder biopsy was from the bladder neck. All of the colonic lesions were discovered as small (0.2-1.0 cm) polyps during the time of colonoscopy (3 at the time of routine screening, 2 for the workup of occult blood in the stool). The bladder neck mass was seen on bladder ultrasound after the patient presented with vaginal bleeding. None of the patients had a known history of neurofibromatosis. Histologically, the lesions showed an infiltrative growth pattern and were composed of spindled to predominantly epithelioid cells arranged in nests and whorls. The epicenters of the lesions were located in the lamina propria and extended to the superficial submucosa. The proliferating cells had uniform round to oval nuclei with frequent intranuclear pseudoinclusions and eosinophilic fibrillary cytoplasm. No mitoses were seen. All lesions expressed diffuse S-100 protein, and 3 of 5 lesions stained showed CD34 labeling in supporting cells. All were negative for CD117. All 5 lesions tested were negative for calretenin, while SM31 showed no intralesional neuraxons. One lesion was stained for epithelial membrane antigen and was negative. One lesion was associated with superficial mucosal erosion, and 1 had an inflammatory infiltrate predominantly composed of eosinophils. On follow-up of 5 patients, none has had any symptoms or recurrence of disease. Mucosal epithelioid nerve sheath tumors are a rare entity characterized by prominent epithelioid round to oval cells with an infiltrative growth pattern. These lesions are often discovered incidentally and have a benign clinical course.

Adult↗

A comparison of interobserver reproducibility of Gleason grading of prostatic carcinoma in Japan and the United States.

CONTEXT: Gleason grading is now the sole prostatic carcinoma grading system recommended by the World Health Organization. It is imperative that there be good interobserver reproducibility within this system worldwide. To our knowledge, there are no studies, using the same specimens, that compare the interobserver reproducibility of Gleason grading in Japan and the United States. OBJECTIVE: To compare the interobserver reproducibility of Gleason grading of prostatic carcinoma in Japan and the United States using, in Japan, images from the identical biopsy glass slides that were originally graded in the United States. DESIGN: Microsopic images from 37 needle biopsies of prostatic carcinoma were placed on CD-ROM and distributed to 14 Japanese pathologists for grading. These 14 physicians included 8 general pathologists and 6 pathologists with a special interest in urologic pathology. The needle biopsies had been previously reviewed so that a consensus diagnosis could be formed by a panel of urologic pathologists in the United States and Canada. Interobserver agreement with the consensus diagnoses was calculated by determining the overall kappa coefficient for the Japanese pathologists and then compared to the interobserver agreement among American general pathologists who had previously graded identical needle biopsies from which the CD-ROM images had been taken. RESULTS: The interobserver agreement with the consensus diagnoses for the 4 Gleason grading groups (Gleason grades 2-4, 5-6, 7, and 8-10) among the Japanese urologic pathologists in this series of cases was substantial (overall kappa = 0.68), and for the Japanese general pathologists, it was moderate (overall kappa = 0.49), similar to that reported in the earlier study of American general pathologists (overall kappa = 0.44). The major interobserver reproducibility problem for both Japanese and American general pathologists is undergrading. The major areas of undergrading are the underdiagnosis of Gleason scores 5-6 as Gleason scores 2-4, and the underdiagnosis of cribriform sheets and fragments of cribriform Gleason pattern 4 carcinoma as Gleason pattern 3. CONCLUSIONS: The interobserver reproducibility of the Gleason grading for this collection of specimens was similar among Japanese and American general pathologists. The overall kappa values for these generalists of 0.44 and 0.49 are only in the moderate (0.41-0.60) range of interobserver agreement when compared to 0.68, substantial (0.61-0.80) agreement, for Japanese urologic pathologists. Educational efforts to improve Gleason grading have been shown to be effective and are clearly warranted.

Adenocarcinoma↗

Incidental stromal-predominant mixed epithelial-stromal tumors of the kidney: a mimic of intraparenchymal renal leiomyoma.

CONTEXT: Mixed epithelial-stromal tumor of the kidney is a recently recognized benign renal tumor that usually occurs in adult women and typically forms a sizable lesion with solid and cystic areas. The recognized morphologic spectrum of this recently described entity is evolving. OBJECTIVE: To review the clinicopathologic features of 3 small mixed epithelial-stromal tumors of the kidney that were incidental findings in kidneys removed for other reasons. DESIGN: The clinical presentation and morphologic findings of the 3 cases were reviewed. A panel of immunohistochemical stains was performed. SETTING: Academic medical center. RESULTS: All 3 lesions contained predominantly fascicles of smooth muscle mimicking leiomyoma, but they also had cellular subpopulations of smaller, müllerian-appearing stromal cells. Tubules present within the lesion were most abundant at the periphery, suggesting that they might be entrapped. Although only the spindled smooth muscle cells were immunoreactive for muscle markers desmin and actin, both the spindled smooth muscle cells and the cellular müllerian-appearing stromal cells demonstrated diffuse nuclear labeling for estrogen and progesterone receptors. CONCLUSIONS: Mixed epithelial-stromal tumor of the kidney may present as an incidental stromal-predominant lesion within the kidney. Such lesions are easily confused with leiomyomas or stromal-predominant angiomyolipomas.

Adult↗

Characteristics of insignificant clinical T1c prostate tumors. A contemporary analysis.

BACKGROUND: The authors examined the cases of men who had undergone radical prostatectomy for low-volume clinical T1c prostate carcinoma that was judged to be 'insignificant' on the basis of previously established preoperative clinicopathologic parameters. Pathologic findings subsequently were analyzed for correlations with extent of disease in an attempt to validate the contemporary usefulness of existing parameters for predicting the 'significance' of prostate tumors. METHODS: A series of 237 men who had undergone radical prostatectomy for T1c disease between December 2000 and August 2003 was evaluated. Insignificant prostate carcinoma as assessed on biopsy was defined according to the 1994 Epstein criteria, which were as follows: prostate-specific antigen density < 0.15 ng/mL, Gleason score < or = 6, fewer than 3 cores containing prostate carcinoma, and < or = 50% involvement of any core with prostate carcinoma. Postsurgical pathologic findings were analyzed for potential correlations with the Epstein criteria. RESULTS: According to the Epstein needle biopsy criteria, organ-confined prostate carcinoma was detected in 91.6% of all patients, whereas the remaining 8.4% of patients were found to have non-organ-confined disease. Comparison of pathologic findings and Epstein biopsy criteria revealed that alteration of the original criteria did not improve the detection of non-organ-confined prostate carcinoma. CONCLUSIONS: The findings made in the current study suggest that the majority of patients with T1c prostate carcinoma have insignificant disease. Furthermore, it was found that the Epstein criteria for identifying insignificant prostate carcinoma remained a useful tool in the making of treatment-related decisions.

Adult↗

Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma.

PURPOSE: In this study, we tested the ability of a panel of hypermethylation markers to improve the sensitivity of histologic prostate cancer detection in sextant needle biopsies. EXPERIMENTAL DESIGN: We obtained fresh-frozen sextant biopsies from 72 excised prostates and directly compared blinded histologic review and quantitative real-time methylation-specific PCR for hypermethylation of four genes, Tazarotene-induced gene 1 (TIG1), adenomatous polyposis coli (APC), retinoic acid receptor beta2 (RARbeta2), and glutathione S-transferase pi (GSTP1) to detect the presence of prostate cancer. Results were compared with the final surgical pathological review of the resected prostates as the gold standard. RESULTS: Histologic review alone detected carcinoma with a sensitivity of 64% (39 of 61 cases) and 100% specificity. Quantitative real-time methylation-specific PCR for TIG1, APC, RARbeta2, and GSTP1 detected carcinoma with a sensitivity of 70%, 79%, 89%, and 75%, respectively, with 100% specificity for all of the genes. Using this panel of methylation markers in combination with histology resulted in the detection of 59 of 61 (97%) cases of prostate with 100% specificity, a 33% improvement over histology alone. CONCLUSION: The use of a panel of methylation markers as an adjunct to histologic review may substantially augment prostate cancer diagnosis from needle biopsies.

Acyltransferases↗

Ability to predict metastasis based on pathology findings and alterations in nuclear structure of normal-appearing and cancer peripheral zone epithelium in the prostate.

PURPOSE: Malignant transformation in the prostate produces significant alterations in glandular architecture (Gleason grade) and nuclear structure that provide valuable prognostic information. Normal-appearing nuclei (NN) adjacent to cancer may also have altered functions in response to malignancy. We studied NN adjacent to peripheral zone (PZ) prostate cancer (PCa), as well as the PZ cancer nuclei (CaN) using quantitative image cytometry. The nuclear structure information was combined with routine pathological findings to predict metastatic PCa progression and/or death. EXPERIMENTAL DESIGN: Tissue microarrays of normal-appearing and cancer areas were prepared from 182 pathologist-selected paraffin blocks. Feulgen-stained CaN and NN were captured from the tissue microarrays using the AutoCyte Pathology Workstation. Multivariate logistic regression was used to calculate quantitative nuclear grade (QNG) solutions based on nuclear morphometric descriptors determined from NN and CaN. Multivariate logistic regression and Kaplan-Meier plots were also used to predict risk for distant metastasis and/or PCa-specific death using QNG solutions and routine pathology. RESULTS: The pathology model yielded an area under the receiver operator characteristic curve of 72.5%. The QNG-NN and QNG-CaN solutions yielded an area under the receiver operator characteristic curve of 81.6 and 79.9%, respectively, but used different sets of nuclear morphometric descriptors. Kaplan-Meier plots for the pathology variables, the QNG-NN and QNG-CaN solutions, were combined with pathology to defined three statistically significantly distinct risk groups for distant metastasis and/or death (P < 0.0001). CONCLUSIONS: Alterations in cancer or normal-appearing nuclei adjacent to peripheral zone cancer areas can predict PCa progression and/or death. The QNG-NN and QNG-CA solutions could be combined with pathology variables to improve the prediction of distant metastasis.

Adult↗

Biochemical failure after radical prostatectomy in men with pathologic organ-confined disease: pT2a versus pT2b.

BACKGROUND: The 1997 TNM staging system for prostate carcinoma defines a pT2a disease as a tumor histologically involving one lobe of the prostate and pT2b disease as a tumor histologically involving both prostatic lobes. Whether this distinction provides prognostic significance is unclear. The authors evaluated biochemical outcomes between men with pT2aN0 and pT2bN0 disease. METHODS: The authors identified 1606 men with organ-confined disease (pT2N0) who were treated with radical prostatectomy between 1982 and 2003 by one surgeon. Clinical characteristics were compared between men with pT2a and pT2b tumors using rank-sum analysis, and prostate-specific antigen (PSA) recurrence data were compared using log-rank analysis. The significant independent predictors of PSA recurrence were determined using a multivariate Cox proportional hazards model. RESULTS: There were no significant differences between men with pT2a and pT2b tumors at the time of surgery in terms of clinicopathologic characteristics (biopsy and pathologic Gleason score, serum PSA level, clinical stage, and age). Log-rank analysis revealed no significant differences in time to PSA recurrence between men with pT2a and pT2b tumors (P = 0.755). The 10-year PSA progression-free survival rate was 95% (confidence interval [CI], 92-97%) for men with pT2a tumors and 93% (CI, 90-95%) for men with pT2b tumors. Multivariate analysis showed that the significant predictors of PSA recurrence included serum PSA level, biopsy and pathologic Gleason score, and clinical stage. In the current cohort of men with organ-confined disease, pathologic stage (pT2a vs. pT2b) was not a significant predictor of PSA recurrence on multivariate analysis. CONCLUSIONS: There was no difference in PSA recurrence rates between men with pT2aN0 versus pT2bN0 tumors. In men with organ-confined disease, radical prostatectomy provided excellent 10-year PSA progression-free survival regardless of tumor burden (pT2a vs. pT2b). Consideration should be given to modifying the TNM staging system to eliminate substratification of pT2 tumors.

Aged↗

Pathological and molecular mechanisms of prostate carcinogenesis: implications for diagnosis, detection, prevention, and treatment.

Prostate cancer is an increasing threat throughout the world. As a result of a demographic shift in population, the number of men at risk for developing prostate cancer is growing rapidly. For 2002, an estimated 189,000 prostate cancer cases were diagnosed in the U.S., accompanied by an estimated 30,200 prostate cancer deaths [Jemal et al., 2002]. Most prostate cancer is now diagnosed in men who were biopsied as a result of an elevated serum PSA (>4 ng/ml) level detected following routine screening. Autopsy studies [Breslow et al., 1977; Yatani et al., 1982; Sakr et al., 1993], and the recent results of the Prostate Cancer Prevention Trial (PCPT) [Thompson et al., 2003], a large scale clinical trial where all men entered the trial without an elevated PSA (<3 ng/ml) were subsequently biopsied, indicate the prevalence of histologic prostate cancer is much higher than anticipated by PSA screening. Environmental factors, such as diet and lifestyle, have long been recognized contributors to the development of prostate cancer. Recent studies of the molecular alterations in prostate cancer cells have begun to provide clues as to how prostate cancer may arise and progress. For example, while inflammation in the prostate has been suggested previously as a contributor to prostate cancer development [Gardner and Bennett, 1992; Platz, 1998; De Marzo et al., 1999; Nelson et al., 2003], research regarding the genetic and pathological aspects of prostate inflammation has only recently begun to receive attention. Here, we review the subject of inflammation and prostate cancer as part of a "chronic epithelial injury" hypothesis of prostate carcinogenesis, and the somatic genome and phenotypic changes characteristic of prostate cancer cells. We also present the implications of these changes for prostate cancer diagnosis, detection, prevention, and treatment.

Atrophy↗